Attitudes Toward Seeking Mental Health Services and Mobile Technology to Support the Management of Depression Among Black American Women: Cross-Sectional Survey Study.
Depression is a common mental health condition among Black American women. Many factors may contribute to the development of depressive symptoms, such as gender and racial discrimination, financial strain, chronic health conditions, and caregiving responsibilities. Barriers such as the stigmatization of mental illness, less access to treatment, the lack of or inadequate health insurance, mistrust of providers, and limited health literacy prevent marginalized populations from seeking care. Previous literature has shown that mobile health interventions are effective and can increase access to mental health services and resources. We aimed to understand the attitudes and perceptions of Black women toward using mental health services and determine the acceptability and concerns of using mobile technology (ie, voice call, video call, SMS text messaging, and mobile app) to support the management of depression. We launched a self-administered web-based questionnaire in October 2019 and closed it in January 2020. Women (aged ≥18 years) who identify as Black or African American or multiracial (defined as Black or African American and another race) were eligible to participate. The survey consisted of approximately 70 questions and included topics such as attitudes toward seeking professional psychological help, the acceptability of using a mobile phone to receive mental health care, and screening for depression. The findings (n=395) showed that younger Black women were more likely to have greater severity of depression than their older counterparts. The results also revealed that Black women have favorable views toward seeking mental health services. Respondents were the most comfortable with the use of voice calls or video calls to communicate with a professional to receive support for managing depression in comparison with SMS text messaging or mobile apps. The results revealed that higher help-seeking propensity increased the odds of indicating agreement with the use of voice calls and video calls to communicate with a professional to receive support for managing depression by 27% and 38%, respectively. However, no statistically significant odds ratios (all P>.05) were found between help-seeking propensity and respondents' agreement to use mobile apps or SMS text messaging. Moderate to severe depression severity increased the odds of using mobile apps to communicate with a professional to receive support for managing depression by 43%; however, no statistically significant odds ratios existed for the other modalities. Privacy and confidentiality, communication issues (eg, misinterpreting text), and the impersonal feeling of communicating by mobile phone (eg, SMS text messaging) were the primary concerns. Black American women, in general, have favorable views toward seeking mental health services and are comfortable with the use of mobile technology to receive support for managing depression. Future work should address the issues of access and consider the preferences and cultural appropriateness of the resources provided.


Effects of an exogenous beta-amyloid peptide on retention for spatial learning.
Three experiments assessed the effects of beta-amyloid 1-40 (beta A4) on spatial learning in Sprague-Dawley rats. In Experiment 1, rats were trained on a signaled footshock avoidance in a Y-maze. Rats received a single injection of beta A4 or vehicle in both sides of the hippocampus immediately after the fifth trial. The beta A4 group took significantly longer than the vehicle group to learn to avoid the shock when trained to criterion 1 week later, suggesting a detrimental effect of beta A4 on memory consolidation. Experiment 2 used a food reinforcer rather than shock relief under procedures similar to Experiment 1. Again, the beta A4 group took longer to learn the maze to criterion. This shocks that the effect in Experiment 1 was not specific to shock-maintained learning. In Experiment 3, rats were trained to retrieve a food pellet from each arm of an eight-arm radial maze. After training to criterion, beta A4 or vehicle was administered intrahippocampally 30 min before the daily session for 26 sessions. There were no acute or chronic effects of beta A4 injection on radial maze performance, and no aggregation of beta A4 or significant necrosis was observed upon postmortem histological analysis. These experiments suggest that single injections of beta A4 impair memory consolidation, but repeated injections of beta A4 over an extended period do not affect well-learned behavior.


Oncogenic role of long non-coding RNA SNHG12 in gastric cancer cells by targeting miR-16.
The long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) has recently been reported to have an oncogenic role in gastric cancer (GC), but the molecular mechanisms remain largely elusive. In the present study, it was observed that SNHG12 was significantly upregulated in GC tissues and cell lines. High expression of SNHG12 was associated with GC progression and poor prognosis of patients. Knockdown of SNHG12 markedly inhibited the proliferation and migration of the BGC823 and HGC27 GC cell lines. MicroRNA (miR)-16 was identified as a target of SNHG12, and its expression was negatively regulated by SNHG12 in BGC823 and HGC27 cells. In addition, the expression of miR-16 was significantly decreased in GC tissues and cell lines, and inversely associated with the expression of SNHG12 in GC tissues. Furthermore, knockdown of miR-16 impaired the inhibitory effects on GC cell proliferation and migration induced by downregulation of SNHG12. In conclusion, the present study demonstrates that inhibition of SNHG12 suppresses GC cell proliferation and migration by modulation of miR-16 expression, and thus suggests that the SNHG12/miR-16 interaction may be used as a promising target for GC treatment.


Dental Students' Learning Experiences and Preferences Regarding Orofacial Pain: A Cross-Sectional Study.
Pain is a global health problem, the effects of which range from diminished quality of life to pain management costs and loss of work and productivity. Pain in the head and neck region is defined as a separate entity: orofacial pain (OFP). However, some graduates from dental schools have reported feeling less competent in their ability to diagnose OFP than in other areas of dentistry. The aims of this study were to assess how students at one U.S. dental school had learned about OFP and to identify the teaching methods and venues they would like to see enhanced in the school's OFP curriculum. A cross-sectional four-question survey was administered to 140 dental students in their third and fourth years; the survey had a response rate of 53%. Most students reported having gained their OFP knowledge mainly in dental school, and 91.9% selected didactic courses as the main teaching method in which they had learned about this topic. Clinical education was the main teaching venue these students said they would like to see enhanced in order to gain more knowledge in most forms of OFP; this result aligned with their learning preferences in general. These findings may help dental schools design their OFP curricula to take account of students' preferences as well as practical limitations regarding availability of clinical experiences.


Cause of death in demented and non-demented elderly inpatients; an autopsy study of 308 cases.
Few studies evaluated cause of death (COD) in elderly demented and non-demented people, the majority based on death certificates alone. The present study is based on autopsy reports with neuropathological examination of 308 inpatients (58.1% female) over age 60 years (mean: 83.5, SD: +/-8.6). CODs were classified into seven groups. The most common were bronchopneumonia (n=117; 38%) and cardiovascular disease (n=116, 37.7%). In 176 patients (57.1%) neuropathology was indicative for dementia: 76.7% Alzheimer disease (AD), 4.5% vascular dementia, 4.0% mixed type dementia (AD + vascular dementia), and 14.8% other dementias. Main COD significantly differed in demented and non-demented patients: bronchopneumonia (45.5% in demented versus 28.0% in non-demented), cardiovascular disease (46.2% in non-demented versus 31.3% in demented). Whereas there were significant differences in COD between AD patients and non-demented ones (bronchopneumonia versus cardiovascular disease), no differences were seen between the latter and patients with other types of dementia than AD. Our data emphasize the high incidence of bronchopneumonia as a COD in patients suffering from AD.


Online News Coverage of the Sugar-Sweetened Beverages Tax in Malaysia: Content Analysis.
In Malaysia, the Sugar-Sweetened Beverages (SSBs) tax was announced during the parliament's 2019 Budget Speech. The tax was slated to be enforced by April 2019 but was later postponed to July 2019. The announcement has since generated significant media coverage and public feedback. This study presents a qualitative and quantitative cross-sectional study using netnography to examine how Malaysian online news articles responded to the SSBs tax after the announcement and postimplementation. Online news articles published on popular online news platforms from November 2018 to August 2019 were downloaded using NCapture and imported into NVivo for analysis using the inductive approach and thematic content analysis following the initial SSBs implementation announcement. A total of 62 news articles were analyzed. Most of the articles positively portrayed the SSBs tax (46.8%) and highlighted its health impacts (76%). There were 7 key framing arguments identified in the articles. The positive arguments revolved around incentivizing manufacturers to introduce healthier products voluntarily, positive health consequences, the tax's impact on government revenue, and the use of the generated revenue toward beneficial social programs. The opposing arguments included increased operating costs to the manufacturer, the increased retail price of drinks, and how the SSBs tax is not a robust solution to obesity. The top priority sector considered in introducing the tax was the health perspective, followed by economic purposes and creating policies such as regulating the food and drinks industry. The majority of online news articles positively reported the implementation of the SSBs tax in Malaysia. This suggests media played a role in garnering support for the health policy. As such, relevant bodies can use negative findings to anticipate and reframe counteracting arguments opposing the SSBs tax.


FOXA2 attenuates lipopolysaccharide‑induced pneumonia by inhibiting the inflammatory response, oxidative stress and apoptosis through blocking of p38/STAT3 signaling.
Pneumonia is a severe inflammatory disease of the lung. Forkhead box protein A2 (FOXA2) has been demonstrated to serve an important regulatory role in various pulmonary diseases; however, the role of FOXA2 in pneumonia remains to be elucidated. The present study aimed to explore the functional effects and regulatory mechanism of FOXA2 in pneumonia. An in vitro pneumonia model was induced using lipopolysaccharide (LPS) in WI-38 cells. The mRNA and protein expression levels of FOXA2 were determined by reverse transcription-quantitative PCR and western blotting, respectively. Cell viability was assessed using a Cell Counting Kit-8 assay. Inflammatory cytokines were evaluated using ELISA kits and oxidative stress markers were assessed using a malondialdehyde assay kit, superoxide dismutase assay kit and CATalase assay kit. Cell apoptosis was evaluated using flow cytometry and the caspase3 activity was determined. Western blotting was performed to examine the protein expression levels of endoplasmic reticulum stress (ERS)-associated factors. For a rescue assay, a p38 MAPK activator, U46619, was used to investigate the regulatory mechanism of FOXA2 involving p38/STAT3 signaling. FOXA2 was downregulated in LPS-induced WI-38 cells. FOXA2 overexpression alleviated LPS-induced inflammation, oxidative stress, apoptosis and ERS in WI-38 cells. Furthermore, the inhibitory effects of FOXA2 on inflammation, oxidative stress and apoptosis, as well as ERS in LPS-induced WI-38 cells were partly weakened by additional treatment with U46619. In conclusion, FOXA2 served a protective role against LPS-induced pneumonia by regulating p38/STAT3 signaling, providing a novel idea for the development of targeted therapeutic strategies for pneumonia.


