Morphological and molecular characterization of Hemicycliophora subbotini n. sp. (Tylenchida: Hemicycliophoridae) from China.
Sheath nematodes of the genus Hemicycliophora are migratory root-ectoparasites of many crops, but the damage is documented for only a few species. Hemicycliophora subbotini n. sp., isolated in Hangzhou, Zhejiang, China, from the rhizosphere of camphor tree (Cinnamomum camphora (L.) Presl), is described and characterized morphologically and molecularly with important morphological details elucidated by SEM studies. The new species can be characterized by the conoid lip region, with bulging oral disc protruding beyond the first annulus in some specimens. Oral disc narrow ovate, amphidial apertures covered by lateral plates, lying in the same plane as oral disc when observed en face. Stylet 118 (108-125) μm long and flexible, stylet knobs concave shaped having a slight cavity. The excretory pore is located 1-2 annuli posterior to the base of pharyngeal bulb. Vulval lips slightly modified with small vulval sleeve, spermatheca rounded to oblong. Anus located 18 (15-22) annuli posterior to vulva. Tail elongated, with conoid or slightly offset spike having a narrowly rounded terminus. The study provides the first description of a new Hemicycliophora species from China. Phylogenetic analyses based on D2-D3 expansion segments of the 28S and ITS fragments revealed the new species forming a separate clade from other Hemicycliophora species which supported the status as a new species of this genus.


Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer.
Gemcitabine (GEM) and paclitaxel (PTX) are effective combination anticancer agents against non-small-cell lung cancer (NSCLC). At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic) and PTX (hydrophobic) into simplex tumor-targeted nanostructured lipid carriers (NLCs) for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N-acetyl-d-glucosamine (NAG) is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6-O-methacryloyl-d-galactopyranose)-GEM/PTX (PMAGP-GEM/PTX) conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1) exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor-targeted combination therapy to achieve maximal anticancer efficacy in NSCLC.


Epidermal growth factor receptor mutation in lung cancer are linked to bronchioloalveolar differentiation.
In lung cancer, an association was made between drastic clinical response to epidermal growth factor receptor (EGFR) inhibitors and the presence of somatic mutations within the tyrosine kinase domain of the EGFR. In some cases, patients with partial response or disease stabilization do not always have EGFR-mutated tumors. To go further in the characterization of the EGF pathway, we screened EGFR, ERBB2, ERBB3, KRAS, BRAF, and PIK3CA for mutations in 2 groups of White patients with nonsmall cell lung cancer (45 cancers from women and 46 cancers from men). Associations between TP53 mutations, clinicopathologic parameters, and EGF pathway molecular alterations were analyzed. All mutations were exclusive and essentially found in EGFR and KRAS. We demonstrated that EGFR mutations were linked to female sex, absence of smoking, late age at diagnosis, and adenocarcinoma (ADC) with bronchioloalveolar (BAC) features. Moreover, in invasive ADC with BAC component, microdissection assays showed that mutations were retrieved in both tumor subtypes suggesting that EGFR mutations appear early in lung carcinogenesis. On the contrary, KRAS mutations correlated with smoking, younger age at diagnosis, and ADC subtype regardless of BAC differentiation. These results suggest the existence of distinct carcinogenesis pathways both leading to disruption of EGF regulation and targeted either by tobacco carcinogens or by unidentified toxic. The identification of BAC features in ADC helps clustering patients that are more likely to fit the EGFR-mutated group.


Use of Integrative Medicine in the United States Military Health System.
Integrative medicine (IM) is a model of care which uses both conventional and nonconventional therapies in a "whole person" approach to achieve optimum mental, physical, emotional, spiritual, and environmental health, and is increasingly popular among patients and providers seeking to relieve chronic or multifactorial conditions. The US Department of Defense (DoD) shows particular interest in and usage of IM for managing chronic conditions including the signature "polytrauma triad" of chronic pain, traumatic brain injury (TBI), and posttraumatic stress disorder (PTSD) among its beneficiaries in the Military Health System (MHS). These modalities range from conventional nondrug, nonsurgical options such as cognitive-behavioral therapy to nonconventional options such as acupuncture, chiropractic, and mind-body techniques. These are of particular interest for their potential to relieve symptoms without relying on opiates, which impair performance and show high potential for abuse while often failing to provide full relief. This review describes the use of IM in the MHS, including definitions of the model, common therapies and potential for use, and controversy surrounding the practice. More research is needed to build a comprehensive usage analysis, which in turn will inform sound clinical and financial practice for the MHS and its beneficiaries.


Racial inequality in obstetric good practices and interventions in labor and birth care in Rede Cegonha.
This study aimed to evaluate the racial inequality on childbirth care at the Rede Cegonha (Stork Network) using obstetric good practice and interventions indicators. Racial inequality, measured by the total effect of ethnicity/skin color in the crude model, was seen in many indicators. After adjusting for mediators, such as age, schooling, parity, high-risk hospital, and geographic macro-regions, the persistent direct effect suggests racial discrimination against black women with lower partograph completion (PR 0.88; 95% CI 0.80-0.95). Black women stayed less in lithotomy (PR 0.93; 95% CI 0.89-0.98), performed less episiotomy (PR 0.81; 95% CI 0.68 - 0.96), and had less episiotomy suturing pain (PR 0.66; 95% CI 0.51 - 0.87) when compared to white women, suggesting more good practice applied to black women. However, according to the interventionist care model still adopted by many professionals, these practices are routine, and lower achievement in black women would be better interpreted as evidence of racial discrimination against these women. For other outcomes, the ethnicity/skin color effect disappeared after adjusting for mediators, suggesting mitigation or disappearance of the skin color effect in some practices/interventions in childbirth.


Effectiveness evaluation of two volumizing hyaluronic acid dermal fillers in a controlled, randomized, double-blind, split-face clinical study.
Enhancement of the midface can be achieved with volumizing hyaluronic acid (HA) fillers. The objective of this study was to compare the safety and effectiveness of Cohesive Polydensified Matrix® 26 mg/mL HA gel (CPM-26) and Vycross® 20 mg/ml HA gel (VYC-20) in a controlled, randomized, evaluator-blind, split-face clinical study. Subjects with moderate-to-severe malar volume loss on the Merz Aesthetics Scale (MAS) received CPM-26 on one side and VYC-20 on the contralateral side of the face. Effectiveness assessments were performed by blinded evaluators including photographic and live MAS ratings and live Global Aesthetic Improvement Scale (GAIS) ratings. Calculations of anatomical volume variations at month 3 (M3), month 6 (M6), month 12 (M12) and month 18 (M18) were also performed. Non-inferiority of CPM-26 versus VYC-20 was demonstrated at M3 (primary end point) based on MAS. GAIS rating showed that significantly more subjects had better improvement with CPM-26 than with VYC-20 at month 1, M3, M12 and M18 (p=0.0032, p=0.0074, p=0.0384 and p=0.0110, respectively). Standardized evaluation of volume variations from baseline to M3, M12 and M18 showed that CPM-26 created more volume augmentation at all time points, and the difference was significant at M3. CPM-26 was non-inferior to VYC-20 based on MAS ratings at M3 and demonstrated a favorable safety and effectiveness profile for midfacial volume enhancement with results lasting up to M18.


Connecting thermal performance curve variation to the genotype: a multivariate QTL approach.
Thermal performance curves (TPCs) are continuous reaction norms that describe the relationship between organismal performance and temperature and are useful for understanding trade-offs involved in thermal adaptation. Although thermal trade-offs such as those between generalists and specialists or between hot- and cold-adapted phenotypes are known to be genetically variable and evolve during thermal adaptation, little is known of the genetic basis to TPCs - specifically, the loci involved and the directionality of their effects across different temperatures. To address this, we took a multivariate approach, mapping quantitative trait loci (QTL) for locomotor activity TPCs in the fly, Drosophila serrata, using a panel of 76 recombinant inbred lines. The distribution of additive genetic (co)variance in the mapping population was remarkably similar to the distribution of mutational (co)variance for these traits. We detected 11 TPC QTL in females and 4 in males. Multivariate QTL effects were closely aligned with the major axes genetic (co)variation between temperatures; most QTL effects corresponded to variation for either overall increases or decreases in activity with a smaller number indicating possible trade-offs between activity at high and low temperatures. QTL representing changes in curve shape such as the 'generalist-specialist' trade-off, thought key to thermal adaptation, were poorly represented in the data. We discuss these results in the light of genetic constraints on thermal adaptation.


The effects of psychological distance on abstraction: Two meta-analyses.
Psychological distance and abstraction both represent key variables of considerable interest to researchers across cognitive, social, and developmental psychology. Moreover, largely inspired by construal level theory, numerous experiments across multiple fields have now connected these 2 constructs, examining how psychological distance affects the level of abstraction at which people mentally represent the world around them. The time is clearly ripe for a quantitative synthesis to shed light on the relation between these constructs and investigate potential moderators. To this end, we conducted 2 meta-analyses of research examining the effects of psychological distance on abstraction and its downstream consequences. Across 106 papers containing a total of 267 experiments, our results showed a reliable and medium-sized effect of psychological distance on both level of abstraction in mental representation and the downstream consequences of abstraction. Importantly, these effects replicate across time, researchers, and settings. Our analyses also identified several key moderators, including the size of the difference in distance between 2 levels of a temporal distance manipulation and the dependent variable's capacity to tap processing of both abstract and concrete features (rather than only one or the other). We discuss theoretical and methodological implications, and highlight promising avenues for future research.


