Properties of mixed monolayers of clinical lung surfactant, serum albumin and hydrophilic polymers.
It is now established that the surface activity of the clinically used lung surfactant is reduced by serum proteins and can be restored by adding the hydrophilic polymers. The mechanisms of lung surfactant inactivation by serum proteins and restoring effect by the hydrophilic polymers remain not completely understood. In this paper the state and rheological dilatational properties of surface films formed from clinical lung surfactant Exosurf, Survanta, Curosurf and Alveofact in the presence of serum albumin (BSA) and hydrophilic polymers polyvinylpyrrolidone (PVP), polyethylene glycol (PEG) and Dextran were studied. The obtained results suggest that the lung surfactant and BSA mixtures spread at air-water interface form a DPPC/BSA mixed monolayers with lower content of DPPC. The presence of hydrophilic polymers PVP, PEG and Dextran restore the DPPC content in the surface film. The effectiveness of the DPPC spreading and formation of better compacted film increases in order Exosurf, Survanta, Curosurf, Alveofact. The obtained results are in accordance with the generally admitted ideas about the mechanisms of serum protein inactivation and restoring effect of hydrophilic polymers based on the previously studies of the lung surfactant adsorption rate.


Religion, faith and the empowerment process: stories of Iranian people with diabetes.
Empowerment concerning people with diabetes is well researched. However, few researchers specifically focus on the barriers to and facilitators of empowerment in Iranian people with diabetes. Understanding the factors could help health professionals facilitate self-empowerment more effectively. This study aims to determine the barriers to and facilitators of empowerment in Iranian people with diabetes. A qualitative exploratory study was conducted using in-depth interviews to collect the data from 11 women and men in 2007. Themes were identified using constant comparative analysis method. Common barriers to empowerment were similar to other chronic diseases: prolonged stress, negative view about diabetes, ineffective health-care systems, poverty and illiteracy. Diabetes education, fear of diabetes' complications, self-efficacy and hope for a better future emerged as being crucial to empowerment. Facilitators specific to Iranians were: the power of religion and faith, the concept of the doctor as holy man, accepting diabetes as God's will, caring for the body because it was God's gift and support from families especially daughters. Empowerment was strongly influenced by cultural and religious beliefs in Iran and the power of faith emerged as an important facilitator of diabetes empowerment. The findings will help health professionals understand how Iranian people with diabetes view life and the factors that facilitate empowerment.


Room volume classification from room impulse response using statistical pattern recognition and feature selection.
Classification of the room volume from the room impulse response (RIR) can be useful in acoustic scene analysis applications, using RIR that is provided directly, or estimated from audio recordings. Current methods for estimating the room volume from the RIR require the source-to-receiver distance, and may be sensitive to differences in absorption. A room volume classification method is presented that does not require the source-to-receiver distance, and which is potentially robust to differences in absorption. Room volume features are defined that are related to the room volume and may be extracted from the RIR. Gaussian mixture models are trained to model room volume classes. Room volume is classified according to a maximum likelihood criterion that is normalized with a background model. Feature selection is performed with different classification error criteria. Both simulated and measured RIRs were examined, achieving an equal error rate of 0.1% and 19.1%, respectively.


[Spatial organisation of the cortico-striatal projection system in the dog brain].
Cortico-striatal projections of the dog brain caudate nucleus and putamen were shown to originate from widespread cortical areas, the cells of the origin being located both in supra- and subgranular cortical layers. The "motor" and the "limbic" portions of the neostriatum were separated on the basis of their predominant projections from functionally different cortical areas, the fact suggesting a parallel processing in the frontal cortico-basal ganglionar circuits. The findings suggest presence of both convergence and divergence patterns in the parallel processing.


Histologic Discordance Between Primary Tumor and Nodal Metastasis in Breast Cancer: Solving a Clinical Conundrum in the Era of Genomics.
Next-generation sequencing (NGS) technologies have become increasingly used for managing breast cancer. In addition to the conventional use of NGS for predicting recurrence risk and identifying potential actionable mutations, NGS can also serve as a powerful tool to understand clonal origin and evolution of tumor pairs and play a unique role in clarifying complex clinical presentations. We report an unusual case of early-stage breast cancer in which the primary tumor and draining axillary node were histologically discordant. The primary tumor was invasive lobular carcinoma, whereas the nodal metastasis was invasive ductal carcinoma. This discordance led us to question whether the tumors had the same origin. NGS performed on both specimens identified no overlapping variants, leading us to conclude that the patient had two separate primary breast cancers, with the nodal tumor representing metastasis from an occult breast cancer. DNA sequencing of the primary tumor and the nodal metastasis allowed us to predict the patient's recurrence risk, and we initiated adjuvant chemotherapy and hormonal therapy based on these results. This case illustrates the utility of NGS for successfully managing a rare and challenging case. KEY POINTS: A degree of molecular concordance is expected for tumors originating from a common stem or progenitor cell. Histological discordance and absence of any genomic overlap should raise suspicion for two separate primary tumors. Paired DNA sequencing of the primary tumor and nodal metastasis can inform clinical decisions when primary breast tumor and axillary metastasis are histologically discordant. Molecular/Precision Oncology Tumor Board is the best setting to facilitate such decisions in these challenging cases. Paired DNA sequencing under these rare circumstances may suggest an occult breast tumor.


Protein stabilization via hydrophilization. Covalent modification of trypsin and alpha-chymotrypsin.
This paper experimentally verifies the idea presented earlier that the contact of nonpolar clusters located on the surface of protein molecules with water destabilizes proteins. It is demonstrated that protein stabilization can be achieved by artificial hydrophilization of the surface area of protein globules by chemical modification. Two experimental systems are studied for the verification of the hydrophilization approach. The surface tyrosine residues of trypsin are transformed to aminotyrosines using a two-step modification procedure: nitration by tetranitromethane followed by reduction with sodium dithionite. The modified enzyme is much more stable against irreversible thermoinactivation: the stabilizing effect increases with the number of aminotyrosine residues in trypsin and the modified enzyme can become even 100 times more stable than the native one. Alpha-chymotrypsin is covalently modified by treatment with anhydrides or chloroanhydrides of aromatic carboxylic acids. As a result, different numbers of additional carboxylic groups (up to five depending on the structure of the modifying reagent) are introduced into each Lys residue modified. Acylation of all available amino groups of alpha-chymotrypsin by cyclic anhydrides of pyromellitic and mellitic acids results in a substantial hydrophilization of the protein as estimated by partitioning in an aqueous Ficoll-400/Dextran-70 biphasic system. These modified enzyme preparations are extremely stable against irreversible thermal inactivation at elevated temperatures (65-98 degrees C); their thermostability is practically equal to the stability of proteolytic enzymes from extremely thermophilic bacteria, the most stable proteinases known to date.


Streptokinase vs heparin for deep venous thrombosis. Can lytic therapy be justified?
Lytic therapy, most notably streptokinase, holds great promise in the treatment of acute deep venous thrombosis. In 19 published trials, this form of lytic therapy has been shown to be associated with greater venous valvular and venous patency preservation, implying better short-term and long-term outcome. Unfortunately, closer examination of the data reveals several flaws, including overreliance on venogram data and lack of adequate long-term follow-up. Streptokinase, as well as other forms of lytic therapy, has not gained widespread acceptance in the treatment of acute deep venous thrombosis, and, until better data become available, such reluctance seems justified.


Atomic force microscopy of Connexin40 gap junction hemichannels reveals calcium-dependent three-dimensional molecular topography and open-closed conformations of both the extracellular and cytoplasmic faces.
Atomic force microscopy was used to study the three-dimensional molecular topography and calcium-sensitive conformational changes of Connexin40 hemichannels (connexons) reconstituted in 1,2-dioeloyl-sn-glycero-3-phosphatidylcholine lipid bilayers. Two classes of objects were observed that differed in their protrusion heights above the bilayer (2.6 versus 4.2 nm). Comparison to reconstituted connexons containing Connexin40 truncated to eliminate most of its C-terminal cytoplasmic domain showed that the two height classes corresponded to the shorter extracellular and taller cytoplasmic aspects of the hemichannels and that the C-terminal tail of Connexin40 contributes ∼1.6 nm in thickness. Hemichannels imaged in solutions containing < 10 μm Ca(2+) showed 3.1-3.2 nm depressions (openings) in 30% of the cytoplasmic faces and 65% of the extracellular faces, and high-resolution three-dimensional topography of extracellular or cytoplasmic aspects of some connexons was observed. After addition of 3.6 mm Ca(2+), > 75% of the connexons in either orientation adopted closed conformations. In contrast, hemichannels imaged in the presence of 0.1 mm EDTA showed large (5.6- to 5.8-nm diameter) openings in nearly all hemichannels regardless of orientation, and detailed topography was visible in many connexons. Real-time imaging following the addition of 3.6 mm Ca(2+) showed transitions of both extracellular and cytoplasmic orientations from "open" into "closed" conformations within several minutes. These studies provide the first high-resolution topographic information regarding a connexin with a large cytoplasmic domain and suggest that the extramembranous portions of Connexin40 contribute to a channel entrance that is relaxed by chelation of residual divalent cations.


[Spontaneous hemoperitoneum caused by intraabdominal variceal rupture in a patient with liver cirrhosis. Clinical case].
Spontaneous hemoperitoneum secondary to intraabdominal variceal rupture, is an uncommon and highly lethal complication of cirrhosis. We report a case of a 68 years old male submitted because of abdominal pain and fainting. The clinical and laboratory work up concluded that the patient had cirrhosis and hemoperitoneum. He was operated on and the exploration showed a massive hemoperitoneum caused by bleeding gastrosplenic varices. The patient died in the immediate postoperative period.


