[Pathogenetic variants of liver steatosis: diagnostic approach using serum lipid levels].
Hepatic steatosis may develop secondary to abnormalities in lipid and/or glucose metabolism. We presume that a phenotype of lipid profile may represent pathogenetic variant of steatosis. liver steatosis had been diagnosed on ultrasonography in 108 patients (27 with alcoholic liver disease, 28 with chronic HCV hepatitis and 21 with chronic HBV hepatitis; 34 patients with chronic viral hepatitis (CVH) had alcohol abuse). Serum levels of total cholesterol (TC), its fractions and triglycerides (TG) were assessed by standard tests. chi2 (chi-square) criterion was used to assess reliability of the lipid parameters deviation, alcohol-induced (AI), virus-induced (VI) and mixed pathogenetic variants of liver steatosis had been identified. TC level >200 mg/dL, LDL-cholesterol >120 mg/dL, TG >150 mg/dL, and normo- or hypoglycemia were typical, while TC level<180 mg/dL and hyperglycemia were not found in patients with AI steatosis. TC level<180 mg/dL, LDL-cholesterol<100 mg/dL and TG<150 mg/dL were typical for VI steatosis. 46,4% of patients with HCV hepatitis and 19% of patients with HBV hepatitis had TC level<140 mg/dL and LDL-cholesterol<70 mg/dL. In patients with CVH and alcohol abuse a mixed variant of liver steatosis has been diagnosed, their serum lipid levels were lower than those in patients with alcoholic liver disease, and insignificantly higher than those in patients with CVH. Conclusions. Determination of pathogenetic type of steatosis in patients with fatty infiltration of the liver is adjunctive to the diagnosis and is a screening test for patients with CVH. Serum levels of HDL-cholesterol below normal values were frequently seen in patient with III grade steatosis.


Diagnostic accuracy of urinary intestinal fatty acid binding protein in detecting colorectal anastomotic leakage.
Anastomotic leakage (AL) remains a severe complication following colorectal surgery, having a negative impact on both short- and long-term outcomes. Since timely detection could enable early intervention, there is a need for the development of novel and accurate, preferably, non-invasive markers. The aim of this study was to investigate whether urinary intestinal fatty acid binding protein (I-FABP) could serve as such a marker. This prospective multicenter cross-sectional phase two diagnostic study was conducted at four centers in the Netherlands between March 2015 and November 2016. Urine samples of 15 patients with confirmed colorectal AL and 19 patients without colorectal AL on postoperative day 3 were included. Urinary I-FABP levels were determined using enzyme-linked immunosorbent assays and adjusted for urinary creatinine to compensate for renal dysfunction. Urinary I-FABP levels were significantly elevated in patients with confirmed AL compared to patients without AL on postoperative day 3 (median: 2.570 ng/ml vs 0.809 ng/ml, p = 0.006). The area under the receiver operating characteristics curve (AUROC) was 0.775, yielding a sensitivity of 80% and specificity of 74% at the optimal cutoff point (> 1.589 ng/ml). This difference remained significant after calculation of I-FABP/creatinine ratios (median: 0.564 ng/µmol vs. 0.158 ng/µmol, p = 0.040), with an AUROC of 0.709, sensitivity of 60% and specificity of 90% at the optimal cutoff point (> 0.469 ng/µmol). Levels of urinary I-FABP and urinary I-FABP/creatinine were significantly elevated in patients with confirmed AL following colorectal surgery, suggesting their potential as a non-invasive biomarker for colorectal anastomotic leakage.


Effects of calcium, pH, and blockiness on kinetic rheological behavior and microstructure of HM pectin gels.
The kinetic behavior during gel formation and the microstructure of 0.75% high methoxyl (HM) pectin gels in 60% sucrose have been investigated by oscillatory measurements and transmission electron microscopy for three comparable citrus pectin samples differing in their degree of blockiness (DB). Ca2+ addition at pH 3.0 resulted in faster gel formation and a lower storage modulus after 3 h for gels of the blockwise pectin A. For gels of the randomly esterified pectin B, the Ca2+ addition resulted in faster gel formation and a higher storage modulus at pH 3.0. At pH 3.5, both pectins A and B were reinforced by the addition of Ca2+. In the absence of Ca2+, the shortest gelation time was obtained for the sample with the highest DB. Microstructural characterization of the gel network, 4 and 20 h after gel preparation, showed no visible changes on a nanometer scale. The microstructure of pectins A and B without Ca2+ was similar, whereas the presence of Ca2+ in pectin A resulted in an inhomogeneous structure.


[Should sex specific differences in venous diseases be explained by pregnancies and hormone intake?].
Diseases of the venous system are among the most frequently occurring diseases in the German population. However, the last comprehensive population-based German data were obtained in 1979. Since then, diagnostic methods have improved substantially. Here, we examine the prevalence of venous diseases in women and their association with pregnancies and intake of hormones. We conducted a population-based cross-sectional study in Bonn and rural environments (Recruitment period: 11/2000 - 11/2001; response: 59 %; 3072 study participants (1350 men, 1722 women), 18 to 79 years of age; investigation: standardised medical history, physical examination, duplex sonography, photography and CEAP-classification of veins of the legs). The following definitions were used: 1) Varicosis: clinical classification C2-C6 (primary varicosis only, excluding those showing spider-bursts exclusively); 2) Chronic venous insufficiency (CVI): C3-C6. For women, the risk factors examined were the number of pregnancies (P) and intake of hormones. Odds ratios (OR) and 95 % confidence intervals (95 %-CI) were calculated by multiple logistic regression (adjusted for age, region of residence and socioeconomic status). In addition, never pregnant women and men were compared regarding the two outcome variables. 713 participants (23 %) had varicosis and 522 (17 %) CVI. The OR for women (reference group: men) was OR = 1.4, 95 %-CI: 1.25 - 1.79 (varicosis) and OR = 1.2, 95 %-CI: 0.93 - 1.42 (CVI). There was a positive dose-response relationship between the number of pregnancies and varicosis: 1 P: OR = 1.3 (95 %-CI: 0.89 - 1.96), 2 P: OR = 1.4 (95 %-CI: 1.00 - 2.07), 3 P: OR = 1.6 (95 %-CI: 1.05 - 2.41), 4 P: OR = 1.9 (95 %-CI: 1.18 - 3.20), > or = 5 P: OR = 2.2 (95 %-CI: 1.28 - 3.74) and this trend was similar for CVI. Never-pregnant women (n = 518) and men had a similar prevalence. We did not see a consistent effect of intake of hormones in varicosis (OR = 0.9 [95 %-CI: 0.68 - 1.22]), but a negative association with CVI (OR = 0.6 [95 %-CI: 0.47 - 0.89]). Our results confirm the known association between diseases of the venous system and pregnancies, which seem to explain a big share of the sex-specific differences in the prevalence of these diseases.


Minimus: a fast, lightweight genome assembler.
Genome assemblers have grown very large and complex in response to the need for algorithms to handle the challenges of large whole-genome sequencing projects. Many of the most common uses of assemblers, however, are best served by a simpler type of assembler that requires fewer software components, uses less memory, and is far easier to install and run. We have developed the Minimus assembler to address these issues, and tested it on a range of assembly problems. We show that Minimus performs well on several small assembly tasks, including the assembly of viral genomes, individual genes, and BAC clones. In addition, we evaluate Minimus' performance in assembling bacterial genomes in order to assess its suitability as a component of a larger assembly pipeline. We show that, unlike other software currently used for these tasks, Minimus produces significantly fewer assembly errors, at the cost of generating a more fragmented assembly. We find that for small genomes and other small assembly tasks, Minimus is faster and far more flexible than existing tools. Due to its small size and modular design Minimus is perfectly suited to be a component of complex assembly pipelines. Minimus is released as an open-source software project and the code is available as part of the AMOS project at Sourceforge.


Control of mammary stem cell function by steroid hormone signalling.
The ovarian hormones oestrogen and progesterone profoundly influence breast cancer risk, underpinning the benefit of endocrine therapies in the treatment of breast cancer. Modulation of their effects through ovarian ablation or chemoprevention strategies also significantly decreases breast cancer incidence. Conversely, there is an increased risk of breast cancer associated with pregnancy in the short term. The cellular mechanisms underlying these observations, however, are poorly defined. Here we demonstrate that mouse mammary stem cells (MaSCs) are highly responsive to steroid hormone signalling, despite lacking the oestrogen and progesterone receptors. Ovariectomy markedly diminished MaSC number and outgrowth potential in vivo, whereas MaSC activity increased in mice treated with oestrogen plus progesterone. Notably, even three weeks of treatment with the aromatase inhibitor letrozole was sufficient to reduce the MaSC pool. In contrast, pregnancy led to a transient 11-fold increase in MaSC numbers, probably mediated through paracrine signalling from RANK ligand. The augmented MaSC pool indicates a cellular basis for the short-term increase in breast cancer incidence that accompanies pregnancy. These findings further indicate that breast cancer chemoprevention may be achieved, in part, through suppression of MaSC function.


The Robust EM-type Algorithms for Log-concave Mixtures of Regression Models.
Finite mixture of regression (FMR) models can be reformulated as incomplete data problems and they can be estimated via the expectation-maximization (EM) algorithm. The main drawback is the strong parametric assumption such as FMR models with normal distributed residuals. The estimation might be biased if the model is misspecified. To relax the parametric assumption about the component error densities, a new method is proposed to estimate the mixture regression parameters by only assuming that the components have log-concave error densities but the specific parametric family is unknown. Two EM-type algorithms for the mixtures of regression models with log-concave error densities are proposed. Numerical studies are made to compare the performance of our algorithms with the normal mixture EM algorithms. When the component error densities are not normal, the new methods have much smaller MSEs when compared with the standard normal mixture EM algorithms. When the underlying component error densities are normal, the new methods have comparable performance to the normal EM algorithm.


Middle East Respiratory Syndrome Coronavirus and Severe Acute Respiratory Syndrome Coronavirus.
Emerging infectious diseases continue to be of a significant importance worldwide with the potential to cause major outbreaks and global pandemics. In 2002, the world had witnessed the appearance of the severe acute respiratory syndrome coronavirus in China which disappeared abruptly within 6 months. About a decade later, a new and emerging novel coronavirus named the Middle East respiratory syndrome coronavirus (MERS-CoV) was described in a patient from Saudi Arabia. These two coronaviruses shared multiple similarities in the epidemiology, clinical presentations, and posed challenges in its prevention and management. Seven years since its discovery, MERS-CoV continues to be a lethal zoonotic pathogen capable of causing severe pneumonia with high case fatality rates and the ability to cause large health care-associated outbreaks.