Upregulated Linc01836 in Serum Promisingly Serving as a Diagnostic and Prognostic Biomarker for Colorectal Cancer.
Objectives: Colorectal cancer (CRC) is a common carcinoma of the gastrointestinal tract with high incidence and mortality worldwide. Studies have shown that long noncoding RNAs (lncRNAs) play important roles in CRC. Our purpose is to investigate the potential of serum Linc01836 as a diagnostic and prognostic marker in CRC. Methods: We evaluated the expression of Linc01836 via quantitative real-time polymerase chain reaction (qRT-PCR). The serum CEA, CA19-9, Cyfra21-1, and CA72-4 concentrations were measured by Architect I4000 SR. Receiver operating characteristic (ROC) curves were plotted to estimate the diagnostic value in CRC. Relationship between serum Linc01836 expression and clinicopathological characteristics of CRC cases was analyzed via chi-square test. The underlying mechanism of Linc01836 on the development and prognosis in CRC was predicted by bioinformatic analysis. Results: The method of qRT-PCR for Linc01836 detection was confirmed with high precision and specificity. Serum Linc01836 expression in CRC patients was significantly higher than that in healthy donors (p < 0.0001) and benign patients (p < 0.0001), and declined after resection (p < 0.01). High expression of Linc01836 was associated with histological stage (p = 0.002) and lymph node metastasis (p = 0.006). In addition, serum Linc01836 could effectively differentiate CRC patients from the healthy folks, with favorable area under the curve (AUC) of 0.809 (95% CI: 0.757-0.861, p < 0.001). What is more, the combination of serum Linc01836, CEA, and Cyfra21-1 could improve diagnostic sensitivity (92.0%). Linc01836 was averagely located in the nucleus and cytoplasm, suggesting that it might participate in CRC progression and prognosis through the crosstalk among lncRNAs, miRNAs, and mRNAs. Conclusion: Linc01836 may serve as a valuable noninvasive biomarker for population screening, early detection, and clinical surveillance of CRC.


The role of dimensionality in the decay of surface effects.
We computationally investigate the decay of surface effects in one-, two-, and three-dimensional materials using two-band tight-binding models. These general models facilitate a direct comparison between materials of differing dimensionality, which reveals that material dimensionality (not material-specific chemistry/physics) is the primary factor controlling the decay of surface effects. Our results corroborate more sophisticated, material-specific studies, finding that surface effects decay after ∼10, ∼25, and ≳ 100 layers in three-dimensional, two-dimensional, and one-dimensional materials, respectively. Physically, higher-dimensional materials screen surface effects more efficiently, as theoretically described by integration over each layer's Brillouin zone. Finally, we discuss several implications of these results.


[Pancreas scan (author's transl)].
A Review and a report of our ten years experience with pancreas scans. The diagnostic value of 75Selen-Methionine (75Se) scan is limited because of the lack of organ specificity of this substance. There is no improvement by pharmacological stimulation of the pancreas or subtraction techniques of the 75Se-activity in the liver. In the early phase after the injection of 75Se the distribution is more favourable for the pancreas compared to liver and intestine. Four descriptive terms are in use: normal, spotted, organ defect, and lack of uptake. There are no specific signs for pancreatitis, carcinoma, or exocrine dysfunction. Considering these limiting factors the use of pancreas scans is valuable to exclude pancreatic diseases.


Differential Risk of Cognitive Impairment across Paid and Unpaid Occupations in the Middle-Age Population: Evidence from the Korean Longitudinal Study of Aging, 2006-2016.
To examine and quantify the risk of cognitive impairment across a variety of occupations including unpaid work in a middle-age population using the dataset of a nationally representative longitudinal survey. A total of 20,932 observations of 5865 subjects aged 45-64 were obtained from six waves of the Korean Longitudinal Study of Aging (2006-2016). A dichotomous outcome variable was constructed on the basis of the Korean Versions of the Mini-Mental State Examination scores, and occupations were grouped into 10 occupation categories, including unpaid housekeepers. Socio-demographics, lifestyle, and medical conditions were used as covariates in mixed logistic regression models. Adjusted odds ratios and predicted probabilities of cognitive impairment were computed and adjusted for a complex survey design. In longitudinal models with all studied covariates, the risk of cognitive impairment differed significantly across occupation categories, but the association of occupation with the risk of cognitive impairment was the same between genders. In terms of the predicted probability, the risk of cognitive impairment in the unpaid housekeepers' category (11.2%, 95% confidence interval (CI): 10.4% to 11.9%) was the highest among occupation categories, being three times higher than in the professionals' and related workers' category (3.7%, 95% CI: 1.6% to 5.7%). Public policies based on studies of the risk of cognitive impairment across different occupations in the middle-age population should be designed so as to prevent cognitive impairment in the middle-age population as well as their older life stages, particularly targeting high-risk groups such as people engaged in unpaid domestic and care activities.


Strategies and criteria for the development of molecular biomarkers of senescence.
While it may be possible to employ panels of molecular parameters which correlate with senescence in vivo or in vitro, in a manner analogous to the use of mutagenesis assays for economic carcinogen screening, such an endeavor would at present be impeded by the absence of a clear mechanistic rationale for focusing on particular biomarkers, and by the complexity of the senescent phenotype and its multilevel interactions. Nevertheless, insight into the mechanism(s) of senescence may derive indirectly from correlative studies, or directly from strategies of molecular intervention, provided that such studies meet reasonable criteria for relevance and functionality. Even the control of expression of a single gene may be quite complex, with multigenic interactions and the potential to produce a cascade affecting many downstream genes. In order to understand such processes, functional assays and selective systems will need to be developed.


Silkworm as an experimental animal for research on fungal infections.
Silkworm, Bombyx mori, has various advantages as an experimental animal, such as the low cost for rearing and fewer ethical problems. Models utilizing silkworms of infection with pathogenic bacteria have been established for identification of genes encoding virulence factors by large-scale in vivo screening. In this review, we describe recent progress in the study of silkworm infection models for elucidating the mechanisms of fungi infection. Silkworm infection models have been established for Candida albicans, Candida tropicalis, Candida glabrata and Cryptococcus neoformans, which are yeast type fungi, and Aspergillus fumigatus, Arthroderma vanbreuseghemii, Arthroderma benhamiae, Microsporum canis, Trichophyton rubrum, and Rhizopus oryzae, which are filamentous fungi. Novel genes encoding virulence factors in C. albicans and C. glabrata have been identified by using the silkworm infection models. We here outline the benefits of using silkworm infection models and a strategy for identifying the genes responsible for pathogenicity of microorganisms such as fungi. © 2019 The Authors. Microbiology and Immunology Published by The Societies and John Wiley & Sons Australia, Ltd.


Successful pregnancy following mid-trimester evacuation through a transabdominal cervical cerclage.
Preterm birth remains a major challenge in modern obstetrics and is increasing, even among low-risk primiparous women. Very few interventions have made a positive impact on outcome although cervical cerclage appears to benefit some women. Transabdominal cervical cerclage can be highly successful and should be considered in women with previous failed transvaginal cerclage, but requires operative abdominal delivery as it cannot be removed. The authors report the first case they are aware of, where a spontaneous abortion occurred with a transabdominal cerclage in situ and a mid-trimester dilation and evacuation was performed through the cerclage at 18 weeks gestation, instead of a hysterotomy. A subsequent pregnancy was successful and it was the first to go full term.


[Laparoscopic promontal fixation: assessment of 100 cases].
Aim of the study is to evaluate long term results of 100 patients treated laparoscopically to repair genital prolapse and urinary incontinence. A retrospective review analysis of 100 women, who underwent laparoscopic genital prolapse repair at Primary Referral University Hospital in Clermont-Ferrand. Patients characteristics, preoperatory exams, intraoperative, postoperative and outpatient clinic data were collected and analyzed. The mean operative time was 172 minutes. One laparotomy conversion was required, due to a technical problem. The mean hospitalization stay was 4.7 days. Two patients required a reintervention during their hospitalization stay, due to a complication. All the patients were reviewed during the 6 months later the intervention. The follow-up is between 6 months and 3 years. The average degree of cystocele and hysterocele was ameliorated from stage 3 to stage 0, the average stage of rectocele was ameliorated from stage 2 to stage 0, finally the average stage of vault prolapse was ameliorated from stage 1 to stage 0. The incidence of genuine stress incontinence was 47% in the preoperative time and only 4% at the long follow-up. We had a total 4% rate of mesh vaginal erosion. The laparoscopic sacrocolpopexy is an effective and safe technique to repair the major pelvic prolapses.


VSIG4 mediates transcriptional inhibition of Nlrp3 and Il-1β in macrophages.
Hyperactivation of the NLRP3 inflammasome contributes to the pathogenesis of multiple diseases, but the mechanisms underlying transcriptional regulation of Nlrp3 remain elusive. We demonstrate here that macrophages lacking V-set and immunoglobulin domain-containing 4 (Vsig4) exhibit significant increases in Nlrp3 and Il-1β transcription, caspase-1 activation, pyroptosis, and interleukin-1β (IL-1β) secretion in response to NLRP3 inflammasome stimuli. VSIG4 interacts with MS4A6D in the formation of a surface signaling complex. VSIG4 occupancy triggers Ser232 and Ser235 phosphorylation in MS4A6D, leading to activation of JAK2-STAT3-A20 cascades that further results in nuclear factor κB suppression and Nlrp3 and Il-1β repression. Exaggerated NLRP3 and IL-1β expression in Vsig4-/- mice is accountable for deleterious disease severity in experimental autoimmune encephalomyelitis (EAE) and resistance to dextran sulfate sodium (DSS)-induced colitis. The agonistic VSIG4 antibodies (VG11), acting through NLRP3 and IL-1β suppression, show significant therapeutic efficacy in mouse EAE. These findings highlight VSIG4 as a prospective target for treating NLRP3-associated inflammatory disorders.


Initiation of chromosome replication in dnaA and dnaC mutants of Escherichia coli B/r F.
Regulatory aspects of chromosome replication were investigated in dnaA5 and dnaC2 mutants of the Escherichia coli B/r F. When cultures growing at 25 degrees C were shifted to 41 degrees C for extended periods and then returned to 25 degrees C, the subsequent synchronous initiations of chromosome replication were spaced at fixed intervals. When chloramphenicol was added coincident with the temperature downshift, the extend of chromosome replication in the dnaA mutant was greater than that in the dnaC mutant, but the time intervals between initiations were the same in both mutants. Furthermore, the time interval between the first two initiation events was unaffected by alterations in the rate of rifampin-sensitive RNA synthesis or cell mass increase. In the dnaC2 mutant, the capacities for both initiations were achieved in the absence of extensive DNA replication at 25 degrees C as long as protein synthesis was permitted, but the cells did not progress toward the second initiation at 25 degrees C when both protein synthesis and DNA replication were prevented. Cells of the dnaA5 mutant did not achieve the capacity for the second initiation event in the absence of extensive chromosome replication, although delayed initiation may have taken place. A plausible hypothesis to explain the data is that the minimum interval is determined by the time required for formation of a supercoiled, membrane-attached structure in the vicinity of oriC which is required for initiation of DNA synthesis.


