Does like attract like? Exploring the relationship between errors and representational structure in connectionist networks.
Many cognitive psychological studies assume that error probabilities reflect the structure of cognitive representations (e.g., if the representations of two lexical items overlap, they are more likely to interact in a word exchange error than are two lexical items with nonoverlapping representations). However, since errors directly reflect the properties of neurobiological structures and processes, this assumption rests on the correspondence between cognitive and neurobiological elements. Analytical and simulation studies of connectionist networks are used to examine the consequences of different cognitive-neurobiological relationships (e.g., localist vs. distributed representations) for effects of representational structure on error probabilities. The results reveal that such effects are influenced by the nature of the relationship between network and cognitive representations. While errors on localist network representations always reflect the degree to which cognitive representations overlap, distributed representations only do so under specific conditions. Furthermore, the effects of cognitive representational structure on error probabilities are shown to be stronger under localist than under distributed representations.


[Distribution of cervical metastases from carcinoma of the cervicofacial region].
The primary goal in the therapy of patients with cervico-facial cancers has been always the control of loco-regional disease. It is more difficult to control metastasis than primary tumor. According to numerous authors, metastases to cervical lymphonodus reduce the survival of patients with planocellular cancer of the upper aero-digestive pathways for about 50%. Precise classification of primary tumor and regional lymphonodus is highly significant for adequate and timely treatment of patients with cancers of cervico-facial region. The objective of our study was to make clinical classification of cervico-facial tumors and to establish the distribution of nodes according to node groups and cervical levels. In our series of 319 subjects, T2 category of primary tumors was most prevalent accounting for 40.44%. Clinically palpable lymphonodes were found in 87.15%, with most prevalent N1 category accounting for 42.95%. The incidence of clinically negative cervical nodus (N0) was reported in 12.85%. The nodes of the upper, medium and lower jugular group were most frequent in cancers of the larynx and pharynx. In cancer of the oral cavity, submental and submandibular nodes were the most commonly involved. In distribution of nodes based on oncological cervical levels, 45.86% of nodes at level II of the neck were found in laryngeal cancer, while 40% the neck level I was involved in the cancer of the oral cavity. In epipharyngeal cancer, 3.15% of cervical metastases were detected in the posterior triangle of the neck. The incidence of cervical metastases in specific primary localizations has a significant role for indications of one of the dissections of the neck.


MasterOfPores: A Workflow for the Analysis of Oxford Nanopore Direct RNA Sequencing Datasets.
The direct RNA sequencing platform offered by Oxford Nanopore Technologies allows for direct measurement of RNA molecules without the need of conversion to complementary DNA, fragmentation or amplification. As such, it is virtually capable of detecting any given RNA modification present in the molecule that is being sequenced, as well as provide polyA tail length estimations at the level of individual RNA molecules. Although this technology has been publicly available since 2017, the complexity of the raw Nanopore data, together with the lack of systematic and reproducible pipelines, have greatly hindered the access of this technology to the general user. Here we address this problem by providing a fully benchmarked workflow for the analysis of direct RNA sequencing reads, termed MasterOfPores. The pipeline starts with a pre-processing module, which converts raw current intensities into multiple types of processed data including FASTQ and BAM, providing metrics of the quality of the run, quality-filtering, demultiplexing, base-calling and mapping. In a second step, the pipeline performs downstream analyses of the mapped reads, including prediction of RNA modifications and estimation of polyA tail lengths. Four direct RNA MinION sequencing runs can be fully processed and analyzed in 10 h on 100 CPUs. The pipeline can also be executed in GPU locally or in the cloud, decreasing the run time fourfold. The software is written using the NextFlow framework for parallelization and portability, and relies on Linux containers such as Docker and Singularity for achieving better reproducibility. The MasterOfPores workflow can be executed on any Unix-compatible OS on a computer, cluster or cloud without the need of installing any additional software or dependencies, and is freely available in Github (https://github.com/biocorecrg/master_of_pores). This workflow simplifies direct RNA sequencing data analyses, facilitating the study of the (epi)transcriptome at single molecule resolution.


Sacral Neuromodulation for defecation disorders after non oncologic pelvic surgery.
Defecation disorders (DD) can sometimes affect the outcomes of pelvic or colorectal surgery. The aim of the present study is to evaluate the role of sacral neuromodulation for the treatment of constipation and other evacuation disorders after surgery. A retrospective analysis in all the consecutive patients that underwent sacral nerve modulation (SNM) for DD arisen or worsened after pelvic or colorectal surgery was performed from January 2010 to December 2020. DD were defined starting from Rome IV Criteria, and according to manometric results, all patients were further divided into the two subgroups: inadequate defecatory propulsion and dyssynergic defecation. Cleveland Clinic Constipations Score (CCCS) and SF-36 have been evaluated in the time. Thirty-seven patients have been included in the study. Twenty-seven out of thirty-seven (73.3%) patients had experienced sufficient benefits to implant the definitive device, and 22 patients (59.4% of tested and 81.5% of permanently implanted) still had the device functioning after a mean follow-up of 6.3 years. The most represented manometric pattern was inadequate propulsive function (59% of patients). CCCS at preoperative assessment for all patients was 17.5 with a reduction to 10.4 at the first year of follow-up (p < 0.001). SNM appears to be a feasible, safe, and well-tolerated procedure with durable benefit in the long-term treatment of defecatory dysfunction after pelvic or colorectal surgery for benign diseases.


The impact of mitral regurgitation on patients undergoing catheter ablation of atrial fibrillation.
Mitral regurgitation (MR) causes left atrium (LA) enlargement and subsequent atrial fibrillation (AF). The presence of MR may increase recurrence rates after AF ablation. The purpose of this study was to determine the impact of MR on recurrence rates after catheter ablation of AF. We compared 95 patients with moderate or greater baseline MR (defined by MR jet area to LA area ratio ≥ 0.2) and AF undergoing ablation to 95 randomly selected patients without significant MR undergoing AF ablation. Electrocardiographic recurrence at 1-year follow-up was the primary outcome. Patients in the MR cohort had mean MR/LA ratio 0.37 vs. 0.09 in controls (P< 0.0001). Mitral regurgitation patients had larger LA dimension (4.5 vs. 4.1 cm, P< 0.0001) and more persistent AF (71 vs. 28%, P< 0.0001). Mitral regurgitation patients had higher recurrence rates than controls (61 vs. 46%, P= 0.04). The degree of MR was higher in patients with recurrence (MR/LA ratio 0.25 vs. 0.20, P= 0.03), as was LA dimension (4.5 vs. 4.1 cm, P< 0.0001). In multivariate analyses, only LA size was an independent predictor of recurrence (odds ratio 2.9 per centimetre increase in LA dimension, P= 0.005). Fifty-five percent of MR patients had normal leaflet motion, with MR likely due to atrial remodelling secondary to AF. Mitral regurgitation was associated with increased AF recurrence after AF ablation, but its impact was mediated by LA size. Left atrium size was the only independent predictor of AF recurrence. The high percentage of MR that was likely secondary to AF may have impacted our findings and deserves further study.


Quality Improvement Initiative for Family-Centered Care in the Neonatal Intensive Care Unit of a Tertiary Hospital in South Africa.
The introduction of family-centered care in the neonatal intensive care unit was identified as a high priority to facilitate bonding and attachment with potential positive outcomes for the parents and infants. The aim of the study was, therefore, to develop and implement a quality improvement initiative to foster family-centered care in a tertiary neonatal intensive care unit from birth onward. A pretest posttest intervention design was used using mixed methods over 3 phases to determine the perceived level of family-centered care according to healthcare professionals and parents using self-administered questionnaires; to develop and implement a quality improvement initiative to enhance family-centered care in a neonatal intensive care unit using a nominal group technique, followed by the quality improvement process; and to evaluate the outcomes of the initiative by repeating the self-administered questionnaires to parents and staff. Various activities were introduced as part of the initiative such as early breastfeeding, early introduction of parents to their infant, open visitation policy, and involvement in caring activities. The perceived level of care according to staff and parents increased. It is expected to enhance bonding and attachment between the infants and their parents, with consequential long-term positive outcomes.


