Genetic therapy, person-regarding reasons and the determination of identity -- a reply to Robert Elliot.
I have outlined two ways of defending the claim that there are so-called person-regarding reasons for practising gene therapy on human conceptuses. One is metaphysical and concerns our nature and identity. The upshot of it is that, in cases of most interest, this therapy does not affect our identity, by bringing into existence anyone of our kind who would not otherwise have existed. The other defence is value theoretical and claims that even if genetic therapy were to affect the identity of beings of our kind, there could still be person-regarding reasons for performing it, since we can be benefited and harmed by being caused to exist or not to exist. Robert Elliot has attacked both of these lines, and my present objective is to show how his criticisms can be deflected.


Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects.
The endometrium is ground zero when it comes to understanding how implantation occurs and how it might also fail, resulting in infertility or pregnancy loss. Many of the causes of diminished uterine receptivity are acquired during a woman's lifetime. Endometriosis, a major inflammatory disease affecting women, is also a leading cause of infertility and miscarriage. Once established, the inflammatory changes can, in some women, lead to progesterone resistance and downstream changes in endometrial gene expression. Much is now known about how inflammation translates to progesterone resistance and infertility, but much remains to be learned. In this review we provide an overview for understanding how the endometrium becomes dysfunctional, what biomarkers may hold promise for the diagnosis of endometriosis, and how progesterone resistance leads to infertility. Understanding the pathophysiology of this disease will likely lead to better treatment options.


Therapeutic Alliance and Group Cohesion in an Online Support Program for Adolescent and Young Adult Cancer Survivors: Lessons from "Recapture Life".
Psychological support services for adolescent and young adults (AYAs) with cancer are moving online and are increasingly peer based. It is unclear whether online service delivery impacts critical therapeutic elements such as collaborative patient-therapist rapport and group cohesion. AYA cancer survivors (N = 39) participating in a six-week online cognitive-behavioral therapy group program-"Recapture Life"-rated their perception of therapeutic alliance and group cohesion. Participant-rated alliance and group cohesion were high throughout the program, and therapist-rated participant openness, trust, and motivation strengthened over time. The findings provide further support for the expansion of AYA cancer support services to the online domain.


[Inhibition of TAK1 aggravates airway inflammation by increasing RIPK1 activity and promoting macrophage death in a mouse model of toluene diisocyanate-induced asthma].
To explore the effect of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice. Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated. TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05). Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.


Structure and superconductivity of LiFeAs.
Lithium iron arsenide phases with compositions close to LiFeAs exhibit superconductivity at temperatures at least as high as 16 K, demonstrating that superconducting [FeAs](-) anionic layers with the anti-PbO structure type occur in at least three different structure types and with a wide range of As-Fe-As bond angles.


The development of an empirical psychosocial taxonomy for patients with diabetes.
The main purpose of this study was to develop and to cross-validate an empirically derived psychosocial taxonomy of patients with diabetes. In the first study, 101 patients with Type I or Type II diabetes completed the Multidimensional Diabetes Questionnaire. Cluster analysis identified three clusters, labeled adaptive copers, low support-low involvement, and spousal overinvolvement. In the second study, the taxonomy was cross-validated using an independent sample of 132 patients with long-standing Type II diabetes. The results confirmed that the multivariate classification system was unique and highly accurate. External validation, using general psychological as well as diabetes-specific measures, supported the validity and distinctiveness of the patients' profiles. These findings help establish a multiaxial psychosocial taxonomy of diabetes and may have significant implications for the management of patients with diabetes.


[Therapeutic window analysis of Tripterygium wilfordii processed by liquorice: an instantiation using allergic contact dermatitis].
The present study was aimed to explore the dose-toxicity-effect relationship of Tripterygium wilfordii Hook f( TW) processed by liquorice,to establish the safe and effective therapeutic window,and further to provide scientific reference for the clinical use of TW. The toxicity and anti-inflammatory effect of six doses of raw TW and TW processed by liquorice( 0. 78,1. 56,3. 12,6. 24,12. 48,15. 60 g·kg-1) in 1-fluoro-2,4-dinitrobenzene( DNFB)-induced allergic contact dermatitis( ACD) model were mainly examined by histopathology and serum biochemistry. The liver biochemical parameters including ALT and AST,related inflammatory factors including TNF-α and IL-2,together with liver index,kidney index and the other pharmacodynamic indicators,were examined and compared. The results showed that compared with the control group,the serum levels of TNF-α and IL-2 of the model group were significantly increased( P<0. 01),which proved that the ACD model was successful. The comprehensive analysis of liver biochemical indexes,serum inflammatory factors and the other indexes showed that the safe and effective therapeutic window of TW processed by liquorice was 3. 12-12. 48 g·kg-1. The results showed the therapeutic window of TW processed by liquorice was much broader than that of raw TW. And it could provide scientific reference for the clinical rational use of TW.


[Cytogenetic, gynaecological and sonographic aspects of twin pregnancy with parental Robertsonian translocation 13/14 (author's transl)].
A prenatal chromosome analysis for a parental Robertsonian translocation 13/14 is absolutely imperative. In the present case of a twin pregnancy, it was possible to present the chromosome complement of only one foetus. Since this foetus showed the Robertsonian translocation in the same form as the phenotypically healthy mother, and since the ultrasound findings were normal, it was concluded that foetus I was normal. Further measures for the cytogenetic analysis of foetus II were abandoned after the first amniotic sample could not be analysed. At the time of the amniocentesis this child was retarded when compared to foetus I. Since the life expectancy of a possibly chromosomally unbalanced child is slight, it was not necessary for the parents to take further steps. During the rest of the pregnancy however, this difference in the development of the children evened out unexpectedly and two phenotypically healthy children were born. The implications of a delayed growth rate as an indication of abnormal foetal development are discussed.


[Prophylaxis of thrombosis in surgical gynecology and obstetrics (author's transl)].
An account is given of possible approaches and means available today to cope with physical and medicamentous prophylaxis of thrombosis in gynecologico-obstetric practice. Literature is evaluated, and preference is given to methods which have been safely established by verifiable diagnostic techniques as being applicable to prophylaxis of thrombosis. Due consideration is given to individual inclinations to thrombosis and haemorrhage. Therefore, emphasis is laid on low doses of heparin or dextran.


Diagnostic accuracy of tuberculin skin test self-reading by HIV patients in a low-resource setting.
The World Health Organization recommends tuberculin skin tests (TSTs) where feasible to identify individuals most likely to benefit from isoniazid preventive therapy (IPT). The requirement for TST reading after 48-72 h by a trained nurse is a barrier to implementation and increases loss to follow-up. Patients with human immunodeficiency virus (HIV) infection were recruited from a primary care clinic in South Africa and trained by a lay counsellor to interpret their own TST. The TST was placed by a nurse, and the patient was asked to return 2 days later with their self-reading result, followed by blinded reading by a trained nurse (reference). Of 227 patients, 210 returned for TST reading; 78% interpreted their test correctly: those interpreting it as negative were more likely to be correct (negative predictive value 93%) than those interpreting it as positive (positive predictive value 42%); 10/36 (28%) positive TST results were read as negative by the patient. Patients with HIV in low-resource settings can be trained to interpret their own TST. Those interpreting it as positive should return to the clinic within 48-72 h for confirmatory reading and IPT initiation; those with a negative interpretation can return at their next scheduled visit and initiate IPT at that time if appropriate.


Lipidomic Profiling of Bronchoalveolar Lavage Fluid Extracellular Vesicles Indicates Their Involvement in Lipopolysaccharide-Induced Acute Lung Injury.
Emerging data support the pivotal role of extracellular vesicles (EVs) in normal cellular physiology and disease conditions. However, despite their abundance, there is much less information about the lipid mediators carried in EVs, especially in the context of acute lung injury (ALI). Our data demonstrate that C57BL/6 mice subjected to intranasal Escherichia coli lipopolysaccharide (LPS)-induced ALI release, a higher number of EVs into the alveolar space, compared to saline-treated controls. EVs released during ALI originated from alveolar epithelial cells, macrophages, and neutrophils and carry a diverse array of lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFA). The eicosanoids in EVs correlated with cellular levels of arachidonic acid, expression of cytosolic phospholipase A2, cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome epoxygenase p450 proteins in pulmonary macrophages. Furthermore, EVs from LPS-toll-like receptor 4 knockout (TLR4-/-) mice contained significantly lower amounts of COX and LOX catalyzed eicosanoids and ω-3 PUFA metabolites. More importantly, EVs from LPS-treated wild-type mice increased TNF-α release by macrophages and reduced alveolar epithelial monolayer barrier integrity compared to EVs from LPS-treated TLR4-/- mice. In summary, our study demonstrates for the first time that the EV carried PUFA metabolite profile in part depends on the inflammatory status of the lung macrophages and modulates pulmonary macrophage and alveolar epithelial cell function during LPS-induced ALI.


Strategies for identifying predictive biomarkers and subgroups with enhanced treatment effect in clinical trials using SIDES.
Several approaches to identification of predictive biomarkers and subgroups of patients with enhanced treatment effect have been proposed in the literature. The SIDES method introduced in Lipkovich et al. (2011) adopts a recursive partitioning algorithm for screening treatment-by-biomarker interactions. This article introduces an improved biomarker discovery/subgroup search method (SIDEScreen). The SIDEScreen method relies on a two-stage procedure that first selects a small number of biomarkers with the highest predictive ability based on an appropriate variable importance score and then identifies subgroups with enhanced treatment effect based on the selected biomarkers. The two-stage approach helps increase the signal-to-noise ratio by screening out noninformative biomarkers. We evaluate operating characteristics of the standard SIDES method and two SIDEScreen procedures based on fixed and adaptive screens. Our main finding is that the adaptive SIDEScreen method is a more flexible biomarker discovery tool than SIDES and it better handles multiplicity in complex subgroup search problems. The methods presented in the article are illustrated using a clinical trial example.