Copper catalyzed enantioselective intramolecular aminooxygenation of alkenes.
The copper-catalyzed enantioselective intramolecular aminooxygenation of alkenes is reported herein. This is the first report of an enantioselective intramolecular alkene aminooxygenation process. N-Arylsulfonyl-2-allylanilines and 4-pentenylarylsulfonamides cyclize in high yield and with good enantioselectivity, providing new chiral methyleneoxy-functionalized dihydroindolines and pyrrolidines. Tetramethylaminopyridyl radical (TEMPO) serves as both the source of the oxygen and the stoichiometric oxidant. These reactions are catalyzed by copper(II) triflate, complexed with (4S,5R)-Bis-Phbox. The unprotected aminoalcohols can be obtained by sequential dissolving metal reductions of the N-S and O-N bonds.


Attitudes of and influences on residents in English Canadian radiology programs regarding interventional radiology: results of a national survey by the Canadian Interventional Radiology Association (CIRA).
There has been a North American trend toward reduced application to the subspecialty of Interventional Radiology (IR). Out of fear of a looming manpower shortage, this survey was conducted to better understand awareness and attitudes toward IR by radiology residents-in-training. An anonymous online survey was emailed to the Diagnostic Radiology Residency Program Director/Department Chairperson of each of the 13 English medical schools in Canada, to be forwarded to each respective Radiology Residency Program's radiology residents. The survey was open for a period of 1 month. The survey consisted of 29 questions, which could be answered online using a web-based program. Responses to questions were tabulated and comments recorded. A total of 84 survey responses were received of a possible 333 (25%), including responses from each of the 13 English Programs. Responses regarding demographics, training, careers aspirations and motivations, and influences were collected. Fifty-one percent of respondents reported being either "moderately" or "very" interested in the field of IR; however, only 13% reported intention to perform an IR fellowship. A number of issues were identified as dissuading current radiology residents from pursuing IR, including income, work hours and hours of on-call, and turf issues. A number of issues were identified as factors which prevented residents with an interest in IR from applying to IR fellowships. These must be addressed to increase IR recruitment rates of radiology residents.


Trap-Integrated Superconducting Nanowire Single-Photon Detectors with Improved RF Tolerance for Trapped-Ion Qubit State Readout.
State readout of trapped-ion qubits with trap-integrated detectors can address important challenges for scalable quantum computing, but the strong rf electric fields used for trapping can impact detector performance. Here, we report on NbTiN superconducting nanowire single-photon detectors (SNSPDs) employing grounded aluminum mirrors as electrical shielding that are integrated into linear surface-electrode rf ion traps. The shielded SNSPDs can be operated at applied rf trapping potentials of up to 54 Vpeak at 70 MHz and temperatures of up to 6 K, with a maximum system detection efficiency of 68 %. This performance should be sufficient to enable parallel high-fidelity state readout of a wide range of trapped ion species in typical cryogenic apparatus.


Expression of a mutated form of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO).
Phosphatidylinositol (PI) 3-kinase plays an important role in a variety of biological processes, including proliferation and apoptosis. PI3-kinase is a heterodimer consisting of an 85 kDa adapter protein (p85) containing one SH3 domain and two SH2 domains and a 110 kDa catalytic subunit (p110). Recently an oncogenic form of p85 named p65-PI3K lacking the C-terminal SH2 domain has been cloned from an irradiation-induced murine thymic lymphoma and transgenic mice expressing p65-PI3K in T lymphocytes develop a lymphoproliferative disorder. Here we describe the cloning of a C-terminal truncated form of p85 expressed in a human lymphoma cell line (CO) with a T cell phenotype derived from a patient with Hodgkin's disease. As a result of a frame-shift mutation at amino acid 636, p76 is lacking most of the C-terminal SH2 domain, but contains the inter-SH2 domain and is associated with an active form of PI3-kinase. A PI3-kinase-dependent constitutive activation of Akt was detected in CO cells which was only partially reduced after serum starvation. Treatment of CO cells with the PI3-kinase inhibitor wortmannin resulted in a concentration-dependent inhibition of cell proliferation associated with an increased number of apoptotic cells. This is the first detection of a mutated form of the p85 subunit of PI3-kinase in human hematopoietic cells further underlining a potential role of PI3-kinase/Akt signaling in human leukemogenesis.


Underestimated risk from ozonation of wastewater containing bromide: Both organic byproducts and bromate contributed to the toxicity increase.
Ozonation is widely used in wastewater treatment but the associated byproduct formation is a concern. When ozonation is used in the presence of bromide, bromate is generally considered as a major byproduct, and few studies have examined the toxicity of organic byproducts. This study was designed to investigate the cytotoxicity, genotoxicity and DNA/RNA oxidative damage to Chinese hamster ovary (CHO) cells of organic extracts from ozonated wastewater in the absence or presence of bromide. Ozonation effectively detoxified secondary effluents containing no bromide. However, ozonation significantly increased the cytotoxicity and genotoxicity of the effluents spiked with a bromide concentration as low as 100 μg/L, compared with the bromide-free effluent. When the bromide concentration in the effluent was increased to 2000 μg/L, ozonation resulted in 1.4-1.5 times the cytotoxicity and 1.5-5.0 times the genotoxicity of the non-ozonated secondary effluent. Besides, the oxidative stress (including reactive oxygen species and reactive nitrogen species) and DNA/RNA oxidative damage also became more severe and a high level of 8-hydroxy-(deoxy)guanosine was detected in the CHO cell nucleus in the presence of bromide. Cytotoxicity and genotoxicity were found to increase with the formation of total organic bromine (TOBr). When the CHO cells were exposed to both the organic byproducts and bromate formed from wastewater containing 500 and 2000 μg/L bromide, bromate significantly increased oxidative stress and DNA/RNA oxidative damage at relatively high concentration factors, suggesting both organic byproduct and bromate can contribute to toxicity increase. During ozonation of the effluent containing bromide, particular attention should be paid to the organic byproducts such as TOBr.


Differential effect of gender on the sizes of the bones in the axial and appendicular skeletons.
Recent observations suggest that throughout life the size of the vertebral bodies in females is smaller than that in males even after accounting for differences in body size. To confirm these reports and to determine whether similar differences exist in the appendicular skeleton, detailed measurements of the sizes of the vertebrae and the femur were obtained using computed tomography in 30 pairs of prepubertal boys and girls matched for age, height, and weight. Anthropometric parameters as well as gender influenced the cross-sectional area of the vertebrae. Heavier children had greater vertebral cross-sectional area than slender children regardless of gender, and the vertebral bodies were found to be significantly smaller in girls than in matched boys (approximately 11%), both using Student's t test (P < 0.0001) and its multivariate analog, the Hotelling's T2 test (P < 0.0001). In contrast to these findings in the axial skeleton, gender status did not influence the size of the bones in the appendicular skeleton, and neither the cross-sectional area (3.28 +/- 0.84 vs. 3.10 +/- 0.56 cm2) nor the cortical bone area (1.80 +/- 0.37 vs. 1.85 +/- 0.36 cm2) at the midshaft of the femur differed between boys and girls. These values, however, correlated strongly with all anthropometric indexes, and multiple regression analyses indicated that both measurements were primarily related to weight. The results suggest that although increases in mechanical loading associated with growth are the main determinant of the cross-sectional properties of the appendicular skeleton in children, factors other than body mass and related to gender have a significant role in the regulation of the sizes of the bones in the axial skeleton.


Self-reported hepatitis C(HCV) testing among people living with human immunodeficiency virus (PLWH).
We aimed to identify disparities in self-reported HCV testing among persons living with HIV (PLWH) in Florida. We utilized a cross-sectional study of 646 PLWH from the Florida Cohort study's baseline survey. Our analysis included chi-squared tests and logistic regression. Participants that were 55 years old or above had more than twice the odds of reporting a past HCV test than those 18-34 years old (OR 2.47, 95% CI 1.22-5.0), which contrasted with Non-Hispanic Blacks who had lower odds of reporting a past HCV test than non-Hispanic Whites (OR 0.63, 95% CI 0.35-1.1). Drug use was also associated with higher odds of reporting a past HCV test for injection drugs (OR 2.9, 95% CI 1.0-8.43) and non-injection drugs (OR 1.52 CI 0.99-2.21). Individuals with education beyond high school had higher odds of reporting a past HCV test than those that did not attend/complete high school (OR 1.9 CI 1.11-3.16). Our findings highlight the success of the Center for Disease Control and the U.S. Preventive Services Task Force's campaign in groups at high risk of HCV, such as baby boomers and Injection Drug Users (IDUs). However, they also reflect the current low HCV testing in PLWH that are 18-34 years old, have a low level of education, and are non-Hispanic Black. Our findings are of crucial public health significance because untreated HCV in PLWH is a major cause of severe liver disease and death. They reveal the current deficiencies in HCV testing, which is the initial step to identify underlying reasons for inadequate testing in specific groups and develop practical solutions.


The national determinants of deforestation in sub-Saharan Africa.
For decades, the dynamics of tropical deforestation in sub-Saharan Africa (SSA) have defied easy explanation. The rates of deforestation have been lower than elsewhere in the tropics, and the driving forces evident in other places, government new land settlement schemes and industrialized agriculture, have largely been absent in SSA. The context and causes for African deforestation become clearer through an analysis of new, national-level data on forest cover change for SSA countries for the 2000-2005 period. The recent dynamic in SSA varies from dry to wet biomes. Deforestation occurred at faster rates in nations with predominantly dry forests. The wetter Congo basin countries had lower rates of deforestation, in part because tax receipts from oil and mineral industries in this region spurred rural to urban migration, declines in agriculture and increased imports of cereals from abroad. In this respect, the Congo basin countries may be experiencing an oil and mineral fuelled forest transition. Small farmers play a more important role in African deforestation than they do in southeast Asia and Latin America, in part because small-scale agriculture remains one of the few livelihoods open to rural peoples.


