[HIV/AIDS Competence Network. An example for research networking in Germany].
Thanks to a nationwide network of specialized, clinic-associated outpatient facilities and competent registered physicians, the quality of care for HIV-infected patients in Germany is high. Although basic HIV research is also well advanced in several centers, in contrast Germany's clinical HIV research is barely discemable on an international level. This deficit is primarily due to a lack of clinical studies involving patients from across the country and the fact that no national patient cohort system exists which could provide a basis for such clinical studies. The competence network HIV/AIDS aims to overcome this shortcoming by serving as a comprehensive, nationwide research alliance. The established patient cohort is linked to 13 projects. The infrastructure required for communications and data exchange will be based on a telematics platform. There will also be various service facilities established within the network, creating an organizational structure to promote the horizontal exchange of information between centers, as well as establish the vertical exchange of knowledge between physicians, patients, public health policy makers, and the general public.


Differential sorting of tyrosine kinases and phosphotyrosine phosphatases acting on band 3 during vesiculation of human erythrocytes.
One of the most intensively studied post-translational modifications of erythrocyte proteins is the phosphorylation of tyrosine residues of band 3, which is strictly regulated in vivo by PTKs (protein-tyrosine kinases) and PTPs (protein-phosphotyrosine phosphatases). Two PTKs (p72(syk) and p56/53(lyn)) and two PTP activities (PTP1B and SHPTP-2) have been immunologically identified so far in mature human erythrocytes. We have shown previously that band 3 undergoes tyrosine phosphorylation upon a decrease in cell volume, as occurs when erythrocytes treated with Ca(2+)/Ca(2+) ionophore (A23187) lose KCl and release microvesicles. Similar levels of band 3 tyrosine phosphorylation in vesicles and in the parent cells are induced by this treatment. However, we have found that tyrosine phosphorylation of band 3 in vesicles is more stable than in whole erythrocytes. Examination of how the identified PTPs and PTKs are partitioned between the vesicles and the remnant cells during vesiculation reveals that PTP1B, unlike the PTKs, is retained entirely in the parent cell compartment. Since a tight association between PTP1B and band 3 has been documented previously, we have investigated the partitioning of PTP1B and band 3 between the membrane and the membrane-skeletal fractions prepared from resting or Ca(2+)/A23187-treated cells. Our results rule out the possibility that the preferential retention of PTP1B within the cell was due to an increase in the amount of membrane-skeleton-associated band 3 (and of PTP1B) during the release of spectrin-free vesicles, suggesting a more complex modality of interaction of PTP1B with band 3 in the erythrocyte membrane. Analysis of erythrocytes of different cell ages revealed that PTP1B, unlike the other enzymes examined, was quantitatively conserved during erythrocyte aging. This suggests important roles for the down-regulation of tyrosine phosphorylation of band 3 in erythrocyte physiology, and for vesiculation as a mechanism of human erythrocyte senescence.


Induction of the interleukin-2 receptor (p55) by interferons.
The effect of human interferon (IFN) on the interleukin-2 receptor (IL-2R, p55) expression by peripheral blood mononuclear cells was investigated both in vitro and in vivo. IL-2R induction was assessed by the soluble IL-2R level in vitro and in vivo, which was measured by ELISA using two monoclonal antibodies to IL-2R(p55). Serum levels of sIL-2R increased significantly during IFN-alpha or IFN-beta therapy in 13 patients with chronic hepatitis B. When mononuclear cells were cultured with IFNs-alpha, -beta, or -gamma, the sIL-2R levels in the supernatant increased significantly. Dual flow cytometric analysis demonstrated that IL-2R was expressed on CD4+ and CD20+ mononuclear cells treated with IFN-alpha in vitro. CD4+ T cells and B cells may release sIL-2R when these cells are stimulated with IFN-alpha. RNA isolated from mononuclear cells treated with IFN-alpha contained increased levels of IL-2R-specific mRNA, as indicated by Northern blot analysis using an IL-2R-specific mRNA probe. These findings help to indicate how IFN plays a role in the regulation of the immune response, because IL-2R induction is known to be associated with lymphocyte activation.


THE EXTENT OF INTROGRESSION OUTSIDE THE CONTACT ZONE BETWEEN NOTROPIS CORNUTUS AND NOTROPIS CHRYSOCEPHALUS (TELEOSTEI: CYPRINIDAE).
The cyprinid fishes, Notropis cornutus and N. chrysocephalus, hybridize in a long, narrow zone in the midwestern United States. To quantify the extent of introgression of genetic markers outside of this zone, samples were collected along transects starting near the region of contact (as defined by morphological characters), followed by samples progressively more distant. Diagnostic allozymic and mitochondrial DNA (mtDNA) restriction site markers were used to estimate the extent of introgression outside of the zone, while polymorphic allozyme and mtDNA markers were used to evaluate the potential for gene flow among populations within transects. Analysis of populations from the northern transect provided evidence for differentiation of populations for some of the markers; however, on average, enough gene flow has occurred to overcome substantial differentiation. Introgressed mtDNA and allozyme haplotypes were rare and found only in the population closest to the contact zone. The rarity of introgressed alleles in the more northern populations is consistent with the recent origin of these populations after the Wisconsin glaciation (less than 12,000 years bp) and/or selection maintaining the northern boundary of the contact zone. Analysis of populations from the southern transect revealed evidence for population subdivision but no evidence for introgression at the diagnostic allozyme loci; however, nearly all individuals from this transect possessed introgressed mtDNA haplotypes, with samples furthest from the contact zone exhibiting the highest frequencies of introgression. Patterns of variation for one of the polymorphic allozyme markers (Est-A) and introgressed mtDNAs were highly correlated, suggesting that allozymic heterogeneity at this locus is also the result of introgression. The most likely explanation for these data is that these introgressed haplotypes are indicators of a more southern position of the contact zone during the Pleistocene, with the contact zone shifting northward with the recession of the glacial front. Such movement implicates selection in the maintenance of distributional limits of these species, and hence, the width and position of the contact zone.


Management and outcomes of pediatric patients transported by emergency medical services in a Canadian prehospital system.
There is uncertainty around the types of interventions that are provided by emergency medical services (EMS) to children during prehospital transport. We describe the patient characteristics, events, interventions provided and outcomes of a cohort of children transported by EMS. This prospective cohort study was conducted in a city of 750 000 people with a 2-tiered EMS system. All children <16 years of age who were attended by EMS during a 6-month period were enrolled. Data were extracted from ambulance call reports and hospital charts, and analyzed using descriptive statistics. During the study period there were 1377 pediatric EMS calls. Mean age was 8.2 years (standard deviation 5.4), and the most Common diagnoses were trauma (44.9%), seizure (11.8%) and respiratory distress (8.8%). The ambulance return code was Urgent in 7%, Prompt in 57%, Deferrable in 8% and Not Transported in 28%. Fifty-six percent received either an Advanced Life Support or Basic Life Support prehospital intervention. Common procedures included cardiac monitoring (20.0%), oxygen administration (19.8%), blood glucose monitoring (16.3%), spine board (12.2%), limb immobilization (11.1%) and cervical collar (10.0%). Uncommon procedures included administering medications intravenously (IV) (1.4%), bag-valve-mask ventilation (0.3%) and endotracheal intubation (0.1%). Seventy-eight percent of attempted IV lines were successful. Only 9.0% of EMS-transported children were admitted to hospital, and 2.2% were admitted to the intensive care unit. This first study of Canadian pediatric prehospital interventions shows a high rate of non-transport, and a low rate of Urgent transports and hospital admissions for children. Very few children receive prehospital airway management, ventilation or IV medications; consequently EMS personnel have little opportunity to maintain these pediatric skills in the field.


Utility and safety of axillary conduits during endovascular repair of thoracoabdominal aneurysms.
Endovascular treatment of thoracoabdominal aortic aneurysms (TAAAs) with branched and fenestrated stent grafts often requires upper extremity arterial access for antegrade delivery of bridging covered stents into the visceral arteries. Axillary, brachial, and radial artery approaches have been described, but data on the safety and utility of the different approaches remain limited. We have preferentially used axillary artery conduits for upper extremity arterial access during endovascular repair of TAAA and describe our technique and report our experience herein. Thirty-two patients were treated within an investigator-sponsored investigational device exemption clinical trial of endovascular repair of TAAAs using custom-manufactured stent grafts. In 29 of these cases, the axillary artery was exposed through an infraclavicular incision, and an axillary conduit was used for antegrade delivery of bridging visceral artery stent components. In all cases, a 12F sheath was placed through the conduit for delivery of stent graft components. The left axillary artery was used in 27 of these 29 cases, and the right axillary artery was used in 2 patients. Proximal brachial artery access was used in two patients, and one patient did not require upper extremity access. Aneurysms treated included pararenal (n = 3) and Crawford TAAA extent I (n = 1), extent II (n = 3), extent III (n = 10), and extent IV (n = 15). Patients have been followed up to 2 years after the procedure, with a mean follow-up of 226 days. Axillary conduits were used to deliver a total of 170 stent components placed into 81 branches and 27 fenestrations with 99.1% technical success (one accessory renal branch could not be cannulated). There were no intraoperative complications related to the construction or use of the conduit. There were two postoperative complications (6.9%) potentially attributable to the conduit; one patient experienced ipsilateral hand weakness and one patient had postoperative minor stroke, which resolved by the first postoperative visit. There were no cases of arm ischemia, wound hematoma, or reoperation related to the conduit. The use of an axillary conduit during endovascular repair of complex aortic aneurysms provides safe and effective upper extremity access for delivery of visceral branches. Moreover, axillary conduits facilitate delivery of 12F sheaths without interrupting upper extremity perfusion and provide a shorter working distance compared with brachial artery approaches.