Horizontal sacrum as an indicator of a tethered spinal cord.
The horizontal sacrum has never been described as an indicator of a tethered spinal cord following myelomeningocele closure. We retrospectively analyzed 30 children with a myelomeningocele for this progressive change and its correlation with symptoms. At least two lateral radiographs over time were examined and the lumbosacral angle (LSA) was measured. We found that the majority of these children had an LSA that was greater than would be expected in patients with late and decreased ambulatory abilities. Also, we observed that the LSA was often inappropriately increased at the time many of these patients presented with symptoms indicative of a tethered spinal cord. We hypothesize that the LSA in this group of children is altered by a tethered spinal cord and that the horizontal nature of the sacrum may predate the clinically appreciable symptoms of a tethered spinal cord.


Enzymatic Hydrolysis of Polyester Thin Films at the Nanoscale: Effects of Polyester Structure and Enzyme Active-Site Accessibility.
Biodegradable polyesters have a large potential to replace persistent polymers in numerous applications and to thereby reduce the accumulation of plastics in the environment. Ester hydrolysis by extracellular carboxylesterases is considered the rate-limiting step in polyester biodegradation. In this work, we systematically investigated the effects of polyester and carboxylesterase structure on the hydrolysis of nanometer-thin polyester films using a quartz-crystal microbalance with dissipation monitoring. Hydrolyzability increased with increasing polyester-chain flexibility as evidenced from differences in the hydrolysis rates and extents of aliphatic polyesters varying in the length of their dicarboxylic acid unit and of poly(butylene adipate-co-terephthalate) (PBAT) polyesters varying in their terephthalate-to-adipate ratio by Rhizopus oryzae lipase and Fusarium solani cutinase. Nanoscale nonuniformities in the PBAT films affected enzymatic hydrolysis and were likely caused by domains with elevated terephthalate contents that impaired enzymatic hydrolysis. Yet, the cutinase completely hydrolyzed all PBAT films, including films with a terephthalate-to-adipate molar ratio of one, under environmentally relevant conditions (pH 6, 20 °C). A comparative analysis of the hydrolysis of two model polyesters by eight different carboxylesterases revealed increasing hydrolysis with increasing accessibility of the enzyme active site. Therefore, this work highlights the importance of both polyester and carboxylesterase structure to enzymatic polyester hydrolysis.


Does hospital setting influence shoulder replacement revision rate? A national comparison of outcomes between private and public settings.
Australian healthcare relies on both private and public sectors to meet the demand for surgical care. Rapid growth of shoulder replacement surgery highlights a disparity in service provision, with two-thirds occurring privately. This study aimed to assess the influence of hospital setting on shoulder replacement revision rate at a national level. All primary shoulder replacements recorded by the Australian Orthopaedic Association National Joint Replacement Registry from April 2004 to December 2020 were included. Private and public settings were compared for stemmed total shoulder replacement (sTSR) for osteoarthritis (OA), reverse total shoulder replacement (rTSR) for OA/cuff arthropathy (CA), and rTSR for fracture. The primary outcome was cumulative percent revision (CPR), with Kaplan-Meier estimates of survivorship to determine differences between private and public hospitals, recorded as hazard ratios (HR). Secondary analyses investigated differences between hospital settings, targeting hospital outliers for revision and prosthesis selection. Primary sTSR (OA) demonstrated a higher revision rate in private hospitals compared to public hospitals (HR = 1.27; P = 0.001), as did rTSR (OA/CA) after 3 months (HR = 1.33; P = 0.003). However, no significant difference was observed for primary rTSR (fracture) (HR = 1.10; P = 0.484). Restricting rTSR (OA/CA) to the best performing prosthesis combinations eliminated the difference between private and public outcomes (HR 1.10; P = 0.415). No other secondary analysis altered the primary result. Differences exist between private and public hospitals for revision rate following primary shoulder replacement. Prosthesis selection accounts for some of the variation. Further analysis into patient specific characteristics is necessary to better understand these disparities.


Is orthodontic treatment without premolar extractions always non-extraction treatment?
While it is common in contemporary orthodontic and orthopaedic treatment to commence treatment for many growing patients during the mixed-dentition, the creation of anterior space, often involving the attempted distalization or holding-back of the upper and lower permanent molar teeth has been shown to commonly result in posterior space deficiencies. Although the extractions of permanent premolar teeth may have been avoided, the developing second and third permanent molars are often affected, so that third molar impaction results in many cases. This is not to say that orthodontic treatment carried-out without premolar extractions is not ideal in many cases, but on the available evidence, so-called absolute 'non-extraction' protocols should be questioned, so that both the dental profession and the public at large are not misled.


[Changes in the cellular composition of the deciduous membrane in physiologic pregnancy and late toxicosis].
Cytochemical characteristics of the decidual membrane at a physiologically normal pregnancy and in cases of late toxicosis are presented. Three main cell types of the decidual membrane are defined: large decidual cells (LDC), small decidual cells (SDC) and granular cells of endometrium, or K-cells. Part of each cell type in the decidual membrane is determined. At physiologically normal pregnancy the part of the LDC makes 50-60% in the membranes and 80-85% in the basal plate of the placenta; SDC--10-18% in the fetal membranes and 1-2% in the basal plate of the placenta; K-cells--0.5-1%. At late toxicosis of pregnancy there is a change in relative and absolute amount of the decidual cells: the part of the LDC decreases up to 26-40% in the fetal membranes and up to 55% in the basal plate of the placenta; part of the K-cells at a slight form of preeclampsia rises up to 3-4%, at a severe form--up to 11-12%. The change in cell composition results in certain disturbances of physiological equilibrium of biologically active substances produced by the decidual cells. This correlates with the severity and clinical manifestations of the late toxicosis of pregnancy. Correlation of the decidual cells disfunction, directed to regulation of their reproduction and functioning, can become one of the elements of pathogenic treatment of the late toxicosis of pregnancy.


Recent advances of thermally responsive nanogels for cancer therapy.
Thermally responsive nanogel drug delivery systems (TRNDDS) have been widely investigated as a new strategy for active targeting tumor therapy, as these can accumulate on the tumor site and/or release the payload at the desired site by structure changes rapidly once stimulated by temperature changes. In this review, we discuss the evolution of TRNDDS and future perspectives for antitumor drug and gene delivery. With further understanding of the specificity of tumor site at the cellular and molecular level, in parallel with the development of nanomaterial design and preparation, TRNDDS show great potential for tumor targeting therapy.


Advanced hematite nanomaterials for newly emerging applications.
Because of the combined merits of rich physicochemical properties, abundance, low toxicity, etc., hematite (α-Fe2O3), one of the most chemically stable compounds based on the transition metal element iron, is endowed with multifunctionalities and has steadily been a research hotspot for decades. Very recently, advanced α-Fe2O3 materials have also been developed for applications in some cutting-edge fields. To reflect this trend, the latest progress in developing α-Fe2O3 materials for newly emerging applications is reviewed with a particular focus on the relationship between composition/nanostructure-induced electronic structure modulation and practical performance. Moreover, perspectives on the critical challenges as well as opportunities for future development of diverse functionalities are also discussed. We believe that this timely review will not only stimulate further increasing interest in α-Fe2O3 materials but also provide a profound understanding and insight into the rational design of other materials based on transition metal elements for various applications.


Photosynthetic Conversion of Carbon Dioxide to Oleochemicals by Cyanobacteria: Recent Advances and Future Perspectives.
Sustainable production of biofuels and biochemicals has been broadly accepted as a solution to lower carbon dioxide emissions. Besides being used as lubricants or detergents, oleochemicals are also attractive biofuels as they are compatible with existing transport infrastructures. Cyanobacteria are autotrophic prokaryotes possessing photosynthetic abilities with mature genetic manipulation systems. Through the introduction of exogenous or the modification of intrinsic metabolic pathways, cyanobacteria have been engineered to produce various bio-chemicals and biofuels over the past decade. In this review, we specifically summarize recent progress on photosynthetic production of fatty acids, fatty alcohols, fatty alk(a/e)nes, and fatty acid esters by genetically engineered cyanobacteria. We also summarize recent reports on fatty acid and lipid metabolisms of cyanobacteria and provide perspectives for economic cyanobacterial oleochemical production in the future.


Subjective and objective measures of the patient experience before, during, and after intravitreal anti-vascular endothelial growth factor injections.
To assess patient experience of intravitreal injections using vital-signs, visual-experience, pain-rating and emotional response during intravitreal anti-VEGF injections. A prospective observational study of patient experience of intravitreal anti-VEGF injections done following metrics were collected pre-injection, during injection, and post-injection: pain assessment using visual analog score, fear-response rating, visual-experience questionnaire, and vital-signs. A total of one-hundred-and-seventy-four patients undergoing intravitreal anti-VEGF injections for retinal pathologies were included in the study. Mean age was 58.8 ± 10.4 years in <5 injection group (n = 133) and 59.02 ± 9.0 years in ≥5 injection group (n = 41) (P = 0.90).During injection, 90.2% of patients in <5 injection group reported moderate or severe pain compared to 78% of patients in ≥5 injection group. In pre and post-injection phases, mild-to-moderate pain was reported in both groups (P = <0.001). Ninety-two (52.9%) patients reported having a mild frightening experience. There was no statistical significance in patients assessment of fear with respect to age, sex, or number of injections. The Systolic Blood Pressure (SBP) during and following injection ((SBP 171.7 ± 21.1,150.8 ± 16.2) procedures was significantly higher in cases with <5 injections when comparing to cases with >5 injections (SBP 159.7 ± 26.4, 143.2 ± 17.0) (P = 0.003), (P = 0.011). DBP, heart rate, pulse rate measurements were similar among patients in all phases of the study. We report a large sample size with comprehensive assessments of the patient experience. Higher pain ratings in the <5 injection group, the increase in the SBP in the pre-and during injection phases, and the overall rating of mild-to-moderate fear during the procedure.