Mutagenicity, clastogenicity and cytotoxicity of procarcinogens in a rat hepatoma cell line competent for xenobiotic metabolism.
The present studies were aimed at evaluating the suitability of the differentiated Reuber hepatoma cells H4IIEC3/G- for monitoring permanent damage to the DNA caused by hepatotrophic chemicals. First we determined the profile of xenobiotic metabolizing enzymes. The cells expressed various cytochrome P-450-dependent monooxygenases, UDP-glucuronosyl-, phenol sulpho- and glutathione S-transferase, cytochrome c (P-450) reductase and carboxylesterases. We then established the conditions for genotoxicity testing in H4IIEC/G- cells. Induction of resistance against 6-thioguanine and appearance of micronuclei served as indicators for mutagenicity and clastogenicity, respectively. 6-Thioguanine-resistant H4IIEC3/G- cells were phenotypically stable for at least 30 cell cycles; recovery of 6-thioguanine-resistant cells was not significantly affected by the number of cells seeded for mutant selection up to at least 10(6) cells/100-mm dish; expression time of chemically induced mutants was 12-15 days; a period of 24 h after treatment appeared to be sufficient to allow for the formation of micronuclei. Finally we tested the genotoxic effects of promutagens which are typically activated or inactivated in liver. Aflatoxin B1, N-nitrosodiethylamine and cyclophosphamide were genotoxic to H4IIEC3/G- cells at concentrations of 10-30 nM, 2-20 mM and 1 mM, respectively. N-Nitrosodimethylamine and benzo[a]pyrene were not or only weakly cytotoxic and genotoxic to the cells, but this appears most likely to be due to protective mechanisms rather than to lack of metabolic activation. The results indicate that differentiated hepatoma cells such as H4IIEC3/G- offer a means of studying the potential of chemicals for inducing permanent DNA damage in liver cells.


Current options for the treatment of impetigo in children.
Impetigo contagiosa is a common, superficial, bacterial infection of the skin characterised by an inflamed and infected epidermis caused by Staphylococcus aureus, Streptococcus pyogenes or both. The less common bullous impetigo is characterised by fragile fluid-filled vesicles and flaccid blisters, and is invariably caused by pathogenic strains of S. aureus. In bullous impetigo, exfoliative toxins are produced, although these are restricted to the area of infection and bacteria can be cultured from the blister contents. In the rare variant, staphylococcal scalded skin syndrome, the exfoliative toxins are spread haematogenously from a localised source causing widespread epidermal damage at distant sites.


Suppression of Mammary Carcinogenesis Through Early Exposure to Dietary Lipotropes Occurs Primarily In Utero.
The study determined whether feeding during lactation affects the suppressive effect of maternal dietary lipotropes (i.e., methionine, choline, folate, and vitamin B12) on mammary carcinogenesis. Pregnant Sprague-Dawley rats were randomly allocated to the control diet during pregnancy and lactation (CC), lipotropes-fortified diet during pregnancy (LC), lipotropes-fortified diet during pregnancy plus lactation (LL), or lipotropes-fortified diet during lactation (CL). Randomly selected female offspring from each group were injected intraperitoneally with 50 mg/kg body weight of N-nitroso-N-methylurea at 50 days of age to induce mammary tumors. The LC and LL diets significantly increased tumor latency and survival (P < 0.05). Tumor volumes were significantly suppressed in LC and LL offspring as compared with the CC and CL pups (3759.1 ± 563.0 and 3603.7 ± 526.1 vs. 7465.0 ± 941.1 and 5219.3 ± 759.8 mm(3), respectively; P < 0.05). Both LC and LL lowered tumor multiplicity as compared with CC and CL (P < 0.05). The LC and LL diets repressed transcription of histone deacetylase (HDAC) 1 as well as total HDAC enzyme activity as compared with CC and CL diets (P < 0.05). Data suggest that the tumor suppressive effect of maternal dietary lipotropes is primarily in utero and may be linked to regulation of proteins involved in chromatin remodeling.


The impact of duplex scanning in phlebology.
Chronic venous disease (CVD) is a tremendous medical and economic burden on society. In the past two decades the use of duplex ultrasound has emerged as the diagnostic method of choice for the diagnosis and management of CVD. In this article, we describe the specific techniques used in the assessment of the superficial, perforating, and deep venous systems. We also discuss the methods of ulcer bed and chronic obstruction evaluation. The contributions of the duplex ultrasound to the understanding of the pathophysiology and improvement of treatments for chronic venous disease are reviewed.


Characteristics of and calcium requirements for histamine release from rat peritoneal mast cells treated with concanavalin A.
Concanavalin A (Con A) produced a selective release of histamine from rat peritoneal mast cells in the presence and absence of added calcium. Secretion under both conditions was enhanced by adenosine, but only the former release was potentiated by phosphatidyl serine (PS). The latter release was abolished by depletion of intracellular reservoirs of calcium and probably reflected mobilization of these stores. A brief exposure to chelating agents enhanced the response to Con A whereas supramaximal concentration of calcium depressed the response. This result suggests that superficial calcium-stores in the membrane may regulate movement of the cation into the cytosol. The activated state induced by Con A and PS was particularly stable and did not decay with time over a 30 min period. The kinetics of the release process were independent of added calcium, indicating that calcium-translocation is not the rate-limiting step in the exocytotic mechanism.


Squamous cell carcinoma and meningomyelocele.
A case of invasive squamous cell carcinoma arising in the skin overlying a large lumbar meningomyelocele is reported. This case is unique in that a chronic neurocutaneous fistula was not present. It is proposed that chronic irritation of the meningomyelocele was the primary factor in the pathogenesis of the cancer.


Interventions to improve patient comprehension in informed consent for medical and surgical procedures: a systematic review.
Patient understanding in clinical informed consent is often poor. Little is known about the effectiveness of interventions to improve comprehension or the extent to which such interventions address different elements of understanding in informed consent. . To systematically review communication interventions to improve patient comprehension in informed consent for medical and surgical procedures. Data Sources. A systematic literature search of English-language articles in MEDLINE (1949-2008) and EMBASE (1974-2008) was performed. In addition, a published bibliography of empirical research on informed consent and the reference lists of all eligible studies were reviewed. Study Selection. Randomized controlled trials and controlled trials with nonrandom allocation were included if they compared comprehension in informed consent for a medical or surgical procedure. Only studies that used a quantitative, objective measure of understanding were included. All studies addressed informed consent for a needed or recommended procedure in actual patients. Data Extraction. Reviewers independently extracted data using a standardized form. All results were compared, and disagreements were resolved by consensus. Data Synthesis. Forty-four studies were eligible. Intervention categories included written information, audiovisual/multimedia, extended discussions, and test/feedback techniques. The majority of studies assessed patient understanding of procedural risks; other elements included benefits, alternatives, and general knowledge about the procedure. Only 6 of 44 studies assessed all 4 elements of understanding. Interventions were generally effective in improving patient comprehension, especially regarding risks and general knowledge. Limitations. Many studies failed to include adequate description of the study population, and outcome measures varied widely. . A wide range of communication interventions improve comprehension in clinical informed consent. Decisions to enhance informed consent should consider the importance of different elements of understanding, beyond procedural risks, as well as feasibility and acceptability of the intervention to clinicians and patients. Conceptual clarity regarding the key elements of informed consent knowledge will help to focus improvements and standardize evaluations.


Psychological aspects of bereavement in adults: preliminary development of the bereavement experiences index.
This study's aim was to produce a measure of the cognitive and affective impact of bereavement and to investigate the psychometric properties and potential utility of the measure. Using a mixed correlational and comparative design, the bereavement experiences of widows who had time to anticipate their partner's death were compared with those who had no such time. In the first stage of this two-stage study, seven widows completed semi-structured interviews regarding bereavement-related cognitions and affect. A set of bereavement-related statements was derived and formed the Bereavement Experiences Index (BEI). In the second stage, the BEI and a measure of psychological disturbance were administered to 20 additional widows. Unexpected bereavement led to greater psychological impact than expected loss although longer periods of expectation were positively correlated with higher levels of grief-related social dysfunction symptoms. This preliminary version of the BEI showed potential as a measure of grief responses with predictable links to psychological distress. The findings suggested a relationship between the time available to prepare for a loss and the development of psychological disturbance.


[Are risk factors in prenatal and perinatal period important for develompent of schizophrenia?]
Schizophrenia is an important psychical disease of multifactorial origin and not yet clear etiology. In prenatal and perinatal period some potential risk factors for schizophrenia are taken into consideration. Case-control study of 815 subjects, 407 cases and 408 controls was performed in 2013 to 2015. In this study environmental and genetic risk factors were evaluated including potential risk factors of prenatal and perinatal period. Statistically important difference was found in child-birth done by cesarean section (p = 0.009) and in patients with schizophrenia were 15.7% complications in the course of childbirth (p < 0.001). Hypoxia, passed umbilical cord were the most frequent complications. In prenatal period premature childbirth, injury and psychical complications were the most frequent. On the other hand difference in weight and length of newborns, breast feeding and infection during pregnancy were found not statistically important. In this study statistically important diference were found in way of carrying childbirth and in some complications during pregnancy and delivery. Influence of infection during pregnancy and influence of weight and length of newborn were not demonstrated.


[Consensus document about the nutritional evaluation and management of eating disorders: anorexia nervosa, bulimia nervosa, binge eating disorder, and others].
Eating disorders (ED) are characterized by persistent changes in eating habits that negatively affect a person's health and psychosocial abilities. They are considered psychiatric disorders, highly variable in their presentation and severity, with a huge impact on nutrition, which conditions various therapeutic approaches within a key multidisciplinary context. A group of experts in nutrition, we decided to set up a task force adscribed to the "Sociedad Española de Nutrición Parenteral y Enteral" (SENPE), which has stated as one of its goals the development of a consensus document to generate a protocol based on the best scientific evidence and professional experience available in order to improve health care in this field.