Canonical models for torus canards in elliptic bursters.
We revisit elliptic bursting dynamics from the viewpoint of torus canard solutions. We show that at the transition to and from elliptic burstings, classical or mixed-type torus canards may appear, the difference between the two being the fast subsystem bifurcation that they approach: saddle-node of cycles for the former and subcritical Hopf for the latter. We first showcase such dynamics in a Wilson-Cowan-type elliptic bursting model, then we consider minimal models for elliptic bursters in view of finding transitions to and from bursting solutions via both kinds of torus canards. We first consider the canonical model proposed by Izhikevich [SIAM J. Appl. Math. 60, 503-535 (2000)] and adapted to elliptic bursting by Ju et al. [Chaos 28, 106317 (2018)] and we show that it does not produce mixed-type torus canards due to a nongeneric transition at one end of the bursting regime. We, therefore, introduce a perturbative term in the slow equation, which extends this canonical form to a new one that we call Leidenator and which supports the right transitions to and from elliptic bursting via classical and mixed-type torus canards, respectively. Throughout the study, we use singular flows ( ε=0) to predict the full system's dynamics ( ε>0 small enough). We consider three singular flows, slow, fast, and average slow, so as to appropriately construct singular orbits corresponding to all relevant dynamics pertaining to elliptic bursting and torus canards. Finally, we comment on possible links with mixed-type torus canards and folded-saddle-node singularities in non-canonical elliptic bursters that possess a natural three-timescale structure.


DNA methylation and the regulation of aldolase B gene expression.
DNA methylation was studied as a potential factor for the regulation of tissue-specific and developmentally specific expression of the rat aldolase B gene. We examined cytosine methylation in the HpaII and HhaI recognition sequences in the aldolase B gene in aldolase expressing and nonexpressing tissues and cells. Out of the 15 methyl-sensitive restriction sites examined, the sites in the 3'-half and 3'-flanking regions were found to be heavily methylated in all the tissues or cells, regardless of the level of aldolase B gene expression. However, the methylation pattern in the region immediately upstream and in the 5'-half of the gene exhibited tissue-specificity: the site located about 0.13 kb upstream of the cap site (just next to the CCAAT box), and the sites in the first intron (intron 1) were heavily methylated in nonexpressing cells and tissues (ascites hepatoma AH130 and brain), whereas those in an expressing tissue (liver) were considerably less methylated. These results suggest that cytosine methylation at the specific sites in the 5'-flanking and 5'-half regions of the gene is associated with repression of the gene activity. However, the gene is still substantially methylated in the fetal liver on day 16 of gestation, when it is in a committed state for rapid activation in the period immediately afterwards (Numazaki et al. (1984) Eur. J. Biochem. 152, 165-170). This suggests that demethylation of the methylated cytosine residues in the specific gene region is not necessarily required before activation of the gene during development, but it may occur along with or after the activation.


Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata.
Purkinje cells have specialized intrinsic ionic conductances that generate high-frequency action potentials. Disruptions of their Ca or Ca-activated K (KCa) currents correlate with altered firing patterns in vitro and impaired motor behavior in vivo. To examine the properties of somatic KCa currents, we recorded voltage-clamped KCa currents in Purkinje cell bodies isolated from postnatal day 17-21 mouse cerebellum. Currents were evoked by endogenous Ca influx with approximately physiological Ca buffering. Purkinje somata expressed voltage-activated, Cd-sensitive KCa currents with iberiotoxin (IBTX)-sensitive (>100 nS) and IBTX-insensitive (>75 nS) components. IBTX-sensitive currents activated and partially inactivated within milliseconds. Rapid, incomplete macroscopic inactivation was also evident during 50- or 100-Hz trains of 1-ms depolarizations. In contrast, IBTX-insensitive currents activated more slowly and did not inactivate. These currents were insensitive to the small- and intermediate-conductance KCa channel blockers apamin, scyllatoxin, UCL1684, bicuculline methiodide, and TRAM-34, but were largely blocked by 1 mM tetraethylammonium. The underlying channels had single-channel conductances of ∼150 pS, suggesting that the currents are carried by IBTX-resistant (β4-containing) large-conductance KCa (BK) channels. IBTX-insensitive currents were nevertheless increased by small-conductance KCa channel agonists EBIO, chlorzoxazone, and CyPPA. During trains of brief depolarizations, IBTX-insensitive currents flowed during interstep intervals, and the accumulation of interstep outward current was enhanced by EBIO. In current clamp, EBIO slowed spiking, especially during depolarizing current injections. The two components of BK current in Purkinje somata likely contribute differently to spike repolarization and firing rate. Moreover, augmentation of BK current may partially underlie the action of EBIO and chlorzoxazone to alleviate disrupted Purkinje cell firing associated with genetic ataxias.


Preparation and preclinical evaluation of a freeze-dried formulation of a novel combined multivalent whole-cell/B-subunit oral vaccine against enterotoxigenic Escherichia coli diarrhea.
A promising liquid killed multivalent whole-cell plus enterotoxin B-subunit oral vaccine against enterotoxigenic Escherichia coli (ETEC), the primary cause of diarrhea among children in low-income countries and travelers to these areas, has recently been developed and tested in preclinical and phase-I and phase-II clinical studies. The vaccine contains killed E. coli bacteria over-expressing the main ETEC colonization factors (CFs) CFA/I, CS3, C5 and C6, and a recombinant enterotoxin B subunit protein (LCTBA) given together with a recently developed enterotoxin-derived adjuvant, dmLT. A dry-powder vaccine formulation should be advantageous especially for use in low-income countries. Here we describe a method to produce a dry-powder formulation by freeze-drying of the vaccine using inulin as stabilizer. Although not completely preventing aggregation of bacteria during freeze-drying, the stabilizer provided both improved overall bacterial morphology and almost complete recovery of the CF and B subunit antigens. Most importantly, oral-intragastric immunization of mice with the freeze-dried vaccine together with dmLT adjuvant elicited strong intestinal mucosal and serum antibody responses against all vaccine antigens, which were comparable to those achieved with the liquid vaccine. Our results indicate the feasibility to use freeze-drying with inulin as stabilizer for preparing a dry-powder formulation of the novel ETEC vaccine with retained oral-mucosal immunogenicity compared to the liquid formulation.


Anaplastic T-Cell Lymphoma Associated with Hemophagocytic Syndrome: A Case Report.
Hemophagocytic syndrome (HPS) is mostly associated with malignant and infectious diseases. The causes and prognosis of this clinical syndrome depend on the underlying disease. And also treatment of this disease must be arranged according to the underlying causes. While non-Hodgkin's lymphomas (NHL) associated with HPS has been frequently observed, anaplastic T-cell NHL associated with HPS has been rarely reported. In this article we report a case of Ki-1+ anaplastic T-cell lymphoma associated with HPS in a 16-year-old woman who presented with fever and lymphadenopathy.


Substance use and risky sexual behaviours among street connected children and youth in Accra, Ghana.
Research on street children and youth has shown that this population is at high risk for substance use. Though risky sexual behaviours have been investigated and widely reported among street youth in resource constrained-settings, few studies have explored the relationship between substance use and other risk behaviours. This study was therefore conducted to examine the association between substance use and risky sexual behaviours among homeless youth in Ghana. A cross-sectional survey of a convenient sample of 227 (122 male and 105 female) street connected children and youth was conducted in Ghana in 2012. Using self-report measures, the relationship between substance use and risky sexual behaviours was examined using logistic regression. Substance use was relatively high as 12% and 16.2% reported daily use of alcohol and marijuana respectively. There were age and sex differences in substance use among the sample. As compared to males, more females had smoked cigarettes, used alcohol and marijuana. While alcohol use decrease with age, marijuana use on the other hand increases with age. Results from multivariate analysis revealed that having ever drunk alcohol and alcohol use in the past one month were independently associated with all the four indices of risky sexual behaviour (ever had sex, non-condom use, multiple sexual partners and survival sex). Both marijuana use and smoking of cigarettes were associated with having ever had sex, multiple sexual partners and survival sex. Other drug use was independently associated with non-condom use. Substance use seems to serve as a possible risk factor for sexual risk behaviours among homeless youth. Harm reduction interventions are needed to prevent street children and youth from engaging in substance use and risky sexual behaviours. Such programmes should pay special attention to females and younger children who are highly susceptible to the adverse conditions on the street.


Genetic variation of the gene coding for microRNA-204 (miR-204) is a risk factor in acute myeloid leukaemia.
MicroRNAs (miRNAs or miRs) are small molecules known to be involved in post-transcriptional gene expression. Many of them have been shown to influence risk for various diseases. Recent studies suggest that lower expression of miR-204, a gene coding for miRNA-204, is correlated with shorter survival in patients with acute myeloid leukaemia (AML). This observation prompted us to analyse the effect of two polymorphisms of the miR-204 gene, one in the upstream flanking region (rs718447 A > G) and the other inside the gene itself (rs112062096 A > G), both also in intron 3 of the TRPM3 gene. The study was conducted on DNA samples isolated from AML patients (n = 95) and healthy individuals (n = 148), who were genotyped using the Light SNiP assays. The miR-204 rs718447 GG homozygosity was found to constitute a risk factor associated with susceptibility to AML (73/95 vs 92/148, AML patients vs healthy controls, OR = 2.020, p = 0.017). Additionally, this genotype was more frequent in patients with subtypes M0-M1 in the French-American-British (FAB) classification as compared to patients with subtypes M2-M7 (23/25 vs 39/57, p = 0.026). We also found that presence of allele A was linked to longer survival of AML patients. Our results show that polymorphism in miR-204 flanking region may constitute a risk and prognostic factor in AML.


Estrogen receptor alpha gene relationship with peak bone mass and body mass index in Chinese nuclear families.
Estrogen receptor alpha (ER-alpha) plays an important role in mediating estrogen signaling. Studies in Caucasian populations have shown that it is involved in endocrine-related diseases such as osteoporosis and obesity. In the present study, we first used a quantitative transmission disequilibrium test (QTDT) to examine the relationship between this gene and both the osteoporosis-related phenotype bone mineral density (BMD), and the obesity-related phenotype body mass index (BMI), in 384 Chinese nuclear families. We genotyped a dinucleotide repeat marker (TA)n, and a long-range haplotype was reconstructed using this marker and two other restriction fragment length polymorphism (RFLP) markers at PvuII and XbaI loci. Although we found significant total association [allele (TA)21 with hip BMD (P=0.001), and haplotype Px(TA)21 with spine (P=0.0007) and hip (P=0.0006) BMD], the more reliable within-family associations were not significant between these phenotype pairs. No linkage signal was obtained for either spine BMD or hip BMD. We found no association or linkage between any of the three studied polymorphisms and the long-range haplotypes of the ER-alpha gene and BMI. Our study does not support an association of the ER-alpha gene with BMD and BMI in the Chinese population.


Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency.
alpha-Lipoic acid, an essential cofactor in mitochondrial dehydrogenases, has recently been shown to be a potent antioxidant in vitro, as well as being capable of regenerating vitamin E in vitro. In this study, using a new animal model for rapid vitamin E deficiency in adult animals and a new technique for tissue extraction of oxidized and reduced alpha-lipoic acid, we examined the antioxidant action of alpha-lipoic acid in vivo. Vitamin E-deficient adult hairless mice displayed obvious symptoms of deficiency within five weeks, but if the diet was supplemented with alpha-lipoic acid the animals were completely protected. At five weeks on a vitamin E-deficient diet animals exhibited similar decreases in tissue vitamin E levels, whether supplemented or unsupplemented with alpha-lipoic acid: vitamin E levels in liver, kidney, heart, and skin decreased 70 to 85%; levels in brain decreased only 25%. These data show that there was no effect of alpha-lipoic acid supplementation on vitamin E tissue concentrations, arguing against a role for alpha-lipoic acid in regenerating vitamin E in vivo.


Proteome analysis identified maspin as a special feature of papillary thyroid carcinoma.
This study aimed at investigating new mechanisms of carcinogenesis in thyroid cancer at the molecular level and at finding potential protein markers involved in the initiation of the different histological subtypes. For this, we performed differential proteome analysis on primary cultured thyrocytes (PT) and transformed thyrocytes (TT) derived from 238Pu alpha-particle irradiation using 2-dimensional electrophoresis (2-DE) and peptide mass fingerprinting (PMF) with matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS). Image analysis showed that one protein was very strongly expressed in TT; 55 proteins were weaker, different in intensity, including 26 spots that were increased in PT, and 29 spots were decreased. The hot spot was identified as maspin, a unique member of the serpin family considered to be a class II tumor suppressor gene. To clarify the role of maspin in thyroid carcinogenesis we searched for protein expression in 20 normal (tumor-free) tissues, as well as in 20 follicular adenomas (FAD), 20 papillary carcinomas (PTC), 20 follicular carcinomas (FTC), 20 poorly differentiated carcinomas (PDTC), and 20 undifferentiated carcinomas (UTC). Maspin protein expression was detectable in none of the cases of normal tumor-free thyroid tissue, nor in FAD, FTC, PDTC and UTC. In contrast 14 of 20 PTC (70%) showed a moderate or strong cytoplasmic staining; 4 of these 14 cases had a moderate cytoplasmic and nuclear staining. In conclusion, we hypothesize that maspin protein expression is a special feature in the cascade of PTC genesis and that the way of initiating PTC is different from other thyroid carcinoma types.


[Examining the diagnostic accuracy of a new migraine screener].
Migraine affects more than 10% of the Hungarian population, causes significant disability and severely affects patients' generic and condition-specific quality of life. Despite these facts, a significant proportion of patients is not diagnosed and not treated adequately. Headache centres can provide care for only a fraction of all patients. The task of primary care providers would be greatly simplified by a reliable self-administered migraine screening questionnaire. To develop a short and reliable questionnaire as a migraine screening tool. Outpatients at the Headache Service, Department of Neurology, Semmelweis University completed a self-administered questionnaire which contained 9 yes/no questions about their headaches' characteristics. The number of 'yes' answers (the patients' total score) was evaluated in connection with the diagnosis based on the International Headache Society criteria. We calculated the sensitivity, specificity, positive and negative predictive value as well as the misclassification rate for each total score value and used these to establish the final cutoff value of the questionnaire. 306 patients (242 females, mean age 39.1 ± 13.3 years) were enrolled. The diagnosis was migraine in 244. Completing the questionnaire did not pose any difficulty for the patients. At a cutoff value of 5 points the questionnaire's sensitivity was 0.96 and specificity was 0.61. The positive predictive value was 0.91 and the negative pre- dictive value was 0.81. The misclassification rate was 0.11. Our results show that the questionnaire may help the diagnosis of migraine. In order to use it in medical practice, its further evaluation is necessary on a large representative sample of the Hungarian population.


Inhibition of bacterial plasmid replication by stereoselective binding by tricyclic psychopharmacons.
Several dibenzazepines, thioxanthene, and phenothiazine stereoisomers were studied for their abilities to inhibit plasmid replication, intracellular transfer of R-plasmid, bacterial ATP-ase, and mouse serum cholinesterase isoenzyme. Partially saturated derivative of desipramine inhibited plasmid replication and transfer, but the fully saturated derivative was inactive. The inhibition of plasmid curing and transfer patterns did not correlate with the inhibition of ATP-ase and cholinesterase. Trans-clopenthixol was more effective in plasmid elimination than the cis-isomer. On the other hand, the cis-isomer inhibited ATP-ase and cholinesterase more than the trans-isomer. The levo- and dextro-methoxytrimeprazine also inhibited plasmid replication and enzyme activity. We believe that the tricyclic configuration of the drugs tested for stereospecific binding to bacterial receptors is more important than its side chain orientation. We believe that there is a similarity between bacterial receptor sites and neural receptor sites. Therefore, this model may be useful in the study of neuropharmacological agents as potential antibacterial agents.


Single cell susceptibility to SARS-CoV-2 infection is driven by variable cell states.
The ability of a virus to infect a cell type is at least in part determined by the presence of host factors required for the viral life cycle. However, even within cell types that express known factors needed for infection, not every cell is equally susceptible, suggesting that our knowledge of the full spectrum of factors that promote infection is incomplete. Profiling the most susceptible subsets of cells within a population may reveal additional factors that promote infection. However, because viral infection dramatically alters the state of the cell, new approaches are needed to reveal the state of these cells prior to infection with virus. Here, we used single-cell clone tracing to retrospectively identify and characterize lung epithelial cells that are highly susceptible to infection with SARS-CoV-2. The transcriptional state of these highly susceptible cells includes markers of retinoic acid signaling and epithelial differentiation. Loss of candidate factors identified by our approach revealed that many of these factors play roles in viral entry. Moreover, a subset of these factors exert control over the infectable cell state itself, regulating the expression of key factors associated with viral infection and entry. Analysis of patient samples revealed the heterogeneous expression of these factors across both cells and patients in vivo. Further, the expression of these factors is upregulated in particular inflammatory pathologies. Altogether, our results show that the variable expression of intrinsic cell states is a major determinant of whether a cell can be infected by SARS-CoV-2.


Gap junction Delta-2b (gjd2b/Cx35.1) depletion causes hyperopia and visual-motor deficiencies in the zebrafish.
The zebrafish is a powerful model to investigate the developmental roles of electrical synapses because many signaling pathways that regulate the development of the nervous system are highly conserved from fish to humans. Here, we provide evidence linking the mammalian connexin-36 (Cx36) ortholog gjd2b/Cx35.1, a major component of electrical synapses in the zebrafish, with a refractive error in the context of morphological, molecular, and behavioral changes of zebrafish larvae. Two abnormalities were identified. The optical coherence tomography analysis of the adult retina confirmed changes to the refractive properties caused by eye axial length reduction, leading to hyperopic shifts. The gjd2b/Cx35.1 depletion was also correlated with morphological changes to the head and body ratios in larvae. The differential expression of Wnt/ß-catenin signaling genes, connexins, and dopamine receptors suggested a contribution to the observed phenotypic differences. The alteration of visual-motor behavioral responses to abrupt light transitions was aggravated in larvae, providing evidence that cone photoreceptor cell activity was enhanced when gjd2b/Cx35.1 was depleted. The visual disturbances were reversed under low light conditions in gjd2b -/- /Cx35.1-/- larvae. Since qRT-PCR data demonstrated that two rhodopsin genes were downregulated, we speculated that rod photoreceptor cells in gjd2b/Cx35.1-/- larvae were less sensitive to bright light transitions, thus providing additional evidence that a cone-mediated process caused the VMR light-ON hyperactivity after losing Cx35.1 expression. Together, this study provides evidence for the role of gjd2b/Cx35.1 in the development of the visual system and visually guided behaviors.


Submarine optical fiber cable: development and laying results.
This paper describes the structural design, trial production, and laying results for submarine optical fiber cables that can be deployed in shallow seas between islands and/or channel crossings without repeaters. Structural design methods for the submarine optical fiber cable are proposed, which take into consideration suppressing cable elongation under tension and excess loss under hydraulic pressure. This paper describes good laying results for the cable using this structural design method. The average loss for single-mode fibers was 0.72 dB/km, and the average loss for multimode fibers was 0.81 dB/km for a 10.2-km long cable operated at 1.3-microm wavelength.


Mental health, compliance with measures and health prospects during the COVID-19 epidemic: the role of health literacy.
The importance of health literacy in dealing with the COVID-19 epidemic has been emphasized but scarcely addressed empirically. In this study, the association of health literacy with mental health, compliance with COVID-19 preventive measures and health prospects was assessed in a Belgian context. Data were extracted from the third of a series of cross-sectional online COVID-related surveys (n = 32,794). Data collection took place for 1 week starting the 28th of May 2020. People residing in Belgium and aged 18 years or older could participate. Data were collected on sociodemographic background, health literacy, multimorbidity, mental health (depression, anxiety, sleeping disorder, vitality), knowledge about COVID-19, compliance with COVID-19 measures (hygiene, physical distance, covering mouth and nose on public transport and in places where physical distance cannot be respected), and health prospects (risk for health when returning to normal life and possibility of infection). Prevalence Ratio (PR) of poor mental health, non-compliance with the measures and health prospects in relation to health literacy were calculated using Poisson regressions. People showing sufficient health literacy were less likely to suffer from anxiety disorders (PR = 0.47, 95% CI = [0.42-0.53]), depression (PR = 0.46, 95% CI = [0.40-0.52]) and sleeping disorders (PR = 0.85, 95% CI = [0.82-0.87]), and more likely to have optimal vitality (PR = 2.41, 95% CI = [2.05-2.84]) than people with low health literacy. They were less at risk of not complying with the COVID-19 measures (PR between 0.60 and 0.83) except one (covering mouth and nose in places where physical distance cannot be respected). Finally, they were less likely to perceive returning to normal life as threatening (PR = 0.70, 95% CI = [0.65-0.77]) and to consider themselves at risk of an infection with COVID-19 (PR = 0.75, 95% CI = [0.67-0.84]). The associations remained significant after controlling for COVID-19 knowledge and multimorbidity. These results suggest that health literacy is a crucial factor in managing the COVID-19 epidemic and offer a perspective for future studies that target health literacy in the context of virus outbreaks.