[Hypoplasia of intra- and extrahepatic bile ducts associated with congenital abnormalities].
The present report deals with a patient affected by Alagille's syndrome. The clinical hallmark of this syndrome is chronic cholestasis with ductular and extrahepatic hypoplasia and associated multiple congenital malformations. The diagnosis was made by hepatobiliary scanning with TC99-HIDA, transendoscopic cholangiography and liver biopsy.


Inequalities in premature mortality from ischaemic heart disease in the WHO European region.
Ischaemic heart disease (IHD) is one of the leading causes of premature mortality. Our aim was to analyse standardised premature mortality rates from IHD by geographical groups in the age group 45-59 years. We performed a retrospective, quantitative analysis of age-standardized mortality rates from IHD between 1990-2014 per 100,000 population in Western European (WE: N = 17), Eastern European countries (EE: N = 10), and countries of the former Soviet Union (fSU: N = 15) within the European Region of the World Health Organisation (WHO) based on data retrieved from the WHO European Mortality Database. Descriptive statistics, time series analysis and statistical tests were used for the analyses (ANOVA, Kruskal-Wallis test, Mann-Whitney test, paired t-test). On average, age-standardized death rates (ASDR) from IHD per 100,000 population were the lowest in WE (men 1990: 143.67, 2014: 50.29; women 1990: 29.06, 2014: 9.89), and the highest in fSU (men 1990: 358.69, 2014: 253.25; women 1990: 99.78, 2014: 57.85). Between 1990 and 2014, all three groups experienced significant decrease in ASDR both in men and women (fSU: -29.39%, -42.02%; EE: -49.41%, -50.57%; WE: -64.99%, -65.97%, respectively) (p < 0.05). Between 1990 and 2004, ASDR decreased in WE in both sexes (p < 0.001), in EE among males (p = 0.032). Between 2004 and 2014, ASDR from IHD decreased significantly in both sexes in fSU and WE, in EE only among women (p < 0.05). During the whole period analysed, ischaemic heart disease mortality significantly decreased in both sexes in all the groups.


Arthroscopically assisted reduction of an unstable severe slipped capital femoral epiphysis: a case report.
Slipped capital femoral epiphysis (SCFE) is considered to be one of the most common disorders of the hip in children and adolescents. If left untreated, it may lead to progressive deformity, pain and decreased range of motion, and predisposes to early onset degenerative arthritis. Surgical treatment is advised, with in situ pinning across the physis being the gold standard for stable slips. Closed or open reduction can be considered in unstable or severe types. We report the arthroscopically assisted reduction of an unstable severe SCFE, followed by canulated screw fixation. A follow-up of 2.5 years shows an excellent clinical and acceptable radiological outcome. Our case demonstrates that arthroscopically assisted reduction of a slipped capital femoral epiphysis is feasible. Although the technique is technically challenging and requires familiarity with arthroscopy of the hip, it has some clear benefits as compared with both closed and open reduction techniques. Arthroscopically assisted reduction may therefore be a safe and effective treatment in unstable, severe SCFE.


113Cd solid-state NMR for probing the coordination sphere in metal-organic frameworks.
Spectroscopic techniques are a powerful tool for structure determination, especially if single-crystal material is unavailable. (113)Cd solid-state NMR is easy to measure and is a highly sensitive probe because the coordination number, the nature of coordinating groups, and the geometry around the metal ion is reflected by the isotropic chemical shift and the chemical-shift anisotropy. Here, a detailed investigation of a series of 27 cadmium coordination polymers by (113)Cd solid-state NMR is reported. The results obtained demonstrate that (113)Cd NMR is a very sensitive tool to characterize the cadmium environment, also in non-single-crystal materials. Furthermore, this method allows the observation of guest-induced phase transitions supporting understanding of the structural flexibility of coordination frameworks.


The role of the zinc finger protein ZC3H32 in bloodstream-form Trypanosoma brucei.
Kinetoplastids rely heavily on post-transcriptional mechanisms for control of gene expression, with regulation of mRNA processing, translation and degradation by RNA-binding proteins. ZC3H32 is a cytosolic mRNA-binding protein with three non-canonical CCCH zinc finger domains. It is much more abundant in bloodstream-form Trypanosoma brucei than in procyclic forms. Tethering of ZC3H32 to a reporter mRNA suppressed translation and resulted in mRNA degradation, and deletion analysis suggested that this activity was present in both the N- and C-terminal domains, but not the central zinc finger-containing domain. Tandem affinity purification, however, revealed no interaction partners that might account for this activity. RNASeq analyses did not yield any evidence for sequence-specific binding or regulation of specific mRNAs. The presence of ZC3H32 homologues in monogenetic and free-living Euglenids also argues against a role in developmental regulation, although its function may have diverged in evolution. T. brucei ZC3H32 might be implicated in basal mRNA metabolism, with this role perhaps being taken over by another protein in procyclic forms.


Comparative molecular analysis of the prokaryotic diversity of two salt mine soils in southwest China.
While much is known about the microbial diversity in some hypersaline environments, little is known about those of salt mine tunnel soils. The objective of this study was to conduct a comprehensive phylogenetic comparison of the archaeal and bacterial communities present in Yipinglang salt mine (YPL) and Qiaohou salt mine (QH) tunnels differing in salinity and salt composition using 16S rRNA gene clone libraries. Two hundred twenty-eight sequences for QH and 182 sequences for YPL were analyzed by amplified ribosomal DNA-restriction analysis. Libraries revealed 44 bacterial and 57 archaeal different operational taxonomic units belonging to at least 8 bacterial and 3 archaeal divisions, but not all divisions were observed in both salt mines. The bacterial community affiliated with the Bacteroidetes was the most abundant (60% of clones) in QH, while the community in YPL was dominated by δ-Proteobacteria (45% of clones). All archaeal clones from QH were affiliated with Halobacteriaceae. In contrast, in the YPL library, 49% of clones belonged to Halobacteriaceae, 31% of clones related to unclassified archaea, and 21% of clones belonged to Crenarchaeota. Bioinformatic analysis and comparisons showed that the clone libraries were significantly different between two salt mines.


Using case mix and adverse event outcome reports for outcome-based quality monitoring.
The OBQM process is similar to many of the QI/PI processes that agencies have used in the past. The Adverse Event Outcome and Cse Mix Reports, based on OASIS data, provide agencies with clinical out come data that can be used to improve quality of care. The reposts are a first step in the effort to bring the home care industry to a new era of using patient-centered data as the basis for improving services.


Hyperthyroidism Improves the Pathological Condition of Nonalcoholic Steatohepatitis: A Case of Nonalcoholic Steatohepatitis with Graves' Disease.
3,5,3'-triiodo-L-thyronine regulates the glucose metabolism, lipid metabolism, and hepatic steatosis. Several groups have shown the relationships between hypothyroidism and nonalcoholic fatty liver and hypothyroidism and nonalcoholic steatohepatitis (NASH). However, the effect of hyperthyroidism on NASH has not yet been investigated. We herein report effects of thyroid hormone on the pathological condition of NASH in a patient with NASH complicated by Graves' disease. In our case, the liver enzyme level improved with the increasing thyroid hormone level; however, the liver enzyme level was aggravated with the improving thyroid hormone level. Therefore, hyperthyroidism may improve the pathological condition of NASH.


Immunological relationships of OMC-1, an endogenous virus of owl monkeys, with mammalian and avian type C viruses.
The relationships between OMC-1, an endogenous oncovirus of owl monkey, and representatives of the three oncoviral genera have been investigated by radioimmunological techniques. The major structural protein of OMC-1 was shown to share antigenic determinants with the corresponding proteins of certain type C viruses of rodent, feline, and cervine origin. It was not possible to demonstrate antigenic cross-reactivity between OMC-1 and endogenous type C viruses of baboons. These findings argue that OMC-1 and baboon endogenous viruses do not represent direct descendants of an ancestor virus that became integrated within primates prior to the divergence of New and Old World species. A close antigenic relationship was established between the major structural proteins of OMC-1, an endogenous virus of deer (deer kidney virus), and avian reticuloendotheliosis viruses. These findings establish OMC-1 and deer kidney virus in the evolutionary lineage that may have led to the generation of avian reticuloendotheliosis virus, a group of oncogenic viruses capable of crossing the interclass barrier between mammals and birds.


Intraoperative identification and effective "blood patch" prevention of persistent air leak in lung resections.
Persistent air leak (PAL) is the most common complication after lung resection, requiring additional treatments and hospital stay. Intraoperative prevention of PAL is usually left to the surgeon's subjective judgement, with inconsistent results. The aim of the study was to establish systematic, reproducible quantification of air leaks at thoracotomy in order to identify those which are potentially persistent, to be preventively treated by intraoperative "blood patch" pneumo-stasis. In a consecutive series of 570 lung resections, parenchymal suture air tightness was tested intraoperatively at end-inspiratory pressure intervals from 15 to 35 cm H2O. Air leaks at 15 cm H2O (n=40) were considered too critical, while air escape beyond 30 cm H2O (n=437) was deemed quickly self-sealing postoperatively; these conditions were managed by further surgery and standard chest tubes only, respectively. Air leaks between 16 and 30 cm H20 (n=93) were assumed to be the main source of postoperative PAL and were preventively treated with 50 cc of blood left in the cavity for 3 hours after closing the thoracotomy. Chest tubes were set up so as to avoid tension pneumothorax or occult bleeding. No early or late major complications were related to the intraoperative "blood patch" procedure. The cumulative incidence of PAL was 1.4%, most of which (6/8) belonging to the group leaking air in the 16-30 cm H2O pressure interval. In contrast, the PAL rate in the 437 patients reputed to be at low risk was 0.2%. The overall mean hospital stay was 7.2 days, the mean duration of chest tube duration 3.5 days, and the complication rate 15%. According to our retrospective data, air leaks occurring between 16 and 30 cm H2O of pressure in the intubated lung were identified as carrying the highest risk of becoming persistent postoperatively; intraoperative "blood patch" pneumo-stasis is a convenient and successful preventive method to minimize PAL occurrence in this group of patients.


