High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients.
Gastric cancer (GC) remains an aggressive malignancy with a high rate of mortality, being the third leading cause of cancer-related death. More than one million newly diagnosed cases and 782685 deaths due to GC were reported in 2018. GC is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these patients. The discovery of new biomarkers useful in the early diagnosis of GC is mandatory. To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients. Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1. Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue. The circulating level of COL10A1 was also evaluated by ELISA in plasma of gastric adenocarcinoma patients. Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients. Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue (P < 0.05). COL10A1 seems to show an elevated expression from the beginning of carcinogenesis, in the early stages, and its increased level remains elevated during cancer progression. A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also identified. Moreover, increased COL10A1 plasma level was associated with poor survival of the patients. Plasma COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve (AUC) of 0.9171 (P = 0.0002), sensitivity of 87.76%, and specificity of 100.0%. Furthermore, this study demonstrated the potential role of plasma COL10A1 in the early detection of GC, as in the early stage, we obtained an AUC of 0.8789 (P = 0.0030), sensitivity of 81.25%, and specificity of 100.0%. Circulating expression level of COL10A1 is significantly increased in gastric adenocarcinoma patients being associated with poor survival and is a potential biomarker for early detection of GC.


[An unusual complication of calculous cholecystitis: transparietal migration of a calculus into a circumscribed peritoneal sac without a fistulous passage].
A rare complication of calculous cholecystitis (calculous that had migrated from the gallbladder and held in a circumscribed peritoneal sac with no fistula between this and the gallbladder) was observed in a woman who had been suffering from dropsy of the gallbladder with calculi for some 13 years. The most recent literature on acute and chronic perforations of the gall bladder and on known pathogenetic mechanisms regarding transparietal migration of calculi and the establishment of bilio-digestive and bilio-biliar fistulas is reviewed. A number of hypotheses are put forward to explain the unusual operative finding but the impossibility of formulating any precise preoperative diagnosis is recognized and it is stressed that many cases are recognized only following surgery.


Disparities in receipt of recommended care among younger versus older medicare beneficiaries: a cohort study.
Although health disparities have been documented between Medicare beneficiaries based on age (<65 years vs. older age groups), underuse of recommended medical care in younger beneficiaries has not been thoroughly investigated. In this study, we aim to identify and characterize vulnerabilities of the younger Medicare age group (aged <65 years) in relation to older age groups (aged 65-74 years and ≥75 years) and to explore age group as a determinant of use of recommended care among Medicare beneficiaries. We conducted a cohort study of community-dwelling Medicare beneficiaries who participated in the Medicare Current Beneficiary Survey between 2001 and 2008 (N = 30,117). Age group characteristics were compared using cross-sectional data at baseline. During follow-up, we assessed the association between age and receipt of recommended care on 38 recommended care indicators, adjusting for sociodemographic and clinical characteristics. Follow-up periods differed by component indicator. At baseline, a higher proportion of younger beneficiaries experienced social disadvantage, disability and certain morbidities than older age groups. During follow-up, younger beneficiaries were significantly less likely to receive overall recommended care compared to those 65-74 years of age (adjusted odds ratio and 95% confidence interval: 0.75, 0.70-0.80). In addition, male gender, non-Hispanic black race, less than high school education, living alone, with children or with others, psychiatric disorders and higher activity limitation stages were all associated with underuse of recommended care. Younger Medicare beneficiary status appears to be an independent risk factor for underuse of appropriate care. Support to ameliorate disparities in different social and health aspects may be warranted.


Na+ Ions Induce the Pirouetting Motion and Catalytic Activity of [2]Rotaxanes.
We have prepared [2]rotaxanes, the behavior of which as switchable catalysts depends on their pirouetting motion, which can be controlled through the addition and removal of Na+ ions. At least three sequential on/off cycles of a Michael reaction can be performed in situ when using the NaTFPB/[2.2.2]cryptand reagent pair to switch "on" and "off" the catalytic ability of the [2]rotaxanes.


Deceived by orchids: sex, science, fiction and Darwin.
Between 1916 and 1927, botanists in several countries independently resolved three problems that had mystified earlier naturalists - including Charles Darwin: how did the many species of orchid that did not produce nectar persuade insects to pollinate them? Why did some orchid flowers seem to mimic insects? And why should a native British orchid suffer 'attacks' from a bee? Half a century after Darwin's death, these three mysteries were shown to be aspects of a phenomenon now known as pseudocopulation, whereby male insects are deceived into attempting to mate with the orchid's flowers, which mimic female insects; the males then carry the flower's pollen with them when they move on to try the next deceptive orchid. Early twentieth-century botanists were able to see what their predecessors had not because orchids (along with other plants) had undergone an imaginative re-creation: Darwin's science was appropriated by popular interpreters of science, including the novelist Grant Allen; then H.G. Wells imagined orchids as killers (inspiring a number of imitators), to produce a genre of orchid stories that reflected significant cultural shifts, not least in the presentation of female sexuality. It was only after these changes that scientists were able to see plants as equipped with agency, actively able to pursue their own, cunning reproductive strategies - and to outwit animals in the process. This paper traces the movement of a set of ideas that were created in a context that was recognizably scientific; they then became popular non-fiction, then popular fiction, and then inspired a new science, which in turn inspired a new generation of fiction writers. Long after clear barriers between elite and popular science had supposedly been established in the early twentieth century, they remained porous because a variety of imaginative writers kept destabilizing them. The fluidity of the boundaries between makers, interpreters and publics of scientific knowledge was a highly productive one; it helped biology become a vital part of public culture in the twentieth century and beyond.


[Course of the resistance of Staphylococcus aureus to pefloxacin. A study based on 782 strains isolated in 1985 and 1986].
We studied the evolution of the resistance of Staphylococcus aureus to pefloxacin during 1985 and 1986 in eight hospital units. The pefloxacin resistant Staphylococcus aureus, which amounted to 8.9% in 1985 reached 27% in 1986. They are found mainly among the methicillin-resistant Staphylococcus. There is no obvious relationship between this resistance and the consumption of pefloxacin in each of the units.


Effects of gabexate mesilate, a protease inhibitor, on human sphincter of Oddi motility.
Gabexate mesilate is an antiprotease drug, which reduced the severity of pancreatitis and frequency of post-ERCP pancreatitis. In dogs gabexate inhibits sphincter of Oddi motility but no data are available in humans. The aim of this study was to verify by manometry the action of gabexate on human sphincter of Oddi motility. We enrolled 12 patients with idiopathic recurrent pancreatitis (eight males, five females, mean age 46 +/- 8 years). Standard preendoscopic sphincter of Oddi manometry was done in basal conditions and during infusion of gabexate 20 mg/min: basal pressure, amplitude and frequency of phasic contractions, and motility index (amplitude per frequency) were calculated before and after gabexate injection. Statistical analysis was performed by using Wilcoxon rank test for paired data. Six patients had a manometric diagnosis of stenosis (basal pressure greater than 40 mm Hg); six had normal findings. Phasic activity was not evaluable in five patients with stenosis. Basal pressure was unaffected by drug infusion, while gabexate caused a significant reduction of phasic activity, both in terms of frequency (4.5 +/- 1 vs 3.6 +/- 1; P < 0.05) and amplitude (157.4 +/- 44 vs 80.0 +/- 32; P < 0.05) of contractions. Motility index was reduced on average by 49%. In conclusion, this pilot study confirms, in patients with acute recurrent pancreatitis, the inhibitory action of gabexate on sphincter of Oddi motility already described in dogs. This action needs to be revaluated at therapeutic dosages. On the other hand, prophylactic use of the drug should be avoided during sphincter of Oddi manometry, in order to avoid false negative results.


In situ separation of bacterial trapping and killing functions of the perfused liver.
CF-1 mice cleared and killed 80% of a 1.2 x 10(9) intravenous dose of Salmonella typhimurium after 30 min. The perfused mouse liver trapped 70% of a similar dose of S. typhimurium in a single pass, but in the perfusion model no significant killing of the trapped organisms was observed. The perfused rat liver also avidly trapped bacteria. Because of its larger size, we have been able to devise techniques to experimentally distinguish between the bacterial trapping and killing functions of this organ. When the liver was washed free of blood with sterile M-199, over 70 to 80% of a 10(6) to 10(10) dose of viable S. typhimurium was trapped after a single pass, but no significant bacterial killing was observed. When blood or plasma was added to the perfusion medium, over 50% of the trapped bacteria were killed in 15 to 30 min. Phase contrast and electron micrographs of perfused livers showed extensive extracellular trapping of bacteria in the sinusoids. Our data show that humoral factors are apparently not necessary for efficient trapping of live Salmonella by the perfused rat liver but are an absolute requirement for bacterial activity of the organ.


Comprehensive expression analysis of rice Armadillo gene family during abiotic stress and development.
Genes in the Armadillo (ARM)-repeat superfamily encode proteins with a range of developmental and physiological processes in unicellular and multicellular eukaryotes. These 42 amino acid, long tandem repeat-containing proteins have been abundantly recognized in many plant species. Previous studies have confirmed that Armadillo proteins constitute a multigene family in Arabidopsis. In this study, we performed a computational analysis in the rice genome (Oryza sativa L. subsp. japonica), and identified 158 genes of Armadillo superfamily. Phylogenetic study classified them into several arbitrary groups based on a varying number of non-conserved ARM repeats and accessory domain(s) associated with them. An in-depth analysis of gene expression through microarray and Q-PCR revealed a number of ARM proteins expressing differentially in abiotic stresses and developmental conditions, suggesting a potential roles of this superfamily in development and stress signalling. Comparative phylogenetic analysis between Arabidopsis and rice Armadillo genes revealed a high degree of evolutionary conservation between the orthologues in two plant species. The non-synonymous and synonymous substitutions per site ratios (Ka/Ks) of duplicated gene pairs indicate a purifying selection. This genome-wide identification and expression analysis provides a basis for further functional analysis of Armadillo genes under abiotic stress and reproductive developmental condition in the plant lineage.