Ecumenical in spite of ourselves: a Protestant assessment of Roman Catholic, Eastern Orthodox, and Anglican Catholic approaches to bioethics.
A Christian approach to the issues that constitute bioethics is inevitable for us who cherish the truth of historic, creedal, trinitarian Christianity. Scripture teaches and the Greek and Latin Church Fathers as well as the Reformers aver that man, created in the image of God, has an inherent, if vestigial, sense of right and wrong and a conscience however marred by the fall and by rebellion. We must believe that we share this most basic ecumenism with all humanity, not because of rational observation and analysis of nature, but because Scripture reveals it. We who are convinced of the truth of historic, creedal, trinitarian Christianity have a high view of Scripture and hold it to be infallible and utterly trustworthy irrespective of the importance we assign to our specific post-biblical traditional distinctives. This is a narrower but much more vital ecumenism than the first. Faithful adherence to Scripture inevitably manifests itself in remarkably similar priorities and values, often, lamentably, not because of, but in spite of, ourselves.


Prevalence and risk factors of HIV and syphilis, and knowledge and risk behaviors related to HIV/AIDS among men who have sex with men in Chongqing, China.
High HIV prevalence and incidence burdens have been reported in men who have sex with men (MSM) in Chongqing, China. We aimed to estimate the prevalence of HIV and other sexually transmitted infections (STIs), to appraise the knowledge and risk behaviors related to HIV/AIDS among MSM, and to analyze the possible causes of deviation between behavior and knowledge to make better strategies. We recruited 617 MSM from February to July in 2008 by using a respondent-driven sampling (RDS) method in Chongqing, China. Through the collection of questionnaire-based data and biological testing results from all objects, we launched a cross-sectional survey. STATA/SE was used for data analysis by frequency, ANOVA, rank sum test and logistic regression models. MSM with syphilis (OR=4.16, 95%CI: 2.35-7.33, P<0.0001) were more likely to be HIV infected. Being a company employee (OR=3.64, 95%CI: 1.22-10.08, P<0.0001) and having bought male for sex (OR=3.52, 95%CI: 1.10-11.32, P<0.034) were associated with a higher probability of syphilis. MSM with younger age, higher education and greater monthly income had a higher mean knowledge score. MSM who had HIV testing had a higher mean knowledge score than those who never had. Students, venues for finding sex partners by Internet and homosexuals in MSM had a higher mean knowledge score compared to other occupations, venues for finding sex partners and sexual orientation. There is an urgent need for delivery of barrier and biomedical interventions with coordinated behavioral and structural strategies to improve the effect of HIV interventions among MSM.


Characteristics of bilateral hand function in individuals with unilateral dystonia due to perinatal stroke: sensory and motor aspects.
The authors assessed bilateral motor and sensory function in individuals with upper limb dystonia due to unilateral perinatal stroke and explored interrelationships of motor function and sensory ability. Reach kinematics and tactile sensation were measured in 7 participants with dystonia and 9 healthy volunteers. The dystonia group had poorer motor (hold time, reach time, shoulder/elbow correlation) and sensory (spatial discrimination, stereognosis) outcomes than the control group on the nondominant side. On the dominant side, only sensation (spatial discrimination, stereognosis) was poorer in the dystonia group compared with the control group. In the dystonia group, although sensory and motor outcomes were uncorrelated, dystonia severity was related to poorer stereognosis, longer hold and reach times, and decreased shoulder/elbow coordination. Findings of bilateral sensory deficits in dystonia can be explained by neural reorganization. Visual compensation for somatosensory changes in the nonstroke hemisphere may explain the lack of bilateral impairments in reaching.


Home range size, vegetation density, and season influences prey use by coyotes (Canis latrans).
To ensure reproductive success, Canis species establish contiguous mosaics of territories in suitable habitats to partition space and defend limiting resources. Consequently, Canis species can exert strong effects on prey populations locally because of their year-round maintenance of territories. We assessed prey use by coyotes (Canis latrans) by sampling scats from within known territories in southeastern Alabama and the Savannah River area of Georgia and South Carolina. We accounted for the size and habitat composition of coyote home ranges to investigate the influence of space use, vegetation density, and habitat type on coyote diets. Coyote use of prey was influenced by a combination of mean monthly temperature, home range size, vegetation density, and hardwood forests. For example, coyote use of adult white-tailed deer (Odocoileus virginianus) was associated with cooler months and smaller home ranges, whereas use of rabbits (Sylvilagus spp.) was associated with cooler months, larger home ranges, and less vegetation density. Coyotes in our study relied primarily on nutritionally superior mammalian prey and supplemented their diet with fruit when available, as their use of mammalian prey did not appreciably decrease with increasing use of fruit. We suggest that differential use of prey by coyotes is influenced by habitat heterogeneity within their home ranges, and prey-switching behaviors may stabilize local interactions between coyotes and their food resources to permit stable year-round territories. Given that habitat composition affects coyote prey use, future studies should also incorporate effects of habitat composition on coyote distribution and abundance to further identify coyote influences on prey communities.


Withdrawal of care: a 10-year perspective at a Level I trauma center.
Withdrawal or limitation of care (WLC) in trauma patients has not been well studied. We reviewed 10 years of deaths at our adult Level I trauma center to identify the patients undergoing WLC and to describe the process of trauma surgeon-managed WLC. This is a retrospective review of WLC. Each patient was assigned to one of three modes of WLC: care withdrawn, limited or no resuscitation, or organ harvest. Frequency, timing, and circumstances of WLC, including family involvement, ethics committee consultation, palliative care, and hospice, were reviewed. From 2000 through 2009, 375 patients died with WLC (54% of all deaths; 93% at ≥ 24 hours). For age ≥ 65 years, 80% were WLC. Overall, 15% had advance directive documents. Traumatic brain or high cervical spine injury was the cause of death in 63%. Factors associated with WLC included age, comorbidities, injury mechanism and severity, and nontrauma activation status. At time of death, 316 (84%) WLC were under trauma surgeon management. In this group, mode of WLC was care withdrawn in 74%, organ harvest in 20%, and limited or no resuscitation in 6%. Rationale for WLC in non-organ harvest patients was poor neurologic prognosis in 86% and futility in 76%. When family was identified, end-of-life discussions with physicians occurred in 100%. Conflicts over WLC occurred in 6.6% and were not associated with any demographic group. Ethics committee was involved in 2.8%. For care-withdrawn patients, median time to death from first WLC order was 6.6 hours. Palliative care and hospice consults (6% and 9%) increased yearly. WLC occurred in over 50% of all trauma deaths and exceeded 90% at ≥ 24 hours. Hospice and palliative care were increasingly important adjuncts to WLC. Guidelines for WLC should be developed to ensure quality end-of-life care for trauma patients in whom further care is futile. III, therapeutic study.


FungiProteomeDB: a database for the molecular weight and isoelectric points of the fungal proteomes.
Proteins' molecular weight (MW) and isoelectric point (pI) are crucial for their subcellular localization and subsequent function. These are also useful in 2D gel electrophoresis, liquid chromatography-mass spectrometry and X-ray protein crystallography. Moreover, visualizations like a virtual 2D proteome map of pI vs. MW are worthwhile to discuss the proteome diversity among different species. Although the genome sequence data of the fungi kingdom improved enormously, the proteomic details have been poorly elaborated. Therefore, we have calculated the MW and pI of the fungi proteins and reported them in, FungiProteomeDB, an online database (DB) https://vision4research.com/fungidb/. We analyzed the proteome of 685 fungal species that contain 7 127 141 protein sequences. The DB provides an easy-to-use and efficient interface for various search options, summary statistics and virtual 2D proteome map visualizations. The MW and pI of a protein can be obtained by searching the name of a protein, a keyword or a list of accession numbers. It also allows querying protein sequences. The DB will be helpful in hypothesis formulation and in various biotechnological applications. Database URL https://vision4research.com/fungidb/.


Origin of worldwide cultivated barley revealed by NAM-1 gene and grain protein content.
The origin, evolution, and distribution of cultivated barley provides powerful insights into the historic origin and early spread of agrarian culture. Here, population-based genetic diversity and phylogenetic analyses were performed to determine the evolution and origin of barley and how domestication and subsequent introgression have affected the genetic diversity and changes in cultivated barley on a worldwide scale. A set of worldwide cultivated and wild barleys from Asia and Tibet of China were analyzed using the sequences for NAM-1 gene and gene-associated traits-grain protein content (GPC). Our results showed Tibetan wild barley distinctly diverged from Near Eastern barley, and confirmed that Tibet is one of the origin and domestication centers for cultivated barley, and in turn supported a polyphyletic origin of domesticated barley. Comparison of haplotype composition among geographic regions revealed gene flow between Eastern and Western barley populations, suggesting that the Silk Road might have played a crucial role in the spread of genes. The GPC in the 118 cultivated and 93 wild barley accessions ranged from 6.73 to 12.35% with a mean of 9.43%. Overall, wild barley had higher averaged GPC (10.44%) than cultivated barley. Two unique haplotypes (Hap2 and Hap7) caused by a base mutations (at position 544) in the coding region of the NAM-1 gene might have a significant impact on the GPC. Single nucleotide polymorphisms and haplotypes of NAM-1 associated with GPC in barley could provide a useful method for screening GPC in barley germplasm. The Tibetan wild accessions with lower GPC could be useful for malt barley breeding.


Obstructive sleep apnoea and obesity.
Obstructive sleep apnoea (OSA) and obesity are two common conditions affecting the Australian population; obesity is the major risk factor for OSA. The objectives of this article are to review the interactions between obesity and OSA, including the increased cardiovascular risk, and highlight the importance of using OSA diagnosis as a critical time to address obesity itself and other cardiovascular risk factors. Snoring and symptoms of OSA frequently worsen during periods of rapid weight gain. Obesity and metabolic factors (eg hypertension, hyperlipidaemia, insulin resistance) are commonly present at the time of OSA diagnosis. Severe OSA is an independent risk factor for cardiovascular disease and stroke. Continuous positive airway pressure (CPAP) treatment is safe and effective, reduces sleepiness, and improves mood and quality of life; however, the cardiovascular benefits of CPAP are uncertain. Weight loss leads to variable improvement in OSA, is most effective in milder OSA, and has a greater benefit on cardiovascular risk than CPAP.