Behavior of matrix parameters and their correlation to micro-pollutant degradation during treatment of real wastewater by carrier-bound photocatalytic ozonation.
Immobilized titanium dioxide catalysts were used within a photocatalytic immersion rotary body reactor, which was connected to a substream ozonation unit to remove micro-pollutants from wastewater. Within this work data on the behavior of cumulative parameters during treatment of wastewater by photocatalysis and photocatalytic ozonation are provided. The investigated parameters are spectral absorption coefficient at 254 nm (SAC254), total organic carbon (TOC) and chemical oxygen demand (COD). All experiments were carried out using secondary effluent from the same wastewater treatment plant. For the parameter SAC254, consistent concentration curves and dependencies to operational parameters of the experimental system could be measured. The measurements of the parameters TOC and COD showed greater uncertainties, although basic trends could nonetheless be observed. A good linear correlation (R2 < 0.85) between the reduction of SAC254 and 8 micro-pollutants for photocatalysis and photocatalytic ozonation was found. This confirms the suitability of the SAC254 as a control parameter for a large-scale application of a photocatalytic 4th treatment stage. A linear correlation between measured TOC and COD degradation rates was possible with a coefficient of determination of 0.58-0.86. The simultaneous decrease of TOC and COD is an indicator for a mineralization of the treated wastewater matrix.


Preferential Nucleation during Polymorphic Transformations.
Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR's) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR's with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller - and therefore nucleation more probable - with increasing number of special OR's. These insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material.


Embedding Number-Combinations Practice Within Word-Problem Tutoring.
Two aspects of mathematics with which students with mathematics learning difficulty (MLD) often struggle are word problems and number-combination skills. This article describes a math program in which students receive instruction on using algebraic equations to represent the underlying problem structure for three word-problem types. Students also learn counting strategies for answering number combinations that they cannot retrieve from memory. Results from randomized-control trials indicated that embedding the counting strategies for number combinations produces superior word-problem and number-combination outcomes for students with MLD beyond tutoring programs that focus exclusively on number combinations or word problems.


Concentrations of insulin and thyroid hormones in the serum of landlocked sea lampreys (Petromyzon marinus) of three larval year classes, in larvae exposed to two temperature regimes, and in individuals during and after metamorphosis.
Serum concentrations of thyroxine (T4) triiodothyronine (T3), and insulin were measured in landlocked sea lampreys (Petromyzon marinus) of three larval year classes (II to IV), larvae in two fixed temperatures (13 and 21 degrees), individuals during metamorphosis (stages 3-7), and juveniles immediately following metamorphosis. There was no difference in serum insulin levels in the larval year classes but the concentrations of both T4 and T3 increased during the protracted larval life to reach a maximum in individuals of metamorphosing size (age) without initiating early (pro) metamorphic events. A lower temperature depressed serum insulin and elevated T4 levels but had no effect on T3. As expected, metamorphosis was marked by a sharp decrease in both serum T4 and T3 by stage 3. Insulin did not change until stage 6 when an elevated serum concentration probably corresponded with development of the endocrine pancreas. Serum T4 and T3, but not insulin, levels decreased during feeding in the early juvenile period. Serum concentrations of these hormones during larval growth, varied temperature exposure, and metamorphic development provide some new insight into the intricacies of lamprey metamorphosis.


How do peri-implant biologic parameters correspond with implant survival and peri-implantitis? A critical review.
The aim of this critical review was to evaluate whether commonly used biologic diagnostic parameters correspond to implant survival and peri-implantitis prevalence. Publications from 2011 to 2017 were selected by an electronic search using the Pubmed database of the US National Library of Medicine. Prospective and retrospective studies with a mean follow-up time of at least 5 years and reporting prevalence of peri-implantitis as well as mean bone loss and standard deviation were selected. The correlation between reported prevalence of peri-implantitis and reported implant survival, mean follow-up time, mean bone loss, mean probing depth, and mean bleeding on probing was calculated. Mean bone loss and standard deviation were used for estimation of proportion of implants with bone loss exceeding 1, 2, and 3 mm. Full-text analysis was performed for 255 papers from 4,173 available ones, and 41 met all the inclusion criteria. The overall mean weighted survival rate was 96.9% (89.9%-100%) and the reported prevalence of peri-implantitis ranged between 0% and 39.7%, based on 15 different case definitions. The overall weighted bone loss was 1.1 mm based on 8,182 implants and an average mean loading time ranging from 5 to 20 years. No correlation was found between mean bone loss and the reported prevalence of peri-implantitis. The estimated prevalence of implants with bone loss above 2 mm was 23%. The overall weighted mean probing depth was 3.3 mm, and mean weighted bleeding was 52.2%. Only a weak correlation was found between survival and function time (r = -0.49). There was no relation between the probing depth or bleeding and the mean bone loss, mean follow-up time, and reported prevalence of peri-implantitis. Biologic parameters mean probing depth and mean bleeding on probing do not correlate with mean bone loss and this irrespective of follow-up. Case definition for peri-implantitis varied significantly between studies indicating that an unambiguous definition based on a specified threshold for bone loss is not agreed upon in the literature.


Multimode illumination for speckle reduction and angle neutrality in millimeter wave active imaging: range and time-resolved mode averaging.
Active illumination is an attractive approach for millimeter and submillimeter wave imaging because of its generally larger signal margins and capacity for range determination. However, the resultant speckle from diffuse targets and the requirement that specular targets have strategic angular alignment are significant shortcomings. As a result, many, if not most, demonstrations of active imaging have involved the use of strategically oriented specular targets. We have previously shown [J. Opt. Soc. Am. A29, 2643 (2012)10.1364/JOSAA.29.002643JOAOD61084-7529] that spatially time-resolved modulated multimode mixing approaches mitigate these issues. In this paper, we extend this work to demonstrate the use of range resolved multimode mixing as an alternative means to provide statistically independent images for speckle reduction averaging. We also demonstrate the use of systematic illumination of spatial modes in a "grassy field" geometry.


Small cell lung cancer (SCLC) incidence and trends vary by gender, geography, age, and subcategory based on population and hospital cancer registries in Hebei, China (2008-2017).
Lung cancer is the leading cause of morbidity and mortality worldwide. Small cell lung cancer (SCLC) has been determined to be the most lethal lung malignancy. Few studies have previously analyzed the epidemiological characteristics of SCLC in China. This study analyzed the epidemiological characteristics of SCLC aiming to provide a reference for the prevention of SCLC in Hebei Province. The epidemiological characteristics of SCLC using lung cancer data based on population and hospital cancer registries in Hebei Province between 2008 and 2017 were analyzed. The proportion of both population- and hospital-based SCLC cases displayed a significant increasing trend. Moreover, the proportion of males was higher than that for female based on population- and hospital-based cases. The proportion of hospital-based SCLC cases in counties was higher than that in cities, whereas there were no significant regional differences between cities and counties based on population. The proportion of both population- and hospital-based SCLC cases decreased consistently with increasing age. There was a difference between population- and hospital-based distribution of subcategories of SCLC. Significant increases in the proportion of both population- and hospital-based SCLC cases over recent years, particularly in males and in patients aged over 55 years, were observed. Research on the pathogenesis of SCLC in these patients and prevention is urgently required.


Rupture of sinus of Valsalva aneurysm: a rare cause of acute ischaemic chest pain in the emergency department.
Acute chest pain is a leading cause of emergency department (ED) visits in the adult population. However, patients with a life-threatening cause of chest pain comprise only a small fraction, hence identification of those who need immediate intervention is very important. One rare cause is rupture of the aneurysm, which may present with a wide variety of symptomatology, including anginal chest pain. In a busy ED, evaluation of chest pain suggestive of myocardial ischaemia needs to cater to early identification of acute coronary syndrome (ACS), limit over investigating patients for low or intermediate probability of ACS and appropriate decision making for discharge, to reduce ED over boarding. Validated scores for evaluating the low or intermediate probability chest pain like the HEART pathway may miss such rare diagnoses in the absence of ECG changes, requiring high degree of suspicion and individualisation of patient care.


Behaviour Evaluation Scales For Pediatric Dental Patients - Review And Clinical Experience.
The present article makes a review of the relevant literature on the scales used in the assessment of behaviour of pediatric dental patients as well as presents the results we have had of using a modified Kurosu Behaviour Evaluation Scale to assess a study sample. The review makes a critical analysis of current evaluation methods and the design of assessment scales. The assessment tools most commonly used in pediatric dentistry are presented in a chronological order from the past to the present. The clinical study we conducted used a modified Behaviour Evaluation Scale developed by Kurosu for the assessment of the behaviour of children. The study showed that during dental treatment of children in the age range of 6 to 12 years the prevailing objective behaviour characteristics in accordance with Kurosu's behaviour evaluation scale are related to the eyes and the facial expression. The findings from the literature review and the results of our study warrant further studies to develop easy-to-use assessment tools that would enhance the objective assessment of behaviour.