Specific and intraspecific molecular typing of lactococci based on polymorphism of DNA encoding rRNA.
The rRNA gene restriction patterns or species of the genus Lactococcus were determined. Chromosomal DNA was digested with endonucleases and probed with radiolabelled DNA complementary to rRNA synthesized by random oligonucleotide priming using reverse transcriptase. Highly discriminatory restriction patterns were obtained which served to distinguish the five currently recognized lactococcal species. In addition the observed variations in the patterns at intra-specific level indicate that rRNA gene restriction fingerprinting may be of value in distinguishing the individual strains for epidemiological studies, and monitoring and checking authenticity of starter strains.


Conducting a multidisciplinary morbidity and mortality conference in the trauma-surgical intensive care unit.
The trauma-surgical intensive care unit at Harborview Medical Center has developed a multidisciplinary case review process to allow discussion of complications and issues in an open forum among multiple services. Conducted monthly, this meeting provides a forum for clear communication between members of the patient care team with the goal of developing best practices, system changes, and policies that will minimize risk for the patients and provide education for the staff.


Clinical progress in impending central retinal vein occlusion.
Impending central retinal vein occlusion is associated with mild or no loss of vision; however, its progress and vision prognosis have not been clearly defined until now. Therefore, we studied the progress and prognoses in patients with impending central retinal vein occlusion. For this study, we selected ten subjects who had been diagnosed with impending central retinal vein occlusion, and we retrospectively reviewed their progress and prognoses. The average age of the subjects was 31.0 years (18 to 48 years). Eight patients were male and two were female. The average observational period was 5.5 months. Six out of ten subjects were found to have no underlying systemic disease, four subjects had underlying disease. All ten patients were affected unilaterally. When initially tested, the affected eyes showed an average vision of LogMar 0.30. The final vision test revealed an average of LogMar 0.04, which indicates good progress and prognosis. In one patient, retinal hemorrhage and macular edema progressively worsened after the diagnosis, and the patient was treated with radial optic neurotomy. The cases of impending central retinal vein occlusion that we observed seemed to primarily affect young patients with generally good prognoses. However, in some cases, the degrees of obstruction and hemorrhage increased as time progressed. This suggests that impending central retinal vein occlusion could develop into the prodromal phase of an acute attack.


Patterned fabrication of single ZnO nanorods and measurement of their optoelectrical characteristics.
This work develops a new process of growing well ordered ZnO nanorods in large scale on the Si(111) substrate. Nanosphere lithography (NSL) was adopted to produce a matrix in an extensive area. A pattern with a controlled amount of gold was formed through the nanosphere mask. The ZnO nanorods were then grown on a patterned Au/Si substrate through a metal catalytic vapor-liquid-solid (VLS) process. The structure and characteristics of ZnO nanorods were investigated by XRD, SEM and TEM. The hexagonal nanorods were dominated at (0002) direction with a lattice constant of approximately 5.03 A. The optoelectronical properties were studied by PL emission spectroscopy. A strong UV emission at 380 nm was observed. The band gap of the single ZnO nanorod was directly measured to be 3.36 eV using a conductive AFM. The superiority of patterned ZnO nanorods indicates their great potential in field emission display arrays.


Qualitative Comparative Analysis: A Mixed-Method Tool for Complex Implementation Questions.
The translation and scale-up of evidence-based programs require new methods to guide implementation decisions across varying contexts. As programs are translated to real-world settings, variability is introduced. Some program components may have minor roles to play in producing positive outcomes, and some may have major roles, but only if adapted to meet different contextual demands. While some sources of variability are likely to improve program outcomes, we currently lack methods that allow us to determine the critical components or combinations of components that serve as causal pathways to a desired outcome and then to advise practitioners accordingly. In this paper, we introduce a promising tool for this purpose and illustrate its use in a translational research context. Qualitative Comparative Analysis (QCA) is often used to examine causality in situations that have complex, multiply-determined outcomes. The basic premise of QCA is that different sets of causal conditions, or causal pathways, may lead to a single outcome (the principle of equifinality). We applied QCA to a selection of the highest- and lowest-performing programs from a multi-year two-state dissemination of The Strengthening Families Program for Parents and Adolescents 10-14 to determine which components or combinations of components at the implementation, program delivery, and participant levels produced desired participant outcomes. In particular, we examined which components were necessary (i.e., in the absence of these factors, the outcome didnot occur), and which were sufficient (i.e., in the presence of these factors, the outcome always occurred). Results demonstrated that certain conditions were necessary for program success. In addition, given those necessary conditions, there were two sets of conditions sufficient to produce success, regardless of the presence or absence of any of the others. QCA, not previously used in prevention science research, helps to illuminate causal pathways, leading to concrete, evidence-based implementation decisions that facilitate generalization and scale-up.


Reactions of doubly ionized benzene with nitrogen and water: a nitrogen-mediated entry into superacid chemistry.
Even in the highly diluted gas phase, rather than electron transfer the benzene dication C(6)H(6)(2+) undergoes association with dinitrogen to form a transient C(6)H(6)N(2)(2+) dication which is best described as a ring-protonated phenyl diazonium ion. Isotopic labeling studies, photoionization experiments using synchrotron radiation, and quantum chemical computations fully support the formation of protonated diazonium, which is in turn a prototype species of superacidic chemistry in solution. Additionally, reactions of C(6)H(6)(2+) with background water involve the transient formation of diprotonated phenol and, among other things, afford a long-lived C(6)H(6)OH(2)(2+) dication, which is attributed to the hydration product of Hogeveen's elusive pyramidal structure of C(6)H(6)(2+), as the global minimum of doubly ionized benzene. Nitrogen is essential for the formation of the C(6)H(6)OH(2)(2+) dication in that it mediates the formation of the water adduct, while the bimolecular encounter of the C(6)H(6)(2+) dication with water only leads to (dissociative) electron transfer.


Colony-stimulating factor 2 enhances the developmental competence of yak (Poephagus grunniens) preimplantation embryos by modulating the expression of heat shock protein 70 kDa 1A.
Colony-stimulating factor 2 (CSF2) is known to promote the development and survival of rodents and ruminants preimplantation embryos; however, the effect of CSF2 on yak embryos has not been reported. The objective of this study was to investigate the effects of CSF2 on the developmental competence of yak embryos cultured in vitro in modified synthetic oviduct fluid (mSOF) medium and on the expression pattern of heat shock protein 70 kDa 1A (HSPA1A). In each experiment, cumulus-oocyte complexes (COCs) were matured in vitro and fertilized with frozen-thawed semen. Zygotes were treated with varying concentrations of CSF2 (0, 10, 50, 100 ng/mL) until day 8 after fertilization. Embryo development was calculated as the percentage of oocytes that formed embryos at the 2-cell, 4-cell, 8-cell, 16-cell, morula and blastocyst stages. The total cell numbers (TCN) per blastocyst and their allocation to the inner cell mass (ICM) and trophectoderm (TE) lineages were determined using differential CDX2 staining. The expression of HSPA1A was examined by quantitative real-time PCR (qRT-PCR) and immunochemistry to determine the mRNA and protein levels. The results showed that treatment with 50 ng/mL CSF2 significantly (P < 0.05) increased the rate of blastocyst formation (19.01% versus 9.93%) and the TCN per blastocyst (96.94 versus 81.41) compared to the control group. However, no significant differences were observed in the other stages of development. qRT-PCR analysis confirmed that treatment with 50 ng/mL CSF2 significantly (P < 0.05) inhibited the expression of HSPA1A mRNA in blastocysts cultured in vitro relative to the control group, but there were no significant differences between the other treatment groups. Immunocytochemical analysis confirmed that HSPA1A protein accumulation was gradually reduced in yak blastocysts cultured in 0, 10, 100 or 50 ng/mL CSF2, however, no significant differences were observed between the 10 and 100 ng/mL treatments (P > 0.05). In conclusion, these findings demonstrate that CSF2 inhibits the expression of HSPA1A to facilitate yak blastocyst formation and increase cell numbers.


Social reactions to child sexual abuse disclosures: a critical review.
Recent studies have examined disclosure of child sexual abuse to determine the correlates and consequences of telling others about this form of victimization. The present article reviews the current empirical literature on disclosure and reactions to adult survivors to assess what is known about the process of disclosure and whether telling others is therapeutic and leads to positive outcomes. Most studies assessing social reactions in detail have concerned adult survivors retrospectively reporting on their disclosures of child sexual abuse. Few empirical studies have been conducted in this area but research suggests that few victims tell anyone about child sexual abuse as children, and that the type of reactions to disclosure vary according to when disclosure occurs (childhood or adulthood), the extent and nature of the disclosure, and the person to whom one discloses. Clear evidence shows that negative social reactions are harmful to survivors' well-being, but better assessment of specific reactions and their effects are needed in theoretically-based studies to evaluate how these responses affect survivors' recovery in the context of other variables. Suggestions for future research on social reactions of others to adult survivors disclosing child sexual abuse are presented.


Genetic differentiation of water buffalo (Bubalus bubalis) populations in China, Nepal and south-east Asia: inferences on the region of domestication of the swamp buffalo.
Data from three published studies of genetic variation at 18 microsatellite loci in water buffalo populations in China (18 swamp type, two river type), Nepal (one wild, one domestic river, one hybrid) and south-east Asia (eight swamp, three river) were combined so as to gain a broader understanding of genetic relationships among the populations and their demographic history. Mean numbers of alleles and expected heterozygosities were significantly different among populations. Estimates of θ (a measure of population differentiation) were significant among the swamp populations for all loci and among the river populations for most loci. Differentiation among the Chinese swamp populations (which was due primarily to just one population) was much less than among the south-east Asian. The Nepal wild animals, phenotypically swamp type but genetically like river type, are significantly different from all the domestic river populations and presumably represent the ancestral Bubalus arnee (possibly with some river-type introgression). Relationships among the swamp populations (D(A) genetic distances, principal component analysis and structure analyses) show the south-east Asian populations separated into two groups by the Chinese populations. Given these relationships and the patterns of genetic variability, we postulate that the swamp buffalo was domesticated in the region of the far south of China, northern Thailand and Indochina. Following domestication, it spread south through peninsular Malaysia to Sumatra, Java and Sulawesi, and north through China, and then to Taiwan, the Philippines and Borneo.