Risk-Adjusting Mortality in the Nationwide Veterans Affairs Healthcare System.
The US Veterans Affairs (VA) healthcare system began reporting risk-adjusted mortality for intensive care (ICU) admissions in 2005. However, while the VA's mortality model has been updated and adapted for risk-adjustment of all inpatient hospitalizations, recent model performance has not been published. We sought to assess the current performance of VA's 4 standardized mortality models: acute care 30-day mortality (acute care SMR-30); ICU 30-day mortality (ICU SMR-30); acute care in-hospital mortality (acute care SMR); and ICU in-hospital mortality (ICU SMR). Retrospective cohort study with split derivation and validation samples. Standardized mortality models were fit using derivation data, with coefficients applied to the validation sample. Nationwide VA hospitalizations that met model inclusion criteria during fiscal years 2017-2018(derivation) and 2019 (validation) were included. Model performance was evaluated using c-statistics to assess discrimination and comparison of observed versus predicted deaths to assess calibration. Among 1,143,351 hospitalizations eligible for the acute care SMR-30 during 2017-2019, in-hospital mortality was 1.8%, and 30-day mortality was 4.3%. C-statistics for the SMR models in validation data were 0.870 (acute care SMR-30); 0.864 (ICU SMR-30); 0.914 (acute care SMR); and 0.887 (ICU SMR). There were 16,036 deaths (4.29% mortality) in the SMR-30 validation cohort versus 17,458 predicted deaths (4.67%), reflecting 0.38% over-prediction. Across deciles of predicted risk, the absolute difference in observed versus predicted percent mortality was a mean of 0.38%, with a maximum error of 1.81% seen in the highest-risk decile. The VA's SMR models, which incorporate patient physiology on presentation, are highly predictive and demonstrate good calibration both overall and across risk deciles. The current SMR models perform similarly to the initial ICU SMR model, indicating appropriate adaption and re-calibration.


Immunologic injury in measles virus infection. III. Presence and characterization of human cytotoxic lymphocytes.
Human peripheral blood leukocytes (PBL) from patients with chronic measles virus infection (SSPE) or from immune, adult humans (convalescent from acute childhood measles virus infection) are cytotoxic for target cells infected with measles virus as measured by a 51Cr assay. Specific release of 51Cr by immune PBL occurred both with and without human antibodies added to measles virus-infected cultures. Maximal killing in the absence of added antibodies to measles virus was usually detected only after 15 to 18 hr of incubation and with a high PBL to target ratio (100:1). When antibody to measles virus was added, PBL-mediated killing of virus-infected cells was not blocked. Instead, killing was enhanced and maximal lysis occurred with fewer PBL and a shorter incubation time. This cytotoxic reaction was inhibited in a dose-response manner upon the addition of Fab fragments of IgG containing antibodies to measles virus. On the average 4 to 5 x 105 antibody molecules bound per infected target cell before initiation of antibody-enhanced PBL killing. Depletion of either glass-adhering or E-rosette-forming cells did not reduce PBL killing of measles virus-infected target cells in either system. In contrast, removal of non-E rosette or of EAC rosette-forming population of PBL almost completely abrogated cytotoxicity. When Fc-bearing cells were removed, killing of virus-infected target cells was concomitantly reduced. Lysis of measles virus-infected target cells did not require histocompatibility between the PBL and the target cell. Further, immunospecific lymphocyte killing was not enhanced by such a histocompatibility fit. These experiments indicate first, that the effector PBL involved in lysis of measles virus-infected targets are not T cells but are probably K cells and, second, that PBL obtained from patients with SSPE are competent in killing measles virus-infected targets. Moreover, sera from SSPE patients did not contain a factor(s) that blocked PBL-mediated cytotoxicity.


Lung inflammation: normal host defense or a complication of some diseases?
The inflammatory response in lung tissue is an important part of host defense that aids in removing microorganisms or particles that have reached the distal airways and alveolar surface. It augments the usual function of alveolar macrophages, immunoglobulins, and other defense mechanisms such as mucociliary clearance. However, excessive or poorly regulated inflammation can be destructive of tissue, thus contributing to many disease processes that can lead to fibrosis and impaired gas exchange. Several examples of diseases that feature inflammation as part of their pathophysiology have been selected for this review; i.e. asthma (especially examining the late-phase reaction that involves PMNs), chronic bronchitis (in which irritants and bacterial products may stimulate mucus secretion and inflammatory cells), interstitial lung diseases (IPF may disclose PMNs but sarcoidosis and hypersensitivity pneumonitis feature collections of activated lymphocytes), and acute lung injury leading to adult respiratory distress syndrome (PMNs and their breakdown products and enzymes incite local destruction of alveolar tissue). In preparation for these disease examples, a thorough review of the normal interactions between alveolar macrophages, various opsonins, complement and chemotactic factors, and the responsiveness of PMNs is given first.


A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: Southwest Oncology Group Study S0605.
Older acute myeloid leukemia (AML) patients with a chromosome 5q deletion have poor outcomes with conventional chemotherapy. This phase 2 study explored the safety and efficacy of single-agent lenalidomide in previously untreated older AML patients with del(5q) who declined standard chemotherapy. Patients were treated with lenalidomide 50 mg daily for 28 days as induction therapy and 10 mg daily for 21 days of a 28-day cycle as maintenance until disease progression or unacceptable toxicity. Among 37 evaluable patients, the median age was 74 years (range, 60-94), 21 (57%) were female, 19 (51%) had prior myelodysplastic syndrome, and 30 (81%) had pretreatment cytogenetic studies evaluated centrally. Six had isolated del(5q), 1 had del(5q) and +8, 23 had complex cytogenetics, and 7 others had del(5q) identified locally. Fourteen patients (38%) completed induction therapy: 7 patients died during induction therapy, 8 had disease progression, 7 had nonfatal adverse events, and 1 entered hospice. Eight patients started maintenance therapy. Five patients (14%) achieved a partial or complete response, 2 with isolated del(5q) and 3 with complex cytogenetics. Relapse-free survival was 5 months (range, 0-19). Median overall survival was 2 months for the entire population. In conclusion, lenalidomide as a single agent has modest activity in older del(5q) AML patients. Southwest Oncology Group Study S0605 is registered at www.clinicaltrials.gov as NCT00352365.


Nationwide epidemiological survey of early chronic pancreatitis in Japan.
The world's first diagnostic criteria for early CP were proposed in 2009 in Japan. This study aimed to clarify the clinico-epidemiological features of early CP in Japan. Patients with early CP who were diagnosed according to the diagnostic criteria for early CP and had visited the selected hospitals in 2011 were surveyed. The study consisted of two-stage surveys: the number of patients with early CP was estimated by the first questionnaire and their clinical features were assessed by the second questionnaire. The estimated number of early CP patients was 5410 (95% confidence interval 3675-6945), with an overall prevalence of 4.2 per 100,000 persons. The number of patients who were newly diagnosed with early CP was estimated to be 1330 (95% confidence interval 1058-1602), with an annual incidence of 1.0 per 100,000 persons. Detailed clinical information was obtained in 151 patients in the second survey. The male-to-female sex ratio was 1.32:1. The mean age was 60.4 and the mean age at disease onset was 55.4. Idiopathic (47.7%) and alcoholic (45.0%) were the two most common etiologies. Proportions of female and idiopathic cases were higher in early CP than in definite CP. Hyperechoic foci without shadowing and stranding were the most common findings on endoscopic ultrasonography. The clinical profiles of early CP patients who showed lobularity with honeycombing on endoscopic ultrasonography or previous episodes of acute pancreatitis were similar to those of definite CP patients. We clarified the current status of early CP in Japan.