High levels of icosapentaenoic acid in the lipids of oyster Crassostrea gigas ranging over both Japan and France.
The lipid and fatty acids of the Pacific oyster, Crassostrea gigas, collected both in Japan and France, were analyzed. Triacylglycerols and sterols were the major classes in the neutral lipids of both populations of C. gigas between the two countries, and they had significant levels of phospholipids (phosphatidylethanolamine and phosphatidylcholine) with ceramideaminoethylphosphonate in their polar tissue lipids. The differences of 18:3n-3 and 22:6n-3 (docosahexaenoic acid; DHA) levels in the depot triacylglycerols suggest the influence of dietary phytoplankton in different environments of the two countries. Although the levels of the fatty acids slightly differed, that of 20:5n-3 (icosapentaenoic acid; EPA, 20.5-24.8%) in the triacylglycerols was specifically the highest fatty acid in all the samples. The major polyunsaturated fatty acids in the polar lipids of all samples were EPA (13.2-17.8% for phosphatidylethanolamine and 13.4-22.7% for phosphatidylcholine) and DHA (18.9-26.8% for phosphatidylethanolamine and 13.1-22.5% for phosphatidylcholine). The fluctuation of total PUFA levels in the polar lipids between samples of both countries suggests the influence of diet. In addition, the consistently high EPA levels in the phospholipids may compensate for the variation in DHA levels.


Facial arterial depth and relationship with the facial musculature layer.
Previous studies have revealed a variation in the origin and distribution patterns of the facial artery. However, the relationship between the facial artery and the facial muscles has not been well described. The purpose of this study was to determine the facial artery depth and relationship with the facial musculature layer, which represents critical information for dermal filler injection and oral and maxillofacial surgery. Fifty-four embalmed adult faces from Korean cadavers (36 male and 18 female cadavers; mean age, 73.3 years) were used in this study. A detailed dissection was performed, with great care being taken to avoid damaging the facial artery underlying the facial skin and muscle. The facial artery was first categorized according to the patterns of its final arterial branches. The branching pattern was classified simply into three types: type I, nasolabial pattern (51.8 percent); type II, nasolabial pattern with an infraorbital trunk (29.6 percent); and type III, forehead pattern (18.6 percent). Each type was further subdivided according to the facial artery depth and relationship with the facial musculature layer as types Ia (37.0 percent), Ib (14.8 percent), IIa (16.7 percent), IIb (12.9 percent), IIIa (16.7 percent), and IIIb (1.9 percent). This study provides new anatomical insight into the relationships between the facial artery branches and the facial muscles, including providing useful information for clinical applications in the fields of oral and maxillofacial surgery.


Observational determination of surface radiative forcing by CO2 from 2000 to 2010.
The climatic impact of CO2 and other greenhouse gases is usually quantified in terms of radiative forcing, calculated as the difference between estimates of the Earth's radiation field from pre-industrial and present-day concentrations of these gases. Radiative transfer models calculate that the increase in CO2 since 1750 corresponds to a global annual-mean radiative forcing at the tropopause of 1.82 ± 0.19 W m(-2) (ref. 2). However, despite widespread scientific discussion and modelling of the climate impacts of well-mixed greenhouse gases, there is little direct observational evidence of the radiative impact of increasing atmospheric CO2. Here we present observationally based evidence of clear-sky CO2 surface radiative forcing that is directly attributable to the increase, between 2000 and 2010, of 22 parts per million atmospheric CO2. The time series of this forcing at the two locations-the Southern Great Plains and the North Slope of Alaska-are derived from Atmospheric Emitted Radiance Interferometer spectra together with ancillary measurements and thoroughly corroborated radiative transfer calculations. The time series both show statistically significant trends of 0.2 W m(-2) per decade (with respective uncertainties of ±0.06 W m(-2) per decade and ±0.07 W m(-2) per decade) and have seasonal ranges of 0.1-0.2 W m(-2). This is approximately ten per cent of the trend in downwelling longwave radiation. These results confirm theoretical predictions of the atmospheric greenhouse effect due to anthropogenic emissions, and provide empirical evidence of how rising CO2 levels, mediated by temporal variations due to photosynthesis and respiration, are affecting the surface energy balance.


Molecular mechanisms underlying the role of the puckered surface in the biocompatibility of black phosphorus.
As a newly emerging two-dimensional material, black phosphorus (BP) has received broad attention in the field of biomedical applications. Prior to its clinical application, its cytotoxicity to cells should be carefully evaluated; however, this field is still in its infancy. Motivated by this, we performed molecular dynamics (MD) simulations to systematically investigate the potential mechanisms of the cytotoxicity of BP to the lipid membrane, including lipid extraction, penetration into the membrane, and the impacts of BP on the physical properties of the membrane. Surprisingly, we observed that BP could not extract lipid molecules from the membrane. The thermodynamic analyses suggested that the puckered surface structure could weaken the interactions between BP and lipid molecules, thus inhibiting the lipid extraction. Additionally, through simulating the spontaneous interaction modes between BP and the lipid membrane, we found that the "passivated" edges of BP prohibited it from penetrating into the membrane. As a result, BP could only spontaneously lie parallel on the surface of the membrane, in which manner BP exerted little influence on the properties of the lipid membrane. To comprehensively appraise the cytotoxicity, we even artificially inserted BP into the membrane and compared the effects of BP and graphene on the properties of the membrane. Simulation results showed that the influences of the inserted BP on the lipid properties were much milder than those of graphene. Overall, the present work suggests that BP possesses distinctive biocompatibility benefiting from its puckered surface structure. This work provides a better understanding of the interactions between BP and the membrane, which may offer some useful suggestions for exploring strategies to improve the biocompatibility of nanomaterials.


Burden of musculoskeletal-related disorders resulting from non-fatal road traffic collisions in Africa: a protocol of a systematic review.
In addition to their high mortality rates, road traffic collisions (RTC) are considered a burden within those who do survive. In Africa, injuries related to RTC have been identified as the 10th most common cause of disability-adjusted life years lost for all ages and categories. Moreover, non-fatal RTC are the biggest cause associated with the burden of musculoskeletal disorders (MSD) in Africa. Despite this, the epidemiology of MSD related to non-fatal RTC within this region is still unknown.The objective of this review is to identify and summarise available data regarding the prevalence, incidence and patterns of MSD resulting from non-fatal RTC in Africa. A systematic review of observational epidemiological studies will be conducted. On October 2019, MEDLINE, Embase, CINAHL Plus, PsycINFO, Web of Science, Global Health and African Journals OnLine will be searched for literature that is in English and published between 1990 and 2018. Two reviewers (MY ad TG) will independently screen results and extract the data, with a third reviewer (FF) resolving any discrepancies through discussion. Additionally, two reviewers (MY and TG) will independently assess the quality of the eligible studies using the US National Institutes of Health National Heart, Lung, and Blood Institute Quality Assessment Tool.Within the eligible studies, data on citation, methods and results will be extracted. Extracted data will be analysed using a narrative synthesis. Findings will be presented in tables, with the main outcomes being prevalence, incidence and disease pattern of MSD and determinants of non-fatal RTC. The final systematic review will be conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. As individual patients will not be involved in this study, no ethical approval will be sought. Findings from this review will be disseminated through peer-reviewed journals and relevant conferences. CRD42019139538.


The dicey role of Dicer: implications for RNAi therapy.
The dynamic properties of RNA interference (RNAi) in cancer biology have led investigators to pursue with significant interest its role in tumorigenesis and cancer therapy. We recently reported that decreased expression of key RNAi enzymes, Dicer and Drosha, in epithelial ovarian cancers was associated with poor clinical outcome in patients. Dicer expression was also functionally relevant in that targeted silencing was limited with RNAi fragments that require Dicer function compared with those that do not. Together, this and other studies suggest that RNAi machinery expression may affect key pathways in tumorigenesis and cancer biology. Understanding alterations in the functional RNAi machinery is of fundamental importance as we strive to develop novel therapies using RNAi strategies.


Identification of genomic regions, genetic variants and gene networks regulating candidate genes for lipid metabolism in pig muscle.
The intramuscular fat content and fatty acid composition of porcine meat have a significant impact on its quality and nutritional value. This research aimed to investigate the expression of 45 genes involved in lipid metabolism in the longissimus dorsi muscle of three experimental pig backcrosses, with a 25% of Iberian background. To achieve this objective, we conducted an expression Genome-Wide Association Study (eGWAS) using gene expression levels in muscle measured by high-throughput real-time qPCR for 45 target genes and genotypes from the PorcineSNP60 BeadChip or Axiom Porcine Genotyping Array and 65 single nucleotide polymorphisms (SNPs) located in 20 genes genotyped by a custom-designed Taqman OpenArray in a cohort of 354 animals. The eGWAS analysis identified 301 eSNPs associated with 18 candidate genes (ANK2, APOE, ARNT, CIITA, CPT1A, EGF, ELOVL6, ELOVL7, FADS3, FASN, GPAT3, NR1D2, NR1H2, PLIN1, PPAP2A, RORA, RXRA and UCP3). Three cis-eQTL (expression quantitative trait loci) were identified for GPAT3, RXRA, and UCP3 genes, which indicates that a genetic polymorphism proximal to the same gene is affecting its expression. Furthermore, 24 trans-eQTLs were detected, and eight candidate regulatory genes were located in these genomic regions. Additionally, two trans-regulatory hotspots in Sus scrofa chromosomes 13 and 15 were identified. Moreover, a co-expression analysis performed on 89 candidate genes and the fatty acid composition revealed the regulatory role of four genes (FABP5, PPARG, SCD, and SREBF1). These genes modulate the levels of α-linolenic, arachidonic, and oleic acids, as well as regulating the expression of other candidate genes associated with lipid metabolism. The findings of this study offer novel insights into the functional regulatory mechanism of genes involved in lipid metabolism, thereby enhancing our understanding of this complex biological process.


