HIV-related needs for safety among male-to-female transsexuals (mak nyah) in Malaysia.
This research, commissioned by the Malaysian AIDS Council in 2007, is qualitative and descriptive in nature. In depth face-to-face interviews were carried out with 15 mak nyah respondents from five major towns. The interviews were guided by an interview schedule that had seven main topics: brief background; hormone-taking behaviour; safe sex; health care; substance abuse; harassment from authorities; and HIV prevention. The HIV problem among the mak nyah, mak nyah sex workers and their clients is critical. Many do not have in-depth HIV/AIDS knowledge and do not practise safe sex. The problem gets worse when most mak nyah do not consider HIV/AIDS as a primary concern because of other pressing problems like employment and discrimination. There are also no HIV prevention activities in many parts of Malaysia. Mak nyah also face constant harassment from enforcement authorities for prostitution. This hampers HIV prevention work.


Access to a scale and self-weighing habits among public housing residents.
Having access to a scale is essential for individuals to engage in self-weighing; however, few studies examine scale access, particularly among low-income individuals. Our objectives were to (i) determine how many public housing residents have access to a scale and (ii) describe their self-weighing habits. We conducted a cross-sectional survey of public housing residents in Baltimore, MD, from August 2014 to August 2015. Participants answered questions about their access to a scale ('yes'/'no') and daily self-weighing habits ('no scale/never or hardly ever' vs. 'some/about half/much of the time/always'). We used t-tests or chi-square tests to examine the association of scale access with respondent characteristics. Overall, 266 adults participated (48% response rate). Mean age was 45 years with 86% women, 95% black and 54% with obesity. Only 32% had access to a scale; however, 78% of those with this access reported engaging in some self-weighing. Residents who lacked access to a scale were younger (P = 0.03), and more likely to be unemployed/disabled (P = 0.01) or food insecure (P < 0.01). While few public housing residents have access to a scale, those who do report daily self-weighing with some regularity. Financial hardship may influence scale access in this population, as potential proxies of this status were associated with no scale access.


[Metabolite changes in the greasy tongue coating of patients with chronic gastritis].
To explore the changes in metabolites in the greasy tongue coating in patients with chronic gastritis. Forty chronic gastritis patients presenting with greasy tongue coating, 30 chronic gastritis patients presenting with non-greasy tongue coating, and 20 healthy control persons presenting with light red tongues and thin white coating were enrolled, and the tongue coating was detected by combining artificial diagnosis and the Z-BOX Tongue Digital Analyzer's diagnosis. Samples of all the tongue coatings were collected before treatment. The metabolic fingerprinting of the tongue coating samples was obtained using ultra-performance liquid chromatography and mass spectrometry (UPLC-MS), and the metabolic components in the tongue coating samples were detected. After this, principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to identify potential metabolic markers. Finally, the components were identified using the Chemspider and HMDB searching. UPLC-MS results were analyzed by OPLS-DA and showed that the metabolites among the three groups were distributed in different regions. The different potential metabolic markers between the patients with or without greasy coating were 3-ketolactose, 2-deoxy-D-ribose, UDP-D-galactose metarhodopsin, ascorbate, picolinate and histidine. The different potential metabolic markers between the greasy coating group and the normal group were 3-ketolactose, UDP-D-galactose, leukotriene A4 and vitamin D(2). The metabolites of the greasy coating group, the non-greasy coating group and the normal group show significant differences in energy metabolism, mainly of glucose metabolism. This demonstrated that glucose metabolism may be one of the mechanisms leading to the formation of greasy coating.


In the real world, people prefer their last whisky when tasting options in a long sequence.
When people in laboratory studies sample products in a sequence, they tend to prefer options presented first and last. To what extent do these primacy and recency effects carry over to real-world settings where numerous sources of information determine preferences? To investigate this question, we coded archival data from 136 actual whisky tastings each featuring seven whiskies. We analyzed people's ratings of whiskies featured at different serial positions in the tastings. We found a recency effect: people gave their highest rating to whiskies in the last position, and voted the last whisky as their favorite more frequently. This recency effect persisted when we controlled for the counter explanation that whiskies with higher alcohol content tended to occupy later serial positions. The recency effect also persisted when we controlled for the age of the whiskies. Taken together, our findings suggest that the order of presentation matters in real-world settings, closely resembling what happens in laboratory settings with longer sequences of options.


Transcriptional profiling of cork oak phellogenic cells isolated by laser microdissection.
The phenylpropanoid pathway impacts the cork quality development. In cork of bad quality, the flavonoid route is favored, whereas in good quality, cork lignin and suberin production prevails. Cork oaks develop a thick cork tissue as a protective shield that results of the continuous activity of a secondary meristem, the cork cambium, or phellogen. Most studies applied to developmental processes do not consider the cell types from which the samples were extracted. Here, laser microdissection (LM) coupled with transcript profiling using RNA sequencing (454 pyrosequencing) was applied to phellogen cells of trees producing low- and good quality cork. Functional annotation and functional enrichment analyses showed that stress-related genes are enriched in samples extracted from trees producing good quality cork (GQC). This process is under tight transcriptional (transcription factors, kinases) regulation and also hormonal control involving ABA, ethylene, and auxins. The phellogen cells collected from trees producing bad quality cork (BQC) show a consistent up-regulation of genes belonging to the flavonoid pathway as a response to stress. They also display a different modulation of cell wall genes resulting into a thinner cork layer, i.e., less meristematic activity. Based on the analysis of the phenylpropanoid pathway regulating genes, in GQC, the synthesis of lignin and suberin is promoted, whereas in BQC, the same pathway favors the biosynthesis of free phenolic compounds. This study provided new insights of how cell-specific gene expression can determine tissue and organ morphology and physiology and identified robust candidate genes that can be used in breeding programs aiming at improving cork quality.


Stress levels and health status of victims of a natural disaster.
Bereaved, property loss, and control groups (N = 155) were compared 11 months after the volcanic eruption of Mt. St. Helens using standardized instruments and structured interviews. It was hypothesized that the greater the loss the greater the stress and the poorer the health. Bereaved subjects reported significantly higher levels of stress and lower levels of mental health, but not physical health. Persons who lost their permanent homes reported high rates of stress, but did not report significantly higher levels of depression, somatization, or poorer physical health. Conceptual and methodological implications are discussed.


Low-grade sarcoma in classical seminoma - the first case reported.
A 30-year-old male with no previous history of neoplastic disease presented with a 5 cm large testicular tumor. Routine histopathological examination and immunohistochemical investigation showed a classical seminoma with a contiguous 8 mm large nodule. The nodule was separated from the tunica albuginea by tubuli seminiferi showing intratesticular germ cell neoplasi not otherwise specified (NOS). The nodule was composed of spindle cells with low-grade nuclear atypia, nuclear and cytoplasmic S100 protein immunoreactivity in 15% of the cells and a proliferative activity of up to 20%. No other germ cell tumor components were found. To the best of our knowledge, we herein present the first tumor of a pure classical seminoma with an associated low-grade sarcomatous component.


MicroRNA 335 is required for differentiation of malignant glioma cells induced by activation of cAMP/protein kinase A pathway.
Glioma is the most common malignant cancer affecting the central nerve system, with dismal prognosis. Differentiation-inducing therapy is a novel strategy that has been preliminarily proved effective against malignant glioma. We have reported previously that activation of cAMP/protein kinase A (PKA) pathway is capable of inducing glioma cell differentiation, characterized by astrocyte-like shape and dramatic induction of astrocyte biomarker glial fibrillary acidic protein (GFAP). However, little progress has been made on molecular mechanisms related. Here we demonstrate that microRNA 335 (miR-335) is responsible for the glioma cell differentiation stimulated by activation of cAMP/PKA pathway. In the cAMP elevator cholera toxin-induced differentiation model of rat C6 glioma cells, miR-335 was significantly up-regulated, which was mimicked by other typical cAMP/PKA pathway activators (e.g., forskolin, dibutyryl-cAMP) and abolished by PKA-specific inhibitor (9R,10S,12S)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i] [1,6]benzodiazocine-10-carboxylic acid, hexyl ester (KT5720). In an assay measuring gain and loss of miR-335 function, exogenetic miR-335 resulted in induction of GFAP, whereas miR-335 specific inhibitor antagomir-335 violently blocked cholera toxin-induced GFAP up-regulation. It is noteworthy that in human U87-MG glioma cells and human primary culture glioma cells, miR-335 also mediated cholera toxin-induced differentiation. Taken together, our findings suggest that miR-335 is potently required for differentiation of malignant glioma cells induced by cAMP/PKA pathway activation, and a single microRNA may act as an important fate determinant to control the differentiation status of malignant gliomas, which has provided a new insight into differentiation-inducing therapy against malignant gliomas.


Alcohol consumption and blood pressure: survey of the relationship at a health-screening clinic.
We studied the association between stated alcohol consumption and blood pressure, making allowance for age, adiposity and smoking in 13535 men and 7385 women who were not receiving antihypertensive treatment. They represented a wide cross-section of the inner Sydney working population with 95% aged between 18 and 70. We found a high degree of linear correlation between stated alcohol consumption and blood pressure, diastolic and systolic. This relationship was independent of age, adiposity and smoking. For each 100 g/week increase in stated alcohol consumption, diastolic blood pressure increased by 0.12 kPa (0.92 mmHg) in men and by 0.20 kPa (1.5 mmHg) in women; no threshold for this effect was evident. A plateau appeared at about 500 g/week. Blood pressure increased significantly with age and adiposity (Quetelet's index). Smoking was associated with a lower diastolic blood pressure. The difference in mean diastolic blood pressure between smokers and non-smokers was 0.20 kPa (1.5 mmHg) for men and 0.27 kPa (2.1 mmHg) for women.