Direct and indirect causes of sex differences in mercury concentrations and parasitic infections in a marine bird.
In many animal species, males and females differ in their levels of contaminants and/or parasitic infections. Most contaminants and gastro-intestinal parasites are obtained through prey ingestion, and thus the causes of sex differences in the distribution of these factors might follow similar pathways. We studied the northern common eider duck (Somateria molissima borealis) as an avian model, and used directed separation path analysis to explore the causes of sex differences in mercury (Hg) and gastro-intestinal helminths. Two trophically transmitted helminths were examined: a cestode (Lateriporus sp.) and an acanthocephalan (Polymorphus sp). We found that the number of Lateriporus sp. varied positively with stable isotope signature (as indicated by δ(15)N in eider breast muscle tissue), and negatively with crustaceans being present in the short term diet. We also found that Polymorphus sp. varied positively with eider tissue stable isotope signature. However, Polymorphus sp. varied negatively with sex indirectly through condition and liver mass. Similarly, Hg concentrations also varied negatively with sex indirectly through condition and liver mass, with both Polymorphus sp. intensity and Hg concentrations significantly higher in males. We found that model fit increased when a negative relationship between the two helminth species was included, suggesting a yet unknown causal mechanism linking these parasites. Our findings suggest that although Hg and gastro-intestinal parasites are both trophically transmitted through the eider's prey items, the factors that contribute towards bioaccumulation of these two burdens differ in source, likely caused by several different factors and may potentially influence each other.


Microbial decolorization of synthetic dyes and reactive dyes of industrial effluents by using a novel fungus Aspergillus proliferans.
A decolorizing fungal strain was isolated and identified by the morphology and genotypic characterization as Aspergillus proliferans. The effect of A. proliferans on decolorization of synthetic dyes (70 mg ml(-1)) and colored effluent was evaluated in liquid culture medium. A. proliferans expressed their effective decolorization activity in effectual decolorization of synthetic dyes and industrial effluent. Synthetic dyes were decolorized by 76 to 89% within 6 days of treatment and 73.5% of color was removed in industrial effluent within 8 days. The addition of optimum carbon and nitrogen sources were effectively stimulated the decolorization activity. The high concentration of glucose repressed the decolorization activity and supplementation of yeast extract has significantly enhanced the effluent decolorization at p < 0.05. Laccase enzyme was isolated from liquid state fermentation, which showed significant enzyme activity (10,200 Uml(-1)) at p < 0.005. The crude enzyme decolorizes the dyes aniline blue and congo red in 14 hours (40.9 to 70%) and the effluent in 14 hours (88.6%). Moreover, the culture free supernatant without the fungal biomass has also effectively decolorized the effluent and synthetic dyes. The fungi Aspergillus proliferans was used not only for decolorization but also for better bioremediation of industrial effluent.


Entamoeba histolytica and Entamoeba dispar: epidemiology and comparison of diagnostic methods in a setting of nonendemicity.
Recent studies suggest that stool antigen assays are more sensitive and specific than microscopy for the diagnosis of Entamoeba histolytica infection. One hundred twelve patients presenting at 3 centers with symptoms or risk factors of E. histolytica infection were prospectively enrolled in this study to evaluate new diagnostic tests for infections with E. histolytica and Entamoeba dispar. Four ELISA-based stool antigen kits for detecting E. histolytica or E. dispar were blindly compared with stool microscopy. Amebic serology was assessed by indirect hemagglutination. When antigen assays were used as the reference standard, microscopy performed at referral centers was more specific (68.4% vs. 9.5%) but less sensitive (70.4% vs. 92.1%) than microscopy performed in community laboratories. Diagnosis with the E. histolytica test and Merlin Optimun S ELISA indicated that only 3 (4.2%) of 72 coproantigen-positive stools were positive for E. histolytica. Indirect hemagglutination was a good predictor of E. histolytica infection when titers of antibody to ameba were >/=1:512.


Fluid regulatory hormone response to exercise after coca-induced body fluid shifts.
To determine the effect of coca chewing on heart rate (HR), mean arterial blood pressure (MAP), and plasma volume and their relationship with the hormones regulating cardiovascular and body fluid homeostasis, 16 male volunteers were examined at rest and during 1 h of cycle exercise at approximately 75% of their peak oxygen uptake in two trials separated by 1 mo. One trial was performed after the subjects chewed a sugar-free chewing gum (Coca- trial), whereas the other was done after the subjects chewed 15 g of coca leaves (Coca+), with the order of the Coca- and Coca+ trials being randomized. Blood samples were taken at rest, before (R1) and after 1-h chewing (R2), and during the 5th, 15th, 30th, and 60th min of exercise. They were analyzed for hematocrit, hemoglobin concentration, red blood cell count, plasma proteins, and for the fluid regulatory hormones, including plasma catecholamines [norepinephrine (NE) and epinephrine], renin, arginine vasopressin, and the atrial natriuretic peptide (ANP). During the control trial (Coca-), from R1 to R2, there was no significant change in hematologic, hormonal, and cardiovascular status except for a small increase in plasma NE. In contrast, it can be calculated that coca chewing at rest induced a significant hemoconcentration (-3.8 +/- 1. 3% in blood and -7.0 +/- 0.7% in plasma volume), increased NE and MAP, and reduced plasma ANP. Chewing coca before exercise reduced the body fluid shifts but enhanced HR response during exercise. These effects were not accompanied by changes in NE, epinephrine, renin, and arginine vasopressin plasma levels. In contrast, plasma ANP response to exercise was lower during the Coca+ trial, suggesting that central cardiac filling was reduced by coca use. It is likely that the reduction in body fluid volumes is a major contributing factor to the higher HR at any given time of exercise after coca chewing.


Towards the existentialist turn in IR: introduction to the symposium on anxiety.
This symposium is a follow-up to the 2019 CEEISA/ISA conference 'International Relations in the Age of Anxiety' held at the Faculty of Political Science, University of Belgrade, Serbia, in June 2019. The central piece in the symposium is the keynote address by Bahar Rumelili on the untapped potential of existentialism in IR followed by highly engaged responses by Felix Berenskötter, Karl Gustafsson, Brent Steele and Andreja Zevnik. In this introduction we first describe the context in which we organised the conference and our motivations to choose the topic of the age of anxiety. We also reflect on how the global pandemic, which erupted in January 2020, made our topic more relevant than ever before. We then briefly introduce each piece and discuss what we see as the key questions they raise.


Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss.
Proton magnetic resonance spectroscopy (MRS) and MRI were carried out in 11 patients with multiple sclerosis who had clinical evidence of severe cerebellar involvement, 11 multiple sclerosis patients (of similar age and disease duration) who had minimal or no signs of cerebellar disease, eight patients with autosomal dominant cerebellar ataxia (ADCA) and 11 healthy controls. In all subjects MRS was localized to cerebellar white matter (volumes of interest 3-6 ml). Apparent metabolite concentrations were calculated using the fully relaxed water spectrum as an internal standard of reference. The patients also underwent MRI to assess cerebellar volume and (in the two multiple sclerosis groups) lesion volume within the posterior fossa. Magnetic resonance spectroscopy from cerebellar white matter showed a highly significant reduction in the concentration of N-acetyl groups (NA) [which consists predominantly of N-acetylaspartate (NAA), a neuronal marker] in the multiple sclerosis group with cerebellar deficit compared with the multiple sclerosis group with minimal or no signs of cerebellar involvement, and healthy controls. Follow-up MRS performed in six of the multiple sclerosis patients 9 months later showed no change in the median NA concentration. The ADCA group showed a significant reduction of NA from a region of cerebellar white matter and also a reduction in the concentration of choline-containing compounds. The multiple sclerosis group with severe cerebellar deficit and the ADCA group both had significant cerebellar atrophy (suggesting nerve cell body and axon loss) compared with the multiple sclerosis patients with minimal or no signs of cerebellar deficit and healthy controls. The multiple sclerosis patients with cerebellar deficit had a significantly greater lesion volume in the posterior fossa, although the proportion of the spectroscopic voxel occupied by lesions was small, suggesting that axonal loss from normal appearing white matter also contributes to the observed reduction in NA. These results support the hypothesis that axonal loss is important in the development of persistent clinical disability in multiple sclerosis.