Metabolic convergence on lipogenesis in RAS, BCR-ABL, and MYC-driven lymphoid malignancies.
Metabolic reprogramming is a central feature in many cancer subtypes and a hallmark of cancer. Many therapeutic strategies attempt to exploit this feature, often having unintended side effects on normal metabolic programs and limited efficacy due to integrative nature of metabolic substrate sourcing. Although the initiating oncogenic lesion may vary, tumor cells in lymphoid malignancies often share similar environments and potentially similar metabolic profiles. We examined cells from mouse models of MYC-, RAS-, and BCR-ABL-driven lymphoid malignancies and find a convergence on de novo lipogenesis. We explore the potential role of MYC in mediating lipogenesis by 13C glucose tracing and untargeted metabolic profiling. Inhibition of lipogenesis leads to cell death both in vitro and in vivo and does not induce cell death of normal splenocytes. We analyzed RNA-seq data sets for common metabolic convergence in lymphoma and leukemia. Using in vitro cell lines derived in from conditional MYC, RAS, and BCR-ABL transgenic murine models and oncogene-driven human cell lines, we determined gene regulation, metabolic profiles, and sensitivity to inhibition of lipogenesis in lymphoid malignancies. We utilize preclinical murine models and transgenic primary model of T-ALL to determine the effect of lipogenesis blockade across BCR-ABL-, RAS-, and c-MYC-driven lymphoid malignancies. Statistical significance was calculated using unpaired t-tests and one-way ANOVA. This study illustrates that de novo lipid biogenesis is a shared feature of several lymphoma subtypes. Using cell lines derived from conditional MYC, RAS, and BCR-ABL transgenic murine models, we demonstrate shared responses to inhibition of lipogenesis by the acetyl-coA carboxylase inhibitor 5-(tetradecloxy)-2-furic acid (TOFA), and other lipogenesis inhibitors. We performed metabolic tracing studies to confirm the influence of c-MYC and TOFA on lipogenesis. We identify specific cell death responses to TOFA in vitro and in vivo and demonstrate delayed engraftment and progression in vivo in transplanted lymphoma cell lines. We also observe delayed progression of T-ALL in a primary transgenic mouse model upon TOFA administration. In a panel of human cell lines, we demonstrate sensitivity to TOFA treatment as a metabolic liability due to the general convergence on de novo lipogenesis in lymphoid malignancies driven by MYC, RAS, or BCR-ABL. Importantly, cell death was not significantly observed in non-malignant cells in vivo. These studies suggest that de novo lipogenesis may be a common survival strategy for many lymphoid malignancies and may be a clinically exploitable metabolic liability. This study does not include any clinical interventions on human subjects.


The importance of pre- and post-test counseling for prenatal cell-free DNA screening for common fetal aneuploidies.
Prenatal cell-free DNA screening for common fetal aneuploidies has rapidly changed the paradigm of prenatal care. Despite its advantages compared to conventional screening methods, its unexpectedly rapid implementation in clinical practice has generated several ethical and medical issues and misconceptions. Aggressive commercial marketing of cell-free DNA screening and media dissemination of misleading information have added confusion. Areas covered: This review provides an extensive update and will focus on the importance of pre-and post-test counseling for prenatal cell-free DNA screening not previously discussed extensively in the available literature. Additionally, we report cell-free DNA screening implementation in the largest obstetrical tertiary unit in Finland which is one of few countries that provides all prenatal screening methods free of charge for all women and has a very high uptake of first-trimester screening. This is not a systematical review, but rather a narrative overview which includes the most relevant and recent original publications and reviews covering this issue. Expert opinion: Despite being the most accurate method for screening of common fetal aneuploidies, the knowledge and counseling should be substantially improved. Cell-free DNA screening is not a replacement for diagnostic testing and its use in prenatal testing is complex and limited.


Amino acid transporter B(0)AT1 (slc6a19) and ancillary protein: impact on function.
Amino acids play an important role in the metabolism of all organisms. Their epithelial re-absorption is due to specific transport proteins, such as B(0)AT1, a Na(+)-coupled neutral amino acid symporter belonging to the solute carrier 6 family. Here, a recently cloned fish orthologue, from the intestine of Salmo salar, was electrophysiologically characterized with the two-electrode voltage clamp technique, in Xenopus laevis oocytes heterologously expressing the transporter. Substrate specificity, apparent affinities and the ionic dependence of the transport mechanism were determined in the presence of specific collectrin. Results demonstrated that like the human, but differently from sea bass (Dicentrarchus labrax) orthologue, salmon B(0)AT1 needs to be associated with partner proteins to be correctly expressed at the oocyte plasma membrane. Cloning of sea bass collectrin and comparison of membrane expression and functionality of the B(0)AT1 orthologue transporters allowed a deeper investigation on the role of their interactions. The parameters acquired by electrophysiological and immunolocalization experiments in the mammalian and fish transporters contributed to highlight the dynamic of relations and impacts on transport function of the ancillary proteins. The comparative characterization of the physiological parameters of amino acid transporters with auxiliary proteins can help the comprehension of the regulatory mechanism of essential nutrient absorption.


Multilayer Regulation of Atomic Boron Nitride Films to Improve Oxidation and Corrosion Resistance of Cu.
The boron nitride (BN) monolayer (1L) with high impermeability and resistivity seems to hold promise as a long-term corrosion barrier for Cu under ambient condition, which is supported by recent researches. Here, we perform a complete study of the alternating temperature tests (the sample is exposed in air for 30 days and subsequently heated at 200 °C for 2 h) and electrochemical measurements on 1L and multilayer BN-coated Cu foils. Results imply that the BN-coated Cu foils are less oxidized than uncoated Cu foils after alternating temperature tests, regardless of the layers of BN. Particularly, the oxidation process proceeds slowly in multilayers because most of the underlying defects are covered with BN layers to suppress the oxygen diffusion in the vertical direction and the oxidation mainly occurs on the wrinkled region of BN films. Electrochemical analyses reveal that the BN layers provide an effective physical barrier against the corrosive medium and inhibit the electron diffusion because of their high electrical insulating behavior and the corrosion resistance of the samples increases with increasing BN layers. These findings indicate that BN films with adequate layers are good candidates for oxidation and corrosion protection at the atomic level, which is vital to many industrial and academic applications.


Frostbite in Oxfordshire: the impact of a severe winter on an unprepared civilian population.
The winter of 1981-1982 in Oxfordshire was unusually cold. During this winter, 18 patients with frostbite were referred to the Peripheral Vascular Service of the Nuffield Department of Surgery. The age-range was 52-83 years. None was diabetic. Seven were smokers. All had frostbite of either feet or fingers, sometimes of both. Patients could be divided into 2 groups based on the severity of their injury. In the first group 10 patients had mild injuries and were managed as outpatients. One patient had terminal phalanges amputated as a day case. Patients in this group had adequate homes and no associated medical disease. Eight patients in the second group had severe frostbite. All were socially disadvantaged and 4 had significant medical disease (mitral valve disease, lymphoma, alcoholism and depression). Because of social circumstances and because it takes time to establish the line of demarcation between healthy and dead tissue, all patients in this group were in hospital for a minimum of 2 months (range 2-10 months). Four patients required skin grafting and 2 needed special shoes to enable them to walk. There needs to be greater public awareness of the dangers and risks of cold injury.


Human leukocyte antigen compatibility in heart transplantation: evidence for a differential role of HLA matching on short- and medium-term patient survival.
Studies of the influence of human leukocyte antigen (HLA) matching on cardiac transplant outcome have proved inconclusive, mainly due to the lack of well-matched grafts. However, a growing number of studies report improved clinical course and patient survival in cases with increased HLA compatibility. Opelz et al. believe these benefits justify the introduction of prospective HLA-matching strategies. We performed univariate and multivariate analyses to examine the short- and medium-term influence of HLA matching on 556 consecutive primary heart transplants performed at a single center between 1983 and 1994. Overall graft survival at 1, 3, and 5 years was 80%, 74%, and 67% respectively. Sixteen (2.9%) grafts failed within 5 days and were not considered in the analysis of the HLA matching and graft survival data. Complete HLA-A, -B, and -DR typing data were available on 477 transplant pairs. The results demonstrate a 12% 1-year survival advantage for 31 patients with zero to two HLA antigen mismatches compared with three to six mismatches. The influence of each individual locus was 6.1%, 8.4%, and 5.4% for zero HLA-A, -B, and -DR mismatches, respectively, compared with two mismatches. However, when outcome from 1 to 5 years was considered, analysis of the role of each locus revealed marked differences. HLAA-matched grafts (n=45) had a 24% lower survival rate compared with two-antigen-mismatched grafts (n=148; 88% [SE 3.1] vs. 64% [SE 8.2], respectively; P=0.009). Furthermore, 34% of HLA-A-matched grafts failed between 1 and 5 years, compared with only 5% of HLA-B-matched grafts (P=0.013). These data suggest that although HLA matching is effective at reducing acute graft loss, in the longer term, HLA-A matching may impair survival. HLA-A may serve as a restriction element for indirect presentation of allopeptides or tissue-specific minor histocompatibility antigens, facilitating chronic graft loss. Therefore, we advocate a differential role for HLA matching over two epochs. A blanket approach to prospective matching for heart transplants may be premature for optimal long-term survival.


Recruitment of Mesenchymal Stem Cells to Damaged Sites by Plant-Derived Components.
Mesenchymal stem cells (MSCs) are capable of differentiating into a limited number of diverse cells and secrete regenerative factors that contribute to the repair of damaged tissue. In response to signals emitted by tissue damage, MSCs migrate from the bone marrow and area surrounding blood vessels within tissues into the circulating blood, and accumulate at the site of damage. Hence, MSC transplantation therapy is beginning to be applied to the treatment of various intractable human diseases. Recent medicinal plants studies have shown that plant-derived components can activate cell functions. For example, several plant-derived components activate cell signaling pathways, such as phosphatidylinositol 3-kinase and mitogen-activated protein kinase (MAPK), enhance expression of the CXCL12/CXCR4 axis, stimulate extracellular matrix remodeling, and consequently, promote cell migration of MSCs. Moreover, plant-derived components have been shown to promote recruitment of MSCs to damaged tissues and enhance healing in disease models, potentially advancing their therapeutic use. This article provides a comprehensive review of several plant-derived components that activate MSC migration and homing to damaged sites to promote tissue repair.