Using a simulation centre to evaluate preliminary acceptability and impact of an artificial intelligence-powered clinical decision support system for depression treatment on the physician-patient interaction.
Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction. Aifred is an artificial intelligence-powered clinical decision support system (CDSS) for the treatment of major depression. Here, we explore the use of a simulation centre environment in evaluating the usability of Aifred, particularly its impact on the physician-patient interaction. Twenty psychiatry and family medicine attending staff and residents were recruited to complete a 2.5-h study at a clinical interaction simulation centre with standardised patients. Each physician had the option of using the CDSS to inform their treatment choice in three 10-min clinical scenarios with standardised patients portraying mild, moderate and severe episodes of major depression. Feasibility and acceptability data were collected through self-report questionnaires, scenario observations, interviews and standardised patient feedback. All 20 participants completed the study. Initial results indicate that the tool was acceptable to clinicians and feasible for use during clinical encounters. Clinicians indicated a willingness to use the tool in real clinical practice, a significant degree of trust in the system's predictions to assist with treatment selection, and reported that the tool helped increase patient understanding of and trust in treatment. The simulation environment allowed for the evaluation of the tool's impact on the physician-patient interaction. The simulation centre allowed for direct observations of clinician use and impact of the tool on the clinician-patient interaction before clinical studies. It may therefore offer a useful and important environment in the early testing of new technological tools. The present results will inform further tool development and clinician training materials.


Rotavirus nonstructural glycoprotein NSP4 alters plasma membrane permeability in mammalian cells.
The endoplasmic reticulum-localized transmembrane glycoprotein NSP4 of rotavirus is a key protein involved in rotavirus cytopathology. We have used a dual-recombinant vaccinia virus system to express NSP4 in monkey kidney epithelial cells at a level comparable to that observed during rotavirus infection. Expression of NSP4 results in loss of plasma membrane integrity, which can be demonstrated by release of both 51Cr and lactate dehydrogenase into the medium. The cytotoxic behavior of NSP4 is dose dependent, and morphological analysis reveals gross changes to cell ultrastructure, indicative of cell death. Thus, intracellular expression of a single rotavirus protein which localizes to the endoplasmic reticulum membrane has profound effects on the stability of the plasma membrane and cell viability. Analysis of NSP4 deletion mutants indicates that a membrane-proximal region located within the cytoplasmic domain may mediate cytotoxicity.


Mutual information does not detect growing correlations in the propensity of a model molecular liquid.
The dynamical spatial correlations detected by the mutual information (MI) in the isoconfigurational particle displacements of a monodisperse molecular viscous liquid are studied via molecular-dynamics simulations by changing considerably both the molecular mobility and the degree of dynamical heterogeneity. Different from atomic liquids, the MI correlation length does not grow on approaching the glass transition by considering the liquid both in full detail as a collection of monomers and as a coarse-grained ensemble of molecular centers of mass. In the detailed picture, it is found that: (i) the MI correlations between monomers are largely due to inter-molecular correlations, (ii) the MI length scale is numerically identical, within the errors, to the correlation length scale of the displacement direction, as drawn by conventional correlation functions. The time evolution of the MI spatial correlations complies with the scaling between the fast vibrational dynamics and the long-time relaxation. Our findings suggest that the characteristics of the MI length scale are markedly system-dependent and not obviously related to dynamical heterogeneity.


Human health risk assessment of exposure to indoor mercury vapour in a Ghanaian artisanal small-scale gold mining community.
People living or working in and around artisanal small-scale gold mining communities can be exposed to mercury vapour, which may negatively affect their health. In this study, the human exposure to air borne mercury in an artisanal mining community in the Upper East region of Ghana was investigated using Lumex RA 915 M mercury analyser, an active sampler. The concentration of mercury in air was measured inside and outside households and was related to human health risk standards. For each household, one measurement was taken from outside and three from inside at different positions. About 91% of the households where amalgam burning was reported had concentrations higher than the USEPA reference dose of 300 ng m-3 whereas 64% of the households where amalgam burning was not reported exceeded the reference dose above. The maximal (upper) instrumental limit (50,000 ng m-3) was passed for the highest concentrations, so, the upper 97.5% concentration was estimated, using censored statistics, to exceed 800,000 ng m-3 for the fireplaces. This exceeds any reported indoor household air concentration of Hg, identified by the literature review in this paper. Estimated hazard quotients were found to range from <1 to 108 within the households that are reported not to burn amalgam. In the households where amalgam burning reportedly takes place, the hazard quotient had a range of 0.01-160. Mercury concentrations measured in households with reported amalgam burning are approximately ten times higher than those households with no reported burning of amalgam. The censored data predicted hazard quotients up to 966. The results indicate that both miners and non-miners of the community are at risk of adverse health effects resulting from inhalation of mercury vapour.


The ethical, social, and cultural dimensions of screening for mental health in children and adolescents of the developing world.
Despite their burden and high prevalence, mental health disorders of children and adolescents remain neglected in many parts of the world. In developing countries, where half of the population is younger than 18 years old, one of every five children and adolescents is estimated to suffer from a mental health disorder. It is then essential to detect these conditions through screening in a timely and accurate manner. But such screening is fraught with considerable ethical, social, and cultural challenges. This study systematically identifies, for the first time, these challenges, along with potential solutions to address them. We report on the results of an international multi- and inter-disciplinary three-round Delphi survey completed by 135 mental health experts from 37 countries. We asked these experts to identify and rank the main ethical, social, and cultural challenges of screening for child and adolescent mental health problems in developing nations, and to propose solutions for each challenge. Thirty-nine significant challenges emerged around eight themes, along with 32 potential solutions organized into seven themes. There was a high degree of consensus among the experts, but a few interesting disagreements arose between members of the panel from high-income countries and those from low- and middle-income nations. The panelists overwhelmingly supported mental health screening for children and adolescents. They recommended ensuring local acceptance and support for screening prior to program initiation, along with careful and comprehensive protection of human rights; integrating screening procedures into primary care; designing and implementing culturally appropriate screening tools, programs, and follow-up; securing long-term funding; expanding capacity building; and task-shifting screening to local non-specialists. These recommendations can serve as a guide for policy and decision-making, resource allocation, and international cooperation. They also offer a novel approach to reduce the burden of these disorders by encouraging their timely and context-sensitive prevention and management.


Ectopic Cervical Thymoma in a Patient Diagnosed with Graves Disease: A Systematic Literature Review.
Thymomas are benign thymic epithelial neoplasms, rarely found outside the anterior mediastinum. Although hyperthyroid states have been associated with thymic hyperplasia, only 3 thymoma cases have been previously reported in patients with Graves Disease (GD), all within the anterior mediastinum. Here, we report a case of ectopic cervical thymoma in a 22-year-old female patient previously treated for GD. The patient underwent ultrasonography, computed tomography, inconclusive fine-needle aspiration, and ultimately gross dissection for diagnostic workup and definitive treatment of an anterior neck mass, producing a 2.5 x 2.3 x 1.5 cm entity consistent with Masaoka stage I and Type B2 thymoma per WHO classification. The patient underwent an uncomplicated subsequent clinical course, with no adjuvant radiotherapy administered. After conducting a systematic literature review, we conclude that of the 109 cases of ectopic cervical thymoma reported, this is the first to describe a case of ectopic cervical thymoma in a patient with a past medical history of GD. For GD patients in stable euthyroid remission with the persistent or recurrent presence of an anterior neck mass, the extrathyroidal origin of the mass should always be considered, including the exceptional presence of a cervical ectopic thymoma.


Immunogenicity and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine as a single-dose booster in Singaporean adults.
Older children and adults, susceptible to pertussis because of waning immunity, may serve as a reservoir of infection, leading to severe disease among young unvaccinated infants. Booster diphtheria-tetanus-acellular pertussis (dTpa) vaccination in older age groups is rare in Singapore, one reason being the increase in reactogenicity with each successive dose. The aim of this study was to assess the immunogenicity, safety and reactogenicity of a reduced antigen, combined dTpa vaccine as a single booster dose in healthy adults aged 18 years or older. A total of 150 healthy adults, 18 to 60 years of age, received a single dose of GlaxoSmithKline Biologicals' dTpa vaccine with reduced content for diphtheria and pertussis, with measurement of pre- and post-vaccination antibody titres. Prior to vaccination, 71.6 percent and 92.6 percent of the subjects had anti-diphtheria and anti-tetanus antibody levels greater than or equal to 0.1 IU/mL, respectively. 46.7 percent, 98.5 percent and 44.4 percent of subjects were seropositive for pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) antibodies, respectively. One month after vaccination, there was an increase in geometric mean titres from pre-vaccination to post-vaccination blood samples for anti-diphtheria (greater than seven-fold), anti-tetanus (greater than five-fold), anti-PT (greater than 11-fold), anti- FHA (greater than 25-fold) and anti-PRN (greater than 31-fold) antibodies. Solicited grade three local symptoms (pain, redness and swelling) were reported in 14.1 percent, 8.1 percent and 10.4 percent of subjects, respectively. No serious adverse events were reported. In summary, the dTpa vaccine is immunogenic, safe and well-tolerated in Singaporean adults.


HARE: Unifying the Human Activity Recognition Engineering Workflow.
Sensor-based human activity recognition is becoming ever more prevalent. The increasing importance of distinguishing human movements, particularly in healthcare, coincides with the advent of increasingly compact sensors. A complex sequence of individual steps currently characterizes the activity recognition pipeline. It involves separate data collection, preparation, and processing steps, resulting in a heterogeneous and fragmented process. To address these challenges, we present a comprehensive framework, HARE, which seamlessly integrates all necessary steps. HARE offers synchronized data collection and labeling, integrated pose estimation for data anonymization, a multimodal classification approach, and a novel method for determining optimal sensor placement to enhance classification results. Additionally, our framework incorporates real-time activity recognition with on-device model adaptation capabilities. To validate the effectiveness of our framework, we conducted extensive evaluations using diverse datasets, including our own collected dataset focusing on nursing activities. Our results show that HARE's multimodal and on-device trained model outperforms conventional single-modal and offline variants. Furthermore, our vision-based approach for optimal sensor placement yields comparable results to the trained model. Our work advances the field of sensor-based human activity recognition by introducing a comprehensive framework that streamlines data collection and classification while offering a novel method for determining optimal sensor placement.