The transcriptome landscape of early maize meiosis.
A major step in the higher plant life cycle is the decision to leave the mitotic cell cycle and begin the progression through the meiotic cell cycle that leads to the formation of gametes. The molecular mechanisms that regulate this transition and early meiosis remain largely unknown. To gain insight into gene expression features during the initiation of meiotic recombination, we profiled early prophase I meiocytes from maize (Zea mays) using capillary collection to isolate meiocytes, followed by RNA-seq. We detected ~2,000 genes as preferentially expressed during early meiotic prophase, most of them uncharacterized. Functional analysis uncovered the importance of several cellular processes in early meiosis. Processes significantly enriched in isolated meiocytes included proteolysis, protein targeting, chromatin modification and the regulation of redox homeostasis. The most significantly up-regulated processes in meiocytes were processes involved in carbohydrate metabolism. Consistent with this, many mitochondrial genes were up-regulated in meiocytes, including nuclear- and mitochondrial-encoded genes. The data were validated with real-time PCR and in situ hybridization and also used to generate a candidate maize homologue list of known meiotic genes from Arabidopsis. Taken together, we present a high-resolution analysis of the transcriptome landscape in early meiosis of an important crop plant, providing support for choosing genes for detailed characterization of recombination initiation and regulation of early meiosis. Our data also reveal an important connection between meiotic processes and altered/increased energy production.


Recommended Guidelines for Developing, Qualifying, and Implementing Complex In Vitro Models (CIVMs) for Drug Discovery.
The pharmaceutical industry is continuing to face high research and development (R&D) costs and low overall success rates of clinical compounds during drug development. There is an increasing demand for development and validation of healthy or disease-relevant and physiological human cellular models that can be implemented in early-stage discovery, thereby shifting attrition of future therapeutics to a point in discovery at which the costs are significantly lower. There needs to be a paradigm shift in the early drug discovery phase (which is lengthy and costly), away from simplistic cellular models that show an inability to effectively and efficiently reproduce healthy or human disease-relevant states to steer target and compound selection for safety, pharmacology, and efficacy questions. This perspective article covers the various stages of early drug discovery from target identification (ID) and validation to the hit/lead discovery phase, lead optimization, and preclinical safety. We outline key aspects that should be considered when developing, qualifying, and implementing complex in vitro models (CIVMs) during these phases, because criteria such as cell types (e.g., cell lines, primary cells, stem cells, and tissue), platform (e.g., spheroids, scaffolds or hydrogels, organoids, microphysiological systems, and bioprinting), throughput, automation, and single and multiplexing endpoints will vary. The article emphasizes the need to adequately qualify these CIVMs such that they are suitable for various applications (e.g., context of use) of drug discovery and translational research. The article ends looking to the future, in which there is an increase in combining computational modeling, artificial intelligence and machine learning (AI/ML), and CIVMs.


The effects of diffusion on an exonuclease/nanopore-based DNA sequencing engine.
Over 15 years ago, the ability to electrically detect and characterize individual polynucleotides as they are driven through a single protein ion channel was suggested as a potential method for rapidly sequencing DNA, base-by-base, in a ticker tape-like fashion. More recently, a variation of this method was proposed in which a nanopore would instead detect single nucleotides cleaved sequentially by an exonuclease enzyme in close proximity to one pore entrance. We analyze the exonuclease/nanopore-based DNA sequencing engine using analytical theory and computer simulations that describe nucleotide transport. The available data and analytical results suggest that the proposed method will be limited to reading <80 bases, imposed, in part, by the short lifetime each nucleotide spends in the vicinity of the detection element within the pore and the ability to accurately discriminate between the four mononucleotides.


Comparing sediment preservation methods for genomic biomonitoring of coastal marine ecosystems.
To avoid loss of genetic information in environmental DNA (eDNA) field samples, the preservation of nucleic acids during field sampling is a critical step. In the development of standard operating procedures (SOPs) for eDNA-based compliance monitoring, the effect of different routinely used sediment preservations on biological community structures serving as bioindicators has gone untested. We compared eDNA metabarcoding results of marine bacterial communities from sample aliquots that were treated with a nucleic acid preservation solution (treated samples) and aliquots that were frozen without further treatment (non-treated samples). Sediment samples were obtained from coastal locations subjected to different stressors (aquaculture, urbanization, industry). DNA extraction efficiency, bacterial community profiles, and measures of alpha- and beta-diversity were highly congruent between treated and non-treated samples. As both preservation methods provide the same relevant information to environmental managers and regulators, we recommend the inclusion of both methods into SOPs for biomonitoring in marine coastal environments.


Comparison of Laser Hemorrhoidoplasty and Milligan-Morgan Hemorrhoidectomy Techniques in the Treatment of Grade 2 and 3 Hemorrhoidal Disease.
The estimated prevalence of hemorrhoidal disease (HD) worldwide ranges from 2.9% to 27.9%. Conservative, medical, non-operative, and surgical therapy approaches are applied in HD treatment. Milligan-Morgan (MM) hemorrhoidectomy which is the most well-known and frequently applied surgical treatment method, and Laser hemorrhoidoplasty (LH) are among the accepted treatment methods in Grade 2-3 HD treatment where medical treatment is insufficient. In this study, the early results of laser hemorrhoidoplasty and Milligan-Morgan hemorrhoidectomy techniques were compared. A randomized clinical trial. The study included ASA 1-3, total 85 patients aged 18-70 years old with symptomatic Grade 2 and Grade 3 hemorrhoidal disease whose symptoms persisted despite at least one month of medical treatment. Fifty-four patients were allocated to Group L, whereas 31 were allocated to Group M. Age, gender, weight, body mass index, preoperative symptoms, presence of additional disease, use of anticoagulant medication, and length of hospital stay of the patients included in the study were recorded. Rescue analgesic used was recorded. Postoperative VAS score and complications were recorded within 10 days. The total energy numbers applied to all packages were recorded. The incidence of minor perioperative hemorrhage was significantly lower in Group L compared to Group M (P = .035). The postoperative 3rd-hour VAS scores were statistically significantly lower in Group L compared to Group (P < .001). At the 3rd hour postoperatively, the need for rescue analgesia was statistically significantly higher in Group M compared to Group L. On the seventh postoperative day, Group M needed considerably more rescue analgesia compared to Group L (P < .001, P = 1.00, P = .035, respectively). The cut-off value of 571 J was calculated in Group L. We believe that it is not an advantageous method compared to MM hemorrhoidectomy, both in terms of patient comfort and cost-effectiveness, since postoperative pain, which is shown as the most important advantage of LH over conventional hemorrhoidectomy methods in the literature, can be relieved with simple NSA-I rescue analgesia in patients undergoing MM. Trial Registration: 03.06.2021/21-63.


Analysis of Leukocyte Subpopulations by Flow Cytometry during Hospitalization Depending on the Severity of COVID-19 Course.
The mechanisms underlying the immune response to coronavirus disease 2019 (COVID-19) and the recovery process have not been fully elucidated. The aim of the study was to analyze leukocyte subpopulations in patients at significant time points (at diagnosis, and 3 and 6 months after infection) selected according to the analysis of changes in the lungs by the CT classification system, considering the severity of the disease. The study groups consisted of severe and non-severe COVID-19 patients. There was a significant decrease in CD8+ T cells, NK and eosinophils, with an increasing percentage of neutrophils during hospitalization. We noticed lower levels of CD4 and CD8 T lymphocytes, eosinophils, basophils, and CD16+ monocytes and elevated neutrophil levels in severe patients relative to non-severe patients. Three months after infection, we observed higher levels of basophils, and after 6 months, higher CD4/CD8 ratios and T cell levels in the severe compared to non-severe group. Non-severe patients showed significant changes in the leukocyte populations studied at time of hospitalization and both within 3 months and 6 months of onset. The CT CSS classification with parameters of the flow cytometry method used for COVID-19 patients determined changes that proved useful in the initial evaluation of patients.


Non-ischaemic cardiomyopathy, sudden death and implantable defibrillators: a review and meta-analysis.
The recent Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial suggested that implantable cardioverter defibrillators (ICDs) do not reduce overall mortality in patients with non-ischaemic cardiomyopathy (NICM), despite reducing sudden cardiac death. We performed an updated meta-analysis to examine the impact of ICD therapy on mortality in NICM patients. A systematic search for studies that examined the effect of ICDs on outcomes in NICM was performed. Our analysis compared patients randomised to an ICD with those randomised to no ICD, and examined the endpoint of overall mortality. Six primary prevention trials and two secondary prevention trials were identified that met the pre-specified search criteria. Using a fixed-effects model, analysis of primary prevention trials revealed a reduction in overall mortality with ICD therapy (RR 0.76, 95% CI 0.65 to 0.91). Although our updated meta-analysis demonstrates a survival benefit of ICD therapy, the effect is substantively weakened by the inclusion of the DANISH trial-which is both the largest and most recent of the analysed trials-indicating that the residual pooled benefit of ICDs may reflect the risk of sudden death in older trials which included patients treated sub-optimally by contemporary standards. As such, these data must be interpreted cautiously. The results of the DANISH trial emphasise that there is no 'one size fits all' indication for primary prevention ICDs in NICM patients, and clinicians must consider age and comorbidity on an individual basis when determining whether a defibrillator is appropriate.


Uncovering developmental time and tempo using deep learning.
During animal development, embryos undergo complex morphological changes over time. Differences in developmental tempo between species are emerging as principal drivers of evolutionary novelty, but accurate description of these processes is very challenging. To address this challenge, we present here an automated and unbiased deep learning approach to analyze the similarity between embryos of different timepoints. Calculation of similarities across stages resulted in complex phenotypic fingerprints, which carry characteristic information about developmental time and tempo. Using this approach, we were able to accurately stage embryos, quantitatively determine temperature-dependent developmental tempo, detect naturally occurring and induced changes in the developmental progression of individual embryos, and derive staging atlases for several species de novo in an unsupervised manner. Our approach allows us to quantify developmental time and tempo objectively and provides a standardized way to analyze early embryogenesis.