A good night's sleep and the habit of net use: perceptions of risk and reasons for bed net use in Bukoba and Zanzibar.
Intensive malaria control interventions in the United Republic of Tanzania have contributed to reductions in malaria prevalence. Given that malaria control remains reliant upon continued use of long-lasting insecticidal bed nets (LLINs) even when the threat of malaria has been reduced, this qualitative study sought to understand how changes in perceived risk influence LLIN usage, and to explore in more detail the benefits of net use that are unrelated to malaria. Eleven focus group discussions were conducted in Bukoba Rural district and in Zanzibar Urban West district in late 2011. Participants were males aged 18 and over, females between the ages of 18 and 49, and females at least 50 years old. The perceived risk of malaria had decreased among the respondents, and malaria control interventions were credited for the decline. Participants cited reductions in both the severity of malaria and in their perceived susceptibility to malaria. However, malaria was still considered a significant threat. Participants' conceptualization of risk appeared to be an important consideration for net use. At the same time, comfort and aspects of comfort (getting a good night's sleep, avoiding biting pests) appeared to play a large role in personal decisions to use nets consistently or not. Barriers to comfort (feeling uncomfortable or trapped; perceived difficulty breathing, or itching/rashes) were frequently cited as reasons not to use a net consistently. While it was apparent that participants acknowledged the malaria-prevention benefits of net use, the exploration of the risk and comfort determinants of net use provides a richer understanding of net use behaviours, particularly in a setting where transmission has fallen and yet consistent net use is still crucial to maintaining those gains. Future behaviour change communication campaigns should capitalize on the non-malaria benefits of net use that provide a long-term rationale for consistent use even when the immediate threat of malaria transmission has been reduced.


TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease.
Epithelial-mesenchymal transition (EMT), a process whereby fully differentiated epithelial cells undergo transition to a mesenchymal phenotype giving rise to fibroblasts and myofibroblasts, is increasingly recognized as playing an important role in repair and scar formation following epithelial injury. The extent to which this process contributes to fibrosis following injury in the lung is a subject of active investigation. Recently, it was demonstrated that transforming growth factor (TGF)-beta induces EMT in alveolar epithelial cells (AEC) in vitro and in vivo, and epithelial and mesenchymal markers have been colocalized to hyperplastic type II (AT2) cells in lung tissue from patients with idiopathic pulmonary fibrosis (IPF), suggesting that AEC may exhibit extreme plasticity and serve as a source of fibroblasts and/or myofibroblasts in lung fibrosis. In this review, we describe the characteristic features of EMT and its mechanistic underpinnings. We further describe the contribution of EMT to fibrosis in adult tissues following injury, focusing especially on the critical role of TGF-beta and its downstream mediators in this process. Finally, we highlight recent descriptions of EMT in the lung and the potential implications of this process for the treatment of fibrotic lung disease. Treatment for fibrosis of the lung in diseases such as IPF has heretofore focused largely on amelioration of potential inciting processes such as inflammation. It is hoped that this review will stimulate further consideration of the cellular mechanisms of fibrogenesis in the lung and especially the role of the epithelium in this process, potentially leading to innovative avenues of investigation and treatment.


Brillouin Optical Correlation Domain Analysis in Composite Material Beams.
Structural health monitoring is a critical requirement in many composites. Numerous monitoring strategies rely on measurements of temperature or strain (or both), however these are often restricted to point-sensing or to the coverage of small areas. Spatially-continuous data can be obtained with optical fiber sensors. In this work, we report high-resolution distributed Brillouin sensing over standard fibers that are embedded in composite structures. A phase-coded, Brillouin optical correlation domain analysis (B-OCDA) protocol was employed, with spatial resolution of 2 cm and sensitivity of 1 °K or 20 micro-strain. A portable measurement setup was designed and assembled on the premises of a composite structures manufacturer. The setup was successfully utilized in several structural health monitoring scenarios: (a) monitoring the production and curing of a composite beam over 60 h; (b) estimating the stiffness and Young's modulus of a composite beam; and (c) distributed strain measurements across the surfaces of a model wing of an unmanned aerial vehicle. The measurements are supported by the predictions of structural analysis calculations. The results illustrate the potential added values of high-resolution, distributed Brillouin sensing in the structural health monitoring of composites.


Neural mechanisms of genetic risk for impulsivity and violence in humans.
Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence.


Overexpression of meloe gene in melanomas is controlled both by specific transcription factors and hypomethylation.
The melanoma antigens MELOE-1 and MELOE-2 are encoded by a messenger, called meloe, overexpressed in melanomas compared with other tumour cell types and healthy tissues. They are both able to elicit melanoma-specific T cell responses in melanoma patients, and MELOE-1-specific CD8 T cells have been involved in melanoma immunosurveillance. With the aim to develop immunotherapies targeting this antigen, we investigated the transcriptional mechanisms leading to the preferential expression of meloe messenger in the melanocytic lineage. We defined the minimal promoter region of meloe gene and identified binding motifs for a set of transcription factors. Using mutagenesis, co-transfection experiments and chromatin immunoprecipitation, we showed that transcription factors involved in meloe promoter activity in melanomas were the melanocytic specific SOX9 and SOX10 proteins together with the activated P-CREB protein. Furthermore, we showed that meloe promoter was hypomethylated in melanomas and melanocytes, and hypermethylated in colon cancer cell lines and mesotheliomas, thus explaining the absence of P-CREB binding in these cell lines. This was a second key to explain the overerexpression of meloe messenger in the melanocytic lineage. To our knowledge, such a dual transcriptional control conferring tissue-specificity has never been described for the expression of tumour antigens.


New cytotoxic dammarane type saponins from Ziziphus spina-christi.
Cancer is the world's second-leading cause of death. Drug development efforts frequently focus on medicinal plants since they are a valuable source of anticancer medications. A phytochemical investigation of the edible Ziziphus spina-christi (F. Rhamnaceae) leaf extract afforded two new dammarane type saponins identified as christinin E and F (1, 2), along with the known compound christinin A (3). Different cancer cell lines, such as lung cancer (A549), glioblastoma (U87), breast cancer (MDA-MB-231), and colorectal carcinoma (CT-26) cell lines, were used to investigate the extracted compounds' cytotoxic properties. Our findings showed significant effects on all the tested cell lines at varying concentrations (1, 5, 10, and 20 µg/mL). The three compounds exhibited potent activity at low concentrations (< 10 μg/mL), as evidenced by their low IC50 values. To further investigate the complex relationships between these identified cancer-relevant biological targets and to identify critical targets in the pathogenesis of the disease, we turned to network pharmacology and in silico-based investigations. Following this, in silico-based analysis (e.g., inverse docking, ΔG calculation, and molecular dynamics simulation) was performed on the structures of the isolated compounds to identify additional potential targets for these compounds and their likely interactions with various signalling pathways relevant to this disease. Based on our findings, Z. spina-christi's compounds showed promise as potential anti-cancer therapeutic leads in the future.


Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project.
Extranodal natural killer (NK) T-cell lymphoma (ENKTL) is a unique clinicopathological entity, typically associated with poor survival outcomes. Most published data have come from east Asian study groups, with little information available from international cohorts. The effects of treatment advances on routine clinical practice across continental territories has not been clear. We aimed to improve understanding of the clinical characteristics and outcomes of patients with ENKTL. We did a substudy of patients with ENKTL from the T-cell Project, a global prospective cohort study. The T-cell Project registered consecutively diagnosed adults (>18 years) with newly diagnosed, untreated mature T-cell or NK lymphomas (WHO 2001 or 2008 classifications) from 74 centres in 13 countries (in Asia, Europe, North America, and South America). In total, 1695 patients with mature T-cell or NK lymphomas were enrolled between Oct 12, 2006 and Feb 28, 2018 in the T-cell Project. The first patient with ENKTL was enrolled on Feb 15, 2007, and the last on May 26, 2017. Data on baseline characteristics, first-line treatment, treatment response, and survival outcomes were recorded in a central database (locked March 30, 2019). The primary outcome was 5-year overall survival. The T-cell Project is registered on ClinicalTrials.gov, NCT01142674. 166 patients were diagnosed with ENKTL, comprising 11% of 1553 eligible registered cases and distributed across 40 participating centres in four continents. At a median follow-up of 44 months (IQR 20-61), overall survival at 5 years was 54% (95% CI 44-63) in patients with nasal disease (n=98) and 34% (27-46) in patients with extranasal disease (n=68). To our knowledge, this study presents the largest international cohort of patients with ENKTL. We describe a clinically significant improvement in the survival of patients with ENKTL treated in routine clinical practice over the past decade, likely to be attributable to the increasing use of treatment protocols specific for ENKTL. The Fondazione Cassa di Risparmio di Modena, the Associazione Angela Serra per la Ricerca sul Cancro, the Fondazione Italiana Linfomi, Allos Therapeutics, Spectrum Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro, and the National Cancer Institute at the National Institutes of Health.


Peripheral quantitative computed tomography in human long bones: evaluation of in vitro and in vivo precision.
Despite the excellent performance in clinical practice and research, the dual-energy X-ray absorptiometry is restricted by the inherent planar nature of the measurement and the inability to discriminate between trabecular and cortical components of bone. Recently, a new peripheral tomographic scanner (Norland/Stratec XCT 3000) was introduced for versatile measurements of human long bone characteristics in vivo, including trabecular and cortical density (TrD and CoD, respectively), respective cross-sectional areas (TrA and CoA), bone strength index (BSI), and bone mineral content (BMC). We evaluated the technical performance of the scanner using different phantoms and determined the in vivo precision of the above-noted applications by measuring twice several sites of upper and lower limbs of 19 and 36 volunteers aged 23-60 years. The bone scans were performed, with intermediate positioning of the subject, at two different anatomic sites of the forearm, three sites of the upper arm, three sites of the shank, and two sites of the thigh, with the respective skeletal sites representing different bone compositions and sizes. According to phantom measurements, the XCT 3000 appeared to be a highly linear, stable, and precise (coefficient of variation [CV] about 0.2%) system in vitro. The soft tissue thickness, however, had a linear effect on density values and a nonlinear effect on BMC, whereas the effect on cross-sectional area was marginal. The in vivo root mean square CV (CVrms) values for the long bone ends ranged from 0.9% (distal tibia) to 2.7% (distal femur) for TrD, from 1.8% (distal femur) to 7.6% (distal radius) for TrA, from 2.0% (distal tibia) to 6.8% (proximal tibia) for CoD, from 1.8% (distal femur) to 4.9% (proximal tibia) for CoA, and from 4.2% (distal tibia) to 7.7% (distal radius) for BSI. The corresponding CVrms values for the long bone shafts ranged from 0.5% (midshaft of humerus) to 1.4% (midshaft of fibula) for CoD, from 1.7% (midshaft of tibia) to 4.6% (proximal shaft of humerus) for CoA, and from 2.5% (midshaft of tibia) to 7.5% (proximal shaft of humerus) for BSI. There was no interoperator effect on precision. This study provided, for the first time, independent precision data for the new XCT 3000 peripheral quantitative computed tomography (pQCT) scanner in various applications of human long bones (radius, ulna, humerus, tibia, fibula, and femur) and gave practical guidelines and procedures on how to employ this versatile method in clinical and research applications. The technical performance of the tested system was excellent and it allowed, with a low radiation dose, precise in vivo evaluation of trabecular and cortical density, cross-sectional area, and BMC of selected skeletal sites. The potential effect of the soft tissue thickness on density and mineral content values need to be recognized. The pQCT measurement seems to be useful in supplementing the integral, planar DXA data and obviously opens new possibilities for clinical practice and research.