Risk Factors in Children Older Than 5 Years With Pneumococcal Meningitis: Data From a National Network.
The occurrence of meningitis in children >5 years old may be associated with specific predisposing factors that can be anatomic, such as cerebrospinal fluid fistula or breach, or related to genetic susceptibility or N inborn or acquired immunologic defect. This study aimed to assess the anatomical and immunologic risk factors in children >5 years old with pneumococcal meningitis and prospectively enrolled in the French national meningitis network. We analyzed all data for children who were 5-15 years old with a diagnosis of pneumococcal meningitis between 2001 and 2013. We describe the frequency and typology of the anatomic or immunologic risk factors, the clinical features and the pneumococcal serotypes. Among the 316 patients with pneumococcal meningitis, the mortality rate was 9.5% and 23.1% of cases presented complications (abscess, coma, hemodynamic failure, thrombophlebitis cerebral or deafness). In total, 108 children (34%) showed risk factors, the most frequent being anatomic: 70 cases (22.8%) were related to a cerebrospinal fluid breach or fistula and 55 (17.9%) to immunodeficiency, primary or acquired. Serotype data were available for 207 pneumococcal isolates (65.5%). The most frequent serotypes were as follows: 3, 18C, 19A and 19F between 2001 and 2009 and 19F, 3, 19A, 12F, 22F, 17F and 24F after 2009. We describe the largest cohort of children >5 years old with pneumococcal meningitis. One third of the children had risk factors justifying a complete immunologic and radiologic work-up.


Processing of chromogranin A by plasmin provides a novel mechanism for regulating catecholamine secretion.
Chromogranin A (CgA) is the major soluble protein in the core of catecholamine-storage vesicles and is also distributed widely in secretory vesicles throughout the neuroendocrine system. CgA contains the sequences for peptides that modulate catecholamine release, but the proteases responsible for the release of these bioactive peptides from CgA have not been established. We show here that the major fibrinolytic enzyme, plasmin, can cleave CgA to form a series of large fragments as well as small trichloroacetic acid-soluble peptides. Peptides generated by plasmin-mediated cleavage of CgA significantly inhibited nicotinic cholinergic stimulation of catecholamine release from PC12 cells and primary bovine adrenal chromaffin cells. We also show that the zymogen, plasminogen, as well as tissue plasminogen activator bind saturably and with high capacity to catecholaminergic (PC12) cells. Occupancy of cell surface binding sites promoted the cleavage of CgA by plasmin. Positive and negative modulation of the local cellular fibrinolytic system resulted in substantial alterations in catecholamine release. These results suggest that catecholaminergic cells express binding sites that localize fibrinolytic molecules on their surfaces to promote plasminogen activation and proteolytic processing of CgA in the environment into which CgA is secreted to generate peptides which may regulate neuroendocrine secretion. Interactions between CgA and plasmin(ogen) define a previously unrecognized autocrine/paracrine system that may have a dramatic impact upon catecholamine secretion.


In vivo assessment of chronological ageing and photoageing in forearm skin using reflectance confocal microscopy.
Skin ageing is a complex process due to intrinsic chronological factors (chronoageing) and extrinsic environmental factors. The primary extrinsic factor is cumulative ultraviolet (UV) exposure, and is therefore termed photoageing. The current standards for measuring cumulative sun damage are biopsy histology and skin microtopography. However, skin biopsies are too invasive for population studies and skin replicas render only superficial skin architecture data. Reflectance confocal microscopy (RCM) is a noninvasive imaging tool that allows for in vivo imaging of the skin at quasihistological resolution. To define and identify RCM features associated with chronological ageing and photoageing on the forearm in two age groups with different skin phototypes and to assess whether these results agree with previous findings. We obtained RCM images of dorsal and volar nonlesional skin of the lower forearm of 75 individuals with skin Fitzpatrick phototypes I-III in two age groups (20-30 years and 50-60 years). From each participant and body site, 21 RCM features were assessed and statistically significant differences between the two age groups and different forearm sites determined. RCM enabled identification of changes in architecture, cell morphology and extracellular matrix (collagen) at the level of the epidermis, dermoepidermal junction and papillary dermis. Changes that were correlated with chronological ageing and which were aggravated on the UV-exposed dorsal forearm were: loss of small skin furrows resulting in wider and less intersecting furrows; irregularity of the epidermal honeycomb pattern; irregularly distributed (mottled) pigmented keratinocytes/melanocytes; irregularity of the papillary rings and/or effacement of the rete ridges; and loss of thin collagen fibres and presence of collagen clods. We have tested previously reported and new parameters for skin ageing evaluation by RCM, and identified 15 statistically significant RCM features that can be used to quantify ageing and photoageing in forearm skin noninvasively.


The structure-specific nicking of small heteroduplexes by the RAG complex: implications for lymphoid chromosomal translocations.
During V(D)J recombination, the RAG complex binds at recombination signal sequences and creates double-strand breaks. In addition to this sequence-specific recognition of the RSS, the RAG complex has been shown to be a structure-specific nuclease, cleaving 3' overhangs and 3' flaps, and, more recently, 10 nucleotides (nt) bubble (heteroduplex) structures. Here, we assess the smallest size heteroduplex that core and full-length RAGs can cleave. We also test whether bubbles adjacent to a partial RSS are nicked any differently or any more efficiently than bubbles that are surrounded by random sequence. These points are important in considering what types and what size of non-B DNA structure that the RAG complex can nick, and this helps assess the role of the RAG complex in mediating lymphoid chromosomal translocations. We find that the smallest bubble nicked by the RAG complex is 3nt, and proximity to a partial or full RSS sequence does not affect the nicking by RAGs. RAG nicking efficiency increases with the size of the heteroduplex and is only about two-fold less efficient than an RSS when the bubble is 6nt. We consider these findings in the context of RAG nicking at non-B DNA structures in lymphoid chromosomal translocations.


Delay-period activity in visual, visuomovement, and movement neurons in the frontal eye field.
In the present study, we examined the role of frontal eye field neurons in the maintenance of spatial information in a delayed-saccade paradigm. We found that visual, visuomovement, and movement neurons conveyed roughly equal amounts of spatial information during the delay period. Although there was significant delay-period activity in individual movement neurons, there was no significant delay-period activity in the averaged population of movement neurons. These contradictory results were reconciled by the finding that the population of movement neurons with memory activity consisted of two subclasses of neurons, the combination of which resulted in the cancellation of delay-period activity in the population of movement neurons. One subclass consisted of neurons with significantly greater delay activity in the preferred than in the null direction ("canonical"), whereas the other subclass consisted of neurons with significantly greater delay activity in the null direction than in the preferred direction ("paradoxical"). Preferred direction was defined by the saccade direction that evoked the greatest movement-related activity. Interestingly, the peak saccade-related activity of canonical neurons occurred before the onset of the saccade, whereas the peak saccade-related activity of paradoxical neurons occurred after the onset of the saccade. This suggests that the former, but not the latter, are directly involved in triggering saccades. We speculate that paradoxical neurons provide a mechanism by which spatial information can be maintained in a saccade-generating circuit without prematurely triggering a saccade.


[Characteristics of sepsis in burn patients today].
An analysis of lethal outcomes following thermal traumas during the recent 8 years has shown sepsis to occupy one of the leading places as a cause of death of burned people. During the recent years the incidence of early sepsis has been increased. This kind of sepsis develops in the period of shock and acute toxemia, is often of lightening character, possesses certain specific morphological features and is caused predominantly by gram-negative flora threatening to patients with critical burns of more than 40% of the body surface.


Multiresponsive and biocompatible self-healing hydrogel: its facile synthesis in water, characterization and properties.
Multiresponsive and biocompatible self-healing ε-PL/A-Pul/BPEI hydrogels were prepared in aqueous solution by Schiff base reaction with aldehyded pullulan (A-Pul), ε-poly-l-lysine (ε-PL) and branched polyethyleneimine (BPEI) as materials. The imine bonds were rapidly cross-linked into a hydrogel network within 80 s. Scanning electron microscopy images showed that the hydrogels exhibited a cross-linked structure with the average pore size from 58 to 82 μm. Rheology tests indicated that the hydrogels maintained good mechanical properties. Water contact angles and swelling studies suggested that the hydrogels could swell in water, with a max swell ratio of 1559%, and pH and temperature had an influence on the equilibrium swelling ratio. The hydrogels could be injected either before or after gelation, and they displayed a self-healing process in ddH2O at room temperature based on the dynamic uncoupling and recoupling of the imine bonds. The MTT assays implied that the hydrogels were non-cytotoxic on mice bone marrow mesenchymal stem cells. Therefore, the hydrogels showed potential application in biomedical fields, and consequently further work was performed using the self-healing hydrogels as drug carriers in in vitro/vivo antitumor studies.


Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the "Flip-Flop" phenomenon).
Atopic dermatitis (AD) and psoriasis vulgaris (PV) are almost mutually exclusive diseases with different immune polarizations, mechanisms and therapeutic targets. Switches to the other disease ("Flip-Flop" [FF] phenomenon) can occur with or without systemic treatment and are often referred to as paradoxical reactions under biological therapy. The objective was to develop a diagnostic algorithm by combining clinical criteria of AD and PV to identify FF patients. The algorithm was prospectively validated in patients enrolled in the CK-CARE registry in Bonn, Germany. Afterward, algorithm refinements were implemented based on machine learning. Three hundred adult Caucasian patients were included in the validation study (n = 238 with AD, n = 49 with PV, n = 13 with FF; mean age 41.2 years; n = 161 [53.7%] female). The total FF scores of the PV and AD groups differed significantly from the FF group in the validation data (p < .001). The predictive mean generalized Youden-Index of the initial model was 78.9% [95% confidence interval 72.0%-85.6%] and the accuracy was 89.7%. Disease group-specific sensitivity was 100% (FF), 95.0% (AD), and 61.2% (PV). The specificity was 89.2% (FF), 100% (AD), and 100% (PV), respectively. The FF algorithm represents the first validated tool to identify FF patients.