Formation of subviral particles by in vitro translation of subgenomic poliovirus RNAs.
Rabbit reticulocyte lysates were programmed with either RNA extracted from purified poliovirus or a mixture of mRNAs encoding the capsid precursor, P1, and proteinase 3CD. In both cases, 14S subunits were formed at 30 degrees C and empty capsids at 37 degrees C. Both the 14S subunits and empty capsids had the expected polypeptide composition and neutralization epitopes. It is concluded that the proteinase 3CD gene is the only viral genetic information needed for the correct processing of P1 and the formation of 14S subunits, and their assembly into antigenically correct empty capsids.


Development of transplantation vasculopathy and progression of donor-transmitted atherosclerosis: comparison by serial intravascular ultrasound imaging.
Transplant coronary artery disease is a combination of atherosclerosis transmitted from the donor and new lesions of allograft vasculopathy. We sought to determine the morphological characteristics of allograft vasculopathy and differentiate it from donor-transmitted atherosclerosis with serial intravascular ultrasound. Intravascular ultrasound examination was performed in 93 patients at 27.2+/-15.0 and 369. 7+/-23.9 days after transplantation. The maximally and minimally diseased sites were selected in each segment as defined by Coronary Artery Surgery Study classification. For each matched site, maximal plaque thickness was measured. Lesions (maximum plaque thickness >/=0.5 mm) present at baseline examination were defined as donor lesions. On follow-up, lesions that developed at previously normal sites were defined as de novo lesions. The distribution and severity of donor and de novo lesions were similar in proximal, mid, and distal segments. The de novo lesions were less focal (43% vs 74%) and more circumferential (69% vs 45%) compared with the donor lesions, but there was significant morphological heterogeneity. Similar numbers of patients with and those without donor lesions developed de novo lesions. Moreover, progression of donor lesions was not associated with the presence or absence of de novo lesions. Differentiation between early allograft vasculopathy from conventional atherosclerosis by distribution and morphology of lesions alone is difficult. Serial intravascular ultrasound imaging with early baseline examination is necessary to make this distinction. This distinction is important because the progression of donor lesions and the development of de novo lesions are independent of each other.


Characterization of a spontaneous mutation in beta-thalassemia associated with advanced paternal age.
We characterized the molecular defect in a Swiss patient with a spontaneous beta-thalassemia mutation. Cloning and DNA sequencing of her beta-globin gene revealed a new frameshift mutation due to a single nucleotide deletion at codon 64 of the beta-globin gene. Restriction site polymorphism showed that the mutation arose on her paternal chromosome. Direct sequencing of a polymerase chain reaction amplified DNA segment showed absence of the lesion in both alleles of her father's beta-globin gene and confirmed the spontaneous nature of this mutation.


Spectral tuning of rhodopsin and visual cone pigments.
Retinal is the light-absorbing biochromophore responsible for the activation of vision pigments and light-driven ion pumps. Nature has evolved molecular tuning mechanisms that significantly shift the optical properties of the retinal pigments to enable their absorption of visible light. Using large-scale quantum chemical calculations at the density functional theory level combined with frozen density embedding theory, we show here how the protein environment of vision pigments tunes the absorption of retinal by electrostatically dominated interactions between the chromophore and the surrounding protein residues. The calculations accurately reproduce the experimental absorption maxima of rhodopsin and the red, green, and blue color pigments. We further identify key interactions responsible for the color-shifting effects by mutating the rhodopsin structure in silico, and we find that deprotonation of the retinyl is likely to be responsible for the blue-shifted absorption in the blue cone vision pigment.


Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children.
Little prospective long-term information is available on the effect of a ketogenic diet on plasma lipoproteins in children with difficult-to-control seizures. To determine the effect in children with intractable seizures of a high-fat ketogenic diet on plasma levels of the major apolipoprotein B (apoB)-containing lipoproteins, low-density lipoprotein (LDL) and very LDL (VLDL); and the major apolipoprotein A-I (apoA-I)-containing lipoprotein, high-density lipoprotein (HDL). A 6-month prospective cohort study of 141 children (mean [SD] age, 5.2 [3.8] years for 70 boys and 6.1 [4.4] years for 71 girls) with difficult-to-treat seizures who were hospitalized for initiation of a high-fat ketogenic diet and followed up as outpatients. This cohort constituted a subgroup of the 371 patients accepted into the ketogenic diet program between 1994 and 2001. A subset of the cohort was also studied after 12 (n = 59) and 24 (n = 27) months. A ketogenic diet consisting of a high ratio of fat to carbohydrate and protein combined (4:1 [n = 102], 3.5:1 [n = 7], or 3:1 [n = 32]). After diet initiation, the calories and ratio were adjusted to maintain ideal body weight for height and maximal urinary ketosis for seizure control. Differences at baseline and 6-month follow-up for levels of total, VLDL, LDL, HDL, and non-HDL cholesterol; triglycerides; total apoB; and apoA-I. At 6 months, the high-fat ketogenic diet significantly increased the mean plasma levels of total (58 mg/dL [1.50 mmol/L]), LDL (50 mg/dL [1.30 mmol/L]), VLDL (8 mg/dL [0.21 mmol/L]), and non-HDL cholesterol (63 mg/dL [1.63 mmol/L]) (P<.001 vs baseline for each); triglycerides (58 mg/dL [0.66 mmol/L]) (P<.001); and total apoB (49 mg/dL) (P<.001). Mean HDL cholesterol decreased significantly (P<.001), although apoA-I increased (4 mg/dL) (P =.23). Significant but less marked changes persisted in children observed after 12 and 24 months. A high-fat ketogenic diet produced significant increases in the atherogenic apoB-containing lipoproteins and a decrease in the antiatherogenic HDL cholesterol. Further studies are necessary to determine if such a diet adversely affects endothelial vascular function and promotes inflammation and formation of atherosclerotic lesions.


Internal fixation of supracondylar femoral fractures: comparative biomechanical performance of the 95-degree blade plate and two retrograde nails.
The biomechanical stability of supracondylar femoral fractures fixed with a condylar blade plate (plate), a Green Seligson Henry nail (GSHN), or a new retrograde unreamed supracondylar femoral nail (new nail) based on the AO unreamed femoral nail were compared. A standardized simulated comminuted supracondylar femoral fracture (segmental defect) in fresh frozen paired cadaveric femora was stabilized with one of the implants. The interfragmentary fracture site stiffness in three directions and axial strength of the fixator-bone construct were compared (pairwise). The plate versus the new nail was (a) axially 10 percent as stiff and 50 percent as strong (ultimate strength), (b) as stiff in A/P bending, and (c) five times more stiff in torsion. Varus angle at failure under axial load was significantly greater for the plate than for the new nail. There were no statistical differences in axial stiffness and ultimate strength between the new nail and the GSHN, but the new nail was 50 percent and 30 percent as stiff in A/P bending and torsion, respectively. The magnitude of deformation at failure under axial loading was similar. In fixation of extraarticular comminuted supracondylar distal femur fractures, results indicate that (a) the new nail provides equal or greater stability than does the plate, except when large torsional loads are anticipated, and (b) the new nail provides stability equal to the GSHN for axial loading and lesser stability against off-axis loads. As is evident in this and other studies, intramedullary implants are less torsionally stiff than are plates. The torsional stiffness of the new nail is expected to be sufficient because it is comparable to many available nails, and low torsional moments are expected for healing femoral supracondylar fractures.