Nitrogen deposition does not enhance Sphagnum decomposition.
Long-term additions of nitrogen (N) to peatlands have altered bryophyte growth, species dominance, N content in peat and peat water, and often resulted in enhanced Sphagnum decomposition rate. However, these results have mainly been derived from experiments in which N was applied as ammonium nitrate (NH4NO3), neglecting the fact that in polluted areas, wet deposition may be dominated either by NO3(-) or NH4(+). We studied effects of elevated wet deposition of NO3(-) vs. NH4(+) alone (8 or 56kgNha(-1)yr(-1) over and above the background of 8kgNha(-1)yr(-1) for 5 to 11years) or combined with phosphorus (P) and potassium (K) on Sphagnum quality for decomposers, mass loss, and associated changes in hummock pore water in an ombrotrophic bog (Whim). Adding N, especially as NH4(+), increased N concentration in Sphagnum, but did not enhance mass loss from Sphagnum. Mass loss seemed to depend mainly on moss species and climatic factors. Only high applications of N affected hummock pore water chemistry, which varied considerably over time. Overall, C and N cycling in this N treated bog appeared to be decoupled. We conclude that moss species, seasonal and annual variation in climatic factors, direct negative effects of N (NH4(+) toxicity) on Sphagnum production, and indirect effects (increase in pH and changes in plant species dominance under elevated NO3(-) alone and with PK) drive Sphagnum decomposition and hummock C and N dynamics at Whim.


Effect of high-dose stereotactic body radiation therapy on liver function in the treatment of primary and metastatic liver malignancies using the Child-Pugh score classification system.
The purpose of this study was to evaluate liver function after high-dose liver stereotactic body radiation therapy (SBRT) in the treatment of metastatic and primary malignancies of the liver using the Child-Pugh score classification system. This was a retrospective analysis of 46 patients treated with SBRT for metastatic and primary malignancies of the liver. Patient, disease, prior treatment, and SBRT dosimetric factors were analyzed to correlate with decline in Child-Pugh class after liver SBRT. Median follow-up was 11.0 months for patients alive at last follow-up. Twenty-three patients (50%) had primary liver malignancies. Median delivered dose was 55 Gy in 5 fractions (range, 36-60 Gy in 3-6 fractions) to 1 lesion (range, 1-4 lesions) measuring 4.0 cm (range, 1.3-12.4 cm). Forty-one patients (89%) received ≥50 Gy in 3 to 6 fractions. Child-Pugh score classification was A in 42 patients (91%). Seven patients (15%) received adjuvant chemotherapy or targeted therapy. Twenty-nine patients (63%) experienced an intrahepatic recurrence after treatment. Ten patients (22%) experienced a decline in Child-Pugh class at a median of 1.6 months (range, 0.2-6 months). Eighty percent experienced a one-category decline. Only the V20, V25, V30, and V50 were correlated with decline in Child-Pugh class on univariate analysis, with V25 being most significant (P = .027). A V25 >32% was associated with a 42% incidence of Child-Pugh class decline compared with 9% for V25 ≤32 (P = .029). For primary liver malignancies, a V25 >36% was associated with a 4-fold increase in the incidence of Child-Pugh class decline (60% vs 15%, P = .021). Approximately one-quarter of patients experience a decline in Child-Pugh class after high-dose liver SBRT. The V25 may be an important dosimetric parameter predicting decline in liver function after treatment.


Nocarimidazoles A and B from a Marine-Derived Actinomycete of the Genus Nocardiopsis.
Chemical investigation of a marine-derived actinomycete isolated from marine sediments collected off the coast of southern California and identified as a Nocardiopsis sp. (strain CNQ115) led to the isolation of two new 4-aminoimidazole alkaloids, nocarimidazoles A (1) and B (2). The chemical structures of nocarimidazoles A and B were assigned by interpretation of NMR spectroscopic data and through methylation to yield monomethyl and dimethyl derivatives. Nocarimidazoles A and B possess a 4-aminoimidazole ring combined with a conjugated carbonyl side chain, which is rarely found in microbial secondary metabolites.


Determination of nitrite and glucose in water and human urine with light-up chromogenic response based on the expeditious oxidation of 3,3',5,5'-tetramethylbenzidine by peroxynitrous acid.
Contamination of food and drinking water by dangerous levels of nitrite has always been of strong concern and toxicity of this inorganic anion calls for convenient detection methods. Although some visible approaches were developed to deal with this problem, using environmentally incompatible organic reagents or functionalized nanoparticles may greatly limit their wide applications. In this article, we report a method to visibly detect nitrite in less than 1 min at room temperature. The efficacy of the method relies on a specific reaction of HNO2 with H2O2 to produce peroxynitrous acid (HOONO), which oxidizes colorless 3,3',5,5'-tetramethylbenzidine (TMB) to its golden yellow diimine product in seconds, with the regeneration of HNO2. Therefore, HNO2 can be regarded as a catalyst for the oxidation of TMB by H2O2. Because color visualization of the TMB-H2O2 system (system I) is dependent upon the concentration of HNO2, it offers a unique avenue for the determination of nitrite. With this method, 1 μM of nitrite could be detected by the perception of yellow color in solution and less than 0.5 μM of nitrite be quantified with a spectrophotometer. The limit of detection (LOD) was 0.1 μM (S/N = 3). More interestingly, we found that the TMB-HNO2 system (system II) could be reversibly designed to detect H2O2 and then glucose with the help of glucose oxidase. We evaluated the applicability of the TMB-HOONO platform in the determination of nitrite in drinking water and urinary glucose, obtaining satisfactory results. Being sensitive, selective, time-efficient, and cost-effective, the two methods derived from the three-component reaction platform are feasible for quantification of nitrite and glucose in routine laboratory practice or rapid assay outside the laboratory.


Heat capacity and nuclear magnetic relaxation times of non-freezing water restrained by polysaccharides, revisited.
Calorimetric and nuclear magnetic relaxation studies on non-freezing water restrained by polysaccharide are introduced together with the historical background of this research field. Non-freezing water restrained by the hydrophilic group of polysaccharide shows no first order thermodynamic phase transition. The amount of non-freezing water calculated from the melting enthalpy of water restrained by various kinds of polysaccharides was collected. Molecular motion of polysaccharides is markedly enhanced by the introduction of non-freezing water and glass transition shifts to the ca. 200 K low temperature side. At the same time, molecular chains rearrange to a more stabilized state, which can be observed as the decrease in heat capacities. 1H nuclear magnetic relaxation studies at a temperature lower than glass transition indicate that a part of the water molecules is closely bound to the backbone proton and is not sufficiently isolated. Calorimetric and nuclear magnetic relaxation studies suggest that non-freezing water inevitably cooperates with matrix polysaccharide molecules.


Animal models of amphetamine psychosis: neurotransmitter release from rat brain slices.
As animal models of psychosis, adult rats were exposed to different types of treatment with amphetamine: (1) subcutaneous implantation with osmotic minipumps or (2) daily intraperitoneal injections for 7 days and (3) one single amphetamine injection. Continuous administration caused tolerance, intermittent injections sensitization and the acute injection a behavioral arousal with stereotypes. All amphetamine treatments diminished the potassium-stimulated (50 mM) release of preloaded labelled dopamine from superfused striatal and frontal cortical slices in vitro. Only acute amphetamine enhanced the release of D-aspartate, an analogue of L-glutamate from frontal cortical slices. The results indicate that amphetamine profoundly affects the brain dopaminergic systems but less the glutamatergic systems. Amphetamine systematically enhanced the release of gamma-aminobutyrate (GABA) from striatal slices, but otherwise the GABAergic systems seem to be more sensitive to handling stress than to the administration of amphetamine. Besides dopaminergic mechanisms other interacting systems must thus be taken into account to explain behavioral responses to amphetamine.


Conserved residues in the extracellular loop 2 regulate Stachel-mediated activation of ADGRG2.
Cleavage and dissociation of a large N-terminal fragment and the consequent unmasking of a short sequence (Stachel) remaining on the N-terminus have been proposed as mechanisms of activation of some members of the adhesion G protein-coupled receptor (aGPCR) family. However, the identity of residues that play a role in the activation of aGPCRs by the cognate Stachel remains largely unknown. Protein sequence alignments revealed a conserved stretch of residues in the extracellular loop 2 (ECL2) of all 33 members of the aGPCR family. ADGRG2, an orphan aGPCR, plays a major role in male fertility, Ewing sarcoma cell proliferation, and parathyroid cell function. We used ADGRG2 as a model aGPCR and generated mutants of the conserved residues in the ECL2 via site-directed mutagenesis. We show that tryptophan and isoleucine in the ECL2 are essential for receptor stability and surface expression in the HEK293 cells. By adjusting the receptor surface expression levels, we show that mutation of these residues of ECL2 ablates the Stachel-mediated activation of multiple signaling pathways of ADGRG2. This study provides a novel understanding of the role of the ECL2 in Stachel-mediated signaling and degradation of ADGRG2, which may lay the foundation for the rational design of therapeutics to target aGPCRs.


Fate of the DNA in plasmid-containing Escherichia coli minicells ingested by human neutrophils.
Escherichia coli minicells containing the plasmid pSC101 (approximately 10 kb) or pBR322 (approximately 4 kb) were opsonized and incubated with human neutrophils. The neutrophils responded to the minicells as they would to native E coli: they ingested the minicells, discharged their granule contents into the minicell-containing phagosomes, and expressed a respiratory burst. After one hour of incubation, the fate of the ingested plasmid DNA was examined. No DNA degradation was detected by trichloroacetic acid precipitation or agarose gel electrophoresis. Moreover, when pBR322 recovered from ingested minicells was transformed into E coli, no mutations in either of the antibiotic resistance genes carried by the plasmid were detected out of many thousand transformants screened. These findings confirm the surprisingly limited effect of neutrophils on ingested DNA.


