The day-to-day reliability of peak fat oxidation and FATMAX.
Prior studies exploring the reliability of peak fat oxidation (PFO) and the intensity that elicits PFO (FATMAX) are often limited by small samples. This study characterised the reliability of PFO and FATMAX in a large cohort of healthy men and women. Ninety-nine adults [49 women; age: 35 (11) years; [Formula: see text]O2peak: 42.2 (10.3) mL·kg BM-1·min-1; mean (SD)] completed two identical exercise tests (7-28 days apart) to determine PFO (g·min-1) and FATMAX (%[Formula: see text]O2peak) by indirect calorimetry. Systematic bias and the absolute and relative reliability of PFO and FATMAX were explored in the whole sample and sub-categories of: cardiorespiratory fitness, biological sex, objectively measured physical activity levels, fat mass index (derived by dual-energy X-ray absorptiometry) and menstrual cycle status. No systematic bias in PFO or FATMAX was found between exercise tests in the entire sample (- 0.01 g·min-1 and 0%[Formula: see text]O2peak, respectively; p > 0.05). Absolute reliability was poor [within-subject coefficient of variation: 21% and 26%; typical errors: ± 0.06 g·min-1 and × / ÷ 1.26%[Formula: see text]O2peak; 95% limits of agreement: ± 0.17 g·min-1 and × / ÷ 1.90%[Formula: see text]O2peak, respectively), despite high (r = 0.75) and moderate (r = 0.45) relative reliability for PFO and FATMAX, respectively. These findings were consistent across all sub-groups. Repeated assessments are required to more accurately determine PFO and FATMAX.


Interventions to reduce occupational stress and burn out within neonatal intensive care units: a systematic review.
Occupational stress is an emerging problem among physician and nurses, and those working in intensive care settings are particularly exposed to the risk of developing burnout. To verify what types of interventions to manage occupational stress and burn out within neonatal intensive care units (NICUs) have been introduced so far and to verify their efficacy among caregivers. PsycINFO (PsycINFO 1967-July week 3 2019), Embase (Embase 1996-2019 week 29) e Medline (Ovid MEDLINE(R) without revisions 1996-July week 2 2019) were systematically searched combining MeSH and free text terms for "burn out" AND "healthcare provider" AND "NICU". Inclusion criteria were interventions directed to healthcare providers settled in NICUs. Only English language papers were included. Six articles were included in the final analysis. All the studies reported an overall efficacy of the interventions in reducing work-related stress, both when individual focused and organisation directed. The analysis revealed low quality of the studies and high heterogeneity in terms of study design, included populations, interventions and their evaluation assessment. There is currently very limited evidence regarding the management of occupational stress and burn out within NICUs. The quality of available studies was suboptimal. The peculiarities of the NICUs should be considered when developing strategies for occupational stress management. Training self-awareness of workers regarding their reactions to the NICU environment, also from the pre-employment stage, could be an additional approach to prevent and manage stress.


Selective Polymyxin Hemoperfusion in Complex Therapy of Sepsis in Children after Cardiac Surgery.
To date, sepsis remains one of the main challenges of intensive care in pediatrics. Newborns with low birth weight and infants with chronic diseases and congenital disorders are particularly at risk. The incidence of infectious complications in pediatric cardiac surgery is known to be approximately 15-30%. The main etiological factor of sepsis is endotoxin. To evaluate the efficiency and safety of polymyxin (PMX) B-immobilized column-direct hemoperfusion in complex intensive therapy of sepsis in children after cardiac surgery with cardiopulmonary bypass. Prospective cohort study. This study enrolled 15 children, aged 9-96 months, with congenital heart diseases and with body weights of 6.2-22.5 kg. The criteria for admission were body weight >6 kg and clinical and laboratory signs of sepsis (microbiological analysis, procalcitonin [PCT] >2 ng/mL, and endotoxin activity assay [ЕАА] >0.6). Intensive care included inotropic and vasopressor support, mechanical ventilation, broad-spectrum antibiotic therapy, and PMX hemoperfusion procedures. Extracorporeal therapy was initiated within 24 h following the sepsis diagnosis. Every patient underwent 2 hemoperfusion sessions with the use of a PMX B-immobilized column; the session duration was 180 min. We noted improvements in hemodynamic parameters, oxygenation index, and laboratory signs of sepsis, with decreases in the endotoxin concentration according to the EAA, PCT, and presepsin levels. The 28-day survival of the patients in this severely affected group was 80%. Main Conclusion: The inclusion of extracorporeal methods of blood purification, aimed at the selective elimination of circulating endotoxin, in the treatment of sepsis increases the survival rates of children after open heart surgery. Second Conclusion: The obtained results of sepsis therapy with PMX hemoperfusion in children after cardiac surgery enable us to suggest the sufficient safety and efficiency of the procedures in this category of severely affected patients.


High-resolution noncontact atomic force microscopy.
Progress in nanoscience and nanotechnology requires tools that enable the imaging and manipulation of matter at the atomic and molecular scale. During the last two decades or so, scanning probe-based techniques have proven to be particularly versatile in this regard. Among the various probe-based approaches, atomic force microscopy (AFM) stands out in many ways, including the total number of citations and the breadth of possible applications, ranging from materials characterization to nanofabrication and biological studies. However, while nanometer scale operation in different environments became routine, atomic resolution imaging remained elusive for a long time. The reason for this initial deficiency was that contact with the sample blunts atomically sharp tips, which are mandatory for successful atomic resolution imaging. This problem was overcome in the mid-1990s with the introduction of noncontact atomic force microscopy (NC-AFM), which represents a version of AFM where the cantilever is oscillated close to the sample surface without actually 'touching' it. This allows the preservation of the atomic sharpness of the tip while interaction-induced changes in the cantilever's resonance frequency are used to quantify the tip-sample distance. Since then, progress has been steady and includes the development of commercial instruments as well as the addition of many new capabilities beyond imaging, such as the identification and manipulation of individual atoms. A series of annual international conferences, starting in Osaka in 1998, have contributed significantly to this outstanding performance. The program of the most recent conference from this series, held in Madrid on 15-19 September 2008, reflects the maturity of this field, with an increasing number of groups developing strong activities that involve novel approaches and applications covering areas well beyond the original vacuum-based imaging. In this special issue of Nanotechnology we present a selection of original papers authored by many of the leading groups in the field with the goal of providing a well-balanced overview on the state-of-the-art in this rapidly evolving field. These papers, many of which are based on notable presentations given during the Madrid conference, feature highlights such as (1) the development of sophisticated force spectroscopy procedures that are able to map the complete 3D tip-sample force field on different surfaces; (2) the considerable resolution improvement of Kelvin probe force microscopy (reaching, in some cases, the atomic scale), which is accompanied by a thorough, quantitative understanding of the contrast observed; (3) the perfecting of atomic resolution imaging on insulating substrates, which helps reshape our microscopic understanding of surface properties and chemical activity of these surfaces; (4) the description of instrumental and methodological developments that pave the way to the atomic-scale characterization of magnetic and electronic properties of nanostructures, and last but not least (5) the extension of dynamic imaging modes to high-resolution operation in liquids, ultimately achieving atomic resolution. The latter developments are already having a significant impact in the highly competitive field of biological imaging under physiological conditions. This special issue of Nanotechnology would not have been possible without the highly professional support from Nina Couzin, Amy Harvey, Alex Wotherspoon and the entire Nanotechnology team at IOP Publishing. We are thankful for their help in pushing this project forward. We also thank the authors who have contributed their excellent original articles to this issue, the referees whose comments have helped make the issue an accurate portrait of this rapidly moving field, and the entire NC-AFM community that continues to drive NC-AFM to new horizons.


Suboptimal splice sites of equine infectious anaemia virus control Rev responsiveness.
The Rev protein of equine infectious anaemia virus (EIAV) was shown previously to stimulate the expression of a heterologous CAT reporter gene when the 3' half of the EIAV genome was present downstream in cis. However, computer analysis could not reveal the existence of a stable RNA secondary structure that could be analogous to the Rev-responsive element of other lentiviruses. In the present study, the inhibitory RNA element designated the cis-acting repressing sequence (CRS) has been localized to the centre of the EIAV genome. The inhibition exerted by this element could be overcome by supplying Rev in trans. The ability of the EIAV CRS to function in a heterologous context suggests that it does not require interactions with other viral proteins. Site-directed mutagenesis showed that the various centrally located suboptimal splice sites of the EIAV genome function as CRS and confer Rev-dependence on the CRS-containing transcripts. In addition, the data suggest that in canine Cf2Th cells, which are highly permissive for EIAV replication, CRS prevents nuclear export of CRS-containing transcripts and the supply of Rev relieves this suppression.


Urinary 8-hydroxy-2-deoxyguanosine and cognitive function in Puerto Rican adults.
DNA oxidative stress has been suggested as an important pathogenic mechanism in cognitive impairment and dementia. With baseline data collected from 2004 to 2008, the authors examined whether urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of global DNA oxidation, was associated with cognitive function in a sample of 1,003 Puerto Rican adults, aged 45-75 years, living in Boston, Massachusetts, and the surrounding area. Cognitive function was measured by using a battery of 7 tests: the Mini-Mental State Examination, word list learning, digit span, clock drawing and figure copying, Stroop, and verbal fluency tests. The primary outcome was a global cognitive score, averaging standardized scores across all cognitive tests. A higher 8-OHdG concentration was significantly associated with lower global cognitive scores, after adjustment for age, education, status of the gene for apolipoprotein E (APOE), and other covariates (P(trend) = 0.01). The difference in the global score, comparing participants in the 2 extreme 8-OHdG quartiles, was -0.11 (95% confidence interval: -0.20, -0.02), which was equivalent to accelerating cognitive aging by about 4 years, as observed in this population. Prospective studies are needed to elucidate whether elevated urinary 8-OHdG concentrations can predict the rate of cognitive decline and incident dementia.


Low calcium intake among African Americans: effects on bones and body weight.
This review was performed to summarize and integrate the evidence relating calcium intake to health status in African Americans, with special attention to bone and fat. Despite lower average calcium intakes, African Americans typically have skeletons more massive than those of whites. This is the result of a relative resistance of the bony resorptive apparatus to parathyroid hormone, which forces better urinary conservation of calcium and, at some life stages, more efficient intestinal calcium absorption as well. This adaptation, however, has other costs and appears to contribute to a greater risk in African Americans for several chronic diseases, including cardiovascular disease and stroke, obesity, and the insulin resistance syndrome. Higher calcium intakes not only support the skeleton in African Americans, just as they do in whites, but reduce the disease burden for other chronic diseases as well.