Identification and characterization of hydrophobic gate residues in TRP channels.
Transient receptor potential (TRP) channels, subdivided into 6 subfamilies in mammals, have essential roles in sensory physiology. They respond to remarkably diverse stimuli, comprising thermal, chemical, and mechanical modalities, through opening or closing of channel gates. In this study, we systematically substituted the hydrophobic residues within the distal fragment of pore-lining helix S6 with hydrophilic residues and, based on Xenopus oocyte and mammalian cell electrophysiology and a hydrophobic gate theory, identified hydrophobic gates in TRPV6/V5/V4/C4/M8. We found that channel activity drastically increased when TRPV6Ala616 or Met617 or TRPV5Ala576 or Met577, but not any of their adjacent residues, was substituted with hydrophilic residues. Channel activity strongly correlated with the hydrophilicity of the residues at those sites, suggesting that consecutive hydrophobic residues TRPV6Ala616-Met617 and TRPV5Ala576-Met577 form a double-residue gate in each channel. By the same strategy, we identified a hydrophobic single-residue gate in TRPV4Iso715, TRPC4Iso617, and TRPM8Val976. In support of the hydrophobic gate theory, hydrophilic substitution at the gate site, which removes the hydrophobic gate seal, substantially increased the activity of TRP channels in low-activity states but had little effect on the function of activated channels. The double-residue gate channels were more sensitive to small changes in the gate's hydrophobicity or size than single-residue gate channels. The unconventional double-reside gating mechanism in TRP channels may have been evolved to respond especially to physiologic stimuli that trigger relatively small gate conformational changes.-Zheng, W., Hu, R., Cai, R., Hofmann, L., Hu, Q., Fatehi, M., Long, W., Kong, T., Tang, J., Light, P., Flockerzi, V., Cao, Y., Chen, X.-Z. Identification and characterization of hydrophobic gate residues in TRP channels.


Present practice of electroconvulsive therapy in Scandinavia.
We have set up guidelines for the practice of electroconvulsive therapy, based on Scandinavian clinical experience and research. Because the therapeutic effect is a result of the cerebral seizure, and the organic side effects partly consequences of the electrical stimulation, the aim should be to induce maximal seizure activity using minimal electrical energy. Essential features of optimal therapy are (1) absence of therapy with benzodiazepines and other anticonvulsant drugs, (2) superficial narcosis, (3) abundant oxygen supply, (4) threshold stimulation with brief-pulse stimuli, and (5) unilateral, parietotemporal, nondominant application of the electrodes. Seizure duration should always be measured to make sure that maximum seizure activity has taken place.


BRMS1 Expression in Surgically Resected Lung Adenocarcinoma Predicts Future Metastases and Is Associated with a Poor Prognosis.
Expression of breast cancer metastasis suppressor 1 gene (BRMS1) is decreased in NSCLC cells and tumors. We hypothesized that intratumoral breast cancer metastasis suppressor 1 (BRMS1) expression is associated with lung adenocarcinoma (LUAD) histologic subtypes and overall survival (OS) and disease-free survival (DFS) in patients undergoing resection for early-stage LUAD. Patients (N = 1030) who underwent complete resection for LUAD with tissue available for histologic evaluation were identified. Tissue microarrays were constructed, and immunostaining was performed and scored for intensity of BRMS1 expression. OS and DFS were estimated (by the Kaplan-Meier method) and compared between groups (by the log-rank test), stratified by stage. Hazard ratios (HRs) for hazard of death and recurrence were estimated using univariable and multivariable Cox proportional hazards models. OS and DFS nomograms were created, and model performance was examined. Intratumoral BRMS1 expression was high in 632 patients (61%) and low in 398 (39%). Low BRMS1 expression was associated with higher pathologic T stage (p = 0.001), larger tumor size (p ≤ 0.0001), greater lymphatic (p = 0.032) and vascular (p = 0.001) invasion, LUAD histologic subtype (p = 0.001), and intermediate and high architectural tumor grade (p = 0.003). Low BRMS1 expression was an independent predictor of worse OS (HR = 1.35, 95% confidence interval: 1.10-1.65, p = 0.004) and DFS (HR = 1.27, 95% confidence interval: 1.05-1.54, p = 0.012). OS and DFS nomograms showed excellent predictive performance based on discrimination and calibration. Among patients with surgically resected LUAD, OS and DFS were significantly worse in cases with low intratumoral BRMS1 expression. Our findings suggest that BRMS1 is an independent biomarker with prognostic significance in surgically resected LUAD.


Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer.
Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. BNIP3 and NIX are critical mediators for the Mieap-regulated mitochondrial quality control. Mieap suppresses murine intestinal tumor via its mitochondrial quality control function. To explore the role of the Mieap-regulated mitochondria quality control function in colorectal cancer patients, we examined the statuses of p53, Mieap, BNIP3 and NIX in 57 primary colorectal cancer tissues. Promoter methylation of the Mieap and BNIP3 genes was found in 9% and 47% of colorectal cancer cases, respectively, whereas p53 mutation was found in more than 50% of colorectal cancer tissues lacking methylation of the Mieap and BNIP3 promoters, implying that the p53/Mieap/BNIP3-regulated mitochondria quality control pathway is inactivated in more than 70% of colorectal cancer patients. In LS174T colorectal cancer cells, hypoxia activated the Mieap-regulated mitochondria quality control function. Knockdown of p53, Mieap or BNIP3 in LS174T cells severely impaired the hypoxia-activated function, leading to the accumulation of unhealthy mitochondria and increase of mitochondrial reactive oxygen species generation. The mitochondrial reactive oxygen species generated by unhealthy mitochondria in the p53/Mieap/BNIP3-deficient cells remarkably enhanced cancer cell migration and invasion under hypoxic condition. These results suggest that the Mieap-regulated mitochondria quality control has a critical role in colorectal cancer suppression in the in vivo hypoxic tumor microenvironment.


[Determination of optimal spontaneous respiration anesthesia for outpatient anesthesiology].
Outpatient surgery presents a number of specific requirements for anesthesia, among which there is safety and that the main point is anesthesia, as well as postanesthesia depression should not be a limiting factor on discharge the patient from hospital. The authors compare 3 current anesthetic methods available in our country: 1) combined general anesthesia based on ketamine, dormicun, and fentanyl, 2) total venous anesthesia (TVA) based on propofol and fentanyl, and 3) anesthesia with sevorane inhalation with preserved spontaneous respiration through a laryngeal mask. Analysis of postoperative cognitive disorders and complications, such as postoperative nausea and vomiting makes combined general anesthesia be excluded from the methods suitable for outpatient operations. TVA and sevorane inhalation anesthesia show comparable results in emergence rate tests, and postanesthetic rehabilitation, the number of postoperative complications. However, less cost and amazing predictability enable the authors to prefer inhalation anesthesia.


Postnatal presence of paraseptal cartilages in humans: a description of morphology and size.
Paraseptal cartilages (PCs) have been the subject of controversy, in that some authors believe them to be absent or rarely present, while others have described them to exist at predictable locations in adult human tissue specimens. This study seeks to determine the presence or absence of PCs in humans and describe their morphology and size. Nasal septal tissue from 19 adults and 1 child were paraffin embedded, coronally sectioned, placed on slides, and stained for microscopic observation. For all specimens, PCs were identified and lengths were calculated. Selected PCs were also digitized in order to calculate volume. Results demonstrated that PCs were present in all 20 tissue specimens and assumed a common morphology. In each, PCs were found to begin as hyaline cartilage lobes that extend projections in a superolateral direction as an anteroposterior course is followed. The projections were found to rotate inferiorly until each PC was found to assume a position that extended below the nasal septum. Length measures in adults ranged from 8,725 to 19,000 microm (x = 14,188.9 microm) and volumes ranged from 7.7 to 24.2 (x = 13.2) x 10(-3) ml. A quantitative comparison to foetal data from a previous study suggests prenatal and/or postnatal growth of PCs. Results from this study support the presence of PCs in adult humans as well as prenatal/postnatal growth of PCs.


Recovery after stroke: the severely impaired are a distinct group.
Stroke causes different levels of impairment and the degree of recovery varies greatly between patients. The majority of recovery studies are biased towards patients with mild-to-moderate impairments, challenging a unified recovery process framework. Our aim was to develop a statistical framework to analyse recovery patterns in patients with severe and non-severe initial impairment and concurrently investigate whether they recovered differently. We designed a Bayesian hierarchical model to estimate 3-6 months upper limb Fugl-Meyer (FM) scores after stroke. When focusing on the explanation of recovery patterns, we addressed confounds affecting previous recovery studies and considered patients with FM-initial scores <45 only. We systematically explored different FM-breakpoints between severe/non-severe patients (FM-initial=5-30). In model comparisons, we evaluated whether impairment-level-specific recovery patterns indeed existed. Finally, we estimated the out-of-sample prediction performance for patients across the entire initial impairment range. Recovery data was assembled from eight patient cohorts (n=489). Data were best modelled by incorporating two subgroups (breakpoint: FM-initial=10). Both subgroups recovered a comparable constant amount, but with different proportional components: severely affected patients recovered more the smaller their impairment, while non-severely affected patients recovered more the larger their initial impairment. Prediction of 3-6 months outcomes could be done with an R2=63.5% (95% CI=51.4% to 75.5%). Our work highlights the benefit of simultaneously modelling recovery of severely-to-non-severely impaired patients and demonstrates both shared and distinct recovery patterns. Our findings provide evidence that the severe/non-severe subdivision in recovery modelling is not an artefact of previous confounds. The presented out-of-sample prediction performance may serve as benchmark to evaluate promising biomarkers of stroke recovery.