[Papillary nephrocarcinoma: radiographic and echographic aspects].
Between 1976 and 1987, 395 patients with kidney tumors were studied with radiological techniques and sonography. In 37 cases (9.4%) histopathology diagnosed pure papillary renal cell carcinoma. Analyzing the radiographic patterns of these neoplasms, the authors observed constantly diminished vascularity (100%), frequent calcifications (35.1%) and necrotic areas (51.3%). Such X-ray features are not specific: nevertheless, their coexistence is strongly suggestive of papillary renal cell cancer. No consistent US pattern was found; however, necrotic areas were easily demonstrated in most cases. It must be stressed how patients with papillary carcinoma experienced a longer postoperative survival; it has not yet been established whether such favorable behavior is due to low biological aggressiveness or to earlier diagnosis.


Effect of applying positive pressure with or without endotracheal suctioning during extubation: a laboratory study.
During invasive mechanical ventilation, secretions accumulate in the subglottic space; consequently, there is a risk of aspiration of these secretions into the airway during cuff deflation and extubation. To minimize this risk, 2 extubation methods are used. The first consists of introducing a suction catheter into the endotracheal tube (ETT) and the trachea. After initiating suctioning, the cuff is deflated and the ETT is removed together with the suction catheter. The second technique involves applying positive pressure to the ETT using a resuscitation bag. Once the manual breath is delivered, the ETT cuff is deflated and the ETT is removed without suction. The aim of this laboratory study is to determine the existence and magnitude of differences in leak volume during cuff deflation and extubation using various combinations of positive pressure with or without endotracheal suctioning. An ETT connected to a ventilator was placed in a model trachea. Colored water was instilled in the space above the cuff. To measure the leak volume, a collection chamber was attached to the distal end of the model. Nine procedures were defined, based on the delivery of different positive pressure levels with or without endotracheal suctioning during extubation. The volume of leakage, in milliliters, was the unit of analysis. Procedures yielding values lower than 1 mL were assessed by the Friedman test, and a P value of less than .05 was considered significant. Post hoc comparisons were performed with a Wilcoxon test, followed by a Bonferroni correction. The application of CPAP 15, pressure support ventilation (PSV)15/10, and PSV 20/5 produced 0.4, 0.2, and 0.1 mL of leak volume, respectively. Statistically significant differences were found between CPAP 15 and PSV 15/10 (P = .003) and between CPAP 15 and PSV 20/5 (P = .01), but not between PSV 15/10 and PSV 20/5 (P = .30). The addition of suctioning increased leak volume, with statistically significant differences between CPAP 15 and CPAP 15 + endotracheal suctioning (P = .001) and between PSV 15/10 and PSV 15/10 + endotracheal suctioning (P = .001). Endotracheal suctioning during cuff deflation and extubation produced greater leakage. Application of CPAP 15, PSV 15/10, and PSV 20/5 resulted in the lowest leak values, with the best results being obtained with the use of PSV 15/10 and PSV 20/5.


Less is more: limiting narcotic prescription quantities for common orthopedic procedures.
Clinicians are now appreciating that the perception of pain is a multifaceted, biopsychosocial construct. Expectation of postsurgical pain is part of this construct and should be considered preoperatively. It is our belief that by establishing reasonable expectations with preoperative teaching, we can minimize narcotic use and lessen untoward issues that can potentially follow. With this goal in mind, we have been using a comprehensive pre- and postoperative program for our outpatient orthopedic surgery patients for the last 5 years, which includes physical, pharmacologic, and simple sport psychological techniques. We reviewed postoperative prescription narcotic purchases in 133 consecutive surgical patients during the last year (2013). All patients were given a prescription postoperatively for 10 hydrocodone 5-mg/acetaminophen 500-mg tablets, with 1 refill. We then contacted the patients' pharmacies to assess the actual amount purchased. Data were available for 100 patients. Of these, 62 patients had undergone "simple" arthroscopies and 38 had had "open" procedures, including 25 anterior cruciate ligament reconstructions, 4 tibial tubercle osteotomies, and various other surgeries. Of the 62 arthroscopies, 24 patients (39%) refilled their prescriptions, with 4 patients (6%) needing > 1 refill. Of the 38 open procedures, 16 patients (42%) refilled their medications, 2 (5%), more than once. Thus, 89% of patients required ≤ 20 narcotic tablets after undergoing common orthopedic operations. No patient needed chronic narcotic medication. Pain is a complex issue and patient expectation of postoperative pain is one aspect that can potentially affect the amount of narcotics used. By preparing the patient both physically and psychologically, we believe the amount of narcotics used postoperatively can be decreased without affecting pain control. As a result, the multiple possible detriments of having more narcotics available than actually necessary would be lessened. By limiting the overall number of narcotic tablets prescribed, decreased use by the patient when such a medication may no longer be appropriate, and minimized use by others in the household who might have access to it would decrease.


Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report.
Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib. We report the case of a 78-year-old non-smoker woman with stage IV EGFR L858R-positive lung adenocarcinoma presented with T790M mutation after five years of treatment with gefitinib. The patient was started on osimertinib, but after two and a half years of treatment experienced disease progression. The analyses of circulating tumor DNA using next-generation sequencing showed, together with the pre-existing T790M and exon 21 L858R, the presence of the EGFR C797G resistance mutation. Our case report revealed a rare EGFR-dependent acquired resistance mutation to osimertinib in circulating tumor DNA. Liquid biopsy appears to be a promising resource to understand the biology of osimertinib resistance by clonal evolution monitoring and the identification of novel resistance mechanisms.


Resuscitative endovascular balloon occlusion of the aorta: current evidence.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) has recently gained popularity as a minimally invasive alternative to open aortic cross-clamping in the management of patients with non-compressible hemorrhage arising below the diaphragm. The purpose of this review is to provide a description of the technical aspects of REBOA use along with an overview of the current animal and clinical data regarding its use.


Prognostic significance of the various classifications for parapharyngeal space involvement in nasopharyngeal carcinoma.
Advanced parapharyngeal space (PPS) involvement showed stronger prognostic value than PPS involvement. The classification of PPS involvement proposed by Min or Sham was the most appropriate classification for parapharyngeal extension in nasopharyngeal carcinoma (NPC). The degree of tumor extension into the PPS should be considered in future TNM staging revisions. This study was conducted to evaluate the prognostic significance of the various classifications for PPS involvement in patients with NPC. From January to July 2000, a total of 176 patients with pathologically diagnosed NPC were prospectively enrolled in this study. The extent of PPS involvement was examined by contrast-enhanced computed tomography (CT) scan and graded according to the four previously reported classifications (Min, Sham, Xiao, and Heng). The incidence of PPS involvement was 81.8%. The 5-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local relapse-free survival rates (LRFS) of the patients with and without PPS involvement were 68.1% and 90.2% (p = 0.010), 66.1% and 87.2% (p = 0.013), 76.7% and 93.6% (p = 0.032), and 84.9% and 93.1% (p = 0.220), respectively. Multivariate analysis showed that PPS involvement (yes vs no) was not an independent prognostic factor. However, graded PPS involvement was an independent factor affecting the prognosis of NPC. When the four classifications were included in a Cox model, it was shown that PPS involvement based on Min's classification was an independent factor for OS (p = 0.001). PPS involvement based on Sham's classification was an independent factor for PFS (p = 0.010) and DMFS (p = 0.009).


Synthesis and antimalarial activity of some 9-substituted artemisinin derivatives.
Several 9-substituted derivatives of the antimalarial drug artemisinin have been prepared by functionalizing the double bond of artemisitene and related compounds. Stereochemical assignments for these compounds were made using a combination of NMR experiments, an X-ray diffraction study of one compound, and chemical correlations of several other compounds with this one compound of unambiguous structure and with its epimer. The compounds synthesized show a wide variation in in vitro antimalarial activity.


Synthesis, Structure and Catalytic Activity of NHC-Ag(I) Carboxylate Complexes.
A general synthetic route was used to prepare 15 new N-heterocyclic carbene (NHC)-Ag(I) complexes bearing anionic carboxylate ligands [Ag(NHC)(O2 CR)], including a homologous series of complexes of sterically flexible ITent ligands, which permit a systematic spectroscopic and theoretical study of the structural and electronic features of these compounds. The complexes displayed a significant ligand-accelerated effect in the intramolecular cyclisation of propargylic amides to oxazolidines. The substrate scope is highly complementary to that previously achieved by NHC-Au and pyridyl-Ag(I) complexes.


Nitrate modifies the assimilation pattern of ammonium and urea in wheat seedlings.
In certain plant species, ammonium or urea nutrition can cause negative effects on plant development which can result in toxic symptoms. Some authors suggest that the presence of nitrate can alleviate these symptoms by increasing ammonium and urea assimilation, avoiding its accumulation. In order to study this hypothesis, wheat (Triticum aestivum L.) seedlings were grown with various nitrogen supplies containing the main nitrogen forms (ammonium, nitrate and urea). Amino acids content and the activity of the three main enzymes involved in nitrogen assimilation (nitrate reductase, glutamine synthetase and urease) were studied. The application of nitrate along with urea and/or ammonium was not associated with a time-sustained increase in the activity of glutamine synthetase and urease. Amino acid analysis revealed that nitrate induced changes in amino acid metabolism enhancing its concentration. Likewise the content of protein was also higher in nitrate-treated plants. These results suggest that the effect of nitrate is compatible with a rapid and transient increase in the activity of glutamine synthetase and urease during the first hour after the onset of treatments. Nevertheless, a possible effect of nitrate reducing ammonium accumulation through the activation of alternative metabolic pathways different from that involving glutamine synthetase cannot be ruled out. Finally, nitrate effects on amino acid concentration indicate that, whereas ammonium assimilation takes place principally in the root, urea and nitrate assimilation occurred in the shoot, under the conditions of the experiment.


Characterization and application of a strain-specific monoclonal antibody against the rhizosphere bacterium Azospirillum brasilense Wa5.
A hybridoma cell line producing a rat monoclonal antibody (MAb Bo-33) directed against lipopolysaccharide of Azospirillum brasilense Wa5 has been established and characterized. Whole bacteria were used as immunogens. The number of antigens per cell was about 1500. The number of antigens per cell of reisolates from the rhizosphere of what was similar to the number of antigens of bacteria cultivated in rich medium. The sensitivity of detection using MAb Bo-33 was about 100 bacteria/ml. Therefore, the MAb was suitable for in situ immunofluorescence detection and a sensitive direct quantification of Azospirillum brasilense Wa5 in rhizosphere extracts.