Pilot plant investigations on cleaning efficiencies to reduce hazelnut cross-contamination in industrial manufacture of cookies.
Shared equipment in industrial food manufacture has repeatedly been described as a potential source of unlabeled food allergens, i.e., hidden allergens. However, the impact of shared equipment on allergen cross-contamination is basically unknown. Therefore, we sought to investigate systematically the extent of hazelnut cross-contamination in fine bakery wares as a model. A product change from cookies with 10% hazelnut to cookies without hazelnuts was simulated on pilot plant equipment. The extent of hazelnut cross-contamination (HNCC) was analyzed by enzyme-linked immunosorbent assay (ELISA) for each production device (kneaders, rotary molder, wire cutting machine, and steel band oven) and various cleaning procedures used between products. The experiments were performed repeatedly with finely ground hazelnuts and with roughly chopped hazelnut kernels. Cross-contamination from chopped kernels was distributed statistically but not homogeneously, and sampling and analysis with the ELISA was therefore not reproducible. Further analysis concentrated on homogenously distributed HNCC from ground hazelnut. Apart from product changes without intermediate cleaning, the highest HNCC was found after mechanical scraping: Up to 100 mg/kg hazelnut protein was found in the follow-up product after processing by one machine. After additional cleaning with hot water, the HNCC decreased regardless of the processing device to levels at or below 1 mg/kg hazelnut protein. In our pilot plant study, the application of an appropriate wet cleaning procedure in combination with quantitative monitoring of the cleaning efficiency reduced the hazelnut protein cross-contamination to a level at which severe hazelnut-related allergic reactions are unlikely to occur.


"Important enough to show the world": Using Authentic Research Opportunities and Micropublications to Build Students' Science Identities.
Primarily undergraduate institutions (PUIs) often struggle to provide authentic research opportunities that culminate in peer-reviewed publications due to "recipe-driven" lab courses and the comprehensive body of work necessary for traditional scientific publication. However, the advent of short-form, single-figure "micropublications" has created novel opportunities for early-career scientists to make and publish authentic scientific contributions on a scale and in a timespan compatible with their training periods. The purpose of this qualitative case study is to explore the benefits accrued by eight undergraduate and master's students who participated in authentic, small-scale research projects and disseminated their work as coauthors of peer-reviewed micropublications at a PUI. In these interviews, students reported that through the process of conducting and publishing their research, they developed specific competencies: reading scientific literature, proposing experiments, and collecting/interpreting publication-worthy data. Further, they reported this process enabled them to identify as contributing members of the greater scientific community.


Laboratory detective work identifies a mishandling problem in sample aliquoting.
Data from a recent ovarian cancer biomarker study using serum aliquots from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial Biorepository showed that CA125II concentrations in these aliquots were significantly lower than those previously measured in the same subjects from the same blood draw. We designed an experiment to investigate whether samples used in the study (reference study) were compromised during the aliquoting process. We measured CA125II in the "sister" vials created during the same aliquoting process as the reference study aliquot, and in "cousin" vials newly aliquoted from another parent vial from the same blood draw, from 15 healthy controls in the study. Because the sister vials were created in a specific order, we also assessed whether there was a CA125II concentration gradient among the sisters. The Wilcoxon signed-rank test was used to test the statistical significance of the observed differences. Mean CA125II concentration (volume-averaged) was greater in the sisters than the cousins in all 15 subjects (p<0.001). The mean coefficient of variation was 0.25 (range: 0.12-0.43) in the sisters and 0.11 (range: 0.-1.1) in the cousins (p<0.008). The mean ratio of CA125II in the 5(th) aliquoted versus the 3(rd) aliquoted sister vial was 1.66 (1.25-2.5, p<0.001). These data suggest that the parent vials were not adequately mixed before they were aliquoted. CA125II in serum can partially precipitate to form a concentration gradient in long-term storage. Rigorous vortexing after thawing and before aliquoting is thus critical.


Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes.
Agents that inhibit platelet function are used routinely in the treatment and prevention of acute coronary syndromes. The main antiplatelet treatments used combine aspirin with one of the thienopyridine P2Y(12) antagonists, either clopidogrel or prasugrel. By blocking the synthesis of thromboxane A(2) in platelets and by blocking the effects of ADP, respectively, these agents reduce platelet activity, platelet aggregation and thrombus formation. Ticagrelor (marketed by AstraZeneca as Brilinta™ in the USA, and as Brilique(®) or Possia(®) in Europe) is a cyclopentyl-triazolo-pyrimidine, a new chemical class of P2Y(12) antagonist that is now approved for use in the wide spectrum of acute coronary syndromes. In this article we provide an overview of ticagrelor. We discuss the differences in mode of action compared with other P2Y(12) antagonists, examine its pharmacodynamic, pharmacokinetic and safety profile, and summarize the various clinical trials that have provided information on its efficacy in combination with aspirin. Ticagrelor appears to overcome some of the difficulties that have been encountered with other antiplatelet treatments, clopidogrel in particular.


Time, place, event of sudden death.
Sudden death, known since antiquity, is almost always due to cardiovascular disorder, but not exclusively to coronary artery disease. It is postulated that two processes, action of pre-existing risk factors (enlarged heart, abnormal conduction, extra systoles, ischemia) and new, untoward events (acute infarction or ischemia) culminate in the catastrophic event. Sudden death is apparently most likely during waking hours; sleep is a lesser risk. Which subjects are at greatest risk and which circumstances are most dangerous remain unknown and are important topics for further investigation.


An exploration of diabetic foot screening procedures data by a multiple correspondence analysis.
Gangrene and amputation are among most feared complications of diabetes mellitus. Early detection of patients at high risk for foot ulceration can prevent foot complications. Regular foot screening (medical history, foot examination and classification into risk groups) was introduced at the out-patient diabetes clinic in Ljubljana in November 1996. We aimed to explore the relationships between the observed variables, check the appropriateness of the risk status classification and of the post-screening decisions. The data of 11.594 patients, obtained in 18 years, were analysed by multiple correspondence analysis (MCA). Most of the observed variables were categorical. The majority of the screened population was free of foot complications. We demonstrated an increasing frequency and severity of foot problems with an increasing age, as well as the association between the loss of protective sensation and the history of foot ulceration, foot deformity and callus formation, the history of foot ulcer or amputation and acute foot ulceration. A new finding was that the location of foot deformity points was closer to female than male gender, indicating the possible role of fashionable high-heel footwear. The appropriateness of therapeutic decisions was confirmed: the points representing absent foot pulses and referral to vascular specialist were close together, as well as points representing foot deformity and special footwear prescription or callus formation and referral to pedicurist. MCA was applied to the data on foot pathology in the population attending the out-patient diabetes clinic. The method proved to be a useful statistical tool for analysing the data of screening procedures.


Delayed reconfiguration of a non-emotional task set through reactivation of an emotional task set in task switching: an ageing study.
In our everyday life, we frequently switch between different tasks, a faculty that changes with age. However, it is still not understood how emotion impacts on age-related changes in task switching. Using faces with emotional and neutral expressions, Experiment 1 investigated younger (n = 29; 18-38 years old) and older adults' (n = 32; 61-80 years old) ability to switch between an emotional and a non-emotional task (i.e. responding to the face's expression vs. age). In Experiment 2, younger and older adults also viewed emotional and neutral faces, but switched between two non-emotional tasks (i.e. responding to the face's age vs. gender). Data from Experiment 1 demonstrated that switching from an emotional to a non-emotional task was slower when the expression of the new face was emotional rather than neutral. This impairment was observed in both age groups. In contrast, Experiment 2 revealed that neither younger nor older adults were affected by block-wise irrelevant emotion when switching between two non-emotional tasks. Overall, the findings suggest that task-irrelevant emotion can impair task switching through reactivation of the competing emotional task set. They also suggest that this effect and the ability to shield task-switching performance from block-wise irrelevant emotion are preserved in ageing.


The nasopharyngeal airway. Assessment of position by fibreoptic laryngoscopy.
Artificial nasopharyngeal airway position and performance were assessed in 120 anaesthetised adult patients. Using a fibreoptic laryngoscope mean distances from nares to larynx were measured at 209 mm (SD 11) in males and 180 mm (SD 11) in females; those from nares to epiglottis were 159 mm (SD 12) in males and 140 mm (SD 11) in females. Nasopharyngeal airways were frequently misplaced, 60% lying beyond the tip of the epiglottis and 13% lodged in the vallecula. Forty-two percent of subjects had clinical evidence of respiratory obstruction. Nasopharyngeal airway compression in the nasopharynx and obstruction by the tongue and soft palate were common causes of respiratory obstruction. Regression analysis revealed that nares-epiglottis length correlated significantly with subject height (t = 3.9, p = 0.0002), but not with three external measurements made around the head and neck. Head flexion and extension resulted in comparatively little relative movement of the nasopharyngeal airway. Nasopharyngeal airway length and diameter should be standardised to optimise performance.


Dehiscent scar in the lower uterine segment after Caesarean section and IVF infertility treatment: a case report.
Caesarean section is the most common obstetric operation associated with short and long term risks, one of which is uterine scar dehiscence. In this case report we describe four cases of in vitro fertilization and embryo transfer (IVF+ET) treatment where the embryo was transferred into the uterus with known scar dehiscence in the lower uterine segment after a previous Caesarean section (SC). All transfers of embryos were ultrasound guided directly into the middle of uterine cavity. All resulting pregnancies continued without problems related to the dehiscent scar and babies were delivered in the third trimester by elective/emergency SC. Our cases suggest that IVF+ET can be offered as an infertility treatment option despite a dehiscent scar in the lower uterine segment after previous SC.


Genome-Wide Association Study Reveals Candidate Genes for Root-Related Traits in Rice.
Root architecture is a determinant factor of drought resistance in rice and plays essential roles in the absorption of water and nutrients for the survival of rice plants. Dissection of the genetic basis for root structure can help to improve stress-resistance and grain yield in rice breeding. In this study, a total of 391 rice (Oryz asativa L.) accessions were used to perform a genome-wide association study (GWAS) on three root-related traits in rice, including main root length (MRL), average root length (ARL), and total root number (TRN). As a result, 13 quantitative trait loci (QTLs) (qMRL1.1, qMRL1.2, qMRL3.1, qMRL3.2, qMRL3.3, qMRL4.1, qMRL7.1, qMRL8.1, qARL1.1, qARL9.1, qTRN9.1, qTRN9.2, and qTRN11.1) significantly associated with the three traits were identified, among which three (qMRL3.2, qMRL4.1 and qMRL8.1) were overlapped with OsGNOM1, OsARF12 and qRL8.1, respectively, and ten were novel QTLs. Moreover, we also detected epistatic interactions affecting root-related traits and identified 19 related genetic interactions. These results lay a foundation for cloning the corresponding genes for rice root structure, as well as provide important genomic resources for breeding high yield rice varieties.