High-density lipoprotein metabolism, composition, function, and deficiency.
To examine the recent advances in our knowledge of HDL metabolism, composition, function, and coronary heart disease (CHD), as well as marked HDL deficiency states because of mutations in the apolipoprotein (apo) A-I, ATP-binding cassette transfer protein A1 and lecithin cholesterol acyltransferase (LCAT) gene loci. It has been documented that apoA-I, myeloperoxidase and paraoxonase 1 (PON1) form a complex in HDL that is critical for HDL binding and function. Myeloperoxidase has a negative impact on HDL function, whereas PON1 has a beneficial effect. Patients who lack apoA-I develop markedly premature CHD. Patients who lack ATP-binding cassette transfer protein A1 transporter function have only very small discoidal preβ-1 HDL, and develop hepatosplenomegaly, intermittent neuropathy and premature CHD, although significant heterogeneity for these disorders has been reported. Patients with LCAT deficiency have abnormal small discoidal LDLs and HDL particles, and develop kidney failure. Enzyme replacement therapy is being developed for the latter disorder. Recent data indicates that proteins other than apoA-I and apoA-II such as MPO and PON1 have important effects on HDL function. There has been considerable recent progress made in our understanding of HDL protein content and function.


Addressing smoking in community drug abuse treatment programs: practical and policy considerations.
Smoking is the leading cause of preventable death in the United States. This public health problem is of particular concern among individuals with substance use disorders in that they smoke at a greater rate than the general public. Smoking-related illness represents a major source of preventable death in persons with drug dependencies. Substance abuse treatment programs have access to persons with substance use disorders and the opportunity to intervene on their smoking; however, nicotine dependence has historically not been viewed in the same light as other drug dependencies by the treatment field. As a result, many persons in these treatment program settings do not receive opportunities to address their smoking. When substance abuse treatment organizations consider implementing smoking policies and services, many questions and choices arise. In practice, a range of approaches has been developed from simple assessment and referral for smoking cessation treatment to implementing smoke-free grounds and requiring that patients stop smoking concurrent with addressing their other drug dependencies. Smoking cessation policy decisions have the potential to directly affect the patients, the workforce, the referral network, and other major stakeholders related to these organizations. The authors consider a range of both practical and policy issues facing treatment organizations and conclude that advances in smoking policy are possible with current resources.


A legacy of tinnitus: multiple head and neck paragangliomas.
We describe the case of a patient who presented with a right-sided glomus jugulare tumor and bilateral glomus vagale tumors. These proved to be nonmalignant paragangliomas on histopathological analysis. Genetic analysis revealed a germline heterozygous missense mutation (Pro81Leu) in the succinate dehydrogenase subunit D (SDHD) gene. We discuss the clinical presentations of the familial paraganglioma syndrome type 1, which is caused by mutations in SDHD, and the implications for the clinical diagnosis and care of such patients.


The proapoptotic protein tBid forms both superficially bound and membrane-inserted oligomers.
Bid is a proapopotic activator protein of the Bcl-2 family that plays a pivotal role in controlling mitochondrial outer membrane permeabilization during apoptosis. Here, we characterized the interaction of fluorescently labeled truncated Bid (tBid) with a mitochondria-like supported lipid bilayer at the single-molecule level. The proteins observed at the membrane exhibited a very wide range of mobility. Confocal images of the membrane displayed both diffraction-limited Gaussian spots and horizontal streaks, corresponding to immobile and mobile tBid species, respectively. We observed 1), fast-diffusing proteins corresponding to a loosely, probably electrostatically bound state; 2), slowly diffusing proteins, likely corresponding to a superficially inserted state; and 3), fully immobilized proteins, suggesting a fully inserted state. The stoichiometry of these proteins was determined by normalizing their fluorescence intensity by the brightness of a tBid monomer, measured separately using fluorescence fluctuation techniques. Strikingly, the immobile species were found to be mainly tetramers and higher, whereas the mobile species had on average a significantly lower stoichiometry. Taken together, these results show that as soluble Bid progresses toward a membrane-inserted state, it undergoes an oligomerization process similar to that observed for Bax.


Macrocephaly-capillary malformation syndrome in a newborn with tetralogy of fallot and sagittal sinus thrombosis.
Macrocephaly-capillary malformation syndrome is characterized by cutaneous vascular malformations with associated anomalies as macrocephaly, macrosomia, hemihypertrophy, hypotonia, developmental delay, lax joints, loose skin, polysyndactyly, and neuroimaging abnormalities. We present a newborn with a prenatal diagnosis of macrosomia and tetralogy of Fallot. He also had macrocephaly; a high forehead; capillary hemangioma on the forehead, upper lip, and philtrum; generalized loose skin; postaxial polydactyly of both hands and feet, with neuroimaging findings of polymicrogyria and thrombosis in sagittal sinus and sinus rectus. His condition was diagnosed as macrocephaly-capillary malformation syndrome in the neonatal period and he died suddenly during sleep at 6 months of age. The clinical course in this syndrome is not as benign as was previously thought. Careful follow-up of these patients with particular emphasis on neuroradiologic and cardiologic evaluation might help decrease the risk of sudden death and to improve long-term outcome.


Mobile Diabetes Intervention for Glycemic Control: Impact on Physician Prescribing.
Of adults with type 2 diabetes, 84% take antihyperglycemic medication. Successful treatment requires active monitoring and medication dose adjustment by health providers. The objective of this study was to determine how a mobile-phone-based coaching system for diabetes management influences physician prescribing behavior. This secondary data analysis is based on a cluster randomized clinical trial that reported patients provided with mobile self-management had reduction in glycated hemoglobin (HbA1c) of 1.9% over 1 year, compared to 0.7% in control patients (P < .001). Participants were primary care patients with type 2 diabetes randomized at physician practice level into a control group (n = 55) and intervention group (n = 62). Main study measures were patients' medication records (medication, dose, frequency, start and end date) abstracted at baseline and study end. Antihyperglycemic medications, including sulfonylureas or thiazolidinediones, and antihypertensive and antilipemic medications were analyzed. A higher percentage of patients in the intervention group had modification and intensification of incretin mimetics during the 1-year study period (9.7% vs 0.0% and 8.1% vs 0.0%, both P = .008). A higher percentage of patients in the intervention group had modification and intensification of metformin (24.2% vs 7.3%, P = .033). The overall difference in physician prescribing of oral antihyperglycemic medications was not statistically significant. Our results suggest mobile diabetes interventions can encourage physicians to modify and intensify antihyperglycemic medications in patients with type 2 diabetes. Differences in physician prescribing behavior were modest, and do not appear to be large enough to explain a 1.2% decrease in HbA1c.


Analysis of intensive care admissions among paediatric obstructive sleep apnoea referrals.
Introduction The aim of this study was to identify the proportion of children referred to a paediatric tertiary referral centre who required admission to the paediatric intensive care unit (PICU) following surgery for obstructive sleep apnoea (OSA) and to establish risk factors for these admissions. Methods Retrospective review of case notes and the operative database was performed for all children undergoing adenotonsillectomy for sleep disordered breathing and OSA symptoms in Great Ormond Street Hospital over a 10-year period. Results Overall, 1,328 children underwent adenotonsillectomy for sleep disordered breathing and OSA. The mean age was 3.1 years (standard deviation [SD]: 1.7 years). A total of 37 (2.8%) were admitted to the PICU postoperatively (mean length of PICU stay: 1.2 days, standard deviation [SD]: 0.6 days) and 282 (21.2%) required nasopharyngeal airway (nasal prong) insertion intraoperatively. The mean length of stay on the ward following surgery was 1.4 days (SD: 0.8 days). Patients with severe OSA (apnoea-hypopnoea index [AHI] >10) and ASA (American Society of Anesthesiologists) grade ≥3 were more likely to require postoperative PICU admission (22/37 vs 381/1,291 [p<0.001] and 29/37 vs 660/1,291 [p=0.001] respectively). Severe OSA was also more common in children who required nasal prong insertion intraoperatively (186/282 vs 217/1,046, p<0.001). Conclusions Very few children referred to a paediatric tertiary referral centre actually require PICU admission following surgery. This may be in part due to the use of a nasopharyngeal airway in patients where postoperative obstruction is anticipated. In children with severe OSA (AHI >10) and an ASA grade of ≥3, nasopharyngeal airway insertion and potential admission to the PICU should be considered.


[Relation of the stability of microbial cells in air to their phospholipid composition].
The phospholipid composition of 8 Escherichia coli strains differing in their capacity for survival in the air with a relative humidity of 30% has been studied. The study has revealed that, irrespective of the phase of growth and the nature of the culture medium, the capacity of E. coli cells for survival in the air is related to their phospholipid composition, this capacity being the higher, the greater the content of total phospholipids and cardiolipin and the lower the concentration of phosphatidyl glycerine.


Health benefits offer rates: is there a nonresponse bias?
To determine whether a nonresponse bias exists in the offer rate for health benefits in firms with fewer than 50 workers and to present a simple adjustment to correct for observed bias. The 2003 Employer Health Benefits Survey (EHBS) conducted by the Kaiser Family Foundation and Health Research and Educational Trust, and a follow-up survey of nonrespondents to the 2003 EHBS. We conducted a follow-up survey to the 2003 EHBS to collect health benefits offering data from firms with fewer than 50 workers. We used McNemar's test to verify that the follow-up survey provided results comparable to the EHBS, and t-tests were used to determine nonresponse bias. We applied a simple weighting adjustment to the EHBS. The data for both the EHBS and the follow-up survey were collected by the same survey research firm. The EHBS interviews the person most knowledgeable about the firm's health benefits, while the follow-up survey interviews the first person who answers the telephone whether they are the most knowledgeable or not. Principal Findings. Firms with 3-9 workers were more likely to exhibit a bias than were firms with 10-24 workers and 25-49 workers. Although the calculated bias for each size category was not significant, there is sufficient evidence to warrant caution when reporting offer rates. Survey nonresponse in the EHBS produces an upward bias on estimates for the offer rates of small firms. Although not significant, this upward bias is because of nonresponse by small firms that do not offer health benefits. Our research is limited in that we only control for differences in the size of the firm.