Polyphenols: Natural Preservatives with Promising Applications in Food, Cosmetics and Pharma Industries; Problems and Toxicity Associated with Synthetic Preservatives; Impact of Misleading Advertisements; Recent Trends in Preservation and Legislation.
The global market of food, cosmetics, and pharmaceutical products requires continuous tracking of harmful ingredients and microbial contamination for the sake of the safety of both products and consumers as these products greatly dominate the consumer's health, directly or indirectly. The existence, survival, and growth of microorganisms in the product may lead to physicochemical degradation or spoilage and may infect the consumer at another end. It has become a challenge for industries to produce a product that is safe, self-stable, and has high nutritional value, as many factors such as physical, chemical, enzymatic, or microbial activities are responsible for causing spoilage to the product within the due course of time. Thus, preservatives are added to retain the virtue of the product to ensure its safety for the consumer. Nowadays, the use of synthetic/artificial preservatives has become common and has not been widely accepted by consumers as they are aware of the fact that exposure to preservatives can lead to adverse effects on health, which is a major area of concern for researchers. Naturally occurring phenolic compounds appear to be extensively used as bio-preservatives to prolong the shelf life of the finished product. Based on the convincing shreds of evidence reported in the literature, it is suggested that phenolic compounds and their derivatives have massive potential to be investigated for the development of new moieties and are proven to be promising drug molecules. The objective of this article is to provide an overview of the significant role of phenolic compounds and their derivatives in the preservation of perishable products from microbial attack due to their exclusive antioxidant and free radical scavenging properties and the problems associated with the use of synthetic preservatives in pharmaceutical products. This article also analyzes the recent trends in preservation along with technical norms that regulate the food, cosmetic, and pharmaceutical products in the developing countries.


Is the GnRH Antagonist Protocol Effective at Preventing OHSS for Potentially High Responders Undergoing IVF/ICSI?
To determine if the GnRH antagonist protocol is effective in preventing ovarian hyperstimulation syndrome (OHSS) in potentially high responders. A total of 660 IVF-ET/ICSI cycles were retrospectively identified. The inclusion criterion was age ≤ 30 years. Cycles were divided into two groups: a GnRHa group and a GnRHant group. In the GnRHa group, the patients received one single injection of 1.0mg-1.3mg Triptorelin in previous mid-luteal phase. In the GnRHant group, a daily dose of 0.25 mg Cetrotide was initiated when a lead follicle obtained a mean diameter of 14 mm, continued up until the day of hCG administration. The duration of stimulation, total dose of Gn, implantation rate, pregnancy rate, and OHSS rate were compared. The duration of stimulation, E2 level on hCG day, numbers of oocytes retrieved, MII oocytes, and high-quality embryos in the GnRHa group were all significantly more than those in the GnRHant group. In the GnRHa group, 83.53% of cancelled fresh-transferred cycles were cancelled because of high risk of OHSS, which was significantly higher than that in the GnRHant group (43.55%, P<0.05). The incidence of OHSS in the GnRHa group was slightly higher than that in the GnRHant group. The implantation and clinical pregnancy rates in the GnRHa group were significantly higher than those in the GnRHant group (37.36% VS 19.25%, 62.78% VS 31.06%; P<0.05). Our study demonstrated that for potentially high responders, the GnRHant protocol can, to some extent, lower the cancellation and incidence rates of OHSS. The GnRHa protocol was superior to the GnRHant protocol in terms of implantation and clinical pregnancy rates.


Low levels of hybridization in two species of African driver ants.
Hybridization in ants can have consequences different from those observed in most other species, with many of the potential deleterious effects being mitigated due to haplodiploidy and eusociality. In some species where colonies are either headed by multiple queens or single queens that mate with many males, hybridization is associated with genetic caste determination, where hybrids develop into workers and purebred individuals develop into queens. A previous study suggested that hybridization occurs between two Dorylus army ant species with multiply mated queens. However, the extent and exact pattern of hybridization have remained unclear, and its possible effect on caste determination has not been investigated. In this study, we aimed to determine the extent and direction of hybridization by measuring how frequently hybrids occur in colonies of both species, and to investigate the possibility of genetic caste determination. We show that hybridization is bidirectional and occurs at equal rates in both species. Hybrid workers make up only 1-2% of the population, and successful interspecific matings represent approximately 2% of all matings in both species. This shows that, although interspecific matings that give rise to worker offspring occur regularly, they are much rarer than intraspecific mating. Finally, we find no evidence of an association between hybridization and genetic caste determination in this population. This means that genetic caste determination is not a necessary outcome of hybridization in ants, even in species where queens mate with multiple males.


Surgical scientific publication and the 1991-1995 war in Croatia.
The aim of this study was to evaluate surgical scientific publication in relation to the 1991-1995 war in Croatia, based on the articles indexed in Medline database that were published in 1980-2005 period. The number of articles was extracted from PubMed and analysed with trend analysis, which is preferred analytic approach over calculation of crude publication rates. The results indicate sporadic pre-war output, which was almost completely reduced by the onset of war. During wartime, a significant increasing trend in the number of published surgical articles that were related to warfare was detected (p = 0.003). During the post-war period a gradual shift towards surgical articles that were not related to warfare was detected, also marked by the significant increasing trend (p = 0.027). Both trends were significantly steeper than the overall Croatian biomedical output, suggesting that surgical scientific articles were being published more dynamically than in other biomedical areas in Croatia. The results suggest that war in Croatia has had a strong modifying effect on the surgical scientific output.


[Single-cell RNA sequencing deciphers transcriptional profiles of hepatocytes in mouse with hepatic alveolar echinococcosis].
To investigate the cell composition and the transcriptional characteristics in microenvironments of hepatic tissues in mice at late stage of Echinococcus multilocularis infection at a single-cell level. Peri-lesion and paired distal hepatic specimens were collected from two BALB/c mice (6 to 8 weeks old) infected with E. multilocularis for single-cell RNA sequencing. The Seurat package in the R software was employed for quality control of data, multi-sample integration and correction of batch effects, and uniform manifold approximation and projection (UMAP) algorithm was used for cell clustering. Cell types were annotated using classical marker genes. Differentially expressed genes were screened in each cell type through differential gene expression analysis, and the biological roles of cells were predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A total of 43 710 cells from peri-lesion and distal hepatic tissues of E. multilocularis-infected mice were analyzed, and were classified into 11 cell types, including neutrophils, T cells, macrophages, granulocyte-monocyte progenitor cells, B cells, plasma cells, basophils, hepatic stellate cells, endothelial cells, hepatocytes, and platelets. T cells were the largest population of immune cells in the microenvironment of hepatic tissues, including five CD4+ T cell subsets, two CD8+ T cell subsets and phosphoantigen-reactive γδT cells. The proportions of CD4+ helper T cells and cytotoxic CD4+ T cells decreased and the proportion of T helper 2 (Th2) cells increased in peri-lesion tissues relative to distal hepatic tissues. In addition, the differentially expressed genes in Th2 cells were associated with negative regulation of the immune system, and the highly expressed genes in cytotoxic CD4+ T cells correlated with activation of the immune system. Single-cell RNA sequencing deciphers the cell composition and distribution in microenvironments of hepatic tissues from mice infected with E. multilocularis, and the increased proportion of Th2 cells in peri-lesion hepatic tissues may be associated with formation of immunosuppressive microenvironments.


The nuclear magnetic resonance solution structure of flavoridin, an antagonist of the platelet GP IIb-IIIa receptor.
The snake venom protein flavoridin, a polypeptide of 70 amino acid residues, is a potent inhibitor of blood platelet aggregation. It binds to cell-surface integrin receptors such as the fibrinogen receptor glycoprotein IIb/IIIa. The inhibitory properties of flavoridin have been attributed to the tripeptide segment Arg-Gly-Asp (residues 49 to 51). This paper describes the determination of the three-dimensional structure of flavoridin in aqueous solution based on two-dimensional nuclear magnetic resonance spectroscopy. A family of 18 conformers was selected to characterize the solution structure. The molecule comprises two structural domains, an N-terminal unit extending from residues 1 to 25, and a C-terminal unit from residues 26 to 70. Whereas the mutual spatial orientation of these regions is not well defined, each one is well organized within itself. The segment 26 to 70, which is homologous to the sequence of the snake toxins echistatin and eristostatin, shows an average value of 1.0 A for the root-mean-square deviations of the backbone atoms among the 18 conformers. The structure of flavoridin consists essentially of non-repetitive elements such as tight turns and loops, whose location and conformation are characterized in this paper. With the exception of two short regions of antiparallel beta-sheet, no classic element of protein secondary structure is present. The six disulphide bridges, which have been mapped by applying a novel computational strategy (see accompanying paper), are the dominant organizational feature of the polypeptide fold of flavoridin. Two of the bridges are located in the N-terminal domain, three in the C-terminal domain and one connects the two structural units. The mobile RGD recognition sequence for integrins is located peripheral to the core region of the C-terminal domain at the most exposed end of a nine residue loop structure, which is attached to a short beta-sheet. The C terminus is close to this loop structure.


Idiopathic Pulmonary Fibrosis in Switzerland: Diagnosis and Treatment.
Idiopathic pulmonary fibrosis (IPF) is a severe progressive and irreversible lung disease. Novel antifibrotic drugs that slow disease progression are now available. However, many issues regarding patient management remain unanswered, such as the choice between available drugs, their use in particular subgroups and clinical situations, time of treatment onset, termination, combination or switch, or nonpharmacologic management. To guide Swiss respiratory physicians in this evolving field still characterized by numerous areas of uncertainty, the Swiss Working Group for interstitial and rare lung diseases of the Swiss Respiratory Society provides a position paper on the diagnosis and treatment of IPF.