Development of enzyme-linked immunosorbent assays for the organophosphorus insecticide EPN.
Competitive enzyme-linked immunosorbent assays (ELISAs) in indirect and direct format were developed for the quantitative detection of the organophosphorus insecticide EPN. Five EPN derivatives (haptens) were synthesized and coupled to carrier proteins to use as an immunogen or as a competitor. Rabbits were immunized with two of the five haptens coupled to KLH for production of polyclonal antibodies, and the sera were screened against one of the haptens coupled to ovalbumin (OVA). Using the serum with the highest specificity and a coating antigen (hapten-OVA conjugate), an indirect (antigen-coated) ELISA was developed, which showed an IC(50) of 5.6 ng/mL with a detection limit of 0.2 ng/mL (20% inhibition). A direct (antibody-coated) ELISA using an enzyme tracer (hapten-enzyme conjugate) was also developed, which showed an IC(50) of 8.4 ng/mL with a detection limit of 0.9 ng/mL (20% inhibition). The antibodies showed negligible cross-reactivity with other organophosphorus pesticides except with the insecticide parathion-ethyl only in the direct ELISA. The recoveries of EPN from spiked samples determined by the indirect ELISAs were between 37 and 164%.


Calcium and Integrin-binding protein 2 (CIB2) controls force sensitivity of the mechanotransducer channels in cochlear outer hair cells.
Calcium and Integrin-Binding Protein 2 (CIB2) is an essential subunit of the mechano-electrical transduction (MET) complex in mammalian auditory hair cells. CIB2 binds to pore-forming subunits of the MET channel, TMC1/2 and is required for their transport and/or retention at the tips of mechanosensory stereocilia. Since genetic ablation of CIB2 results in complete loss of MET currents, the exact role of CIB2 in the MET complex remains elusive. Here, we generated a new mouse strain with deafness-causing p.R186W mutation in Cib2 and recorded small but still measurable MET currents in the cochlear outer hair cells. We found that R186W variant causes increase of the resting open probability of MET channels, steeper MET current dependence on hair bundle deflection (I-X curve), loss of fast adaptation, and increased leftward shifts of I-X curves upon hair cell depolarization. Combined with AlphaFold2 prediction that R186W disrupts one of the multiple interacting sites between CIB2 and TMC1/2, our data suggest that CIB2 mechanically constraints TMC1/2 conformations to ensure proper force sensitivity and dynamic range of the MET channels. Using a custom piezo-driven stiff probe deflecting the hair bundles in less than 10 µs, we also found that R186W variant slows down the activation of MET channels. This phenomenon, however, is unlikely to be due to direct effect on MET channels, since we also observed R186W-evoked disruption of the electron-dense material at the tips of mechanotransducing stereocilia and the loss of membrane-shaping BAIAP2L2 protein from the same location. We concluded that R186W variant of CIB2 disrupts force sensitivity of the MET channels and force transmission to these channels.


Impact of hypoglycemia on daily life of type 2 diabetes patients in Ukraine.
This study evaluates the impact of hypoglycemia on the lives of Ukrainian patients with type 2 diabetes mellitus. The secondary objective was to explore patient-physician relationships and the attitudes of patients towards various informational resources on diabetes management. Three focus groups with 26 patients were conducted. Qualitative information was evaluated using content analysis. The results show that patients with type 2 diabetes mellitus in Ukraine are adapting to potential attacks of hypoglycemia; however, they still experience periodic manifestations of hypoglycemia that significantly affect their psychological well-being. This result is similar to observations made in other countries. Ukrainian patients >40 years old mainly receive information on disease management from endocrinologists, and rarely use internet resources on diabetes management. Information provision was especially important at the early stage of the disease, when patients lack information on hypoglycemia manifestations and could therefore fail to identify and manage it properly.


The mediating role of state maladaptive emotion regulation in the relation between social anxiety symptoms and self-evaluation bias.
Although social anxiety symptoms are robustly linked to biased self-evaluations across time, the mechanisms of this relation remain unclear. The present study tested three maladaptive emotion regulation strategies - state post-event processing, state experiential avoidance, and state expressive suppression - as potential mediators of this relation. Undergraduate participants (N = 88; 61.4% Female) rated their social skill in an impromptu conversation task and then returned to the laboratory approximately two days later to evaluate their social skill in the conversation again. Consistent with expectations, state post-event processing and state experiential avoidance mediated the relation between social anxiety symptoms and worsening self-evaluations of social skill (controlling for research assistant evaluations), particularly for positive qualities (e.g. appeared confident, demonstrated social skill). State expressive suppression did not mediate the relation between social anxiety symptoms and changes in self-evaluation bias across time. These findings highlight the role that spontaneous, state experiential avoidance and state post-event processing may play in the relation between social anxiety symptoms and worsening self-evaluation biases of social skill across time.


Other animal prion diseases.
In addition to bovine spongiform encephalopathy (BSE) of cattle and scrapie of sheep and goats, a few other animal prion diseases have been reported. These include feline spongiform encephalopathy of zoological and domestic cats (FSE) and transmissible spongiform encephalopathy (TSE) of zoological ruminants and non-human primates, as well as chronic wasting disease of deer and elk (CWD) and transmissible mink encephalopathy of farmed mink (TME). The origins of TSE in cats, zoo bovids, and non-human primates are clearly linked to the BSE epidemic; however, the origins of CWD and TME are less clear, but are not epidemiologically linked to the BSE epidemic. Here we review the epidemiology, transmission, clinical features and pathology of these other animal prion diseases.


An atypical case of incontinentia pigmenti with a hypomorphic variant.
Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis that affects skin, hair, teeth, eyes and central nervous system. We present the case of a female patient with mild IP caused by a hypomorphic pathogenic variant of the inhibitor of the kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG) gene. This is the first report of a female IP patient with the hypomorphic variant, NM_001099856.6: c.1423dup, which is causative of anhidrotic ectodermal dysplasia with immune deficiency in males.


Opioid peptide modulation of stress-induced plasma steroid changes in the frog Rana esculenta.
The present paper aims to evaluate whether a neuroendocrine system including opioids accounts for the effects of stress in the frog, Rana esculenta. Using an acute-stress paradigm, the involvement of hypothalamic opioid peptides was investigated biochemically as well as by in vivo studies. HPLC and RIA investigations confirm the presence of beta-endorphin-like peptides in the brain of this frog. Several immunoreactive peaks are present, two of them coeluting with beta-endorphin and acetyl beta-endorphin reference peptides. Quantitative evaluation revealed that the beta-EP content of 24-hr captured animals was higher than that in fresh captured ones. The stress paradigm applied here was consistent with the measurement of plasma androgens and corticosterone levels in females after short-captivity confinement. In comparison with fresh-captured animals, a sharp decrease of these levels was found within 10-24 hr after capture. These effects were reversed by naltrexone, a long-acting opioid antagonist, after 24 hr of treatment. In fact, in the captive animals injected with 100 ng of naltrexone, the plasma androgen titers remained low at the 10th hour postcapture, but rose to the control levels within 24 hr. A similar effect was found for the plasma corticosterone levels. These data demonstrate that, in this anuran, endogenous opioids could mediate the stress-induced inhibition of gonadal function, and perhaps the inhibition of the hypothalamus-pituitary-adrenal axis.


Development of a comprehensive plan for utilization of digester gas moves towards energy self-sufficiency in Chicago, USA.
The Metropolitan Water Reclamation District (MWRD) of Greater Chicago's Stickney Water Reclamation Plant (SWRP) anaerobically digests approximately 430 dry tons per day (dtpd) (390 dry metric tons per day) of solids and produces 3.4 million ft(3)/day (96 thousand m(3)/day) of biogas from the anaerobic digesters, making it one of the largest municipal digester gas complexes in the world. Installation of new treatment processes, as well as future increases in flows and loads to the plant, are expected to significantly increase production of biologically degradable sludge and biogas. This paper presents a comprehensive planning study that was completed to identify and evaluate alternatives for utilization of this biogas. The best, sustainable approach was identified, taking into consideration economics, social impacts, and environmental impacts. The model results indicate that the most economically favorable scenario involves installing a cogeneration facility to produce electricity on-site, and operating it in conjunction with the plant's existing boilers to satisfy the heating needs of the plant. This scenario also provides the greatest reduction in GHG offsets at the power plants.


DNA sequence recognition of thiazole-containing cross-linked polyamides can be favored.
The binding ability of cross-linked thiazolated polyamides (containing the base sequence-reading elements thiazole(Th)-pyrrole(Py)-pyr-role(Py) and thiazole(Th)-imidazole(Im)-pyrrol(Py) to various DNA dodecamers has been investigated. CD titration experiments at high salt concentration demonstrate that the dimers with a heptanediyl linker (C7 dimer) show a significantly higher sequence specificity than their corresponding monomers. The dimer of Th-Py-Py primarily prefers binding to pure AT sequences and that of Th-Im-Py to the dodecamer sequences containing a GC pair within the central sequence (e.g. AACGTT). Surprisingly, the sequence binding ability is strongly influenced by the presence of a T-A step: e.g. Th-Py-Py has a similar affinity to the sequences TTTAAA and ATCGTA; likewise Th-Im-Py shows a preference for these sequences. The CD results correlate with footprinting data. Related biochemical studies on the effect of polyamides on DNA gyrase activity in vitro show that the C7 dimers most effectively inhibit the enzyme activity compared with the monomers and the natural reference minor groove binder distamycin. The highest inhibitory potency is observed for the Th-Py-Py-dimer. The role of the T-A step in binding of the cross-linked dimer to the minor groove is discussed in light of the sequence recognition of the TATA box binding protein.