Current evidence of SARS-CoV-2 vertical transmission: an integrative review.
To review the current scientific evidence of vertical transmission related to coronavirus disease 2019 (COVID-19). An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed) and LILACS databases, using the descriptors "pregnancy" AND "COVID-19" AND "vertical transmission". This search included case reports or case series published up until 17th June 2020 in English or Portuguese. After reading the articles available in their entirety, those related specifically to the potential risks of vertical transmission of COVID-19 during pregnancy were selected. We initially found a total of 57 articles; 26 were carefully screened and 15 were finally selected. Pregnancy can make women more susceptible to infections, especially by viral pathogens, given the various physiological and immunological changes that occur to maintain maternal-fetal balance. It is speculated that the fetus may be a possible target for COVID-19. Few studies (3 out of 15) in our analysis have found positive results for SARS-CoV-2 in fetal membranes, placenta, and in newborns right after birth. Additionally, no difference was noticed when comparing different modes of delivery, and seems reasonable to assume that pregnant women with stable clinical conditions can be encouraged for vaginal delivery. Further studies with a great number of cases are warranted to elucidate whether the virus may be vertically transmitted to the fetus and if any maternal conditions can influence that. Our findings seem to demonstrate that vertical transmission is possible but quite unusual.


Quality of life of long-term survivors of non-small-cell lung cancer.
To describe the quality of life (QOL) among survivors of non-small-cell lung cancer (NSCLC). One hundred forty-two 5-year minimum self-reported disease-free survivors of NSCLC completed QOL instruments (QOL-Survivor and Medical Outcomes Study 36-Item Short Form [SF-36]) and assessments of emotional distress (Center for Epidemiologic Studies Depression Scale [CES-D]), comorbid disease, and tobacco use. Pulmonary function was assessed with a hand-held spirometer. Multivariate regression methods were used on total QOL-Survivor scores and physical (PC) and mental (MC) component scores of the SF-36. The majority (71%) of survivors described themselves as hopeful, and 50% viewed the cancer experience as contributing to positive life changes (QOL-Survivor). Comorbidity was common (60% >or= one condition); 22% had distressed mood (CES-D >or= 16). Most were former smokers (76%); 13% continued to smoke. Half had moderate/severe pulmonary distress (forced expired volume in 1 second [FEV1] < 70% of predicted). Regression models including the set of variables (age, sex, living alone, education, smoking status, pulmonary function category, distressed mood, time since diagnosis, and comorbidity) accounted for 37%, 48%, and 29% in the QOL-total, MC, and PC scores, respectively. Primary predictors of lower QOL scores were white ethnicity and distressed mood (CES-D >or= 16) (34% of the variance explained). The primary predictor of lower MC scores was distressed mood (R(2) = 0.45). Lower PC scores were associated with older age, living alone, FEV1 less than 70% of predicted, distressed mood, time since diagnosis, and more comorbid diseases (R(2) = 0.28). These findings provide the first description of the QOL of long-term survivors of lung cancer. Risk factors for poorer QOL are strongly linked to distressed mood, which is a potential target for intervention.


Targeting the Synapse in Alzheimer's Disease.
Dynamic gain and loss of synapses is fundamental to healthy brain function. While Alzheimer's Disease (AD) treatment strategies have largely focussed on beta-amyloid and tau protein pathologies, the synapse itself may also be a critical endpoint to consider regarding disease modification. Disruption of mechanisms of neuronal plasticity, eventually resulting in a net loss of synapses, is implicated as an early pathological event in AD. Synaptic dysfunction therefore may be a final common biological mechanism linking protein pathologies to disease symptoms. This review summarizes evidence supporting the idea of early neuroplastic deficits being prevalent in AD. Changes in synaptic density can occur before overt neurodegeneration and should not be considered to uniformly decrease over the course of the disease. Instead, synaptic levels are influenced by an interplay between processes of degeneration and atrophy, and those of maintenance and compensation at regional and network levels. How these neuroplastic changes are driven by amyloid and tau pathology are varied. A mixture of direct effects of amyloid and tau on synaptic integrity, as well as indirect effects on processes such as inflammation and neuronal energetics are likely to be at play here. Focussing on the synapse and mechanisms of neuroplasticity as therapeutic opportunities in AD raises some important conceptual and strategic issues regarding translational research, and how preclinical research can inform clinical studies. Nevertheless, substrates of neuroplasticity represent an emerging complementary class of drug target that would aim to normalize synapse dynamics and restore cognitive function in the AD brain and in other neurodegenerative diseases.


Comparative Study of Confidence Intervals for Proportions in Complex Sample Surveys.
The most widespread method of computing confidence intervals (CIs) in complex surveys is to add and subtract the margin of error (MOE) from the point estimate, where the MOE is the estimated standard error multiplied by the suitable Gaussian quantile. This Wald-type interval is used by the American Community Survey (ACS), the largest US household sample survey. For inferences on small proportions with moderate sample sizes, this method often results in marked under-coverage and lower CI endpoint less than 0. We assess via simulation the coverage and width, in complex sample surveys, of seven alternatives to the Wald interval for a binomial proportion with sample size replaced by the 'effective sample size,' that is, the sample size divided by the design effect. Building on previous work by the present authors, our simulations address the impact of clustering, stratification, different stratum sampling fractions, and stratum-specific proportions. We show that all intervals undercover when there is clustering and design effects are computed from a simple design-based estimator of sampling variance. Coverage can be better calibrated for the alternatives to Wald by improving estimation of the effective sample size through superpopulation modeling. This approach is more effective in our simulations than previously proposed modifications of effective sample size. We recommend intervals of the Wilson or Bayes uniform prior form, with the Jeffreys prior interval not far behind.


Transport of cholesterol.
.ur current model for cholesterol transport is summarized in Figure 10. In this figure we have put together the various steps in cholesterol transport that were described previously in this review. Under normal conditions, cholesterol metabolism and transport are well regulated. If the transport system is overloaded for a long time, however, hypercholesterolemia caused mainly by increased plasma LDL may develop in several species, including humans. Under such circumstances reverse transport of cholesterol may also fail, giving rise to deposits of cholesterol. Tissue macrophages may be responsible for this lipid accumulation, because receptor-mediated (adsorptive) endocytosis of lipoprotein-associated cholesterol in these cells is not under negative-feedback control. The deposits are mainly found in tissues poorly supplied with blood and lymph: the skin, tendons, the cornea, and arteries. Overload of cholesterol transport may be the result of too much fat and cholesterol in the diet, giving rise to cholesterol-rich lipoproteins from the gut and to increased production of liver (formula; see text) VLDL, which in humans ends up as LDL. In many individuals, however, no hypercholesterolemia is seen, even after eating large amounts of a "western" diet for decades; others may develop increased LDL on a relatively "prudent" diet. Obviously many of the factors and mechanisms in cholesterol transport are influenced by genetic factors. Although studies of several inborn errors of lipid metabolism have given information about some mechanisms, the quantitatively more important differences in genetic patterns, which determine whether or not a western diet will result in hyperlipidemia, are not well known. Perhaps studies of different forms of apoB and apoE and of HDL subgroups and hyper-alpha-lipoproteinemia will explain why certain individuals develop hypercholesterolemia and premature atherosclerosis. All the recent information related to cholesterol metabolism and transport gives rise to new questions. There are many problems of interest for future research: What are the metabolic differences between the apoB produced in the liver and that produced in the gut? To what extent is the protein moiety of LDL modified in the plasma of blood and lymph and in interstitial tissue? Are such modifications important to whether LDL uptake goes through the classic LDL pathway or through the macrophage (i.e., scavenger?) pathway? Are some changes in apoB important for liver recognition of LDL?(ABSTRACT TRUNCATED AT 400 WORDS)


The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR.
The serine/threonine kinase ULK1 is a mammalian homolog of Atg1, part of the Atg1 kinase complex, which is the most upstream component of the core autophagy machinery conserved from yeast to mammals. In budding yeast, activity of the Atg1 kinase complex is inhibited by TORC1 (target of rapamycin complex 1), but how the counterpart ULK1 complex in mammalian cells is regulated has been unknown. Our laboratories recently discovered that AMPK associates with, and directly phosphorylates, ULK1 on several sites and this modification is required for ULK1 activation after glucose deprivation. In contrast, when nutrients are plentiful, the mTORC1 complex phosphorylates ULK1, preventing its association and activation by AMPK. These studies have revealed a molecular mechanism of ULK1 regulation by nutrient signals via the actions of AMPK and mTORC1.


Second harmonic imaging of exocytosis at fertilization.
Second harmonic generation offers an important alternative and complement to fluorescence for the imaging of cellular structure and function. Staining the eggs of the sea urchin, Lytechinus pictus, with the styryl dye di-8-ANEPPS, we have observed large changes in both second harmonic generation and two-photon fluorescence after fertilization, consistent with the dynamics of exocytosis of cortical granules. With nonlinear imaging on a scanning microscope, we are able to visualize the wave of exocytosis in real time.


Angiopoietin-1 protects 3T3-L1 preadipocytes from saturated fatty acid-induced cell death.
Cross talk between endothelial cells and adipocytes is vital to adipocyte functions, but little is known about the mechanisms or factors controlling the process. Angiogenesis is a critical component linking the endothelium to healthy adipogenesis, yet it is not known if or how it is involved in adipocyte physiology. Therefore, the purpose of this study was to determine the effect of angiopoietin-1 (Ang-1) and -2 (Ang-2) as well as their receptor, Tie-2, on adipocyte physiology. 3T3-L1 pre- and mature adipocytes were found to express Ang-1, Ang-2, and Tie-2, which decrease upon polyunsaturated fatty acid treatment. Furthermore, 3T3-L1 cells treated with recombinant Ang-1 or Ang-2 increased expression of the antiapoptotic gene Bcl-x and decreased expression of the proapoptotic gene Casp-8. Next, preadipocytes were treated with saturated fatty acids (SFAs) to induce cell stress. SFA-mediated splicing of X-box-binding protein-1 was reduced by co-treatment with Ang-1, and cell viability was improved in the presence of SFAs + Ang-1. Taken together, these results indicate that Ang-1 may protect preadipocytes from SFA-induced apoptosis and endoplasmic reticulum stress.