Effects of long-term supplementation of dairy cow diets with rumen-protected conjugated linoleic acids (CLA) on performance, metabolic parameters and fatty acid profile in milk fat.
The supplementation of conjugated linoleic acids (CLA) to the rations of dairy cows represents an opportunity to reduce the content of milk fat. Therefore, CLA have the potential beneficial effect of reducing energy requirements of the early lactating cow. The present study aimed at the examination of long-term and posttreatment effects of dietary CLA intake on performance, variables of energy metabolism-like plasma levels of non esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHB), and fatty acid profile in milk fat. Forty-six pregnant German Holstein cows were assigned to one of three dietary treatments: (1) 100 g/ d of control fat supplement (CON), (2) 50 g/d of control fat supplement and 50 g/ d of CLA supplement (CLA-1) and (3) 100 g/d of CLA supplement (CLA-2). The lipid-encapsulated CLA supplement consisted of approximately 10% of trans-10, cis-12 CLA and cis-9, trans-11 CLA each. The experiment started 1 d after calving and continued for about 38 weeks, divided into a supplementation (26 weeks) and a depletion period (12 weeks). Over the first 7 weeks of treatment, 11 and 16% reductions in dry matter intake compared to control were observed for the cows fed CLA-1 and CLA-2 supplements respectively. Consequently, the calculated energy balance for these two CLA groups was lower compared to the control. Plasma levels of NEFA and BHB remained unaffected. Later in lactation the highest CLA supplementation resulted in a reduction of milk fat content of 0.7%. However, no reduction in milk fat yield, and accordingly no milk fat depression (MFD), could be shown. The trans-10, cis-12 CLA in milk fat increased with increasing dietary CLA supplementation in a dose-dependent manner. The proportion of C16 in milk fat was decreased by the highest CLA supplementation. With the exception of an increase in plasma glucose level in the CLA-2 group, no post-treatment effects were observed. Overall, under the conditions of the present study no improvement in the calculated energy balance by CLA supplementation could be shown for the entire evaluation period.


Conformational Analysis of 1,5-Diaryl-3-Oxo-1,4-Pentadiene Derivatives: A Nuclear Overhauser Effect Spectroscopy Investigation.
1,5-Diaryl-3-Oxo-1,4-Pentadiene derivatives are intriguing organic compounds with a unique structure featuring a pentadiene core, aryl groups, and a ketone group. This study investigates the influence of fluorine atoms on the conformational features of these derivatives in deuterated chloroform (CDCl3) solution. Through nuclear magnetic resonance (NMR) spectroscopy and quantum chemical calculations, we discerned variations in interatomic distances and established predominant conformer proportions. The findings suggest that the non-fluorinated entity exhibits a uniform distribution across various conformer groups. The introduction of a fluorine atom induces substantial alterations, resulting in the predominance of a specific conformer group. This structural insight may hold the key to their diverse anticancer activities, previously reported in the literature.


Prevalence of psychological factors in chronic dermatoses.
Aim To investigate, retrospectively, psychiatric consultation results of inpatients staying in Fırat University Dermatology Clinic. Materials and method Records of 520 inpatients who were treated in Fırat University Dermatology Clinic between May 2000 and May 2003 were examined and their psychiatric consultation reports were retrospectively evaluated. Results Of the 520 patients who were included in the study, 272 were female and 248 were male. Ninety-two patients were asked to have psychiatric consultation and when consultation results of these patients were examined it was seen that 67 of them (61.7%) were given a psychiatric diagnosis. Of the 67 patients who were given a psychiatric diagnosis, 34 (50.7%) were female and 33 (49.3%) were male. Mean age of the patients was 39.4 (the youngest being 24 and the oldest 63). It was established that 35.9% of patients (24 individuals) were diagnosed as depressive disorder, 29.8% (20 individuals) as anxiety disorder, 13.4% (nine individuals) as mixed depressive anxiety disorder, 13.4% (nine individuals) as borderline personality disorder and 7.5% (five individuals) as obsessive-compulsive disorder, and that psychiatric treatment was started in 91% of patients. Dermatological diagnoses of patients who were given psychiatric diagnoses were as follows in order of frequency: psoriasis in 22 patients (32.9%), urticaria in 31 patients (46.2%), prurigo nodularis in five patients (7.4%) and others in nine patients (13.5%), respectively. Conclusions Dermatological diseases and psychiatric disorders frequently go together. Psychiatric treatment was started in a high number of patients who were given psychiatric diagnoses and had dermatological problems in the present study. Referring patients with chronic dermatological problems to the psychiatry clinic with a view to supporting their dermatological treatments, we believe, will increase the success rate of dermatosis treatment.


Salty sisters: The women of halophiles.
A history of halophile research reveals the commitment of scientists to uncovering the secrets of the limits of life, in particular life in high salt concentration and under extreme osmotic pressure. During the last 40 years, halophile scientists have indeed made important contributions to extremophile research, and prior international halophiles congresses have documented both the historical and the current work. During this period of salty discoveries, female scientists, in general, have grown in number worldwide. But those who worked in the field when there were small numbers of women sometimes saw their important contributions overshadowed by their male counterparts. Recent studies suggest that modern female scientists experience gender bias in matters such as conference invitations and even representation among full professors. In the field of halophilic microbiology, what is the impact of gender bias? How has the participation of women changed over time? What do women uniquely contribute to this field? What are factors that impact current female scientists to a greater degree? This essay emphasizes the "her story" (not "history") of halophile discovery.


Comparative investigation of the energetic ion spectra comprising the magnetospheric ring currents of the solar system.
Investigated here are factors that control the intensities and shapes of energetic ion spectra that make up the ring current populations of the strongly magnetized planets of the solar system, specifically those of Earth, Jupiter, Saturn, Uranus, and Neptune. Following a previous and similar comparative investigation of radiation belt electrons, we here turn our attention to ions. Specifically, we examine the possible role of the differential ion Kennel-Petschek limit, as moderated by Electromagnetic Ion Cyclotron (EMIC) waves, as a standard for comparing the most intense ion spectra within the strongly magnetized planetary magnetospheres. In carrying out this investigation, the substantial complexities engendered by the very different ion composition distributions of these diverse magnetospheres must be addressed, given that the dispersion properties of the EMIC waves are strongly determined by the ion composition of the plasmas within which the waves propagate. Chosen for comparison are the ion spectra within these systems that are the most intense observed, specifically at 100 keV and 1 MeV. We find that Earth and Jupiter are unique in having their most intense ion spectra likely limited and sculpted by the Kennel-Petschek process. The ion spectra of Saturn, Uranus, and Neptune reside far below their respective limits and are likely limited by interactions with gas and dust (Saturn) and by the absence of robust ion acceleration processes (Uranus and Neptune). Suggestions are provided for further testing the efficacy of the differential Kennel-Petschek limit for ions using the Van Allen Probes.


Omega-3 fatty acids ameliorate atherosclerosis by favorably altering monocyte subsets and limiting monocyte recruitment to aortic lesions.
Fish oil, containing omega-3 fatty acids, attenuates atherosclerosis. We hypothesized that omega-3 fatty acid-enriched oils are atheroprotective through alteration of monocyte subsets and their trafficking into atherosclerotic lesions. Low-density lipoprotein receptor knockout and apolipoprotein E(-/-) mice were fed diets containing 10% (calories) palm oil and 0.2% cholesterol, supplemented with an additional 10% palm oil, echium oil (containing 18:4 n-3), or fish oil. Compared with palm oil-fed low-density lipoprotein receptor knockout mice, echium oil and fish oil significantly reduced plasma cholesterol, splenic Ly6C(hi) monocytosis by ≈50%, atherosclerosis by 40% to 70%, monocyte trafficking into the aortic root by ≈50%, and atherosclerotic lesion macrophage content by 30% to 44%. In contrast, atherosclerosis and monocyte trafficking into the artery wall was not altered by omega-3 fatty acids in apolipoprotein E(-/-) mice; however, Ly6C(hi) splenic monocytes positively correlated with aortic root intimal area across all diet groups. In apolipoprotein E(-/-) mice, fish oil reduced the percentage of blood Ly6C(hi) monocytes, despite an average 2-fold higher plasma cholesterol relative to palm oil. The presence of splenic Ly6C(hi) monocytes parallels the appearance of atherosclerotic disease in both low-density lipoprotein receptor knockout and apolipoprotein E(-/-) mice. Furthermore, omega-3 fatty acids favorably alter monocyte subsets independently from effects on plasma cholesterol and reduce monocyte recruitment into atherosclerotic lesions.


Reducing LGBTQ+ Physical Activity Disparities Through Improved Measurement and Inclusion of Sexual Orientation in US National Data Sets.
Adequate participation in physical activity (PA) is effective in reducing negative health outcomes, including cardiovascular disease, stroke, type 2 diabetes, as well as stress, anxiety, and depression. However, 1 in 4 adults meet the PA guidelines, with lesbian, gay, bisexual, transgender, and queer (LGBTQ+) persons reporting increased rates of inactivity and higher rates of negative health outcomes. Limited research can be conducted on best methods to promote PA among LGBTQ+ adults as there is a lack of standardized measurements for both sexual orientation status and PA used in US national data set methodologies. A call to action is warranted to highlight the lack of uniform methodologies for collecting both sexual orientation and PA data in national data sets, with an overall goal of promoting inclusion and transparency of sexual orientation as a primary, secondary, and tertiary influence on PA. The current societal disconnect of national data sets collecting sexual orientation does not allow for proper extrapolation within the LGBTQ+ classifications. LGBTQ+ identities each report differing PA and health outcomes, promoting the need for proper sexual orientation measures. Without this inclusion, we will continue to see larger health disparities among LGBTQ+ persons due to outdated measurements in current US national data sets. This commentary provides sexual orientation status on health outcomes linked to physical inactivity, the need to include uniform sexual orientation measures in national data sets, and implications of the inclusion of this measure to conduct PA research as it relates to health outcomes.