Police deaths in New York and London during the twentieth century.
To describe the incidences and causes of occupational police deaths in New York City in the United States and Greater London in the United Kingdom during the twentieth century. To assess the relation between overall societal violence and violence directed toward police officers in these metropolitan areas. Ecological study of New York and London from 1900 through 1999. Intentional and unintentional occupational police mortality rates for New York and London were estimated for each decade. The general population homicide rates of both New York and London were assessed for their correlation with their respective intentional occupational police mortality rates. During the 20th century, 585 police officers in New York and 160 police officers in London died while participating in law enforcement activities. New York had markedly greater intentional police mortality rates compared to London throughout most of the 20th century, but these differences decreased significantly by the end of the century. Intentional gunshot wounds comprised 290 police deaths in New York, but only 14 police deaths in London. In New York, gun shot wounds (both intentional and unintentional) accounted for more occupational police deaths (51.6%) than did all other injury mechanisms combined. In London, motor vehicle collision was the most common cause (47.5%) of occupational police death. There were no apparent correlations between the general population homicide rates and intentional police mortality rates in either New York (r(2) = 0.05, 95% CI -0.77 to 0.81) or London (r(2) = 0.34, 95% CI -0.61 to 0.89). During the 20th century, both intentional and unintentional occupational police mortality rates were significantly greater in New York compared to London. These differences are likely from several socioeconomic, cultural, and occupational factors. The declines in police deaths in New York during the latter part of the 20th century indicate that at least some measures taken by the New York Police Department have been successful at significantly reducing the incidence of both intentional and unintentional police deaths.


Role of the N-terminal transmembrane domain in the endo-lysosomal targeting and function of the human ABCB6 protein.
ATP-binding cassette, subfamily B (ABCB) 6 is a homodimeric ATP-binding cassette (ABC) transporter present in the plasma membrane and in the intracellular organelles. The intracellular localization of ABCB6 has been a matter of debate, as it has been suggested to reside in the mitochondria and the endo-lysosomal system. Using a variety of imaging modalities, including confocal microscopy and EM, we confirm the endo-lysosomal localization of ABCB6 and show that the protein is internalized from the plasma membrane through endocytosis, to be distributed to multivesicular bodies and lysosomes. In addition to the canonical nucleotide-binding domain (NBD) and transmembrane domain (TMD), ABCB6 contains a unique N-terminal TMD (TMD0), which does not show sequence homology to known proteins. We investigated the functional role of these domains through the molecular dissection of ABCB6. We find that the folding, dimerization, membrane insertion and ATP binding/hydrolysis of the core-ABCB6 complex devoid of TMD0 are preserved. However, in contrast with the full-length transporter, the core-ABCB6 construct is retained at the plasma membrane and does not appear in Rab5-positive endosomes. TMD0 is directly targeted to the lysosomes, without passage to the plasma membrane. Collectively, our results reveal that TMD0 represents an independently folding unit, which is dispensable for catalysis, but has a crucial role in the lysosomal targeting of ABCB6.


Increasing circulating sphingosine-1-phosphate attenuates lung injury during ex vivo lung perfusion.
Sphingosine-1-phosphate regulates endothelial barrier integrity and promotes cell survival and proliferation. We hypothesized that upregulation of sphingosine-1-phosphate during ex vivo lung perfusion would attenuate acute lung injury and improve graft function. C57BL/6 mice (n = 4-8/group) were euthanized, followed by 1 hour of warm ischemia and 1 hour of cold preservation in a model of donation after cardiac death. Subsequently, mice underwent 1 hour of ex vivo lung perfusion with 1 of 4 different perfusion solutions: Steen solution (Steen, control arm), Steen with added sphingosine-1-phosphate (Steen + sphingosine-1-phosphate), Steen plus a selective sphingosine kinase 2 inhibitor (Steen + sphingosine kinase inhibitor), or Steen plus both additives (Steen + sphingosine-1-phosphate + sphingosine kinase inhibitor). During ex vivo lung perfusion, lung compliance and pulmonary artery pressure were continuously measured. Pulmonary vascular permeability was assessed with injection of Evans Blue dye. The combination of 1 hour of warm ischemia, followed by 1 hour of cold ischemia created significant lung injury compared with lungs that were immediately harvested after circulatory death and put on ex vivo lung perfusion. Addition of sphingosine-1-phosphate or sphingosine kinase inhibitor alone did not significantly improve lung function during ex vivo lung perfusion compared with Steen without additives. However, group Steen + sphingosine-1-phosphate + sphingosine kinase inhibitor resulted in significantly increased compliance (110% ± 13.9% vs 57.7% ± 6.6%, P < .0001) and decreased pulmonary vascular permeability (33.1 ± 11.9 μg/g vs 75.8 ± 11.4 μg/g tissue, P = .04) compared with Steen alone. Targeted drug therapy with a combination of sphingosine-1-phosphate + sphingosine kinase inhibitor during ex vivo lung perfusion improves lung function in a murine donation after cardiac death model. Elevation of circulating sphingosine-1-phosphate via specific pharmacologic modalities during ex vivo lung perfusion may provide endothelial protection in marginal donor lungs leading to successful lung rehabilitation for transplantation.


An early (sixth-hour) serum bilirubin measurement is useful in predicting the development of significant hyperbilirubinemia and severe ABO hemolytic disease in a selective high-risk population of newborns with ABO incompatibility.
In the era of early discharge of newborns from the hospital, newborns with ABO incompatibility are at especially greater risk for developing a subsequent significant hyperbilirubinemia because some of these infants also may present with some degree of ABO isoimmune disease. In this study, we aimed to determine prospectively the critical serum total bilirubin level to predict significant hyperbilirubinemia and severe hemolytic disease in healthy term newborns with ABO incompatibility based on a serum bilirubin measurement made at a postnatal age at which all newborns are at the hospital before discharge and at which any therapeutic intervention, if necessary, could be started as early as possible. A total of 136 healthy term newborns with ABO (O-A or O-B) blood group incompatibility were followed prospectively with daily serum total bilirubin measurements for the first 5 days of life. Newborns with serum total bilirubin levels of > or =5 mg/dL and an increase in serum total bilirubin concentration of >0.5 mg/dL/h in the first 24 hours, > or =12 mg/dL on day 2, > or =15 mg/dL on day 3, and > or =17 mg/dL on days 4 and 5 were defined to have significant hyperbilirubinemia and were started on phototherapy treatment. Additional treatment modalities, including intense phototherapy, intravenous immunoglobulin treatment, and exchange transfusion, were used when serum bilirubin concentrations exceeded 20 mg/dL or increased by >1 mg/dL/h despite a phototherapy treatment of at least 4 hours. The additional assessment of the predictive ability of the sixth-hour serum total bilirubin value in determining the development of significant hyperbilirubinemia was made on the basis of the placement of any of the first 5 days' serum bilirubin measurements in the > or =90th percentile of the study population. On the basis of the percentile tracks constructed from the 10th, 35th, 50th, 60th, and 90th percentiles of serum total bilirubin values, a nomogram demonstrating the 3 percentile tracks as risk zone demarcators with divided risk zones was produced. Twenty-nine newborns (21.3%) had significant hyperbilirubinemia. There were significant differences between the newborns who did and the newborns who did not develop significant hyperbilirubinemia with respect to the reticulocyte count (4.39 +/- 3.46% vs 2.95 +/- 1.63) and the presence of a direct antiglobulin test positivity (6 of 23 vs 0 of 107) and a sibling with neonatal jaundice (6 of 23 vs 5 of 102). A mean serum bilirubin level of > or =4 mg/dL at the sixth hour of life was determined to have the highest sensitivity (86.2%) and negative predictive value (94.5%) and a positive predictive value of 39.7% to predict the newborns who would develop significant hyperbilirubinemia. At the mean serum bilirubin level of 6 mg/dL, the sensitivity, specificity, and negative and positive predictive values were 100%, 91.5%, 100%, and 35.3%, respectively, in diagnosing 6 cases of severe ABO hemolytic disease. On the hour (age)-specific percentile-based nomogram, the zone above the 90th percentile was determined as high risk and that below the 35th percentile as low risk. The reticulocyte count, a positive direct antiglobulin test, and the presence of a sibling with neonatal jaundice were determined to be the good predictors for the development of significant hyperbilirubinemia and severe hemolytic disease of the newborn. A serum bilirubin measurement and the use of the critical bilirubin levels of 4 mg/dL and 6 mg/dL at the sixth hour of life will predict nearly all newborns who will have significant hyperbilirubinemia and those who will develop severe hemolytic disease of the newborn, respectively. An hour (age)-specific percentile-based nomogram can be used to predict which newborn is at high risk (> or =90th percentile), intermediate risk (35th-90th percentiles), and low risk (<35th percentile) for developing significant hyperbilirubinemia. The 35th and 90th percentile tracks, approximating the serum bilirubin levels of 3.3 mg/dL and 6.5 mg/dL at the sixth hour of life, respectively, can be used as safe risk demarcators in deciding about the time of discharge of ABO-incompatible newborns from the hospital.


Changes in mortality rates and ratios in people with pharmacologically treated type 2 diabetes mellitus between 2001 and 2016 in Hungary.
Type 2 diabetes mellitus (T2DM) is associated with a higher risk of all-cause mortality; however, detailed analyses of subgroups are rare. In this study we analyzed the changes of age- and gender-specific all-cause mortality rates and ratios in T2DM subjects (aged > 40 years) in Hungary between 2001 and 2016. We used the central database of the National Institute of Health Insurance Fund. All-cause mortality rates in patients with T2DM and ratios (T2DM/non-T2DM) were determined in males/females and in different age-groups. Age-adjusted values were used for standardized mortality rates. Among pharmacologically treated T2DM subjects we found 117,700 and 329,845 males, 232,143 and 391,382 females in 2001 and 2016, respectively. Standardized all-cause mortality rate was higher in males than in females in 2001 (4540/100,000 vs. 3365/100,000) which decreased to 4125/100,000 in males (total change: -11.8%, p < 0.0001) and to 2977/100,000 in females (total change: -9.2%; p = 0.0558) in 2016. We found a significant increase (8.35%; p = 0.0272) in standardized all-cause mortality ratios between 2001 and 2016 which was higher in males (11.44%; p = 0.0096) than in females (2.78%; p = 0.3288). We observed the most pronounced increase in younger age-groups (age 41-60 years) in both genders (change varied from 54.2% to 101.8%; p < 0.05) which was due to distinct tendencies in changes of mortality curves. Pharmacologically treated T2DM subjects in lower age-groups (41-60 years) had the highest increase in all-cause mortality ratios between 2001 and 2016 in Hungary. These data indicate that relatively younger patients with T2DM need special attention for improving long-term outcomes.