[Arch first technique using handmade branched graft].
We created a method using handmade branched graft to do the aortic arch surgery easier and safer. We made the branched graft using 12 and 8 mm vascular graft. A 77-year-old man with Stanford type A aortic dissection was operated with this method under deep hypothermia. After aortic root manipulation, perfusion of the aortic arch was stopped and selective cerebral perfusion was established. Left subclavian artery (LSCA) was anastomosed to one of the branches. The perfusion of the LSCA was re-started via one of its branches. Respectively, left common carotid artery and brachiocephalic artery reconstruction and reperfusion were performed in a same fashion. After distal anastomosis, anastomosis between the branched graft and main graft was performed consecutively. Postoperative course was uneventful and there was no complication. The treatment of our branched graft was easier than that of ready-made 4-branched graft. We could perform the operation under clear view for its movability with minimal cerebral ischemic time.


Is paranoid status prognostic of good outcomes? It depends.
Better outcomes for psychiatric inpatients classified as paranoid rather than nonparanoid could be due to group differences in disability levels created by traditional classification approaches. Paranoid functioning, per se, may not predict good institutional outcomes. The authors retrieved community outcome data for 469 inpatients from 19 wards, a subsample of participants that had been previously examined during their inpatient stay. Paranoid groups showed better community outcomes as an artifact of differences in disability levels when classifications were based on the traditional approach that requires a predominance of paranoid over nonparanoid behavior. No differential outcomes appeared when classifications were based on dimensionally measured paranoid functioning alone. In fact, dispositions of patients suggest that staff view paranoid behavior as a negative rather than positive prognostic indicator.


Two regions of the tail are necessary for the isoform-specific functions of nonmuscle myosin IIB.
To function in the cell, nonmuscle myosin II molecules assemble into filaments through their C-terminal tails. Because myosin II isoforms most likely assemble into homo-filaments in vivo, it seems that some self-recognition mechanisms of individual myosin II isoforms should exist. Exogenous expression of myosin IIB rod fragment is thus expected to prevent the function of myosin IIB specifically. We expected to reveal some self-recognition sites of myosin IIB from the phenotype by expressing appropriate myosin IIB rod fragments. We expressed the C-terminal 305-residue rod fragment of the myosin IIB heavy chain (BRF305) in MRC-5 SV1 TG1 cells. As a result, unstable morphology was observed like MHC-IIB(-/-) fibroblasts. This phenotype was not observed in cells expressing BRF305 mutants: 1) with a defect in assembling, 2) lacking N-terminal 57 residues (N-57), or 3) lacking C-terminal 63 residues (C-63). A myosin IIA rod fragment ARF296 corresponding to BRF305 was not effective. However, the chimeric ARF296, in which the N-57 and C-63 of BRF305 were substituted for the corresponding regions of ARF296, acquired the ability to induce unstable morphology. We propose that the N-57 and C-63 of BRF305 are involved in self-recognition when myosin IIB molecules assemble into homo-filament.


PD-1/PD-L pathway and autoimmunity.
Programmed cell death 1 (PD-1) was isolated in 1992 by subtractive-hybridization technique, as a molecule whose expression is enhanced by apoptotic stimuli. Since then we have been analyzing the function of PD-1 in the regulation of immune responses. Generation of PD-1 deficient mice, pathophysiological analyses of autoimmune diseases in PD-1 deficient mice, identification of two ligands, and analyses of downstream events of PD-1 revealed that PD-1 prevents autoimmunity by inhibiting activation of self-reactive lymphocytes. These findings were further applied on human autoimmune diseases and single nucleotide polymorphisms (SNPs) on human PD-1 gene have been reported to link with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and type I diabetes.


Multimode quantum dynamics using Gaussian wavepackets: The Gaussian-based multiconfiguration time-dependent Hartree (G-MCTDH) method applied to the absorption spectrum of pyrazine.
The Gaussian-based multiconfiguration time-dependent Hartree (G-MCTDH) method is applied to calculate the S(2)(pipi( *)) absorption spectrum of the pyrazine molecule, whose diffuse structure results from the ultrafast nonadiabatic dynamics at the S(2)-S(1) conical intersection. The 24-mode second-order vibronic-coupling model of Raab et al. [J. Chem. Phys. 110, 936 (1999)] is employed, along with 4-mode and 10-mode reduced-dimensional variants of this model. G-MCTDH can be used either as an all-Gaussian approach or else as a hybrid method using a partitioning into primary modes, treated by conventional MCTDH basis functions, and secondary modes described by Gaussian particles. Comparison with standard MCTDH calculations shows that the method converges to the exact result. The variational, nonclassical evolution of the moving Gaussian basis is a key element in obtaining convergence. For high-dimensional systems, convergence is significantly accelerated if the method is employed as a hybrid scheme.


Changes in the lipid profile of elite basketball and soccer players after a match.
The lipid profile of elite basketball and soccer athletes was evaluated and compared with that of inactive individuals. Total cholesterol (T-C), low and high density lipoprotein cholesterol (LDL-C and HDL-C), and triglyceride (TG) concentration were measured in the morning and after a soccer or a basketball match. All parameters of lipid profile measured at a fasted and resting state, except HDL-C, were lower in the athletes compared with the controls (p < 0.01). The soccer match resulted in a greater decrease in TG (78.3 ± 6.7 to 70.7 ± 6.3, p < 0.01), T-C (179.3 ± 10.7 to 171.6 ± 9.6, p < 0.01), LDL-C (110.9 ± 8.9 to 103.5 ± 7.5, p < 0.01) compared with the basketball match that resulted only in a decrease in LDL-C (126.8 ± 9.5 to 117.3 ± 9.1, p < 0.01) and an increase in HDL-C that was similar to that observed after the soccer match (9-12%). These findings support the beneficial effects of basketball and soccer on cardiovascular health.


Cord blood-derived mesenchymal stem cell does not stimulate nor inhibits T lymphocytes activation.
The immune modulatory properties of mesenchymal stem cell (MSC) had brought a new insight in cell-based neotherapy. However, recent works of MSC are focused exclusively on bone marrow-derived MSC. We evaluated the immunogenicity of cord blood-derived MSC (CB-MSC) on T lymphocytes. Human peripheral blood mononuclear cells (PBMC) were prepared by density gradient separation and culture with the presence or absence of CB-MSC. PBMC were collected for activation analysis by flow cytometry at 24-, 48-, and 72- hours. The results showed that, CB-MSC does not stimulate nor inhibit T lymphocyte activation.


CD31 defines a subpopulation of human adipose-derived regenerative cells with potent angiogenic effects.
Cellular heterogeneity represents a major challenge for regenerative treatment using freshly isolated Adipose Derived Regenerative Cells (ADRCs). Emerging data suggest superior efficacy of ADRCs as compared to the ex vivo expanded and more homogeneous ADRCs (= ASCs) for indications involving (micro)vascular deficiency, however, it remains unknown which ADRC cell subtypes account for the improvement. Surprisingly, we found regarding erectile dysfunction (ED) that the number of injected CD31+ ADRCs correlated positively with erectile function 12 months after one bolus of autologous ADRCs. Comprehensive in vitro and ex vivo analyses confirmed superior pro-angiogenic and paracrine effects of human CD31+ enriched ADRCs compared to the corresponding CD31- and parent ADRCs. When CD31+, CD31- and ADRCs were co-cultured in aortic ring- and corpus cavernous tube formation assays, the CD31+ ADRCs induced significantly higher tube development. This effect was corroborated using conditioned medium (CM), while quantitative mass spectrometric analysis suggested that this is likely explained by secretory pro-angiogenic proteins including DKK3, ANGPT2, ANAX2 and VIM, all enriched in CD31+ ADRC CM. Single-cell RNA sequencing showed that transcripts of the upregulated and secreted proteins were present in 9 endothelial ADRC subsets including endothelial progenitor cells in the heterogenous non-cultured ADRCs. Our data suggest that the vascular benefit of using ADRCs in regenerative medicine is dictated by CD31+ ADRCs.


Meta-analysis of the effect of animal maturity on muscle characteristics in different muscles, breeds, and sexes of cattle.
The effect of animal maturity on fiber cross-sectional area, percentage of fiber types, activities of isocitrate dehydrogenase (ICDH) and lactate dehydrogenase (LDH), total and insoluble collagen and lipid concentration was investigated in the longis-simus thoracis (LT), semitendinosus (ST), and triceps brachii (TB) muscles. The analysis considered 2,642 muscle samples from bulls, steers, and cows of Aubrac, Charolais, Limousin, Montbéliard, and Salers breeds. For the bulls, the fiber cross-sectional area, percentage of slow oxidative fibers, and ICDH activity showed a quadratic relationship (P < 0.05), and the percentage of fast oxidative-glycolytic and fast glycolytic fibers and LDH activity showed a cubic relationship (P < 0.05) with increased maturity. A linear relationship was observed for the collagen and lipid muscle characteristics. The response equation coefficients for different muscles indicate that development of muscle characteristics is different for each muscle. Compared with the other muscles, ST muscle had a greater fiber cross-sectional area, proportion of fast glycolytic fibers, LDH activity, and collagen content. The LT muscle had a greater proportion of slow-oxidative fibers and lipid (P < 0.05). Within the ST muscle, all characteristics except lipid concentration showed different development between the breeds. Steers showed greater changes in muscle fiber cross-sectional area, percentage of fast oxidative-glycolytic and fast glycolytic fibers, and total lipid in the muscle with increasing maturity compared with bulls. The mean fiber cross-sectional area and percentage of fast glycolytic fibers was greater and the mean lipid concentration was less in bulls compared with steers (P < 0.05). Data for cows were from more mature animals. Muscle characteristics in cows did not show large changes with increasing degree of maturity. Muscle type accounts for a greater proportion of the variation in the muscle characteristics than breed and sex of the animal.