Childhood and adult socioeconomic position, cumulative lead levels, and pessimism in later life: the VA Normative Aging Study.
Pessimism, a general tendency toward negative expectancies, is a risk factor for depression and also heart disease, stroke, and reduced cancer survival. There is evidence that individuals with higher lead exposure have poorer health. However, low socioeconomic status (SES) is linked with higher lead levels and greater pessimism, and it is unclear whether lead influences psychological functioning independently of other social factors. The authors considered interrelations among childhood and adult SES, lead levels, and psychological functioning in data collected on 412 Boston area men between 1991 and 2002 in a subgroup of the VA Normative Aging Study. Pessimism was measured by using the Life Orientation Test. Cumulative (tibia) lead was measured by x-ray fluorescence. Structural equation modeling was used to quantify the relations as mediated by childhood and adult SES, controlling for age, health behaviors, and health status. An interquartile range increase in lead quartile was associated with a 0.37 increase in pessimism score (P < 0.05). Low childhood and adult SES were related to higher tibia lead levels, and both were also independently associated with higher pessimism. Lead maintained an independent association with pessimism even after childhood and adult SES were considered. Results demonstrate an interrelated role of lead burden and SES over the life course in relation to psychological functioning in older age.


Genomic-Enabled Prediction in Maize Using Kernel Models with Genotype × Environment Interaction.
Multi-environment trials are routinely conducted in plant breeding to select candidates for the next selection cycle. In this study, we compare the prediction accuracy of four developed genomic-enabled prediction models: (1) single-environment, main genotypic effect model (SM); (2) multi-environment, main genotypic effects model (MM); (3) multi-environment, single variance G×E deviation model (MDs); and (4) multi-environment, environment-specific variance G×E deviation model (MDe). Each of these four models were fitted using two kernel methods: a linear kernel Genomic Best Linear Unbiased Predictor, GBLUP (GB), and a nonlinear kernel Gaussian kernel (GK). The eight model-method combinations were applied to two extensive Brazilian maize data sets (HEL and USP data sets), having different numbers of maize hybrids evaluated in different environments for grain yield (GY), plant height (PH), and ear height (EH). Results show that the MDe and the MDs models fitted with the Gaussian kernel (MDe-GK, and MDs-GK) had the highest prediction accuracy. For GY in the HEL data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 9 to 32%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 9 to 49%. For GY in the USP data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 0 to 7%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 34 to 70%. For traits PH and EH, gains in prediction accuracy of models with GK compared to models with GB were smaller than those achieved in GY. Also, these gains in prediction accuracy decreased when a more difficult prediction problem was studied.


[Alternative splicing of an ATP-binding cassette transporter ABCC10 in Tetrahymena thermophila].
ATP-binding cassette transporters (ABCT) could generate multiple transcripts through alternative splicing (AS) in mammalian. Some AS introduced PTC (premature terminal codon)-containing isoforms of ABCT couple with NMD (nonsense-mediated mRNA decay) to regulate relevant functions. However, there are no similar reports in lower organisms. This paper focuses on the unicellular protozoa Tetrahymena thermophila, based on the RNA-seq data of Tetrahymena thermophila, identified two alternative splicing variants of gene ABCC10 (SV1 and SV2). The SV2 contained an intron retention event at the fifth intron, and this 49 bp intron resulted in shift-frame and introduced PTC. Then, a knock-down Tetrahymena strain of gene UPF1 which is a key factor of NMD was constructed, and the expression levels of SV2 were performed using a real-time quantitative PCR. The results showed the expression levels of SV2 were up-regulated significantly in knock-down strain, indicating that SV2 was targeted by NMD, which is consistent to the mechanism which the AS introduced PTC-containing isoforms of ABCC proteins can be targeted by NMD in mammalian. Thus, we infer that this mechanism is highly evolutionary conserved in eukaryotes and was already functional in the last eukaryotic common ancestor.


Multiple sclerosis and oral health--an update.
Multiple sclerosis is a chronic, neurodegenerative disease seen in 69.1 per 100,000 person-years in the world. As multiple sclerosis and periodontal disease both have an inflammatory origin, dental professionals should be aware of the link between these two diseases. In patients unable to carry out effective oral hygiene, dental treatment should be done by dental hygienists and/or dentists to prevent dental caries and periodontal disease. It is hoped that by identifying multiple sclerosis patients in dental clinics, the required support and treatment could be provided to these patients to improve their quality of life and that dental professionals would feel comfortable treating patients with multiple sclerosis.


[Emphysematous pyelonephritis: apropos of a case and review of the literature].
Based on a case report and a review of the literature, the authors describe the features of emphysematous pyelonephritis. This rare disease with a poor prognosis constitutes a difficult clinical diagnosis. The positive diagnosis is based on urgent computed tomography. The reference treatment is emergency nephrectomy in an intensive care context.


Wear-resistant diamond nanoprobe tips with integrated silicon heater for tip-based nanomanufacturing.
We report exceptional nanoscale wear and fouling resistance of ultrananocrystalline diamond (UNCD) tips integrated with doped silicon atomic force microscope (AFM) cantilevers. The resistively heated probe can reach temperatures above 600 degrees C. The batch fabrication process produces UNCD tips with radii as small as 15 nm, with average radius 50 nm across the entire wafer. Wear tests were performed on substrates of quartz, silicon carbide, silicon, or UNCD. Tips were scanned for more than 1 m at a scan speed of 25 mum s(-1) at temperatures ranging from 25 to 400 degrees C under loads up to 200 nN. Under these conditions, silicon tips are partially or completely destroyed, while the UNCD tips exhibit little or no wear, no signs of delamination, and exceptional fouling resistance. We demonstrate nanomanufacturing of more than 5000 polymer nanostructures with no deterioration in the tip.


Alpha-ketoglutarate suppresses the NF-κB-mediated inflammatory pathway and enhances the PXR-regulated detoxification pathway.
Alpha-ketoglutarate (AKG) is a critical nutritional factor in the maintenance of intestinal homeostasis. However, the relative mechanism of AKG has not been well understood. It was recently shown that the interaction between nuclear factor kappa B (NF-κB)-mediated inflammatory pathway and pregnane X receptor (PXR)-regulated detoxification pathway is a check and balance mechanism for keeping the homeostatic state of the intestine, preventing the onset of intestinal inflammation which may lead to cancer. In the current study we used lipopolysaccharide (LPS)-challenged piglet and intestinal porcine epithelial cells-J2 models to investigate the effects of dietary AKG supplementation on the intestinal immune system and PXR regulated target expression. We found that LPS induced significant activation of the NF-κB-mediated inflammatory pathway with concomitant impairment of intestinal nutrient absorption. AKG administration increased intracellular AKG and its metabolite concentrations and enhanced the mRNA expression of alpha-ketoglutarate dehydrogenase in vivo and in vitro. Thus dietary AKG supplementation reversed the adverse effects induced by LPS. We also found a strong inhibitory effects on the NF-κB-mediated inflammatory pathway, especially, in the AKG-treated intestinal tissues, LPS-induced NF-κB phosphorylation was inhibited and TNF-α was suppressed. Interestingly, AKG has potent effects in regulating the PXR and its downstream targets such as CYP3As and CYP2Bs in vivo and in vitro, although AKG is not a known PXR ligand. One potential mechanism for the up-regulation of the PXR pathway is through the down-regulation of NF-κB pathway which in turn de-represses the PXR-regulated target expression. Taken together, our results suggest that AKG improves intestinal immune system through modulating the interaction between PXR and NF-κB. Our findings have important implications for the prevention and treatment of intestinal inflammatory diseases in neonates.


An analysis of the increased demands placed on dialysis health care team members by functionally dependent hemodialysis patients.
A team of health care providers is integral to the care of chronic hemodialysis patients and includes nephrologists, social workers, dietitians, and nurses. Increasingly, the chronic hemodialysis population is composed of older patients with multiple comorbid conditions and reduced functional independence. The demands placed on social workers, nurses, and dietitians caring for the increasingly fragile chronic hemodialysis population have not been examined. We compared the interventions required by social workers, dietitians, and nurses caring for two demographically matched chronic hemodialysis patient groups undergoing dialysis in two outpatient units over a 6-month period to examine the demands imposed by these functionally dependent patients. Patients underwent dialysis in either a step-down unit or an ambulatory unit. Patients undergoing dialysis in the step-down unit had more coronary artery disease (6 of 12 patients [50%] versus 1 of 12 patients; P < 0.025) and peripheral vascular disease (6 of 12 versus 0 patients; P < 0. 004). Mean urea reduction ratio, hematocrit, and serum albumin values, as well as number of hospitalizations and mean days hospitalized for the 6-month study period, were not different between the groups. Patients undergoing dialysis in the step-down unit were more likely to have lower scores on activities of daily living (11 +/- 5 versus 15 +/- 3; P < 0.02), live in a nursing home (58% versus 8%; P < 0.01), be nonambulatory (66% versus 0%; P < 0. 01), and have a catheter as permanent dialysis access (66% versus 9%; P < 0.004). Significantly more social worker and dietitian time in hours per week were provided to the patients in the step-down unit (social workers, 259 versus 201 h/wk; P < 0.001; dietitians, 115 versus 96 h/wk; P < 0.001). Similarly, dialysis treatments requiring nursing interventions (treatments with hypotension, 36% versus 13%; obtaining blood cultures, 7% versus 2%; administering intravenous medications, 9% versus 2%; communicating with other health care providers, 3% versus 0.1%; and non-dialysis-related interventions, 5% versus 0.5%; all P < 0.005) were more common in the patients in the step-down unit. We conclude that increased dialysis provider care is required by patients who are functionally dependent and have increased comorbid conditions. The increased demands this fragile patient population places on dialysis providers must be recognized, examined more closely, and reimbursed appropriately.


Mapping the human toxome by systems toxicology.
Toxicity testing typically involves studying adverse health outcomes in animals subjected to high doses of toxicants with subsequent extrapolation to expected human responses at lower doses. The low-throughput of current toxicity testing approaches (which are largely the same for industrial chemicals, pesticides and drugs) has led to a backlog of more than 80,000 chemicals to which human beings are potentially exposed whose potential toxicity remains largely unknown. Employing new testing strategies that employ the use of predictive, high-throughput cell-based assays (of human origin) to evaluate perturbations in key pathways, referred as pathways of toxicity, and to conduct targeted testing against those pathways, we can begin to greatly accelerate our ability to test the vast 'storehouses' of chemical compounds using a rational, risk-based approach to chemical prioritization and provide test results that are more predictive of human toxicity than current methods. The NIH Transformative Research Grant project Mapping the Human Toxome by Systems Toxicology aims at developing the tools for pathway mapping, annotation and validation as well as the respective knowledge base to share this information.