Negatively charged amino acids in the stalk region of membrane proteins reduce ectodomain shedding.
Ectodomain shedding is a post-translational modification mechanism by which the entire extracellular domain of membrane proteins is liberated through juxtamembrane processing. Because shedding rapidly and irreversibly alters the characteristics of cells, this process is properly regulated. However, the molecular mechanisms governing the propensity of membrane proteins to shedding are largely unknown. Here, we present evidence that negatively charged amino acids within the stalk region, an unstructured juxtamembrane region at which shedding occurs, contribute to shedding susceptibility. We show that two activated leukocyte cell adhesion molecule (ALCAM) protein variants produced by alternative splicing have different susceptibilities to ADAM metallopeptidase domain 17 (ADAM17)-mediated shedding. Of note, the inclusion of a stalk region encoded by a 39-bp-long alternative exon conferred shedding resistance. We found that this alternative exon encodes a large proportion of negatively charged amino acids, which we demonstrate are indispensable for conferring the shedding resistance. We also show that the introduction of negatively charged amino acids into the stalk region of shedding-susceptible ALCAM variant protein attenuates its shedding. Furthermore, we observed that negatively charged amino acids residing in the stalk region of Erb-B2 receptor tyrosine kinase 4 (ERBB4) are indispensable for its shedding resistance. Collectively, our results indicate that negatively charged amino acids within the stalk region interfere with the shedding of multiple membrane proteins. We conclude that the composition of the stalk region determines the shedding susceptibility of membrane proteins.


Orthodontic movement into bone defects augmented with bovine bone mineral and fibrin sealer: a reentry case report.
Periodontal disease can lead to migration of anterior teeth with the presence of infrabony defects. This creates the opportunity for treating such patients with a combined orthodontic-periodontic treatment. In the presented clinical case, an adult periodontal patient with extrusion of the maxillary central incisors and an infrabony defect on their lingual aspects was treated. During the surgical procedure, the bone defects were augmented with a combination of porous bovine bone mineral (Bio-Oss) and a fibrin-fibronectin sealing system (Tissucol). Ten days after surgery, the active orthodontic treatment started, and the teeth were intruded and realigned, moving the roots into the defects. After 6 months, the orthodontic appliances were removed and the teeth were retained by means of a resin-bonded splint. At this time, reduction in probing pocket depth and gingival recession was detected. Twelve months after the initial surgery, a reentry procedure was performed, showing complete filling of the predisposing defects with the presence of bone-like hard tissue. These clinical results suggest that teeth can be successfully moved and intruded into bone defects previously augmented with bovine bone substitute and fibrin glue. During the orthodontic treatment, this combined augmentation material was able to be replaced by bone-like hard tissue. At the end of the therapy, an improvement in esthetics and periodontal health status was registered.


Toward the virtual stomach: progress in multiscale modeling of gastric electrophysiology and motility.
Experimental progress in investigating normal and disordered gastric motility is increasingly being complimented by sophisticated multiscale modeling studies. Mathematical modeling has become a valuable tool in this effort, as there is an ever-increasing need to gain an integrative and quantitative understanding of how physiological mechanisms achieve coordinated functions across multiple biophysical scales. These interdisciplinary efforts have been particularly notable in the area of gastric electrophysiology, where they are beginning to yield a comprehensive and integrated in silico organ modeling framework, or 'virtual stomach'. At the cellular level, a number of biophysically based mathematical cell models have been developed, and these are now being applied in areas including investigations of gastric electrical pacemaker mechanisms, smooth muscle electrophysiology, and electromechanical coupling. At the tissue level, micro-structural models are being creatively developed and employed to investigate clinically significant questions, such as the functional effects of ICC degradation on gastrointestinal (GI) electrical activation. At the organ level, high-resolution electrical mapping and modeling studies are combined to provide improved insights into normal and dysrhythmic gastric electrical activation. These efforts are also enabling detailed forward and inverse modeling studies at the 'whole body' level, with implications for diagnostic techniques for gastric dysrhythmias. These recent advances, together with several others highlighted in this review, collectively demonstrate a powerful trend toward applying mathematical models to effectively investigate structure-function relationships and overcome multiscale challenges in basic and clinical GI research.


Characterization of the theorectical radiation dose enhancement from nanoparticles.
Recently, nanoparticles have been considered as a method of providing radiation dose enhancement in tumors. In order to quantify this affect, a dose enhancement factor (DEF) is defined that represents the ratio of the dose deposited in tumor with nanoparticles, divided by the dose deposited in the tumor without nanoparticles. Materials with atomic numbers (Z) ranging from 25 to 90 are considered in this analysis. In addition, the energy spectrum for a number of external beam x-ray sources and common radionuclides are evaluated. For a nanoparticle concentration of 5 mg/ml, the DEF is < 1.05 for Co-60, Ir-192, Au-198, Cs-137, 6, 18, and 25 MV x-rays for all materials considered. However, relatively large increases in the DEF are observed for 50, 80, 100, and 140 KVp x-rays as well as Pd-103 and I-125. The DEF increases for all sources as Z varies from 25-35. From Z = 40-60, the DEF plateaus or slightly decreases. For higher Z materials (Z>70), the DEF increases and is a maximum for the highest Z materials. High atomic number nanoparticles coupled with low energy external beam x-rays or brachytherapy sources offer the potential of significantly enhancing the delivered dose.


Life Space Assessment in Older Women Undergoing Non-Surgical Treatment for Urinary Incontinence.
Urinary incontinence (UI) impacts all aspects of life activities. This study aims to characterize change in mobility within the community utilizing the Life Space Assessment (LSA) questionnaire in women undergoing non-surgical UI treatment. Prospective cohort study, performed from July 2007 to March 2009, which followed women seeking non-surgical UI treatment and assessed their mobility and symptoms using LSA, Urogenital Distress Inventory (UDI-6), and Incontinence Impact Questionnaire (IIQ-7) at baseline and 2, 6, and 12 months post-treatment. Estimated Percent Improvement (EPI) and Patient Satisfaction Question (PSQ) were obtained post-treatment. Outpatient tertiary-care clinic. 70 ambulatory, community-dwelling women, aged 65 years or older, seeking non-surgical care for UI. Multi-component behavioral and/or pharmacologic therapies. We hypothesized LSA would improve with treatment. Repeated measures analysis with Tukey's HSD and backwards selection linear regression model were performed. LSA score decreased from baseline to 2 months (mean±SD; 63±29 to 56±28, p<0.001) and was sustained at 6 and 12 months (54±28, 54±28). UDI scores improved from 36±23 to 25±24, p<0.001, at 2 months, and improvement persisted at 6 and 12 months (22±22, 21±24). Improvements in UDI and patient perceived improvement in UI were not associated with LSA change. Age, race, and depression impacted LSA, which decreased 1-point for each additional year of age (p=0.004), 6-points for each point higher on the Geriatric Depression Scale (GDS) (p=0.002), and 6-points for African American race (p=0.048). Decreased mobility represented by LSA was related to age, depression, and race, but not UI symptom improvement.


[Protective effect of salidroside against high altitude hypoxia-induced brain injury in rats].
To observe the protective effect of salidroside against brain injury in rats exposed to hypobaric hypoxia, and investigate the molecular mechanism of salidroside in the prevention of hypobaric hypoxia-induced brain injury. Rats were placed in experiment module simulating 6000 m altitude to establish acute hypobaric hypoxia-induced brain injury models. Their respiratory frequency was observed and recorded. Cell apoptosis in the hippocampal dentate gyrus (DG) was detected by TUNEL assay; the expressions of Ras homolog family member A (RhoA), phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by Western blotting. After acute exposure to 6000 m altitude, the respiratory frequency of the rats increased remarkably. The simulation of hypobaric hypoxia induced cell apoptosis in hippocampal DG region, and salidroside intervention inhibited the process of cell apoptosis. The expressions of RhoA, p-ERK, p-JNK decreased after hypobaric hypoxia exposure. Salidroside intervention reversed RhoA expression and raised the levels of p-ERK and p-JNK. Acute exposure to hypobaric hypoxia can induce cell apoptosis in rat hippocampal DG, and salidroside can protect the cells from the exposure-induced apoptosis.


More than just the helix: A series of free flaps from the ear.
We herein present our experience using free flaps harvested from the ear region in facial, nasal and intraoral reconstruction. Between 2011 and 2016, 19 patients underwent reconstruction using 20 free flaps from the ear region based on the superficial temporal vessels. There were 10 males and 9 females with a mean age of 57 years. Defect aetiology consisted of post-tumour ablation (n = 15), trauma (n = 2) and burn scar (n = 2). Defect location involved the nose (n = 13), floor of mouth (n = 3), tongue (n = 1), lower eyelid (n = 1), and lower lip (n = 1). Twelve helical, seven temporal artery posterior auricular skin (TAPAS), and one hemiauricular flap were performed. One patient required venous re-anastomosis but complete flap necrosis eventually occurred. This patient later underwent successful contralateral helix flap reconstruction. Overall flap survival was 95%. Follow-up ranged from 12 to 69 months. A moderate to excellent aesthetic and functional outcome was achieved in all cases, but most (13/19) required later minor refinement surgery. As a versatile source of free flap options, the ear can provide more than just the helix.


Sexual activity and condom use among Eastern European adolescents--the Study of Hungarian Adolescent Risk Behaviours.
While rates of HIV and STD infection in Eastern Europe are increasing rapidly, little is known about sexual behaviour, including condom use, among Eastern European youths. The Study of Hungarian Adolescent Risk Behaviours was designed to assess the knowledge, attitudes, and behaviours of adolescents studying in secondary schools in Budapest, Hungary. Students (n =3486) in a random sample of public secondary schools completed a self-administered questionnaire, including measures of sexual activity and condom use. Thirty-eight percent of students reported ever having had vaginal intercourse. Condom use by those reporting having had sex in the past five weeks was classified as consistent/every time (40%); irregular (25.6%); and none (34.3%). Multivariate analysis revealed positive opinions about condoms, fear of AIDS, and initiation of condom use by both partners to predict more frequent condom use. Implications for targeted AIDS/STD education and prevention among adolescents are discussed.