[Late sequelae of small doses of ionizing radiation in humans].
Toxic effects of low doses of ionizing radiation, below 100 rads, may appear within up to 20 years after irradiation. These effects include: increased incidence of leukaemias, pulmonary neoplasms, tumours of the thyroid, stomach and liver. The younger is the organism at the time of radiation exposure the shorter is the latency period of tumour development. Children irradiated in utero with low doses of X-rays exhibit delayed mental development. The period of particular fetal risk is 8-15 weeks of intrauterine life. In the first generation of irradiated males no chromosomal changes were revealed. The free-radical theory of tumour aetiology and the role of factors which may attenuate tumour development on the free-radical pathway are discussed.


Challenges in primary care for diabetes and hypertension: an observational study of the Kolar district in rural India.
Chronic diseases have emerged as the leading cause of death globally, and 20% of Indians are estimated to suffer from a chronic condition. Care for chronic diseases poses a major public health challenge, especially when health care delivery has been geared traditionally towards acute care. In this study, we aimed to better understand how primary care for diabetes and hypertension is currently organised in first-line health facilities in rural India, and propose evidence-based ways forward for strengthening local health systems to address chronic problems. We used qualitative and quantitative methods to gain insight into how care is organised and how patients and providers manage within this delivery system. We conducted in-depth interviews with the medical doctors working in three private clinics and in three public primary health centres. We also interviewed 24 patients with chronic diseases receiving care in the two sub-sectors. Non-participant observations and facility assessments were performed to triangulate the findings from the interviews. The current delivery system has many problems impeding the delivery of quality care for chronic conditions. In both the public and private facilities studied, the care processes are very doctor-centred, with little room for other health centre staff. Doctors face very high workloads, especially in the public sector, jeopardising proper communication with patients and adequate counselling. In addition, the health information system is fragmented and provides little or no support for patient follow-up and self-management. The patient is largely left on their own in trying to make sense of their condition and in finding their way in a complex and scattered health care landscape. The design and organisation of care for persons with chronic diseases in India needs to be rethought. More space and responsibility should be given to the primary care level, and relatively less to the more specialised hospital level. Furthermore, doctors should consider delegating some of their tasks to other staff in the first-line health facility to significantly reduce their workload and increase time available for communication. The health information system needs to be adapted to better ensure continuity of care and support self-management by patients.


Effect of Reveromycin A on experimental tooth movement in OPG-/- mice.
In osteoprotegerin-deficient (OPG-/-) mice, osteoclast activity causes bone resorption to outpace bone formation, leading to the development of severe osteoporosis. Such mice are therefore useful for investigating the alveolar bone of patients with osteoporosis. Reveromycin A (RM-A) was recently identified as the unique agent acting on osteoclast activation. This study aimed to analyze the effect of RM-A on the orthodontic treatment of OPG-/- mice (a model of osteoporosis patients with high levels of bone turnover). We examined alveolar bone remodeling in OPG-/- and wild-type (WT) mice during continuous tooth movement. The orthodontic force was induced by means of a Ni-Ti closed-coil spring to move the maxillary first molar for 14 days. RM-A sodium salt (1 mg/kg) was administered intraperitoneally twice daily. In OPG-/- mice, the tooth movement distance was longer, alveolar bone resorption was enhanced, the osteoclast count was greater, and serum alkaline phosphatase and tartrate-resistant acid phosphatase levels were higher relative to those in WT mice. However, the administration of RM-A in OPG-/- mice reduced these parameters. We conclude that RM-A normalizes bone metabolism and loss of alveolar bone during continuous tooth movement in OPG-/- mice.


The Evaluation of the Reactivating and Neuroprotective Efficacy of Two Newly Prepared Bispyridinium Oximes (K305, K307) in Tabun-Poisoned Rats-A Comparison with Trimedoxime and the Oxime K203.
The ability of two newly developed oximes (K305, K307) to protect tabun-poisoned rats from tabun-induced inhibition of brain acetylcholinesterase, acute neurotoxic signs and symptoms and brain damage was compared with that of the oxime K203 and trimedoxime. The reactivating and neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose were evaluated. The reactivating efficacy of a newly developed oxime K305 is lower compared to the reactivating efficacy of the oxime K203 and trimedoxime while the ability of the oxime K307 to reactivate tabun-inhibited acetylcholinesterase (AChE) in the brain roughly corresponds to the reactivating efficacy of the oxime K203 and it is slightly lower compared to trimedoxime. In addition, only one newly developed oxime (K307) combined with atropine was able to markedly decrease tabun-induced neurotoxicity although it did not eliminate all tabun-induced acute neurotoxic signs and symptoms. These results correspond to the histopathological evaluation of tabun-induced brain damage. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes (especially trimedoxime) in the treatment of acute tabun poisonings.


Sesamol induced apoptotic effect in lung adenocarcinoma cells through both intrinsic and extrinsic pathways.
Sesamol is a phenolic lignan found in sesame seeds (Sesamum indicum L.) and sesame oil. The anticancer effects and molecular mechanisms underlying its apoptosis-inducing effect were investigated in human lung adenocarcinoma (SK-LU-1) cells. Sesamol inhibited SK-LU-1 cell growth with an IC50 value of 2.7 mM and exhibited less toxicity toward normal Vero cells after 48 h of treatment (Selective index = 3). Apoptotic bodies-the hallmark of apoptosis-were observed in sesamol-treated SK-LU-1 cells, stained with DAPI. Sesamol increased the activity of caspase 8, 9, and 3/7, indicating that apoptotic cell death occurred through both extrinsic and intrinsic pathways. Sesamol caused the loss of mitochondrial transmembrane potential signifying intrinsic apoptosis induction. Decreasing Bid expression revealed crosstalk between the intrinsic and extrinsic apoptotic pathways; demonstrating clearly that sesamol induces apoptosis through both pathways in human lung adenocarcinoma (SK-LU-1) cells.


Observation of the topological phase transition from the spatial correlation of a biphoton in a one-dimensional topological photonic waveguide array.
We propose a simple method, using the first singular value (FSV) of the spatial correlation of biphotons, to characterize topological phase transitions (TPTs) in one-dimensional (1D) topological photonic waveguide arrays (PWAs). After analyzing the spatial correlation of biphotons using the singular value decomposition, we found that the FSV of the spatial correlation of biphotons in real space can characterize TPTs and distinguish between the topological trivial and nontrivial phases in PWAs based on the Su-Schrieffer-Heeger model. The analytical simulation results were demonstrated by applying the coupled-mode theory to biphotons and were found to be in good agreement with those of the numerical simulation. Moreover, the numerical simulation of the FSV (of the spatial correlation of biphotons) successfully characterized the TPT in a PWA based on the Aubry-André-Harper and Rice-Mele models, demonstrating the universality of this method for 1D topological PWAs. Our method provides biphotons with the possibility of acquiring information regarding TPTs directly from the spatial correlation in real space, and their potential applications in quantum topological photonics and topological quantum computing as quantum simulators and information carriers.


[Pharmacological studies on rat passive cutaneous anaphylaxis (PCA) (author's transl)].
A study was made of the PCA reaction in rat hind paw for analysis of the mechanisms of the of the anaphylactic release of mediators in vivo. Also studied was the function of cyclic AMP in the anaphylactic release of histamine during PCA induced in rats with homologous and heterologous antibody. A close correlation was seen among edema formation, histamine release and decrease of cyclic AMP during homologous and heterologous PCA. Theophylline, epinephrine and isoproterenol increased the cyclic AMP level and strongly inhibited edema formation and histamine release, in all animals. Aminopyrine and trasylol also increased the cyclic AMP level but aminopyrine did not inhibit either edema formation or histamine release in case of heat labile homocytotropic antibody induced PCA in rats and trasylol did not inhibit histamine release in any animal. Methysergide and mepyramine strongly inhibited histamine release but did not alter cyclic AMP levels. Thus, the increase of the cyclic AMP level did not always inhibit the histamine release during PCA in rats. It has also been demonstrated that the PCA reaction in rat hind paw is a suitable model for studying the mechanisms of the anaphylactic release of mediators in vivo.


Options for Engineering Apomixis in Plants.
In plants, embryogenesis and reproduction are not strictly dependent on fertilization. Several species can produce embryos in seeds asexually, a process known as apomixis. Apomixis is defined as clonal asexual reproduction through seeds, whereby the progeny is identical to the maternal genotype, and provides valuable opportunities for developing superior cultivars, as its induction in agricultural crops can facilitate the development and maintenance of elite hybrid genotypes. In this review, we summarize the current understanding of apomixis and highlight the successful introduction of apomixis methods into sexual crops. In addition, we discuss several genes whose overexpression can induce somatic embryogenesis as candidate genes to induce parthenogenesis, a unique reproductive method of gametophytic apomixis. We also summarize three schemes to achieve engineered apomixis, which will offer more opportunities for the realization of apomictic reproduction.


A role for the Auxin Response Factors ARF6 and ARF8 homologs in petal spur elongation and nectary maturation in Aquilegia.
The petal spur of the basal eudicot Aquilegia is a key innovation associated with the adaptive radiation of the genus. Previous studies have shown that diversification of Aquilegia spur length can be predominantly attributed to variation in cell elongation. However, the genetic pathways that control the development of petal spurs are still being investigated. Here, we focus on a pair of closely related homologs of the AUXIN RESPONSE FACTOR family, AqARF6 and AqARF8, to explore their roles in Aquileiga coerulea petal spur development. Expression analyses of the two genes show that they are broadly expressed in vegetative and floral organs, but have relatively higher expression in petal spurs, particularly at later stages. Knockdown of the two AqARF6 and AqARF8 transcripts using virus-induced gene silencing resulted in largely petal-specific defects, including a significant reduction in spur length due to a decrease in cell elongation. These spurs also exhibited an absence of nectar production, which was correlated with downregulation of STYLISH homologs that have previously been shown to control nectary development. This study provides the first evidence of ARF6/8 homolog-mediated petal development outside the core eudicots. The genes appear to be specifically required for cell elongation and nectary maturation in the Aquilegia petal spur.


Deafness in sarcoidosis.
A case of sarcoidosis and sensori-neural deafness in which the lesion was thought to be cochlear in position is presented and the audiometric findings are discussed in detail. A review of the reported cases shows that sarcoid lesions may involve the hearing mechanism at any point along its neural axis.


