Analysis of enrichment, correlation, and leaching patterns of rare earth elements in coal fly ash assisted by statistical measures.
Coal fly ash (CFA) is a typical industrial solid waste, which has recently been reported to contain rare earth elements (REEs). REEs are important materials in many industrial fields. Therefore, extracting REEs from CFA becomes a win-win strategy to both make full use of CFA and reclaim REEs. However, the stable crystalline structure of CFA is hard to break, which limits the extraction of REEs. The inter-correlation and the leaching patterns of the REEs in CFA also remain unclear. In this work, REEs were enriched by desilication, and the correlation and the influences of multiple acids of the leached REEs were investigated. It was found that desilication could increase the leachable amount of REEs from 137.37 ppm to 346.12 ppm. The light rare earth elements (LREEs) were less inter-correlated than heavy rare earth elements (HREEs) and desilication enhanced the leaching of LREEs more than that of HREEs. The ratio and type of the leaching acids both influenced the extraction of REEs from CFA: HCl and HF played important roles in the extraction from the untreated CFA while HNO3 and HF were more decisive for the desilicated CFA. In addition, we used statistical analysis to quantificationally confirm that desilication and acids both significantly influenced the extraction of REEs. This work provides evidence for the enrichment of REEs in CFA and acid choosing when leaching REEs from CFA.


Pathogenesis of osteoarthritis: chondrocyte replicative senescence or apoptosis?
The aim of this study was to investigate by flow cytometry cellular viability and apoptosis of human chondrocytes isolated from osteoarthritic cartilage and to correlate replicative senescence with apoptosis of these cells. To understand the mechanisms underlying the process of cell death in cartilage destruction, we investigated by flow cytometry cellular viability (Cell viability calcein-AM assay) and apoptosis (Light scattering properties of chondrocytes, study of chondrocyte death using Annexin-V-FITC and propidium iodide double-labeling, caspase-3 activity determination) of human chondrocytes isolated from osteoarthritic and nonosteoarthritic cartilage. Senescent cells were characterized using the senescence-associated-beta-galactosidase marker (SA-beta-Gal marker) by staining with chromogenic substrate (X-Gal) to produce blue coloration of SA-beta-Gal-positive cells and microscopy analysis. The results we obtained show that between 25 and 40% of chondrocytes were in apoptosis and all of them were SA-beta-Gal-positive. These results demonstrate that the death of osteoarthritic chondrocytes is an apoptotic phenomenon which is preceded by an accelerated mechanism of replicative senescence.


Calculation of the inbreeding coefficient.
Wright's rule for calculating the inbreeding coefficient for an arbitrary pedigree is proven for both autosomal and X-linked loci.


Chronic tension-type headache in adolescents. Clinical and psychological characteristics analyzed through self- and parent-report questionnaires.
To analyze the relation between the symptoms reported by adolescents with chronic tension-type headache (CTTH) and their perception of their emotional and behavioral functioning. Two groups of adolescents (clinical group, n = 48; control group, n = 135) and their parents (clinical group, n = 42; control group, n = 128) were studied, respectively, with the Youth Self-Report Questionnaire and the Child Behavior Checklist. Moreover, a secondary analysis was performed, identifying another subgroup of adolescents who reported having headaches. The clinical group of adolescents obtained higher scores than the control group in Internalizing Syndrome; Aggressive Behavior for Externalizing Syndrome; Social, Thought, and Attention Problems; and in all Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)-oriented scales (except conduct problems). Differences between the two groups of parents were found in all the scales. The controls reporting headaches obtained interesting intermediate scores. Adolescents with CTTH show greater emotional and behavioral problems than their healthy peers. Consequently, clinical approaches for proper diagnosis and treatment need to adopt a multidisciplinary prospective.


Solution structure of a zinc finger domain of yeast ADR1.
The "zinc finger" is a 30-residue repeating motif that has been identified in a variety of eukaryotic transcription factors. Each domain is capable of binding a Zn2+ ion through invariant Cys and His residues. We have determined the three-dimensional structure of a synthetic peptide that corresponds to one of the two zinc finger domains in the yeast transcription factor ADR1, using two-dimensional nuclear magnetic resonance spectroscopy. The Zn2(+)-bound structure of the peptide consists of a loop containing the two Cys residues, a "fingertip," a 12- to 13-residue alpha-helix containing the two His residues, and a C-terminal tail. A majority of the interresidue contacts observed involve the seven conserved residues of the prototypic zinc finger (i.e., the four zinc ligands and the three hydrophobic residues), indicating that these residues are largely responsible for the three-dimensional structure of the domain and that all the zinc finger domains of the TFIIIA class will have similar structures. Potential DNA-binding residues are found throughout the structure, with the highest concentration of such residues on the external face of the alpha-helix.


Obesity, obesity-related metabolic conditions, and risk of thyroid cancer in women: results from a prospective cohort study (Sister Study).
Thyroid cancer incidence has increased worldwide. Obesity trends may play a role, but the underlying biological pathways are not well-characterized. Therefore, we examined associations of excess adiposity and obesity-related metabolic conditions with thyroid cancer incidence. From the Sister Study, a cohort of sisters of women with breast cancer, we included 47,739 women who were cancer-free at baseline (2003-2009). Height, weight, waist and hip circumference, and blood pressure were measured at baseline and medical history was self-reported. Cox proportional hazards regression models were adjusted for age (time scale), race/ethnicity, smoking, baseline history of benign thyroid disease, and frequency of routine healthcare visits. During follow-up (median = 12.5; max = 15.9 years), 259 women reported incident thyroid cancer. Body mass index (BMI) (hazard ratio [HR]per-5 kg/m2 = 1.25, 95% CI = 1.14-1.37), waist circumference (HRper-5 cm increase = 1.11, 95% CI = 1.06-1.15), and waist-to-hip ratio (HR ≥0.85-versus-<0.85 = 1.49, 95% CI = 1.14-1.94) were positively associated with thyroid cancer incidence, as were metabolic syndrome (HR = 1.67, 95% CI = 1.24-2.25), dyslipidemia (HR = 1.46, 95% CI = 1.13-1.90), borderline diabetes (HR = 2.06, 95% CI = 1.15-3.69), hypertension (HR = 1.49, 95% CI = 1.12-1.96), and polycystic ovary syndrome (PCOS, HR = 2.10, 95% CI = 1.20-3.67). These associations were attenuated with additional BMI adjustment, although dyslipidemia (HR = 1.35, 95% CI = 1.04-1.75) and PCOS (HR = 1.86, 95% CI = 1.06-3.28) remained associated with thyroid cancer incidence. Hypothyroidism was not associated with thyroid cancer. In this cohort of sisters of women diagnosed with breast cancer, excess adiposity and several obesity-related metabolic conditions were associated with thyroid cancer incidence. These findings provide insights into potential biological mechanisms linking obesity and thyroid cancer. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and National Institute of Environmental Health Sciences (Z01-ES044005).


Mitochondrial genome depletion in human liver cells abolishes bile acid-induced apoptosis: role of the Akt/mTOR survival pathway and Bcl-2 family proteins.
Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Because mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effects of complete mitochondrial genome depletion on the response to bile acid-induced hepatocellular injury. A subline (Rho) of human hepatoma SK-Hep-1 cells totally depleted of mitochondrial DNA (mtDNA) was obtained, and bile acid-induced concentration-dependent activation of apoptosis/necrosis and survival signaling pathways was studied. In the absence of changes in intracellular ATP content, Rho cells were highly resistant to bile acid-induced apoptosis and partially resistant to bile acid-induced necrosis. In Rho cells, both basal and bile acid-induced generation of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, was decreased. Bile acid-induced proapoptotic signals were also decreased, as evidenced by a reduction in the expression ratios Bax-α/Bcl-2, Bcl-xS/Bcl-2, and Bcl-xS/Bcl-xL. This was mainly due to a downregulation of Bax-α and Bcl-xS. Moreover, in these cells the Akt/mTOR pathway was constitutively activated in a ROS-independent manner and remained similarly activated in the presence of bile acid treatment. In contrast, ERK1/2 activation was constitutively reduced and was not activated by incubation with bile acids. In conclusion, these results suggest that impaired mitochondrial function associated with mtDNA alterations, which may occur in liver cells during prolonged cholestasis, may activate mechanisms of cell survival accounting for an enhanced resistance of hepatocytes to bile acid-induced apoptosis.


Urban air pollution and climate change: "The Decalogue: Allergy Safe Tree" for allergic and respiratory diseases care.
According to the World Health Organization, air pollution is closely associated with climate change and, in particular, with global warming. In addition to melting of ice and snow, rising sea level, and flooding of coastal areas, global warming is leading to a tropicalization of temperate marine ecosystems. Moreover, the effects of air pollution on airway and lung diseases are well documented as reported by the World Allergy Organization. Scientific literature was searched for studies investigating the effect of the interaction between air pollution and climate change on allergic and respiratory diseases. Since 1990s, a multitude of articles and reviews have been published on this topic, with many studies confirming that the warming of our planet is caused by the "greenhouse effect" as a result of increased emission of "greenhouse" gases. Air pollution is also closely linked to global warming: the emission of hydrocarbon combustion products leads to increased concentrations of biological allergens such as pollens, generating a mixture of these particles called particulate matter (PM). The concept is that global warming is linked to the emission of hydrocarbon combustion products, since both carbon dioxide and heat increase pollen emission into the atmosphere, and all these particles make up PM10. However, the understanding of the mechanisms by which PM affects human health is still limited. Therefore, several studies are trying to determine the causes of global warming. There is also evidence that increased concentrations of air pollutants and pollens can activate inflammatory mediators in the airways. Our Task Force has prepared a Decalogue of rules addressing public administrators, which aims to limit the amount of allergenic pollen in the air without sacrificing public green areas. Several studies underscore the significant risks of global warming on human health due to increasing levels of air pollution. The impact of climate change on respiratory diseases appears well documented. The last decades have seen a rise in the concentrations of pollens and pollutants in the air. This rise parallels the increase in the number of people presenting with allergic symptoms (e.g., allergic rhinitis, conjunctivitis, and asthma), who often require emergency medical care. Our hope is that scientists from different disciplines will work together with institutions, pharmaceutical companies and lay organizations to limit the adverse health effects of air pollution and global warming.