Quality of Life in Patients With Cancer Under Prolonged Anticoagulation for High-Risk Deep Vein Thrombosis: a Long-Term Follow-Up.
Current guidelines recommend to prolong anticoagulant treatment in patients with cancer with venous thromboembolism (VTE); only few studies evaluated other parameters than cancer itself for selecting patients at higher risk of recurrent VTE. Long-term management of VTE is thus challenged by several controversies mainly for patients compliance. We here report results of a long-term follow-up in patients with deep vein thrombosis under anticoagulant treatment with low-molecular-weight heparin (LMWH) for residual vein thrombosis (RVT) detected at compression ultrasonography (CUS), 6 months after standard anticoagulant treatment. Patients with RVT were deemed at high risk of recurrences and included in the current observational study. They continued LMWH (reduced at 75% standard dose) for further additional 2 years after enrolment or until death. Patients were followed up every 3 months or earlier, if needed. Among ancillary study end points, there was the assessment of patients' quality of life during daily treatment with subcutaneous injections. Quality of life was determined by the EORTC-C30 questionnaire, administered by a skilled psychologist at enrolment and every 6 months follow-up visits. Overall, 128 patients were evaluated during follow-up. Mean global EORTC-C30 score at enrollment and at 6, 12 and 24 months follow-up were 52.1, 51.4, 50.8 and 50.1, respectively. There were no statistically significant differences between scores at enrolment and at the last available follow-up (P = .1). Long-term treatment with LMWH resulted, effective and safe, it was globally well tolerated and exempt of negative impact on quality of life of the enrolled patients. Reported results support long-term anticoagulant treatment with LMWH in cancer patients at risk of recurrent VTE.


The contribution of endoplasmic reticulum stress to liver diseases.
The unfolded protein response (UPR) is an evolutionarily conserved cell signaling pathway that is activated to regulate protein synthesis and restore homeostatic equilibrium when the cell is stressed from increased client protein load or the accumulation of unfolded or malfolded proteins. Once activated, this signaling pathway can either result in the recovery of homeostasis or can activate a cascade of events that ultimately result in cell death. The UPR/endoplasmic reticulum (ER) stress response spectrum and its interplay with other cellular organelles play an important role in the pathogenesis of disease in secretory cells rich in ER, such as hepatocytes. Over the past 2 decades, the contribution of ER stress to various forms of liver diseases has been examined. Robust support for a contributing, as opposed to a secondary role, for ER stress response is seen in the nonalcoholic steatohepatitis, alcoholic liver disease, ischemia/reperfusion injury, and cholestatic models of liver disease. The exact direction of the cause and effect relationship between modes of cell injury and ER stress remains elusive. It is apparent that a complex interplay exists between ER stress response, conditions that promote it, and those that result from it. A vicious cycle in which ER stress promotes inflammation, cell injury, and steatosis and in which steatogenesis, inflammation, and cell injury aggravate ER stress seems to be at play. It is perhaps the nature of such a vicious cycle that is the key pathophysiologic concept. Therapeutic approaches aimed at interrupting the cycle may dampen the stress response and the ensuing injury.


Using Remote Fields for Complex Tissue Engineering.
Great strides have been taken towards the in vitro engineering of clinically relevant tissue constructs using the classic triad of cells, materials, and biochemical factors. In this perspective, we highlight ways in which these elements can be manipulated or stimulated using a fourth component: the application of remote fields. This arena has gained great momentum over the last few years, with a recent surge of interest in using magnetic, optical, and acoustic fields to guide the organization of cells, materials, and biochemical factors. We summarize recent developments and trends in this arena and then lay out a series of challenges that we believe, if met, could enable the widespread adoption of remote fields in mainstream tissue engineering.


On simulation and analysis of variable-rate pumping tests.
Analytical solutions for constant-rate pumping tests are widely used to infer aquifer properties. In this note, we implement a methodology that approximates the time-varying pumping record as a series of segments with linearly varying pumping rates. We validate our approach using an analytical solution for a sinusoidally varying pumping test. We also apply our methodology to analyze synthetic test data and compare the results with those from a commonly used method where rate variations are represented by a series of constant-rate steps.


Effect of various lithotomy positions on lower-extremity blood pressure.
Compartment syndrome of a lower extremity from hypoperfusion is a rare but potentially devastating complication of the lithotomy position during surgery. The aim of this study is to determine the effects of various lithotomy positions on lower-extremity blood pressures. Blood pressure in eight young, healthy people was studied for 10 lithotomy positions. Blood pressure measurements were taken in both the upper arm (brachial artery) and the lower extremity (dorsalis pedis). The heart-to-ankle height gradient in each position was measured, and a predicted lower-extremity systolic pressure was calculated. The measured and predicted lower-extremity systolic blood pressures were compared with repeated measures analysis of variance. As a group, the mean systolic blood pressures in the lower extremities correlated closely with the predicted values. However, the difference between measured and predicted pressures varied among the 10 positions (P < 0.05). Although lower-extremity systolic blood pressures in the young, healthy volunteers correlated with predicted values, there was an additional reduction in pressure associated with the lithotomy position. This surprising finding suggests that a lengthy procedure necessitating the use of a lithotomy position for only a portion should be planned so the remainder of the procedure can take place before establishing the position or so the position can be changed to an alternative position when it is no longer needed.


Dependence of the Nature of the Pedaling Activity on Maximal Aerobic Power in Cycling.
To analyze the effect of the pedaling activity in different 4-min time trials (TT4s) (laboratory and field conditions) and compare TT4 and maximal aerobic power (MAP) determined from the classical incremental exercise test in laboratory. It was hypothesized that the exercises performed on the field would determine higher physical (power output [PO]) and mental involvements due to different environmental conditions. Sixteen male cyclists underwent an incremental test to exhaustion and 3 TT4s under different conditions: cycle ergometer (CE), level ground (LG), and uphill (UP). Correlation was observed for PO with a trivial effect size and narrow limits of agreement between MAP and CE TT4 (r = .96, P < .001). The comparison between the CE, LG, and UP tests indicates that PO was significantly higher in UP than in CE (+8.0%, P < .001) and LG (+11.0%, P < .001). The results suggest that PO depends on the nature of the pedaling activity. Moreover, PO under CE TT4 is a relevant predictor of MAP. It seems important to measure MAP by taking into account the cycling conditions, considering that coaches and scientists use this parameter to assess the aerobic potential of athletes and determine the exercise intensities useful for monitoring adaptation to training.


Effect of Dexmedetomidine Preconditioning on Hepatic Ischemia-Reperfusion Injury in Acute Hyperglycemic Rats.
Acute hyperglycemia frequently occurs in stressful situations, including liver transplantation or hepatic surgery, which may affect the protective effects of dexmedetomidine preconditioning and increase postoperative mortality. Therefore, this study aimed to investigate the effects of dexmedetomidine on hepatic ischemia-reperfusion injury in acute hyperglycemia. Thirty-six Sprague-Dawley rats were randomly assigned to 6 groups, including a combination between 2 glycemic (normo- and hyperglycemia) and 3 ischemia-reperfusion conditions (sham, ischemia-reperfusion only, and dexmedetomidine plus ischemia-reperfusion). Dexmedetomidine 70 μg/kg was preconditioned 30 minutes before ischemic injury. After 6 hours of reperfusion, serum aminotransferase levels were measured to confirm the hepatic tissue injury. Furthermore, inflammatory (nuclear factor-κb, tumor necrosis factor-α, and interleukin-6) and oxidative stress markers (malondialdehyde and superoxide dismutase) were detected. Ischemia-reperfusion injury significantly increased the serum levels of aminotransferase and inflammatory and oxidative stress markers. These ischemia-reperfusion-induced changes were further exacerbated in hyperglycemia and were significantly attenuated by dexmedetomidine preconditioning. However, the effects of dexmedetomidine in hyperglycemia were lesser than those in normoglycemia (P < .05 for aminotransferases, inflammatory markers, malondialdehyde, and superoxide dismutase). These findings suggest that the protective effects of dexmedetomidine preconditioning may be intact against hepatic ischemia-reperfusion injury in acute hyperglycemia. Although its effects appeared to be relatively reduced, this may be because of the increase in oxidative stress and inflammatory response caused by acute hyperglycemia. To determine whether the effects of dexmedetomidine itself would be impaired in hyperglycemia, further study is needed.


Improved knowledge of and difficulties in palliative care among physicians during 2008 and 2015 in Japan: Association with a nationwide palliative care education program.
Palliative care education for health care professionals is a key element in improving access to quality palliative care. The Palliative Care Emphasis Program on Symptom Management and Assessment for Continuous Medical Education (PEACE) was designed to provide educational opportunities for all physicians in Japan. As of 2015, 57,764 physicians had completed it. The objective of this study was to estimate the effects of the program. This study was an analysis of 2 nationwide observational studies from 2008 and 2015. We conducted 2 questionnaire surveys for representative samples of physicians. The measurements used were the Palliative Care Knowledge Test (range, 0-100) and the Palliative Care Difficulties Scale (range, 1-4). Comparisons were made with the unpaired Student t test and with a multivariate linear regression model using 2 cohorts and a propensity score-matched sample. This study analyzed a total of 48,487 physicians in 2008 and a total of 2720 physicians in 2015. Between 2008 and 2015, physicians' knowledge and difficulties significantly improved on the Palliative Care Knowledge Test with total scores of 68 and 78, respectively (P < .001; effect size, 0.40) and on the Palliative Care Difficulties Scale with total scores of 2.65 and 2.49, respectively (P < .001; effect size, 0.29). Propensity-score matching resulted in 619 untrained physicians matched to 619 trained physicians, and physicians who trained with the PEACE program had a higher knowledge score (74 vs 86; P < .001; effect size, 0.64) and a lower difficulties score (2.6 vs 2.3; P < .001; effect size, 0.42). Physicians' knowledge of and difficulties with palliative care improved on a national level. The PEACE program may have contributed to these improvements. Cancer 2018;124:626-35. © 2017 American Cancer Society.