Expression of Low Level of VPS35-mCherry Fusion Protein Diminishes Vps35 Depletion Induced Neuron Terminal Differentiation Deficits and Neurodegenerative Pathology, and Prevents Neonatal Death.
Vps35 (vacuolar protein sorting 35) is a key component of retromer that consists of Vps35, Vps26, and Vps29 trimers, and sortin nexin dimers. Dysfunctional Vps35/retromer is believed to be a risk factor for development of various neurodegenerative diseases. Vps35Neurod6 mice, which selectively knock out Vps35 in Neurod6-Cre+ pyramidal neurons, exhibit age-dependent impairments in terminal differentiation of dendrites and axons of cortical and hippocampal neurons, neuro-degenerative pathology (i.e., increases in P62 and Tdp43 (TAR DNA-binding protein 43) proteins, cell death, and reactive gliosis), and neonatal death. The relationships among these phenotypes and the underlying mechanisms remain largely unclear. Here, we provide evidence that expression of low level of VPS35-mCherry fusion protein in Vps35Neurod6 mice could diminish the phenotypes in an age-dependent manner. Specifically, we have generated a conditional transgenic mouse line, LSL-Vps35-mCherry, which expresses VPS35-mCherry fusion protein in a Cre-dependent manner. Crossing LSL-Vps35-mCherry with Vps35Neurod6 to obtain TgVPS35-mCherry, Vps35Neurod6 mice prevent the neonatal death and diminish the dendritic morphogenesis deficit and gliosis at the neonatal, but not the adult age. Further studies revealed that the Vps35-mCherry transgene expression was low, and the level of Vps35 mRNA comprised only ~5-7% of the Vps35 mRNA of control mice. Such low level of VPS35-mCherry could restore the amount of other retromer components (Vps26a and Vps29) at the neonatal age (P14). Importantly, the neurodegenerative pathology presented in the survived adult TgVps35-mCherry; Vps35Neurod6 mice. These results demonstrate the sufficiency of low level of VPS35-mCherry fusion protein to diminish the phenotypes in Vps35Neurod6 mice at the neonatal age, verifying a key role of neuronal Vps35 in stabilizing retromer complex proteins, and supporting the view for Vps35 as a potential therapeutic target for neurodegenerative diseases.


Provision for children with developmental co-ordination disorder (DCD): audit of the service provider.
The aim of this study was to conduct an audit of parent/carer satisfaction with the service provided for children presenting with movement difficulties [developmental co-ordination disorder (DCD)/dyspraxia] at the out-patient physiotherapy clinic of a specialist tertiary referral paediatric hospital. A postal questionnaire was used to obtain objective and subjective data on the service offered. Factual information on aspects such as waiting time for first appointment, type of intervention offered, etc. was checked against clinical records. Satisfaction with the service was assessed using ratings and open-ended comment. Forty-five families completed the questionnaire. The results showed that the service was generally rated highly. The opportunity to discuss the child's problems and its implications was considered valuable. Among families offered 1 : 1 intervention, a statistically significant correlation emerged between the number of sessions attended and perceived effectiveness. Among families offered a home programme, perceived effectiveness was related to the number of times per week the child practised the programme. This study showed that many children from mainstream schools with co-ordination problems continued to find it difficult to obtain a clear diagnosis. Once a referral and assessment had been achieved, however, parents/carers were shown to be satisfied with the package offered by this service provider.


Drug release behavior of electrospun twisted yarns as implantable medical devices.
In this study, twisted drug-loaded poly(L-lactide) (PLLA) and hybrid poly(L-lactide)/poly(vinyl alcohol) (PLLA/PVA) yarns were produced using an electrospinning technique based on two oppositely charged nozzles. Cefazolin, an antibiotic drug was incorporated in the yarn fibers by addition to the PLLA electrospinning solution. Morphological studies showed that independent of the twist rate, uniform and smooth fibers were formed. The diameter of the electrospun fibers in the yarns decreased at higher twist rates but produced yarns with larger diameters. At increasing twist rates the crystallinity of the fibers in the yarns increased. In the presence of cefazolin the fiber diameter, yarn diameter and crystallinity were always lower than in the non-drug loaded yarns. In addition the yarn mechanical properties revealed a slightly lower strength, modulus and elongation at break upon drug loading. The effect of the twist rate on the cefazolin in vitro release behavior from both PLLA and hybrid yarns revealed similar profiles for both types of drug-loaded yarns. However, the total amount of drug released from the hybrid PLLA/PVA yarns was significantly higher. The release kinetics over a period of 30 d were fitted to different mathematical models. Cefazolin release from electrospun PLLA yarns was governed by a diffusion mechanism and could best be fitted by Peppas and Higuchi models. The models that were found best to describe the drug release mechanism from the hybrid PLLA/PVA yarns were a first-order model and the Higuchi model.


Sonographic detection of small amounts of free peritoneal gas in beagle dogs.
The detection of small amounts of free peritoneal gas in the canine patient can pose a diagnostic dilemma. The objective of this study was to determine how much of this free gas could be detected ultrasonographically. Ultrasound examinations were carried out after increments (0.1 ml) of air were intraperitoneally injected. Via ultrasonography, 0.4 ml of free gas can be reliably detected. The authors concluded that ultrasonography is a very sensitive modality for the detection of small amounts of peritoneal free gas (above 0.4 ml).


Transcriptome profiles of soybean leaves and roots in response to zinc deficiency.
Zinc (Zn) deficiency is a widespread agricultural problem in arable soils of the whole world. However, the molecular mechanisms underlying Zn-deficiency response are largely unknown. Here, we analyzed the transcriptomic profilings of soybean leaves and roots in response to Zn deficiency through Illumina's high-throughput RNA sequencing in order to understand the molecular basis of Zn-deficiency response in the plants. A total of 614 and 1011 gene loci were found to be differentially expressed in leaves and roots, respectively, and 88 loci were commonly found in both leaves and roots. Twelve differentially expressed genes (DEGs) were randomly selected for validation by quantitative reverse transcription polymerase chain reaction, and their fold changes were similar to those of RNA-seq. Gene ontology enrichment analysis showed that ion transport, nicotianamine (NA) biosynthetic process and queuosine biosynthetic process were enriched in the upregulated genes, while oxidation-reduction process and defense response were enriched in the downregulated genes. Among the DEGs, 20 DEGs are potentially involved in Zn homeostasis, including seven ZRT, IRT-related protein (ZIP) transporter genes, three NA synthase genes, and seven metallothionein genes; 40 DEGs are possibly involved in diverse hormonal signals such as auxin, cytokinin, ethylene and gibberellin; nine DEGs are putatively involved in calcium signaling; 85 DEGs are putative transcription factor genes. Nine DEGs were found to contain zinc-deficiency-response element in their promoter regions. These results could provide comprehensive insights into the soybean response to Zn deficiency and will be helpful for further elucidation of the molecular mechanisms of Zn-deficiency response and Zn-deficiency tolerance in plants.


Diabetes noninvasive diagnostics and monitoring through volatile biomarkers analysis in the exhaled breath using optical absorption spectroscopy.
The review is aimed on the analysis the abilities of noninvasive diagnostics and monitoring of diabetes mellitus (DM) and DM-associated complications through volatile molecular biomarkers detection in the exhaled breath. The specific biochemical reactions in the body of DM patients and their associations with volatile molecular biomarkers in the breath are considered. The applications of optical spectroscopy methods, including UV, IR, and terahertz spectroscopy for DM-associated volatile molecular biomarkers measurements, are described. The applications of similar technique combined with machine learning methods in DM diagnostics using the profile of DM-associated volatile molecular biomarkers in exhaled air or "pattern-recognition" approach are discussed.


Impact of expert versus measurement-based occupational noise exposure estimates on exposure-response relationships.
Expert-judgment has frequently been used to assess quantitative exposure for epidemiologic studies, but accuracy varies widely dependent on the type of exposure and the availability of measurements to anchor estimates. There is limited empirical evidence of the sensitivity of exposure-response relationships to expert- versus measurement-based exposure assessment strategies. We examined the sensitivity of the exposure-response relationship between occupational noise exposure and acute myocardial infarction (AMI) mortality using both expert- and measurement-based occupational noise estimates in a retrospective cohort study of sawmill workers (n = 27,499). Expert-based noise estimates were evaluated by four industry experts who rated 54 sawmill jobs on a four-point scale. Measurement-based noise estimates were derived from statistical models that accounted for job, mill, and time period differences. The model-based estimates were adjusted to account for the use of hearing protective devices (HPD). We examined the shape, goodness of fit, precision, and expected versus observed attenuation of the exposure-response relationships between cumulative noise exposure and AMI mortality (910 deaths). The correlations between the expert-based and the measurement-based unadjusted and HPD-adjusted cumulative noise estimates were 0.81 and 0.57, respectively. The HPD-adjusted model-based estimates provided the most precise exposure-response relationship; no associations were observed with the unadjusted or expert-based noise estimates. In a subgroup with minimal HPD use (n = 8,700, 520 deaths), the expert- and model-based noise estimates resulted in similar relative risks; the model-based approach was 12% more precise. The measurement-based approach was more precise, as expected, but experts were reasonably able to rank occupational noise exposures. The experts' assessment was, however, unable to account for HPD use, which made a substantial contribution to exposure misclassification in this study. The experts' noise estimates would be more useful for risk assessment if they were calibrated against units of noise exposure.


Is peroxisome proliferator-activated receptor gamma (PPARγ) a therapeutic target for the treatment of pulmonary hypertension?
Pulmonary hypertension (PH), a progressive disorder associated with significant morbidity and mortality, is caused by complex pathways that culminate in structural and functional alterations of the pulmonary circulation and increases in pulmonary vascular resistance and pressure. Diverse genetic, pathological, or environmental triggers stimulate PH pathogenesis culminating in vasoconstriction, cell proliferation, vascular remodeling, and thrombosis. We conducted a thorough literature review by performing MEDLINE searches via PubMed to identify articles pertaining to PPARγ as a therapeutic target for the treatment of PH. This review examines basic and preclinical studies that explore PPARγ and its ability to regulate PH pathogenesis. Despite the current therapies that target specific pathways in PH pathogenesis, including prostacyclin derivatives, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors, morbidity and mortality related to PH remain unacceptably high, indicating the need for novel therapeutic approaches. Consequently, therapeutic targets that simultaneously regulate multiple pathways involved in PH pathogenesis have gained attention. This review focuses on peroxisome proliferator-activated receptor gamma (PPARγ), a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. While the PPARγ receptor is best known as a master regulator of lipid and glucose metabolism, a growing body of literature demonstrates that activation of PPARγ exerts antiproliferative, antithrombotic, and vasodilatory effects on the vasculature, suggesting its potential efficacy as a PH therapeutic target.