Quantum violation of LGI under an energy constraint for different scenarios systems.
In this paper, we consider a qubit in four scenarios: with drive, without drive, and in the presence of dissipation and dephasing, to investigate the quantum violation of the Leggett-Garg inequality (LGI) in an energy constraint. In the case of the energy constraint, we find that under the coarsening measurement in reference and final resolution, the quantum violation of the LGI for the pure qubit is the most robust; on the other hand, the quantum violation of the LGI for the dephasing qubit is the most vulnerable, and the quantum violation of the LGI for driven qubit lies between that of pure qubit and dissipation qubit. Under the coarsening of measurement temporal reference, the quantum violation of the LGI for the pure qubit is more robust than that of the qubit with driven. Moreover, in the case of a qubit that is subjected to driving and is in the presence of dissipation and dephasing, the robustness of quantum violations of the LGI for these scenario systems will become vulnerable, with the driven intensity and the rate of spontaneous emission increasing, respectively, for coarsening measurement both in reference and in final resolution. In addition, in the energy constraint and the projective measurement, the LGI can attain its maximum violation value, 1.5, for the coherent dynamics; while for drive, dissipative and dephasing qubits, the LGI cannot attain the value of 1.5. For systems in the presence of dissipation and dephasing, we find that in the energy constraint, the robustness of the coarsening measurement in final resolution exhibits more vulnerable than that of the coarsening measurement in reference. And for systems with drive and without drive, the robustness of the coarsening measurement in temporal reference is the most robust, and the robustness of the coarsening of measurement final measurement resolution is the most vulnerable.


Correlation and Identification of Variable number of Tandem repeats of eNOS Gene in Coronary artery disease (CAD).
Endothelium-derived nitric oxide (NO) is synthesized from l-arginine by endothelial nitric oxide synthase (eNOS) encoded by the NOS3 gene on chromosome7. Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; polymorphisms of NOS gene might be associated with increased susceptibility to coronary artery disease (CAD). We therefore undertook this study to determine the association between the occurrence of CAD and eNOS4 b/a polymorphism in South Indian patients. We investigated the polymorphisms in the 27 base-pair tandem repeats in intron4 of the eNOS gene in 100 unrelated CAD patients with positive coronary angiograms and 100 age and sex matched control subjects without any history of symptomatic CAD. The eNOS gene intron4 b/a VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 63, 26 and 11 per cent in CAD subjects, and 72, 20 and 8 per cent in control subjects, respectively. The genotype frequencies did not differ significantly between the two groups. The frequency of the a allele was 0.24 per cent in CAD subjects and 0.18 per cent in control subjects and no significant association was found between patients and control group (P = 0.57, Odds ratio = 3.62). Plasma lipids, glucose and creatinine levels were significantly increased in CAD group. The genotypic frequencies and the allele frequency did not differ significantly between the CAD patients and controls indicating that this polymorphism was not an independent risk factor for the development of CAD in South Indian patients.


DenseMatch: a dataset for real-time 3D reconstruction.
We provide a database aimed at real-time quantitative analysis of 3D reconstruction and alignment methods, containing 3140 point clouds from 10 subjects/objects. These scenes are acquired with a high-resolution 3D scanner. It contains depth maps that produce point clouds with more than 500k points on average. This dataset is useful to develop new models and alignment strategies to automatically reconstruct 3D scenes from data acquired with optical scanners or benchmarking purposes.


Variations in gene expression patterns correlated with phenotype of F-11 tumor cells whose expression of GD3-synthase is suppressed.
Alteration in ganglioside composition in F-11 cells by suppression of GD3-synthase gene expression resulted in greatly reduced tumor growth and metastasis when the cells were injected into nude mice. To identify genes whose expression is correlated with the decreased level of ganglioside GD3, we analyzed gene expression profiles of the GD3-suppressed F-11 cells and the control F-11 cells using DNA microarrays. We identified a set of GD3-related genes, most of which are involved in tumor growth and development. The genes that define the proliferation-transformation signature are down-regulated, such as creatine kinase-B (CKB), upstream stimulation factor 1 (USF-1), type II cAMP-dependent protein kinase regulatory subunit (RII PKA), and tyrosine hydroxylase (TH). On the other hand, the genes that define the differentiation-reverse transformation signature are up-regulated, including p160 myb-binding protein (P160), brain factor-2, insulin-like growth factor-binding protein (IGFBP), and growth/differentiation factor 11. Transcriptional levels of the genes that showed the most distinct GD3-related expression change were validated by reverse transcription-polymerase chain reaction (RT-PCR). Defining GD3-related genes may lead to identification of clinically relevant therapeutics and to understanding of the mechanism(s) by which ganglioside GD3 affects tumor growth and metastasis.


The effect of subadditive pretraining on blocking: limits on generalization.
Recent evidence indicates that prior learning about a set of cues may determine how new cues are processed. If subjects are taught that two reliable predictors of an outcome do not summate when the cues are presented together (i.e., subadditive pretraining), the subjects will tend to show a less profound blocking effect when trained with different cues. Three experiments investigated the conditions necessary for subadditive pretraining to generalize to new cues. Experiment 1 demonstrated that subadditive pretraining is less effective in reducing blocking when it is experienced in a context other than that in which the blocking training is experienced. In Experiment 2, the effectiveness of subadditive pretraining waned with time. Experiment 3 showed that subadditive pretraining is more effective when the temporal characteristics of pretraining cues are similar to those of the cues used in blocking training. These results provide information concerning the conditions under which learning will generalize from one set of cues to another.


Updates on Intraoperative Neurophysiology During Surgery for Spinal Dysraphism.
Spinal dysraphism is a group of disorders resulting from an embryologic failure of spinal cord development which can lead to a radicular-medullary mechanical stretch that generates vascular compromise and hypoxic-ischemic damage to the nervous structures of the conus-cauda region.Thus, the clinical relevance of the different types of spinal dysraphism is related to the possible neurologic deficits resulting from spinal cord tethering. The clinical presentation is heterogenous: from asymptomatic to very compromised patients. The indications and the time of a detethering surgery are still subject of debate, although there is an agreement on the high standards of treatment that have to be offered by the surgery. Intraoperative neurophysiology (ION) contributes to the safety of tethered cord surgery in reducing the risks of iatrogenic neurological damages.


Educating students during a pandemic in the light of research.
The topic of this article is the research that was carried out at the Opole University of Management and Administration during the pandemic. The aim of the research was to answer the question whether and to what extent the COVID-19 pandemic affected the completion of studies by students of the Opole University of Management and Administration. The analysis included the assessment of students from the last semester in the academic year 2018/2019 (before the COVID-19 pandemic) and 2019/2020 (during the COVID-19 pandemic), as well as the results from the diploma examination, the coefficient of similarity of the works to others in the uniform anti-plagiarism system and the planned date of taking the final examination. The research was conducted using the data analysis method. The results showed that the students who were supposed to graduate in the time when the pandemic started, much more often than their predecessors did not take the final examination and were not able to finish writing their diploma papers. Additionally, they had lower grades in their practical subjects.


How to scale up from animal movement decisions to spatiotemporal patterns: An approach via step selection.
Uncovering the mechanisms behind animal space use patterns is of vital importance for predictive ecology, thus conservation and management of ecosystems. Movement is a core driver of those patterns so understanding how movement mechanisms give rise to space use patterns has become an increasingly active area of research. This study focuses on a particular strand of research in this area, based around step selection analysis (SSA). SSA is a popular way of inferring drivers of movement decisions, but, perhaps less well appreciated, it also parametrises a model of animal movement. Of key interest is that this model can be propagated forwards in time to predict the space use patterns over broader spatial and temporal scales than those that pertain to the proximate movement decisions of animals. Here, we provide a guide for understanding and using the various existing techniques for scaling up step selection models to predict broad-scale space use patterns. We give practical guidance on when to use which technique, as well as specific examples together with code in R and Python. By pulling together various disparate techniques into one place, and providing code and instructions in simple examples, we hope to highlight the importance of these techniques and make them accessible to a wider range of ecologists, ultimately helping expand the usefulness of SSA.


Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis.
Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of microRNAs (miRNAs) in AS T cells involved in the pathogenesis of AS. The expression profile of 270 miRNAs in T cells from five AS patients and five healthy controls were analysed by real-time polymerase chain reaction (PCR). Thirteen miRNAs were found potentially differential expression. After validation, we confirmed that miR-16, miR-221 and let-7i were over-expressed in AS T cells and the expression of miR-221 and let-7i were correlated positively with the Bath Ankylosing Spondylitis Radiology Index (BASRI) of lumbar spine in AS patients. The protein molecules regulated by miR-16, miR-221 and let-7i were measured by Western blotting. We found that the protein levels of Toll-like receptor-4 (TLR-4), a target of let-7i, in T cells from AS patients were decreased. In addition, the mRNA expression of interferon (IFN)-γ was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR-4 agonist, inhibited IFN-γ secretion by anti-CD3(+) anti-CD28 antibodies-stimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let-7i enhanced IFN-γ production by anti-CD3(+) anti-CD28(+) lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-γ production by anti-CD3(+) anti-CD28(+) LPS-stimulated AS T cells. In conclusion, we found that miR-16, miR-221 and let-7i were over-expressed in AS T cells, but only miR-221 and let-7i were associated with BASRI of lumbar spine. In the functional studies, the increased let-7i expression facilitated the T helper type 1 (IFN-γ) immune response in T cells.