Ethical issues in restructuring of psychiatric services.
The restructuring of health care services is occurring at an increasing rate. Among those most common are the types known as vertical integration, illustrated by the development of psychiatric services within acute care settings. These restructured psychiatric services have implications for psychiatric care and nursing. In some instances, they raise ethical issues. The purpose of this article is to explore ethical issues in restructuring of psychiatric services and to offer suggestions for retaining quality nursing care.


Neurosensory Symptom Complexes after Acute Mild Traumatic Brain Injury.
Mild Traumatic Brain Injury (mTBI) is a prominent public health issue. To date, subjective symptom complaints primarily dictate diagnostic and treatment approaches. As such, the description and qualification of these symptoms in the mTBI patient population is of great value. This manuscript describes the symptoms of mTBI patients as compared to controls in a larger study designed to examine the use of vestibular testing to diagnose mTBI. Five symptom clusters were identified: Post-Traumatic Headache/Migraine, Nausea, Emotional/Affective, Fatigue/Malaise, and Dizziness/Mild Cognitive Impairment. Our analysis indicates that individuals with mTBI have headache, dizziness, and cognitive dysfunction far out of proportion to those without mTBI. In addition, sleep disorders and emotional issues were significantly more common amongst mTBI patients than non-injured individuals. A simple set of questions inquiring about dizziness, headache, and cognitive issues may provide diagnostic accuracy. The consideration of other symptoms may be critical for providing prognostic value and treatment for best short-term outcomes or prevention of long-term complications.


Occluding junctions in cultured epithelial monolayers.
When MDCK cells are cultured in monolayers, they synthesize, assemble, and seal occluding junctions that limit the paracellular route. These processes may be impaired by inhibitors of the protein synthesis but not by inhibitors of the synthesis of RNA. Once established, the occluding junctions confer to the monolayer an overall electrical resistance of 80-600 omega . cm2. At the microscopical level, the resistance of individual junctions have large variations along the perimeter of a given cell. This agrees with the images of freeze-fracture electron microscopy where the network of the junction varies abruptly from 1 to 10 strands. The junctions are impermeable to macromolecular tracers, have a 9 to 1 Na+/Cl- discrimination, and a cation selectivity following the order: K+ greater than Na+ greater than Rb+ greater than Cs+ greater than Li+. Sealing requires extracellular Ca2+, but the junctions open when the concentration of Ca2+ in the cytoplasm increases. The structural components of the cytoskeleton (microtubules and microfilaments) seem to be involved in the junctional events as revealed by staining with immunofluorescent specific antibodies. If the cells are treated with cytochalasin B, actin microfilaments disorganize, the junctions open, and the electrical resistance across the monolayers falls. The resealing of the tight junction is inhibited by this drug.


Machine Learning for the Prediction of Depression Progression from Inflammation Markers.
Major depressive disorder is one of the major contributors to disability worldwide with an estimated prevalence of 4%. Depression is a heterogeneous disease often characterized by an undefined pathogenesis and multifactorial phenotype that complicate diagnosis and follow-up. Translational research and identification of objective biomarkers including inflammation can assist clinicians in diagnosing depression and disease progression. Investigating inflammation markers using machine learning methods combines recent understanding of the pathogenesis of depression associated with inflammatory changes as part of chronic disease progression that aims to highlight complex interactions. In this paper, 721 patients attending a diabetes health screening clinic (DiabHealth) were classified into no depression (none) to minimal depression (none-minimal), mild depression, and moderate to severe depression (moderate-severe) based on the Patient Health Questionnaire (PHQ-9). Logistic Regression, K-nearest Neighbors, Support Vector Machine, Random Forest, Multi-layer Perceptron, and Extreme Gradient Boosting were applied and compared to predict depression level from inflammatory marker data that included C-reactive protein (CRP), Interleukin (IL)-6, IL-1β, IL-10, Complement Component 5a (C5a), D-Dimer, Monocyte Chemoattractant Protein (MCP)-1, and Insulin-like Growth Factor (IGF)-1. MCP-1 and IL-1β were the most significant inflammatory markers for the classification performance of depression level. Extreme Gradient Boosting outperformed the models achieving the highest accuracy and Area Under the Receiver Operator Curve (AUC) of 0.89 and 0.95, respectively.Clinical Relevance- The findings of this study show the potential of machine learning models to aid in clinical practice, leading to a more objective assessment of depression level based on the involvement of MCP-1 and IL-1β inflammatory markers with disease progression.


Transcription factors NF-kappaB and C/EBPdelta and IL-1-induced expression of surfactant protein A in lung explants during the perinatal period.
Interleukin-1 (IL-1) increases the expression of surfactant protein A (SP-A) in rabbit, lamb and human fetal lung. The upregulation disappears towards term. Among the transcription factors, IL-1 activates nuclear factor kappaB (NF-kappaB) and CCAAT/enhancer-binding protein delta (C/EBPdelta). NF-kappaB presumably has a role in IL-1-induced upregulation of SP-A. Also, C/EBPdelta may regulate SP-A expression. The aim was to study the role of these transcription factors in the induced effect of IL-1 on SP-A expression. Explants from fetal and neonatal rabbit lung were cultured in vitro followed by studies using immunohistochemistry, electrophoretic mobility shift assay and Northern analysis. We found gestation-dependent changes in IL-1-induced immunoreactivities of NF-kappaB and C/EBPdelta in the nuclei of alveolar cells. This increase in nuclear transcription factors correlated with IL-1-induced SP-A expression levels. As studied in the explants from fetal and newborn lung, the SP-A mRNA expression additionally associated with C/EBPdelta mRNA and with the binding of nuclear extracts from the lung explants to the C/EBP consensus probe. On the basis of the present and previous studies, we propose that NF-kappaB and C/EBPdelta have potential mediator roles in IL-1-induced upregulation of SP-A in immature lung.


Consumer Preferences for Skin Cancer Screening Using Mobile Teledermoscopy: A Qualitative Study.
Mobile teledermoscopy is a rapidly advancing technology that promotes early detection and management of skin cancers. Whilst the use of teledermoscopy has proven to be effective and has a role in the detection of skin cancers, patients' attitudes towards the multiple ways in which this technology can be utilised has not been explored. Data were obtained from a large randomised controlled trial comparing mobile teledermoscopy-enhanced skin self-examinations (SSEs) with naked-eye SSE. A semi-structured interview guide was developed by the investigators with questions focusing on people's previous skin screening behaviours and 2 of the major pathways which can be utilised in mobile teledermoscopy: (i) direct-to-consumer and (ii) doctor-to-doctor. All interviews were tape-recorded and transcribed verbatim. Thematic analysis was undertaken by 2 independent researchers. Twenty-eight participants were interviewed. Eighty-six percent of participants (n = 24/28) had previously had a clinical skin examination. Only 18% of participants (n = 5/28) visited the same doctor for each clinical skin examination. Five main themes were identified in the interviews that affected how people felt about the integration of mobile teledermoscopy into skin screening pathways: history of clinical skin examinations, continuity of the doctor-patient relationship, convenience of the direct-to-consumer teledermoscopy, expedited review enhancing the doctor-to-doctor setting and mobile teledermoscopy as a partner-assisted task. Overall mobile teledermoscopy was viewed positively for both direct-to-consumer and doctor-to-doctor interaction. Continuity of care in the doctor-patient relationship was not found to be a priority for clinical skin examination with most participants visiting several doctors throughout their clinical skin examination history.