Access to pulmonary rehabilitation for people from culturally and linguistically diverse communities: A cohort study.
Little is known about the extent of cultural and linguistic diversity among people with chronic obstructive pulmonary disease (COPD) in Australia and if ethno-cultural factors influence engagement in pulmonary rehabilitation (PR). We conducted a prospective cohort study to evaluate the extent of cultural and linguistic diversity among people with COPD and identify variables that influence engagement in PR. Patients with COPD attending the respiratory outpatient clinic at a metropolitan health service completed a study-specific questionnaire with results descriptively analysed. Access issues of awareness, referrals, attendance and completion of PR were examined. A multiple regression analysis was conducted to identify variables that influenced engagement in PR. Ninety-seven participants were recruited, of whom 36 (37%) self-identified a culturally and linguistically diverse (CALD) community. While participants from CALD communities had less awareness of PR as compared with the English Australian group (χ2 (df) = 5.3 (1), p = 0.02), there were no significant between-group differences in number of observed referrals (p = 0.30), attendance (p = 0.50) and completions of PR (p = 0.90). Only 11 (11%) out of 97 participants completed PR. Age (p = 0.006) and being from a CALD community (p = 0.03) were independent factors impacting on the awareness of PR while English proficiency (p = 0.04) was an independent factor impacting on referrals to PR. While older age and being from a CALD community were associated with having less awareness in PR, referrals to, attendance and completion rates of PR were similar regardless of ethnicity.


Effects of soil fines and surfactant sorption on contaminant reduction of coarse fractions during soil washing.
The reduction of contaminants sorbed on the coarse fraction of soils to the level below clean-up requirements is essential for an effective soil washing process. This study investigated the effects of soil texture and surfactant sorption on the reduction of total petroleum hydrocarbons (TPH) in coarse fraction during soil washing. Batch TPH sorption experiments were conducted on soil slurry with various soil fine/coarse ratios and surfactants Octylpheny polyoxyethylene (TX-100) and Dodecylpyridinium chloride (DPC) at the dosage below their saturation levels of sorption. In a sandy loam soil of low silt and clay contents, increasing the fine/coarse ratio from 0.4 to 1.2 without adding surfactants resulted in a reduction of TPH levels in the coarse fraction by 30%. Increasing the fine/coarse ratio along with sorbed surfactant (3000 mg TX-100 or 10,000 mg DPC per kg soil) further reduced TPH concentrations in the coarse fraction. For a silty loam soil already containing a high percentage of fine particles, increasing the fine/coarse ratio from 5.9 to 18.8 without surfactant addition yielded no further TPH reduction in the coarse fraction. On the other hand, surfactant sorption at the fine/coarse ratio of 5.9 improved the washing efficiency of the coarse fraction. These experimental results suggested the importance of high contents of soil fines and surfactant sorption in achieving low contaminant concentrations of coarse fractions during soil washing.


Regioselective Synthesis, NMR, and Crystallographic Analysis of N1-Substituted Pyrazoles.
A systematic study of the N-substitution reactions of 3-substituted pyrazoles under basic conditions has been undertaken. Regioselective N1-alkylation, -arylation, and -heteroarylation of 3-substituted pyrazoles have been achieved using K2CO3-DMSO. The regioselectivity is justified by the DFT calculations at the B3LYP/6-31G**(d) level. A consistent steric effect on chemical shift has been observed for N-alkyl pyrazole analogues. Twenty-five X-ray crystallographic structures have been obtained to confirm the regiochemistry of the major products.


The Association Between Vestibular Physical Examination, Vertigo Questionnaires, and the Electronystagmography in Patients With Vestibular Symptoms.
Dizziness makes up a diagnostic and treatment challenge. The diagnostic accuracy of the medical history and vestibular physical examination in cases of vestibular symptoms is not clear. The aim of this study is to determine the association between vestibular physical examination, vestibular questionnaires, and electronystagmography (ENG) test in patients with vestibular symptoms. This is a prospective study of 135 adults with vestibular symptoms. The subjects underwent targeted physical examination and filled vestibular questionnaires, including the Dizziness Handicap Inventory (DHI), before ENG testing. The results of the physical examination and questionnaires were compared with the final ENG findings. Of patients who had normal ENG results, 32.1% (17/52) showed abnormal physical examination, and 48.8% (40/82) of the patient who had normal physical examination showed abnormal ENG results ( P = .46). Among patients with severe disability by DHI, 46.4% (13/28) had an abnormal ENG, and 42.9% (12/28) had a normal ENG ( P = .39). This study did not demonstrate association between vestibular physical examination, vestibular questionnaires, and ENG results. Although history (augmented by questionnaires) and physical examination are the initial steps in the evaluation of vertigo, the current study suggests that they should be complemented by objective testing for evaluation of inner ear origin of vertigo.


Quantum Transduction with Adaptive Control.
Quantum transducers play a crucial role in hybrid quantum networks. A good quantum transducer can faithfully convert quantum signals from one mode to another with minimum decoherence. Most investigations of quantum transduction are based on the protocol of direct mode conversion. However, the direct protocol requires the matching condition, which in practice is not always feasible. Here we propose an adaptive protocol for quantum transducers, which can convert quantum signals without requiring the matching condition. The adaptive protocol only consists of Gaussian operations, feasible in various physical platforms. Moreover, we show that the adaptive protocol can be robust against imperfections associated with finite squeezing, thermal noise, and homodyne detection, and it can be implemented to realize quantum state transfer between microwave and optical modes.


[Correlation of high-sensitivity CRP concentration with the extent of coronary atherosclerosis in men with symptoms of ischemic heart disease].
Atherogenesis is combined with inflammation of low intensity within endothelium. To-date studies have demonstrated that C-reactive protein is the best marker of this type of inflammation because its concentrations not only reflect the intensity of the process but they also carry prognostic information in apparently healthy general population as well as in patients with symptomatic atherosclerosis. The aim of this study was to evaluate the correlation between high-sensitivity CRP (hsCRP) and the extent of coronary atherosclerosis in men undergoing coronary angiography. The secondary aim was to assess the influence of statin treatment on hsCRP levels by comparing these levels in statin-treated and statin-naive patients. 112 men with symptoms of ischemic heart disease were included in the study. In 98 cases coronary angiography was performed 52 patients were treated with statins. The extent of atherosclerosis in the coronary bed was evaluated according to four indexes: Gensini score (G), Friesinger score (F), Number of Vessels Diseased (NVD) and Arterial Segment Score (ASS). Concentrations of hsCRP concentrations were obtained with NB100 Dade-Behring kit. Pearson correlation coefficient was calculated for CRP concentrations following their logarithmic transformation. Correlation evaluation was confined to statin-naive patients due to convincing data about the influence of statins on CRP levels. A significant correlation between levels of hsCRP and extension of coronary atherosclerosis was found with all used indexes (G: R=0.335; p=0.0151, F: R=0.406; p=0.0028, NVD: R=0.0338; p=0.0142, ASS=0.368; p=0.071). The mean concentration of hsCRP was 27.7% lower in the patients on statins than in statin-naive patients within the low and moderate range of concentrations (up to 70th percentile, 2.4 mg/l) (p<0.02). In 25% of study subjects hsCRP exceeded the level of 3.0 mg/l which is the cut-off value for increased risk of atherothrombotic complications. The study showed a significant correlation between hsCRP and the extent of coronary atherosclerosis in men with symptoms of ischemic heart disease. A significantly lower concentration of hsCRP was observed in the group of patients treated with statins compared to statin-naive patients, which may result from the proposed CRP reducing influence of these drugs. A quarter of study subjects had hsCRP levels exceeding the cut-off value for increased cardiovascular risk.


Topical immunotherapy in combination with anthralin in the treatment of refractory alopecia areata.
Treatment is often challenging in patients with alopecia areata. We often try topical immunotherapy to treat alopecia areata in Japan. Anthralin is sometimes used in other countries. The aim of this study was to examine effectiveness of combination therapy with both topical immunotherapy with squaric acid dibutylester or diphenylcyclopropenone and anthralin in the treatment of refractory alopecia areata. We treat four patients with refractory alopecia areata by topical immunotherapy and anthralin. Two patients had alopecia areata multilocularis and the other two patients had alopecia totalis. The entire scalp was treated with weekly application of squaric acid dibutylester or diphenylcyclopropenone and daily 0.5% anthralin ointment. Patients were followed up weekly, and adverse effects were recorded. One patient with multifocal patches of alopecia areata got complete hair regrowth at week 30, the other patient with multifocal patches of alopecia areata turned for the worse at week 30 and recovered at week 52. Hair regrowth was not seen in the other two patients with alopecia totalis. Localized pruritis and hyperpigmentation of the scalp were seen in two patients. To treat alopecia areata unresponsive to topical immunotherapy alone, topical immunotherapy in combination with anthralin is worth a try.


Performance dependence of a stick-slip piezoelectric actuator on the angle between the piezoelectric stack and mover.
The angle between the piezoelectric stack (PES) and the mover would significantly affect the output performances of stick-slip piezoelectric actuators in theory; however, this issue has not been explored. Accordingly, in this paper, to investigate the effects of the angle, a stick-slip piezoelectric actuator with a changeable angle between the PES and the mover was proposed, and its structure was briefly introduced first. Then, the relationship between the angle and the parasitic motion was theoretically calculated. After that, the output performances of the actuator were characterized under different angles between the PES and the mover. The results indicated that the angle between the PES and the mover significantly affected the one-step maximum displacement and the backward motion. After comprehensive analysis, the best output performances of the actuator were obtained under the angle of 0°.


Apparent changes in body insulation of juvenile king penguins suggest an energetic challenge during their early life at sea.
Little is known about the early life at sea of marine top predators, like deep-diving king penguins (Aptenodytes patagonicus), although this dispersal phase is probably a critical phase in their life. Apart from finding favourable foraging sites, they have to develop effective prey search patterns as well as physiological capacities that enable them to capture sufficient prey to meet their energetic needs. To investigate the ontogeny of their thermoregulatory responses at sea, we implanted 30 juvenile king penguins and 8 adult breeders with a small data logger that recorded pressure and subcutaneous temperature continuously for up to 2.5 years. We found important changes in the development of peripheral temperature patterns of foraging juvenile king penguins throughout their first year at sea. Peripheral temperature during foraging bouts fell to increasingly lower levels during the first 6 months at sea, after which it stabilized. Most importantly, these changes re-occurred during their second year at sea, after birds had fasted for ∼4 weeks on land during their second moult. Furthermore, similar peripheral temperature patterns were also present in adult birds during foraging trips throughout their breeding cycle. We suggest that rather than being a simple consequence of concurrent changes in dive effort or an indication of a physiological maturation process, these seasonal temperature changes mainly reflect differences in thermal insulation. Heat loss estimates for juveniles at sea were initially high but declined to approximately half after ∼6 months at sea, suggesting that juvenile king penguins face a strong energetic challenge during their early oceanic existence.