Completion Lymph Node Dissection for Melanoma Before and After the Multicenter Selective Lymphadenectomy Trial-II in the United States.
The Multicenter Selective Lymphadenectomy Trial-II (MSLT-II) revealed completion lymph node dissection (CLND) after positive sentinel lymph node biopsy (SLNB) did not improve melanoma-specific survival compared with surveillance. Given these findings and the morbidity associated with CLND, this study investigated trends in rates and predictors of CLND after MSLT-II. Analysis of the National Cancer Database was performed for all patients aged ≥18 years with melanoma and a positive SLNB for 2012-2019. Rates of CLND before and after publication of MSLT-II were identified and logistic regression used to identify factors associated with CLND. Patients undergoing CLND declined from 55.9% pre-MSLT-II (n = 9725) to 19.5% post-MSLT-II (n = 9419) (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.29-0.35). CLND was less likely in females (OR 0.83; 95% CI 0.78-0.89), older patients (vs. 18-39 yr; 40-64 yr OR 0.80, 95% CI 0.65-0.98; 65-79 yr OR 0.67, 95% CI 0.53-0.84; >80 yr OR 0.38, 95% CI 0.30-0.49), sicker patients (Deyo category ≥2 OR 0.85, 95% CI 0.73-0.99), thinner primary lesions (vs. 0.01-0.79 mm; 1.01-4.00 mm OR 1.16, 95% CI 1.01-1.33; ≥4.01 mm OR 1.31, 95% CI 1.08-1.59), patients from metro areas (Rural OR 1.31, 95% CI 1.00-1.70; Urban OR 1.15, 95% CI 1.03-1.29), and those treated at lower-volume centers (vs. lowest-volume; highest-volume OR 1.31, 95% CI 1.14-1.50; high-volume OR 1.40, 95% CI 1.24-1.57). MSLT-II has impacted clinical care; however, male gender, thicker lesions, rural/urban residence, younger age, fewer comorbidities, and treatment at higher-volume centers confer a greater likelihood of undergoing CLND. Further investigations should focus on whether these populations benefit from more aggressive surgical care.


The clinical management of hyperglycemia in pregnancy complicated by maturity-onset diabetes of the young.
Women with maturity-onset diabetes of the young (MODY) are often first identified and diagnosed with diabetes during pregnancy. Genetics and hyperglycemia play an important role in determining fetal size in MODY pregnancies. The principal objective of the current study is to determine the outcomes and clinical management of hyperglycemia in pregnancies complicated by glucokinase gene (GCK) and hepatocyte nuclear factor (HNF)-1α MODY mutations. A retrospective chart review of 37 women with a GCK/HNF-1α mutation was conducted. Data on variables such as birthweight, mode of delivery, and the treatment of hyperglycemia were available on 89 pregnancies. The birthweight in unaffected GCK offspring was significantly higher than in the affected GCK offspring (4.8 [4.1-5.2] kg vs 3.2 [3.1-3.7] kg; P = .01). Seven-point home blood glucose monitoring over a 7-day period in each trimester demonstrated higher fasting and postprandial glycemic excursions in the first trimester of GCK pregnancies when compared to HNF-1α pregnancies (fasting 104 [90-115] mg/dL vs 84 [77-88] mg/dL; P = .01 and postprandial 154 [135-196] mg/dL vs 111 [100-131] mg/dL; P = .04) despite insulin treatment. There was a higher percentage of miscarriages in the GCK group when compared to the HNF-1α MODY group (33.3% vs 14%; P = .07), which was similar to the background population. Insulin initiated at an early gestation appeared to lower the incidence of macrosomia in GCK unaffected offspring. Hyperglycemia in HNF-1α pregnancies is easily managed with current insulin protocols; in contrast, glycemic excursions are difficult to manage in GCK pregnancies. There was an increased percentage of miscarriages in GCK pregnancies highlighting the importance of a diagnosis of GCK-MODY in women prior to conception and the necessity for preconception care.


Endurance-trained subjects and sedentary controls increase ventricular contractility and efficiency during exercise: Feasibility of hemodynamics assessed by non-invasive pressure-volume loops.
Pressure-volume (PV) loops can be used to assess both load-dependent and load-independent measures of cardiac hemodynamics. However, analysis of PV loops during exercise is challenging as it requires invasive measures. Using a novel method, it has been shown that left ventricular (LV) PV loops at rest can be obtained non-invasively from cardiac magnetic resonance imaging (CMR) and brachial pressures. Therefore, the aim of this study was to assess if LV PV loops can be obtained non-invasively from CMR during exercise to assess cardiac hemodynamics. Thirteen endurance trained (ET; median 48 years [IQR 34-60]) and ten age and sex matched sedentary controls (SC; 43 years [27-57]) were included. CMR images were acquired at rest and during moderate intensity supine exercise defined as 60% of expected maximal heart rate. Brachial pressures were obtained in conjunction with image acquisition. Contractility measured as maximal ventricular elastance (Emax) increased in both groups during exercise (ET: 1.0 mmHg/ml [0.9-1.1] to 1.1 mmHg/ml [0.9-1.2], p<0.01; SC: 1.1 mmHg/ml [0.9-1.2] to 1.2 mmHg/ml [1.0-1.3], p<0.01). Ventricular efficiency (VE) increased in ET from 70% [66-73] at rest to 78% [75-80] (p<0.01) during exercise and in SC from 68% [63-72] to 75% [73-78] (p<0.01). Arterial elastance (EA) decreased in both groups (ET: 0.8 mmHg/ml [0.7-0.9] to 0.7 mmHg/ml [0.7-0.9], p<0.05; SC: 1.0 mmHg/ml [0.9-1.2] to 0.9 mmHg/ml [0.8-1.0], p<0.05). Ventricular-arterial coupling (EA/Emax) also decreased in both groups (ET: 0.9 [0.8-1.0] to 0.7 [0.6-0.8], p<0.01; SC: 1.0 [0.9-1.1] to 0.7 [0.7-0.8], p<0.01). This study demonstrates for the first time that LV PV loops can be generated non-invasively during exercise using CMR. ET and SC increase ventricular efficiency and contractility and decrease afterload and ventricular-arterial coupling during moderate supine exercise. These results confirm known physiology. Therefore, this novel method is applicable to be used during exercise in different cardiac disease states, which has not been possible non-invasively before.


Temporal modulation transfer functions measured from auditory-nerve responses following sensorineural hearing loss.
The ability of auditory-nerve (AN) fibers to encode modulation frequencies, as characterized by temporal modulation transfer functions (TMTFs), generally shows a low-pass shape with a cut-off frequency that increases with fiber characteristic frequency (CF). Because AN-fiber bandwidth increases with CF, this result has been interpreted to suggest that peripheral filtering has a significant effect on limiting the encoding of higher modulation frequencies. Sensorineural hearing loss (SNHL), which is typically associated with broadened tuning, is thus predicted to increase the range of modulation frequencies encoded; however, perceptual studies have generally not supported this prediction. The present study sought to determine whether the range of modulation frequencies encoded by AN fibers is affected by SNHL, and whether the effects of SNHL on envelope coding are similar at all modulation frequencies within the TMTF passband. Modulation response gain for sinusoidally amplitude modulated (SAM) tones was measured as a function of modulation frequency, with the carrier frequency placed at fiber CF. TMTFs were compared between normal-hearing chinchillas and chinchillas with a noise-induced hearing loss for which AN fibers had significantly broadened tuning. Synchrony and phase responses for individual SAM tone components were quantified to explore a variety of factors that can influence modulation coding. Modulation gain was found to be higher than normal in noise-exposed fibers across the entire range of modulation frequencies encoded by AN fibers. The range of modulation frequencies encoded by noise-exposed AN fibers was not affected by SNHL, as quantified by TMTF 3- and 10-dB cut-off frequencies. These results suggest that physiological factors other than peripheral filtering may have a significant role in determining the range of modulation frequencies encoded in AN fibers. Furthermore, these neural data may help to explain the lack of a consistent association between perceptual measures of temporal resolution and degraded frequency selectivity.


Self-assembled prodrugs: an enzymatically triggered drug-delivery platform.
Enzyme catalysis as a tool to disassemble supramolecular hydrogels to control the release of encapsulated drugs provides an opportunity to design a wide range of enzyme-specific low-molecular-weight hydrogelators. In this proof-of-concept work, we report the synthesis of low-molecular-weight amphiphilic prodrugs as hydrogelators from a well-known drug acetaminophen (which belongs to a class of drugs called analgesics (pain relievers) and antipyretics (fever reducers)). We have shown the ability of prodrugs to self-assemble to form hydrogels that could subsequently encapsulate a second drug such as curcumin, which is a known chemopreventive and anti-inflammatory hydrophobic drug. Upon enzyme-triggered degradation, the hydrogel released single or multiple drugs at physiologically simulated conditions in vitro. Given that the degradation products consist of the drug and a fatty acid, this approach has an advantage over polymer-based prodrugs that generate polymer fragments with heterogeneous chain lengths upon degradation that may present complex toxicity profiles. Additionally, drug-release occurred without burst release. Spectrophotometric experiments supported the drug-release, and the rate was controlled by modulation of temperature and enzyme concentration. Mesenchymal stem cells treated with prodrugs retained their stem cell properties including the capacity of multi-lineage differentiation, and maintained their adhesive and proliferation capacities with high viability. The present biomaterials could have broad applications as drug-delivery vehicles and cell invasive matrices.


Testosterone-indued focal myocarditis in rats. II. Morphological and biochemical observations of the adrenal in relation to the pathogenetical mechanism of cardiac lesions.
Correlative morphological and biochemical studies were made on the adrenal of rats treated with daily subcutaneous injections of testosterone propionate in a dose of 50 mg/kg for 30 consecutive days. Histologically, there is a thinning of the zona fasciculata with a decrease of cell numbers, swelling of the cell body and the occurrence of large lipid droplets in the cytoplasm. Electron microscopic examination revealed swelling of mitochondria with reduction of cristae and hypertrophy of smooth-surfaced endoplasmic reticulum with cluster formation or whirl-like arrangement. In in vitro biochemical experiments, it was noted that conversion of deoxycorticosterone to corticosterone or 18-hydroxydeoxy-corticosterone was decreased to 45% of the control level in the testosterone-treated group.


Energy transfer between fusion biliproteins co-expressed with phycobiliprotein in Escherichia coli.
In cyanobacteria, phycobiliproteins (PBS) show excellent energy transfer among the chromophores absorbing over most of the visible. The energy transfers are used to study phycobilisome assembly and bioimaging. Using All4261GAF2(C81L) as energy donor, ApcE(1-240/Δ87-130) as energy acceptor, we co-expressed fusion protein ApcE(1-240/Δ87-130)::All4261GAF2(C81L) with phycobiliprotein in Escherichia Coli and studied the energy transfer between two protein domains. With N-terminal His6 tag, ApcE(1-240/Δ87-130)::All4261GAF2(C81L) cannot be purified by nickel-affinity column. We added six histidines in the C-terminal of ApcE(1-240/Δ87-130)::All4261GAF2(C81L) and co-expressed it with phycobiliprotein. ApcE(1-240/Δ87-130)::PCB-All4261GAF2(C81L)His6 was purified successfully and only singly chromophorylated at All4261GAF2(C81L)His6 domain. The singly chromophorylate ApcE(1-240/Δ87-130)::PCB-All4261GAF2(C81L)His6 was incubated with fresh PCB and the doubly chromophorylated PCB-ApcE(1-240/Δ87-130)::PCB-All4261GAF2(C81L)His6 was obtained. The double chromophored fusion protein absorbed light in the range of 615-660 nm, and fluoresced only at 668 nm. Photochemistry analysis showed that excitation energy transfer from the short-wavelength absorbing at All4261GAF2(C81L) domain was achieved successfully to the long-wavelength absorbing at the ApcE(1-240/Δ87-130) domain.