Fidelity to a behavioral intervention to improve goals of care decisions for nursing home residents with advanced dementia.
Ensuring fidelity to a behavioral intervention implemented in nursing homes requires awareness of the unique considerations of this setting for research. The purpose of this article is to describe the goals of care cluster-randomized trial and the methods used to monitor and promote fidelity to a goals of care decision aid intervention delivered in nursing homes. The cluster randomized trial tested whether a decision aid for goals of care in advanced dementia could improve (1) the quality of communication and decision-making, (2) the quality of palliative care, and (3) the quality of dying for nursing home residents with advanced dementia. In 11 intervention nursing homes, family decision-makers for residents with advanced dementia received a two-component intervention: viewing a video decision aid about goals of care choices and then participating in a structured decision-making discussion with the nursing home care plan team, ideally within 3 months after the decision aid was viewed. Following guidelines from the National Institutes of Health Behavior Change Consortium, fidelity was assessed in study design, in nursing home staff training for intervention implementation, and in monitoring and receipt of the intervention. We also monitored the content and timing of goals of care discussions. Investigators enrolled 151 family decision-maker/resident dyads in intervention sites; of those, 136 (90%) received both components of the intervention, and 92%-99% of discussions addressed each of four recommended content areas-health status, goals of care, choice of a goal, and treatment planning. A total of 94 (69%) of the discussions between family decision-makers and the nursing home care team were completed within 3 months. The methods we used for intervention fidelity allowed nursing home staff to implement a goals of care decision aid intervention for advanced dementia. Key supports for implementation included design features that aligned with nursing home practice, efficient staff training, and a structured guide for goals of care discussions between family decision-makers and staff. These approaches may be used to promote fidelity to behavioral interventions in future clinical trials.


Metformin Antagonizes Ovarian Cancer Cells Malignancy Through MSLN Mediated IL-6/STAT3 Signaling.
Ovarian cancer is the most lethal gynecological malignancy, and chemotherapy remains the cornerstone for ovarian cancer management. Due to the unsatisfactory prognosis, a better understanding of the underlying molecular carcinogenesis is urgently required. Assays for determining cell growth, cell motility, and apoptosis were employed to evaluate the potential antitumor effects of metformin against ovarian cancer cells. Molecular biological methods were employed to explore the underlying mechanism. Human ovarian cancer samples and Gene Expression Profiling Interactive Analysis (GEPIA) dataset were used for uncovering the clinical significances of mesothelin (MSLN) on ovarian cancer. In the present work, we found that metformin treatment led to cell growth and cell migration inhibition, and induced cell apoptosis. Metformin administration also impaired cancer cell stemness and the capillary-like structure formation capacity of SKOV3 cells. On mechanism, metformin treatment remarkably reduced mesothelin (MSLN) expression, downregulated IL-6/STAT3 signaling activity, subsequently resulted in VEGF and TGFβ1 expression. We also observed an oncogenic function of MSLN on ovarian cancer. Collectively, our findings suggested that metformin exerts anticancer effects by suppressing ovarian cancer cell malignancy, which attributed to MSLN inhibition mediated IL6/STAT3 signaling and VEGF and TGFβ1 downregulation.


Unstable Bony Chance Fracture Successfully Treated With Teriparatide in Patient With Ankylosed Spine: A Case Report and Review of the Literature.
Background: Ankylosed spines with ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis (DISH) are prone to fractures due to osteoporosis and fracture instability from long lever arm. In such cases, surgical management is the main treatment option. Case presentation: We report a first case of successful treatment of unstable bony Chance fracture at thoracolumbar junction in DISH patient using teriparatide and review previous literature on ankylosed spine fractures treated with teriparatide. An 82-year-old male patient presented with back pain after falling from a 3 m height 3 months ago. Imaging studies showed L1 unstable flexion-distraction injury (bony Chance fracture) and intravertebral vacuum cleft in ankylosed spine due to DISH. Conservative treatment, teriparatide and orthosis, was determined as the most appropriate approach because the patient declined surgery and presented with tolerable mechanical back pain without any neurologic deficits. Solid bony union was successfully achieved without any complications after 1-year treatment. Conclusion: Although surgical management is strongly recommended for unstable fracture in ankylosed spine, non-surgical treatment including teriparatide and orthosis might be safer and effective options in bony Chance fracture without neurologic deficits and intractable mechanical pain.


Astaxanthin attenuates contrast agent-induced acute kidney injury in vitro and in vivo via the regulation of SIRT1/FOXO3a expression.
The study was processed to investigate the effect of astaxanthin (AST; 3,3-dihydroxybeta, beta-carotene-4,4-dione) on the acute kidney injury induced by iohexol and the relationship with SIRT1/FOXO3a signal pathway. Thirty male Sprague Dawley rats were randomly divided into five groups as follows: control group (CON; olive oil only), contrast media group, astaxanthin control group (100 mg/kg), low astaxanthin dose group (LAG, 50 mg/kg) and high astaxanthin dose group (HAG, 100 mg/kg). As followed, serum creatinine (SCr), blood urea nitrogen (BUN), the oxidative stress markers and apoptosis-related proteins were detected. Human proximal tubular epithelial cells (HK-2) were cultured in DMEM/F12 medium in vitro and then randomly divided into appropriate experimental groups: normal group (N), dimethyl sulfoxide (DMSO), iohexol group (I), iohexol + (1.0, 10.0 μmol/L) astaxanthin group (I + LAST; I + HAST), iohexol + SIRT1 inhibitors (nicotinamide) group (NA) and iohexol + si-RNA FOXO3a group (si-RNA FOXO3a); when cultured for 24 h, cell proliferation ability was tested by cell counting kit (CCK-8), reactive oxygen species (ROS) were detected by flow cytometry and the expression of SIRT1 and FOXO3a were observed using western blot. At the end of the experiment, the levels of SCr, BUN and malondialdehyde (MDA) were all increased in the CM group. The LAG and HAG reduce superoxide anion (SOD) activity, catalase (CAT) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) content, as well as SCr and BUN level. Moreover, apoptosis-associated proteins, caspase 3 p17, bax and bcl-2 were upregulated. In HK-2 cells, after adding iohexol, proliferation and intracellular ROS levels were significantly increased. Using astaxanthin in advance after the intervention, the result is opposite. SIRTl inhibitors NA can reduce the expression of SIRTl and decrease the expression of FOXO3a protein. Si-RNA FOXO3a reduces the expression of FOXO3a but had no significant effect on the expression of SIRT1. Our study demonstrates that the intervention of astaxanthin could attenuate the oxidative stress and apoptosis in contrast-induced acute kidney injury (CI-AKI), and the SIRT1/FOXO3a pathway participates in the contrast-induced apoptosis of HK-2 cells. Finally, astaxanthin reduces CI-AKI by suppression of apoptosis, which may be through inhibition of SIRT1/FOXO3a pathways.


The Campylobacter jejuni glycome.
Microbial cell surface glycans in the form of glycolipids and glycoproteins frequently play important roles in cell-cell interaction and host immune responses. Given the likely importance of these surface structures in the survival and pathogenesis of Campylobacter jejuni, a concerted effort has been made to characterise these determinants genetically and structurally since the genome was sequenced in 2000. We review the considerable progress made in characterising the Campylobacter glycome including the lipooligosaccharide (LOS), the capsule and O- and N-linked protein glycosylation systems, and speculate on the roles played by glycan surface structures in the life-cycle of C. jejuni.


Interface microstructure effects on dynamic failure behavior of layered Cu/Ta microstructures.
Structural metallic materials with interfaces of immiscible materials provide opportunities to design and tailor the microstructures for desired mechanical behavior. Metallic microstructures with plasticity contributors of the FCC and BCC phases show significant promise for damage-tolerant applications due to their enhanced strengths and thermal stability. A fundamental understanding of the dynamic failure behavior is needed to design and tailor these microstructures with desired mechanical responses under extreme environments. This study uses molecular dynamics (MD) simulations to characterize plasticity contributors for various interface microstructures and the damage evolution behavior of FCC/BCC laminate microstructures. This study uses six model Cu/Ta interface systems with different orientation relationships that are as- created, and pre-deformed to understand the modifications in the plasticity contributions and the void nucleation/evolution behavior. The results suggest that pre-existing misfit dislocations and loading orientations (perpendicular to and parallel to the interface) affect the activation of primary and secondary slip systems. The dynamic strengths are observed to correlate with the energy of the interfaces, with the strengths being highest for low-energy interfaces and lowest for high-energy interfaces. However, the presence of pre-deformation of these interface microstructures affects not only the dynamic strength of the microstructures but also the correlation with interface energy.


Bionic hand as artificial organ: Current status and future perspectives.
Even though the hand comprises only 1% of our body weight, about 30% of our central nervous systems (CNS) capacity is related to its control. The loss of a hand thus presents not only the loss of the most important tool allowing us to interact with our environment, but also leaves a dramatic sensory-motor deficit that challenges our CNS. Reconstruction of hand function is therefore not only an essential part of restoring body integrity and functional wholeness but also closes the loop of our neural circuits diminishing phantom sensation and neural pain. If biology fails to restore meaningful function, today we can resort to complex mechatronic replacement that have functional capabilities that in some respects even outperform biological alternatives, such as hand transplantation. As with replantation and transplantations, the challenge of bionic replacement is connecting the target with the CNS to achieve natural and intuitive control. In recent years, we have developed a number of strategies to improve neural interfacing, signal extraction, interpretation and stable mechanical attachment that are important parts of our current research. This work gives an overview of recent advances in bionic reconstruction, surgical refinements over technological interfacing, skeletal fixation, and modern rehabilitation tools that allow quick integration of prosthetic replacement.