Bcl-2 mediates sex-specific differences in recovery of mice from LPS-induced signs of sickness independent of IL-6.
Chronic pulmonary diseases are more common in boys than in girls. Therefore, we investigated the differences in signs of sickness in male and female mice that were exposed to lipopolysaccharide (LPS) by intranasal instillation. Because apoptosis is important in the resolution of inflammation, we tested the hypothesis that reduced levels of Bcl-2, a regulator of apoptosis, may play a role in gender-specific differences in response to inflammation. Bcl-2 wild-type (+/+) female mice recovered from an LPS-induced drop in body temperature and loss in body weight significantly faster than male (+/+) mice. Female heterozygous (+/-) mice showed reduced Bcl-2 levels and exhibited a slower recovery than female (+/+) mice that was similar to the recovery pattern in male (+/+) and (+/-) mice. Interleukin-6 (IL-6) activity levels in the bronchoalveolar lavage fluid were higher in male than in female mice but were not different between (+/+) and (+/-) mice. We conclude that Bcl-2 plays a role in mediating the faster recovery of female (+/+) mice from LPS-induced signs of sickness independent of IL-6. These studies indicate that apoptotic mechanisms may be involved in gender-specific differences in chronic pulmonary diseases.


Critical role of environmental factors in the pathogenesis of psoriasis.
Psoriasis is a common cutaneous disease with multifactorial etiology including genetic and non-genetic factors, such as drugs, smoking, drinking, diet, infection and mental stress. Now, the role of the interaction between environmental factors and genetics are considered to be a main factor in the pathogenesis of psoriasis. However, it is a challenge to explore the mechanisms how the environmental factors break the body balance to affect the onset and development of psoriasis. In this article, we review the pathogenesis of psoriasis and summarize numerous clinical data to reveal the association between environmental factors and psoriasis. In addition, we focus on the mechanisms of environmental risk factors impact on psoriasis and provide a series of potential treatments against environmental risk factors.


Articulated Instruments and 3D Visualization: A Synergy? Evaluation of Execution Time, Errors, and Visual Fatigue.
Objective. The introduction of advanced endoscopic systems, such as the Storz Image1S and the Olympus Endoeye, heralds a new era of 3-dimensional (3D) visualization. The aim of this report is to provide a comprehensive overview of the neurophysiology of 3D view, its relevance in videoscopy, and to quantify the benefit of the new 3D technologies for both rigid and articulated instruments. Method. Sixteen medical students without any laparoscopic experience were trained each for a total of 27 hours. Proficiency scores were determined for rigid and articulated instruments under 2D and 3D visualization conditions. Results. A reduction in execution time of 14%, 28%, and 36% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. A reduction in errors of 84%, 92%, and 87% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. Conclusion. 3D visualization greatly augments endoscopic procedures. The advanced endoscopic systems employed in the recent study caused no visual fatigue or discomfort. The benefit of 3D was most distinct with articulated instruments.


Enzymic development of the small intestine: are glucocorticoids necessary?
The aim of this study was to determine the extent to which the postnatal maturation of intestinal hydrolases in the rat is dependent on the developmental rise of circulating corticosterone that occurs at the end of the 2nd wk of life. Pups were adrenalectomized (adX) on day 9 (i.e., before the developmental surge of corticosterone begins) and were killed on days 17, 20, 23, and 26. Serum corticosterone was measured to eliminate any incompletely adX animals. The rates of the developmental increases of sucrase and maltase activities and the developmental decreases of lactase and acid beta-galactosidase activities were depressed in adX pups aged 23 days and younger as compared with sham-operated controls. Administration of corticosterone (10 micrograms X g body wt-1 X day-1) to adX pups restored the developmental changes of these enzyme activities to rates equal to or greater than those in the sham-operated pups. By 26 days of age, all four enzyme activities of adX pups had reached their normal ontogenic plateau. We conclude that adrenal corticosteroids are potent determinants of the rate of developmental changes of intestinal hydrolases but that these hormones are not necessary for enzymes to eventually reach adult activities.


Recent Advances in Fibrosis and Scar Segmentation From Cardiac MRI: A State-of-the-Art Review and Future Perspectives.
Segmentation of cardiac fibrosis and scars is essential for clinical diagnosis and can provide invaluable guidance for the treatment of cardiac diseases. Late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been successful in guiding the clinical diagnosis and treatment reliably. For LGE CMR, many methods have demonstrated success in accurately segmenting scarring regions. Co-registration with other non-contrast-agent (non-CA) modalities [e.g., balanced steady-state free precession (bSSFP) cine magnetic resonance imaging (MRI)] can further enhance the efficacy of automated segmentation of cardiac anatomies. Many conventional methods have been proposed to provide automated or semi-automated segmentation of scars. With the development of deep learning in recent years, we can also see more advanced methods that are more efficient in providing more accurate segmentations. This paper conducts a state-of-the-art review of conventional and current state-of-the-art approaches utilizing different modalities for accurate cardiac fibrosis and scar segmentation.


Cell surface characterization of Yarrowia lipolytica IMUFRJ 50682.
In the present work, the surface characteristics of a wild-type strain of Yarrowia lipolytica (IMUFRJ50682) were investigated. Six different methods to characterize cell surfaces--adhesion to polystyrene; hydrophobic interaction chromatography (HIC); microbial adhesion to solvents (MATS) test; zeta potential; microbial adhesion to hydrocarbons (MATH) test; and contact angle measurement (CAM)--were employed to explain the cell surface behaviour of Y. lipolytica (IMUFRJ50682). This Y. lipolytica strain presents significant differences at the cell surface compared with another Y. lipolytica strain (W29) previously reported in the literature. The main difference is related to the higher cell adhesion to non-polar solvents. The proteins present on the cell wall of Y. lipolytica IMUFRJ50682 seem to play an important role in these particular surface characteristics because of the consistent reduction of this yeast hydrophobic character after the action of pronase on its cell wall.


Antibodies to and elevations of beta 2 microglobulin in the serum of ankylosing spondylitis patients.
Antibodies to beta 2 microglobulin are found in systemic lupus erythematosus patients and are important in the lymphocytotoxic reactions of sera from such patients. In this study, beta 2 microglobulin antibodies were measured with the use of an enzyme-linked immunosorbent assay with purified beta 2 microglobulin antigen and peroxidase-labeled anti-human IgG or IgM. IgG antibodies to beta 2 microglobulin were found in 68% of 22 patients with ankylosing spondylitis. This incidence was higher than the 5% in 80 controls (P less than 0.01) and similar to the 71% incidence found in 35 patients with systemic lupus erythematosus. Eleven (27%) of 41 patients with rheumatoid arthritis had elevated levels of antibodies to beta 2 microglobulin (P less than 0.01). The mean antibody levels expressed in enzyme units were 0.125 for patients with ankylosing spondylitis, 0.157 for those with systemic lupus erythematosus, 0.101 for those with rheumatoid arthritis, and 0.067 for controls. IgM anti-beta 2 microglobulin was not significantly different from controls. A competitive binding assay with enzyme-labeled beta 2 microglobulin was used to determine serum beta 2 microglobulin. These values were also found to be elevated in 48% of patients in all 3 disease categories (P less than 0.01). Beta 2 microglobulin antibodies and serum beta 2 microglobulin did not correlate with each other, renal diseases or antinuclear antibodies in patients with systemic lupus erythematosus, with rheumatoid factor or severity of articular disease in patients with rheumatoid arthritis, or with peripheral arthritis or iritis in those with ankylosing spondylitis. Although antibodies to beta 2 microglobulin might reflect a general disturbance of immune regulation in patients with systemic lupus erythematosus, their presence in those with ankylosing spondylitis, a disease closely associated with a specific HLA allotype and not usually associated with formation of autoantibody, suggests that they might play a role in the pathogenesis of the latter disease.


[Activity of the antioxidant system in patients with idiopathic proctocolitis and the effect of 5-aminosalicylic acid (Salofalk)].
There is a close relationship between inflammation and reactive oxygen species (ROS). Primary source of ROS are activated leucocytes. Antioxidant system protects organism against the deleterious effect of ROS. The aim of the present study was to follow the activity of antioxidant system in blood and colonic mucosa of 17 patients with idiopathic proctocolitis. All patients were treated with 5-aminosalicylic acid (Salofalk), 7 patients with a combination of prednison. The following biochemical parameters were ascertained: malondialdehyde (MDA) and ceruloplasmin in serum, glutathione (GSH) and activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocytes and colonic mucosa. Before treatment there was found: an increase of MDA and all antioxidant enzyme activities, an a decrease of GSH. After 3 weeks of therapy in 59% of patients, initial clinical remission was observed without serious improvement of biochemical parameters. After 10 weeks of therapy the clinical course improved in all patients, a significant decrease of MDA and activities of all antioxidant enzymes as well as an increase of GSH were stated. The authors assume that IP was positively affected by 5-ASA, and in some patients by its combination with prednisom. The effect of 5-ASA is based on its known antiinflammatory impact and its functioning as a "scavanger" of free radicals (or ROS). (Tab. 1, Fig. 3, Ref. 23.)