[Bronchial hyperreactivity: state and perspective of drug intervention].
A decreased threshold of bronchial contractility under the influence of nonspecific and specific factors (bronchial hyperreactivity--BHR) is a disposing factor and precondition to the development of asthmatic disease. Probably the disturbance of the barrier function of the bronchial epithelium plays a central role in bronchial hyperreactivity. The release of phospholipid mediators from membrane phospholipids might be decisive for the establishment of bronchial hyperreactivity. This is documented, before all, by the decreasing effect of glucocorticosteroids upon the hyperreactivity since their pharmacologic efficacy is realized in first line by an inhibition of the release of arachidonic acid. We are arguing that an endogenously not compensated basical release of arachidonic acid and platelet activating factor is causally related to bronchial hyperreactivity. Prevention of asthma as well as therapy must aim at systematic reduction of bronchial hyperreactivity. Beside glucocorticosteroids and other inhibitors of phospholipase could prospectively be of therapeutic interest inhibitors of synthesis or antagonists of 5-lipoxygenase, of platelet activating factor, of leukotrienes or thromboxanes. There exist theoretical bases for practical measures of directed prevention of asthma in persons at risk. Their efficiency still awaits scientific evaluation.


Role of Solvent in Electron-Phonon Relaxation Dynamics in Core-Shell Au-SiO2 Nanoparticles.
Relaxation dynamics of plasmons in Au-SiO2 core-shell nanoparticles have been followed by femtosecond pump-probe technique. The effect of excitation pump energy and surrounding medium on the time constants associated with the hot electron relaxation has been elucidated. A gradual increase in the electron-phonon relaxation time with pump energy is observed and can be attributed to the higher perturbation of the electron distribution in AuNPs at higher pump energy. Variation in time constants for the electron-phonon relaxation in different solvents is rationalized on the basis of their thermal conductivities, which govern the rate of dissipation of heat of photoexcited electrons in the nanoparticles. On the other hand, phonon-phonon relaxation is found to be much less effective than electron-phonon relaxation for the dissipation of energy of the excited electron and the time constants associated with it remain unaffected by thermal conductivity of the solvent.


Preliminary report of expression of bax in oral cavity pathologies.
Bax is considered one of major effectors of apoptosis--programmed cell death. Immunohistochemical analysis of in vitro patterns of bax expression was mostly investigated in mammalian cell lines and tissues. The present study is the first in vivo molecular analysis of bax expression in oral cavity pathologies. The study population consisted of 45 patients with hyperplasia, neoplasm in situ malignancy, and carcinoma. Biopsies were taken from incision line, tumour section, and healthy tissue. bax expression was investigated depending on the site of biopsy material sampling and final histopathology result. No statistically significant difference was demonstrated in bax expression between four hyperplasia subgroups. However, statistically significant differences in bax expression were found between the three basic study groups (P = 0.001). Statistically significant differences in bax expression were demonstrated depending on tissue collection site (P = 0.0002). We conclude that differences in bax expression may play a role in the pathogenesis of neoplastic disease.


Evaluation of hypothermic heart preservation with University of Wisconsin solution in heterotopically and orthotopically transplanted canine hearts.
In simple cold storage of the heart, 4 hours has been proved to be a clinically safe ischemic time. The University of Wisconsin solution has been reported to extend cold ischemic time in preservation of the liver, kidney, and pancreas. The purpose of this study is to clarify the safe cold ischemic time in heart preservation with University of Wisconsin solution experimentally in heterotopically and orthotopically transplanted canine hearts. In heterotopic heart transplantation, 120 minutes after reperfusion, maximum slope of the left ventricular end-systolic pressure-volume relationship was recovered to 94% +/- 13% in the 4-hour simple cold preservation group with GIK solution and 104% +/- 11% in the 8-hour simple cold preservation group with University of Wisconsin solution but was not recovered in the 8-hour simple cold preservation with GIK solution and 16-hour simple cold preservation with University of Wisconsin solution groups. One hundred twenty minutes after reperfusion, myocardial tissue blood flow measured by laser Doppler flowmeter was recovered to 90% +/- 19% after 4 hours with simple cold preservation with GIK solution and 98% +/- 9% after 8 hours with simple cold preservation with University of Wisconsin solution but was not recovered after 8 hours with simple cold preservation with GIK solution and 16 hours with simple cold preservation with University of Wisconsin solution.(ABSTRACT TRUNCATED AT 250 WORDS)


Myosin XI is associated with fitness and adaptation to aridity in wild pearl millet.
Phenotypic changes in plants can be observed along many environmental gradients and are determined by both environmental and genetic factors. The identification of alleles associated with phenotypic variations is a rapidly developing area of research. We studied the genetic basis of phenotypic variations in 11 populations of wild pearl millet (Pennisetum glaucum) on two North-South aridity gradients, one in Niger and one in Mali. Most of the 11 phenotypic traits assessed in a common garden experiment varied between the populations studied. Moreover, the size of the inflorescence, the number of flowers and aboveground dry mass co-varied positively with a decrease in rainfall. To decipher the genetic basis of these phenotypes, we used an association mapping strategy with a mixed model. We found two SNPs on the same myosin XI contig significantly associated with variations in the average number of flowers. Both the allele frequency of the two SNPs and the average number of flowers co-varied with the rainfall gradient on the two gradients. Interestingly, this gene was also a target of selection during domestication. The Myosin XI gene is thus a good candidate for fitness-related adaptation in wild populations.


Frontal cortex contributes to human memory formation.
The contribution of medial temporal lobe structures to memory is well established. However recent brain-imaging studies have indicated that frontal cortex may also be involved in human memory formation. Specific frontal areas are recruited during a variety of procedures that promote memory formation, and the laterality of these areas is influenced by the type of information contained in the memory. Imaging methods that capture momentary changes in brain activity have further shown that the likelihood of memory formation correlates with the level of activity in these areas. These results, taken in the context of other studies, suggest that memory formation depends on joint participation of frontal and medial temporal lobe structures.


Immunogenic and antigenic epitopes of immunoglobulins I. Cross-reactivity of murine monoclonal antibodies to human IgG with the immunoglobulins of certain animal species.
Antibody-producing hybridoma clones have been isolated following immunization of mice with human IgG. Twenty-five monoclonal antibodies (nine anti-C gamma 3, fourteen anti-C gamma 2, one anit-kappa and one anti-lambda) were selected for study of their cross-reactivity with the IgG of fifteen mammalian species and chicken immunoglobulin. Each antibody exhibited a unique reaction profile suggesting that human IgG expresses a very large repertoire of immunogenic epitopes. Whilst some antibodies showed a very restricted cross-reactivity profile for others a very wide reactivity profile was observed-including two clones producing autoantibodies. Antibodies demonstrating cross-reactivity between human Fc gamma and 7S chicken immunoglobulin allow its definitive assignment as a homologue of human IgG. Four clones demonstrated specificity for bovine IgG subclass gamma 1 and gamma 2 and the degree of reactivity allows their application to qualitative and quantitative assay systems. These studies suggest new perspectives for the characterization of immunoglobulins and the standardization of anti-immunoglobulin reagents.


Walter Edward Dandy (1886-1946): The epitome of adroitness and dexterity in Neurosurgery.
Walter Edward Dandy did pioneering work in Neurosurgery in the early part of the 19th century. He worked all his life at the Johns Hopkins Hospital in USA and contributed extensively to research in hydrocephalus, the physiology of the cerebrospinal fluid and devised the technique of pneumoencephalography, apart from performing the first clipping operation in cerebral aneurysm and the division of the trigeminal nerve in neuralgic pain. This article summarizes his immense contributions in the field of Neurosurgery.


MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8.
microRNAs are aberrantly expressed during the development and progression of a variety of human cancers, including colorectal cancer (CRC). Of these microRNAs, microRNA-375 (miR-375) was previously observed to be downregulated in human colorectal cancer(CRC) plasma and tissues, but its functions are largely unknown. Here, we investigated the impact of miR-375 on CRC metastasis. Specifically, miR-375 expression was significantly decreased in human CRC tissues compared with their matched noncancerous tissues (NCTs), and low levels of miR-375 predicted tumor metastatic potential. The up-regulation of miR-375 suppressed colorectal cancer cell migration and invasion in vitro and reduced tumor metastases in murine models established by both orthotopic implantation and spleen injection. Furthermore, we identified Frizzled 8 (FZD8) as a direct target of miR-375 in CRC, and miR-375 negatively regulated Wnt/β-catenin signaling by suppressing FZD8. More importantly, FZD8 expression inversely correlated with overall survival in human CRC patients and is a likely independent predictor of survival. Therefore, we concluded that miR-375 functions as a tumor-suppressive microRNA by directly acting upon FZD8, which may serve as a new therapeutic target to inhibit tumor metastasis in CRC.


Overpopulation of Omega; in pp collisions: a way to distinguish statistical hadronization from string dynamics.
The Omega/Omega ratio originating from string decays is predicted to be larger than unity in proton-proton interactions at SPS energies ( E(lab) = 160 GeV). The antiomega dominance increases with decreasing beam energy. This surprising behavior is caused by the combinatorics of quark-antiquark production in small and low-mass strings. Since this behavior is not found in a statistical description of hadron production in proton-proton collisions, it may serve as a key observable to probe the hadronization mechanism in such collisions.