QT interval dispersion in young women with anorexia nervosa.
To evaluate the degree of QT dispersion in a group of young women in the starvation phase of anorexia nervosa (AN) and its relation to left ventricular (LV) mass. Sixteen patients with self-induced starvation were matched with 16 women of normal weight and 16 constitutionally thin women (body mass index <20 kg/m2). Starving patients and control patients underwent an electrocardiogram and echocardiogram. QT intervals were measured from surface electrocardiograms and QT dispersion was defined as the difference between maximum QT and minimum QT occurring in any of the 12 leads. LV-chamber mass was significantly less in women with AN than in thin and normal-weight women. QT dispersion was significantly greater in AN than in the thin and control groups (QT dispersion: 50 +/- 14 vs 34 +/- 9 and 37 +/- 11 ms, P <.001; QT interval dispersion corrected for heart rate: 49+12 vs 34 +/- 9 and 36 +/- 7 ms, P <.01, respectively). A significant relation between QT dispersion and LV-mass index (r = -0.726, P <.01), and between QTc dispersion and LV mass index (r = -0.693, P < 0.01) were found only in the patients with AN. Starving patients show an increased QT dispersion related to reduced LV mass. This result could represent a useful indicator of arrhythmic risk and sudden death in AN.


[CD4+ alpha beta T cell and gamma delta T cell responses to BCG in patients with pulmonary tuberculosis--comparison with healthy controls].
We demonstrated that CD4+ alpha beta (CD4+) and gamma delta T cell subsets from healthy donors had similar effector functions (cytotoxicity and cytokine production) in response to mycobacterial antigens, despite differences in the antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis, this study was undertaken to compare T cell functions between patients with pulmonary tuberculosis with no complications and healthy controls. Both resting and activated CD4+ and gamma delta T cells from the patient group proliferated in response to live BCG at a significantly lower rate than those from the control group. The cytotoxicity of BCG-pulsed monocytes and IFN-gamma production in both the CD4+ and gamma delta T cells from patients was significantly lower than those of controls. In contrast to IFN-gamma, significantly higher IL-10 production by both CD4+ and gamma delta T cells from patients was detected. The proliferative responses to BCG by CD4+ and gamma delta T cells from patients after antituberculous therapy were partially restored, but remained at lower levels compared with controls. These results suggest that not only a general deterioration in CD4+ and gamma delta T cells effector functions, but also suppressive factors (such as IL-10) might be responsible for the pathogenesis of pulmonary tuberculosis, and that the low response to BCG by both CD4+ and gamma delta T cells in patients with tuberculosis is in part attributable to patient predisposition.


Oligonucleotide site-directed mutagenesis in Xenopus egg extracts.
Addition of M13mp18 single-stranded DNA annealed with an oligonucleotide to a Xenopus egg extract results in a rapid and efficient incorporation of the oligonucleotide in a complete double-stranded supercoiled molecule. Both the efficiency of DNA synthesis and the recovery of complete double-stranded molecules are increased relative to the reaction carried out by the classical technique using the E. coli Klenow DNA polymerase, DNA ligase, dNTPs, ATP and ions. Site specific mutagenesis was assayed by reverting a point mutation in the lacz region of M13mp18. The color assay described by Messing and sequencing of the DNA extracted from isolated plaques was used to check for the reversion. A 2 hr incubation of the heteroduplex carrying the mutagenic oligonucleotide in the Klenow-ligase-dNTP mixture allows a recovery of 6% mutant phage after transformation of competent cells with the reaction products. Using the Xenopus egg extract, 83% mutant phage were recovered after the same incubation time, in reactions entirely performed in parallel. The Xenopus extract is stable and contains all components required for the assay, including all ionic and protein factors; thus the only addition is the annealed DNA. Such an eukaryotic system is therefore an attractive alternative to the reconstituted prokaryotic DNA polymerase-DNA ligase system for site specific mutagenesis.


Prolonged extracorporeal life support for bridging to transplant: technical and mechanical considerations.
Through July 1995, the Extracorporeal Life Support Organization (ELSO) registry listed 87 patients who received extracorporeal life support (ECLS) as a bridge to cardiac transplantation with a survival rate of 41%. At Arkansas Children's Hospital, 17 patients (aged between two days and 24 years) with diagnoses of dilated cardiomyopathy (seven), postcardiotomy (seven) and acute viral myocarditis (three) were bridged with ECLS. Mechanical complications only occurred in two patients, neither of which necessitated withdrawal of ECLS. Decompression of the left heart was performed in 11 patients, six via a surgically placed vent and five with a blade/balloon artial septostomy. Documented infection occurred in 11/17 patients, but only one patient died from infection. Fifteen of 17 patients (88%) recovered or were transplanted, of which 13 (76%) were discharged home. With left-heart decompression and appropriate treatment of infection, ECLS may be used as a bridge to cardiac transplantation or until the return of cardiac function.


On the interpretive process in psychoanalysis.
The concept of interpretation and its function in the psychoanalytic process is updated by emphasizing the analyst's contributions to the psychoanalytic treatment process through his interpretations of resistance and transference. By incorporating Kohut's recent contributions to the psychoanalysis of narcissistic personality disorders into our general considerations regarding the process of interpretation, we have been aided in our effort to unify the theory of the psychoanalytic treatment process. We offer a broadened definition of the interpretative process and stress the added "interpersonal" dimension of resistance and transference, namely, those elements in the development of both, which are affected by the analyst;s personality and the manner of his interpretive and noninterpretive interventions. This makes the artificially sharp dichotomy between verbal and nonverbal interpretations or between interpretations and noninterpretive interventions unnecessary. The recognition of the "self-object" role of the analyst in the narcissistic transferences not only lends more precision to our understanding of archaic narcissistic experiences (whishes, demands, fantasies, etc.), but makes their interpretation within the transference our preferred analytic response. The need to foster the so-called "real relationship" between patient and analyst and the need to deal with such "nontransference" aspects of the relationship noninterpretively is thus replaced with interpretive interventions. To underline our emphasis on the analyst;s contributions to the analytic process, clinical samples and brief vignettes illustrate the manner in which interpretations may retard or promote the analytic process.


Ethological validation and the assessment of anxiety-like behaviours: methodological comparison of classical analyses and structural approaches.
The research on emotional reactivity usually implies the use of standardised behavioural tests that provide a quick idea of the effect of a treatment on the reactivity of subjects to potentially dangerous situations. Many validity criteria have been considered to evaluate these tests. This validity concept supports the idea that animals' behaviour in these tests model human anxiety. Generally, those criteria repeatedly labelled as "ethological validation" refer to the analogy between animals and human in the meaning of the test situation. Although the content of the ethological validation concept is heterogeneous, it is steadily related to a fixed interpretation of the behavioural items produced in a given experimental setting. The basic assumption of such reasoning is that the behavioural items would always be expressed in the same behavioural context whatever the subject, its gender, strain or species, thoroughly asserting a predefined subjective state. Using multivariate and textual analysis, we found evidence that the "ethological validation" recourse to an a priori interpretation for a given behavioural variable may be deceptive. We defend the idea that the meaning of a behavioural variable should be restricted to the general context where it arose. Theoretical propositions and methodological options are discussed.


Interaction of the disintegrin and cysteine-rich domains of ADAM12 with integrin alpha7beta1.
We describe a novel interaction between the disintegrin and cysteine-rich (DC) domains of ADAM12 and the integrin alpha7beta1. Integrin alpha7beta1 extracted from human embryonic kidney 293 cells transfected with alpha7 cDNA was retained on an affinity column containing immobilized DC domain of ADAM12. 293 cells stably transfected with alpha7 cDNA adhered to DC-coated wells, and this adhesion was partially inhibited by 6A11 integrin alpha7 function-blocking antibody. The X1 and the X2 extracellular splice variants of integrin alpha7 supported equally well adhesion to the DC protein. Integrin alpha7beta1-mediated cell adhesion to DC had different requirements for Mn2+ than adhesion to laminin. Furthermore, integrin alpha7beta1-mediated cell adhesion to laminin, but not to DC, resulted in efficient cell spreading and phosphorylation of focal adhesion kinase (FAK) at Tyr397. We also show that adhesion of L6 myoblasts to DC is mediated in part by the endogenous integrin alpha7beta1 expressed in these cells. Since integrin alpha7 plays an important role in muscle cell growth, stability, and survival, and since ADAM12 has been implicated in muscle development and regeneration, we postulate that the interaction between ADAM12 and integrin alpha7beta1 may be relevant to muscle development, function, and disease. We also conclude that laminin and the DC domain of ADAM12 represent two functional ligands for integrin alpha7beta1, and adhesion to each of these two ligands via integrin alpha7beta1 triggers different cellular responses.


Correlation between Echo-Tracking Parameters and In Vitro Measurements of Arterial Contraction and Relaxation in Rats Fed a High-Cholesterol Diet.
Echo-tracking (ET) is a new technique that allows the assessment of arterial function and stiffness. This study aimed to ascertain the utility of the echo-tracking (ET) technique to assess vascular stiffness in rats with hypercholesterolemia and atherosclerosis. ET was used to measure the arterial stiffness of the aorta in cholesterol-fed Sprague-Dawley rats (group T1, n=10, for 4 weeks; group T2, n=10, for 12 weeks) and normal control rats (group C1, n=10; group C2, n=10). In vitro isometric tension experiments were used to measure the maximum contractile tension (MCT) and maximum relaxation percentage (MRR%) of aortic rings. Indicators of arterial stiffness and aortic MCT and MRR% were compared between groups using linear regression analysis. Light microscopic evaluation was used to demonstrate atherosclerotic changes in the aorta. The rat models were successfully induced; pathological examination of the aortas showed significant atherosclerosis in group T2, but not in groups C1, C2, or T1. The arterial stiffness parameters obtained using ET and aortic rings in vitro showed significant impairments in T1 and T2 rats compared with C1 and C2 controls (all P<0.05 vs. controls). In addition, these impairments were greater in the T2 group than in the T1 group (all P<0.05). Finally, MRR% correlated with the distensibility coefficient (r=0.396, P=0.012), arterial compliance (r=0.317, P=0.047), stiffness parameter b (r=-0.406, P=0.009) and one-point pulse wave β (r=-0.434, P=0.005). These results suggest that ET could be used to evaluate the changes in arterial wall elasticity associated with atherosclerosis and hypercholesterolemia.