Prognostic significance of peritoneal lavage cytology in patients with colorectal cancer.
The clinical significance of peritoneal lavage cytology for patients with gastric cancer is recognized, whereas that for patients with colorectal cancer remains controversial. The present study used a nationwide registry to clarify the prognostic significance of peritoneal lavage cytology in patients with colorectal cancer. We retrospectively analyzed factors associated with recurrence and survival in patients with T3-T4 colorectal cancer without distant metastasis taken from the nationwide registry of the Japanese Society for Cancer of the Colon and Rectum between 1984 and 1999. Among 34,554 patients in this study, not all of whom received peritoneal lavage cytology, 35 had positive peritoneal lavage cytology. Gender (P = 0.0004), tumor location (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001), lymph node metastasis (P < 0.0001) and peritoneal cytology (P = 0.015) were risk factors for peritoneal recurrence. Multivariate analysis revealed that tumor location (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001) and lymph node metastasis (P < 0.0001) were independent risk factors for peritoneal metastasis. Gender (P < 0.0001), tumor location (P < 0.0001), age (P < 0.0001), histological grade (P < 0.0001), depth of tumor invasion (P < 0.0001), lymph node metastasis (P < 0.0001) and peritoneal cytology (P = 0.0004) were independent prognostic factors according to the Cox proportional hazards model. Positive peritoneal lavage cytology was associated with poorer survival in patients with stage II and III colorectal cancer. Positive cytology might be a good indicator of candidates for intensive adjuvant chemotherapy. The benefit of intensive adjuvant chemotherapy for such patients should be validated in prospective trials.


Epicardial ablation of atrial fibrillation on the beating heart without cardiopulmonary bypass.
The Cox-Maze procedure is the gold standard in surgical treatment of atrial fibrillation. Alternative techniques using cryoablation, radiofrequency, or microwaves have been proven to be equally effective. However, up to now, all techniques require the opening of the atria and, hence, the use of extracorporeal circulation. We describe a technique to perform epicardial ablation of atrial fibrillation on the beating heart without the use of cardiopulmonary bypass.


Pattern component ratio in pattern-reversal VEP: normative data and clinical applications.
It has been well established that there is a reliable implicit time to the VEP positive component (ca 100 msec) in response to pattern reversal. This has become a valuable test of the status of the visual system. Recent data suggest that activity around 200 msec is another useful measure of the cortical response to pattern alternation. We have carried out a normative study of the relative amplitudes of the two components. Among adults with normal visual acuity activity around 200 msec is directly related to the spatial frequency of the stimulus, peaking markedly in amplitude at a narrow range of spatial frequencies. This is in sharp contrast to the earlier component, which does not exhibit such sensitive size differentiation. Recently we have used the ratio between the late and early component amplitudes as a quantitative indicator of the efficiency of higher-level processing of pattern information. We present our normative data and illustrate the effects of decreased visual responses not related to known peripheral optical problems. The results of this work are also interpreted as showing basic characteristics of information processing in the visual system, in that higher spatial frequencies are processed by a continuum of rather sharply tuned cortical processes, with the higher spatial frequencies being processed later in time.


[Detrusor-sphincter dyssynergia: four case reports and literature review].
Detrusor-sphincter dyssynergia is responsible for major impairment and is factor for social and professional activity repercussions. We have studied the clinical and urodynamic finding in four patients (two men and two women) with detrusor-sphincter dyssynergia. Mean age is 36 years (26-44 years). Dyssynergia was secondary to tuberculosis meningitis in one case, surgery for rectal adenocarcinoma in one case, tight vertebral canal in one case and in one case the cause is indeterminate. The detrusor-sphincter dyssynergia were treated by autocatheterism in two cases, antibiotherapy antituberculosis associated with an anticholinergic drugs in one case and by alpha-blockers agent in another. Quasi-complete salvage of the motor deficit and the dysfonctional voiding in a patient treated by antibiotherapy antituberculosis associated with an anticholinergic drugs. As well, maid evolution in patient treated by alpha-blockers agent and who practice self catheterization. Optimal treatment is unknown, and the existence of several cures indicated the limit of all therapeutic methods.


Increased binding of beta-2-microglobulin to blood cells in dialysis patients treated with high-flux dialyzers compared with low-flux membranes contributed to reduced beta-2-microglobulin concentrations. Results of a cross-over study.
Patients on long-term dialysis eventually develop amyloid deposits with beta2-microglobulin as a predominant component. Although several studies have suggested that high-flux membranes reduce beta2-microglobulin in plasma compared with low-flux dialyzers, the mechanisms underlying this observation are still discussed. We revisited this important subject and measured beta2-microglobulin in the plasma of healthy individuals (n = 8), and patients undergoing hemodialysis (n = 20) who for assigned periods of time were either treated with a low-flux membrane (cuprophan) or high-flux (polyamide) dialyzer with an ELISA. The number of blood cells was determined by FACS. Beta2-microglobulin was also measured on the surface of granulocytes, lymphocytes, and monocytes before, directly after, and 4 h after hemodialysis. Expression of beta2-microglobulin, c-fos, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 mRNA was determined in whole blood samples with quantitative RT-PCR using an internal standard in parallel. In the second part of the study, patients were assigned in a two-group cross-over design either to low- or high-flux dialyzers (n = 9 in each group), and dialyzer membranes were changed every 4 weeks for two consecutive periods. Serum beta2-microglobulin concentrations were measured at the end of each period. Healthy controls had a low plasma beta2-microglobulin level of 1.2 +/- 0.3 mg/l. Before hemodialysis, patients on low-flux dialyzers had a plasma beta2-microglobulin level of 42.0 +/- 14.0 mg/l, patients treated with high-flux dialyzers 21.5 +/- 10.8 mg/l (p < 0.05 vs. low-flux dialyzers). In contrast, there was no significant difference in plasma concentrations of active transforming growth factor-beta1 with the two different membrane types. The difference in serum beta2-microglobulin between low- and high-flux membranes was more prominent directly after hemodialysis as well as 4 h after hemodialysis compared with the values directly before the start of treatment. At all studied time-points, leukocytes and platelets were significantly higher in patients on low-flux membranes. Healthy control persons exhibited a significantly higher amount of beta2-microglobulin bound to granulocytes, lymphocytes, and monocytes compared with dialysis patients. Interestingly, beta2-microglobulin bound to granulocytes, lymphocytes, and monocytes was significantly increased in patients treated with high-flux membranes compared with low-flux filters. Quantitative RT-PCR revealed no significant difference in beta2-microglobulin expression in whole blood before hemodialysis, directly after hemodialysis, and 4 h after hemodialysis. However, TNF-alpha and c-fos transcripts were significantly higher in whole blood obtained from patients treated with low-flux membranes compared to high-flux dialyzers. The two-group cross-over study over three periods of 4 weeks revealed that switching from low-flux to high-flux dialyzers significantly reduced serum beta2-microglobulin levels. Patients treated with a polyamide high-flux membrane had lower beta2-microglobulin concentrations compared with those patients on low-flux dialyzers. This difference might not be mediated by an increase in beta2-microglobulin mRNA, but may be caused by less beta2-microglobulin released from the blood cells in patients treated with high-flux dialyzers, in addition to a better beta2-microglobulin clearance.


Effects of the Incubation Period of Pleurotus ostreatus on the Chemical Composition and Nutrient Availability of Solid-State-Fermented Corn Stover.
The current study aimed to optimize and improve the feeding value of Pleurotus ostreatus-fermented corn stover by evaluating the effects of five solid-state fermentation times and three in vitro fermentation periods on the chemical composition, dry matter disappearance (DMD), microbial mass and volatile fatty acid (VFA) production of treated and untreated corn stover. The study utilized a 3 × 5 factorial design, with eight replicates per treatment. Dry matter, crude protein (CP), ash and non-fiber carbohydrate (NFC) contents increased quadratically (p < 0.05) with increases in the solid-state fermentation time. Increases of 44.4-59.1%, 20.6-78.6% and 40.5-121% were noted for the CP, ash and NFC contents, respectively. Organic matter, ether extract, neutral detergent fiber and hemicellulose contents decreased quadratically (p < 0.05) across the treatments. Similar trends were noted for DM and fiber disappearance in the treatments. The total gas production and in vitro true dry matter digestibility (IVTDMD) increased quadratically, while microbial mass and in vitro apparent DMD increased in a linear manner. The total VFA, propionate and butyrate contents increased linearly. Both the acetate content and the A:P ratio decreased in a linear manner. The results show that the rumen fermentation pathway favors the production of propionate, with increases in propionate production of 7.46 and 8.30% after 2 and 4 wk, respectively. The study showed that a 2 wk period of solid-state fermentation is sufficient to provide a bio-transformed cow-calf feed resource from P. ostreatus-treated corn stover.


Positive Association Between Cognitive Function and Cerebrospinal Fluid Orexin A Levels in Alzheimer's Disease.
Recently, many studies have investigated the association between orexin A and Alzheimer's disease (AD). However, it remains to be determined whether the observed changes in orexin A levels are associated with pathological changes underlying AD, or cognitive function. In particular, a direct association between cerebrospinal fluid (CSF) orexin A levels and cognitive function has not been reported to date. The aim of this study was to identify whether there is a direct association between the orexinergic system and cognitive function in AD. For this study, we included 22 patients with AD and 25 control subjects who underwent general physical, neurological, and psychiatric examinations, neuroimaging, and CSF collection by lumbar puncture were enrolled. Correlations between CSF orexin A levels and CSF AD biomarker levels (i.e., levels of phosphorylated tau [p-tau], Aβ42, and Aβ42/Aβ40) were assessed to confirm the results of previous studies. Moreover, the correlation between CSF orexin A levels and Mini-Mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) scores were analyzed. There was a significant positive correlation between CSF orexin-A levels and cognitive function (MMSE scores: r = 0.591, p = 0.04, MoCA score: r = 0.571, p = 0.006) in AD patients. This is the first study to our knowledge demonstrating an association between cognitive function and CSF orexin A levels in AD. Our results suggest the possibility that orexinergic system overexpression is not always a negative factor for cognitive function In AD.