Endogenous Platelet-Rich Plasma Supplements/Augments Growth Factors Delivered via Porous Collagen-Nanohydroxyapatite Bone Substitute for Enhanced Bone Formation.
Polymer (acrylate) and ceramic bone cements are extensively used as bone void fillers and for implant fixation in orthopedics. These materials have micro- to nonporous architectures. Postimplantation, they may cause hypoxic and exothermic injuries to already compromised damage site. These materials also have limited interaction with surrounding tissue. In this work we have developed composite collagen-nanohydroxyapatite (CS) bone filler, mimicking porous architecture of trabecular bone. It was functionalized with clinically available bone active agents like bone morphogenetic protein-2 (rhBMP-2) and zoledronic acid (ZA). We investigated synergistic effects of the bone active molecules and endogenous platelet rich plasma (PRP), a source of growth factors on mineralization. Porous CS and collagen/gelatin/chiotosan polymer scaffold (SC) (without nanohydroxyapatite) were synthesized using cryogelation. PRP (10 μL) (∼5 × 106 cells), rhBMP-2 (5 μg) and ZA (10 μg) were used to functionalize scaffolds. Bone formation was evaluated at ectopic sites in abdominal pouch and 4.0 mm critical defect in tibia metaphysis of rats. Tissue mineralization was evaluated by micro-CT and histological analysis 12 weeks postimplantation. In vitro cell based studies revealed, PRP functionalization enhances osteoblast proliferation and activity on scaffolds. In vivo BMP+ZA+PRP functionalized scaffolds had higher amount (28 mm3) of mineralized tissue formation as compared to empty defect (20 mm3), suggesting that PRP can augment the osteoinductive properties of functionalized scaffolds both in vitro and in vivo. Enhanced cell infiltration and mineralization can be achieved via CS in comparison to SC, implying their use as porous bone void fillers and substitutes for autografts.


Methods of interval selection, presence of noise and their effects on detectability of repetitions and prolongations.
Accurate methods for locating specific types of stuttering events are necessary for diagnosis, treatment, and prognosis. A factor that could add variability to assessment of stuttering is noise on recordings. The effects of noise were assessed by adding noise to intervals of speech containing all fluent material, fluent material with a repetition, or fluent material with a prolongation. These intervals allow a unique dysfluency response to be made. A statistical analysis of the occurrence of such intervals in spontaneous speech showed that only a limited number of intervals met these criteria. This demonstrated that selecting intervals at random from spontaneous speech (as in time interval analysis procedure) will infrequently lead to a unique and unambiguous dysfluency specification for the interval. Intervals were selected for testing from the intervals that met the stipulated criteria. These were presented for dysfluency judgment when the position of the stuttering within an interval was varied and with different amounts of added noise (no added noise, 3 dB, and 6 dB of noise relative to mean speech amplitude). Accuracy in detecting stuttering type depended on noise level and the stuttering's position in the interval, both of which also depended on the type of stuttering: Noise level affected detection of repetitions more than prolongations: Repetitions were more difficult to detect when they occurred at the end of an interval whereas prolongations were more difficult to detect when they were at the beginning of an interval. The findings underline the importance of adopting rigorous recording standards when speech is to be employed to make stuttering assessments.


[Structural recovering in Andean successional forests from Porce (Antioquia, Colombia)].
Places subjected to natural or human disturbance can recover forest through an ecological process called secondary succession. Tropical succession is affected by factors such as disturbances, distance from original forest, surface configuration and local climate. These factors determine the composition of species and the time trend of the succession itself. We studied succession in soils used for cattle ranching over various decades in the Porce Region of Colombia (Andean Colombian forests). A set of twenty five permanent plots was measured, including nine plots (20 x 50 m) in primary forests and sixteen (20 x 25 m) in secondary forests. All trees with diameter > or =1.0 cm were measured. We analyzed stem density, basal area, above-ground biomass and species richness, in a successional process of ca. 43 years, and in primary forests. The secondary forests' age was estimated in previous studies, using radiocarbon dating, aerial photographs and a high-resolution satellite image analysis (7 to >43 years). In total, 1,143 and 1,766 stems were measured in primary and secondary forests, respectively. Basal area (5.7 to 85.4 m2 ha(-1)), above-ground biomass (19.1 to 1,011.5 t ha(-1)) and species richness (4 to 69) directly increased with site age, while steam density decreased (3,180 to 590). Diametric distributions were "J-inverted" for primary forests and even-aged size-class structures for secondary forests. Three species of palms were abundant and exclusive in old secondary forests and primary forests: Oenocarpus mapora, Euterpe precatoria and Oenocarpus bataua. These palms happened in cohorts after forest disturbances. Secondary forest structure was 40% in more than 43 years of forest succession and indicate that many factors are interacting and affecting the forests succession in the area (e.g. agriculture, cattle ranching, mining, etc.).


A phase II study of everolimus in patients with advanced solid malignancies with TSC1, TSC2, NF1, NF2 or STK11 mutations.
Activation of the mTOR pathway has been implicated in the development of several malignancies and alterations in TSC1, TSC2, STK11 and NF1, can lead to the dysregulation of this pathway. Furthermore, mutations in TSC1 and NF2 are known to confer sensitivity to everolimus-an mTOR inhibitor. Based on these data, a single-arm, open label, single-institution phase II basket study was designed to assess the activity of everolimus in patients with solid malignancies whose tumors harbored mutations in TSC1, TSC2, NF1, NF2, or STK11. A total of 12 patients with histologically confirmed diagnosis of advanced solid tumors (metastatic, recurrent, or unresectable) with mutations in TSC1, TSC2, NF1, NF2 or STK11 genes, who had failed at least one line of standard of care systemic therapy, were enrolled to this open label, single-arm study. Presence of mutations in TSC1, TSC2, NF1, NF2 or STK11 genes was assessed using targeted-next generation sequencing (NGS). All eligible patients were treated with everolimus at an initial dose of 10 mg orally once daily in cycles of 28 days. The primary endpoint of this study was overall response rate (ORR). Of 12 patients enrolled, 8 were evaluable for response at the end of 2 cycles. One complete response (CR) was observed (12.5%) and one patient (12.5%) had stable disease (SD), while six (75%) patients showed disease progression. Everolimus was overall well tolerated with anemia, decreased neutrophil and lymphocyte counts, peripheral edema and hyperglycemia representing the most common adverse events. One patient discontinued treatment due to a treatment related grade 4 pericardial effusion. Both patients with CR or SD had a diagnosis of lung adenocarcinoma with NF1 or STK11 mutations, respectively. Although this study failed to meet its prespecified ORR threshold for success of 30% or higher, exploratory analyses suggest potential activity for everolimus in a subset of patients with lung adenocarcinomas with STK11 or NF1 mutations. Further studies are necessary to systematically explore the clinical activity of everolimus, potentially as a combination therapy, in these patients.


Transcriptional regulation of p57kip2 expression during development, differentiation and disease.
p57kip2 is the most complex member of the CIP/KIP family of cyclin-dependent kinase inhibitors and plays a fundamental role in regulating cell cycle and differentiation during mammalian development. Consistently with a key role for p57kip2 in the spatial and temporal control of cell proliferation, its expression is fine-tuned by multiple regulatory mechanisms, resulting in a tissue-, developmental phase- and cell type-specific pattern. Moreover, p57kip2 is an imprinted gene, further supporting the importance of its proper expression dosage. Importantly, misregulation of p57kip2 expression has been associated, more frequently than mutations in its coding region, to human growth disorders, such as Beckwith-Wiedemann and Silver-Russell syndromes, as well as to the onset of several types of cancers. This review will summarize the molecular mechanisms regulating p57kip2 transcription during differentiation and development, their relationship with the imprinting control and their alterations in growth-related diseases and cancer. Particular attention will be given to the role of epigenetic mechanisms, involving DNA methylation, histone modifications, long-range chromatin interactions and non-coding RNAs in modulating and integrating the functions of cis-regulatory elements and trans-acting factors.


Actin capping protein alpha maintains vestigial-expressing cells within the Drosophila wing disc epithelium.
Tissue patterning must be translated into morphogenesis through cell shape changes mediated by remodeling of the actin cytoskeleton. We have found that Capping protein alpha (Cpa) and Capping protein beta (Cpb), which prevent extension of the barbed ends of actin filaments, are specifically required in the wing blade primordium of the Drosophila wing disc. cpa or cpb mutant cells in this region, but not in the remainder of the wing disc, are extruded from the epithelium and undergo apoptosis. Excessive actin filament polymerization is not sufficient to explain this phenotype, as loss of Cofilin or Cyclase-associated protein does not cause cell extrusion or death. Misexpression of Vestigial, the transcription factor that specifies the wing blade, both increases cpa transcription and makes cells dependent on cpa for their maintenance in the epithelium. Our results suggest that Vestigial specifies the cytoskeletal changes that lead to morphogenesis of the adult wing.


BioKA: a curated and integrated biomarker knowledgebase for animals.
Biomarkers play an important role in various area such as personalized medicine, drug development, clinical care, and molecule breeding. However, existing animals' biomarker resources predominantly focus on human diseases, leaving a significant gap in non-human animal disease understanding and breeding research. To address this limitation, we present BioKA (Biomarker Knowledgebase for Animals, https://ngdc.cncb.ac.cn/bioka), a curated and integrated knowledgebase encompassing multiple animal species, diseases/traits, and annotated resources. Currently, BioKA houses 16 296 biomarkers associated with 951 mapped diseases/traits across 31 species from 4747 references, including 11 925 gene/protein biomarkers, 1784 miRNA biomarkers, 1043 mutation biomarkers, 773 metabolic biomarkers, 357 circRNA biomarkers and 127 lncRNA biomarkers. Furthermore, BioKA integrates various annotations such as GOs, protein structures, protein-protein interaction networks, miRNA targets and so on, and constructs an interactive knowledge network of biomarkers including circRNA-miRNA-mRNA associations, lncRNA-miRNA associations and protein-protein associations, which is convenient for efficient data exploration. Moreover, BioKA provides detailed information on 308 breeds/strains of 13 species, and homologous annotations for 8784 biomarkers across 16 species, and offers three online application tools. The comprehensive knowledge provided by BioKA not only advances human disease research but also contributes to a deeper understanding of animal diseases and supports livestock breeding.