Optoelectronic properties of CdSe0.75S0.25 nanocrystals assembled into micro-electrodes.
CdSe0.75S0.25 semiconductor nanocrystals were synthesized by chemical colloidal route. The crystal structure, morphology and optical properties of synthesized CdSe0.75S0.25 nanocrystals were characterized by XRD, TEM and UV-Vis absorption spectroscopy respectively. The crystal structure of CdSe0.75S0.25 is face-centered Cubic sphalerite phase. The average size is about 7 nm in diameter. A gold tip-to-tip structure electrode with the gap size -20 microm was fabricated using conventional optical lithography technique followed by film deposition and standard lift-off process. An optoelectronics device was fabricated based on CdSe0.75S0.25 by assembling nanocrystals into electrodes by using dielectrophoresis (DEP) process. The electrical transport properties and opto-electrical transport properties of the fabricated device were measured at temperature range from 5 K to 305 K. The results show that the resistance of CdSe0.75S0.25 NCs increases with the temperature decreases, indicating a typical semiconductor behavior. An obvious photoconductive behavior was observed, demonstrated potential application in nano-optoelectronics devices. After data analyzing, the conductivity shows the 0.5 exponent of Efros-Shklovskii variable-range-hopping (ES-VRH) model.


Identification of an Iron Metabolism-Related lncRNA Signature for Predicting Osteosarcoma Survival and Immune Landscape.
Background: Long noncoding RNAs (lncRNAs) act as epigenetic regulators in the process of ferroptosis and iron metabolism. This study aimed to identify an iron metabolism-related lncRNA signature to predict osteosarcoma (OS) survival and the immune landscape. Methods: RNA-sequencing data and clinical information were obtained from the TARGET dataset. Univariate Cox regression and LASSO Cox analysis were used to develop an iron metabolism-related lncRNA signature. Consensus clustering analysis was applied to identify subtype-based prognosis-related lncRNAs. CIBERSORT was used to analyze the difference in immune infiltration and the immune microenvironment in the two clusters. Results: We identified 302 iron metabolism-related lncRNAs based on 515 iron metabolism-related genes. The results of consensus clustering showed the differences in immune infiltration and the immune microenvironment in the two clusters. Through univariate Cox regression and LASSO Cox regression analysis, we constructed an iron metabolism-related lncRNA signature that included seven iron metabolism-related lncRNAs. The signature was verified to have good performance in predicting the overall survival, immune-related functions, and immunotherapy response of OS patients between the high- and low-risk groups. Conclusion: We identified an iron metabolism-related lncRNA signature that had good performance in predicting survival outcomes and showing the immune landscape for OS patients. Furthermore, our study will provide valuable information to further develop immunotherapies of OS.


The Role of Transabdominal Ultrasound Elastography in Gastrointestinal Non-Liver Diseases: Current Application and Future Prospectives.
Ultrasound imaging is the first-line investigation for patients with abdominal symptoms, as it effectively depicts the gastrointestinal tract and enables the diagnosis of multiple pathological conditions. Among different recent ultrasound technological advancements, elastography enables the evaluation of various tissue characteristics, such as neoplastic transformation or fibroinflammatory status. In recent years, ultrasound elastography has been utilized extensively for the study of liver diseases and in numerous other clinical settings, including gastrointestinal diseases. Current guidelines suggest the use of transabdominal ultrasound elastography to characterize bowel wall lesions, to assess gastrointestinal contractility, to diagnose and grade chronic pancreatitis; however, no specific indications are provided. In the present paper, we summarize the evidence concerning the application of different ultrasound elastography modalities in gastrointestinal non-liver diseases.


Renal effects of contrast media.
A brief overview of the renal effects of contrast media (CM) is presented. Many of the physiologic actions of CM are indistinguishable from those of mannitol matched for osmolality. The pathophysiology of CM-induced acute renal failure remains obscure.


Modulating the Balance of Synaptic and Extrasynaptic NMDA Receptors Shows Positive Effects against Amyloid-β-Induced Neurotoxicity.
Alzheimer's disease (AD) patients suffer a disturbance in the balance between synaptic (GluN2A, mediating the protective pathway) and extrasynaptic NMDA receptors (NMDARs) (GluN2B, mediating the excitotoxic pathway), and, therefore, restoring the balance of GluN2A and GluN2B should be beneficial for AD. In this study, the GluN2B-selective antagonist, ifenprodil, and the non-selective NMDAR agonist, NMDA, had little effect on amyloid-β (Aβ)-induced long-term potentiation deficits. Enhancing the activity of GluN2A had a protective effect against Aβ, and specific activation of GluN2A and inhibition of GluN2B showed a better protective effect. In Aβ ICV-injected animals, the combination of ifenprodil and D-cycloserine (a co-activator of NMDRs similar to D-serine) led to greater improvement in behavior tests (nest building, novel object recognition, and Morris water maze) than ifenprodil (Morris water maze) or D-cycloserine (nest building) alone. Signal pathway analysis showed that Aβ disturbed the GluN2A/GluN2B-related pathway. The ratio of GluN2A to GluN2B decreased in Aβ-treated animals, and TORC dephosphorylation and ERK1/2 activation, which could be initiated by GluN2A, also decreased in the hippocampal tissues of Aβ-treated animals. As a result, the activation of CREB and the content of brain-derived BDNF decreased. The combination of ifenprodil and D-cycloserine reversed the signal pathway more significantly than ifenprodil or D-cycloserine alone, indicating that Aβ-induced toxicology was mediated both by functionally inhibiting GluN2A and enhancing GluN2B. These results indicate that enhancing synaptic NMDARs and inhibiting extrasynaptic NMDARs concurrently showed protective effects against Aβ-induced neurotoxicity, suggesting that modulation of the balance between GluN2A and GluN2B could be a potential strategy for AD drug development and therapy.


[Rotatory instability of the knee joint in cases of previously treated "Unhappy Triad" (author's transl)].
The combined injury of the ligaments and capsular structures of the knee joint always causes rotatory instability as the sum of all or some a.m. injuries (Slocum; Nicholas). This has to be taken into account in the operative treatment. We have followed 14 patients with old "unhappy triad" injuries who had been operated upon with the question in mind whether the usual procedures with reefing of the ligaments or plastic replacements including meniscectomies, but without paying attention to the lax posterior capsule could correct the typical anteromedial rotatory instability. The results showed that this was true only in about half the cases. The remaining patients continued to complain about instability in the operated knee joint. Objectively, the pre-operatively positive rotatory drawer sign remained unchanged. Therefore we conclude that the anteromedial rotatory instability of the knee joint can be improved by the procedure devised by Slocum and Nicholas.


Three-dimensional echocardiography for the assessment of left ventricular geometry and papillary muscle morphology in hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HC) is characterized by left ventricular (LV) hypertrophy and associated with papillary muscle (PM) abnormalities. The aim of this study was to evaluate the utility of three-dimensional echocardiography (3DE) for the geometric assessment of LV hypertrophy and PM morphology. The study included 24 patients with an established diagnosis of HC and 31 healthy controls. 3DE was performed using an iE33 or EPIQ 7C ultrasound system with an X5-1 transducer. QLAB software was used for the 3D analysis of LV wall thickness (LVWT) and PM morphology and hypertrophy; the number and cross-sectional area (CSA) of anterolateral and posteromedial PMs; and the presence of bifid or accessory PMs. Patients with HC had a larger LVWT compared to controls in all segments (p < 0.001), and LVWT was largest in the midventricular septal segment (2.12 ± 0.68 cm). The maximum LVWT followed a spiral pattern from the LV base to the apex. The CSA of both anterolateral and posteromedial PMs was larger in patients with HC than in controls (1.92 vs. 1.15 cm2; p = 0.001 and 1.46 vs. 1.08 cm2; p = 0.033, respectively). The CSA of the posteromedial PM was larger in patients with LVOT obstruction than in those without (2.64 vs 1.16 cm2, p = 0.021). 3DE allows the assessment of LV geometry and PM abnormalities in patients with HC. 3DE demonstrated that the maximum hypertrophy was variable and generally located in a spiral from the LV base to the apex.


Expired hydrocarbons in patients with chronic liver disease.
Fifty patients with various types of liver disease and twenty-one healthy subjects were examined for lipoperoxidation in vivo by gaschromatographic assay of volatile hydrocarbons (ethane, ethylene, propane, n-butane, n-pentane) in breath gases. In 15 patients with alcoholic cirrhosis the amount of expired pentane was greater than in all the other groups examined. No significant increase of exhaled ethane, in contrast, was detected in the same patients. These results seem to indicate that pentane is a more sensitive index than ethane for ethanol-induced lipoperoxidation. This simple and non-invasive method opens up promising new opportunities for clarifying in humans, the role of lipoperoxidation in ethanol-induced liver damage, as well as in other chronic liver disease.


A new gnathiid (Crustacea: Isopoda) parasitizing two species of requiem sharks from Lizard Island, Great Barrier Reef, Australia.
Third-stage juveniles (praniza 3) of Gnathia grandilaris n. sp. were collected from the gill filaments and septa of 5 requiem sharks, including a white tip reef shark, Triaenodon obesus, and 4 grey reef sharks, Carcharhinus amblyrhynchos, at Lizard Island, Great Barrier Reef, Australia, in March 2002. Some juvenile gnathiids were then maintained in fresh sea water until they molted to adults. Adult males appeared 19 days following detachment of juveniles from host fishes, but no juveniles molted successfully into females. The current description is based, therefore, on bright field and scanning electron microscopy observations of adult males and third-stage juveniles. Unique features of the male include the triangular-shaped inferior medio-frontal process, 2 areolae on the dorsal surface of the pylopod, and a slender pleotelson (twice as long as wide) with lateral concavities. The third-stage juvenile has distinctive white pigmentation on the black pereon when alive, while the mandible has 9 triangular backwardly directed teeth. This species has the largest male and third-stage juvenile of any Gnathia spp. from Australia and of any gnathiid isopods associated with elasmobranchs.


The possible contribution of neuronal nicotinic acetylcholine receptors in depression.
Although tobacco use and smoking were introduced long ago, it was only recently that the nicotine contained in the tobacco leaves was recognized as an addictive substance acting on the central nervous system (CNS). However, even prior to this recognition, several studies have reported an association between smoking and psychiatric disorders. One of the many observations was that smoking cessation is accompanied by a marked increase in the probability of major depression. In parallel with the discovery of the neuronal nicotinic acetylcholine receptors and their extensive expression in the CNS, this association sheds new light on the influence of cholinergic transmission in depression. In this article, we examine the various modes of action of nicotine in the CNS and discuss the mechanisms by which this alkaloid can prevent or precipitate mood disorders, and the possibility of discovering new therapeutic avenues for the treatment of depression.