Targeted delivery of dexamethasone in acute pneumonia.
Pneumonia has contributed to significant mortality owing to the irreversible injury to the lungs and severe inflammation of the tissue. Dexamethasone (DEX) is regarded as an effective drug to relieve the level of pneumonia, while the adverse effect of which is non-negligible. Here, we developed a targeted delivery strategy based on platelet-derived extracellular vesicles (PEVs), which are naturally occurring nanoparticles released by platelets, for DEX delivery in acute pneumonia, aiming to reduce the side effects and improve the therapeutic efficacy. Our strategy may shed light on the problems in DEX-based acute pneumonia therapy clinically.


Clinical aspects of metastases.
In the short term the major hope for reducing cancer mortality is to effect a reduction in the number of patients who develop malignant disease and in the proportion of cancer patients who present with metastases. Hitherto the major emphasis of clinical research on metastases has been directed at detection and elimination rather than prevention or early diagnosis. Extensive data relating histological class and tumour stage to risk of metastasis and metastatic pattern have been compiled from studies of relapse and from invasive and non-invasive staging procedures. However, the biological events involved in the metastatic process and the factors which influence it in relation to the natural history of primary human tumours are poorly understood. Information describing metastatic heterogeneity in individual patients, in terms of therapeutic response or intrinsic sensitivity to cytotoxic agents, is scanty. Similarly, the characteristics of human metastases in relation to the clonal heterogeneity of primary tumours are poorly defined. The clinical application of molecular biological techniques, which has led to the association of gene amplification with tumour behaviour in a range of sites, offers the prospects of improved tumour localization and therapy and, in the longer term, of tumour control by interventions based on a knowledge of the mechanisms that regulate cell growth and differentiation.


Penumbra and re-canalization acute computed tomography in ischemic stroke evaluation: PRACTISE study protocol.
Rationale Multimodal imaging, including computed tomography angiography and computed tomography perfusion imaging, yields additional information on intracranial vessels and brain perfusion and can differentiate between ischemic core and penumbra which may affect patient selection for intravenous thrombolysis. Hypothesis The use of multimodal imaging will increase the number of patients receiving intravenous thrombolysis and lead to better treatment outcomes. Sample size 400 patients. Methods and design PRACTISE is a prospective, multicenter, randomized, controlled trial in which patients presenting within 4.5 h of symptom onset are randomized to either the current evidence-based imaging (NCCT alone) or additional multimodal computed tomography imaging (NCCT + computed tomography angiography + computed tomography perfusion). Clinical decisions on intravenous recombinant tissue plasminogen activator are documented. Total imaging time in both arms and time to initiation of treatment delivery in those treated with intravenous recombinant tissue plasminogen activator, is recorded. Follow-up will include brain imaging at 24 h to document infarct size, the presence of edema and the presence of intra-cerebral hemorrhage. Clinical evaluations include NIHSS score at baseline, 24 h and day 7 ± 2, and mRS at day 90 to define functional outcomes. Study outcomes The primary outcome is the proportion of patients receiving intravenous recombinant tissue plasminogen activator. Secondary end-points evaluate times to decision-making, comparison of different image processing software and clinical outcomes at three months. Discussion Multimodal computed tomography is a widely available tool for patient selection for revascularization therapy, but it is currently unknown whether the use of additional imaging in all stroke patients is beneficial. The study opened for recruitment in March 2015 and will provide data on the value of multimodal imaging in treatment decisions for acute stroke.


Analysis of the FASSST rotational spectrum of NCNCS in view of quantum monodromy.
Quantum monodromy has a strong impact on the ro-vibrational energy levels of chain molecules whose bending potential energy function has the form of the bottom of a champagne bottle (i.e. with a hump or punt) around the linear configuration. NCNCS, cyanogen iso-thiocyanate, is a particularly good example of such a molecule and clearly exhibits a distinctive monodromy-induced dislocation of the energy level pattern at the bending-rotation energy at the top of the potential energy hump. Indeed, NCNCS [B. P. Winnewisser et al., Phys. Rev. Lett. 2005, 95, 243002] and the water molecule [N. F. Zobov et al., Chem. Phys. Lett. 2005, 414, 193-197] were the first two molecules for which experimental confirmation of quantum monodromy was obtained. We used the fast scan sub-millimetre spectroscopic technique (FASSST) to extend the measurements and spectral analysis to pure rotational transitions (end-over-end) in bending vibrational states lying well above the monodromy point. The analysis of 9204 lines assigned to 7 vibrational states, presented here, shows that the topological properties of the bending potential function are mapped onto every aspect of the ro-vibrational energy levels involving excitation of the quasi-linear bending vibration. In order to model the large amplitude dynamics of such a molecular system, and also to achieve some insight beyond satisfactory parameters for reproducing the spectrum, we used the generalized semi-rigid bender (GSRB) Hamiltonian, which is described in some detail. This Hamiltonian provides a good description of the energy levels over the seven bending states observed, coming close to experimental accuracy. Due to high J values of the measured rotational transitions (J</= 116), the least squares fitting procedure was applied not directly to the measured frequencies, but to effective constants derived from fitting the transition frequencies to a set of polynomials in J(J + 1) yielding effective B(eff) and D(eff) constants. The GSRB wave functions are used to show that the expectation values of any quantity which varies with the large amplitude bending coordinate will also have monodromy-induced dislocations. This includes the electric dipole moment components. High level ab initio calculations not only provided the molecular equilibrium structure of NCNCS, but also the electric dipole moment components mu(a) and mu(b) as functions of the large-amplitude bending coordinate. Calculated expectation values of these quantities for individual ro-vibrational levels show the now recognizable monodromy pattern. Finally, a generalization of the quasi-linear parameter gamma(0) is suggested.


Characteristics and outcomes of patients with COVID-19 in Hainan, South China.
As an international tourist center, Hainan province includes both imported and local COVID-19 cases. This study aimed to investigate the clinical characteristics and outcomes of COVID-19 patients in Hainan, China.COVID-19 patients hospitalized in Hainan affiliated Hospital of Hainan Medical University in January to March 2020 were retrospectively assessed. Routine blood tests, blood gas analyses, and computed tomography imaging were performed within 24 hours. Virus nucleic acid was detected every other day. The patients were divided into local resident and traveler groups, and differences in clinical data as well as leukocyte, lymphocyte, and neutrophil levels were analyzed.A total of 70 patients aged 51.23 ± 13.54 years were assessed, including 16 local residents and 54 travelers. Of these, 55 cases (78.6%) had fever, 47 (67.1%) had cough and sputum, and 9 (12.9%) had chest dyspnea; 60 and 10 cases were mild/common and severe/critical, respectively. Sex, basic diseases, smoking history and drinking history, Charlson Comorbidity Index, symptoms, time of onset to admission, clinical severity, white blood cell count, lymphocyte count, neutrophil count, oxygen inhalation, mechanical ventilation, glucocorticoid therapy, treatment, admission to ICU, hospital stay, and mortality were similar between the 2 groups.The warm and humid climate of Hainan does not seem to significantly affect patient features and outcomes from COVID-19. Unnecessary travel to tourist areas should be avoided.


Checkpoint blockade immunotherapy relies on T-bet but not Eomes to induce effector function in tumor-infiltrating CD8+ T cells.
Coinhibitory receptor blockade is a promising strategy to boost T-cell immunity against a variety of human cancers. However, many patients still do not benefit from this treatment, and responders often experience immune-related toxicities. These issues highlight the need for advanced mechanistic understanding to improve patient outcomes and uncover clinically relevant biomarkers of treatment efficacy. However, the T-cell-intrinsic signaling pathways engaged during checkpoint blockade treatment are not well defined, particularly for combination approaches. Using a murine model to study how effector CD8(+) T-cell responses to tumors may be enhanced in a tolerizing environment, we identified a critical role for the T-box transcription factor T-bet. Combination blockade of CTLA-4, PD-1, and LAG-3 induced T-bet expression in responding tumor/self-reactive CD8(+) T cells. Eradication of established leukemia using this immunotherapy regimen depended on T-bet induction, which was required for IFNγ production and cytotoxicity by tumor-infiltrating T cells, and for efficient trafficking to disseminated tumor sites. These data provide new insight into the success of checkpoint blockade for cancer immunotherapy, revealing T-bet as a key transcriptional regulator of tumor-reactive CD8(+) T-cell effector differentiation under otherwise tolerizing conditions.


[Hyperfractionated radiation therapy combined with concomitant chemotherapy for inoperable stage III non-small cell lung cancer: clinical analysis of 70 cases].
To evaluate the effect of hyperfractionated radiation therapy and concomitant chemotherapy for inoperable stage III non-small cell lung cancer (NSCLC). Seventy patients were randomized equally into two group. The therapy group received radiotherapy with hyperfractionated radiation therapy combined with concomitant chemotherapy, and the control group was treated with chemotherapy only. The overall response rate, including the rate of both complete (CR) and partial responses (PR), in the therapy group was 60.0% with a CR rate of 8.6%. The overall response rate in the control group was 40.0% with a CR rate of 5.7%. The difference in overall response rate was statistically significant between the two groups (P<0.05). The median survival time, 1- and 2-years survival rate were 12.8 months, 48.6%, and 25.7%, respectively, in the hyperfractionated radiotherapy group, and 9.4 months, 34.3%, and 17.1%, respectively, in the chemotherapeutic group (P 0.031). The major toxic effects of the chemotherapy were myelosuppression and radiation esophagitis. Hyperfractionated radiation therapy plus concomitant chemotherapy with paclitaxel for inoperable stage III NSCLC improves the short-term response of the patients, but fail to raise the survival rate.


A regression framework for brain network distance metrics.
Analyzing brain networks has long been a prominent research topic in neuroimaging. However, statistical methods to detect differences between these networks and relate them to phenotypic traits are still sorely needed. Our previous work developed a novel permutation testing framework to detect differences between two groups. Here we advance that work to allow both assessing differences by continuous phenotypes and controlling for confounding variables. To achieve this, we propose an innovative regression framework to relate distances (or similarities) between brain network features to functions of absolute differences in continuous covariates and indicators of difference for categorical variables. We explore several similarity metrics for comparing distances (or similarities) between connection matrices, and adapt several standard methods for estimation and inference within our framework: standard F test, F test with individual level effects (ILE), feasible generalized least squares (FGLS), and permutation. Via simulation studies, we assess all approaches for estimation and inference while comparing them with existing multivariate distance matrix regression (MDMR) methods. We then illustrate the utility of our framework by analyzing the relationship between fluid intelligence and brain network distances in Human Connectome Project (HCP) data.