Atomic-scale distribution of water molecules at the mica-water interface visualized by three-dimensional scanning force microscopy.
We have developed a method referred to as three-dimensional scanning force microscopy (3D-SFM) which enables us to visualize water distribution at a solid-liquid interface with an atomic-scale resolution in less than 1 min. The 3D-SFM image obtained at a mica-water interface visualizes 3D distributions of adsorbed water molecules above the center of hexagonal cavities and the laterally distributed hydration layer. The atomically resolved 3D-SFM image showing mirror symmetry suggests the existence of surface relaxation of the cleaved mica surface next to the aqueous environment.


What is the meaningful measure of neuronal spike train activity?
Neuronal spike train activity is conventionally viewed in terms of certain measures of central tendency (mean or median of intervals between discrete events or mean rate of such events) and their associated measures of variability (S.D., skew, etc.). Less commonly, investigators will compute the probabilities of occurrence in an Information Theory context. Another rarely considered measure of spike trains is serial ordering. Seldom is more than one of these approaches applied to the same spike train, and we are unaware of any case where all 3 have been applied to the same train. In order to test the inter-relationships among these approaches, we examined the same spike trains with all 3 analytic methods. Measures of central tendency were taken from the original absolute interval values, whereas entropy and serial order (Markov order) were computed from the sequences of patterns of adjacent intervals, expressed in the same non-parametric format. We found that entropy (measure of uncertainty) did not correlate well with the degree of serial ordering (Markov order). Entropy also did not correlate well with measures of central tendency (median or mean interval, or impulses/s) nor with the variability of such measures. An inverse correlation was seen between Markov order and several measures of central tendency (mean interval and rate) as well as with several measures of variability. The implications of these analyses extend beyond the analysis of spike trains to most all biological and physical time series. For neurophysiologists, these analyses may challenge our common assumptions about the most appropriate way to describe and interpret neuronal spike train activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Olanzapine in treatment of patients with bipolar 1 disorder and panic comorbidity: a case study.
Anxiety disorders are frequently co-morbid with bipolar disorders (BP). Anxiety symptoms can have a great impact on course of illness and patient's quality of life. Olanzapine is the first antipsychotic approved as a mood stabilizing agent. In this paper two cases of BP 1 disorder where panic attacks co-occur treated with olanzapine were presented. In both cases olanzapine showed very good effects in treatment of panic symptoms within the course of BP disorder.


End-of-Life Transitions and Hospice Utilization for Adolescents: Does Having a Usual Source of Care Matter?
Adolescents with life-limiting illnesses have intensive end-of-life trajectories and could benefit from initiation of hospice services. The medical home model, which includes having a usual source of primary care, may help facilitate quality outcomes at the end-of-life for adolescents. The purpose of this study was to determine the relationship between having a usual source of primary care on hospice utilization and end-of-life transitions among adolescents between 15-20 years with a life-limiting illness. A retrospective cohort design used 2007-2010 California Medicaid claims data (n=585). Our dependent variables were hospice utilization (i.e., hospice enrollment, hospice length of stay) and the independent variable was usual source of primary care. Multivariate regression techniques including least squares regression, multivariate logistic regression, and negative binomial regression were used in the analysis of the relationship between usual source of primary care and hospice utilization and end-of-life transitions. Ten percent of our sample utilized hospice services. Having a usual source of primary care was associated with an increase in hospice enrollment, hospice length of stay, and end-of-life transitions. Adolescents with a cancer diagnosis were more likely to enroll in hospice services. For adolescents at the end of life, having a usual source of primary care had a significant impact on hospice enrollment and length of stay. This study is among the first to demonstrate a relationship between primary care and hospice use among this vulnerable population.


High density- and beta-lipoprotein screening for risk of coronary artery disease in the context of new findings on reverse cholesterol transport.
This article considers how high density lipoproteins (HDL) act as anti-arteriosclerotic agents, examines the usefulness of HDL indexes alone and in conjunction with other markers of coronary artery disease (CAD), and discusses how HDL markers compare with what one might expect from known metabolic mechanisms. This is accomplished by: (i) an overview of mechanisms associated with CAD, especially new findings regarding reverse cholesterol transport; (ii) a brief review of the clinical literature on biochemical markers for automated use; and (iii) analysis of data for persons with or without angiographically documented CAD. Based on these considerations, the ratio of optimized apo A-I/apo B appears superior to lipoprotein lipid markers for predicting the risk of CAD. Yet the ratio shows poor diagnostic accuracy by itself; it yields poorer diagnostic accuracy than would be expected from assessing the metabolic pathways. Discrimination is improved by using the ratio in conjunction with risk factors defined by the National Cholesterol Education Program (NCEP). Based on receiver-operator characteristic (ROC) curve data, this approach increases the accuracy by 13-14% above that obtained with current lipid markers; it improves discrimination more than the use of inflammatory markers. Apolipoprotein testing is better related to the mechanisms of cholesterol transport, is widely available, and requires only two tests, compared to three, to improve discrimination. However, inclusion of inflammatory markers may need to be considered in the future, when more information is available about their functions and clinical value.


SARS-CoV-2 Bearing a Mutation at the S1/S2 Cleavage Site Exhibits Attenuated Virulence and Confers Protective Immunity.
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) possesses a discriminative polybasic cleavage motif in its spike protein that is recognized by the host furin protease. Proteolytic cleavage activates the spike protein, thereby affecting both the cellular entry pathway and cell tropism of SARS-CoV-2. Here, we investigated the impact of the furin cleavage site on viral growth and pathogenesis using a hamster animal model infected with SARS-CoV-2 variants bearing mutations at the furin cleavage site (S gene mutants). In the airway tissues of hamsters, the S gene mutants exhibited low growth properties. In contrast to parental pathogenic SARS-CoV-2, hamsters infected with the S gene mutants showed no body weight loss and only a mild inflammatory response, thereby indicating the attenuated variant nature of S gene mutants. This transient infection was sufficient for inducing protective neutralizing antibodies that cross-react with different SARS-CoV-2 lineages. Consequently, hamsters inoculated with S gene mutants showed resistance to subsequent infection with both the parental strain and the currently emerging SARS-CoV-2 variants belonging to lineages B.1.1.7 and P.1. Taken together, our findings revealed that the loss of the furin cleavage site causes attenuation in the airway tissues of hamsters and highlighted the potential benefits of S gene mutants as potential immunogens. IMPORTANCE SARS-CoV-2 uses its spike protein to enter target cells. The spike protein is cleaved by a host protease, and this event facilitates viral entry and broadens cell tropism. In this study, we employed SARS-CoV-2 mutants lacking the S protein cleavage site and characterized their growth and pathogenicity using hamsters, a laboratory animal model for SARS-CoV-2 infection. These mutants exerted low pathogenicity but induced sufficient levels of neutralizing antibodies in hamsters, which protected hamsters from rechallenge with pathogenic clinical SARS-CoV-2 strains. These virus mutants may be used as protective immunogens against SARS-CoV-2 infection.


An analysis of synergistic sensitization.
The molecular theory of cell survival predicts that a synergistic interaction on cell survival may be expected when DNA-damaging agents are used in combination with ionizing radiation. The synergism is expected to result from the interaction of DNA single-strand damage induced by the agent and single-stand breaks induced by the radiation. Mathematically this is expressed by an increase in the alpha coefficienty of the survival equation S = exp - (alpha D + beta D2), the beta coefficient remaining constant. Two examples of synergistic interaction with ionizing radiation are analysed, a chemical used in tumour therapy and ultra-violet light. The implication of this analysis for sensitization in radiation therapy are discussed.


[Coverage extraction and up-scaling of sparse desert vegetation in arid area].
Five kinds of remote sensing inversion models, i.e., linear spectral un-mixing model, sub-pixel un-mixing model, maximal gradient difference model, and two modified maximal gradient difference models, were used to derive f(c) from remote sensing data, and the results were compared with those measured in field, aimed to select appropriate model for deriving the data of the coverage of sparse desert vegetation in arid area. The virtual multi-scale coverage images were generated by using the simple mean scale extending method to verify the inversion information from MODIS data. It was shown that linear un-mixing spectral model had a higher precision than the other models, being applicable for deriving the data of the coverage of sparse desert vegetation, but the selection of end member was rather difficult and affected the application of the model. Sub-pixel un-mixing model was universal, high precision could be obtained based on finely detailed vegetation map, but needed to measure lots of parameters. Maximal gradient difference model was simple and easy to perform, by which, the values of the coverage of crops and bare land predicted with the original model were close to the field-measured results, but the values of the coverage of sparse vegetation were underestimated. The results predicted by the modified three-band maximal gradient difference models were close to the field-measured values, and the inversed results of vegetation coverage under different scales were ideal, indicating that these models were reliable to effectively extract the information of the coverage of sparse vegetation in arid area.


Indomethacin and cognitive function in healthy elderly volunteers.
1. Cognitive function was studied after single and multiple doses of indomethacin (I) and matched placebo (P) in 20 healthy elderly volunteers using a double-blind crossover design. 2. Arousal, attention, integration, coordination, memory and mood were investigated using a battery of psychomotor tests and the Hospital Anxiety and Depression Scale. Assessments were performed before and after the first and last doses of a 7 day course of medication. 3. Critical flicker fusion threshold fell by a mean of 1.96% on indomethacin compared with a 1.13% rise on placebo 5 h after the first dose (P = 0.029). A beneficial effect on choice reaction time latency (P = 0.012) was seen both after acute and continuing administration of indomethacin. Performance at the most discriminating level (level 3) of the paired word association test was significantly better following 8 days of treatment with indomethacin in the younger (55-65 year-old) age group (P = 0.001). 4. There was no significant difference in performance on the symbol-digit substitution test and the continuous attention task. No change was seen in hospital anxiety and depression scale scores. 5. These results suggest that performance on tests of sensorimotor coordination and short term memory may improve in healthy volunteers following indomethacin administration, whereas tests of attention and psychomotor speed remain unaffected. However, further controlled studies in rheumatic patients are needed to evaluate fully the psychomotor effects of indomethacin and other NSAIDs in clinical practice.