SP1-induced lncRNA MCF2L-AS1 promotes cisplatin resistance in ovarian cancer by regulating IGF2BP1/IGF2/MEK/ERK axis.
Cisplatin resistance is a huge problem encountered in ovarian cancer treatment. Our study probed the roles and the underlying mechanisms of lncRNA MCF2L-AS1 in ovarian cancer cisplatin-resistance. SKOV3 and IGROV-1 cells were subjected to gradually increasing concentrations of cisplatin to construct ovarian cancer cisplatin-resistance cells. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and PI staining. The relationships between SP1, MCF2L-AS1 and insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) were verified by RNA pull-down, RIP, ChIP and dual-luciferase reporter gene assay, respectively. Tumor xenograft experiment was employed to evaluate the effects of MCF2L-AS1 silencing on ovarian cancer cisplatin-resistance in vivo. TUNEL staining and immunohistochemistry were performed in tumor tissue. MCF2L-AS1 and IGF2BP1 were upregulated in cisplatin-resistant cells. MCF2L-AS1 silencing suppressed cell proliferation of cisplatin-resistant cells, while promoted the apoptosis, suggesting that MCF2L-AS1 knockdown suppressed ovarian cancer cells cisplatin-resistance. Meanwhile, MCF2L-AS1 silencing enhanced cisplatin sensitivity in ovarian cancer parental cells and IGF2BP1 overexpression impaired cisplatin sensitivity of parental cells. MCF2L-AS1 activated IGF2/MEK/ERK pathway through interacting with IGF2BP1. Transcription factor SP1 activated MCF2L-AS1 expression. MCF2L-AS1 knockdown inhibited ovarian cancer cisplatin-resistance in vivo. SP1-induced MCF2L-AS1 promoted ovarian cancer cisplatin-resistance through activation of IGF2/MEK/ERK pathway via interacting with IGF2BP1.


Relic populations of Fukomys mole-rats in Tanzania: description of two new species F. livingstoni sp. nov. and F. hanangensis sp. nov.
Previous studies of African mole-rats of the genera Heliophobius and Fukomys (Bathyergidae) in the regions of East and south central Africa have revealed a diversity of species and vicariant populations, with patterns of distribution having been influenced by the geological process of rifting and changing patterns of drainage of major river systems. This has resulted in most of the extant members of the genus Fukomys being distributed west of the main Rift Valley. However, a small number of isolated populations are known to occur east of the African Rift Valley in Tanzania, where Heliophobius is the most common bathyergid rodent. We conducted morphological, craniometric and phylogenetic analysis of mitochondrial cytochrome b (cyt b) sequences of two allopatric populations of Tanzanian mole-rats (genus Fukomys) at Ujiji and around Mount Hanang, in comparison with both geographically adjacent and more distant populations of Fukomys. Our results reveal two distinct evolutionary lineages, forming clades that constitute previously unnamed species. Here, we formally describe and designate these new species F. livingstoni and F. hanangensis respectively. Molecular clock-based estimates of divergence times, together with maximum likelihood inference of biogeographic range evolution, offers strong support for the hypothesis that vicariance in the Western Rift Valley and the drainage patterns of major river systems has subdivided populations of mole-rats. More recent climatic changes and tectonic activity in the "Mbeya triple junction" and Rungwe volcanic province between Lakes Rukwa and Nyasa have played a role in further isolation of these extra-limital populations of Fukomys in Tanzania.


A requiem for BMI in the clinical setting.
Quetelet reported in the nineteenth century that body weight varies across adults with the square of height. Quetelet's index, now known as BMI, is accepted by most health organizations as a first-level measure of body fat and as a screening tool for diagnosing excess adiposity. Modern imaging methods now, however, indicate that BMI has limited predictive value for estimating body fat and lean mass at the individual level. The use of BMI as a measure of body composition in the clinical setting should therefore be challenged. Recent studies enrolling cancer and surgical patients reported discrepant outcomes when BMI was used as a body composition surrogate. Sarcopenia, loss of muscle mass and function, which affects the elderly and those with chronic and acute diseases, is not accurately diagnosed with BMI. The distribution of adipose tissue is not characterized by BMI, specific measures of which have greater predictive value for metabolic impairments and clinical outcomes. BMI, as the traditional tool for assessing malnutrition and obesity, is not appropriate to accurately differentiate between important body weight components and therefore should not be used for making clinically important decisions at the individual patient level.


[Diagnosis and evaluation of climacteric symptoms. The "Menopause Rating Scale" MRS helps in diagnosis and evaluation of therapeutic effectiveness].
For the evaluation of climacteric symptoms, Kupperman and his collaborators worked out guidelines as long ago as 1953. As time passed, however, their validity was increasingly called into question. In the nineteen-seventies, on the basis of large epidemiological studies, the conclusion was drawn that merely the symptoms hot flushes and vaginal atrophy were specific to the menopause, while other, largely psychological, complaints represented a "domino effect", so to speak. In contrast to this, the scale (Menopause Rating Scale [MRS]) presented here also permits the identification of emotional complaints. In addition, urinary tract problems, joint and muscle pain, and sexual disorders are also rated. For each of the ten symptom groups, a graphical rating scale ranging from 0.0 (no symptoms) to 1.0 (severe symptoms) is available that permits a synoptic individual complaints profile of the patient to be established.


[Cellular content of mixed saliva sediment in patients with chronic mucosal inflammation].
A comparative analysis was made of the saliva sediment cell composition in healthy patients and patients with chronic mucosal inflammation. Migration of leucocytes to the oral cavity was registered in patients with chronic inflammatory processes. A reliable increase in the number of epithelial cells with high degree of destruction was determined in saliva in addition to the appearance of cubic epithelial cells. These results indicate certain violation of epithelial reparation. It is proposed to use a quantitative analysis of saliva sediment for estimating functional conditions of mucosa.


Isolation and genetic analysis of mutations at the SerH immobilization antigen locus of Tetrahymena thermophila.
Multiple alleles at the SerH locus specify the major cell surface protein (immobilization antigen) of the ciliate Tetrahymena thermophila. Following mutagenesis of SerH1 homozygotes, two mutations, H1-1 and H1-2, were recovered in heterozygous form. Mutant homozygotes do not express H1 antigen, nor is H1 expressed in F1 progeny of crosses to wild-type strains homozygous for SerH2 or SerH3. H1-1 and H1-2 segregate without recombination from these wild-type alleles in expected F2 and testcross Mendelian ratios. H1-1 and H1-2 do, however, complement each other to express H1 antigen. Experiments suggest this complementation is due neither to recombination during macronuclear development nor to interallelic complementation of defective SerH1 gene products. These results suggest that SerH1 is intact in one mutant, and possibly both, although no such allele has been segregated in testcross progeny (N = 205). The hypothesis is presented that complementation between H1-1 and H1-2 is due to interaction between allele-specific regulators closely linked to the SerH1 gene.


[Alagille syndrome].
Alagille syndrome (AS) is a multisystemic disease autosomal dominant, with variable expression. The major clinical manifestations are: chronic cholestasis, congenital heart disease, posterior embryotoxon in the eye, characteristic facial phenotype, and butterfy vertebrae. AS is caused by mutations in JAGGED1 (more than 90%) and in NOTCH2. Differential diagnosis include: infections, genetic-metabolic diseases, biliary atresia, idiopathic cholestasis. Cholestasis, pruritus and xanthomas have been successfully treated with choleretic agents (ursodeoxycholic acid) and other medications (cholestyramine, rifampin, naltrexone). In certain cases, partial external biliary diversion has also proved successful. Liver transplantation is indicated in children with cirrhosis and liver failure.