Ascites in poultry: recent investigations.
In recent years, ascites research has centred on gaining an increased understanding of pulmonary hypertension syndrome together with the potential role of primary cardiac pathologies. The impact at a cellular level of factors which trigger ascites and substances that protect against it has also been documented. Primary pulmonary hypertension has been induced when birds are exposed to hypoxia during incubation. The conditions experienced during this phase of development may impact on the ability of the bird to regulate its basal metabolic rate through endocrine signals controlled by thyroid activity. The extent of ventilation in the lung influences the ability of the bird to oxygenate haemoglobin. Ventilation/ perfusion mismatches may occur prior to or post-hatching. This factor has been studied extensively using the pulmonary artery/bronchus clamp model. At high altitude, a decreased ventilation/perfusion ratio may occur following the effective increase in physiological dead space due to the lowered oxygen tension at the level of the parabronchi. This explains the mechanism by which ascites is triggered by hypoxia in this particular situation. The effects of ascites are ameliorated by the use of beta agonists and dietary arginine, which act by increasing ventilation and blood flow in the lungs and thus correcting a ventilation/perfusion mismatch. Transient bacterial and viral infections may also influence the induction of pulmonary hypertension. The increases in blood viscosity associated with ascites are most probably a consequence of the condition rather than a cause. A bird may alleviate the effects of pulmonary hypertension by decreasing blood viscosity through inhibition of platelet function, increased erythrocyte deformability and the production of coronary relaxants. Evidence is accumulating that primary cardiac pathology may be associated with a number of ascites cases. Broilers that subsequently develop ascites, exhibit lower heart rates than their normal flock mates. Furthermore, during ascites, hypoxic broilers exhibit bradycardia as opposed to the expected tachycardia. In these cases, a tachycardia induced by feed restriction may protect the bird by raising its cardiac output. Right atrio-ventricular regurgitant flow velocities in chickens are relatively slow compared with similar regurgitant flows induced by pulmonary hypertension in other species. The conduction system in the avian heart is specialized and contains a recurrent bundle branch that innervates the right atrio-ventricular valve, thus initiating active valve closure before right ventricular systole. This predisposes the heart to right ventricular volume overload through a valvular incompetance following a failure of valvular innervation. The resultant elevated diastolic wall stress can trigger the production of angiotensin II and its converting enzyme, which mediate ventricular hypertrophy. Subclinical myocardial damage, irrespective of its cause, can be detected by the presence of troponin T in the blood. Reactive oxygen species may damage cell membranes compromising cellular function in a number of body systems. A positive correlation exists between oxidized glutathione concentrations and right ventricular weight ratio. This indicates a failure to cope with oxidative stress at the level of the respiratory membrane. It is not known if it is possible to modulate levels of antioxidants at this location and hence protect the bird. The final description of the ascites aetiology may lie in the concept of a circuit of events between the cardiac, pulmonary and vascular systems that satisfy the metabolic requirements of the bird. A deficit in one of these systems, at a level that prevents adequate compensation from other components, triggers the pathological cascade that results in the end point of clinical ascites.


An unexpected switch in the modulation of AI-2-based quorum sensing discovered through synthetic 4,5-dihydroxy-2,3-pentanedione analogues.
Quorum sensing (QS) has traditionally referred to a mechanism of communication within a species of bacteria. However, emerging research implicates QS in interspecies communication and competition, and such systems have been proposed in a wide variety of bacteria. The AI-2-based QS system represents the most studied of these proposed interspecies systems, and has been proposed to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the treatment of bacterial infections and the study of unknown AI-2-based QS systems. Toward this end, we have designed and synthesized a panel of 4,5-dihydroxy-2,3-pentanedione/AI-2 analogues and evaluated their effects on the AI-2 QS of various bacteria. The panel of compounds exhibited differential effects in the bacterial cell lines examined, providing a platform for the development of broad-spectrum modulators of AI-2-based QS.


Toll-like receptor 8 deletion accelerates autoimmunity in a mouse model of lupus through a Toll-like receptor 7-dependent mechanism.
Systemic lupus erythematosus is an autoimmune disorder characterized by increased levels of lymphocyte activation, antigen presentation by dendritic cells, and the formation of autoantibodies. This leads to immune complex-mediated glomerulonephritis. Toll-like receptor 7 (T7) and TLR9 localize to the endosomal compartment and play important roles in the generation of autoantibodies against nuclear components, as they recognize RNA and DNA, respectively. In contrast, very little is known about endogenous TLR8 activation in mice. We therefore tested whether TLR8 could affect autoimmune responses in a murine model of lupus. We introduced a Tlr8 null mutation into C57BL/6 mice congenic for the Nba2 (NZB autoimmunity 2) locus and bearing the Yaa (Y-linked autoimmune acceleration) mutation containing a tlr8 duplicated gene, and monitored disease development, autoantibody production, and glomerulonephritis-associated mortality. Cellular responses were investigated in female Nba2.TLR8(-/-) mice bearing no copy of tlr8. The TLR8 deficiency accelerated disease progression and mortality, increased the number of circulating antibodies and activated monocytes, and heightened cellular responses to TLR7 ligation. TLR8-deficient antigen-presenting cells exhibited increased levels of MHC class II expression. The ability of dendritic cells to present antigens to allogeneic T cells after TLR7 ligation was also improved by TLR8 deficiency. TLR8 deletion accelerated autoimmunity in lupus-prone mice in response to TLR7 activation. Antigen-presenting cell function seemed to play a key role in mediating the effects of TLR8 deficiency.


Fifty years of somatosensory research: from the Semmes-Weinstein monofilaments to the Weinstein Enhanced Sensory Test.
In this paper, the author's long history with somatosensation is overviewed with special emphasis on the creation of objective tests of sensibility. Objective testing is discussed using numerous examples from the author's experiences. The creation of the Semmes-Weinstein monofilaments is discussed. Tests employing the Semmes-Weinstein monofilaments, two-point discrimination, and point localization are discussed with reference to the fact that these tests reflect specific differences between the central and peripheral nervous systems. Towards that end, contrasts are made between the Semmes-Weinstein esthesiometer and both the two-point discrimination and the point-localization tests. A new enhancement of the original Semmes-Weinstein monofilament test, the Weinstein Enhanced Sensory Test (WEST), is introduced. Advantages of the WEST are discussed.


Soil contamination in China: current status and mitigation strategies.
China faces great challenges in protecting its soil from contamination caused by rapid industrialization and urbanization over the last three decades. Recent nationwide surveys show that 16% of the soil samples, 19% for the agricultural soils, are contaminated based on China's soil environmental quality limits, mainly with heavy metals and metalloids. Comparisons with other regions of the world show that the current status of soil contamination, based on the total contaminant concentrations, is not worse in China. However, the concentrations of some heavy metals in Chinese soils appear to be increasing at much greater rates. Exceedance of the contaminant limits in food crops is widespread in some areas, especially southern China, due to elevated inputs of contaminants, acidic nature of the soil and crop species or cultivars prone to heavy metal accumulation. Minimizing the transfer of contaminants from soil to the food chain is a top priority. A number of options are proposed, including identification of the sources of contaminants to agricultural systems, minimization of contaminant inputs, reduction of heavy metal phytoavailability in soil with liming or other immobilizing materials, selection and breeding of low accumulating crop cultivars, adoption of appropriate water and fertilizer management, bioremediation, and change of land use to grow nonfood crops. Implementation of these strategies requires not only technological advances, but also social-economic evaluation and effective enforcement of environmental protection law.


Discovery of 4-amino and 4-hydroxy-1-aroylindoles as potent tubulin polymerization inhibitors.
1-Aroylindoline, 1-aroyl-1,2,3,4-tetrahydroquinoline, and 1-aroylindole derivatives were synthesized and evaluated for anticancer activity. The 4-amino and 4-hydroxy-1-aroylindoles 26 and 27 with IC 50 of 0.9 and 0.6 microM, respectively, exhibited antitubulin activity superior or comparable to that of colchicine and combretastatin A-4. They also showed antiproliferative activity with IC 50 of 0.3-5.4 nM in a set of human cancer cell lines.


Effect of barley straw and Egyptian clover hay on the rumen fermentation and structure and fibrolytic activities of rumen bacteria in dromedary camel.
Understanding the regulations of rumen microbiota and their fibrolytic capabilities under different forages are essential to improve rumen fermentation and animal feed efficiency. This study aimed to evaluate the changes in the rumen fermentation and the structure and fibrolytic activities of rumen bacteria in camels fed barley straw and Egyptian clover hay. Three fistulated camels were fed a diet containing barley straw for 30 days; then transitioned to a diet containing Egyptian clover hay for 30 days. In addition, bacterial media enriched with xylan and different cellulose sources, namely, filter paper, wheat straw, and alfalfa hay, were used to evaluate the ability of camel rumen bacteria to produce xylanase and cellulase enzymes. The camel group fed Egyptian clover hay showed higher crude protein intake, rumen ammonia, total volatile fatty acids, and acetic acid. Moreover, the camel group fed barley straw showed higher neutral detergent fiber intake, rumen pH, and propionic and butyric acids. Principal component analysis showed that bacterial communities were separated based on the forage type. Forage type affected the composition of rumen bacteria and most of the bacterial community was assigned to phylum Bacteroidetes and Firmicutes. Egyptian clover hay diet increased the proportions of genus Prevotella and Ruminococcus; while fed barley straw diet increased the Butyrivibrio, RC9_gut_group, and Fibrobacteres. The bacterial culture of the Egyptian clover hay fed group produced the greatest xylanase and the bacterial culture of the barley straw fed group produced the maximum cellulase. Egyptian clover hay is recommended to feed camels in intensive production. Moreover, the bacterial community in the camel rumen is a promising source of lignocellulolytic enzymes.


Reverse shoulder prosthesis: implementation and experience in Croatia.
Reverse shoulder prosthesis has become one of the most often used prosthetic implants in shoulder replacement surgery. It has a wide spectrum of indications, starting from comminuted humeral fractures and posttraumatic arthritis to arthritis caused by the rotator cuff loss. Its application at our hospital began in 2004, at first in few specific cases and with time in ever growing number of patients. Over 8 years, more than 250 reverse shoulder prostheses were implanted at our institution. In addition, our surgeons supervised its application in other hospitals all over Croatia. In the postoperative course, the shoulder was immobilized for 4-6 weeks with a thoracobrachial cast. After removal of the cast, physical therapy was initiated. The length of physical therapy program depended upon many factors. As a rule, immobilization lasted longer in patients that were operated on due to posttraumatic arthritis and those that suffered from deltoid muscle atrophy and shoulder contracture before surgery. Complications included dislocation of the prosthesis shortly after surgery (in the first four weeks) and infection. Infection was a special problem and treatment included even explantation of the prosthesis.