Pitch cue learning in chinchillas: the role of spectral region in the training stimulus.
Chinchillas were trained to discriminate a cosine-phase harmonic tone complex (COS) from wideband noise (WBN) and tested in a stimulus generalization paradigm with tone complexes in which phase differed between frequency regions. In this split-phase condition, responses to complexes made of random-phase low frequencies, cosine-phase high frequencies were similar to responses to the COS-training stimulus. However, responses to complexes made of cosine-phase low frequencies, random-phase high frequencies were generally lower than their responses to the COS-training stimulus. When tested with sine-phase (SIN) and random-phase (RND) tone complexes, responses were large for SIN, but were small for RND. Chinchillas were then trained to discriminate infinitely-iterated rippled noise (IIRN) from WBN and tested with noises in which the spectral ripple differed between frequency regions. In this split-spectrum condition, responses were large to noises made of rippled-spectrum low frequencies, flat-spectrum high frequencies, whereas responses were generally lower to noises made of flat-spectrum low frequencies, rippled-spectrum high frequencies. The results suggest that chinchillas listen across all frequencies, but attend to high frequencies when discriminating COS from WBN and attend to low frequencies when discriminating IIRN from WBN.


[The imaging of organ transplants in children].
Imaging plays a major role in organ transplantation. It allows to show or to rule out numerous complications whose clinical and biologic picture is often little specific. Due to the fragility of these immunodepressed children, ultrasonography performed at the patient's bed side, is a irreplaceable supervision tool. Its association to pulsed Doppler was recently an important contribution to the diagnosis of hepatic and renal vascular lesions. The techniques of investigation which require the patient transport and anesthesia are performed only by second intention. The place of interventional radiology, especially in the treatment of hepatic and renal complications, should be emphasized.


Bone age assessment based on deep neural networks with annotation-free cascaded critical bone region extraction.
Bone age assessment (BAA) from hand radiographs is crucial for diagnosing endocrinology disorders in adolescents and supplying therapeutic investigation. In practice, due to the conventional clinical assessment being a subjective estimation, the accuracy of BAA relies highly on the pediatrician's professionalism and experience. Recently, many deep learning methods have been proposed for the automatic estimation of bone age and had good results. However, these methods do not exploit sufficient discriminative information or require additional manual annotations of critical bone regions that are important biological identifiers in skeletal maturity, which may restrict the clinical application of these approaches. In this research, we propose a novel two-stage deep learning method for BAA without any manual region annotation, which consists of a cascaded critical bone region extraction network and a gender-assisted bone age estimation network. First, the cascaded critical bone region extraction network automatically and sequentially locates two discriminative bone regions via the visual heat maps. Second, in order to obtain an accurate BAA, the extracted critical bone regions are fed into the gender-assisted bone age estimation network. The results showed that the proposed method achieved a mean absolute error (MAE) of 5.45 months on the public dataset Radiological Society of North America (RSNA) and 3.34 months on our private dataset.


Syndrome of orthostatic headaches and diffuse pachymeningeal gadolinium enhancement.
To characterize clinical and imaging features, biopsy findings, etiologic factors, and outcome in the syndrome of intracranial hypotension, headaches, and diffuse pachymeningeal gadolinium enhancement on magnetic resonance imaging (MRI). We describe our experience with 26 consecutive patients with orthostatic headaches and diffuse pachymeningeal gadolinium enhancement, for all of whom clinical, imaging, and follow-up data were available. For 10 patients who had undergone meningeal biopsy, slide material was also reviewed. The 15 men and 11 women ranged from 24 to 76 years of age. All 26 patients had postural headaches; in 22 patients, the headaches were completely alleviated by recumbency. Nausea or emesis, neck pain, horizontal diplopia, changes in hearing, photophobia, upper limb pains or paresthesias, visual blurring, or dysgeusia was noted in some of the patients. Cardinal MRI features were diffuse pachymeningeal gadolinium enhancement (100%), subdural collections of fluid (69%), and evidence of descent of the brain (62%) that sometimes resembled type I Chiari malformation. Cerebrospinal fluid (CSF) opening pressures were 40 mm or less in only 46%. In three patients, CSF pressures were consistently no less than 90 and as high as 130 mm of water. A variable pleocytosis of 5 or more cells/mm3 was noted in 15 patients (more than 40 cells/mm3 in 4 patients). A variable increase in CSF protein was noted in at least one spinal tap in 23 patients. Six patients had overdraining CSF shunts; CSF leak was documented in another 11 patients. Shunt revision or ligation and surgical correction of the leak led to a resolution of the clinical and MRI abnormalities in all cases thus treated. Improvement occurred with epidural blood patch in four patients. Three of the 12 patients treated supportively have remained symptomatic. Histologically, a thin subdural zone of fibroblasts and thin-walled vessels was noted in an amorphous matrix. Two patients with prolonged symptoms had a more pronounced proliferative reaction. The syndrome of low-pressure headaches and pachymeningeal gadolinium enhancement is being recognized with increasing frequency. The source of the CSF leak can be demonstrated in many patients. Meningeal abnormalities are likely attributable to decreased CSF volume and hydrostatic CSF pressure changes. The prognosis is typically good.


Body position does not affect the hemodynamic response to venous air embolism in dogs.
Current therapy for massive venous air embolism (VAE) includes the use of the left lateral recumbent (LLR) position. This recommendation is based on animal studies, conducted 50 yr ago, which looked primarily at survival. Little is known, however, about the concomitant hemodynamic response after VAE in various body positions. The purpose of this study was to investigate the hemodynamic and cardiovascular changes in various body positions after VAE. Twenty-two mechanically ventilated supine mongrel dogs received a venous air infusion of 2.5 mL/kg at a rate of 5 mL/s. One minute after the infusion, 100% oxygen ventilation was commenced and the body position of the dogs was changed to either the LLR (n = 6), the LLR with the head 10 degrees down (LLR-10 degrees; n = 6) or the right lateral recumbent (RLR; n = 5) position. Five dogs were maintained in the supine position (SUP; n = 5). One dog died in every group except in the SUP group, where all the dogs recovered. There were no significant differences among the various body positions in terms of heart rate, mean arterial pressure, pulmonary artery pressure, central venous pressure, left ventricular end-diastolic pressure, or cardiac output. The acute hemodynamic changes occurring during the first 5-15 min after VAE recovered to 80% of control within 60 min. Our data suggest that body repositioning does not influence the cardiovascular response to VAE. Specifically, our data do not support the recommendation of repositioning into the LLR position for the treatment of VAE.


Synbiotics Improved Stool Form via Changes in the Microbiota and Short-Chain Fatty Acids in Hemodialysis Patients.
Hemodialysis patients often develop constipation. We analyzed the advantage of synbiotics over prebiotics based on the stool form due to the intestinal environment in hemodialysis patients. Patients received either synbiotics or prebiotics for four weeks. The synbiotics group was treated with partially hydrolyzed guar gum containing Bifidobacterium longum BB536, while the prebiotics group was treated with the same fiber alone. The defecation status was assessed using the Bristol Stool Form Scale and abdominal bloating was evaluated using a visual analog scale. The fecal microbiota, measured by a terminal restriction fragment length polymorphism analysis, and the fecal short-chain fatty acid concentrations, measured by gas chromatography, were compared between the two groups. Synbiotics ingestion improved the individual stool form and abdominal bloating, and increased Bifidobacterium, which produces short-chain fatty acid, 13.9-fold after ingestion. In particular, acetic acid increased 2.5-fold in the synbiotics group. On the other hand, butyric acid increased 3.0-fold in the prebiotics group. Synbiotics improved the stool form in hemodialysis patients due to the composition of the intestinal microbiota and short-chain fatty acid concentrations.


Creutzfeldt-Jakob disease associated with a V203I homozygous mutation in the prion protein gene.
We report a Japanese patient with Creutzfeldt-Jakob disease (CJD) with a V203I homozygous mutation of the prion protein gene (PRNP). A 73-year-old woman developed rapidly progressive gait disturbance and cognitive dysfunction. Four months after the onset, she entered a state of an akinetic mutism. Gene analysis revealed a homozygous V203I mutation in the PRNP. Familial CJD with a V203I mutation is rare, and all previously reported cases had a heterozygous mutation showing manifestations similar to those of typical sporadic CJD. Although genetic prion diseases with homozygous PRNP mutations often present with an earlier onset and more rapid clinical course than those with heterozygous mutations, no difference was found in clinical phenotype between our homozygous case and reported heterozygous cases.


Effectiveness and safety of non-vitamin K oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke: A systematic review and meta-analysis.
Current evidence regarding the clinical outcomes of non-vitamin K oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and previous stroke are inconclusive, especially in patients with previous intracranial haemorrhage (ICrH). We aim to undertake a systematic review and meta-analysis assessing the effectiveness and safety of NOACs versus warfarin in AF patients with a history of stroke. We searched studies published up to 10th December 2022 on PubMed, Medline, Embase and Cochrane Central Register of Controlled Trials. Studies on adults with AF and previous ischemic stroke (IS) or IrCH receiving either NOACs or warfarin and capturing outcome events (thromboembolic events, ICrH, and all-cause mortality) were eligible for inclusion. Six randomized controlled trials (including 19489 patients with previous IS) and fifteen observational studies (including 132575 patients with previous IS and 13068 patients with previous ICrH ) were included. RCT data showed that compared with warfarin, NOACs were associated with a significant reduction in thromboembolic events (OR 0.85, 95% CI 0.75-0.96), ICrH(OR 0.57, 95% CI 0.36-0.90) and all-cause mortality (OR 0.88, 95% CI 0.80 to 0.98). In analysing observational studies, similar results were retrieved. Moreover, patients with previous ICrH had a lower OR on thromboembolic events than those with IS (OR 0.66, 95% CI 0.46-0.95 versus OR 0.80, 95% CI 0.70-0.93) in the comparison between NOACs and warfarin. Observational data showed that in AF patients with previous stroke, NOACs showed better clinical performance compared to warfarin and the benefits of NOACs were more pronounced in patients with previous IrCH versus those with IS. RCT data also showed NOACs are superior to warfarin. However, current RCTs only included AF patients who survived an IS and further large RCTs focus on patients with previous ICrH are warranted.