Oxygen plus pressure plus time: the etiology of bronchopulmonary dysplasia.
Ten infants developed the chronic pulmonary syndrome designated bronchopulmonary dysplasia, following artificial (assisted) ventilation using a volume-regulated positive-pressure respirator. Despite previous reports implicating elevated oxygen concentrations for prolonged periods of time, only two infants required more than 80% oxygen for more than 24 hours, and only one infant required 60% oxygen for more than 100 hours. "Immature" lungs when exposed to inspired oxygen concentrations over 40% for as little as three days via positive-pressure ventilation may develop bronchopulmonary dysplasia. The role of the underlying disease and the relationship with Wilson-Mikity syndrome remain uncertain.


Cannabis Use, Screen Time, and Internalizing Symptoms among Canadian Youth: Testing Mediation Pathways.
Background: Existing research suggests positive correlations between screen time sedentary behaviors (STSB) and substance use, including cannabis use, among youth. However, little research has examined what factors mediate these relationships.Methods: This study examined mediating pathways among STSB, internalizing symptoms (IS), and cannabis use in a linked longitudinal sample of 28 269 Canadian youth who participated in the COMPASS study over a two-year period (2017/18 to 2018/19). Structural equation modeling examined two main hypotheses cross-sectionally and over time: 1) if IS mediated associations between STSB and cannabis use frequency, and 2) if STSB mediated associations between IS and cannabis use frequency. Results: Results demonstrated significant partial mediation effects for both hypotheses. For example, indirect effects indicated that IS mediated the association between STSB and cannabis use both cross sectionally (95% CI: 0.021, 0.029) and longitudinally (95% CI: 0.006, 0.010). STSB also mediated associations between IS and cannabis use cross sectionally (95% CI: 0.015, 0.023) and longitudinally (95% CI: 0.010, 0.014). This study demonstrated that the associations between STSB, internalizing symptoms and cannabis use are complex, involving mediation in both directions.Discussion: These findings can be used to inform public health initiatives that aim to take a comprehensive approach to addressing negative health behaviors and outcomes, as it is clear that the multi-directional relationships between STSB and mental health may in-turn impact other health behaviors. Future research should continue to examine mediating factors between STSB and substance use among youth, including exploration of associations with other substances.Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2021.1922455 .


Proteomic analysis of eIF-5A in lung adenocarcinomas.
We examined the eIF-5A protein expression in 93 lung adenocarcinomas and 10 uninvolved lung samples using quantitative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) analysis with identification by mass spectrometry and 2-D Western blots. The same tissue samples were examined for the eIF-5A mRNA expression using oligonucleotide microarrays, and the cellular localization of the eIF-5A protein was examined using immunohistochemical analysis on tissue arrays. Higher eIF-5A protein expression was present in tumors showing poor differentiation, 12/13(th) codon K-ras mutations, p53 nuclear accumulation, and tumors with positive lymphocytic response. The eIF-5A mRNA was also significantly increased in lung adenocarcinomas compared to normal lung, but the eIF-5A protein expression was not correlated to its mRNA levels indicating that the increase in the eIF-5A protein expression in lung tumors is post-transcriptionally/translationally/post-translationally regulated. Patients having a higher eIF-5A protein expression showed a relatively poorer survival suggesting the use of eIF-5A as prognostic marker in lung adenocarcinoma. Moreover, the investigation on agents that inhibit eIF-5A function is encouraged.


Endothelin causes prolonged inhibition of nicotinic transmission in feline colonic parasympathetic ganglia.
The action of endothelin (0.03-1 microM) on neurons in colonic parasympathetic ganglia of cats was studied in vitro, using intracellular microelectrode recording techniques. Electrical stimulation of the pelvic nerve evoked excitatory postsynaptic potentials (EPSPs) and orthodromic action potentials that were reversibly blocked by (+)-tubocurarine, hexamethonium, or external solutions containing nominal zero calcium and elevated magnesium. Endothelin blocked orthodromic action potentials and caused a concentration-dependent prolonged reversible depression of fast EPSPs. Endothelin had minimal effects on nicotinic depolarizations evoked by pressure application of acetylcholine. Endothelin also caused membrane depolarization (2-12 mV) followed by membrane hyperpolarization (1-8 mV). The depolarization and hyperpolarization were associated with a decrease and increase in membrane input resistance, respectively. The actions of endothelin were not altered by superfusion of the ganglia with external solutions containing atropine (300 nM), yohimbine (300 nM), naloxone (1 microM), or substance P (3 microM). We conclude that endothelin modulates synaptic transmission by slow membrane depolarization, membrane hyperpolarization, and prolonged depression of fast EPSPs. We suggest that the blockade of orthodromic action potentials and the depression of fast EPSPs is primarily due to inhibition of release of acetylcholine from presynaptic terminals.


REM sleep behavior disorder: motor manifestations and pathophysiology.
Patients with REM sleep behavior disorder (RBD) enact violent dreams during REM sleep in the absence of normal muscle atonia. This disorder is highly frequent in patients with synucleinopathies (60%-100% of patients) and rare in patients with other neurodegenerative disorders. The disorder is detected by interview plus video and sleep monitoring. Abnormal movements expose the patients and bed partners to a high risk of injury and sleep disruption. The disorder is usually alleviated with melatonin and clonazepam. Limb movements are mainly minor, jerky, fast, pseudohallucinatory, and repeated, with a limp wrist during apparently grasping movements, although body jerks and complex violent (fights) and nonviolent culturally acquired behaviors are also observed. Notably, parkinsonism disappears during RBD-associated complex behaviors in patients with Parkinson's disease and with multiple system atrophy, suggesting that the upper motor stream bypasses the basal ganglia during REM sleep. Longitudinal studies show that idiopathic RBD predisposes patients to later develop Parkinson's disease, dementia with Lewy bodies, and, more rarely, multiple system atrophy, with a rate of conversion of 46% within 5 years. During this time window, patients concomitantly develop nonmotor signs (decreased olfaction and color vision, orthostatic hypotension, altered visuospatial abilities, increased harm avoidance) and have abnormal test results (decreased putamen dopamine uptake, slower EEG). Patients with idiopathic RBD have higher and faster risk for conversion to Parkinson's disease and dementia with Lewy bodies if abnormalities in dopamine transporter imaging, transcranial sonography, olfaction, and color vision are found at baseline. They constitute a highly specific target for testing neuroprotective agents.


Identification of atrial fibrillation-related circular RNAs and constructing the integrative regulatory network of circular RNAs, microRNAs and mRNAs by bioinformatics analysis.
Atrial fibrillation (AF) is the most common cardiac arrhythmia with a high incidence of stroke. Many circular RNAs (circRNAs) have been demonstrated they are elated to various heart diseases and may play important roles in diagnostics or many pathophysiological processes. Nevertheless, there is Few studies on circRNAs functions in persistent AF. To identify AF-related circRNAs and construct the integrative regulatory network of circular RNAs, miRNAs, and mRNAs, we collected human right atrial appendage tissues from 5 patients suffering persistent AF (AF group) and 5 patients with normal sinus rhythm (NSR group) and characterized the global changes in circRNA expression with high-throughput sequencing technology. The differential expression of circRNAs and the interactions between circRNAs and microRNAs were analyzed. The microRNA expression file GSE68475 dataset was downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed microRNAs. The target genes of overlapped miRNAs were predicted by using DIANA-TarBase v8. We constructed the circRNA- miRNA-mRNA network using Cytoscape (version 3.4.0) and the network topology was analyzed by utilizing CentiScaPe app. Results showed that all of 600 differentially expressed circRNAs related to AF were screened, including 340 up-regulated and 260 down-regulated circRNAs. An integrative regulatory network was constructed, which included 30 circRNAs, 9 miRNAs and 130 target mRNAs of these miRNAs. It was concluded that that 30 circRNAs, including 8 upregulated circRNAs and 22 downregulated circRNAs, were predicted to highly possibly function as sponges of 9 miRNAs to regulate gene expression by using bioinformatics analysis. Moreover, the interactions of hsa-miR-339-5p with its related circRNAs and target mRNAs constructed the hub regulatory network in persistent AF by utilizing topology analysis. Our proposed regulatory network of circRNAs-miRNAs-mRNAs may provide new insight into the potential mechanism underlying persistent AF. Additionally, these important molecular may become novel biomarkers providing a new strategy in diagnosis and therapy of AF.


Sex-Related Discrepancies in the Access to Optimal Care and Outcomes After Traumatic Spinal Cord Injury: A Retrospective Cohort Study Using Data From a Canadian Registry.
To compare males and females who were stratified into subgroups corresponding to premenopausal, perimenopausal, and postmenopausal ages, regarding access to optimal care and their outcomes after traumatic spinal cord injury (tSCI). Retrospective cohort study. Eighteen acute care centers and 13 rehabilitation facilities across Canada. This study included 5571 individuals with tSCI at C1-L2 who were enrolled in the Rick Hansen Spinal Cord Injury Registry from July 2004 to September 2019 (N=5571). Females were compared with males in the younger (aged ≤40 years), middle-aged (ages 41-50), and older (aged >50 years) subgroups. Not applicable. Females were compared with males in each subgroup with regard to their demographic data, pre-existing comorbidities, injury characteristics, management choices, access to optimal care, and clinical, neurologic, and functional outcomes after tSCI. In the younger subgroups, females (n=408) were significantly younger, had a greater proportion of aboriginals and transportation-related tSCIs, underwent surgical treatment more often, and had a greater sensory score change than males (n=1613). In the middle-aged subgroups, females (n=174) had a greater proportion of high-thoracic tSCIs than males (n=666). In the older subgroups, females (n=660) were significantly older, had more fall-related and less severe tSCIs, had a shorter stay at the rehabilitation center, had less spasticity, and were discharged home less often than males (n=2050). The results of this study suggest some sex-related differences in individuals' demographics and injury characteristics, but fewer discrepancies between females and males regarding their access to optimal care and outcomes after tSCI. Overall, future clinical trials could consider inclusion of males and females of all age groups to enhance recruitment and augment generalizability.