No scavenging and the hypertensive effect of hemoglobin-based blood substitutes.
The major pathway for nitric oxide scavenging in red cells involves the direct reaction of the gas with HbO2 to form nitrate and the ferric form of the protein, metHb. Because both atoms of O2 are incorporated into nitrate, this process is called NO dioxygenation (NOD). The NOD reaction involves an initial, very rapid bimolecular addition of NO to bound O2 to form a transient Fe(III)-peroxynitrite complex, which can be observed spectrally at alkaline pH. This intermediate rapidly isomerizes at pH 7 (t1/2 <== 1 ms) to metHb and NO3-, which is nontoxic and readily transported out of red cells and excreted. The rate of NO consumption by intracellular HbO2 during normal blood flow is limited by diffusion up to and into the red cells and is too slow to interfere significantly with vasoregulation. In contrast, extracellular HbO2 is highly vasoconstrictive, and the resultant hypertension is a significant side effect of most hemoglobin-based blood substitutes. The major cause of this blood pressure effect seems to be the high rate of NO dioxygenation by cell-free HbO2, which can extravasate into the vessel walls and interfere directly with NO signaling between endothelial and smooth muscle cells. This interpretation is supported by a strong linear correlation between the magnitude of the blood pressure effect caused by infusion of cross-linked recombinant hemoglobin tetramers in vivo and the rate of NO dioxygenation by these proteins measured in vitro.


Thermal decomposition of developing enamel.
The decomposition of forming, maturing, and mature enamel was studied between room temperature and 1,000 degrees C by powder X-ray diffraction and infrared absorption methods. In mature dental enamel, carbonate decomposition proceeds relatively fast until 500 degrees C and at a slower rate beyond it. In forming and maturing enamel, decomposition is faster and is completed around 800 degrees C. The formation of beta-Ca3(PO4)2 is observed in dental enamel at 500 degrees C. At 1,000 degrees C, the apatite phase in forming and maturing enamel transforms almost completely to beta-Ca3(PO4)2, whereas in mature enamel, even at 1,000 degrees C, only partial decomposition occurs. Infrared results show the appearance in dental enamel of (1) A-type carbonate at room temperature and in the 500-900 degrees C range, in addition to the commonly observed B-type carbonate, and (2) intermediate CO2 molecules during carbonate decomposition (200-500 degrees C).


Is craniofacial dysmorpholgy correlated with structural brain anomalies in schizophrenia?
This study aimed to examine the relationship between craniofacial dysmorphology and anomalies of brain morphology in schizophrenia. Assessments of craniofacial dysmorphology and magnetic resonance imaging of brain were performed independently of each other and blind to each other in 24 males with schizophrenia and 16 male controls. Ventricular cerebrospinal fluid volume was negatively correlated with total dysmorphology score in males with schizophrenia (i.e., the larger the ventricular cerebrospinal fluid volume, the lower the total dysmorphology score) but not in male controls. These findings suggest that craniofacial dysmorphology and anomalies of brain morphology may be associated with independent processes in the etiology of schizophrenia.


Multicenter, noninterventional, post-marketing surveillance study to evaluate dosing of recombinant human follicle-stimulating hormone using the redesigned follitropin alfa pen in women undergoing ovulation induction.
This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH) using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI) alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles ≥15 mm). Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population). The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%), 50.0 IU (n=1,056 from N=3,189; 33.1%), and 75.0 IU (n=738 from N=3,189; 23.1%) on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%), 50.0 IU (n=922 from N=3,189; 28.9%), and 75.0 IU (n=895 from N=3,189; 28.1%) on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU) of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI.


A Human Retinal Pigment Epithelium-Based Screening Platform Reveals Inducers of Photoreceptor Outer Segments Phagocytosis.
Phagocytosis is a key function in various cells throughout the body. A deficiency in photoreceptor outer segment (POS) phagocytosis by the retinal pigment epithelium (RPE) causes vision loss in inherited retinal diseases and possibly age-related macular degeneration. To date, there are no effective therapies available aiming at recovering the lost phagocytosis function. Here, we developed a high-throughput screening assay based on RPE derived from human embryonic stem cells (hRPE) to reveal enhancers of POS phagocytosis. One of the hits, ramoplanin (RM), reproducibly enhanced POS phagocytosis and ensheathment in hRPE, and enhanced the expression of proteins known to regulate membrane dynamics and ensheathment in other cell systems. Additionally, RM rescued POS internalization defect in Mer receptor tyrosine kinase (MERTK) mutant hRPE, derived from retinitis pigmentosa patient induced pluripotent stem cells. Our platform, including a primary phenotypic screening phagocytosis assay together with orthogonal assays, establishes a basis for RPE-based therapy discovery aiming at a broad patient spectrum.


Characterization of a non-structural 147-kDa precursor polypeptide of echovirus 33 and its immunogenicity in man.
Zinc chloride (0.9 mM)--an inhibitor of the processing of the initial polypeptides of Picornaviridae--was used to accumulate large precursors of echovirus 33 (EV33) and notably two proteins of 147- and 97-kDa. Polyclonal hyperimmune sera were raised in mice against these polypeptides and assayed by immunoblotting against EV33-infected cells blocked or not with ZnCl2, showing that protein 147--2ABC3ABCD according to the L434 convention--can be considered to be the precursor of the two non-structural proteins P2 and P3. Sixty-three serum specimens from subjects exhibiting varying antibody status against EV33 by seroneutralization were investigated by immunoblotting against an EV33 ZnCl2-blocked antigen. Some subjects infected with EV33 were shown to elicit antibodies which recognize the non-structural precursor polypeptides, a fact whose clinical significance needs further evaluation.


Immunolocalization of Bcl-2 oncoprotein in amlodipine-induced gingival overgrowth.
Drug-induced gingival overgrowth (DIGO) is one of the unwanted side effects of amlodipine therapy, but the pathogenesis still remains unclear. Apoptosis, which plays a ubiquitous role in tissue homeostasis, including gingiva, may be involved in the development of gingival enlargement. (i) To study the distribution of Bcl-2 in healthy and overgrown gingival tissues. (ii) To compare and correlate the Bcl-2 expression in gingival samples from subjects on amlodipine therapy to the findings in healthy controls. A total of 25 subjects were recruited for the study - 15 hypertensive patients and 10 systemically healthy subjects. Both the groups were analyzed for Bcl-2 expression using immunohistochemistry. Few of the control specimens showed weak positivity to Bcl-2 antibody, with the distribution limited to the basal cell layers alone, whereas 10 hyperplastic specimens expressed Bcl-2 and, unlike the control group, the distribution pattern was seen in both basal and suprabasal layers. The results indicate that the pathogenesis of amlodipine-induced gingival overgrowth might involve inhibition of apoptosis, especially with morphogenesis of hyperplastic gingival epithelia.


Safety and effectiveness of adding fentanyl or sufentanil to spinal anesthesia: systematic review and meta-analysis of randomized controlled trials.
Spinal infusions of either fentanyl or sufentanil have been reported in international reports, articles, and scientific events worldwide. This study aimed to determine whether intrathecal fentanyl or sufentanil offers safety in mortality and perioperative adverse events. MEDLINE (via PubMed), EMBASE, CENTRAL (Cochrane library databases), gray literature, hand-searching, and clinicaltrials.gov were systematically searched. Randomized controlled trials with no language, data, or status restrictions were included, comparing the effectiveness and safety of adding spinal lipophilic opioid to local anesthetics (LAs). Data were pooled using the random-effects models or fixed-effect models based on heterogeneity. The initial search retrieved 4469 records; 3241 records were eligible, and 3152 articles were excluded after reading titles and abstracts, with a high agreement rate (98.6%). After reading the full texts, 76 articles remained. Spinal fentanyl and sufentanil significantly reduced postoperative pain and opioid consumption, increased analgesia and pruritus. Fentanyl, but not sufentanil, significantly reduced both postoperative nausea and vomiting, and postoperative shivering; compared to LAs alone. The analyzed studies did not report any case of in-hospital mortality related to spinal lipophilic opioids. The rate of respiratory depression was 0.7% and 0.8% when spinal fentanyl or sufentanil was added and when it was not, respectively. Episodes of respiratory depression were rare, uneventful, occurred intraoperatively, and were easily manageable. There is moderate to high quality certainty that there is evidence regarding the safety and effectiveness of adding lipophilic opioids to LAs in spinal anesthesia.


Topical application of Aloe gel and/or olive oil combination promotes the wound healing properties of streptozotocin-induced diabetic rats.
Diabetic wounds are characterized by a delayed closure rate due to the excess inflammation and the inhibition of angiogenesis. Natural products derived from Aloe vera have shown great promise due to their healing magnificent properties. Olive oil is another natural product with anti-microbial and anti-inflammatory properties that may contribute to the healing process. In the present investigation, we tried to evaluate the efficacy of topical application of Aloe gel and/or olive oil in the enhancement of diabetic wounds using histological and immunohistochemical analysis. Excisional wounds were created on the back skin of streptozotocin-induced diabetic rats. Topical treatments of Aloe gel and/or olive oil were applied separately and in a combination (AVO) daily for experimental groups. Macroscopic and microscopic observations of the excision wounds were monitored at time intervals (3, 6, 9, 14 days) post-wounding. Macroscopic observations of the AVO group exhibited almost complete healing at day 14, while other groups were still in progress. Similarly, immunohistochemical analysis of the AVO group showed a mild expression pattern of NF-κB.. While, the cell proliferation (Ki-67), and angiogenesis (CD34) markers were upregulated. Conclusively, the obtained results showed that the AVO combination effectively improved the healing process in diabetic excisional wounds with significant differences in the healing kinetics compared to wounds that received Aloe gel or olive oil separately.