Evaluation of antinociceptive effect of methanolic leaf and root extracts of Clitoria ternatea Linn. in rats.
Clitoria ternatea Linn. (C. ternatea) is an Ayurvedic herb traditionally used as medicine to relieve inflammatory, rheumatism, ear diseases, fever, arthritis, eye ailments, sore throat and body ache. This study aims to evaluate and elucidate the possible mechanism underlying the antinociceptive action of methanolic extracts of C. ternatea leaf and root using several antinociception models. The different antinociception models such as hot plate, tail-flick and formalin tests were used along with naloxone (a non-selective opioid antagonist) to establish the antinociceptive activity of both leaf and root extracts. Both C. ternatea leaf and root extracts markedly demonstrated antinociceptive action in experimental animals. Results of formalin test showed that the antinociceptive activity of the extracts may be mediated at both central and peripheral level. Moreover, the results of hot plate and tail-flick tests further implies that C. ternatea root extract mediates antinociceptive activity centrally at supraspinal and spinal levels whereas, the C. ternatea leaf extract's antinociceptive activity is mediated centrally at supraspinal level only. It is believed that the opioid receptors are probably involved in antinociceptive activity of both C. ternatea root extract. Our studies support the traditional use of C. ternatea leaf and root against pain. The extracts can also be utilised as a new source of central analgesics in treatment of pain.


Carbonized Polymer Dots for Controlling Construction of MoS2 Flower-Like Nanospheres to Achieve High-Performance Li/Na Storage Devices.
Despite being one of the most promising materials in anode materials, molybdenum sulfide (MoS2 ) encounters certain obstacles, such as inadequate cycle stability, low conductivity, and unsatisfactory charge-discharge (CD) rate performance. In this study, a novel approach is employed to address the drawbacks of MoS2 . Carbon polymer dots (CPDs) are incorporated to prepare three-dimensional (3D) nanoflower-like spheres of MoS2 @CPDs through the self-assembly of MoS2 2D nanosheets, followed by annealing at 700 °C. The CPDs play a main role in the creation of the nanoflower-like spheres and also mitigate the MoS2 nanosheet limitations. The nanoflower-like spheres minimize volume changes during cycling and improve the rate performance, leading to exceptional rate performance and cycling stability in both Lithium-ion and Sodium-ion batteries (LIBs and SIBs). The optimized MoS2 @CPDs-2 electrode achieves a superb capacity of 583.4 mA h g-1 at high current density (5 A g-1 ) after 1000 cycles in LIBs, and the capacity remaining of 302.8 mA h g-1 after 500 cycles at 5 A g-1 in SIBs. Additionally, the full cell of LIBs/SIBs exhibits high capacity and good cycling stability, demonstrating its potential for practical application in fast-charging and high-energy storage.


[Special surgical treatment of patients with nodular tumors of the thyroid gland against the background of diffuse toxic goiter].
The authors have analyzed the results of treatment of 147 patients with diffuse toxic goiter (DTG) operated upon in the St. Petersburg Center of the surgery of the endocrine system organs. Questions of surgical strategy are considered when DTG is combined with nodular forms. The diagnostic potentialities of the methods used are assessed. The incidence of carcinomas in patients with nodular formations and DTG was determined. It was shown that the presence of nodules in the thyroid gland did not influence the nearest and distant results when using the corresponding surgical strategy.


Predicting biodegradation.
Biodegradation is important for natural and industrial cycling of environmental chemicals. Industries and government regulators increasingly seek to know the fate of chemicals in the environment and thus prevent potential negative impacts on human or ecosystem health. However, millions of organic compounds are known, and most will remain unstudied with respect to biodegradation. This necessitates the development of organized biodegradation information coupled with predictive methods. Biodegradation prediction methods are being developed using the information contained in the University of Minnesota Biocatalysis/ Biodegradation database. Heuristic rules are derived from compiled biodegradation information. Additional rules are generated by deconstructing compounds into a set of the 40 most common organic functional groups. The rules consist of deriving biochemically plausible catabolic reactions for each of the functional groups. More complex compounds, containing multiple functional groups, are analysed using higher order rules requiring prioritizing enzymatic attack and reactions cleaving functional groups. While biodegradation prediction, like weather prediction, will never be perfect, it can be an important tool for guiding industry, regulators and experimentalists.


Studies on recombination in heterologous crosses of Rous sarcoma virus.
Ts mutants in src from the Prague and Schmidt-Ruppin strains of Rous sarcoma virus (RSV) were used to superinfect chicken and quail cells chronically infected with the Bryan strain of RSV. No wild-type recombinants and few double-defective virions were produced. These results indicate that genetic recombination does not occur with high frequency in these heterologous crosses even if all infectious virus is derived from doubly infected cells.


The valuation of social rewards in schizophrenia.
Social impairment in schizophrenia is often thought to reflect poor social cognition. Here we examine responses to social rewards, an aspect of social functioning that is not featured prominently in the literature. The goal of this experiment was to explore whether people with schizophrenia (a) undervalue social rewards, and (b) whether the undervaluation of social rewards was related to motivation and pleasure deficits in schizophrenia and decreased social functioning. People with schizophrenia and healthy participants completed a game (Shore & Heerey, 2011) to explore preferences for different types of social (polite and genuine smiles) and nonsocial (monetary) rewards from computerized opponents. Preferences for reward types were quantified for each participant based on choice behavior during the game. Participants also completed a smile discrimination task to assess their ability to discriminate these types of smiles. Analyses revealed that people with schizophrenia (N = 41) treated genuine smiles as significantly less rewarding than did healthy participants (N = 29), despite showing a similar preference for monetary rewards. The undervaluation of social rewards was not related to the ability to discriminate between the smiles. The current findings provide preliminary evidence of reduced social reward valuation among individuals with schizophrenia, which may have implications for behavior in face-to-face social interactions. (PsycINFO Database Record


Transverse confinement of waves in three-dimensional random media.
We study the transmission of a tightly focused beam through a thick slab of three-dimensional disordered medium in the Anderson localized regime. We show that the transverse profile of the transmitted beam exhibits clear signatures of Anderson localization and that its mean square width provides a direct measure of the localization length. For a short incident pulse, the width is independent of absorption.


Elastic anisotropy and collagen orientation of osteonal bone are dependent on the mechanical strain distribution.
There is evidence that the collagen microarchitecture of bone is influenced by mechanical stresses or strains. We hypothesized that peak functional strains correlate with the elastic anisotropy and collagen orientation of bone tissue and that the bone anisotropy might be changed by altering the strain patterns in canine radii for 12 months. We tested these hypotheses in studies using nine adult foxhounds. The baseline group (n = 3) had three rosette strain gauges placed around the midshaft of the radius, and strain distributions were measured during walking. The osteotomy group (n = 3) had 2 cm of the ulna surgically removed, and the sham group (n = 3) received a sham osteotomy. The osteotomy and sham groups were allowed free movement in cages with runs for 12 months, after which strain distributions were measured on the radii during walking. Bone-tissue anisotropy and collagen architecture were measured in radii from which the in vivo longitudinal strain patterns had been measured. The collagen birefringence patterns were measured with use of a circularly polarized light technique, and the elastic anisotropy of the bone, mineral, and collagen matrix was evaluated with a novel acoustic microscopy technique. Peak longitudinal strains in the radius correlated with the normalized longitudinal structure index (a polarized light measure of collagen birefringence) and the tissue anisotropy ratio. The average anisotropy ratio was 1.28+/-0.01 in the posterior (compressive) cortex and 1.43+/-0.01 in the anterior (tensile) cortex (these values are significantly different at p < 0.0001). The ulnar osteotomy changed the strain pattern on the radius, causing increased tensile strains in the medial cortex by more than 5-fold that were associated with a significant increase in the anisotropy ratio in the bone tissue. The longitudinal structure index was strongly correlated (r = 0.62, p < 0.005) with the anisotropy ratio of demineralized bone but was not correlated with that of deproteinized bone; this indicates that it reflects collagen fibril orientation in the bone matrix. These results indicate that mechanical strains affect both collagen and mineral microarchitecture in bone tissue, i.e., tensile strains are associated with increased tissue anisotropy and compressive strains, with decreased anisotropy.


Oral cancer: FAQ.
The efficacy of clinical examination in detecting intraoral malignances has recently been called into question, as it does not accurately predict the histological diagnosis. A brief re-examination of one study provides some insights into what this means to the clinician. Making a diagnosis on the basis of a clinical examination may result in a false-positive finding and unnecessary treatment. However, a more significant concern would be a false-negative finding, in which disease is present but not detected and therefore not treated. The most effective preventive strategy is to help patients reduce or eliminate dangerous habits, and to remain alert for signs of potentially malignant or early-stage lesions, and perform routine visual and tactile examinations of all patients. A working knowledge of the clinical epidemiology of oral cancer, familiarity with the risk factors, signs and symptoms, together with continued vigilance in the form of regular, systematic and thorough clinical examination remains the most basic means of ensuring early detection of oral cancer and providing the best care possible.


Neuropilin 1: A Novel Entry Factor for SARS-CoV-2 Infection and a Potential Therapeutic Target.
The novel coronavirus disease 2019 (COVID-19) pandemic is severely challenging the healthcare systems and economies of the world, which urgently demand vaccine and therapy development to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, advancing our understanding of the comprehensive entry mechanisms of SARS-CoV-2, especially the host factors that facilitate viral infection, is crucial for the discovery of effective vaccines and antiviral drugs. SARS-CoV-2 has previously been documented to reach cells by binding with ACE2 and CD147 receptors in host cells that interact with the spike (S) protein of SARS-CoV-2. A novel entry factor, called neuropilin 1(NRP1), has recently been discovered as a co-receptor facilitating the entry of SARS-CoV-2. NRP1 is a single-pass transmembrane glycoprotein widely distributed throughout the tissues of the body and acts as a multifunctional co-receptor to bind with different ligand proteins and play diverse physiological roles as well as pathological and therapeutic roles in different clinical conditions/diseases, including COVID-19. The current review, therefore, briefly provides the overview of SARS-CoV-2 entry mechanisms, the structure of NRP1, and their roles in health and various diseases, as well as extensively discusses the current understanding of the potential implication of NRP1 in SARS-CoV-2 entry and COVID-19 treatment.