Purification of glysojanin, an antifungal protein, from the black soybean Glycine soja.
A monomeric protein, with a molecular mass of 25 kDa and an N-terminal sequence resembling a segment of chitin synthase, was isolated from the seeds of the black soybean Glycine soja. The protein, designated glysojanin, demonstrated potent antifungal activity against the fungi Fusarium oxysporum and Mycosphaerella arachidicola. It inhibited HIV-1 reverse transcriptase with an IC50 of 47 micromol/L, [methyl-3H]thymidine incorporation by mouse spleen cells with an IC50 of 175 micromol/L, and translation in the rabbit reticulocyte lysate with an IC50 of 20 micromol/L. Glysojanin was purified using a procedure that involved ion-exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion-exchange chromatography by fast protein liquid chromatography on Mono S, and gel filtration by fast protein liquid chromatography on Superdex 75.


Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation.
Imatinib mesylate (STI571) is a promising new treatment for chronic myelogenous leukemia (CML). The effect of imatinib mesylate on primitive malignant progenitors in CML has not been evaluated, and it is not clear whether suppression of progenitor growth represents inhibition of increased proliferation, induction of apoptosis, or both. We demonstrated here that in vitro exposure to concentrations of imatinib mesylate usually achieved in patients (1-2 microM) for 96 hours inhibited BCR/ABL-positive primitive progenitors (6-week long-term culture-initiating cells [LTCICs]) as well as committed progenitors (colony-forming cells [CFCs]). No suppression of normal LTCICs and significantly less suppression of normal CFCs were observed. A higher concentration of imatinib mesylate (5 microM) did not significantly increase suppression of CML or normal LTCICs but did increase suppression of CML CFCs, and to a lesser extent, normal CFCs. Analysis of cell division using the fluorescent dye carboxyfluorescein diacetate succinimidyl ester indicated that imatinib mesylate (1-2 microM) inhibits cycling of CML primitive (CD34(+)CD38(-)) and committed (CD34(+)CD38(+)) progenitors to a much greater extent than normal cells. Conversely, treatment with 1 to 2 microM imatinib mesylate did not significantly increase the percentage of cells undergoing apoptosis. Although a higher concentration of imatinib mesylate (5 microM) led to an increase in apoptosis of CML cells, apoptosis also increased in normal samples. In summary, at clinically relevant concentrations, imatinib mesylate selectively suppresses CML primitive progenitors by reversing abnormally increased proliferation but does not significantly increase apoptosis. These results suggest that inhibition of Bcr-Abl tyrosine kinase by imatinib mesylate restores normal hematopoiesis by removing the proliferative advantage of CML progenitors but that elimination of all CML progenitors may not occur.


Individual flexor tendon identification within the carpal tunnel: A semi-automated analysis method for serial cross-section MR images.
Carpal tunnel syndrome is commonly viewed as resulting from chronic mechanical insult of the median nerve by adjacent anatomical structures. Both the median nerve and its surrounding soft tissue structures are well visualized on magnetic resonance (MR) images of the wrist and hand. Addressing nerve damage from impingement of flexor digitorum tendons co-occupying the tunnel is attractive, but to date has been restricted by lack of means for making individual identifications of the respective tendons. In this image analysis work, we have developed a region-growing method to positively identify each individual digital flexor tendon within the carpal tunnel by tracking it from a more distal MR section where the respective tendon identities are unambiguous. Illustratively, the new method was applied to MRI scans from four different subjects in a variety of hand poses. Conventional shape measures yielded less discriminatory information than did evaluations of individual tendon location and arrangement. This new method of rapid identification of individual tendons will facilitate analysis of tendon/nerve interactions within the tunnel, thereby providing better information about mechanical insult of the median nerve.


Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis.
This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design. Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%. Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5-30)] than in OA cats [14 (8.5-28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed. Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment.


Regional and disease-related differences in properties of the equine temporomandibular joint disc.
Temporomandibular joint (TMJ) disorders affect up to 12% of the human population, and naturally occurring TMJ diseases are increasingly recognized in animals. The TMJ disc plays a major role in TMJ disorders in people, but little is known about its role in TMJ pathology in animals. This study characterizes differences in properties of equine TMJ discs associated with age, disc region, and presence of TMJ osteoarthritis (OA). Discs were dissected from both TMJ's of sixteen horses euthanized for reasons unrelated to this study. Each joint was grossly evaluated and scored as normal, mild OA, or severe OA. Samples from the rostral, caudal, lateral, central, and medial regions of the disc were subject to compressive testing, quantitative biochemistry, and histology. Samples from the lateral, central, and medial region were tested for tensile properties in the rostrocaudal and mediolateral directions. We found that the equine TMJ disc is highly anisotropic, and its glycosaminoglycan (GAG) content and compressive stiffness vary between disc regions. The disc also exhibits increasing GAG content and compressive stiffness with increasing age. While equine TMJ disc properties are generally similar to other herbivores, greater compressive stiffness throughout the disc and greater GAG content in its rostral region suggest that mechanical demands on the TMJ disc differ between horses and other species. Importantly, a region-specific decrease in compressive stiffness was observed associated with joint disease and corresponded to cartilage erosions in the underlying condylar surface.


Characterization of extraintestinal pathogenic Escherichia coli isolated from captive wild felids with bacteremia.
Diseases caused by extraintestinal pathogenic Escherichia coli (ExPEC) in wild felids are rarely reported. Although urinary tract infections are infrequently reported in domestic cats, such infections when present are commonly caused by ExPEC. The present work characterized ExPEC strains isolated from 2 adult felines, a snow leopard (Panthera uncia) and a black leopard (Panthera pardus melas), that died from secondary bacteremia associated with urinary tract infections. Isolates from both animals were classified into the B2 phylogenetic group and expressed virulence genotypes that allowed them to cause severe disease. In addition, strains from the black leopard showed multidrug resistance.


Cross-talk in host-parasite associations: What do past and recent proteomics approaches tell us?
A cross-talk in host-parasite associations begins when a host encounters a parasite. For many host-parasite relationships, this cross-talk has been taking place for hundreds of millions of years. The co-evolution of hosts and parasites, the familiar 'arms race' results in fascinating adaptations. Over the years, host-parasite interactions have been studied extensively from both the host and parasitic point of view. Proteomics studies have led to new insights into host-parasite cross-talk and suggest that the molecular strategies used by parasites attacking animals and plants share many similarities. Likewise, animals and plants use several common molecular tactics to counter parasite attacks. Based on proteomics surveys undertaken since the post-genomic era, a synthesis is presented on the molecular strategies used by intra- and extracellular parasites to invade and create the needed habitat for growth inside the host, as well as strategies used by hosts to counter these parasite attacks. Pitfalls in deciphering host-parasite cross-talk are also discussed. To conclude, helpful advice is given with regard to new directions that are needed to discover the generic and specific molecular strategies used by the host against parasite invasion as well as by the parasite to invade, survive, and grow inside their hosts, and to finally discover parasitic molecular signatures associated with their development.


Seroprevalence of anti-Toxoplasma gondii antibodies in wild boars (Sus scrofa), hunting dogs, and hunters of Brazil.
Seroprevalence of Toxoplasma gondii has been extensively studied in wild boars worldwide due to the emerging risk for human infection through meat consumption. However, this is the first study that reports toxoplasmosis seroprevalence in wild boars, wild boar hunters and their hunting dogs. The aim of the present study was to evaluate the seroprevalence of anti-T. gondii antibodies in the complex wild boars, hunting dogs and hunters, and to determine the risk factors associated with seropositivity in southern and central-western Brazil. Overall, anti-T. gondii seropositivity was observed in 15/71 (21.1%) wild boars by modified agglutination test (MAT); and 49/157 (31.2%) hunting dogs and 15/49 (32.7%) hunters by indirect immunofluorescent antibody test (IFAT). Seroprevalence of toxoplasmosis in Brazilian wild boars was within the national and international range, posting wild boars as potential environmental sentinels for T. gondii presence. In addition, the findings have comparatively shown that wild boars have been less exposed to infection than hunting dogs or hunters in both Brazilian regions. Seropositivity for T. gondii was statistically higher in 12/14 (85.7%) captured wild boars when compared to 5/57 (7.0%) free-range wild boars (p = 0.000001). Similarly, captured wild boars from anthropized areas were more likely to be seropositive than of natural regions (p = 0.000255). When in multiple regression model, dogs with the habit of wild boar hunting had significant more chance to be positive (adjusted-OR 4.62 CI 95% 1.16-18.42). Despite potential as sentinels of environmental toxoplasmosis, seroprevalence in wild boars alone may provide a biased basis for public health concerns; thus, hunters and hunting dogs should be always be included in such studies. Although hunters should be aware of potential T. gondii infection, wild boars from natural and agricultural areas may present lower protozoa load when compared to wild boars from anthropized areas, likely by the higher presence of domestic cats as definitive hosts.