Systematic review: relationships between sleep and gastro-oesophageal reflux.
Gastro-oesophageal reflux disease (GERD) adversely impacts on sleep, but the mechanism remains unclear. To review the literature concerning gastro-oesophageal reflux during the sleep period, with particular reference to the sleep/awake state at reflux onset. Studies identified by systematic literature searches were assessed. Overall patterns of reflux during the sleep period show consistently that oesophageal acid clearance is slower, and reflux frequency and oesophageal acid exposure are higher in patients with GERD than in healthy individuals. Of the 17 mechanistic studies identified by the searches, 15 reported that a minority of reflux episodes occurred during stable sleep, but the prevailing sleep state at the onset of reflux in these studies remains unclear owing to insufficient temporal resolution of recording or analysis methods. Two studies, in healthy individuals and patients with GERD, analysed sleep and pH with adequate resolution for temporal alignment of sleep state and the onset of reflux: all 232 sleep period reflux episodes evaluated occurred during arousals from sleep lasting less than 15 s or during longer duration awakenings. Six mechanistic studies found that transient lower oesophageal sphincter relaxations were the most common mechanism of sleep period reflux. Contrary to the prevailing view, subjective impairment of sleep in GERD is unlikely to be due to the occurrence of reflux during stable sleep, but could result from slow clearance of acid reflux that occurs during arousals or awakenings from sleep. Definitive studies are needed on the sleep/awake state at reflux onset across the full GERD spectrum.


Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.
Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (<34 weeks gestation) with 14 matched normotensive controls, as well as 15 cases late-onset preeclampsia (>34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder.


Leptomeningeal carcinomatosis in small cell carcinoma of the prostate.
Leptomeningeal carcinomatosis in small cell carcinoma of the prostate is rare. A 69-year-old man visited our hospital due to dysuria and edema. Bilateral hydronephrosis and lymph node metastases due to a pelvic tumor were observed. Although the prostate-specific antigen level was normal, the tumor was suspected to originate from the prostate. He underwent percutaneous nephrostomy and prostate biopsy. Histopathology revealed small cell carcinoma accompanied by increased pro-gastrin-releasing peptide and neuron-specific enolase levels. After receiving systemic chemotherapy with carboplatin and etoposide and radiation therapy for prostate, these lesions gradually decreased in size, and tumor markers normalized. Ten months after the initial diagnosis, he developed consciousness disorder and seizure. Magnetic resonance imaging revealed leptomeningeal carcinomatosis without any other recurrences and elevated tumor markers. He died 4 weeks after these symptoms appeared. Careful monitoring of the central nervous system should be considered in small cell carcinoma of the prostate patients.


Assessment of topical therapy of the burn wound with silver sulphadiazine after its use for 15 years in a burn unit.
A comparative study of patients receiving or not receiving topical applications of 1 per cent silver sulphadiazine cream as treatment for burn wounds has shown that the drug is still effective in significantly reducing the amount of bacterial contamination of burn wounds, even after 15 years of use in our Burn Unit. Consequently the overall mortality due to burn wound sepsis has been decreased in this Burn Unit.


Demonstration of the fra(X) in lymphocytes, fibroblasts, and bone marrow in a patient with a testicular tumour.
A man aged 34, whose mental retardation and appearance were consistent with the fra(X)(q28) syndrome, had a craggy lump in his left testis. The fragile X was found in lymphocytes, fibroblasts, and bone marrow. The testicular tumour was benign and inflammatory in nature and within the testis spermatogenesis was absent.


Body weight change during use of a monophasic oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene with a comparison of the women who completed versus those who prematurely discontinued intake.
Evaluation of the impact of an oral contraceptive on body weight with a comparison ofwomen who completed versus women who prematurely discontinued intake. Data on body weight were retrospectively analyzed from four large prospective clinical trials with an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene (EE/GSD). A total of 1971 young fertile women were included in the evaluation, and 1467 completed 12 cycles. We found no clinically relevant change of body weight during treatment with an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene in the vast majority of users after 12 treatment cycles. The mean change of body weight was less than 0.3 kg in this time period for all users. Nearly 70% of women experienced a minor change in their body weight of +/- 2 kg. An additional 13% lost more than 2 kg body weight in the course of 12 treatment cycles. A total of 11% increased their weight by 2-4 kg. A total of 1255 (85.5%) of women had a body mass index (BMI) of < or = 25 at baseline compared to 1253 (85.4%) after 12 cycles of treatment. There was no significant difference in the change ofbody weight between the women completing 12 cycles of treatment and those who prematurely discontinued EE/GSD. This retrospective analysis confirms that there was only a negligible change of body weight during intake of an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene. There was no difference in weight change between the women completing the study or discontinuing intake.


Cytotoxic effects of Cochlospermum regium (Mart & Schrank) Pilger aqueous root extract on mammalian cells.
We investigated the effect of Cochlospermum regium (Mart & Schrank) Pilger aqueous root extract on Chinese hamster ovarian (CHO)-K1 cells. The extract significantly decreased proliferation of CHO-K1 cells (EC(50)=1.5mg/mL). Apoptosis induction was analysed by fluorescent microscopy. Cell cultures treated with Cochlospermum regium extract for 4h contained 13.6% apoptotic cells after 24h (investigated by fluorescent DNA-microscopy with acridine orange/ethidium bromide staining). Characteristic chromatin condensation and fragmentation, verified by 4',6-diamidino-2-phenylindole (DAPI) staining, was observed in the cells after treatment with Cochlospermum regium extract. The results confirm the toxicity of Cochlospermum regium root extract to immortal, non-tumorigenic mammalian cells in vitro.


N-cadherin deficiency impairs pericyte recruitment, and not endothelial differentiation or sprouting, in embryonic stem cell-derived angiogenesis.
Endothelial cells express two classical cadherins, VE-cadherin and N-cadherin. VE-cadherin is absolutely required for vascular morphogenesis, but N-cadherin is thought to participate in vessel stabilization by interacting with periendothelial cells during vessel formation. However, recent data suggest a more critical role for N-cadherin in endothelium that would regulate angiogenesis, in part by controlling VE-cadherin expression. In this study, we have assessed N-cadherin function in vascular development using an in vitro model derived from embryonic stem (ES) cell differentiation. We show that pluripotent ES cells genetically null for N-cadherin can differentiate normally into endothelial cells. In addition, sprouting angiogenesis was unaltered, suggesting that N-cadherin is not essential for the early events of angiogenesis. However, the lack of N-cadherin led to an impairment in pericyte covering of endothelial outgrowths. We conclude that N-cadherin is necessary neither for vasculogenesis nor proliferation and migration of endothelial cells but is required for the subsequent maturation of endothelial sprouts by interacting with pericytes.


Autoantibody-mediated cytotoxicity in paediatric opsoclonus-myoclonus syndrome is dependent on ERK-1/2 phophorylation.
Paediatric opsoclonus-myoclonus syndrome (OMS) is in 50% of the cases associated with a neuroblastoma as a paraneoplastic syndrome and is associated with surface-binding antibodies against cerebellar granular neurons (CGN). To evaluate possible pathogenic effects of these autoantibodies on CGN we examined their influence on the MAPKinase enzymes ERK-1/2 and p38 using flow cytometry and phospho-specific antibodies. OMS IgG but not IgG from neuroblastoma without OMS or healthy controls induced phosphorylation of ERK-1/2 in cerebellar granular neurons (p<0.01). No effect on p38 phosphorylation or on HEK293 control cell line could be detected. IgG-mediated phosphorylation of ERK-1/2 was associated with an increased cytotoxicity of CGN, which could be blocked by ERK-1/2 pathway inhibitor U0126. We here show that IgG-mediated anti-neuronal cytotoxicity in OMS is mediated by ERK-1/2 phosphorylation in CGN.


bcl-2 expression is reciprocal to p53 and c-myc expression in metastatic human colorectal cancer.
Apoptosis (programmed cell death) inhibition may be an important mechanism by which gastrointestinal mucosal cells containing damaged DNA evade normal clearance mechanisms and grow to become invasive tumours. Since bcl-2 is an apoptosis inhibitor, bcl-2 mRNA expression was measured in 21 metastases of colorectal cancer using reverse transcription-polymerase chain reaction analysis. The mean bcl-2 mRNA expression (0.45 U, P < 0.0001) was lower than that of normal mucosal controls (= 1 U). p53 expression was inversely correlated with bcl-2 expression (P = 0.021) in 19 evaluable samples, and in tumours where p53 expression was over twice that of normal colonic mucosal values, bcl-2 mRNA was significantly decreased (mean 0.30, P = 0.0052). c-myc was also inversely correlated with bcl-2 expression (P = 0.025). Decreased bcl-2 expression in metastatic colorectal cancer may be partly due to allelic loss, given the proximity of bcl-2 to the frequently deleted DCC gene on chromosome 18q. However, the inverse correlation to p53/c-myc suggests an active downregulation of bcl-2, possibly following delegation of its apoptosis inhibiting role to other genes.


Effect of clay pretreatment on photofermentative hydrogen production from olive mill wastewater.
The aim of this paper was to gain further insight into the effect of the clay pretreatment process on photofermentative hydrogen production. This two-stage process involved a clay pretreatment step followed by photofermentation which was performed under anaerobic conditions with the illumination by Tungsten lamps. Rhodobacter sphaeroides O.U.001 was used for photofermentation. Higher amounts of color (65%), total phenol (81%) and chemical oxygen demand (31%) removal efficiencies were achieved after clay pretreatment process. During photofermentative hydrogen production with the effluent of clay pretreatment process, the main organic compounds resulting higher hydrogen production rates were found to be acetic, lactic, propionic, and butyric acids. Compared to photofermentation using raw olive mill wastewater ( 16LH2/LOMW), the amount of photofermentative hydrogen production was doubled by using the effluent of the clay pretreatment process (31.5LH2/LOMW). The reasons for the improvement of hydrogen production by clay treatment can be attributed to the high removal of the hardly biodegradable compounds such as phenols; minor removal of organic acids, sugars and amino acids that are known to enhance photofermentative hydrogen production; and the color depletion of raw OMW which might cause a shadowing effect on the photosynthetic bacteria.