Molecular behavior in living mitotic cells of human centromere heterochromatin protein HPLalpha ectopically expressed as a fusion to red fluorescent protein.
We constructed stable mammalian cell lines in which human heterochromatin protein HP1alpha and kinetochore protein CENP-A were differentially expressed as fusions to red (RFP-HP1) and green fluorescent proteins (GFP-CENP-A). Heterochromatin localization of RFP-HP1 was clearly shown in mouse and Indian muntjac cells. By preparing mitotic chromosome spreads, the inner centromere localization of RFP-HP1 was observed in human and Indian muntjac cells. To characterize its molecular behavior in living mitotic cells, time-lapse images of RFP-HP1 were obtained by computer-assisted image analyzing system, mainly with mouse cells. In G2 phase, a significant portion of RFP-HP1 diffused homogeneously in the nucleus and further dispersed into the cytoplasm soon after the nuclear membrane breakdown, while some remained in the centromeric region. Simultaneous observations with GFP-CENP-A in human cells showed that RFP-HP1 was located just between the sister kinetochores and then aligned to the spindle midzone. With the onset of anaphase, once it was released from there, it moved to the centromeres of segregating chromosomes or returned to the spindle equator. As cytokinesis proceeded, HP1alpha was predominantly found in the newly formed daughter nuclei and again displayed a heterochromatin-like distribution. These results suggested that, although the majority of HP1alpha diffuses into the cytoplasm, some populations are retained in the centromeric region and involved in the association and segregation of sister kinetochores during mitosis.


Care Arrangements of Older Adults: What They Prefer, What They Have, and Implications for Quality of Life.
Meeting individual preferences for long-term services and supports (LTSS) is a policy priority that has implications for quality of care. Evidence regarding preferences is sparse. In addition, little is known regarding whether preferences and care arrangements match for those receiving care, and implications for quality of life. A random sample (n = 1,783 in 2012) of National Health and Aging Trends Study participants were asked the best care option for someone 80+ who needs help with personal care and mobility. Analyses examine variations in care preferences, the relationship of preferences to care arrangements, and the association of matched preference and care arrangements to quality of life indicators. Care preferences vary by demographics. Equal proportions (3 in 10) of older adults chose assisted living or continuing care retirement communities (CCRC), care in own home with family help, and care in own home with paid help, as the best options. Persons in assisted living/CCRC settings were significantly more likely to choose this option as best. Only 1 in 3 older persons receiving care are in arrangements that match preferences. No association with quality of life indicators was found. Aging in place remains the care preference of a majority, but close to one-third chose assisted living/CCRC, suggesting preferences are evolving. Aligning care preferences and arrangements is a policy goal, but many do not achieve a match and there remain gaps in understanding trajectories in preferences and care arrangements and implications for quality of life.


Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis.
Resistance to stress-induced apoptosis was examined in cells in which the expression of hsp70 was either constitutively elevated or inducible by a tetracycline-regulated transactivator. Heat-induced apoptosis was blocked in hsp70-expressing cells, and this was associated with reduced cleavage of the common death substrate protein poly(ADP-ribose) polymerase (PARP). Heat-induced cell death was correlated with the activation of the stress-activated protein kinase SAPK/JNK (c-Jun N-terminal kinase). Activation of SAPK/JNK was strongly inhibited in cells in which hsp70 was induced to a high level, indicating that hsp70 is able to block apoptosis by inhibiting signaling events upstream of SAPK/JNK activation. In contrast, SAPK/JNK activation was not inhibited by heat shock in cells with constitutively elevated levels of hsp70. Cells that constitutively overexpress hsp70 resist apoptosis induced by ceramide, a lipid signaling molecule that is generated by apoptosis-inducing treatments and is linked to SAPK/JNK activation. Similar to heat stress, resistance to ceramide-induced apoptosis occurs in spite of strong SAPK/JNK activation. Therefore, hsp70 is also able to inhibit apoptosis at some point downstream of SAPK/JNK activation. Since PARP cleavage is prevented in both cell lines, these results suggest that hsp70 is able to prevent the effector steps of apoptotic cell death. Processing of the CED-3-related protease caspase-3 (CPP32/Yama/apopain) is inhibited in hsp70-expressing cells; however, the activity of the mature enzyme is not affected by hsp70 in vitro. Caspase processing may represent a critical heat-sensitive target leading to cell death that is inhibited by the chaperoning function of hsp70. The inhibition of SAPK/JNK signaling and apoptotic protease effector steps by hsp70 likely contributes to the resistance to stress-induced apoptosis seen in transiently induced thermotolerance.


The Protective Effect of A Short Peptide Derived From Cold-Inducible RNA-Binding Protein in Renal Ischemia-Reperfusion Injury.
Extracellular cold-inducible RNA-binding protein (CIRP) functions as damage-associated molecular pattern and has been demonstrated to be responsible in part for the damage occurring after renal ischemia-reperfusion (I/R). A short peptide derived from CIRP, named C23, binds to myeloid differentiation factor 2, a Toll-like receptor 4 coreceptor. We hypothesize that C23 reduces renal ischemia-reperfusion (RIR) injury by blocking CIRP. We observed that pretreatment with C23 significantly decreased the levels of recombinant mouse CIRP-induced tumor necrosis factor-α (TNF-α) in a dose-dependent fashion in cultured macrophages. C57BL/6 mice were subjected to bilateral renal pedicle clamps for 35 min to induce ischemia, followed by reperfusion for 24 h and harvest of blood and renal tissue. C23 peptide (8 mg/kg) or vehicle was injected intraperitoneally at the beginning of reperfusion. Plasma TNF-α, interleukin 1 beta (IL-1β), and IL-6 levels were decreased in C23-treated RIR mice as compared with vehicle-treated mice by 74%, 85%, and 68%, respectively. Expressions of TNF-α and keratinocyte chemoattractant in the kidneys from C23-treated mice were decreased by 55% and 60%, respectively. Expression of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in the kidney of C23-treated mice were significantly reduced by 46% and 55%, respectively. Renal tissue histological assessments revealed significant reduction in damage score by 44% in C23-treated mice. Finally, a survival study revealed a significant survival advantage with a 70% survival rate in C23 group vs. 37% in vehicle group. Thus, C23 has potential as a novel therapy for the patients suffering from I/R-induced renal injury.


Stabilizing the HIV/AIDS workforce: lessons from the New York City experience.
The Ryan White Title I Personnel Needs Study described here is an evaluation of the human resource needs of HIV/AIDS service agencies in New York City. The research presented here was conducted in collaboration with researchers from the Medical and Health Research Association and the New York City Department of Health and the Planning and Evaluation Committee of the New York City HIV Health and Human Services Planning Council. The assessment is divided into two components. The first component is a survey of 100 key informants from HIV/ AIDS service agencies. The second component is a detailed staffing survey of 70 personnel directors of HIV/AIDS service agencies. HIV/AIDS service directors perceived staff recruitment as a more difficult process than staff retention, regardless of agency type. Vacancy rates at the surveyed agencies varied by professional category; they were especially high in the category of nurse practitioners (13%) and outreach/education workers (15%). Agencies stressed that incentives that would positively affect recruitment and retention should be tailored to address the concerns of varied health care and social service professionals. In addition, agencies were not routinely able to provide some incentives deemed effective such as higher salaries, housing subsidies, and smaller caseloads. To reduce recruitment and retention problems, agency informants recommended a variety of incentive programs including malpractice insurance for physicians, flexible hours for full-time employees (including case managers, nurses, physician's assistants), smaller caseloads, and a decrease in the proportion of staff time devoted to direct client contact. Overall health care trends including truncated federal budgets, state Medicaid cutbacks, and the rapid conversion to managed care all affect the quality of patient care and of the work setting for health care and social service providers serving persons with AIDS. Medical Subject Headings (MeSH): AIDS, health personnel, employment supported, employee workload, staff attitude.


Nutrient extraction by cold-exposed mice: a test of digestive safety margins.
We examined the size of the "safety margin," if any, by which the small intestine's daily capacities to absorb nutrients exceed prevailing daily intakes of those nutrients. This safety margin, also known as reserve capacity, is widely assumed to be enormously large. As a test, we suddenly transferred mice from an ambient temperature of 22 to 6 degrees C and measured food intake, apparent digestive efficiency, intestinal morphometrics, and intestinal brush-border uptake capacities for D-glucose and L-proline over the next 28 days. Food intake jumped 68% within the first 12 h and rose in 2 days to a new plateau level 2.5 times the previous intake. Nevertheless, apparent digestive efficiency remained unchanged, even within the first 12 h, and intestinal transit times also remained unchanged, implying the existence of at least some safety margin. Masses of the small and large intestine, liver, kidneys, and spleen nevertheless increased within 4 days by 16-20%. Glucose and proline uptakes per milligram intestine increased by approximately 5%, so that the intestine's summed uptake capacities for these solutes increased by 24-26%. The animal's intestinal adaptation expressed in these increased uptake capacities implies that safety margins at the new plateau value of food intake would otherwise have been dangerously narrow. Comparison of calculated summed uptake capacities with measured dietary intakes suggests that safety margins are approximately 220-300% in mice at 22 degrees C, only 27-50% in mice at 6 degrees C before intestinal adaptation, but 60-88% in mice at 6 degrees C after intestinal adaptation.