Long-term outcome after deferral of revascularization in patients with intermediate coronary stenosis and gray-zone fractional flow reserve.
A strategy of deferred percutaneous coronary intervention for coronary stenosis with fractional flow reserve (FFR) 0.75-0.80, termed the gray zone, remains a matter of debate. The aim of this study was to assess the safety of deferring revascularization for patients with FFR 0.75-0.80 compared with those with FFR >0.80. We assessed 3-year clinical outcome in 150 patients with angiographically intermediate stenosis who had revascularization deferred on the basis of FFR ≥ 0.75 (FFR 0.75-0.80, n=56; FFR >0.80, n=94). Target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR) was evaluated during follow-up. Cardiac death was observed in 1 patient with FFR 0.75-0.80. There was no target vessel-related MI in either group. The incidence of ischemia-driven TVR was higher in patients with FFR 0.75-0.80 than in those with FFR >0.80 (14% vs. 3%, P=0.020). TVF-free survival was significantly worse for the patients with FFR 0.75-0.80 than those with FFR >0.80 (hazard ratio, 5.2; 95% confidence intervals: 1.4-19.5; P=0.015). Patients with FFR 0.75-0.80 were at higher risk of TVF mainly due to TVR than those with FFR >0.80.


Fabrication of multiresponsive shell cross-linked micelles possessing pH-controllable core swellability and thermo-tunable corona permeability.
A double hydrophilic ABC triblock copolymer, poly(2-(diethylamino)ethyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate)-b-poly(N-isopropylacrylamide) (PDEA-b-PDMA-b-PNIPAM), containing the well-known pH-responsive PDEA block and thermoresponsive PNIPAM block, was synthesized by atom transfer radical polymerization via sequential monomer addition using ethyl 2-chloropropionate as the initiator. The obtained triblock copolymer exhibits interesting "schizophrenic" micellization behavior in aqueous solution, and supramolecularly self-assembles into three-layer "onion-like" PNIPAM-core micelles at acidic pH's and elevated temperatures and PDEA-core micelles with "inverted" structures at alkaline pH's and room temperature. In both cases, dynamic laser light scattering (LLS) and optical transmittance reveal the presence of near-monodisperse micelles, and the micelle formation/inversion process is fully reversible. Novel shell cross-linked (SCL) micelles with pH-responsive PDEA cores and thermoresponsive PNIPAM coronas were then facilely fabricated from the PDEA-b-PDMA-b-PNIPAM triblock copolymer by cross-linking the PDMA inner shells with 1,2-bis(2-iodoethoxy)ethane. The reversible pH-dependent swelling/shrinking of PDEA cores and thermosensitive collapse/aggregation of PNIPAM coronas of the obtained SCL micelles were investigated in detail by dynamic LLS, optical transmittance, and transmission electron microscopy. As the structurally stable SCL micelles possess pH-controllable core swellability and thermo-tunable corona permeability, the release profile of a model hydrophobic drug, dipyridamole, initially loaded within the hydrophobic PDEA core, can be dually controlled by both the solution pH and the temperature. This represents the first report of SCL micelles with multiresponsive cores and coronas, which may find practical applications in fields such as drug delivery and smart release.


3D kinematics using dual quaternions: theory and applications in neuroscience.
In behavioral neuroscience, many experiments are developed in 1 or 2 spatial dimensions, but when scientists tackle problems in 3-dimensions (3D), they often face problems or new challenges. Results obtained for lower dimensions are not always extendable in 3D. In motor planning of eye, gaze or arm movements, or sensorimotor transformation problems, the 3D kinematics of external (stimuli) or internal (body parts) must often be considered: how to describe the 3D position and orientation of these objects and link them together? We describe how dual quaternions provide a convenient way to describe the 3D kinematics for position only (point transformation) or for combined position and orientation (through line transformation), easily modeling rotations, translations or screw motions or combinations of these. We also derive expressions for the velocities of points and lines as well as the transformation velocities. Then, we apply these tools to a motor planning task for manual tracking and to the modeling of forward and inverse kinematics of a seven-dof three-link arm to show the interest of dual quaternions as a tool to build models for these kinds of applications.


Association of tea and its extracts with colorectal adenomas: meta-analysis and systematic review.
There are many studies on the association of tea and its extracts with colorectal adenomas, but the results have varied. The study aims to investigate the effect of tea and its extracts on colorectal adenomas using meta analysis and systematic review. Literature was obtained through PubMed, Cochrane Library, Embase and Chinese BioMedical Literature Service System since the establishment of the database until April 31, 2023. Search terms include adenomas, polyps, colorectal, rectal, rectum, tea, epigallocatechin, drinking and beverages. Meta-regression analysis was used to infer the source of heterogeneity. Heterogeneity was assessed using I2 statistics and Q test. The effect measures were odds ratio (OR) and 95% confidence interval (95% CI). Stata17.0 software was used for data processing. The findings indicated that study design (t = 0.78, P = 0.454), types of tea intake (t = 1.35, P = 0.205), occurrences (t = -0.19, P = 0.852), regions (t = 1.13, P = 0.281) and grades of adenomas (t = 0.06, P = 0.952) were statistical homogeneity. Tea and its extracts were negatively correlated with the risk of colorectal adenomas (OR = 0.81, 95% CI: 0.66-0.98). No publication bias was found in this study (t = -0.22, P = 0.828) and the results are robust. This study suggests that tea and its extracts have a certain protective effect on colorectal adenomas, which provides scientific evidence for preventive strategies for colorectal adenomas. As for the causal relationship between tea and its extracts on colorectal adenomas, further prospective studies are needed.


[Endonasal anatomy of lacrimal sac and its clinical significance in dacryocystorhinostomy].
To explore the intranasal surface localization of the lacrimal sac in endoscopic dacryocystorhinostomy. Fifteen adult cadavers (30 sides) were studied, the data of projection position of the lacrimal sac on the lateral wall of nasal cavity were measured. In 2/3 cadavers, the lacrimal sac is located above the axilla of the middle turbinate, and 1/3 lies below it. A majority of the lacrimal sac (2/3) are located below the entry point of the common lacrimal canaliculus, about 1/3 lies above it. Inner canthal ligament projects on the middle of the lacrimal sac, almost equal to the level of common lacrimal canaliculus. Thirty-two cases (thirty-nine sides) of chronic dacryocystitis were followed-up > 6 months after operation. Thirty-five sides were cured, 2 sides improved and 2 sides ineffective. The cure rate was 89.8%, improve rate 5.1% and ineffective rate 5.1%, respectively, and the total effective rate was 94.9%. The central position of dacryocystorhinostomy should be 0.2 cm above the front of the axilla of the middle turbinate, to make an curved mucous membrane incision 0.8 cm above and 0. 4 cm below the front of the axilla of the middle turbinate and bone ostium about 1.2 cm x 1.0 cm. It is the best position in endoscopic dacryocystorhinostomy. Locating the inner canthal ligament with a bayonet type forceps to find the projection of lacrimal sac is also a simple and easy method.


Ion dynamic characterization using phase-resolved laser-induced fluorescence spectroscopy in a Hall effect thruster.
Significant information on the dynamics of the plasma constituents in Hall effect thrusters can be obtained using minimally intrusive techniques, such as laser-induced fluorescence (LIF) diagnostics. Indeed, LIF provides an excellent tool to determine the ion velocity distribution function with high spatial resolution. Even in a steady-state operation, recording time-resolved maps of the velocity distribution is relevant due to persisting time-dependent features of the thruster discharge. One of the preeminent phenomena that render the ion velocity distribution to be time dependent is commonly attributed to the breathing mode, characterized by pronounced oscillations in the discharge current. The goal of this work is to propose a new technique for plasma dynamic studies based on LIF spectroscopy with phase-resolution during the breathing period. For this purpose, the Hilbert transform is used to define the instantaneous phase of oscillation of the thruster current. Ion velocity distribution modification over assigned phases of oscillation is measured simultaneously and in real-time thanks to a fully numerical analysis of the data.


Cognitive foundations of organizational learning: re-introducing the distinction between declarative and non-declarative knowledge.
Contemporary research into socio-cognitive foundations of organizational learning tends to disregard the distinction between declarative and non-declarative knowledge. By reviewing the literature from organizational learning research and cognitive psychology we explain that this distinction is crucial. We describe the foundations of organizational learning by referring to models that consider the interplay between individual and collective knowledge-related processes in organizations. We highlight the existence of a research gap resulting from the finding that these approaches have widely neglected the existence of different types of knowledge. We then elaborate on characteristics of declarative and non-declarative knowledge in general, consider organizations as structures of distributed cognition, and discuss the relationship between organizational knowledge and practice. Subsequently, we examine the role of declarative and non-declarative knowledge in the context of organizational learning. Here, we analyze (1) the cognitive and social mechanisms underlying the development of declarative and non-declarative knowledge within structures of distributed cognition; and (2) the relationship between alterations in declarative and non-declarative types of knowledge on the one hand and changes in organizational practice on the other. Concluding, we discuss implications of our analysis for organizational learning research. We explain how our integrative perspective may offer starting points for a refined understanding of the sub-processes involved in organizational learning and unlearning and may support a better understanding of practical problems related to organizational learning and change.


The antifilarial activity of a marine red alga, Botryocladia leptopoda, against experimental infections with animal and human filariae.
The antifilarial activity of the marine red alga Botryocladia leptopoda against rodent and human lymphatic filarial parasites is described. The animal filarial species included Litomosoides sigmodontis and Acanthocheilonema viteae maintained in cotton rats and Mastomys coucha, respectively, while a subperiodic strain of the human lymphatic filarial parasite Brugia malayi was maintained in M. coucha. The crude extract and its hexane fraction brought about a marked reduction in the peripheral microfilarial level in both of the rodent filarial parasites L. sigmodontis and A. viteae. The microfilaricidal effect began slowly from day 8 or 15 after initiation of treatment and increased with time with a very high efficacy at the end of the observation period against both rodent filariids. The microfilaricidal efficacy was, however, not as prominent in the case of B. malayi. The antifilarial activity, which occurred in the hexane fraction, exerted action at a much lower dose. The product killed a significant proportion of A. viteae and L. sigmodontis adult parasites. In the case of B. malayi, although the macrofilaricidal efficacy was much less than that of the rodent parasites, it (hexane fraction) caused sterilization of a significant proportion of the surviving female parasites. The present findings indicate the possibility of developing an adulticidal and female sterilizing agent against filarial parasites from a marine red alga.