Blood chemical changes and renal histological alterations induced by gentamicin in rats.
Gentamicin is an effective widely used antibiotic, but the risk of nephrotoxicity and oxidative damage limit its long-term use. Hence, the current study aims to elucidate such hazardous effects. To achieve the study aim male Wistar albino rats (Rattus norvegicus) were exposed to gentamicin to investigate the resultant blood chemical changes and renal histological alterations. In comparison with control rats, gentamicin produced outstanding tubular, glomerular and interstitial alterations that included degeneration, necrosis, cytolysis and cortical tubular desquamation together with mesangial hypercellularity, endothelial cell proliferation and blood capillary congestion. Compared with control animals significant blood chemical changes (P < 0.05) including free radicals, ALT, AST, ALP, serum creatinine and serum urea were recorded in gentamicin-injected animals. The findings revealed that exposure to gentamicin can induce significant histological alterations in the kidney as well as remarkable blood chemical changes that might indicate marked renal failure.


Anterior segment imaging-based subdivision of subjects with primary angle-closure glaucoma.
PurposeThe purpose of this study was to identify whether it was possible to subdivide subjects with primary angle-closure glaucoma (PACG) based on anterior segment optical coherence tomography (ASOCT) imaging, and to determine the characteristics of such subgroups.MethodsWe evaluated 210 subjects with PACG. All subjects underwent gonioscopy and ASOCT imaging. Customized software was used to measure ASOCT parameters. An agglomerative hierarchical clustering method was first used to determine the optimum number of parameters to be included in the determination of subgroups. Then, the best number of subgroups was determined using Akaike Information Criterion (AIC) and Gaussian Mixture Model (GMM) methods.ResultsThe mean age of the subjects was 67.9 years, and 53.3% were female. Following the hierarchical clustering, four parameters (iris area, anterior chamber depth (ACD), anterior chamber width (ACW), and lens vault (LV)) were chosen to be representative of related parameters. The optimal number of subgroups using GMM analysis and AIC was 3. Subgroup 1 (N=89; 42.4%) was characterized by a large iris area, subgroup 2 (N=24; 11.4%) by a large LV and a shallow ACD, whereas subgroup 3 (N=97; 46.2%) displayed only intermediate values across iris area, LV, and ACD.ConclusionsWe identified three distinct subgroups of PACG subjects based on ASOCT imaging.


Hepatic resection alone versus in combination with pre- and post-operative transarterial chemoembolization for the treatment of hepatocellular carcinoma: A systematic review and meta-analysis.
The prognosis of hepatocellular carcinoma (HCC) treated with hepatic resection may be improved by the adjunctive use of transarterial chemoembolization (TACE). This study aimed to systematically compare the outcomes between hepatic resection with and without TACE groups. All relevant randomized controlled trials (RCTs) and non-RCTs were searched by the PubMed, EMBASE, and Cochrane Library databases. Overall survival (OS) and disease-free survival (DFS) were two major outcomes. Meta-analyses were performed according to the timing of TACE (pre- or post-operative TACE). Subgroup analyses were also performed. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated. Overall, 55 papers were included (14 RCTs and 41 non-RCTs). Overall meta-analyses demonstrated that OS and DFS were statistically similar between hepatic resection with and without pre-operative TACE groups (HR = 1.01, 95%CI = 0.87-1.19, P = 0.87; HR = 0.91, 95%CI = 0.82-1.01, P = 0.07). Subgroup analyses of RCTs or non-RCTs showed that OS and DFS remained statistically similar between hepatic resection with and without pre-operative TACE groups. Subgroup analysis of incomplete or no tumor necrosis showed that OS was worse in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group. By contrast, subgroup analysis of complete tumor necrosis showed that DFS was better in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group.Overall meta-analyses demonstrated that OS and DFS were better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group (HR = 0.85, 95%CI = 0.72-1.00, P = 0.06; HR = 0.83, 95%CI = 0.73-0.94, P = 0.004). Subgroup analyses of RCTs, vascular invasion, or large HCC showed that OS and DFS remained better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group. By contrast, subgroup analyses of non-RCTs, no vascular invasion, or small HCC showed that OS and DFS were statistically similar between the two groups. Post-operative TACE, rather than pre-operative TACE, may be considered as an adjunctive treatment option for HCC treated with hepatic resection.


Multiple roles of the general regulatory factor Abf1 in yeast ribosome biogenesis.
In Saccharomyces cerevisiae, the large majority of the genes coding for cytoplasmic ribosomal proteins (RPs) depend on the general regulatory factor Rap1 for their transcription, but a small cohort of them relies on Abf1 regulatory activity. A recent study showed that unlike Rap1, whose association with RP gene promoters is not affected by environmental changes causing RP gene repression/reactivation, Abf1 association with both RP gene and ribosome biogenesis (Ribi) gene promoters dynamically responds to changes in growth conditions. This observation changes the paradigm of general regulatory factors as relatively static DNA-binding proteins constitutively bound to highly active promoters, and point to Abf1, which binds hundreds of non-RPG promoters within the yeast genome, as a possible key regulatory switch in nutrient- and stress-dependent transcriptional modulation. Moreover, the frequent presence of Abf1 binding sites in the promoters of mitochondrial RP genes evokes the possibility that Abf1 might orchestrate still unexplored levels of co-regulation involving growth-related gene networks in yeast cells.


Analysis of tumor response and clinical factors associated with vitiligo in patients receiving anti-programmed cell death-1 therapies for melanoma: A cross-sectional study.
Clinical factors associated with vitiligo in patients receiving anti-programmed cell death-1 (PD-1) remain unknown. To better characterize the occurrence of vitiligo in patients receiving anti-PD-1. The present single-center ambispective cohort study included patients with melanoma treated with anti-PD-1. Progression-free survival, overall survival, and objective tumor response were compared between patients with and those without vitiligo using Kaplan-Meier curves and the log-rank test. Demographic and clinical factors associated with vitiligo were evaluated using multivariate logistic regression. Of the 457 patients included in the study, vitiligo developed in 85 patients. The clinical presentation of vitiligo consisted of the presence of ovalar and multiple flecked white macules, mainly located on chronic sun-exposed areas. The presence of vitiligo was associated with a significant improvement in overall survival and progression-free survival (P < .001). A Cox proportional hazards model estimation demonstrated markedly improved survival in patients with vitiligo compared with those without vitiligo (aHR [overall survival], 0.20; 95% CI, 0.12-0.33; P < .001; and aHR [progression-free survival], 0.33; 95% CI, 0.23-0.47; P < .001). In the multivariate logistic regression analyses, men showed an independent increased risk of the development of vitiligo (odds ratio, 1.66). In contrast, the presence of pulmonary metastases was found to be an independent factor associated with a reduced risk of the development of vitiligo (odds ratio, 0.50). Single-center ambispective cohort. Vitiligo in patients receiving anti-PD-1 for advanced melanoma is associated with a better outcome. A gender effect associated with the development of vitiligo will need further investigation.


[Gallbladder calculi: cholesterol concentration and its radiologic correlates].
Cholesterol concentration in the gallstones of 84 patients obtained by surgery is studied and radiologic correlation of the stones (lucency and opaqueness) is established with relation to cholesterol concentration. We conclude that 70% of gallstones in our population, contain greater than or equal to 80% of cholesterol and the radiographic appearance of stones in functioning gallbladder is a good method to predict cholesterol content in gallstones.


Muscle force depends on the amount of transversal muscle loading.
Skeletal muscles are embedded in an environment of other muscles, connective tissue, and bones, which may transfer transversal forces to the muscle tissue, thereby compressing it. In a recent study we demonstrated that transversal loading of a muscle with 1.3Ncm(-2) reduces maximum isometric force (Fim) and rate of force development by approximately 5% and 25%, respectively. The aim of the present study was to examine the influence of increasing transversal muscle loading on contraction dynamics. Therefore, we performed isometric experiments on rat M. gastrocnemius medialis (n=9) without and with five different transversal loads corresponding to increasing pressures of 1.3Ncm(-2) to 5.3Ncm(-2) at the contact area between muscle and load. Muscle loading was induced by a custom-made plunger which was able to move in transversal direction. Increasing transversal muscle loading resulted in an almost linear decrease in muscle force from 4.8±1.8% to 12.8±2% Fim. Compared to an unloaded isometric contraction, rate of force development decreased from 20.2±4.0% at 1.3Ncm(-2) muscle loading to 34.6±5.7% at 5.3Ncm(-2). Experimental observation of the impact of transversal muscle loading on contraction dynamics may help to better understand muscle tissue properties. Moreover, applying transversal loads to muscles opens a window to analyze three-dimensional muscle force generation. Data presented in this study may be important to develop and validate muscle models which enable simulation of muscle contractions under compression and enlighten the mechanisms behind.


Indoor coal ash and school and social competency among children aged 6-14 years.
A child's ability to succeed in social interactions and in a school setting are important for their development and growth. Exposure to environmental pollutants has been associated with poorer school performance and fewer social interaction in children. Fly ash, a waste product generated when burning coal for energy, is comprised of small glass spheres with neurotoxic heavy metal(loid)s found to be risk factors for learning and social problems in school. The purpose of this novel study was to assess the association of fly ash in children's homes with school and social competency. We recruited children aged 6-14 years old from communities located within 10 miles of two coal-burning power plants. In homes of the participants, fly ash was collected on polycarbonate filters using personal modular impactors. We measured school competency and social competency using the validated Child Behavioral Checklist. Using Tobit and linear regression we investigated the relationship of indoor fly ash with school and social competency. Forty-three percent of children in the study had fly ash in their homes. In covariate-adjusted Tobit models, children with fly ash in their homes scored on average 2.63 (95% CI: -4.98, -0.28) points lower on the school competency scale than peers without ash in their homes. We did not observe that fly ash in homes was related with lower social competency. Results from this study suggest that children with fly ash in their homes had poorer performance in the school setting, compared to peers without fly ash in their homes. In the US, coal-fired power plants are being closed, however health concerns about pollution from coal ash storage facilities remains. Findings from this study can provide impetus for creating of public health policy and to highlight the need future research on children's exposure to fly ash. Children's growth and development are impacted by their social interactions and ability to perform in school settings. Environmental pollutants may impact these essential elements of development. Millions of children are exposed to fly ash which is a waste product generated from burning coal. Fly ash, an environmental health threat throughout the world, is comprised of small glass spheres with trace concentrations of neurotoxic metal(loid)s. Findings from this research show that children with fly ash in their homes are significantly more likely to have poorer school performance than children without fly ash in their homes.


[Application of radiofrequency ablation for treatment of localized renal carcinoma].
An evaluation of the results of radiofrequency ablation of renal clear-cell carcinoma (pT1aN0M0) in 7 patients is presented. The longest follow-up was 26 months, the shortest--4 months. No complication was reported. A review of the literature and our own experience point to radiofrequency ablation being an effective procedure of thermotherapy for small-size peripheral renal neoplasms.