[Topic problems of gerontology in otorhinolaryngology].
The paper characterizes age-specific involution of the ENT tissues, acoustic and vestibular analyzers, hearing and equilibrium defects. Original investigations of the authors give wider possibilities of early detection of age-related failure of the internal ear functions. Relevant tests are proposed.


Prevalence of Alcohol Misuse and Follow-Up Care in a National Sample of OEF/OIF VA Patients With and Without TBI.
Information on prevalence and management of alcohol misuse among Afghanistan and Iraq veterans with traumatic brain injury (TBI) is limited. This study compared rates of alcohol misuse and follow-up care-brief intervention (BI) and addiction treatment-among Afghanistan and Iraq veterans with and without TBI receiving care from the Department of Veterans Affairs (VA). The sample included veterans ages 18 and older screened with the Alcohol Use Disorders Identification Test alcohol consumption questions (AUDIT-C) in 2012 who received VA health care in the prior year (N=358,417). Overall and age-specific estimates of alcohol misuse (AUDIT-C score ≥5) were compared for men and women with and without TBI by logistic regression. BI and addiction treatment after screening were compared between groups by using multivariable logistic regression. Alcohol misuse was higher among men with TBI than among men without TBI (20.3%, 95% confidence interval [CI]=19.9-20.8, versus 16.4%, CI=16.3-16.6) and among women with TBI than among women without TBI (6.8%, CI=5.8-8.1, versus 5.6%, CI=5.4-5.8); younger (age <30) patients with TBI had the highest rates. BI rates did not differ by TBI status (76.4%-80.2%). Addiction treatment rates for those with severe misuse were higher among those with TBI (men, 20.0%, CI=18.4-21.6, versus 15.4%, CI=14.9-15.9; women, 36.6%, CI=21.8-51.3, versus 21.1%, CI=18.2-24.0). Alcohol misuse is common among Iraq and Afghanistan veterans with TBI, particularly young men. BI rates were high and did not vary by TBI status, although addiction treatment rates were higher among patients with TBI than among those without TBI.


Eyelid involvement in acanthosis nigricans: the importance of systemic screening.
A 53-year-old man presented with thickening and hyperpigmentation of the eyelids. After the diagnosis of acanthosis nigricans was made, further investigation of a possible underlying disorder, including biochemical and instrumental examinations, indicated the presence of glucose intolerance, which had been diagnosed 3 years after the clinical appearance of acanthosis nigricans. Eyelid involvement in acanthosis nigricans is rare. Ophthalmologists should be aware of the possibility that acanthosis nigricans can exist in the periocular area and perform a systemic assessment of the patient for the presence of an underlying condition.


Fusion proton diagnostic for the C-2 field reversed configuration.
Measurements of the flux of fusion products from high temperature plasmas provide valuable insights into the ion energy distribution, as the fusion reaction rate is a very sensitive function of ion energy. In C-2, where field reversed configuration plasmas are formed by the collision of two compact toroids and partially sustained by high power neutral beam injection [M. Binderbauer et al., Phys. Rev. Lett. 105, 045003 (2010); M. Tuszewski et al., Phys. Rev. Lett. 108, 255008 (2012)], measurements of DD fusion neutron flux are used to diagnose ion temperature and study fast ion confinement and dynamics. In this paper, we will describe the development of a new 3 MeV proton detector that will complement existing neutron detectors. The detector is a large area (50 cm(2)), partially depleted, ion implanted silicon diode operated in a pulse counting regime. While the scintillator-based neutron detectors allow for high time resolution measurements (∼100 kHz), they have no spatial or energy resolution. The proton detector will provide 10 cm spatial resolution, allowing us to determine if the axial distribution of fast ions is consistent with classical fast ion theory or whether anomalous scattering mechanisms are active. We will describe in detail the diagnostic design and present initial data from a neutral beam test chamber.


Bioactivity of neem, Azadirachta indica, against spittlebug Mahanarva fimbriolata (Hemiptera: Cercopidae) on sugarcane.
The effect of neem, Azadirachta indica A. Juss, on some biological parameters of Mahanarva fimbriolata (Stil) (Hemiptera: Cercopidae) was studied in the laboratory by using NeemAzal-T/S, Nimkol-LS, and an aqueous neem seed extract. Initially, the LC,, was estimated for nymphs. Later, nymphs fed on sugarcane, Saccharum officinarum L., roots were sprayed with the respective LC,, for each product. The adults were maintained in cages on sugarcane plants sprayed at the base with the maximum rate recommended commercially for the crop (3 liter/ha). Moistened cotton discs surrounding the base of the plant were used as oviposition substrates. The LCso values estimated for NeemAzal, Nimkol, and aqueous extract were 0.014, 0.225, and 0.611%, respectively. There was a reduction in spittlebug longevity, regardless of sex, in relation to the control. Males exposed to the neem products, and aqueous extract showed longevity reductions of approximately 50%, whereas for females the reductions were 55-60%. The neem products and extract reduced fecundity by 75-85%. Morphological and physiological changes were observed in 9% of the eggs from individuals submitted to NeemAzal. Neem-based products, especially NeemAzal, have potential for the control of M. fimbriolata.


Economic impact of decreasing stocking densities in broiler production in Belgium.
Stocking density is a prominent topic in public debates on animal welfare and was one of the reasons for the European Commission to set limits to the stocking density on broiler farms. The objective of this paper was to calculate in detail the financial impact of changes in technical and management variables due to decreasing stocking densities in line with new European Union (EU) regulations. Therefore, the productive performance indicators such as BW, mortality, or feed conversion and farm technical data such as water consumption and heating of 3 independent experiments conducted at a poultry research station in Flanders (Belgium) were combined. Using the partial budget technique only those elements that change with stocking density have been taken into account. Reducing stocking density implies a recalculation of all costs on a reduced number of birds. This yields an economic situation that leaves hardly any profit margin for most of the broiler producers under the present market conditions. It was found that the critical threshold of stocking density for maintaining profitability under the present market and technical conditions is around 46 kg/m(2), thus well above the EU maximum of 42 kg/m(2). It is shown, however, that with changing broiler feed and meat prices, the impact might be less negative in economic terms.


Characterization of human T cells that regulate neutrophilic skin inflammation.
It is unknown whether neutrophilic inflammations can be regulated by T cells. This question was analyzed by studying acute generalized exanthematous pustulosis (AGEP), which is a severe drug hypersensitivity resulting in intraepidermal or subcorneal sterile pustules. Recently, we found that drug-specific blood and skin T cells from AGEP patients secrete high levels of the potent neutrophil-attracting chemokine IL-8/CXCL8. In this study, we characterize the phenotype and function of CXCL8-producing T cells. Supernatants from CXCL8(+) T cells were strongly chemotactic for neutrophils, CXCR1, and CXCR2 transfectants, but not for transfectants expressing CXCR4, CX3CR1, human chemokine receptor, and RDC1. Neutralization experiments indicated that chemotaxis was mainly mediated by CXCL8, but not by granulocyte chemotactic protein-2/CXCL6, epithelial cell-derived neutrophil attractant-78/CXCL5, or growth-related oncogene-alpha,beta,gamma/CXCL1,2,3. Interestingly, approximately 2.5% of CD4(+) T cells in normal peripheral blood also produced CXCL8. In addition to CXCL8, AGEP T cells produced large amounts of the monocyte/neutrophil-activating cytokine GM-CSF, and the majority released IFN-gamma and the proinflammatory cytokine TNF-alpha. Furthermore, apoptosis in neutrophils treated with conditioned medium from CXCL8(+) T cells could be reduced by 40%. In lesional skin, CXCL8(+) T cells consistently expressed the chemokine receptor CCR6, suggesting a prominent role for CCR6 in early inflammatory T cell recruitment. Finally, our data suggest that CXCL8-producing T cells facilitate skin inflammation by orchestrating neutrophilic infiltration and ensuring neutrophil survival, which leads to sterile pustular eruptions found in AGEP patients. This mechanism may be relevant for other T cell-mediated diseases with a neutrophilic inflammation such as Behçet's disease and pustular psoriasis.


Indistinguishability of temporally separated pairwise two-photon state of thermal photons in Franson-type interferometry.
The phenomenon of Franson interference with time-energy entangled photon pairs beyond the single-photon coherence length observed upon nonlocal measurement at two space-like separated locations is of particular research interest. Herein, we determine the coherence length of temporally separated pairwise two-photon (TSPT) states of thermal photons emitted from a warm atomic ensemble in Franson-type interferometry, with the setup consisting of two spatially separated unbalanced Michelson interferometers beyond the coherence length of a thermal photon. Using a novel method of square-modulated thermal photons, we show that the sinusoidal Franson-type interference fringe of thermal photons is determined by the presence or absence of TSPT states (corresponding to the time delay between the long and short paths in Franson-type interferometry). We find that the indistinguishability of the TSPT state in the Franson-type interference is independent of the temporal separation of the thermal photons in the TSPT states.


Relationship between clinical experiences and internal medicine clerkship performance.
This study was conducted to assess the associations between several clerkship process measures and students' clinical and examination performance in an internal medicine clerkship. We collected data from the internal medicine clerkship at one institution over a 3-year period (classes of 2010-2012; n = 507) and conducted correlation and multiple regression analyses. We examined the associations between clerkship process measures (student-reported number of patients evaluated, percentage of core problems encountered, total number of core problems encountered, total number of clinics attended) and four clerkship outcomes (clinical points [a weighted summation of a student's clinical grade recommendations], ambulatory clinical points [the out-patient portion of clinical points], examination points [a weighted summation of scores on three clerkship examinations], and National Board of Medical Examiners examination score). After controlling for pre-clerkship ability and gender, percentage of core problems was significantly associated with ambulatory clinical points (b = 3.84, total model R(2) = 0.14). Further, number of patients evaluated was significantly associated with clinical points (b = 0.19, total model R(2) = 0.22), but only for students who undertook first-quarter clerkships, who reported higher numbers of patients. Notwithstanding a few positive (but small) associations, the results from this study suggest that clinical exposure is, at best, weakly associated with internal medicine clerkship performance.