Do Body Mass Index Levels Correlate with Tinnitus Among Teachers?
Introduction Working conditions can contribute to the development of lifestyle-related diseases among teachers, including obesity and tinnitus. Describing tinnitus in relation to characteristics and comorbidities can help the treatment and prognosis of teachers affected by this symptom. Objective To verify a possible association between tinnitus complaint and body mass index (BMI) in teachers. Methods Cross-sectional study with a sample of teachers who responded to the Visual Analog Scale (VAS) and to the Tinnitus Handicap Inventory (THI). The BMI (kg/m2) was calculated based on self-reported body weight (in kilograms) divided by height (in meters squared). Nonparametric statistics were applied adopting a significance level < 0.05 Results A total of 83 teachers were assessed, with a mean age 48 ± 9.7 years old; 63.9% ( n = 53) were females; 44.6% were eutrophic ( n = 37), and 16.9% ( n = 14) were obese. Of the total, 19.3% ( n = 16) reported tinnitus. No differences were found between the groups and BMI ( p > 0.05), although there was a significant difference between the Tinnitus and No Tinnitus groups for age ( p < 0.001). The chi-squared test showed an association between age group and tinnitus ( p < 0.028); those with tinnitus were in the 49 to 65 years old age group. In addition, there was a moderate correlation between tinnitus parameters (VAS; THI-Functional; THI-Total) and BMI. Conclusion There was a moderate correlation between tinnitus parameters and BMI indicating that, as the BMI increased, so did the impact of tinnitus in the lives of the teachers. Body mass index should be considered a factor in tinnitus assessment and rehabilitation process.


Vastatin (the NC1 domain of human type VIII collagen a1 chain) is linked to stromal reactivity and elevated in serum from patients with colorectal cancer.
Vastatin, a fragment derived from type VIII collagen, is one of the least studied collagen-derived matrikines. Vastatin can be detected in serum but little is known regarding the relevance of serum vastatin in colorectal cancer (CRC). In this study, serum vastatin was measured (ELISA) in 67 healthy controls and 48 CRC patients prior to resection and compared to clinicopathological parameters and serum biomarkers of stromal reactivity (C3M, VICM). Impact of resection and chemotherapy were evaluated by comparing baseline values with a 3-month follow-up sample (n = 23). Serum vastatin was detectable in 114 of 115 subjects. At baseline vastatin was elevated in CRC compared to controls (P < 0.001) with a diagnostic accuracy (AUROC) of 0.865, p < 0.0001. Vastatin correlated with age in controls but not in patients with CRC; no association was seen with clinicopathological parameters. Vastatin was independently associated with C3M (stepwise linear regression coefficient 0.25, p = 0.046). Overall, no difference was seen in vastatin levels between baseline and follow-up. In conclusion, vastatin is elevated in serum from patients with CRC and correlate with interstitial matrix degradation (C3M). This indicates that vastatin is linked to stromal reactivity and suggests that vastatin has biomarker potential in CRC. The association with clinicopathological parameters and treatment effect needs further evaluation.


Causal relationship from heart failure to kidney function and CKD: A bidirectional two-sample mendelian randomization study.
Heart Failure (HF) is a widespread condition that affects millions of people, and it is caused by issues with the heart and blood vessels. Even though we know hypertension, coronary artery disease, obesity, diabetes, and genetics can increase the risk of HF and Chronic Kidney Disease (CKD), the exact cause of these conditions remains a mystery. To bridge this gap, we adopted Mendelian Randomization (MR), which relies on genetic variants as proxies. We used data from European populations for our Bidirectional Two-Sample MR Study, which included 930,014 controls and 47,309 cases of HF from the HERMES consortium, as well as 736,396 controls and 51,256 cases of CKD. We also employed several MR variations, including MR-Egger, Inverse Variance Weighted (IVW), and Weighted Median Estimator (WME), to guarantee the results were accurate and comprehensive.). In this study, the MR analysis found that individuals with a genetic predisposition for HF have an elevated risk of CKD. Our study revealed a significant association between the genetic prediction of HF and the risk of CKD, as evidenced by the IVW method [with an odds ratio (OR) of 1.12 (95% CI, 1.03-1.21), p = 0.009] and the WME [with an OR of 1.14 (95% CI, 1.03-1.26), p = 0.008]. This causal relationship remained robust even after conducting MR analysis while adjusting for the effects of diabetes and hypertension, yielding ORs of 1.13 (IVW:95% CI, 1.03-1.23), 1.12 (MR-Egger: 95% CI, 0.85-1.48), and 1.15 (WME:95% CI, 1.04-1.27) (p = 0.008). However, in the reverse analysis aiming to explore CKD and renal function as exposures and HF as the outcome, we did not observe a statistically significant causal link between CKD and HF. Our study demonstrates the significance of HF in CKD progression, thus having meaningful implications for treatment and the potential for discovering new therapies. To better understand the relationship between HF and CKD, we need to conduct research in a variety of populations.


Neural correlates of the emergence of consciousness of thirst.
Thirst was induced by rapid i.v. infusion of hypertonic saline (0.51 M at 13.4 ml/min). Ten humans were neuroimaged by positron-emission tomography (PET) and four by functional MRI (fMRI). PET images were made 25 min after beginning infusion, when the sensation of thirst began to enter the stream of consciousness. The fMRI images were made when the maximum rate of increase of thirst occurred. The PET results showed regional cerebral blood flow changes similar to those delineated when thirst was maximal. These loci involved the phylogenetically ancient areas of the brain. fMRI showed activation in the anterior wall of the third ventricle, an area that is key in the genesis of thirst but is not an area revealed by PET imaging. Thus, this region plays as major a role in thirst for humans as for animals. Strong activations in the brain with fMRI included the anterior cingulate, parahippocampal gyrus, inferior and middle frontal gyri, insula, and cerebellum. When the subjects drank water to satiation, thirst declined immediately to baseline. A precipitate decline in intensity of activation signal occurred in the anterior cingulate area (Brodmann area 32) putatively related to consciousness of thirst. The intensity of activation in the anterior wall of the third ventricle was essentially unchanged, which is consistent with the fact that a significant time (15-20 min) would be needed before plasma Na concentration changed as a result of water absorption from the gut.


Downregulation of Transcription Factor Sp1 Suppresses Malignant Properties of A549 Human Lung Cancer Cell Line with Decreased β4-Galactosylation of Highly Branched N-Glycans.
Dramatic changes in the glycan structures of cell surface proteins have been observed upon malignant transformation of cells as induced by the altered expression levels of glycosyltransferases. Such changes are closely associated with the malignant properties of cancer cells. Transcription factor Sp1 regulates the gene expression of various molecules including glycosyltransferases. Herein, we investigated whether or not Sp1-downregulation affects to N-glycosylation of glycoproteins and malignant properties of A549 human lung cancer cell line. We established a stable clone whose Sp1-expression level was reduced to 50% of a control clone by RNA interference. Lectin blotting revealed that the β4-galactosylation of highly branched N-glycans decreases mainly in cell adhesion molecule, E-cadherin. The analysis of underlying mechanism for decreased β4-galactosylation of N-glycans showed that the gene expression level of β4-galactosyltransferase (β4GalT) 1 decreases dramatically by downregulation of Sp1 without changes in those of β4GalT2 and N-acetylglucosaminyltransferase V. Mutations in the Sp1-binding sites of the β4GalT1 gene promoter showed that the promoter activity decreases significantly, indicating that the gene expression is regulated by Sp1. These results indicate that the β4-galactosylation of highly branched N-glycans decreases by downregulation of Sp1 through the reduced expression of the β4GalT1 gene. Furthermore, the Sp1-downregulated cells showed the suppression of the anchorage-independent growth in soft agar and migratory activity when compared to the control cells. The present study demonstrates that downregulation of Sp1 suppresses the malignant properties of A549 cells through the decreased β4-galactosylation of highly branched N-glycans.