The Karlsburg type 1 diabetes risk study of a normal schoolchild population: association of beta-cell autoantibodies and human leukocyte antigen-DQB1 alleles in antibody-positive individuals.
The intent of this study was to analyze the prevalence of diabetes-associated autoantibodies (AAbs) at or above the 99(th) percentile as well as their association with human leukocyte antigen (HLA)-DQB1 alleles in a normal population of 6,337 schoolchildren. AAbs against glutamic acid decarboxylase (GADA), tyrosine phosphatase IA-2 (IA-2A), and/or insulin (IAA) were detected by (125)I-antigen binding and islet cell antibodies (ICA) immunohistochemically in 181 (2.86%) schoolchildren. HLA-DQB1 alleles were analyzed in 178/181 children and subsequently compared with 119 controls. 2.37% (150/6,337) possessed only one AAb, whereas 0.49% (31/6,337) had multiple AAbs but at increased levels (P < 0.001). Subjects with GADA, IA-2A, or IAA revealed an increased frequency of the diabetes-associated HLA-DQB1 alleles *0302 and/or *02 (P = 0.001-0.006) as well as a decreased frequency in the protective allele *0602 (P < 0.001-0.022). DQB1*0602 was completely absent within children with multiple AAbs or with GADA, IA2-A, or IAA at or above the 99.9(th) percentile. In comparison to children with single AAbs, the frequency of associated/protective alleles of children with multiple AAbs was enhanced/diminished (P = 0.004-0.009). The study shows that also in the general population the multiple AAbs or high level single AAbs predict rather certainly a HLA-DQB1-mediated diabetes susceptibility as shown for first degree relatives of type 1 diabetic patients.


In Vitro Synergistic Enhancement of Newcastle Disease Virus to 5-Fluorouracil Cytotoxicity against Tumor Cells.
Chemotherapy is one of the antitumor therapies used worldwide in spite of its serious side effects and unsatisfactory results. Many attempts have been made to increase its activity and reduce its toxicity. 5-Fluorouracil (5-FU) is still a widely-used chemotherapeutic agent, especially in combination with other chemotherapies. Combination therapy seems to be the best option for targeting tumor cells by different mechanisms. Virotherapy is a promising agent for fighting cancer because of its safety and selectivity. Newcastle disease virus is safe, and it selectively targets tumor cells. We previously demonstrated that Newcastle disease virus (NDV) could be used to augment other chemotherapeutic agents and reduce their toxicity by halving the administered dose and replacing the eliminated chemotherapeutic agents with the Newcastle disease virus; the same antitumor activity was maintained. In the current work, we tested this hypothesis on different tumor cell lines. We used the non-virulent LaSota strain of NDV in combination with 5-FU, and we measured the cytotoxicity effect. We evaluated this combination using Chou-Talalay analysis. NDV was synergistic with 5-FU at low doses when used as a combination therapy on different cancer cells, and there were very mild effects on non-cancer cells. The combination of a virulent, non-pathogenic NDV-LaSota strain with a standard chemotherapeutic agent, 5-FU, has a synergistic effect on different tumor cells in vitro, suggesting this combination could be an important new adjuvant therapy for treating cancer.


Doping of Tetraalkylammonium Salts in Polyethylenimine Ethoxylated for Efficient Electron Injection Layers in Solution-Processed Organic Light-Emitting Devices.
For efficient electron injection, a method to control the work functions (WFs) of ZnO electrodes in organic light-emitting devices (OLEDs) is reported in this study. First, ZnO was modified by doping of tetraalkylammonium salts (TRAX) into polyethylenimine ethoxylated (PEIE) for the WF control. Tetrabutylammonium salts (TBAX), where X = chloride, bromide, iodide, acetate, thiocyanate, and tetrafluoroborate anions, were doped into PEIE. A WF of nondoped PEIE-modified ZnO was 3.65 eV, whereas TBAX-doped PEIE-modified ZnO exhibited WFs ranging from 3.52 to 3.00 eV depending on the anion. TBAX salts exhibited different electron-donating capabilities depending on the anion, and the doping of TBAX with a large electron-donating capability exhibited a large WF reduction effect. In addition, tetraethyl- and tetrahexylammonium chlorides were doped into PEIE. PEIE doped with TRACl containing long alkyl chains exhibited a large WF reduction effect due to its low electron-accepting capabilities. In addition, the WF reduction mechanism was considered by the depth direction analysis of the PEIE:TBAX films. Finally, the ZnO/PEIE:TRAX bilayers were applied as electron injection layers in poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] emissive-layer-based OLEDs with an inverted structure. The ZnO/PEIE:TBAX devices with low WFs exhibited low driving voltages.


Cytosolic Hsp60 can modulate proteasome activity in yeast.
Hsp60, an essential oligomeric molecular mitochondrial chaperone, has been subject to rigorous basic and clinical research. With yeast as a model system, we provide evidence for the ability of cytosolic yHsp60 to inhibit the yeast proteasome. (i) Following biological turnover of murine Bax (a proteasome substrate), we show that co-expression of cytosolic yHsp60 stabilizes Bax, enhances its association with mitochondria, and enhances its killing capacity. (ii) Expression of yHsp60 in the yeast cytosol (yHsp60c) inhibits degradation of a cytosolic protein ΔMTS-Aco1 tagged with the degron SL17 (a ubiquitin-proteasome substrate). (iii) Conditions under which Hsp60 accumulates in the cytosol (elevated Hsp60c or growth at 37 °C) correlate with reduced 20 S peptidase activity in proteasomes purified from cell extracts. (iv) Elevated yHsp60 in the cytosol correlate with accumulation of polyubiquitinated proteins. (v) According to 20 S proteasome pulldown experiments, Hsp60 is physically associated with proteasomes in extracts of cells expressing Hsp60c or grown at 37 °C. Even mutant Hsp60 proteins, lacking chaperone activity, were still capable of proteasome inhibition. The results support the hypothesis that localization of Hsp60 to the cytosol may modulate proteasome activity according to cell need.


Clinical encounters may not be responding to patients' search for meaning and control over non-specific chronic low back pain - an interpretative phenomenological analysis.
Considering the need to study the experiences of individuals with musculoskeletal problems in contexts that have not yet been investigated as well as the relevance of fostering a research agenda towards person-centred care, this study aimed to explore the experiences of non-specific chronic low back pain from the perspective of Portuguese individuals living with it. An interpretative phenomenological analysis was employed to explore the experiences of eight participants, who were recruited purposefully from two primary care centres and one clinic. Semi-structured one-to-one interviews were carried out, audio-recorded and transcribed verbatim. Three themes were generated as interrelated parts of an extended account that explored the participants' meaning making of their experience: "Non-specific chronic low back pain as a disruptive experience"; "Searching for the meaning of non-specific chronic low back pain"; and, "Clinical encounters that perpetuate the lack of understanding about non-specific chronic low back pain." This study offers insight into the Portuguese individuals' experiences of non-specific chronic low back pain. Particularly, it suggests that clinical encounters may not be aligned with patients' needs and expectations. These findings may help clinicians in transferring this knowledge to therapeutic approaches to individuals with similar experiences/contexts.IMPLICATIONS FOR REHABILITATIONPatients with NSCLBP need to understand their pain and to retain a sense of control over their lives.Encounters with health professionals may perpetuate the lack of understanding about pain and strategies to control it, as patients consider themselves unable to have an active role in the decision-making and are disempowered to deal with their pain.Health professionals should involve patients and promote the co-construction of an explanation that integrates both health professionals' knowledge and patients' narratives.There is a need to align both the patients' and health professionals' perspectives regarding health care in order to implement patient-centred and individually tailored treatment.


Psychological Distress and Health Insurance Coverage among Formerly Incarcerated Young Adults in the United States.
The United States incarcerates more people per capita than any other nation. Studies have consistently demonstrated higher prevalence of serious mental illness among the incarcerated. Although health care may be available to individuals while incarcerated, research is needed to understand the context of health care coverage and mental health after incarceration. The purpose of this study is to estimate the point prevalence of psychological distress (PD) among young adults with incarceration experience, while comparing the prevalence to that of young adults in the general population. Additionally, this study characterizes the relationship between incarceration experience and PD, while also examining this association given an individual's health insurance coverage status among young adults. Lastly, we examine if other individual, contextual, and behavioral factors influences the relationship between incarceration experience and PD, in addition to their health insurance coverage status. This study utilizes data from the 2008 panel of the National Longitudinal Survey of Youth 97, a population based survey dataset from the U.S. Department of Labor. Andersen's Behavioral Model of Health Services Use provided the conceptual framework for the study. The Mental Health Index 5 (MHI-5) was used to determine PD or normal mental health. Chi-square testing and multivariate logistic regression were performed to examine incarceration experience in association to PD. The sample with incarceration experience reported almost double the proportion of PD (21%) compared to those without an incarceration experience (11%). Young adults who have been incarcerated reported greater odds of PD than those with no incarceration experience (COR 2.18; 95% CI, 1.68-2.83) and the association was diminished in the presence of health insurance status and model covariates. Future health prevention and health management efforts should consider the impact of health insurance coverage status, health behaviors, and life satisfaction on mental health status among young adults with incarceration experience.


Chlamydia trachomatis diagnostics.
Nucleic acid amplification (NAA) assays for the diagnosis of Chlamydia trachomatis infections started to appear in the peer reviewed literature about 12 years ago and during that period we have seen an incredible effort put into the development and evaluation of commercially developed NAA kits to diagnose and treat infections.