Sulindac induced regression of colorectal adenomas in familial adenomatous polyposis: evaluation of predictive factors.
Sulindac, a non-steroidal anti-inflammatory drug, causes regression of colorectal adenomas in patients with familial adenomatous polyposis (FAP) but the response is variable. Specific clinical factors predictive of sulindac induced regression have not been studied. 22 patients with FAP were given sulindac 150 mg orally twice a day. Polyp number and size were determined before treatment and at three months. The relation of nine clinical factors to polyp regression (per cent of baseline polyp number after treatment) was evaluated by univariate and multivariate analysis. After three months of sulindac, polyp number had decreased to 45 per cent of baseline and polyp size to 50 per cent of baseline (p < 0.001 and p < 0.01, respectively). Univariate analysis showed greater polyp regression in older patients (p = 0.004), those with previous colectomy and ileorectal anastomosis (p = 0.001), and patients without identifiable mutation of the APC gene responsible for FAP (p = 0.05). With multivariate regression analysis, response to sulindac treatment was associated with previous subtotal colectomy. Sulindac treatment seems effective in producing regression of colorectal adenomas of FAP patients with previous subtotal colectomy regardless of baseline polyp number and size. Changed sulindac metabolism, reduced area of the target mucosa, or changed epithelial characteristics after ileorectal anastomosis may explain these findings.


Enhanced Angiogenesis in HUVECs Preconditioned with Media from Adipocytes Differentiated from Lipedema Adipose Stem Cells In Vitro.
Lipedema is a connective tissue disorder characterized by increased dilated blood vessels (angiogenesis), inflammation, and fibrosis of the subcutaneous adipose tissue. This project aims to gain insights into the angiogenic processes in lipedema using human umbilical vein endothelial cells (HUVECs) as an in vitro model. HUVECs were cultured in conditioned media (CM) collected from healthy (non-lipedema, AQH) and lipedema adipocytes (AQL). The impacts on the expression levels of multiple endothelial and angiogenic markers [CD31, von Willebrand Factor (vWF), angiopoietin 2 (ANG2), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMPs), NOTCH and its ligands] in HUVECs were investigated. The data demonstrate an increased expression of CD31 and ANG2 at both the gene and protein levels in HUVECs treated with AQL CM in 2D monolayer and 3D cultures compared to untreated cells. Furthermore, the expression of the vWF, NOTCH 4, and DELTA-4 genes decreased. In contrast, increased VEGF, MMP9, and HGF gene expression was detected in HUVECs treated with AQL CM cultured in a 2D monolayer. In addition, the results of a tube formation assay indicate that the number of formed tubes increased in lipedema-treated HUVECs cultured in a 2D monolayer. Together, the data indicate that lipedema adipocyte-CM promotes angiogenesis through paracrine-driven mechanisms.


TOF-SIMS characterization of impurity enrichment and redistribution in solid oxide electrolysis cells during operation.
TOF-SIMS analyses of state-of-the-art high temperature solid oxide electrolysis cells before and after testing under different operating conditions were performed. The investigated cells consist of an yttria stabilized zirconia (YSZ) electrolyte, a La1-xSrxMnO3-δ composite anode and a Ni-YSZ cermet cathode. The surfaces and cross-sections of the cells were analyzed, and several elemental impurities like Si, Ca and Na were identified and spatially mapped and their enrichment and migration during operation is reported. With advancing operation time, the concentration of these elements, especially Na and Ca, increases. For Si, a concentration gradient is found from the gas inlet to the gas outlet. Additionally, a loss of Ni percolation in the active cathode is observed in the same area where the Si enrichment is found. Based on the obtained TOF-SIMS results, the influence of the operating conditions on degradation is discussed.


The Changing Landscape of Pediatric Migraine Therapy: A Review.
Migraine is a disabling and prevalent condition that affects the pediatric and adolescent population. This review describes current acute and preventive migraine pharmacologic therapies for the pediatric and adolescent population. Multiple pharmacotherapies that have been used in the treatment of acute headache and prevention in pediatric migraine are reviewed. There have been recent advances in the management of migraines among pediatric and adolescent patients, including US Food and Drug Administration approval of triptans for acute management in children as young as 6 years, and the first prospective, randomized, double-blind, placebo-controlled comparative study of preventive pharmacotherapy in pediatric migraine. A major challenge of evidence-based research in pediatric and adolescent migraine is the significant placebo effect. Although progress is being made in the management of migraines among pediatric and adolescent patients, there remains much work to be done.


The "quality" of JBI qualitative research synthesis: a methodological investigation into the adherence of meta-aggregative systematic reviews to reporting standards and methodological guidance.
Approaches to the synthesis of qualitative research have existed for more than 20 years and have evolved significantly during that time. One common approach is meta-aggregation, as advocated by JBI. There is now a considerable number of published reviews that claim to follow the JBI approach to meta-aggregation. This methodological review sought to determine the extent to which a selection of these reviews follow the available guidance, with a view to establishing compliance and identifying potential areas for improvement. The JBI Database of Systematic Reviews and Implementation Reports (JBISRIR) was searched from 2015 to 2017 to identify all qualitative systematic reviews following the JBI approach. Citations were screened by two independent reviewers, and data extraction was conducted independently by at least two reviewers. Eligible reviews were then assessed against the JBI methodological guidance and ENTREQ statement to determine compliance. From the search, 33 health care-related reviews that met the inclusion criteria were identified. Several areas were identified where reviewers consistently made errors or did not clearly report their findings, including study screening and selection issues (particularly how this was done and by whom), transparent rationale for study exclusion, who performed data extraction and how, processes for developing synthesized findings, and the development and presentation of recommendations. Although qualitative synthesis has come a long way, there are still some areas for improvement in conduct and reporting. This has implications for those who develop guidance and provide education to systematic reviewers.


Consolidation of Imaging Modalities Utilizing Digitally Assisted Visualization Systems: The Development of a Surgical Information Handling Cockpit.
The management of vitreoretinal cases is ever-evolving, paralleled by rapid advancements in operative imaging modalities. In this article, we describe an advanced application of digitally assisted vitreoretinal surgery (DAVS) that involves the consolidation of pre-existing ancillary imaging technology into a single same-screen viewing platform. Forty-four eyes of 44 patients were operated using same screen simultaneous viewing of the primary three-dimensional high definition (3DHD) surgical field and simultaneous auxiliary video feed viewing of all currently approved ocular endoscopy (n=12), intraoperative optical coherence tomography (iOCT) units (n=24), or computer feeds from the EHR/image management software (n=8). All surgeries were successful with excellent functional and anatomic outcomes. DAVS facilitated same screen viewing of multiple video/information feeds was notable for improved ergonomics, surgical efficiency, and precision when compared to viewing the surgical field and auxiliary video feeds separately. We describe a new concept for the vitreoretinal operating room - a DAVS-based surgical information handling cockpit - integrating FDA approved ocular endoscopy (n=1), microscope-integrated iOCT units (n=3), and one EHR/Image management solution with the primary surgical field 3DHD feed. We suggest same screen viewing of multiple video and other clinical information feeds is a promising modality that may be considered in the management of patients with surgical vitreoretinal disease and should be purposefully incorporated into future iterations of DAVS technology platforms.


Application of in vivo brain imaging technology in the basic research of acupuncture-moxibustion for encephalopathy.
Acupuncture-moxibustion is remarkably effective on encephalopathy, but its mechanism is unclear. With the continuous development of imaging technology, the in vivo brain imaging technology has been used increasingly in life science research and it also becomes a more effective tool for the basic research of acupuncture-moxibustion in treatment of encephalopathy. The paper summarizes the application of its technology in the basic research of acupuncture-moxibustion for encephalopathy and the characteristics of imaging, as well as the advantages and shortcomings. It is anticipated that the references may be provided for the basic research of acupuncture-moxibustion in treatment of encephalopathy and be conductive to the modernization of acupuncture-moxibustion.


Executive functions and child problem behaviors are sensitive to family disruption: a study of children of mothers working overseas.
Mothers in Sri Lanka are increasingly seeking overseas employment, resulting in disruption of the childcare environment. The present study was designed to evaluate the effects of maternal migration on executive function (EF) and behavior, thereby also contributing to the scientific understanding of environmental effects--or more specifically family effects--on children's neurocognitive functioning. A sample of 60 healthy 11-year-old children whose mothers had been working overseas for more than 1 year formed the study group, and a comparison group was recruited from the same schools. Evaluations were made twice over a 1-year interval with regard to the EF components inhibition and working memory as well as teacher ratings of internalizing and externalizing behavior. The children in the study group were found to have poorer EF and higher levels of externalizing behaviors. A composite score of inhibition partially mediated the group effect on externalizing behavior. Current home environment was assessed using the HOME scale, was poorer for the study group and was related to EF, but not to behavior problems. Keeping in mind the correlational nature of the present data, our results were discussed in relation to studies showing cognitive effects of stress.


Gaseous nitrogen emissions and mineral nitrogen transformations as affected by reclaimed effluent application.
Irrigation with reclaimed effluent (RE) is essential in arid and semiarid regions. Reclaimed effluent has the potential to stimulate gaseous N losses and affect other soil N processes. No direct measurements of the N2 and N2O emissions from Mediterranean soils have been conducted so far. We used the 15N gas flux method in a field and a laboratory experiment to study the effect of RE irrigation on gaseous N losses and other N transformations in a Grumosol (Chromoxerert) soil. The fluxes of N2, N2O, and NH3 were measured from six Grumosol lysimeters following application of either fresh water or RE. The N fertilizer was applied either as 15NH4 or 15NO3. Only up to 0.3% from the applied N fertilizer was lost as N2O + NH3. Reclaimed effluent enhanced the losses of NH3, but did not affect those of N2O. Nitrification and denitrification were equally important to N2O production. Laboratory incubations were performed to both confirm the influence of the irrigation water type and to test the effect of moisture content. Significant quantities of N2 and N2O (up to 3.1% of the applied fertilizer) were emitted from saturated soils. Reclaimed effluent application did not induce higher N2O emissions, yet significantly more (approximately 33%) N2 was emitted from RE-irrigated soils. Denitrification contributed up to 75% of the N2O amounts emitted from saturated soils. Reclaimed effluent application inhibited nitrification in the Grumosol by 15 to 25% and induced NO2 accumulation in soils incubated at a field-capacity moisture content.