Exercise capacity and all-cause mortality in African American and Caucasian men with type 2 diabetes.
The purpose of this study was to assess the association between exercise capacity and mortality in African Americans and Caucasians with type 2 diabetes and to explore racial differences regarding this relationship. African American (n = 1,703; aged 60 +/- 10 years) and Caucasian (n = 1,445; aged 62 +/- 10 years) men with type 2 diabetes completed a maximal exercise test between 1986 and 2007 at the Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California. Three fitness categories were established (low-, moderate-, and high-fit) based on peak METs achieved. Subjects were followed for all-cause mortality for 7.3 +/- 4.7 years. The adjusted mortality risk was 23% higher in African Americans than in Caucasians (hazard ratio 1.23 [95% CI 1.1-1.4]). A graded reduction in mortality risk was noted with increased exercise capacity for both races. There was a significant interaction between race and METs (P < 0.001) and among race and fitness categories (P < 0.001). The association was stronger for Caucasians. Each 1-MET increase in exercise capacity yielded a 19% lower risk for Caucasians and 14% for African Americans (P < 0.001). Similarly, the risk was 43% lower (0.57 [0.44-0.73]) for moderate-fit and 67% lower (0.33 [0.22-0.48]) for high-fit Caucasians. The comparable reductions in African Americans were 34% (0.66 [0.55-0.80]) and 46% (0.54 [0.39-0.73]), respectively. Exercise capacity is a strong predictor of all-cause mortality in African American and Caucasian men with type 2 diabetes. The exercise capacity-related reduction in mortality appears to be stronger and more graded for Caucasians than for African Americans.


A large-scale gene expression comparison of microdissected, small-sized endometrial cancers with or without hyperplasia matched to same-patient normal tissue.
Type I endometrial cancer is accompanied by hyperplasia and type II endometrial cancer is not. The purpose of our study is to identify genes involved in carcinogenesis of endometrial cancer, especially those differentially expressed by type I and type II cancers. Using a cDNA array technique, we examined expression of 1176 cancer-related genes in endometrial cancer cells sampled from 21 tumors with a diameter of <10 mm, and we compared the expression patterns of the tumor cells with expression patterns of corresponding normal endometrial cells. Of these, 10 cases were type I cancers, and 11 cases were type II cancers. Laser capture microdissection directed precise separation of cells of interest from stromal cells. In cancer cells relative to normal cells, we identified genes that were commonly up- and down-regulated. Then we identified genes differentially expressed by the two types of cancer. Finally, in situ protein expression of some of these gene products was examined using immunohistochemistry. Of 1176 genes examined, 32 genes were up-regulated, and 58 were down-regulated in cancer cells (P < 0.05). Between the two types of cancer, 45 genes were highly expressed in type I cancers, and 24 were highly expressed in type II. Immunohistochemistry confirmed that P-cadherin expression was cancer specific, and vascular endothelial growth factor-C and MLH1 expression were limited to type I and type II cancers, respectively. A more accurate way of assessing gene expression during endometrial carcinogenesis shows evidence of providing candidate genes for use in conquering endometrial carcinoma.


Genotoxic, cytotoxic, and cytopathological effects in rats exposed for 18 months to a mixture of 13 chemicals in doses below NOAEL levels.
The present study investigates the genotoxic and cytotoxic effects of long term exposure to low doses of a mixture consisting of methomyl, triadimefon, dimethoate, glyphosate, carbaryl, methyl parathion, aspartame, sodium benzoate, EDTA, ethylparaben, buthylparaben, bisphenol A and acacia gum in rats. Four groups of ten Sprangue Dawley rats (5 males and 5 females per group) were exposed for 18 months to the mixture in doses of 0xNOAEL, 0.0025xNOAEL, 0.01xNOAEL and 0.05xNOAEL (mg/kg bw/day). After 18 months of exposure, the rats were sacrificed and their organs were harvested. Micronuclei frequency was evaluated in bone marrow erythrocytes whereas the organs were cytopathologically examined by the touch preparation technique. The exposure to the mixture caused a genotoxic effect identified only in females. Cytopathological examination showed specific alterations of tissue organization in a tissue-type dependent manner. The observed effects were dose-dependent and correlated to various tissue parameters. Specifically, testes samples revealed degenerative and cellularity disorders, liver hepatocytes exhibited decreased glycogen deposition whereas degenerative changes were present in gastric cells. Lung tissue presented increased inflammatory cells infiltration and alveolar macrophages with enhanced phagocytic activity, whereas brain tissue exhibited changes in glial and astrocyte cells' numbers. In conclusion, exposure to very low doses of the tested mixture for 18 months induces genotoxic effects as well as monotonic cytotoxic effects in a tissue-dependent manner.


Cancer/testis antigen expression as a predictor for epidermal growth factor receptor mutation and prognosis in lung adenocarcinoma.
Immune therapy targeting cancer/testis (CT) antigens improve the survival in several types of solid tumours. The expression of CT antigens is related to poor survival in non-small-cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutation is the best predictive factor for the sensitivity to tyrosine kinase inhibitors in lung adenocarcinoma. The aim of this study was to elucidate the correlation between the expression of CT antigens and clinicopathological factors, including the EGFR mutation, and to analyse the prognosis in lung adenocarcinoma. Data were collected from a total of 281 lung adenocarcinoma patients who underwent surgery. Among them, 125 cases, whose specimens were too small to extract sufficient DNA and/or RNA, and 2 cases with the coexistence of another histological lung cancer were excluded. A total of 154 patients were reviewed. The expression of CT antigens (melanoma-associated antigen gene [MAGE]-A4 and KK-LC-1) and the EGFR-activating mutation (L858R point mutation in exon 21 and inframe deletion in exon 19) was evaluated by using polymerase chain reaction amplification. The expression of MAGE-A4 and KK-LC-1 was detected in 14 (9%) and 54 patients (35%) with adenocarcinoma. The EGFR-activating mutation was found in 64 patients (42%). Univariate and multivariate analyses demonstrated that tumours expressing at least one CT antigen were associated with no EGFR mutation (odds ratio = 0.3; 95% confidence interval, 0.14-0.71; P < 0.01). A survival analysis was performed in 135 patients who underwent complete resection and the 5-year overall survival rate was 71.1% in those with any expression of CT antigens and 83.2% in those without expression of the genes (P < 0.04). Two different therapeutic targets, EGFR-activating mutation and CT antigen, have a negative relationship with each other.


How parental levels of empathy and alexithymia influence their perception of child's behavior.
Literature states that parents of individuals affected by autism spectrum disorder (ASD) can present social and cognitive deficits, restricted behavior patterns and psychiatric difficulties, without meeting standard diagnostic criteria for ASD ("broader autism phenotype"). We explored the relationship between parenting of children affected by ASD and levels of empathy and lack of emotion understanding (alexithymia). We enlisted 58 families in which a child was affected by ASD. Parents' empathy and alexithymia were respectively assessed by means of Empathy Quotient (EQ) and Toronto Alexithymia Scale (TAS-20). Additionally, we included the assessment of the perception of children's behavior through the Child Behavior Checklist (CBCL). Our findings suggest that most parents have normal empathy and do not show significant alexithymia. We found lower EQ and higher TAS-20 scores being more frequent in fathers. Moreover, each parent's empathy degree negatively relates to his/her alexithymia and vice versa, showing that these two features are inversely correlated. Our study unveiled a strong correlation between maternal empathy and alexithymia and child's externalizing problems, as reported by mothers. Our data reveal differences in mothers and fathers' empathy and alexithymia profiles and confirm the importance of considering both parents' points of view either in the diagnostic and the therapeutic interventions. Parental empathy and alexithymia levels not only play a fundamental role in the evaluation of child's difficulties but can also influence the development of a good relationship with the child for what concerns affective resonance.


An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state.
Aging of hematopoietic stem cells (HSCs) leads to several functional changes, including alterations affecting self-renewal and differentiation. Although it is well established that many of the age-induced changes are intrinsic to HSCs, less is known regarding the stability of this state. Here, we entertained the hypothesis that HSC aging is driven by the acquisition of permanent genetic mutations. To examine this issue at a functional level in vivo, we applied induced pluripotent stem (iPS) cell reprogramming of aged hematopoietic progenitors and allowed the resulting aged-derived iPS cells to reform hematopoiesis via blastocyst complementation. Next, we functionally characterized iPS-derived HSCs in primary chimeras and after the transplantation of re-differentiated HSCs into new hosts, the gold standard to assess HSC function. Our data demonstrate remarkably similar functional properties of iPS-derived and endogenous blastocyst-derived HSCs, despite the extensive chronological and proliferative age of the former. Our results, therefore, favor a model in which an underlying, but reversible, epigenetic component is a hallmark of HSC aging.


Functional State of the Motor Centers of the Lumbar Spine after Contusion (Th8-Th9) with Application of Methylprednisolone-Copolymer at the Site of Injury.
Spinal cord injuries must be treated as soon as possible. Studies of NASCIS protocols have questioned the use of methylprednisolone therapy. This study aimed to evaluate the effect of local delivery of methylprednisolone succinate in combination with a tri-block copolymer in rats with spinal cord injury. The experiments were conducted in accordance with the bioethical guidelines. We evaluated the state of the motor centers below the level of injury by assessing the amplitude of evoked motor responses in the hind limb muscles of rats during epidural stimulation. Kinematic analysis was performed to examine the stepping cycle in each rat. Trajectories of foot movements were plotted to determine the range of limb motion, maximum foot lift height, and lateral deviation of the foot in rats on the 21st day after spinal cord injury. We have shown that the local application of methylprednisolone succinate in combination with block copolymer leads to recovery of center excitability by 21 days after injury. In rats, they recovered weight-supported locomotion, directional control of walking, and balance. The proposed assessment method provides valuable information on gait disturbances following injury and can be utilized to evaluate the quality of therapeutic interventions.