Novel Fluorescent Microemulsion: Probing Properties, Investigating Mechanism, and Unveiling Potential Application.
Nanoscale microemulsions have been utilized as delivery carriers for nutraceuticals and active biological drugs. Herein, we designed and synthesized a novel oil in water (O/W) fluorescent microemulsion based on isoamyl acetate, polyoxyethylene castor oil EL (CrEL), and water. The microemulsion emitted bright blue fluorescence, thus exhibiting its potential for active drug detection with label-free strategy. The microemulsion exhibited excitation-dependent emission and distinct red shift with longer excitation wavelengths. Lifetime and quantum yield of fluorescent microemulsion were 2.831 ns and 5.0%, respectively. An excellent fluorescent stability of the microemulsion was confirmed by altering pH, ionic strength, temperature, and time. Moreover, we proposed a probable mechanism of fluorochromic phenomenon, in connection with the aromatic ring structure of polyoxyethylene ether substituent in CrEL. Based on our findings, we concluded that this new fluorescent microemulsion is a promising drug carrier that can facilitate active drug detection with a label-free strategy. Although further research is required to understand the exact mechanism behind its fluorescence property, this work provided valuable guidance to develop new biosensors based on fluorescent microemulsion.


Differential requirement for IFN-gamma in CTL maturation in acute murine graft-versus-host disease.
Although IFN-gamma is the archetypal Th1 cytokine, its role in CTL maturation is uncertain. We used an in vivo mouse model of CTL development, parent-into-F(1) acute graft-vs-host disease (AGVHD), to evaluate this issue. In AGVHD, transfer of naive parental T cells into F(1) hosts stimulates the development of allospecific CTL effectors that eliminate host lymphocytes, particularly B cells. Complete elimination of IFN-gamma, using IFN-gamma-deficient donors and administering anti-IFN-gamma mAb, suppressed B cell elimination, down-regulated TNF-alpha production, and enhanced Th2 cytokine production, but did not allow the B cell expansion characteristic of chronic GVHD (CGVHD). Because complete CTL inhibition results in full-blown CGVHD that is IFN-gamma independent, these observations indicate that IFN-gamma elimination only partially blocks CTL development. IFN-gamma elimination did not inhibit donor T cell engraftment or activation in the AGVHD model, but almost completely blocked Fas/Fas ligand (FasL) gene expression, protein up-regulation, and Fas/FasL-mediated CTL killing. In contrast, IFN-gamma elimination only partially inhibited perforin gene expression and perforin-mediated CTL activity. The contributions of IFN-gamma to CTL development were indirect, because IFN-gamma receptor-deficient donor cells differentiated normally into allospecific CTLs. Consistent with the view that the Fas/FasL and perforin pathways each mediate CTL killing in AGVHD, the absence of both perforin and IFN-gamma (perforin knockout donor cells and anti-IFN-gamma mAb) converted AGVHD to CGVHD. Thus, both IFN-gamma-dependent induction of Fas/FasL and IFN-gamma-independent induction of perforin contribute to CTL-mediated elimination of host B cells in AGVHD. Suppression of both pathways is required for typical CGVHD development.


Modulation of keratinocyte proliferation in vitro by endogenous prostaglandin synthesis.
To understand the relationship between the proliferation of epidermis and its arachidonic acid metabolism, we studied human keratinocytes grown in vitro at confluent or nonconfluent densities. Keratinocyte cultures incubated with [14C]arachidonic acid synthesized prostaglandin (PG)E2 PGD2, PGF2 alpha, and small quantities of 6-keto-F1 alpha. Nonconfluent cultures, however, synthesized fourfold more PGE2 than did confluent cultures. When proliferation was studied using [3H]thymidine incorporation into DNA, it was found that this increased synthesis of PGE2 was accompanied by a fourfold increase in the rate of proliferation. When PGE2 synthesis was inhibited by indomethacin, the rate of proliferation of nonconfluent cultures was decreased 40%, while the rate of proliferation of confluent cultures was unchanged. Addition of 1 ng/ml of PGE2, but not PGF2 alpha, PGD2, or a stable analog of PGI2 to the indomethacin-treated nonconfluent cultures restored the initial rate of proliferation. These results suggest that PGE2 is a growth-promoting autocoid for epidermis. The synthesis of PGE2 by epidermis may be enhanced in wound healing and disease states where epidermal continuity is disrupted.


The Active Malformations Surveillance Program, Boston in 1972-2012: Methodology and demographic characteristics.
Malformations surveillance programs have been carried out in consecutive populations of newborn infants at single hospitals, as well as in several hospitals in defined populations. A surveillance program begins with the review of the findings recorded by the examining pediatrician in each infant's medical record. The results of diagnostic tests, consultations, and imaging studies are obtained, also, from that infant's medical record. Some malformations surveillance programs identify additional malformations over several months, as the infants have hospitalizations and additional diagnostic testing. 289,365 infants (liveborn, stillborn, and fetuses in pregnancies terminated because of anomalies) were surveyed from 1972 to 2012 at an urban maternity center in Boston to identify each infant with one or more malformations. Each mother was interviewed to obtain demographic characteristics, results of prenatal testing, family history, and information about exposures in pregnancies. Specific diagnoses were established by the study geneticists. 7,020 (2.4%) of the 289,365 infants surveyed had one or more malformations. The etiologies identified included chromosome abnormalities, phenotypes attributed to dominant or recessive autosomal or X-linked mutations, vascular disruption, environmental factors, and complications of twinning. The surveillance of a large consecutive population of newborn infants, stillbirths, and aborted fetuses can identify with high reliability all infants with one or more malformations. This process of ascertainment of affected newborns can be used to improve genetic counseling, identify "new" phenotypes, and serve as a system for testing new technologies to establish more causes of congenital malformations.


Multicentric osteolytic lesion of the middle finger of the hand. Case report.
Giant cell-rich osteolytic lesions may have overlapping clinical, radiologic, and histopathologic features, with an important degree of difficulty of diagnosis and treatment. We report a case of double osteolytic lesion at the middle-finger in a young man without previous history of hand trauma. He underwent en-bloc resection of the bone lesions and reconstruction by graft of hydroxyapatite, resulting in a good morpho-functional result. Histological diagnosis was giant cell reparative granuloma (GCRG), although several features were considered atypical, including the appearance of the giant cells and the areas of the stroma that more closely resembled a giant cell tumor. GCRG is a benign rare intraosseous lesion and the true nature is controversial and unknown. The theories are that it could be a reactive lesion, a developmental anomaly or a benign neoplasm. It appears as an osteolytic lesion that must be considered in the differential diagnosis of other "critical" bone lesions similar in clinical, as well as radiologic and pathological appearance. Further characterization studies are helpful and necessary for the proper management.


Autophagy-related gene LAPTM4B promotes the progression of renal clear cell carcinoma and is associated with immunity.
Renal cell carcinoma (RCC) is a common urologic disease. Currently, surgery is the primary treatment for renal cancer; immunotherapy is not as effective a treatment strategy as expected. Hence, understanding the mechanism in the tumor immune microenvironment (TME) and exploring novel immunotherapeutic targets are considered important. Recent studies have demonstrated that autophagy could affect the immune environment of renal cell carcinoma and induce proliferation and apoptosis of cancer cells. By comparing lysosomal genes and regulating autophagy genes, we identified the LAPTM4B gene to be related to RCC autophagy. By analyzing the TCGA-KIRC cohort using bioinformatics, we found M2 macrophages associated with tumor metastasis to be significantly increased in the immune microenvironment of patients with high expression of LAPTM4B. GO/KEGG/GSEA/GSVA results showed significant differences in tumor autophagy- and metastasis-related pathways. Single-cell sequencing was used to compare the expression of LAPTM4B in different cell types and obtain the differences in lysosomal and autophagy pathway activities in different ccRCC cells. Subsequently, we confirmed the differential expression of LAPTM4B in renal cell carcinoma of different Fuhrman grades using western blotting. Downregulation of LAPTM4B expression significantly reduced the proliferation of renal cell carcinoma cells and promoted cell apoptosis through cell experiments. Overall, our study demonstrated that the autophagy-related gene LAPTM4B plays a critical role in the TME of RCC, and suggested that LAPTM4B is a potential therapeutic target for RCC immunotherapy.


Equity Promoting Integrated Care: Definition and Future Development.
Over the last three decades, integrated care has emerged as an important health system strategy to improve population health while addressing the unique needs of structurally marginalised communities. However, less attention has been given to the role of integrated care in addressing issues related to inequities in health and health care. In this commentary we introduce the concept of Equity Promoting Integrated Care (EPIC) that situates integrated care in a social justice context to frame the actions necessary to center equity as a priority for integrated care. We suggest that efforts to advance the design and implementation of integrated care should focus on three avenues for future research and practice, namely, the collaborative mobilization of a global network of integrated care stakeholders to advocate for social justice and health equity, investing in equity-focused approaches to implementation science that highlight the importance of social concepts such as colonialism and intersectionality to advance the theory and practice of implementing EPIC models of care, and leveraging innovative approaches to measuring equity-related aspects of integrated care to inform continuous improvement of health systems.


Photoenzymatic epoxidation of styrenes.
Two-component-diffusible-flavomonooxygenases are versatile biocatalysts for selective epoxidation-, hydroxylation- or halogenation reactions. Their complicated molecular architecture can be simplified using photochemical regeneration of the catalytically active, reduced FADH2 prosthetic group. In this contribution we provide the proof-of-concept and characterization for the direct regeneration of the styrene monooxygenase from Pseudomonas.


Simulation of pulsatile flow of blood in stenosed coronary artery bypass with graft.
In this paper, we investigate the behavior of the pulsatile blood flow in a stenosed right coronary artery with a bypass graft. The human blood is assumed to be a non-Newtonian fluid and its viscous behavior is described by the Carreau model. The transient phenomena of blood flow though the stenosed region and the bypass grafts are simulated by solving the three dimensional unsteady Navier-Stokes equations and continuity equation. The influence of the bypass angle on the flow interaction between the jet flow from the native artery and the flow from the bypass graft is investigated. Distributions of velocity, pressure and wall shear stresses are determined under various conditions. The results show that blood pressure in the stenosed artery drops dramatically in the stenosis area and that high wall shear stresses occur around the stenosis site.