Simulation Analysis and Comparison of Point of Care Testing and Central Laboratory Testing.
Background. In response to demand for fast and efficient clinical testing, the use of point-of-care testing (POCT) has become increasingly common in the United States. However, studies of POCT implementation have found that adopting POCT may not always be advantageous relative to centralized laboratory testing. Methods. We construct a simulation model of patient flow in an outpatient care setting to evaluate tradeoffs involved in POCT implementation across multiple dimensions, comparing measures of patient outcomes in varying clinical scenarios, testing regimes, and patient conditions. Results. We find that POCT can significantly reduce clinical time for patients, as compared to traditional testing regimes, in settings where clinic and central testing areas are far apart. However, as distance from clinic to central testing area decreased, POCT advantage over central laboratory testing also decreased, in terms of time in the clinical system and estimated subsequent productivity loss. For example, testing for pneumonia resulted in an estimated average of 27.80 (central lab) versus 15.50 (POCT) total lost productive hours in a rural scenario, and an average of 14.92 (central lab) versus 15.50 (POCT) hours in a hospital-based scenario. Conclusions. Our results show that POCT can effectively reduce the average time a patient spends in the system for varying condition profiles and clinical scenarios. However, the number of total lost productive hours, a more holistic measure, is greatly affected by testing quality, where POCT often is at a disadvantage. Thus, it is important to consider factors such as clinical setting, target condition, testing costs, and test quality when selecting appropriate testing regime.


Comparative karyometry in Bowen's disease and bowenoid papulosis. Derivation of a nuclear atypia index.
Bowen's disease and bowenoid papulosis are two diseases that are currently viewed as low grade in situ carcinomas of the epidermis. Their distinction is sometimes disputed. We undertook a morphometric comparison of the size and shape of nuclei in these diseases. We also derived an index of nuclear atypia combining changes in the medians and coefficients of variation of nuclear areas, and variation in the nuclear contour indexes. Significant differences were found in the morphometric parameters between Bowen's disease and bowenoid papulosis. The etiology, clinical aspects and karyometric evaluations allow a distinction between these two diseases.


Case report: Novel TBX5-related pathogenic mechanism of Holt-Oram syndrome.
Introduction: Holt-Oram syndrome (HOS) is a rare genetic disorder characterized by upper limb abnormalities, congenital heart defects, and/or conduction abnormalities. Sequence alteration of T-box transcription factor 5 (TBX5) is correlated with the incidence of HOS. Case description: We present the case of a 24-year-old female with upper limb alterations (congenital dysplasia in the wrist and elbow joints) and an anomalous left main trunk arising from the right coronary sinus. The patient inherited a base T (reference C) at rs883079 from her mother and base C (reference T) at rs10850326 from her father, both of which belong to the 3'-untranslated region (UTR) of the TBX5 gene; no alterations in TBX5 expression or single-nucleotide polymorphisms (SNPs) in other exon areas were found. We explored the effects of TBX5 on cardiomyocytes using the HL-1 cell line and TBX5-knockdown cells. Discussion: Quantitative polymerase chain reaction analysis demonstrated that TEKT2, TEKT4, and SPTB expression decreased after TBX5 knockdown, while chromatin immunoprecipitation analysis further revealed that TBX5 binds to the TEKT2, TEKT4, and SPTB promoter regions to promote gene transcription. Our findings support a novel TBX5-related pathogenic mechanism in HOS.


Cross-sectional analysis of two social determinants of health in California cities: racial/ethnic and geographic disparities.
To study the magnitude and direction of city-level racial and ethnic differences in poverty and education to characterise health equity and social determinants of health in California cities. We used data from the American Community Survey, United States Census Bureau, 2006-2010, and calculated differences in the prevalence of poverty and low educational attainment in adults by race/ethnicity and by census tracts within California cities. For race/ethnicity comparisons, when the referent group (p2) to calculate the difference (p1-p2) was the non-Hispanic White population (considered a historically advantaged group), a positive difference was considered a health inequity. Differences with a non-White reference group were considered health disparities. Cities of the State of California, USA. Within-city differences in the prevalence of poverty and low educational attainment disfavoured Black and Latinos compared with Whites in over 78% of the cities. Compared with Whites, the median within-city poverty difference was 7.0% for Latinos and 6.2% for Blacks. For education, median within-city difference was 26.6% for Latinos compared with Whites. In a small, but not negligible proportion of cities, historically disadvantaged race/ethnicity groups had better social determinants of health outcomes than Whites. The median difference between the highest and lowest census tracts within cities was 14.3% for poverty and 15.7% for low educational attainment. Overall city poverty rate was weakly, but positively correlated with within-city racial/ethnic differences. Disparities and inequities are widespread in California. Local health departments can use these findings to partner with cities in their jurisdiction and design strategies to reduce racial, ethnic and geographic differences in economic and educational outcomes. These analytic methods could be used in an ongoing surveillance system to monitor these determinants of health.


Out of the frying pan and into the fire? Due diligence warranted for ADE in COVID-19.
Antibody-dependent enhancement (ADE) is an atypical immunological paradox commonly associated with dengue virus re-infection. However, various research models have demonstrated this phenomenon with other viral families, including Coronaviridae. Recently, ADE in SARS-CoV-2 has emerged as one hypothesis to explain severe clinical manifestations. Whether SARS-CoV-2 is augmented by ADE remains undetermined and has therefore garnered criticism for the improper attribution of the phenomenon to the pandemic. Thus, critical evaluation of ADE in SARS-CoV-2 vaccine development will be indispensable to avoid a global setback and the erosion of public trust.


Role of MiR-155 Signal Pathway in Regulating Podocyte Injury Induced by TGF-β1.
Transforming growth factor beta 1 (TGF-β1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of miR-155 on podocyte injury induced by TGF-β1 and to determine further molecular mediators involved in the effects of miR-155. Conditionally immortalized podocytes were cultured in vitro and they were divided into four groups: control; TGF-β1 treatment; TGF-β1 with miR-155 knockdown [using antisense oligonucleotides against miR-155 (ASO-miR-155)] and TGF-β1 with negative control antisense oligonucleotides (ASO-NC). Real time RT-PCR and Western blot analysis were employed to determine the mRNA and protein expression of nephrin, desmin and caspase-9, respectively. Flow cytometry was used to examine the apoptotic rate of podocytes and DAPI fluorescent staining was used to determine apoptotic morphology. In addition, we examined the levels of miR-155, TGF-β1, nephrin, desmin and caspase-9 in glomerular tissues of nephropathy induced by intravenous injections of adriamycin in rats. mRNA and protein expression of desmin and caspase-9 was increased in cultured TGF-β1-treated podocytes, whereas nephrin was decreased as compared with the control group. Importantly, miR-155 knockdown significantly attenuated upregulation of desmin and caspase-9, and alleviated impairment of nephrin induced by TGF-β1. Moreover, the number of apoptotic podocytes was increased after exposure to TGF-β1 and this was alleviated after miR-155 knockdown. Knocking down miR-155 also decreased an apoptosis rate of TGF-β1-treated podocytes. Note that negative control antisense oligonucleotides failed to alter an increase of the apoptosis rate in TGF-β1-treated podocytes. Consistent with in vitro results, expression of miR-155, TGF-β1, desmin and caspase-9 was increased and nephrin was decreased in glomerular tissues with nephropathy in vivo experiments. TGF-β1 impairs the protein expression of nephrin and amplifies the protein expression of desmin and caspase -9 via miR-155 signal pathway. Inhibition of miR-155 alleviates these changes in podocytes-treated with TGF-β1 and attenuated apoptosis of podocytes. Our data suggest that miR-155 plays a role in mediating TGF-β1-induced podocyte injury via nephrin, desmin and caspase-9. Results of the current study also indicate that blocking miR-155 signal has a protective effect on podocyte injury. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of podocyte injury observed in glomerulosclerosis.


Vogt-koyanagi-harada syndrome.
Vogt-Koyanagi-Harada syndrome is a bilateral, chronic, diffuse granulomatous panuveitis frequently associated with neurological, auditory, and integumentary manifestations. It is also one of the most common forms of uveitis among pigmented races including Chinese patients. This article reviews the current developments of Vogt-Koyanagi-Harada syndrome, including epidemiology, etiology, clinical features, observational techniques, genetics, treatment, and prognosis. Increasing reports have been published to describe the clinical features of Vogt-Koyanagi-Harada syndrome in various ethnic populations from different parts of the world. In spite of tremendous progress in laboratory and clinical research, the etiology of Vogt-Koyanagi-Harada syndrome is still not completely known. Numerous studies indicate an autoimmune nature for this disease. A recent study has shown that Th17, a new subset of T cell, plays an important role in the initiation and maintenance of this disease. Early and aggressive systemic corticosteroids are still the mainstay of initial therapy for Vogt-Koyanagi-Harada syndrome. However, nonsteroid immunomodulatory therapy, including cyclosporine, chlorambucil, cyclophosphamide, and azathioprine have brought out encouraging results. Improved visual outcomes in patients with Vogt-Koyanagi-Harada syndrome in recent years have been reported when compared with decades ago, presumably due to the more aggressive use of immunosuppressive agents. Although the prognosis for VKH syndrome was greatly improved, future prospective, controlled, multi-center studies are needed to determine the optimal treatment regime for this disease. The IL17/23 pathway may provide a novel therapeutic target to control inflammation in VKH syndrome.


[Aquatic animals and use of centrifuge in space experiments].
There are some experiments which do not need a centrifuge apparatus in space, however, for other space experiments the use of centrifuge is indispensable as the control. The characteristics of these two types of space experiments are explained. Generally, the more quantitatively the phenomenon is analyzed, the greater the need of centrifuge apparatus becomes. The centrifuge in space can realize various gravity values ranging from 0 to 1 G, and this will extend the present biology to a more universal biology.