Intensity discrimination as a function of stimulus level with electric stimulation.
Difference limens (DLs) for changes in electric current were measured from multiple electrodes in each of eight cochlear-implanted subjects. Stimuli were 200-microseconds/phase biphasic pulse trains delivered at 125 Hz in 300-ms bursts. DLs were measured with an adaptive three-alternative forced-choice procedure. Fixed-level psychometric functions were also obtained in four subjects to validate the adaptive DLs. Relative intensity DLs, specified as Weber fractions in decibels [10 log (delta I/I)] for standards above absolute threshold, decreased as a power function of stimulus intensity relative to absolute threshold [delta I/I = beta (I/I0) alpha] in the same manner as Weber fractions for normal acoustic stimulation reported in previous studies. Exponents (alpha) of the power function for electric stimulation ranged from -0.4 to -3.2, on average, an order of magnitude larger than exponents for acoustic stimulation, which range from -0.07 to -0.11. Normalization of stimulus intensity to the dynamic range of hearing resulted in Weber functions with similar negative slopes for electric and acoustic stimulation, corresponding to an 8-dB average improvement in Weber fractions across the dynamic range. Sensitivity to intensity change ¿10 log beta¿ varied from -0.42 to -13.5 dB compared to +0.60 to -3.34 dB for acoustic stimulation, but on average was better with electric stimulation than with acoustic stimulation. Psychometric functions for intensity discrimination yielded Weber fractions consistent with adaptive procedures and d' was a linear function of delta I. Variability among repeated Weber-fraction estimates was constant across dynamic range. Relatively constant Weber fractions across all or part of the dynamic range, observed in some subjects, were traced to the intensity resolution limits of individual implanted receiver/stimulators. DLs could not be accurately described by constant amplitude changes, expressed as a percentage of dynamic range ¿delta A(% DR)¿. Weber fractions from prelingually deafened subjects were no better or worse than those from postlingually deafened subjects. The cumulative number of discriminable intensity steps across the dynamic range of electric hearing ranged from as few as 6.6 to as many as 45.2. Physiologic factors that may determine important features of electric intensity discrimination are discussed in the context of a simple, qualitative, rate-based model. These factors include the lack of compressive cochlear preprocessing, the relative steepness of neural rate-intensity functions, and individual differences in patterns of neural survival.


Simple technique for culture of highly differentiated cells from dog tracheal epithelium.
Cultures of dog tracheal epithelium have proved very useful in studies of ion transport. Their short-circuit current (Isc), however, is usually much less than the original tissue. We have tested a variety of conditions in an attempt to produce large numbers of cells with electrical properties comparable with the original tissue. Of several growth supports, human placental collagen (HPC) gave the best results. When plated at 2.5 x 10(5) cells/cm2 onto HPC, cells grown in serum-free, growth factor-supplemented medium (GF medium) showed increases in cells per unit area, thickness of cell sheet, numbers of domes, numbers of apical microvilli, and degree of basolateral membrane interdigitation compared with cells grown in medium containing 5% fetal calf serum (FCS medium). Transepithelial resistance (Rte) and the increases in Isc and intracellular Ca in response to isoproterenol were also increased. However, baseline Isc and adenosine 3',5'-cyclic monophosphate levels were not changed. The improved electrical properties were maintained for up to 4 mo. GF medium combined with an air interface produced further increases in Rte, Isc, and changes in Isc in response to amiloride and isoproterenol. Ultrastructural features such as the presence of cilia, greater thickness of the cell sheet, and increased amplification of apical and basolateral membranes also indicated improved differentiation. Our results show that GF medium and an air interface can be combined with a simple growth support and a relatively low-plating density to allow the easy production of greater than 500 cm2 of cultured cells from a single trachea, with a level of differentiation similar to that of the original tissue.


Family supportive supervisor behaviors and organizational culture: Effects on work engagement and performance.
Informed by social information processing (SIP) theory, in this study, we assessed the associations among family supportive supervisor behaviors (FSSBs) as perceived by subordinates, subordinate work engagement, and supervisor-rated work performance. Moreover, we explored the role of family supportive organizational culture as a contextual variable influencing our proposed associations. Our findings using matched supervisor-subordinate data collected from a financial credit company in Mexico (654 subordinates; 134 supervisors) showed that FSSBs influenced work performance through subordinate work engagement. Moreover, the positive association between subordinates' perceptions of FSSBs and work engagement was moderated by family supportive organizational culture. Our results contribute to emerging theories on flexible work arrangements, particularly on family supportive work policies. Moreover, our findings carry practical implications for improving employee work engagement and work performance. (PsycINFO Database Record


Pesticide and trace metal occurrence and aquatic benchmark exceedances in surface waters and sediments of urban wetlands and retention ponds in Melbourne, Australia.
Samples of water and sediments were collected from 24 urban wetlands in Melbourne, Australia, in April 2010, and tested for more than 90 pesticides using a range of gas chromatographic (GC) and liquid chromatographic (LC) techniques, sample 'hormonal' activity using yeast-based recombinant receptor-reporter gene bioassays, and trace metals using spectroscopic techniques. At the time of sampling, there was almost no estrogenic activity in the water column. Twenty-three different pesticide residues were observed in one or more water samples from the 24 wetlands; chemicals observed at more than 40% of sites were simazine (100%), atrazine (79%), and metalaxyl and terbutryn (46%). Using the toxicity unit (TU) concept, less than 15% of the detected pesticides were considered to pose an individual, short-term risk to fish or zooplankton in the ponds and wetlands. However, one pesticide (fenvalerate) may have posed a possible short-term risk to fish (log10TUf > -3), and three pesticides (azoxystrobin, fenamiphos and fenvalerate) may have posed a risk to zooplankton (logTUzp between -2 and -3); all the photosystem II (PSII) inhibiting herbicides may have posed a risk to primary producers in the ponds and wetlands (log10TUap and/or log10TUalg > -3). The wetland sediments were contaminated with 16 different pesticides; no chemicals were observed at more than one third of sites, but based on frequency of detection and concentrations, bifenthrin (33%, maximum 59 μg/kg) is the priority insecticide of concern for the sediments studied. Five sites returned a TU greater than the possible effect threshold (i.e. log10TU > 1) as a result of bifenthrin contamination of their sediments. Most sediments did not exceed Australian sediment quality guideline levels for trace metals. However, more than half of the sites had threshold effect concentration quotients (TECQ) values >1 for Cu (58%), Pb (50%), Ni (67%) and Zn (63%), and 75% of sites had mean probable effect concentration quotients (PECQ) >0.2, suggesting that the collected sediments may have been having some impact on sediment-dwelling organisms.


Brevetoxins, unique activators of voltage-sensitive sodium channels, bind to specific sites in rat brain synaptosomes.
The polyether lipid-soluble toxins isolated from the marine dinoflagellate Ptychodiscus brevis (formerly Gymnodinium breve) have been determined to bind to a unique site associated with rat brain synaptosomes. Using [3H]brevetoxin PbTx-3 as a specific probe, binding was determined at 4 degrees in rat brain synaptosomes using a rapid centrifugation technique. Rosenthal analysis yields a KD of 2.9 nM and a Bmax of 6.8 pmol of toxin/mg of protein. Labeled probe can be displaced by unlabeled PbTx-3, PbTx-2, or synthetic PbTx-3 (reduced PbTx-2) but not by a nontoxic, synthetic oxidized derivative of PbTx-2. Competition experiments using natural toxin probes specific for sites 1-4 of the voltage-dependent sodium channel have illustrated that PbTx-3 does not bind to any of the previously described sites associated with the channel. A fifth site is proposed. In addition, because of the varied nomenclature associated with the brevetoxins, a new classification system is proposed.


Scattering matrix elements of fractal-like soot agglomerates.
The possibility of measuring scattering-matrix (Mueller matrix) elements of soot agglomerates with laser diagnostic techniques is explored. To show this, we calculated the scattering-matrix elements of arbitrary-shaped soot agglomerates. The sensitivity of scattering-matrix elements to optical and morphological characteristics of fractal-like soot agglomerates is discussed. Finally, possible measurement techniques are suggested to identify soot structures from scattering-matrix elements.


Identification of mutations in circulating cell-free tumour DNA as a biomarker in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is increasing globally. Prognostic biomarkers are urgently needed to guide treatment and reduce mortality. Tumour-derived circulating cell-free DNA (ctDNA) is a novel, minimally invasive means of determining genetic alterations in cancer. We evaluate the accuracy of ctDNA as a biomarker in HCC. Plasma cell-free DNA, matched germline DNA and HCC tissue DNA were isolated from patients with HCC (n = 51) and liver cirrhosis (n = 10). Targeted, multiplex polymerase chain reaction ultra-deep sequencing was performed using a liver cancer-specific primer panel for genes ARID1A, ARID2, AXIN1, ATM, CTNNB1, HNF1A and TP53. Concordance of mutations in plasma ctDNA and HCC tissue DNA was determined, and associations with clinical outcomes were analysed. Plasma cell-free DNA was detected in all samples. Lower plasma cell-free DNA levels were seen in Barcelona Clinic Liver Cancer (BCLC A compared with BCLC stage B/C/D (median concentration 122.89 ng/mL versus 168.21 ng/mL, p = 0.041). 29 mutations in the eight genes (21 unique mutations) were detected in 18/51 patients (35%), median 1.5 mutations per patient (interquartile range 1-2). Mutations were most frequently detected in ARID1A (11.7%), followed by CTNNB1 (7.8%) and TP53 (7.8%). In patients with matched tissue DNA, all mutations detected in plasma ctDNA detected were confirmed in HCC DNA; however, 71% of patients had mutations identified in HCC tissue DNA that were not detected in matched ctDNA. ctDNA is quantifiable across all HCC stages and allows detection of mutations in key driver genes of hepatic carcinogenesis. This study demonstrates high specificity but low sensitivity of plasma ctDNA for detecting mutations in matched HCC tissue.