Comparison of two enteric-coated acetylsalicylic acid preparations by monitoring steady-state levels of salicylic acid and its metabolites in plasma and urine.
In a randomized three-way crossover study, 12 healthy male volunteers were given multiple oral doses, i.e. 1.5 g b.i.d. for 7 days, of two different types of enteric-coated acetylsalicylic acid (ASA) preparations, one being a conventional enteric-coated tablet (ET) and the other enteric-coated granules (EG) in a capsule; conventional ASA tablets were used as a reference. Plasma levels and excretion of salicylic acid and some of its metabolites were investigated under steady-state conditions. Plasma salicylic acid (SA) and salicyluric acid (SUA) levels were determined using a liquid chromatographic method. Two separate analyses were done to quantitate the metabolites in urine. SA, SUA, and gentisic acid were each assayed by the method used for plasma. Total salicylate was also determined. There was no significant difference in urinary excretion of total salicylate between the three formulations. A diurnal variation in the excretion of SUA and SA in urine was found. The two enteric-coated formulations provided significantly higher morning plasma concentrations than the conventional aspirin. The AUC was found to be significantly higher for ET than for the other two formulations. EG gave more uniform plasma levels during the studied 12-h intervals and also less inter- and intra-individual variations than ET, indicating that a b.i.d. regimen may be suitable for EG.


Supermarket retailers' perspectives on healthy food retail strategies: in-depth interviews.
Excess calorie consumption and poor diet are major contributors to the obesity epidemic. Food retailers, in particular at supermarkets, are key shapers of the food environment which influences consumers' diets. This study seeks to understand the decision-making processes of supermarket retailers-including motivators for and barriers to promoting more healthy products-and to catalogue elements of the complex relationships between customers, suppliers, and, supermarket retailers. We recruited 20 supermarket retailers from a convenience sample of full service supermarkets and national supermarket chain headquarters serving low- and high-income consumers in urban and non-urban areas of New York. Individuals responsible for making in-store decisions about retail practices engaged in online surveys and semi-structured interviews. We employed thematic analysis to analyze the transcripts. Supermarket retailers, mostly representing independent stores, perceived customer demand and suppliers' product availability and deals as key factors influencing their in-store practices around product selection, placement, pricing, and promotion. Unexpectedly, retailers expressed a high level of autonomy when making decisions about food retail strategies. Overall, retailers described a willingness to engage in healthy food retail and a desire for greater support from healthy food retail initiatives. Understanding retailers' in-store decision making will allow development of targeted healthy food retail policy approaches and interventions, and provide important insights into how to improve the food environment.


Functional Study of Novel Bartter's Syndrome Mutations in ClC-Kb and Rescue by the Accessory Subunit Barttin Toward Personalized Medicine.
Type III and IV Bartter syndromes (BS) are rare kidney tubulopathies caused by loss-of-function mutations in the CLCNKB and BSND genes coding respectively for the ClC-Kb chloride channels and accessory subunit barttin. ClC-K channels are expressed in the Henle's loop, distal convoluted tubule, and cortical collecting ducts of the kidney and contribute to chloride absorption and urine concentration. In our Italian cohort, we identified two new mutations in CLCNKB, G167V and G289R, in children affected by BS and previously reported genetic variants, A242E, a chimeric gene and the deletion of the whole CLCNKB. All the patients had hypokalemia and metabolic alkalosis, increased serum renin and aldosterone levels and were treated with a symptomatic therapy. In order to define the molecular mechanisms responsible for BS, we co-expressed ClC-Kb wild type and channels with point mutations with barttin in HEK 293 cells and characterized chloride currents through the patch-clamp technique. In addition, we attempted to revert the functional defect caused by BS mutations through barttin overexpression. G167V and A242E channels showed a drastic current reduction compared to wild type, likely suggesting compromised expression of mutant channels at the plasma membrane. Conversely, G289R channel was similar to wild type raising the doubt that an additional mutation in another gene or other mechanisms could account for the clinical phenotype. Interestingly, increasing ClC-K/barttin ratio augmented G167V and A242E mutants' chloride current amplitudes towards wild type levels. These results confirm a genotype-phenotype correlation in BS and represent a preliminary proof of concept that molecules functioning as molecular chaperones can restore channel function in expression-defective ClC-Kb mutants.


Microglia: key elements in neural development, plasticity, and pathology.
A century after Cajal identified a "third element" of the nervous system, many issues have been clarified about the identity and function of one of its major components, the microglia. Here, we review recent findings by microgliologists, highlighting results from imaging studies that are helping provide new views of microglial behavior and function. In vivo imaging in the intact adult rodent CNS has revolutionized our understanding of microglial behaviors in situ and has raised speculation about their function in the uninjured adult brain. Imaging studies in ex vivo mammalian tissue preparations and in intact model organisms including zebrafish are providing insights into microglial behaviors during brain development. These data suggest that microglia play important developmental roles in synapse remodeling, developmental apoptosis, phagocytic clearance, and angiogenesis. Because microglia also contribute to pathology, including neurodevelopmental and neurobehavioral disorders, ischemic injury, and neuropathic pain, promising new results raise the possibility of leveraging microglia for therapeutic roles. Finally, exciting recent work is addressing unanswered questions regarding the nature of microglial-neuronal communication. While it is now apparent that microglia play diverse roles in neural development, behavior, and pathology, future research using neuroimaging techniques will be essential to more fully exploit these intriguing cellular targets for effective therapeutic intervention applied to a variety of conditions.


Burn wound healing and treatment: review and advancements.
Burns are a prevalent and burdensome critical care problem. The priorities of specialized facilities focus on stabilizing the patient, preventing infection, and optimizing functional recovery. Research on burns has generated sustained interest over the past few decades, and several important advancements have resulted in more effective patient stabilization and decreased mortality, especially among young patients and those with burns of intermediate extent. However, for the intensivist, challenges often exist that complicate patient support and stabilization. Furthermore, burn wounds are complex and can present unique difficulties that require late intervention or life-long rehabilitation. In addition to improvements in patient stabilization and care, research in burn wound care has yielded advancements that will continue to improve functional recovery. This article reviews recent advancements in the care of burn patients with a focus on the pathophysiology and treatment of burn wounds.


Why does work cause fatigue? A real-time investigation of fatigue, and determinants of fatigue in nurses working 12-hour shifts.
One of the striking regularities of human behavior is that a prolonged physical, cognitive, or emotional activity leads to feelings of fatigue. Fatigue could be due to (1) depletion of a finite resource of physical and/or psychological energy or (2) changes in motivation, attention, and goal-directed effort (e.g. motivational control theory). To contrast predictions from these two views in a real-time study of subjective fatigue in nurses while working. One hundred nurses provided 1,453 assessments over two 12-hr shifts. Nurses rated fatigue, demand, control, and reward every 90 min. Physical energy expenditure was measured objectively using Actiheart. Hypotheses were tested using multilevel models to predict fatigue from (a) the accumulated values of physical energy expended, demand, control, and reward over the shift and (b) from distributed lag models of the same variables over the previous 90 min. Virtually all participants showed increasing fatigue over the work period. This increase was slightly greater when working overnight. Fatigue was not dependent on physical energy expended nor perceived work demands. However, it was related to perceived control over work and perceived reward associated with work. Findings provide little support for a resource depletion model; however, the finding that control and reward both predicted fatigue is consistent with a motivational account of fatigue.


A major natural genetic variation associated with root system architecture and plasticity improves waterlogging tolerance and yield in soybean.
Natural genetic variations in waterlogging tolerance are controlled by multiple genes mapped as quantitative trait loci (QTLs) in major crops, including soybean (Glycine max L.). In this research, 2 novel QTLs associated with waterlogging tolerance were mapped from an elite/exotic soybean cross. The subsequent research was focused on a major QTL (qWT_Gm03) with the tolerant allele from the exotic parent. This QTL was isolated into near-isogenic backgrounds, and its effects on waterlogging tolerance were validated in multiple environments. Fine mapping narrowed qWT_Gm03 into a genomic region of <380 Kbp excluding Rps1 gene for Phytophthora sojae resistance. The tolerant allele of qWT_Gm03 promotes root growth under nonstress conditions and favourable root plasticity under waterlogging, resulting in improved waterlogging tolerance, yield, and drought tolerance-related traits, possibly through more efficient water/nutrient uptakes. Meanwhile, involvement of auxin pathways was also identified in the regulation of waterlogging tolerance, as the genotypic differences of qWT_Gm03 in waterlogging tolerance and formation of adventitious/aerial roots can be complemented by an exogenous auxin-biosynthesis inhibitor. These findings provided genetic resources to address the urgent demand of improving waterlogging tolerance in soybean and revealed the determinant roles of root architecture and plasticity in the plant adaptation to waterlogging.


Safety and efficacy of the feed additive consisting of endo-1,4-beta-xylanase produced by Trichoderma reeseiCBS 143953 (Danisco Xylanase 40000 G/L) for poultry and porcine species (Danisco Animal Nutrition).
Danisco Xylanase 40000 G/L is the trade name of the feed additive under assessment and contains endo-1,4-beta-xylanase produced by a genetically modified strain of Trichoderma reesei. It is authorised for use in chickens for fattening, laying hens, ducks, turkeys for fattening, all minor poultry species, weaned piglets and pigs for fattening. This scientific opinion concerns the request for the renewal of the authorisation of the additive for the species/categories for which there is an authorisation, a reduction of the minimum recommended level in turkeys for fattening and the extension of use to all poultry species (other than ducks) for fattening or reared for laying/breeding and for laying, suckling piglets and minor growing porcine species. The applicant provided evidence that the additive currently in the market complies with the conditions of the authorisation. There is no new evidence that would lead the EFSA Panel on Additives and products or Substances used in Animal Feed (FEEDAP) to reconsider previous conclusions that the additive remains safe for the animal species/categories, the consumer and the environment under the authorised conditions of use. This conclusion applies also to the new target species/categories for which a request of use is made. The additive is not irritant to skin but should be considered as a possible eye irritant and, in common with other proteinaceous substances, respiratory sensitiser. There was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation for chickens for fattening, laying hens, ducks, all minor poultry species, weaned piglets and pigs for fattening. The additive has the potential to be efficacious at 625 U/kg complete feed in all poultry species for fattening (including turkeys) or reared for laying/breeding, and for laying and 2,000 U/kg complete feed in suckling piglets and all minor growing porcine species.