Influence of Class V preparation on in vivo temperature rise in anesthetized human pulp during exposure to a Polywave® LED light curing unit.
This in vivo study evaluated pulp temperature (PT) rise in human premolars having deep Class V preparations during exposure to a light curing unit (LCU) using selected exposure modes (EMs). After local Ethics Committee approval, intact first premolars (n=8) requiring extraction for orthodontic reasons, from 8 volunteers, received infiltrative and intraligamental anesthesia and were isolated using rubber dam. A minute pulp exposure was attained and sterile probe from a wireless, NIST-traceable, temperature acquisition system was inserted into the coronal pulp chamber to continuously monitor PT (°C). A deep buccal Class V preparation was prepared using a high speed diamond bur under air-water spray cooling. The surface was exposed to a Polywave® LED LCU (Bluephase 20i, Ivoclar Vivadent) using selected EMs, allowing 7-min span between each exposure: 10-s in low (10-s/L), 10-s (10-s/H), 30-s (30-s/H), or 60-s (60-s/H) in high mode; and 5-s-Turbo (5-s/T). Peak PT values and PT increases over physiologic baseline levels (ΔT) were subjected to 1-way, repeated measures ANOVAs, and Bonferroni's post-hoc tests (α=0.05). Linear regression analysis was performed to establish the relationship between applied radiant exposure and ΔT. All EMs produced higher peak PT than the baseline temperature (p<0.001). Only 60-s/H mode generated an average ΔT of 5.5°C (p<0.001). A significant, positive relationship was noted between applied radiant exposure and ΔT (r2=0.8962; p<0.001). In vivo exposure of deep Class V preparation to Polywave® LED LCU increases PT to values considered safe for the pulp, for most EMs. Only the longest evaluated EM caused higher PT increase than the critical ΔT, thought to be associated with pulpal necrosis.


[Recording of the anterior temporal spikes and acute waves by the method of bipolar EEG].
The author shows, with special reference to EEG examination of 20 patients suffering from temporal epilepsy, how methodological errors made in the use of bipolar wiring may lead to the exclusion of anterior temporal spikes and pointed waves from recording. In view of this circumstance, emphasis is laid on the necessity of combining two projections of bipolar wiring and the most efficient succession of their use is suggested: first variable-area and then longitudinal. This is justified by the fact that variable-area wiring compares favourably with longitudinal wiring in the recognition of anterior temporal specific paroxysmal complexes.


ATP-Gated Potassium Channels Contribute to Ketogenic Diet-Mediated Analgesia in Mice.
Chronic pain is a substantial health burden and options for treating chronic pain remain minimally effective. Ketogenic diets are emerging as well-tolerated, effective therapeutic strategies in preclinical models of chronic pain, especially diabetic neuropathy. We tested whether a ketogenic diet is antinociceptive through ketone oxidation and related activation of ATP-gated potassium (KATP) channels in mice. We demonstrate that consumption of a ketogenic diet for one week reduced evoked nocifensive behaviors (licking, biting, lifting) following intraplantar injection of different noxious stimuli (methylglyoxal, cinnamaldehyde, capsaicin, or Yoda1) in mice. A ketogenic diet also decreased the expression of p-ERK, an indicator of neuronal activation in the spinal cord, following peripheral administration of these stimuli. Using a genetic mouse model with deficient ketone oxidation in peripheral sensory neurons, we demonstrate that protection against methylglyoxal-induced nociception by a ketogenic diet partially depends on ketone oxidation by peripheral neurons. Injection of tolbutamide, a KATP channel antagonist, prevented ketogenic diet-mediated antinociception following intraplantar capsaicin injection. Tolbutamide also restored the expression of spinal activation markers in ketogenic diet-fed, capsaicin-injected mice. Moreover, activation of KATP channels with the KATP channel agonist diazoxide reduced pain-like behaviors in capsaicin-injected, chow-fed mice, similar to the effects observed with a ketogenic diet. Diazoxide also reduced the number of p-ERK+ cells in capsaicin-injected mice. These data support a mechanism that includes neuronal ketone oxidation and activation of KATP channels to provide ketogenic diet-related analgesia. This study also identifies KATP channels as a new target to mimic the antinociceptive effects of a ketogenic diet.


[Stress cine MRI for detection of coronary artery disease].
Stress testing is the cornerstone in the diagnosis of patients with suspected coronary artery disease (CAD). Stress echocardiography has become a well-established modality for the detection of ischemia-induced wall motion abnormalities. However, display and reliable interpretation of stress echocardiography studies are user-dependent, the test reproducibility is low, and 10 to 15 % of patients yield suboptimal or non-diagnostic images. Due to its high spatial and contrast resolution, MRI is known to permit an accurate determination of left ventricular function and wall thickness at rest. Early stress MRI studies provided promising results with respect to the detection of CAD. However, the clinical impact was limited due to long imaging time and problematic patient monitoring in the MRI environment. Recent technical improvements - namely ultrafast MR image acquisition - led to a significant reduction of imaging time and improved patient safety. Stress can be induced by physical exercise or pharmacologically by administration of a beta1-agonist (dobutamine) or vasodilatator (dipyridamole and adenosine). The best developed and most promising stress MRI technique is a high-dose dobutamine/atropine stress protocol (10, 20, 30, 40 microgram/kg/min; optionally 0.25-mg fractions of atropine up to maximal dose 1 mg). Severe complications (myocardial infarction, ventricular fibrillation and sustained tachycardia, cardiogenic shock) may be expected in 0.25 % of patients. Currently, data of three high-dose dobutamine stress MRI studies are available, revealing a good sensitivity (83 - 87 %) and specificity (83 - 86 %) in the assessment of CAD. The direct comparison between echocardiography and MRI for the detection of stress-induced wall motion abnormalities yielded better results for dobutamine-MRI in terms of sensitivity (86.2 % vs. 74.3 %; p < 0.05) and specificity (85.7 % vs. 69.8 % p < 0.05) as compared to dobutamine stress echocardiography. The superior results of MRI can mainly be explained by the better image quality with sharp delineation of the endocardial and epicardial borders. Currently, stress MRI is already a realistic clinical alternative for the non-invasive assessment of CAD in patients with impaired image quality in echocardiography.


Evidence that folding of an RNA tetraloop hairpin is less cooperative than its DNA counterpart.
Hairpin secondary structural elements play important roles in the folding and function of RNA and DNA molecules. Previous work from our lab on small DNA hairpin loop motifs, d(cGNAg) and d(cGNABg) (where B is C, G, or T), showed that folding is highly cooperative and obeys indirect coupling, consistent with a concerted transition. Herein, we investigate folding of the related, exceptionally stable RNA hairpin motif, r(cGNRAg) (where R is A or G). Previous NMR characterization identified a complex network of seven hydrogen bonds in this loop. We inserted three carbon (C3) spacers throughout the loop and found coupling between G1 of the loop and the CG closing base pair, similar to that found in DNA. These data support a GNRA motif being expandable at any position but before the G. Thermodynamic measurements of nucleotide-analogue-substituted oligonucleotides revealed pairwise-coupling free energies ranging from weak to strong. When coupling free energies were remeasured in the background of changes at a third site, they remained essentially unchanged even though all of the sites were coupled to each other. This type of coupling, referred to as "direct", is peculiar to the RNA loop. The data suggest that, for small stable loops, folding of RNA obeys a model with nearest-neighbor interactions, while folding of DNA follows a more concerted process in which the stabilizing interactions are linked through a conformational change. The lesser cooperativity in RNA loops may provide a more robust loop that can withstand mutations without a severe loss in stability. These differences may enhance the ability of RNA to evolve.


Degradation of pre-beta-high density lipoproteins and their binding activity to human blood monocytes.
We have previously reported that high density lipoprotein3 (HDL3), apolipoprotein A-I (apoA-I) rich lipoprotein, binds specifically to the surface of human blood monocytes. Pre-beta-HDL with a pre-beta mobility on agarose gels is an apoA-I (MW 28 kDa)-rich and a lipid-poor lipoprotein. In the present study, we found that pre-beta-HDL purified by ion-exchange chromatography was susceptible to degradation if isolated in the absence of anti-proteases, resulting in the smaller lyso-pre-beta-HDL. The mass of lyso-pre-beta-HDL was confirmed using a delayed extraction matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (DE-MALDI-TOF MS), which showed a fragment of approximately 22,378.9 Da. We further investigated limited proteolysis of apo A-I purified from human plasma HDL with various proteases, and cleavage appeared to be limited to the C-terminal end of apo A-I (amino acids 188-223). The ability of pre-beta-HDL and lyso-pre-beta-HDL to compete for HDL binding to monocytes was determined using a flow cytometry-based assay. Pre-beta-HDL competed efficiently for binding whereas lyso-pre-beta-HDL was significantly less effective. The data may indicate that the binding sites on monocytes specifically recognize apoA-I. We suggest that limited proteolysis around amino acids 188-223 of apo A-I may affect lipid binding, which may in turn affect HDL structure and function.


Sociodemographic and clinical correlates of migrant status in adults with psychotic disorders: data from the Australian Survey of High Impact Psychosis.
The links between migrant status and psychosis have attracted considerable attention in recent decades. The aim of the study was to explore the demographic and clinical correlates of migrant v. Australia-born status in individuals with psychotic disorders using a large community-based sample. Data were drawn from a population-based prevalence survey of adults with psychotic disorders. Known as the Survey of High Impact Psychosis (SHIP), it was conducted in seven Australian catchment areas in 2010. Logistic regression was used for the main analyses, examining associations of migrant status with sociodemographic and clinical variables. Of the 1825 participants with psychotic disorders, 17.8% (n = 325) were migrants, of whom 55.7% (n = 181) were male. Compared to Australia-born individuals with psychosis, migrants were more likely to be currently married, to have completed a higher level at school, to have left school later, and to be employed with full-time jobs. Migrants with psychosis were either no different from or less impaired or disadvantaged compared to their Australian-born counterparts on a range of clinical and demographic variables. In a sample of individuals with psychotic disorders, there was no evidence to suggest that migrant status was associated with worse clinical or socio-economic outcomes compared to their native-born counterparts.