Renal response in real-world carfilzomib- vs bortezomib-treated patients with relapsed or refractory multiple myeloma.
In the phase 3 ENDEAVOR study, carfilzomib-dexamethasone (Kd) improved survival over bortezomib-dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (RRMM), regardless of baseline renal function. This real-world study compared renal response in patients with RRMM (1-3 prior lines) and renal impairment (estimated glomerular filtration rate ≤50 mL/min) treated with Kd vs Vd. Electronic medical records data from the Oncology Services Comprehensive Electronic Records database were assessed (from January 2012 through February 2018). Time to renal response (defined according to International Myeloma Working Group criteria) was evaluated using the Kaplan-Meier method and log-rank test. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for renal overall response (ROR) and renal complete response (RCR) using Cox proportional hazard models adjusted for baseline covariates. Included were 543 Kd-treated and 1005 Vd-treated patients. In line 2 (2L), compared with Vd, Kd achieved significantly higher ROR (51.4% vs 39.6%; P < .0001) and RCR (26.6% vs 22.2%; P = .0229). After baseline covariate adjustment, 2L patients receiving Kd vs Vd were 45% more likely to achieve ROR (IRR, 1.45; 95% CI, 1.18-1.78), and 68% were more likely to achieve RCR (IRR, 1.68; 95% CI, 1.24-2.28). The renal response benefit with Kd remained consistent in 2L to line 4 (4L). In a combined analysis of patients receiving Kd and Vd (2L and 2L-4L), renal responders had longer overall survival and time to next treatment than renal nonresponders. These results demonstrate improved real-world effectiveness of Kd over Vd in RRMM renal rescue, and the positive association between renal response and improved survival.


Tonic electromyographic activity following bilateral tonic-clonic seizures is associated with periictal respiratory dysfunction and postictal generalized EEG suppression.
No biomarkers reliably predict risk for sudden unexpected death in epilepsy (SUDEP). Postictal generalized electroencephalography (EEG) suppression (PGES) is a possible biomarker for SUDEP risk. However, its utility in predicting SUDEP remains uncertain. We had observed that postictal tonic electromyography (PTEMG) activity follows some generalized convulsive seizures (GCS). PTEMG activity and PGES may have a common pathophysiologic basis. PGES is associated with periictal respiratory distress. There is evidence that tonic EMG occurs with brain hypoxia. Thus PTEMG activity may be related to seizure-associated hypoxemia. Pronounced variation occurs among expert clinicians in identifying PGES, thereby limiting its utility as a biomarker. Characteristics of PTEMG activity and its relationship to preceding GCS have not been explored. We studied PTEMG activity characteristics, its relationship to the preceding seizure and associated respiratory dysfunction. We reviewed 145 GCS in 66 patients undergoing video-EEG telemetry (VET). The presence of PTEMG activity was defined when tonic EMG occurred for at least 3 seconds following seizure termination and was identified with filter settings at 5-200 Hz. Duration of PTEMG activity, the seizure, PGES, seizure-associated peripheral capillary oxygen saturation (SpO2 ) change, and end-tidal CO2 were analyzed. We compared data from GCS with and without PTEMG activity. Ninety of 145 seizures with GCS had PTEMG activity. The remainder had postictal slowing without PTEMG activity, and cessation of activity was followed by EEG slowing. Duration of the initial PTEMG discharge was 39.1 (mean) ± (standard deviation) 17.9 seconds. SpO2 nadir was lower (P = 0.005) in seizures with PTEMG activity than in those without (72% vs 77%). End-tidal CO2 was higher (P = 0.05) in seizures with PTEMG activity than in those without (63 vs 56 mm Hg). PGES duration was 35.6 ± 22.2 seconds and associated with duration of PTEMG activity (P < 0.001). The novel finding is that PTEMG activity occurs following 62% of GCS and that seizures with PTEMG activity have greater severity of respiratory dysfunction than seizures without. PTEMG activity is readily discerned by visual analysis of VET at appropriate filter settings and has the potential of being a complementary or surrogate biomarker of PGES for assessing SUDEP risk.


[Dependence of the dynamics of the multiplication of bacteria in the genus Citrobacter on the temperature factor and on the product type in experimental contamination].
A study was made of the time course of the reproduction of bacteria of the Citrobacter genus in milk, sausage meat and vermicelli during experimental contamination, with incubation of cultures at 3 temperature regimens (24, 37 and 44 degrees C). Estimation of the results of experiments was performed by counting the number of the colonies on the surface of 2% beef-extract agar. It was established that within the first 6 h, at 24 and 37 degrees C there was an identical growth of the number of microorganisms in all the foods under study. During incubation at 44 degrees C (for 4-8 h), there was a slower reproduction of bacteria in milk as compared with sausage meat. It was revealed that food consistency had an effect on the intensity of the reproduction of bacteria of the Citrobacter genus depending on the time of incubation and temperature.


Pneumococcal capsular polysaccharide structure predicts serotype prevalence.
There are 91 known capsular serotypes of Streptococcus pneumoniae. The nasopharyngeal carriage prevalence of particular serotypes is relatively stable worldwide, but the host and bacterial factors that maintain these patterns are poorly understood. Given the possibility of serotype replacement following vaccination against seven clinically important serotypes, it is increasingly important to understand these factors. We hypothesized that the biochemical structure of the capsular polysaccharides could influence the degree of encapsulation of different serotypes, their susceptibility to killing by neutrophils, and ultimately their success during nasopharyngeal carriage. We sought to measure biological differences among capsular serotypes that may account for epidemiological patterns. Using an in vitro assay with both isogenic capsule-switch variants and clinical carriage isolates, we found an association between increased carriage prevalence and resistance to non-opsonic neutrophil-mediated killing, and serotypes that were resistant to neutrophil-mediated killing tended to be more heavily encapsulated, as determined by FITC-dextran exclusion. Next, we identified a link between polysaccharide structure and carriage prevalence. Significantly, non-vaccine serotypes that have become common in vaccinated populations tend to be those with fewer carbons per repeat unit and low energy expended per repeat unit, suggesting a novel biological principle to explain patterns of serotype replacement. More prevalent serotypes are more heavily encapsulated and more resistant to neutrophil-mediated killing, and these phenotypes are associated with the structure of the capsular polysaccharide, suggesting a direct relationship between polysaccharide biochemistry and the success of a serotype during nasopharyngeal carriage and potentially providing a method for predicting serotype replacement.


Tropopause detection by partial specular reflection with very-high-frequency radar.
The tropopause can be detected and its altitude determined routinely with the use of meter-wavelength, very-high-frequency radar. At meter wavelengths and at vertical incidence, the tropopause is revealed by partial specular reflection from stable atmospheric layers. The echoes received at vertical incidence as a result of partial specular reflection are greatly enhanced over echoes received at oblique incidence arising from turbulent scatter. Very-high-frequency radars utilizing partial specular reflection promise a major advance in the remote sensing of the atmosphere.


Chloride and membrane potential dependence of sodium ion-proline symport.
Proline accumulation by renal proximal tubule brush border membrane vesicles is Na+ dependent, but little is known about the role of anions or membrane potential on proline uptake. Recent studies in a variety of transport systems, including rat renal brush border membrane vesicles, indicate that halide anions chloride (Cl-) and bromide (Br-) are essential for glycine, beta-alanine, gamma-aminobutyric acid, and taurine uptake, so the possibility that Na(+)-proline symport is Cl- dependent was explored. Also, the role of membrane potential on transport was assessed by determining the effect of external anions with different membrane permeabilities. The ratio of initial rate Cl- stimulated to thiocyanate (SCN)(-)-stimulated uptake values serves to measure Cl- dependence. The initial rate of proline uptake to equilibrium value was 3.11 +/- 0.5 (SE) in the presence of Cl- versus SCN-. The ratio for D-glucose, whose uptake is governed only by electrogenic status of the membrane, was 0.61 +/- 0.47 (P less than 0.001 versus proline). In another series of experiments, uptake values for various anions as a percent of equilibrium (I/E x 100) were: SCN-, 84.9 +/- 10.9; NO3, 49.9 +/- 11.0; SO4(2-), 27.3 +/- 4.4; F-, 68.5 +/- 18.3; Cl-, 164.1 +/- 44.6; Br-, 150.6 +/- 30.2; I-, 56.7 +/- 13.5. The stoichiometry of uptake by Hill plot analysis of proline uptake in the presence of varying concentrations of Na+ (0 to 100 mM) and Cl- (0 to 100 mM) was 2Na+:1Cl-:1 proline.(ABSTRACT TRUNCATED AT 250 WORDS)


Super-resolved angular displacement estimation based upon a Sagnac interferometer and parity measurement.
Super-resolved angular displacement estimation is of crucial significance to the field of quantum information processing. Here we report an estimation protocol based on a Sagnac interferometer fed by a coherent state carrying orbital angular momentum. In a lossless scenario, through the use of parity measurement, our protocol can achieve a 4ℓ-fold super-resolved output with quantum number ℓ; meanwhile, a shot-noise-limited sensitivity saturating the quantum Cramér-Rao bound is reachable. We also consider the effects of several realistic factors, including nonideal state preparation, photon loss, and inefficient measurement. Finally, with mean photon number N¯=2.297 and ℓ = 1 taken, we experimentally demonstrate a super-resolved effect of angular displacement with a factor of 7.88.


[Potentially addictive drugs on reimbursable prescription for chronic severe pain].
Changes in the Norwegian drug reimbursement system in 2008 included the establishment of a new reimbursement code (-71) which authorises coverage of expenditures for potentially addictive drugs in patients with severe, predominantly non-malignant, chronic pain. This reform has hitherto not been evaluated. We assessed national data on drug reimbursements in accordance with code -71 for the period 2008-2011, and anonymised copies of all confirmation letters granting reimbursements according to code -71 in Central Norway (three counties) for 2010. Approximately 1300 individual applicants' gender and age, diagnosis, potentially addictive drug applied for, drug dose, and identity and specialty of the prescribing physician, were recorded. From the time of establishment, reimbursement code -71 has been utilised by an increasing number of individuals, encompassing close to 10,000 subjects in 3rd quarter 2011. Almost one-third of the approved applications were for pregabalin, and the rest were for various opioids. The diagnoses were most often derived from the musculoskeletal and nervous systems, and were often nonspecific. A considerable number of treatment regimens were not in accordance with current principles for the management of chronic non-malignant pain, and drug doses were at times remarkably high. Aspects of this drug reimbursement regulation should be closely monitored, and may be in need of changes.