Recognition of pain and use of analgesia in horses by veterinarians in New Zealand.
To explore attitudes towards and use of analgesia in horses by veterinarians in New Zealand. A postal questionnaire was sent out to 457 veterinarians identified as working with horses in New Zealand. Questions covered demographics and practice data; analgesic drugs available for use and used in practice; analgesic management of specific conditions including assessment of pain, drugs used, and frequency of cases; factors influencing the choice and use of analgesic agents; and attitudes and personal experience. Ninety-seven questionnaires containing useable data were received, a response rate of 23%. Respondents' demographics corresponded with those of the veterinary population at the time. Phenylbutazone, flunixin, xylazine, ketamine, butorphanol, dexamethasone and lignocaine were the drugs most commonly used. Respondents allocated pain scores with a range of at least eight points (on a scale of 1 to 10) between lower and upper scores for 13/17 conditions and procedures presented. Respondents identified analgesic potency and anti-inflammatory effect as the most important factors in their choice of drug. Sixty-three percent and 59% of respondents considered their knowledge of recognition of pain and analgesia, respectively, to be adequate. The results of the survey indicate that analgesia was widely used for horses amongst responding veterinarians. However, there were a number of areas where there appeared to be a lack of consensus amongst respondents in their management of pain in horses, and these included assessment of pain, administration of analgesics, and, indeed, what constitutes analgesia. While analgesia of horses is widely practised in New Zealand, it would appear that a lack of consistency amongst veterinarians could indicate less than optimal pain relief in some cases and for some procedures.


Cimetidine: an advance in gastric ulcer treatment?
Sixty patients with endoscopically confirmed gastric ulceration took part in a single-blind trial of cimetidine 1 g daily compared with conventional treatment--namely, carbenoxolone in patients aged under 60 and Caved-(S) in those over 60. Twenty-nine patients received cimetidine: in 12 (41%) ulcer healing was complete after one month, in 26 (90%) healing was complete after two months, and all ulcers were healed after three months of treatment. In the under-60s, ulcers were healed in a greater proportion of patients given cimetidine than in those given carbenoxolone. The difference, however, was significant only at the 5% level, which owing to small numbers was of doubtful clinical validity. In the over-60s cimetidine and Caved-(S) were of similar efficacy. The 54 patients with healed ulcers are being followed up for two years; so far there have been 16 recurrences (30%). Further trials are needed, which should include maintenance treatment aimed at lowering the unacceptably high recurrence rate.


Clinical Application of Prothrombin Complex Concentrate in Blood Management in Patients.
Management of patients receiving anticoagulants is a major factor in achieving better outcomes. Anticoagulant therapy may need to be discontinued or rapidly reversed before urgent surgery or invasive procedures. In these situations, treatment with concentrated vitamin K, fresh frozen plasma, and/or clotting factors can achieve more rapid anticoagulant reversal than can drug discontinuation alone. Activated prothrombin complex concentrate is used to treat hemophiliac patients with acquired factor VIII inhibitors. Nonactivated prothrombin complex concentrates are used for anticoagulant reversal. The concentrates are effective within minutes of dosing, providing a nearly immediate decrease in the international normalized ratio. The concentrates are lyophilized powders that can be quickly reconstituted, do not require ABO blood typing before use, and contain 25 times the concentration of vitamin K-dependent clotting factors compared with fresh frozen plasma. Studies suggest that the concentrates are associated with better clinical end points than is fresh frozen plasma.


[Neurochemical features of the ventral pallidum in realization of the antiaversive effects of anxiolytics in different models of anxiety].
Preliminary intraperitoneal injections of some combinations of adreno- and dopaminomimetics, monoamines, and mediator amino acids (as well as of their agonists and antagonists) followed by microinjections of the same combinations into the ventral pallidum reveal differences in the functional significance of the neurochemical profile of this paleostriatum formation in realization of the anxiety states of different genesis, as manifested in the "illuminated site avoidance" and the "threatening situation" tests in rats. The pharmacological analysis based on the local injection of anxiosedative and anxioselective agents into the ventral paleostriatum showed that the antiaversive action of campirone is revealed under the conditions of dominating fear motivation, while that analogous action of chlordiazepoxide, phenibut and indoter is revealed under negative stressful zoosocial impacts and is realized by serotonin- and GABA-ergic (rather than by cathecholamine- and glutaminergic) aversive systems of the ventral pallidum.


Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer.
The role of prostate-specific antigen (PSA) or kallikrein-related peptidase 3 (KLK3) as a biomarker for prostate cancer is well known; however, the precise physiological role of it's serine protease activity in prostate cancer remains a mystery. PSA is produced at high levels by both androgen-dependent and -independent prostate cancers. Studies have documented high levels of active PSA in the milieu surrounding osseous and soft tissue metastases. This evidence, coupled with growing experimental evidence, suggests that PSA plays an important role in the pathobiology of prostate cancer. These observations support the development of PSA-selective inhibitors as useful tools for the targeted treatment and imaging of prostate cancer. Here, we review the research that has been conducted to date on developing selective inhibitors for PSA. The different approaches used to determine PSA substrate specificity and for creating inhibitors are discussed. In addition, the unique active site characteristics of PSA and how these motifs aided our research in developing PSA targeted agents are highlighted.


A1C and survival in maintenance hemodialysis patients.
The optimal target for glycemic control has not been established in diabetic dialysis patients. To address this question, the national database of a large dialysis organization (DaVita) was analyzed via time-dependent survival models with repeated measures. Of 82,933 patients undergoing maintenance hemodialysis (MHD) in DaVita outpatient clinics over 3 years (July 2001 through June 2004), 23,618 diabetic MHD patients had A1C measurements at least once. Unadjusted survival analyses indicated paradoxically lower death hazard ratios (HRs) with higher A1C values. However, after adjusting for potential confounders (demographics, dialysis vintage, dose, comorbidity, anemia, and surrogates of malnutrition and inflammation), higher A1C values were incrementally associated with higher death risks. Compared with A1C in the 5-6% range, the adjusted all-cause and cardiovascular death HRs for A1C > or = 10% were 1.41 (95% CI 1.25-1.60) and 1.73 (1.44-2.08), respectively (P < 0.001). The incremental increase in death risk for rising A1C values was monotonic and robust in nonanemic patients (hemoglobin > 11.0 g/dl). In subgroup analyses, the association between A1C > 6% and increased death risk was more prominent among younger patients, those who had undergone dialysis for > 2 years, and those with higher protein intake (> 1 g x kg(-1) x day(-1)), blood hemoglobin (> 11 g/dl), or serum ferritin values (> 500 ng/ml). In diabetic MHD patients, the apparently counterintuitive association between poor glycemic control and greater survival is explained by such confounders as malnutrition and anemia. All things equal, higher A1C is associated with increased death risk. Lower A1C levels not related to malnutrition or anemia appear to be associated with improved survival in MHD patients.


A Systematic Review and Meta-Analysis of Ginkgo biloba in Neuropsychiatric Disorders: From Ancient Tradition to Modern-Day Medicine.
Ginkgo biloba (Gb) has demonstrated antioxidant and vasoactive properties as well as clinical benefits in several conditions such as ischemia, epilepsy, and peripheral nerve damage. Additionally, Gb is supposed to act as potential cognitive enhancer in dementia. So far, several trials have been conducted to investigate the potential effectiveness of Gb in neuropsychiatric conditions. However, the results of these studies remain controversial. We conducted a systematic review and a meta-analysis of three randomised controlled trials in patients with schizophrenia and eight randomised controlled trials in patients with dementia. Gb treatment reduced positive symptoms in patients with schizophrenia and improved cognitive function and activities of daily living in patients with dementia. No effect of Gb on negative symptoms in schizophrenic patients was found. The general lack of evidence prevents drawing conclusions regarding Gb effectiveness in other neuropsychiatric conditions (i.e., autism, depression, anxiety, attention-deficit hyperactivity disorder, and addiction). Our data support the use of Gb in patients with dementia and as an adjunctive therapy in schizophrenic patients.


[Home enteral nutrition in Madrid].
The consumption of products of home enteral nutrition financed by the national system of health, has experimented a remarkable increment. The purpose of this present paper is to evaluate the changes during the last four years (1998-2001), the differences between the costs in which a product is checked and the market occupation of each product. Analysing the official social security forms which were dispensed by pharmacies of Madrid, a study was realized attending to type of product, number of units, cost of each and manufactures industries. As these products are covered by the Spanish Defence of Competition, the data related to the costs has been taken individually of each social security form. The increment between november of 1998 and may of 2000 in packings (66.6%) and costs (over 100%). Consumption shared unequally by three manufactures. The average cost increases 25.9%, whereas the utilization of standard products decreases in favor of more specific modified products. The difference between the cost in which a product is checked, depending on the pharmacy which dispenses it, reaches a 120%. The trend of increased consumption in packings maintains stable until the year 2000, slowing down in 2001, whereas the costs maintain this trend to increase. There is a remarkable increment in products in which administration involves a continuous infusion.


Incidence and mechanism of spurious increase in serum thyrotropin.
We previously reported spuriously high values for thyrotropin (TSH), presumably owing to an antibody in human serum that reacts with both reagent rabbit antibodies in an immunoradiometric assay (IRMA). We used this IRMA to measure TSH. Five of 20 sera from laboratory animal handlers showed spuriously high values. When we added 2 mL of nonimmune rabbit serum per liter to the labeled IRMA rabbit antibody reagent and reassayed the five affected specimens, the results were within the reference interval. Smaller additions partly corrected the TSH values, but nonimmune sera of eight other species had no effect. Substitution of goat solid-phase antibody decreased, but did not eliminate, the increases in TSH in three of the five affected sera. Chromatographic properties, results of rheumatoid factor testing, and measurement of human anti-rabbit immunoglobulin suggest that the interference is ascribable to an antibody of the IgG class that reacts with rabbit antibody. Evidently, antibody interference with IRMA procedures may be common in certain populations. It can be avoided by including nonimmune serum corresponding to the species used to produce reagent antibody.


Cohort Profile: The Shanghai Men's Health Study.
The Shanghai Men's Health Study (SMHS) is a population-based cohort study of 61,480 men aged 40-74 years, launched in 2002 in urban Shanghai to investigate the contribution of lifestyle/environmental factors and genetic susceptibility to cancer and other non-communicable diseases (NCDs). At baseline, trained interviewers collected detailed information on personal and dietary habits, occupational/medical history and physical activity, and took anthropometric measurements (response rate: 74%). Blood, urine and DNA were collected from 75%, 89% and 89% of participants, respectively. The cohort has been followed up through a combination of in-person surveys every 3-4 years and annual record linkage with cancer and vital statistics registries. Response rates for in-person follow-up surveys were over 91% and coverage for mortality nearly 100%. SMHS participants have a high smoking rate (58.6%) and moderate alcohol-drinking rate (29.3%), but low obesity rate (2.6%). They have a low calorie intake from fat (16.2% of total calorie intake) and protein (16.4%), high calorie intake from carbohydrates (67.4%), and high intake of soy food, cruciferous vegetables and fish (156.5, 110.6 and 51.7 g/day, respectively). With its unique exposure pattern and wealth of data and biological samples, the SMHS is well positioned for long-term research into NCD aetiology and prognosis. Information about accessing the SMHS resources can be found at: http://www.mc.vanderbilt.edu/swhs-smhs/.