Challenges in chronic illness management: a qualitative study of Australian pharmacists' perspectives.
To explore pharmacists' views on managing patients with chronic illness; to understand the incentives and barriers they perceive and the solutions they propose to overcome these barriers. Hospital pharmacists, with experience in managing people with chronic illnesses, working in western Sydney, Australia, were interviewed during June and July 2008. A qualitative study involving group and individual interviews using a semi-structured interview guide. Hospital pharmacists identified lack of communication between different healthcare providers and with patients as a contributing factor to lack of continuity of care and this was perceived as a major barrier in managing patients with chronic illnesses. Pharmacists were also concerned about the effects of medication costs, and poor patient knowledge regarding their disease and medications, and the effects on adherence. Suggested solutions included taking a teamwork approach in the management of chronic illness and providing more information to patients to improve adherence. The identified incentives and barriers have provided valuable information on what pharmacists face in managing patients with chronic illness. Most of the solutions suggested by them have been tested and proven unsuccessful. Develop successful health policy to address the identified barriers remains a challenge.


The role of culture, environment, and religion in the promotion of physical activity among Arab Israelis.
Despite low levels of physical activity among Arabs in Israel, interventions designed to increase physical activity in this population have been scarce. To improve our understanding of the cultural, religious, and environmental barriers and enablers to physical activity, we conducted a qualitative study among Arab Israeli college students in Israel. A total of 45 students participated in 8 focus groups. Purposeful sampling was used to capture the diverse characteristics of participants. Two researchers analyzed the data independently guided by grounded theory. Peer-debriefing sessions were held to group preliminary categories into larger themes. Generally, consensus between researchers was high, and minor differences were resolved. Participants recognized the importance of physical activity in chronic disease prevention, yet most were not regularly physically active. This contradiction could be explained by the fact that many participants lived in an extended-family setting that deemphasized the importance of physical activity. Women often found themselves exercising at odd hours so that they would not be noticed by neighbors. Religion, in comparison, was considered a facilitating factor because the scriptures supported physical activity. Furthermore, an urban environment was an enabling factor because it provided exercise facilities, sidewalks, and a socially acceptable venue for activity. Participants felt resources were not allocated by the government to accommodate physical activity. Increasing Arab Israelis' access to safe and culturally appropriate exercise facilities should become a priority. Thus, policy changes in allocating appropriate funds to promote physical activity must be considered, along with using multiple health promotion strategies.


Co-precipitation synthesis of nanostructured Cu3SbSe4 and its Sn-doped sample with high thermoelectric performance.
Large-scale fabrication of nanostructured Cu3SbSe4 and its Sn-doped sample Cu3Sb0.98Sn0.02Se4 through a low-temperature co-precipitation route is reported. The effects of hot-pressing temperatures, time and Sn doping on the thermoelectric properties of Cu3SbSe4 are explored. The maximum figure of merit ZTmax obtained here reaches 0.62 for the un-doped Cu3SbSe4, which is three times as large as that of Cu3SbSe4 synthesized by the fusion method. Due to the ameliorated power factor by optimized carrier concentration and the reduced lattice thermal conductivity by enhanced phonon scattering at grain interfaces, Sn doping leads to an improvement of thermoelectric performance as compared to Cu3SbSe4. The maximum ZT for Cu3Sb0.98Sn0.02Se4 is 1.05 in this work, which is 50% larger than the largest value reported.


Fecal-Oral Transmission of SARS-CoV-2 In Children: is it Time to Change Our Approach?
Starting from 2 pediatric cases of COVID-19, with confirmation at nasopharyngeal and rectal swabs, we considered the lesson learnt from previous Coronavirus epidemics and reviewed evidence on the current outbreak. Surveillance with rectal swabs might be extended to infants and children, for the implications for household contacts and isolation timing.


Comparative proteomic analysis of bronchoalveolar lavage of familial and sporadic cases of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive deterioration of the alveolar integrity. Among IPF identified phenotypes, that of familial (f-)IPF is usually associated with several gene mutations which are seldom observed in sporadic (s-)IPF. This study aimed at investigating the molecular patterns and variability in f-IPF and s-IPF patients through a differential proteomic analysis. Protein patterns of bronchoalveolar lavage fluid (BALF) samples from 10 familial and 17 sporadic IPF patients were compared using 2D electrophoresis and mass spectrometry. Principal component analysis (PCA) was applied to proteomic data and an enrichment analysis was also performed to characterize specific pathogenic mechanisms and to identify potential biomarkers. BALF samples from f-IPF showed 87 protein spots differentially expressed than those from s-IPF samples; once identified, these spots revealed 22 unique proteins. The functional analysis showed that the endothelial reticulum stress probably plays a central pathogenetic role in f-IPF with an up-regulation of proteins involved in wounding and immune responses, coagulation system, and ion homeostasis. Up-regulated proteins in the s-IPF group were those involved in the oxidative stress response. PCA analysis of differentially expressed proteins clearly distinguished f-IPF from s-IPF patients, and in agreement with radiological and histological patterns, pointed out a higher heterogeneity in f-IPF than s-IPF samples. The 'Slit/Robo signaling', 'clathrin-coated vesicle' and 'cytoskeleton remodelling', were extrapolated by 'pathways analysis' and the results of 'diseases (by biomarkers)' highlighted a 'connective tissue and autoimmune disease', two aspects of increasing interest in IPF.


Pharmacological and Electroceutical Targeting of the Cholinergic Anti-Inflammatory Pathway in Autoimmune Diseases.
Continuous dialogue between the immune system and the brain plays a key homeostatic role in various immune responses to environmental cues. Several functions are under the control of the vagus nerve-based inflammatory reflex, a physiological mechanism through which nerve signals regulate immune functions. In the cholinergic anti-inflammatory pathway, the vagus nerve, its pivotal neurotransmitter acetylcholine, together with the corresponding receptors play a key role in modulating the immune response of mammals. Through communications of peripheral nerves with immune cells, it modulates proliferation and differentiation activities of various immune cell subsets. As a result, this pathway represents a potential target for treating autoimmune diseases characterized by overt inflammation and a decrease in vagal tone. Consistently, converging observations made in both animal models and clinical trials revealed that targeting the cholinergic anti-inflammatory pathway using pharmacologic approaches can provide beneficial effects. In parallel, bioelectronic medicine has recently emerged as an alternative approach to managing systemic inflammation. In several studies, nerve electrostimulation was reported to be clinically relevant in reducing chronic inflammation in autoimmune diseases, including rheumatoid arthritis and diabetes. In the future, these new approaches could represent a major therapeutic strategy for autoimmune and inflammatory diseases.


Depuration of striped venus clam (Chamelea gallina L.): effects on microorganisms, sand content, and mortality.
This study was focused on the evaluation of the microbiological indices, defined by European legislation, before and after the depuration of clams (Chamelea gallina) landed in category B seawater. The survival of depurated clams and the meat yield were also evaluated. The results obtained from October 2002 to September 2003 evidenced a mean microbial reduction during depuration of 62% for Escherichia coli and 54% for fecal coliforms (FC). All the samples had FC counts below the limit after 24 h depuration with the exception of the August samples. E. coli was found in concentration slightly higher than the legal limit only in the samples of December and January. In August, the E. coli concentration did not decrease during the depuration, while in the other samples significant reduction of E. coli concentration was observed. Salmonella spp. and V. parahaemolyticus were never detected in the clams harvested between March and September. Vibrio alginolyticus was found in the clams harvested in May and September both before and after the depuration process. The viability of clam was not negatively affected by depuration, in fact, an increase of viability was observed with the exception of the samples of April. The meat yield was not influenced by the depurative treatment in C. gallina; the mean value found before depuration, 10.47% (with 1.95 SD), did not significantly vary after the treatment (10.58%, SD 2.07). In conclusion, the depuration conditions can improve the quality of C. gallina; however, its effects on microbiological quality depended on environmental conditions.


Comparison of in vivo and in vitro tests of resistance in patients treated with chloroquine in Yaoundé, Cameroon.
The usefulness of an isotopic in vitro assay in the field was evaluated by comparing its results with the therapeutic response determined by the simplified WHO in vivo test in symptomatic Cameroonian patients treated with chloroquine. Of the 117 enrolled patients, 102 (87%) completed the 14-day follow-up, and 95 isolates obtained from these patients (46 children, 49 adults) yielded an interpretable in vitro test. A total of 57 of 95 patients (60%; 28 children and 29 adults) had an adequate clinical response with negative smears (n = 46) or with an asymptomatic parasitaemia (n = 11) on day 7 and/or day 14. The geometric mean 50% inhibitory concentration of the isolates obtained from these patients was 63.3 nmol/l. Late and early treatment failure was observed in 29 (30.5%) and 9 (9.5%) patients, respectively. The geometric mean 50% inhibitory concentrations of the corresponding isolates were 173 nmol/l and 302 nmol/l. Among the patients responding with late and early treatment failure, five isolates and one isolate, respectively, yielded a discordant result (in vivo resistance and in vitro sensitivity). The sensitivity, specificity, and predictive value of the in vitro test to detect chloroquine-sensitive cases was 67%, 84% and 86%, respectively. There was moderate concordance between the in vitro and in vivo tests (kappa value = 0.48). The in vitro assay agrees relatively well with the therapeutic response and excludes several host factors that influence the results of the in vivo test. However, in view of some discordant results, the in vitro test cannot substitute for in vivo data on therapeutic efficacy. The only reliable definition of "resistance" in malaria parasites is based on clinical and parasitological response in symptomatic patients, and the in vivo test provides the standard method to determine drug sensitivity or resistance as well as to guide national drug policies.


A Posting Peculiarity.
The definitions of "radiation area," "high radiation area," and "very high radiation area," provided by the U.S. Department of Energy in 10 CFR Part 835.2, and by the Nuclear Regulatory Commission in 10 CFR Part 20.1003, appear to require redundant posting. This is counterintuitive and would be confusing if the regulations were followed as currently written. We suspect that this is unintentional. However, until the relevant regulations are revised, it is recommended that licensees request written clarification from the regulators to ensure that they are able to demonstrate regulatory compliance.