Collective behavior and virulence arsenal of the fish pathogen Piscirickettsia salmonis in the biofilm realm.
Piscirickettsiosis is a fish disease caused by the Gram-negative bacterium Piscirickettsia salmonis. This disease has a high socio-economic impact on the Chilean salmonid aquaculture industry. The bacterium has a cryptic character in the environment and their main reservoirs are yet unknown. Bacterial biofilms represent a ubiquitous mechanism of cell persistence in diverse natural environments and a risk factor for the pathogenesis of several infectious diseases, but their microbiological significance for waterborne veterinary diseases, including piscirickettsiosis, have seldom been evaluated. This study analyzed the in vitro biofilm behavior of P. salmonis LF-89T (genogroup LF-89) and CA5 (genogroup EM-90) using a multi-method approach and elucidated the potential arsenal of virulence of the P. salmonis LF-89T type strain in its biofilm state. P. salmonis exhibited a quick kinetics of biofilm formation that followed a multi-step and highly strain-dependent process. There were no major differences in enzymatic profiles or significant differences in cytotoxicity (as tested on the Chinook salmon embryo cell line) between biofilm-derived bacteria and planktonic equivalents. The potential arsenal of virulence of P. salmonis LF-89T in biofilms, as determined by whole-transcriptome sequencing and differential gene expression analysis, consisted of genes involved in cell adhesion, polysaccharide biosynthesis, transcriptional regulation, and gene mobility, among others. Importantly, the global gene expression profiles of P. salmonis LF-89T were not enriched with virulence-related genes upregulated in biofilm development stages at 24 and 48 h. An enrichment in virulence-related genes exclusively expressed in biofilms was also undetected. These results indicate that early and mature biofilm development stages of P. salmonis LF-89T were transcriptionally no more virulent than their planktonic counterparts, which was supported by cytotoxic trials, which, in turn, revealed that both modes of growth induced important and very similar levels of cytotoxicity on the salmon cell line. Our results suggest that the aforementioned biofilm development stages do not represent hot spots of virulence compared with planktonic counterparts. This study provides the first transcriptomic catalogue to select specific genes that could be useful to prevent or control the (in vitro and/or in vivo) adherence and/or biofilm formation by P. salmonis and gain further insights into piscirickettsiosis pathogenesis.


sdef: an R package to synthesize lists of significant features in related experiments.
In microarray studies researchers are often interested in the comparison of relevant quantities between two or more similar experiments, involving different treatments, tissues, or species. Typically each experiment reports measures of significance (e.g. p-values) or other measures that rank its features (e.g genes). Our objective is to find a list of features that are significant in all experiments, to be further investigated. In this paper we present an R package called sdef, that allows the user to quantify the evidence of communality between the experiments using previously proposed statistical methods based on the ranked lists of p-values. sdef implements two approaches that address this objective: the first is a permutation test of the maximal ratio of observed to expected common features under the hypothesis of independence between the experiments. The second approach, set in a Bayesian framework, is more flexible as it takes into account the uncertainty on the number of genes differentially expressed in each experiment. We used sdef to re-analyze publicly available data i) on Type 2 diabetes susceptibility in mice on liver and skeletal muscle (two experiments); ii) on molecular similarities between mammalian sexes (three experiments). For the first example, we found between 68 and 104 genes commonly perturbed between the two tissues, using the two methods described above, and enrichment of the inflammation pathways, which are related to obesity and diabetes. For the second example, looking at three lists of features, we found 110 genes commonly perturbed between the three tissues, using the same two methods, and enrichment on genes involved in cell development. sdef is an R package that provides researchers with an easy and powerful methodology to find lists of features commonly perturbed in two or more experiments to be further investigated. The package is provided with plots and tables to help the user visualize and interpret the results. The Windows, Linux and MacOS versions of the package, together with the documentation are available on the website http://cran.r-project.org/web/packages/sdef/index.html.


[Effect of septal damage on alcoholic motivation in the rat].
Interconnection between predisposition to depressive-like state (DS) in stress situation and heightened addiction to ethanol was studied in nonlinear male white rats. Electrolytic lesion of the septum in animals inclined to the development of DS, led to a change from the passive type of reaction in stress conditions to the active type. The rate of formation of alcoholic motivation in these animals decreased in comparison with sham-operated rats. The effect of the septal lesion in rats with formed addiction to alcohol was less expressed. Conclusion is made that the passive type of reaction in extreme conditions is significant for the formation of alcohol motivation in rats, especially at early stages.


Assessing the Returns to Land and Greenhouse Gas Savings from Producing Energy Crops on Conservation Reserve Program Land.
Using land already enrolled in the Conservation Reserve Program (CRP) in the eastern region of the U.S. for producing energy crops for bioenergy while reducing land rental payments offers the potential for lowering the program costs, increasing returns to CRP landowners, and displacing greenhouse gas (GHG) emissions from fossil fuels. We develop an integrated modeling approach to analyze the combination of biomass prices and CRP land rental payment reductions that can incentivize energy crop production on CRP land and its potential to increase soil carbon stocks and displace fossil fuel emissions. We find that conversion of 3.4 million ha in the CRP can be economically viable at a minimum biomass price of $75 Mg-1 with full CRP land rental payment or at $100 Mg-1 with 75% of this land rental payment; this conversion can result in savings of 0.52 and 1.25 billion Mg CO2-eq in life-cycle emissions through the displacement of energy-equivalent fossil fuels and coal-based electricity, respectively, and an additional 0.11 billion Mg CO2-eq soil carbon sequestration relative to the status quo, with CRP left unharvested over the 2016-2030 period. The soil carbon debt due to the transition from unharvested CRP land to energy crops is short-lived and more than offset by the reduction in fossil fuel emissions. The net discounted benefits from producing energy crops on CRP land through a reduced need for government payments to maintain existing enrollment, higher returns to CRP landowners, and the value of the reduction in GHG emissions could be as high as $16-$30 billion by using them for cellulosic biofuels to displace gasoline and $35-$68 billion by displacing coal-based electricity over the 2016-2030 period if biomass prices are $75-$125 Mg-1 and land rental payments are reduced by 25%.


Human lymphocytes bear membrane receptors for C3b and C3d.
Human peripheral blood lymphocytes have membrane receptors for EAC43b (sheep erythrocytes sensitized with antibody and complement) and also for EAC43d, obtained by treating EAC43b with C3b inactivator. Human granulocytes bind only EAC43b, C3 fragments obtained by limited trypsin digestion of purified human C3 display both C3b and C3d sites, since they inhibit rosette formation of lymphocytes with EAC43b and EAC43d. These findings raise the possibility that C3b and C3d receptor sites may be selectively distributed among normal subpopulations of B lymphocytes as well as among leukemic leukocytes.


Reducing Errors in Radiology Specimen Labeling Through Use of a Two-person Check.
Improper specimen labeling of biopsy samples can cause substantial harm to patients through diagnostic delays, administration of inappropriate treatments, and can result in a loss of trust in the healthcare system. Specimen labeling errors are considered a relevant safety metric in our department and tracked on a rolling basis. One imaging section was noted to have nearly completely eliminated these errors through implementation of a 2-person check prior to submission to pathology. The purpose of this intervention was to identify the causes of continued specimen labeling errors in radiology and to standardize the specimen labeling workflow across the department of radiology to include the best practice identified in breast imaging utilizing a 2-person check. Preintervention, 31 specimen labeling errors were reported by the procedural staff over a period of 149 weeks resulting in an error rate of 0.21 errors per week. Postintervention, 3 specimen labeling errors occurred in the next 46 weeks resulting in a rate of 0.07 errors per week, a 68.8% decrease in the specimen labeling error rate. This quality improvement project highlights the process flaws which contribute to medical errors and demonstrates a potential pathway to try and reduce these errors and patient harm without significant investment in capital or new technology.


Cardiovascular-Specific Mortality and Kidney Disease in Patients Undergoing Vascular Surgery.
Acute kidney injury (AKI) affects as many as 40% of patients undergoing surgery and is associated with increased all-cause mortality. Chronic kidney disease (CKD) is a well-known risk factor for cardiovascular mortality. To determine the association between kidney disease and long-term cardiovascular-specific mortality after vascular surgery. A single-center cohort of 3646 patients underwent inpatient vascular surgery from January 1, 2000, to November 30, 2010, at a tertiary care teaching hospital. To determine cause-specific mortality for patients undergoing vascular surgery, a proportional subdistribution hazards regression analysis was used to model long-term cardiovascular-specific mortality while treating any other cause of death as a competing risk. Kidney disease constituted the main covariate after adjusting for baseline patient characteristics, surgery type, and admission hemoglobin level. Final follow-up was completed July 2014 to assess survival through January 31, 2014, and data were analyzed from June 1, 2014, to September 7, 2015. Perioperative AKI, presence of CKD, and overall and cause-specific mortality. Among the 3646 patients undergoing vascular surgery, perioperative AKI occurred in 1801 (49.4%) and CKD was present in 496 (13.6%). The top 2 causes among the 1577 deaths in our cohort were cardiovascular disease (845 of 1577 [53.6%]) and cancer (173 of 1577 [11.0%]). Adjusted cardiovascular mortality estimates at 10 years were 17%, 31%, 30%, and 41%, respectively, for patients with no kidney disease, AKI without CKD, CKD without AKI, and AKI with CKD. Adjusted hazard ratios (95% CIs) for cardiovascular mortality were significantly elevated among patients with AKI without CKD (2.07 [1.74-2.45]), CKD without AKI (2.01 [1.46-2.78]), and AKI with CKD (2.99 [2.37-3.78]) and were higher than those for other risk factors, including increasing age (1.03 per 1-year increase; 1.02-1.04), emergent surgery (1.47; 1.27-1.71), and admission hemoglobin levels lower than 10 g/dL (1.39; 1.14-1.69) compared with a hemoglobin level of 12 g/dL or higher. Perioperative AKI is common in patients undergoing vascular surgery and is associated with a high risk for cardiovascular-specific mortality comparable to that seen with CKD. These findings reinforce the importance of preoperative and postoperative risk stratification for kidney disease and the implementation of strategies now available to help prevent perioperative AKI.