Deep learning to detect significant coronary artery disease from plain chest radiographs AI4CAD.
The predictive role of chest radiographs in patients with suspected coronary artery disease (CAD) is underestimated and may benefit from artificial intelligence (AI) applications. To train, test, and validate a deep learning (DL) solution for detecting significant CAD based on chest radiographs. Data of patients referred for angina and undergoing chest radiography and coronary angiography were analysed retrospectively. A deep convolutional neural network (DCNN) was designed to detect significant CAD from posteroanterior/anteroposterior chest radiographs. The DCNN was trained for severe CAD binary classification (absence/presence). Coronary angiography reports were the ground truth. Stenosis severity of ≥70% for non-left main vessels and ≥ 50% for left main defined severe CAD. Information of 7728 patients was reviewed. Severe CAD was present in 4091 (53%). Patients were randomly divided for algorithm training (70%; n = 5454) and fine-tuning/model validation (10%; n = 773). Internal clinical validation (model testing) was performed with the remaining patients (20%; n = 1501). At binary logistic regression, DCNN prediction was the strongest severe CAD predictor (p < 0.0001; OR: 1.040; CI: 1.032-1.048). Using a high sensitivity operating cut-point, the DCNN had a sensitivity of 0.90 to detect significant CAD (specificity 0.31; AUC 0.73; 95% CI DeLong, 0.69-0.76). Adding to the AI chest radiograph interpretation angina status improved the prediction (AUC 0.77; 95% CI DeLong, 0.74-0.80). AI-read chest radiographs could be used to pre-test significant CAD probability in patients referred for suspected angina. Further studies are required to externally validate our algorithm, develop a clinically applicable tool, and support CAD screening in broader settings.


Increased prostacyclin metabolites and decreased red cell deformability in patients with systemic sclerosis and Raynauds syndrome.
Patients with systemic sclerosis (SS) often suffer from Raynaud's Syndrome (RS). As prostacyclin (PGI2) is of benefit in the treatment of RS in SS, we have measured endogenous stable metabolites of PGI2 (PGI2m) in 42 patients with Raynaud's Phenomenon (RP) of varying aetiology (15 SS patients, 15 patients with Raynaud's Disease (RD) but no other symptoms, and 12 other RS patients with probable connective tissue disorder). Results were compared with 15 matched controls. Since abnormally rigid red blood cells (RBC) may occur in SS, we also measured RBC deformability (filtration technique). Results show that the SS group have significantly elevated PGI2m levels compared to patients with RD alone and normal controls. In addition, SS patients have more rigid RBC. If all 42 patients with RS were analysed, a significant correlation between PGF and RBC filtration was obtained. The cells of SS patients are resistant to the effects of PGI2 and it would appear that as a compensatory mechanism, production of PGI2 is increased. Treatment with exogenous PGI2 may overcome this resistance and improve microcirculatory flow. The more rigid RBC in SS may also be related to the increased endogenous PGI2. These results may have important clinical implications and allow new therapeutic approaches.


Borderline personality traits do not influence response to TMS.
Comorbid personality disorders are common in patients with major depressive disorder (MDD). Individuals with comorbid borderline personality disorder (BPD) may be less responsive to electroconvulsive therapy (ECT), but it remains unclear whether BPD affects responsiveness to transcranial magnetic stimulation (TMS). We sought to investigate the association between BPD and response to TMS. We conducted a retrospective analysis of individuals receiving TMS (n=356) at McLean Hospital. We also included individuals receiving ECT (n=1434) as a control. All individuals completed the McLean Screening Instrument for BPD (MSI-BPD) at baseline. Response to treatment was measured by the Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR). We performed general linear models (GLMs) to assess the effect of BPD on treatment response to TMS and ECT. At baseline, the ECT group had a higher average QIDS-SR score (21.4 vs. 20.3, p<0.05). For both treatment groups, the number of treatments had a significant effect on depression severity. For the TMS group, there was no significant Group x Time interaction on QIDS-SR score (p=0.18). However, for individuals receiving ECT, there was a significant Group x Time interaction on QIDS-SR score (p=0.02), suggesting that BPD significantly impaired response. These results suggest that borderline personality traits did not affect treatment response to TMS for MDD. BPD traits modestly predicted response to ECT, which is consistent with the literature. These results require replication in a clinical trial.


Prognostic Effect of Renal Function in Ambulatory Patients With Heart Failure and Reduced Ejection Fraction: The Kidney Is a Marker of Cardiac Function.
Chronic kidney disease is a frequent comorbidity in heart failure (HF), associated with increased mortality. The impact of temporal evolution of kidney function in HF prognosis is largely unknown. We evaluated the effect of renal function over time in all-cause mortality among ambulatory patients with HF. We retrospectively analyzed data from 560 patients with HF with left ventricular systolic dysfunction followed for a median of 25.1 months at an outpatient clinic. Demographics and comorbidities were collected at baseline. Creatinine values were abstracted from records at each clinical visit. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and was categorized into 3 classes. Extended Cox models were performed to study the association between time-varying eGFR and death. Patients' mean age was 67.5 ± 13.9 years, 67.0% were men, 46.1% had ischemic etiology, the majority had moderate-to-severe left ventricular systolic dysfunction, and 45.9% had chronic kidney disease at baseline. The eGFR declined approximately 9.0 mL/min/1.73 m2 over 5 years. In crude analysis, time-varying eGFR had a significant dose-dependent association with death (hazard ratio [HR] = 1.34, 95% confidence interval [CI]: 1.03-1.75 for eGFR between 30 and 60 mL/min/1.73 m2; HR = 1.55, 95% CI: 1.11-2.17 for <30 mL/min/1.73 m2). The prognostic value of time-varying eGFR was totally explained by baseline comorbidities, indicators of HF severity and drugs (adjusted HR = 1.11, 95% CI: 0.83-1.48; HR = 1.19, 95% CI: 0.79-1.80, for eGFR 30-60 and <30 mL/min/m2, respectively). Time-varying kidney function is not independently related to poor prognosis in HF. Rather than directly affecting survival, renal impairment is probably a surrogate marker of HF severity.


Association of LINC-PINT polymorphisms with lumbar disc herniation risk among Chinese Han population: a case control study.
Lumbar disc herniation (LDH) is a complex spinal disease, with multiple genetic polymorphisms being related to its risk. Nevertheless, the role of LINC-PINT polymorphisms in LDH risk has remained unknown. Therefore, this study aimed to investigate the association between LINC-PINT polymorphisms and LDH risk. DNA was extracted from 504 LDH patients and 500 healthy controls. Three single nucleotide polymorphisms (SNPs) in LINC-PINT were selected and genotyped using Agena MassARRAY. We used logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) under multiple genetic models to evaluate the association between LINC-PINT polymorphisms and LDH risk. Haploview 4.2 and SNPStats software were used to evaluate the linkage strength of SNPs and the correlation between haplotypes and LDH risk. The impact of SNP-SNP interactions on LDH risk was analyzed using multi-factor dimensionality reduction (MDR). Results showed that rs157916 (G vs. A: OR = 1.23, FDR-p = 0.029) and rs7801029 (G vs. C: OR = 1.39, FDR-p = 0.006; GG vs. CC: OR = 2.34, FDR-p = 0.038; recessive: OR = 2.13, FDR-p = 0.045; additive: OR = 1.39, FDR-p = 0.030) were associated with an increased risk of LDH. Furthermore, LINC-PINT rs157916 and rs780129 were found to be significantly associated with LDH risk in males. The "GGG" haplotype was associated with increased LDH risk (OR = 1.41, FDR-p = 0.006). MDR analysis indicated that the interaction between rs7801029 and rs16873842 was associated with an increased risk of LDH (OR = 1.47, p = 0.004). Additionally, there were significant differences in C-reactive protein levels among different genotypes of rs157916 and rs780129 (p < 0.05). This study suggests that LINC-PINT gene polymorphisms (rs157916 and rs7801029) are considered risk factors for LDH in the Chinese Han population and provide a scientific basis for early screening, prevention, and diagnosis of LDH.


Reduction of glutamate release probability and the number of releasable vesicles are required for suppression of glutamatergic transmission by β1-adrenoceptors in the medial prefrontal cortex.
The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation and behavioral inhibition. Microinjection of β1-adrenoceptor (β1-AR) agonist into the PFC has been shown to impair PFC cognitive function. However, the underlying cellular and molecular mechanisms have not been determined yet. In the present study, we tested the hypothesis that β1-AR mediated modulation of excitatory synaptic transmission contributes to PFC dysfunction. We found that 1) the β1-AR agonist Dobutamine (Dobu) suppressed the amplitude evoked excitatory postsynaptic currents (eEPSCs). 2) Dobu induced a significant suppression of the frequency and amplitude of miniature EPSCs (mEPSCs). 3) Dobu-suppressed glutamate release was mediated via decreasing release probability and the number of releasable vesicles. 4) Dobu suppressed inward currents evoked by puff application of glutamate or NMDA via postsynaptic PKA-dependent pathway. The present study indicates that β1-AR activation suppresses excitatory synaptic transmission in medial PFC (mPFC) via both pre- and post-synaptic PKA-dependent mechanisms. Our results may provide a cellular and molecular mechanism that helps explain β1-AR-induced PFC dysfunction.


[Medical certificates and examinations in family doctor's office. Indications, barriers and relevance of standardization].
In view of medical care being required more and more, the doctors' tight time should be reserved for tasks which correspond to their qualification. A standardization of certificates might save time and improve quality. This paper overviews the role of certificates and the required examinations in family doctor's everyday practice. Current practices, difficulties and suggestions for improvements were worked out in order to illuminate the potential for standardization. In a questionnaire for family doctors data concerning expenditure of time and billing of diverse certificates were collected and quantitatively evaluated. By means of expert interviews difficulties were identified and suggestions for improvement were developed. The use of templates shows a significant saving of time compared to free wording. Also, billing could be enhanced if carried out more systematically. Difficulties are mainly caused by unclear and unrealistic requests. It's worth being proactive and developing a systematic approach in order to save time and to improve the quality of certificates. Templates facilitate modest certificates, while elaborate certificates need adjustable textmodules and checklists. Consistent information and billing promote patients' understanding.