The serious suicide attempt. Five-year follow-up study of 886 patients.
A five-year follow-up study was undertaken of a previously reported 1968 cohort of 886 people who had attempted suicide. The working hypothesis that those who had seriously attempted suicide (21%) would have a higher suicide rate on long-term follow-up was confirmed. During the five-year follow-up period, a total of 34 suicides were found, which represented 3.84% of the total number at risk. Of those who had seriously attempted suicide, 12 (6.45%) of 186 succeeded later; of the other (nonserious or less serious) attempters, 22 (3.1%) of 700 succeeded. The serious-attempter suicide rate was 2.1 times that of the others, and this difference was statistically significant (P less than .05). In addition, patients who made attempts that were judged serious on medical but not on psychiatric grounds were found to have a suicide rate significantly higher (P less than .05) than patients who had made suicide attempts that were not a serious medical threat.


The Quantification of Total Coronary Atheroma Burden - A Major Step Forward.
The extent of coronary artery disease has been shown to be an important indicator of prognosis. Cardiac computed tomography (CT) has the ability to measure plaque, with both coronary artery calcium scanning and CT angiography (CTA), to give a measure of total atheroma burden. Beyond assessing stenosis and atherosclerosis, CTA can assess high-risk plaque. These plaques are thought to be consistent with plaques that are vulnerable and more likely to rupture and cause acute coronary syndromes. However, the high-risk plaque concept suffers from poor reproducibility and poor positive predictive power. Total coronary atheroma burden has been shown to be a better predictor of coronary events than high-risk plaques or stenosis. This paper reviews the literature in this regard and demonstrates total coronary atheroma burden to be the best predictor of future cardiovascular disease. We searched MEDLINE, EMBASE and the Cochrane library database for studies assessing plaque burden and outcomes by CT. We used text words and related Medical Subject Headings (MeSH) for cardiac, calcification, plaque burden, CT, prognosis, mortality, event, death, survival and myocardial infarction.


Isolated abducens nerve palsy: Comparison of microvascular and other causes.
Abducens nerve paralysis is the most common ocular motor neuropathy. In this article, we aimed to compare the causes of isolated abducens nerve palsy in terms of demographic, clinical features, and prognosis. Thirty-six isolated abducens nerve palsy patients were prospectively enrolled in the study. The demographic, clinical features, and prognosis compared in two etiological groups as microvascular and other causes. The most common etiology was microvascular, which was seen in 16/36 (44.4%) patients. Mean clinical recovery time was 2.5±1.3 months (range, 10 days-6 months). When etiological groups were compared as microvascular and other causes, the mean age of the microvascular group was significantly higher (62.8±13.3 vs. 44.5±16.4, p=0.001). Diabetes mellitus was seen significantly higher in the microvascular group than other causes group (p=0.001), but no significant difference was observed in terms of other atherosclerotic risk factors (p>0.05). The fasting blood glucose and hemoglobin A1c value were significantly higher in the microvascular group (p=0.02 and p=0.02, respectively). There was no significant difference in terms of clinical improvement and clinical recovery times between groups (p>0.05). There is no difference between microvascular group and other causes in terms of clinical outcome, while the mean age and presence of diabetes were higher in the microvascular group. The presence of diabetes should be questioned in cases with isolated abducens nerve palsy.


Multiphase autoresonant excitations in discrete nonlinear Schrödinger systems.
Large amplitude, multiphase solutions of periodic discrete nonlinear Schrödinger (NLS) systems are excited and controlled by starting from zero and using a small perturbation. The approach involves successive formation of phases in the solution by driving the system with small amplitude plane wavelike perturbations (drives) with chirped frequencies, slowly passing through a system's resonant frequency. The system is captured into resonance and enters a continuing phase-locking (autoresonance) stage, if the drive's amplitude surpasses a certain sharp threshold value. This phase-locked solution is efficiently controlled by variation of an external parameter (driving frequency). Numerical examples of excitation of multiphase waves and periodic discrete breathers by using this approach for integrable (Ablowitz-Ladik) and nonintegrable NLS discretizations are presented. The excited multiphase waveforms are analyzed via the spectral theory of the inverse scattering method applied to both the integrable and nonintegrable systems. A theory of autoresonant excitation of 0- and 1-phase solutions by passage through resonances is developed. The threshold phenomenon in these cases is analyzed.


Immunosuppression induced by talc granulomatosis in the rat.
Granulomatosis caused by four subcutaneous talc powder-suspension injections induced strong immunosuppression in rats. The disturbance included reduction of mononuclear white blood cell count in the peripheral blood, atrophy of the thymic cortex, spleen enlargement with predominance of red over the white pulp, increase in the number of lymph node germinal centres and a significant delay of the first-set and second-set allograft rejection. Neither phagocytic function of reticuloendothelial system nor erythrocyte count and humoral immune response were found to be altered. Indomethacin suppression of prostaglandin production did not normalize the allograft rejection dynamics. In contrast, splenectomy completely abolished the immunosuppressive effects of granulomatosis. In splenectomized, talc-treated animals WBC counts were not altered and the rejection of allografts was not delayed. Suppression of immune response to alloantigens was transferred to normal and splenectomized recipients by both serum and spleen cells of talc-injected animals. Also, in a cell mixture-transfer experiment, spleen cells from talc-granulomatosis-bearing donors suppressed the immune response induced by lymph node cells from immune donors in T cell-deficient rats. The inability of serum from splenectomized talc-injected rats to transfer the suppression suggested the crucial role of the spleen in the mechanisms leading to suppression in rats bearing talc-granulomatosis.


The link between social communication and mental health from childhood to young adulthood: A systematic review.
This systematic review investigates the current state of the literature on the association between social communication (SC) skills and mental health outcomes in children and young adults. We ran searches using terms describing SC and mental health in the following databases: PubMed, the Psychology and Behavioral Sciences Collection, APA PsychInfo, the Education Resource Information Center (ERIC) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We included studies that both measured SC before age 21 years and assessed a mental health component, such as behavior/conduct problems, anxiety, depression, or emotional problems, before age 30. Only peer-reviewed articles published in or after 2000 were retained. In total, 27 studies were included in the narrative synthesis. Overall, the methodological quality was good. A longitudinal design was used in 12 studies, seven of which sourced data from the Avon Longitudinal Study of Parents and Children. Most studies investigated the broad concept of pragmatic language and its influence on internalizing, externalizing, and peer-relationship problems. The analyzed publications included population-based studies and studies investigating special populations with existing mental health problems or at increased risk of developing them. The population-based cross-sectional studies showed significantly higher rates of SC problems in children with mental health problems while those with a longitudinal design found earlier onset and more persistent mental health problems in children who had the most severe SC difficulties. Studies with special populations confirmed more SC problems as compared to typically developing children and worse mental health outcomes in children with additional SC difficulties. The available literature thus shows consistently significant, mostly moderate associations between SC skills and mental health outcomes. SC difficulties earlier in life can predict mental health problems and impact their trajectories. [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=286598], identifier [CRD42022286598].


An Occupational Therapy and Teaching Partnership: Applying a Scholarship of Practice Model.
Occupational therapists must generate knowledge and evidence that relates specifically to their practice context especially when there is a paucity of literature for emerging areas of practice. This paper describes the process of adopting a scholarship of practice approach with other professionals to generate evidence for practice in mainstream post primary school settings with students with social, emotional and behavioral difficulties (SEBD). Scholarship of practice and clinical reasoning are closely intertwined as therapists generate evidence on their practice to make informed decisions and judgments. In this paper, there are a number of important concepts needing to be highlighted for their meaning in this specific context.


Clinical validation of a multipurpose assay for detection and genotyping of CALR mutations in myeloproliferative neoplasms.
To develop a polymerase chain reaction (PCR)-based approach to detect CALR mutations in myeloproliferative neoplasms (MPNs) in a clinical laboratory. DNA was extracted from bone marrow aspirate samples of 67 JAK2 wild-type MPNs (22 with matched peripheral blood), 54 cases of unclassifiable myelodysplastic syndrome/MPN, and 16 cases of atypical chronic myeloid leukemia. We used genomic DNA to detect somatic mutations in exon 9 of CALR and PCR with fluorescently labeled and M13-tagged primers and subjected the products to capillary electrophoresis (CE) followed by Sanger sequencing. Detailed assay performance characteristics were established. We identified CALR mutations in 19 (28.4%) of 67 JAK2-negative MPNs, including 14 type I (52-base pair [bp] deletion), four type II (5-bp insertions), and one type III (18-bp deletion). All mutations were confirmed by Sanger sequencing. Sensitivity studies showed 2.5% and 5% mutation detection levels by CE and Sanger sequencing, respectively, with high reproducibility. This assay allows for rapid, convenient screening for CALR mutations in MPNs, thereby reducing the number of cases that require assessment by Sanger sequencing, reducing labor and improving turnaround time.


Eat Well Australia: Developing a national strategic framework for public health nutrition.
In Australia, diet-related disease ranks alongside tobacco-related disease as the most important preventable health area, accounting for at least 10% of the total burden of disease. A population approach to improve the nutrition of all Australians is a vital contribution to the nation's overall health and well-being, yet action has often been ineffective, uncoordinated and poorly resourced. Through the National Public Health Partnership's nutrition group, SIGNAL, an ambitious work program has been commenced to address this situation. This includes the development of a national framework for action in public health nutrition 2000-2010. Following extensive consultation with health groups and the food industry, the strategy, Eat Well Australia, is now in a late stage of development. Key priorities have been agreed and focus on: (i) Aboriginal and Torres Strait Islander people; (ii) vulnerable groups; (iii) maternal and child health; (iv) overweight and obesity; and (v) fruit, vegetables and legumes. Eat Well Australia should provide a new pathway for more concerted and integrated action from a wide range of organizations and interest groups. As a core component, SIGNAL has also developed an action plan to promote comsumption of fruits, vegetables and legumes, which should mobilize responses at local, regional and national levels. Close cooperation between the food industry and the governmental and non-governmental sectors will be vital for success. A partnership platform is needed with clearly defined directions, operating principles and roles and responsibilities. Encouragingly, new and energetic alliances are now developing, which will be supported by Eat Well Australia.