Epigallocatechin-3-gallate inhibits photocarcinogenesis through inhibition of angiogenic factors and activation of CD8+ T cells in tumors.
There has been considerable interest in the use of botanical supplements to protect skin from the adverse effects of solar UV radiation, including photocarcinogenesis. We and others have shown that topical application of (-)-epigallocatechin-3-gallate (EGCG) from green tea prevents photocarcinogenesis in mice; however, the chemopreventive mechanism of EGCG in an in vivo tumor model is not clearly understood. In this study, UV-B-induced skin tumors with and without treatment of EGCG ( approximately 1 mg/cm(2)) and age-matched skin biopsies from SKH-1 hairless mice were used to identify potential molecular targets of skin cancer prevention by EGCG. These biopsies were analyzed for various biomarkers of angiogenesis and antitumor immune response using immunostaining, Western blotting and gelatinolytic zymography. We report that compared to non-EGCG-treated tumors, topical application of EGCG in UV-induced tumors resulted in inhibition of protein expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, which play crucial roles in tumor growth and metastasis. In contrast, tissue inhibitor of MMP-1 (TIMP-1), which inhibits MMP activity, was increased in tumors. With respect to the tumor vasculature, EGCG decreased the expression of CD31, a cell surface marker of vascular endothelial cells, and inhibited the expression of vascular endothelial growth factor in tumors, which are essential for angiogenesis. EGCG inhibited proliferating cell nuclear antigen in UV-B-induced tumors as well. Additionally, higher numbers of cytotoxic T lymphocytes (CD8(+) T cells) were detected in EGCG-treated tumors compared with non-EGCG-treated tumors. Together, these in vivo tumor data suggested that inhibition of photocarcinogenesis in mice by EGCG is associated with inhibition of angiogenic factors and induction of antitumor immune reactivity.


COVID-19 diagnosis using clinical markers and multiple explainable artificial intelligence approaches: A case study from Ecuador.
The COVID-19 pandemic erupted at the beginning of 2020 and proved fatal, causing many casualties worldwide. Immediate and precise screening of affected patients is critical for disease control. COVID-19 is often confused with various other respiratory disorders since the symptoms are similar. As of today, the reverse transcription-polymerase chain reaction (RT-PCR) test is utilized for diagnosing COVID-19. However, this approach is sometimes prone to producing erroneous and false negative results. Hence, finding a reliable diagnostic method that can validate the RT-PCR test results is crucial. Artificial intelligence (AI) and machine learning (ML) applications in COVID-19 diagnosis has proven to be beneficial. Hence, clinical markers have been utilized for COVID-19 diagnosis with the help of several classifiers in this study. Further, five different explainable artificial intelligence techniques have been utilized to interpret the predictions. Among all the algorithms, the k-nearest neighbor obtained the best performance with an accuracy, precision, recall and f1-score of 84%, 85%, 84% and 84%. According to this study, the combination of clinical markers such as eosinophils, lymphocytes, red blood cells and leukocytes was significant in differentiating COVID-19. The classifiers can be utilized synchronously with the standard RT-PCR procedure making diagnosis more reliable and efficient.


Surveillance programme for uncompensated work-related diseases in France.
The surveillance programme for uncompensated work-related diseases (UWRDs) in France relies on a network of occupational physicians (OPs) who volunteer to report all UWRDs diagnosed during a biannual 2-week observation period. To describe this programme and the usefulness of its results. During the observation period, OPs record job title and employment sector for each worker. For each potential UWRD, they complete a one-page report form. Between 2007 and 2012, the number of reporting OPs ranged from 705 to 965 and they saw between 78884 and 114154 employees annually. The UWRD incidence rate reports varied from 5 to 5.3% for men and from 6.5 to 7.7% for women, with musculoskeletal disorders (MSDs) being most frequent, followed by mental ill-health. Incidence rates, except for hearing loss, were higher for women than men in all categories and, in 2012, were twice as high for women (3.1%) as for men (1.4%) for mental ill-health. Incidence rates in every category increased with age up to 54 years. The highest rates for MSDs were observed among blue-collar workers (6.9% in women and 4% in men in 2012) and the lowest rates in professionals/managers (1.1 and 0.4%, respectively). Conversely, the latter had the highest incidence of mental health disorders (5.9 and 3.3%). This 'Fortnight' protocol provides useful data on the frequency of diseases linked to employment and allows us to estimate the incidence of UWRDs, whether recognized as compensable or not, as well as their trends over time.


A forced-air ventilation system for rodent cages.
A novel forced-air ventilation system for rodent cages was developed. The apparatus was operated at an air flow rate of 56 L/min when used with a 230 mm wide X 450 mm long X 165 mm deep cage. Air velocity measurements in the cage did not exceed 8 m/min at animal (rat) height. The average NH3 concentration in a cage which housed two 250 g rats was less than 0.3 ppm at the end of the third day, whereas the concentration measured in a cage without the forced-air ventilation system was 150 ppm after 3 days. Tests of the water content of soiled bedding showed the forced-air ventilation system to provide a much drier environment for the rodents.


[Experience of the 7th Central Military Clinical Aviation Hospital in early diagnostics, treatment, rehabilitation, and expert evaluation of cholelithiasis in flying personnel].
The Seventh Central military clinical aviation hospital is experienced in performing laparocholecystectomy (LCE) in pilots afflicted with cholelithiasis (CL). In the period from 1990 to 2001, 92 operations were carried out after which 80 patients (87%) were permitted to fly. Medical discharge of 12 patients (13%) was associated not with CL but with some morphofunctional shifts caused by concomitant diseases. Seven to five-yr. follow-up of the 80 pilots who had returned their flying status after LCE showed their good tolerance for the flight loads.


Mannose-binding lectin codon 54 gene polymorphism and vulvovaginal candidiasis: a systematic review and meta-analysis.
Mannose-binding lectin (MBL) plays a key role in the human innate immune response. It has been shown that polymorphisms in the MBL2 gene, particularly at codon 54 (variant allele B; wild-type allele designated as A), impact upon host susceptibility to Candida infection. This systematic review and meta-analysis were performed to assess the association between MBL2 codon 54 genotype and vulvovaginal candidiasis (VVC) or recurrent VVC (RVVC). Studies were searched in MEDLINE, SCOPUS, and ISI Web of Science until April 2013. Five studies including 704 women (386 cases and 318 controls) were part of the meta-analysis, and pooled ORs were calculated using the random effects model. For subjects with RVVC, ORs of AB versus AA and of BB versus AA were 4.84 (95% CI 2.10-11.15; P for heterogeneity = 0.013; I(2) = 68.6%) and 12.68 (95% CI 3.74-42.92; P for heterogeneity = 0.932, I(2) = 0.0%), respectively. For subjects with VVC, OR of AB versus AA was 2.57 (95% CI 1.29-5.12; P for heterogeneity = 0.897; I (2) = 0.0%). This analysis indicates that heterozygosity for the MBL2 allele B increases significantly the risk for both diseases, suggesting that MBL may influence the women's innate immunity in response to Candida.


MRSA decolonization: success rate, risk factors for failure and optimal duration of follow-up.
Methicillin-resistant Staphylococcus aureus (MRSA) decolonization is a widely established, though controversial part of many MRSA controlling strategies. The aim of this study was to evaluate our decolonization success rate, identify the risk factors for decolonization failure and determine the optimal duration of follow-up in our low MRSA prevalence setting (2.6 % of isolates). Every patient with newly detected MRSA colonization or infection between January 2007 and December 2009 was recruited to the study. The MRSA strategy of our institution (a 700 bed tertiary hospital in eastern Switzerland) consists of a 5-day regimen of nasal mupirocin ointment, chlorhexidin mouth rinse and whole body wash with didecyldimonium chloride. Systemic antibiotics are usually not added to the regimen. We determined a MRSA decolonization success rate of 65 % (33/51) after a median follow-up of 13 months [i.e. a tripling of the spontaneous clearance rate of 22 % (6/27) in the non-decolonized group]. The most important risk factor for decolonization failure was colonization of the respiratory tract [odds risk (OR) 9.1, 95 % confidence interval (CI) 1.2-66.7], as well as isolation of MRSA spa-type 002 ([R 5.8, 95 % CI 1.0-33.3). Of all the episodes of MRSA recurrence, 88 % (14/16) were detected within 270 days after decolonization. High MRSA decolonization success rates can be achieved without the routine use of oral antibiotics. A time period of 1 year after decolonization seems to be a reasonable duration of follow-up in our setting. We encourage other institutions to take into account local MRSA epidemiology (e.g. predominance of certain subtypes) for the management of MRSA patients.


TEAMwork: Testing Emotional Attunement and Mutuality During Parent-Adolescent fMRI.
The parent-child relationship and family context influence the development of emotion regulation (ER) brain circuitry and related skills in children and adolescents. Although both parents' and children's ER neurocircuitry simultaneously affect how they interact with one another, neuroimaging studies of parent-child relationships typically include only one member of the dyad in brain imaging procedures. The current study examined brain activation related to parenting and ER in parent-adolescent dyads during concurrent fMRI scanning with a novel task - the Testing Emotional Attunement and Mutuality (TEAM) task. The TEAM task includes feedback trials indicating the other dyad member made an error, resulting in a monetary loss for both participants. Results indicate that positive parenting practices as reported by the adolescent were positively correlated with parents' hemodynamic activation of the ventromedial prefrontal cortex, a region related to empathy, during these error trials. Additionally, during feedback conditions both parents and adolescents exhibited fMRI activation in ER-related regions, including the dorsolateral prefrontal cortex, anterior insula, fusiform gyrus, thalamus, caudate, precuneus, and superior parietal lobule. Adolescents had higher left amygdala activation than parents during the feedback condition. These findings demonstrate the utility of dyadic fMRI scanning for investigating relational processes, particularly in the parent-child relationship.