Effects of high-intensity interval training and moderate-intensity continuous training on sarcopenia-related parameters in participants with Parkinson's disease: A 24-week randomized pilot trial substudy.
To evaluate the potential efficacy of two different supervised exercise regimens, namely high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on sarcopenia-related parameters in participants with Parkinson's disease (PD). We analyzed data from a randomized controlled pilot trial (CRIS identifier: KCT0007130). An aerobic exercise intervention using a cycle ergometer (40-60 min) in combination with calisthenics (5 min) was performed in three sessions/week for 24 weeks for HIIT (60% maximum aerobic power for 30-50 s with 1-min rest intervals) and MICT (50% peak oxygen consumption) groups. Changes in sarcopenia-related parameters, including appendicular skeletal muscle mass (ASM), ASM index (ASM/height2), handgrip strength, 6-min walking distance, and 30-s chair-stand test (30CST) score, were compared among the HIIT (n = 9), MICT (n = 10), and usual care (n = 11) groups. The HIIT group showed greater increases in leg lean mass (p = 0.011), ASM (p = 0.035), and ASM index (p = 0.025), and greater improvements in 6-min walking distance (p = 0.024) and 30CST scores (p = 0.026) compared with the usual care group. However, among these parameters, only the 30CST score significantly improved in the MICT group compared to the usual care group (p = 0.002). Three of the four (75%) sarcopenic patients who underwent HIIT showed improved sarcopenia after the 24-week exercise intervention, whereas it did not improve in the sarcopenic patients included in the MICT (n = 2) and usual care (n = 2) groups. This study suggests that HIIT may be superior to MICT in improving sarcopenia in patients with PD. Further large-scale investigations are required to confirm our findings.


[Interferon alpha-2a in the treatment of diffuse thoracic angiomatosis in adulthood--a ase report].
A diffuse angiomatosis affecting thoracal organs is a rare, frequently fatal disorder occurring mainly in childhood. The definite diagnosis is usually made by autopsy. A specific treatment does not exist. In the case report presented here we describe the course of an 37-year old patient presenting initially with dyspnea and hemoptysis. Radiological investigations showed a mass lesion in the anterior superior mediastinum, bihilar masses and a periesophageal mass with soft tissue density and a pericardial effusion. Bilateral interstitial infiltrations were also present. CT-guided mediastinal biopsies and bronchial mucosal biopsies were nonspecific. Open-lung biopsy revealed the diagnosis of an extensive diffuse angiomatosis affecting mediastinum, pericardium and pleura. During the 18-month monotherapy with interferon-alpha 2a the patient showed significant improvements of clinical as well as laboratory and radiological parameters. The presented case confirms the experience of several authors, that the diagnosis of a diffuse thoracal authors can only be made by open lung biopsy or autopsy. The presented case also underlines the possibility of a palliative therapy of aggressive angiomatous diseases with interferon-alpha 2a.


Adrenergic signaling mediates mechanical hyperalgesia through activation of P2X3 receptors in primary sensory neurons of rats with chronic pancreatitis.
The mechanism of pain in chronic pancreatitis (CP) is poorly understood. The aim of this study was designed to investigate roles of norepinephrine (NE) and P2X receptor (P2XR) signaling pathway in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Mechanical hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. P2XR-mediated responses of pancreatic dorsal root ganglion (DRG) neurons were measured utilizing calcium imaging and whole cell patch-clamp-recording techniques. Western blot analysis and immunofluorescence were performed to examine protein expression. TNBS injection produced a significant upregulation of P2X3R expression and an increase in ATP-evoked responses of pancreatic DRG neurons. The sensitization of P2X3Rs was reversed by administration of β-adrenergic receptor antagonist propranolol. Incubation of DRG neurons with NE significantly enhanced ATP-induced intracellular calcium signals, which were abolished by propranolol, and partially blocked by protein kinase A inhibitor H-89. Interestingly, TNBS injection led to a significant elevation of NE concentration in DRGs and the pancreas, an upregulation of β2-adrenergic receptor expression in DRGs, and amplification of the NE-induced potentiation of ATP responses. Importantly, pancreatic hyperalgesia was markedly attenuated by administration of purinergic receptor antagonist suramin or A317491 or β2-adrenergic receptor antagonist butoxamine. Sensitization of P2X3Rs, which was likely mediated by adrenergic signaling in primary sensory neurons, contributes to pancreatic pain, thus identifying a potential target for treating pancreatic pain caused by inflammation.


No gender-related bias in COPD diagnosis and treatment in Sweden: a randomised, controlled, case-based trial.
COPD is a major cause of morbidity and mortality. The prevalence, morbidity and mortality of COPD among females have increased. Previous studies indicate a possible gender bias in the diagnosis and management of COPD. The present study aims to determine if there is gender bias in the management of COPD in Sweden. This was a double-blind, randomised (1:1), controlled, parallel-group, web-based trial using the hypothetical case scenario of a former smoker (40 pack-years and quit smoking 3 years ago) who was male or female. The participants were blind to the randomisation and the purpose of the trial. The case progressively revealed more information with associated questions on how the physician would manage the patient. Study participants chose from a list of tests and treatments at each step of the case scenario. In total, 134 physicians were randomised to a male (n=62) or a female (n=72) case. There was no difference in initial diagnosis (61 (98%) male cases and 70 (97%) female cases diagnosed with COPD) and planned diagnostic procedures between the male and female cases. Spirometry was chosen by all the physicians as one of the requested diagnostic tests. The management of the hypothetical COPD case did not differ by sex of the responding physician. In Sweden, diagnosis and management of a hypothetical patient with COPD did not differ by the gender of the patient or physician.


Dandy-Walker variant with precocious puberty: a rare association.
Precocious puberty is characterised by premature appearance of secondary sexual characteristics before the age of 7 years in girls and 9 years in boys. Dandy-Walker malformation comprises a spectrum of intracranial malformations of the posterior fossa. We present a case of a 7-year-old male child who has presented with features of central precocious puberty and on further evaluation has been found to have Dandy-Walker variant and secondary hypothyroidism. The following case report describes this association which is extremely rare and has never been described in literature.


Increased serum cathepsin S in patients with atherosclerosis and diabetes.
Atherosclerosis and diabetes are closely associated and both involve extensive degradation of the aortic elastin. Increased elastase activity has been detected in diabetic animal aortae. We have demonstrated enhanced elastolytic cathepsin S in human atherosclerotic lesions but insufficient amounts of its endogenous inhibitor cystatin C, suggesting alterations of serum cathepsin S and/or cystatin C in patients with atherosclerosis or diabetes. In this study, we measured levels of both cathepsin S and cystatin C in sera from 240 patients by ELISA. Among these patients, 107 had a diagnosis of atherosclerotic stenosis, 103 were diabetic, and 30 had neither condition. Multiple linear regression analysis demonstrated that significantly higher serum levels of cathepsin S in patients with either atherosclerotic stenosis (p<0.04) or diabetes (p=0.0005) persisted after adjustment for cystatin C level, renal function, smoking, and serum glucose levels (p=0.008, p=0.0005). Furthermore, patients with acute (p=0.009) or previous myocardial infarction (p<0.02) or unstable angina pectoris (p<0.05) had elevated levels of cathepsin S after adjustment for smoking, creatinine, cystatin C, and serum glucose. In contrast, serum cystatin C levels were higher in diabetic patients (p=0.00001), but not in atherosclerotic subjects (p=0.14), than in the non-involved population after adjustment for age, smoking, and renal function. Although the pathophysiology of cathepsin S or cystatin C in atherosclerosis and diabetes requires further investigation, increased serum cathepsin S may serve as a biomarker for both diseases.


Use of Hyperspectral Imaging for the Quantification of Organic Contaminants on Copper Surfaces for Electronic Applications.
To correctly assess the cleanliness of technical surfaces in a production process, corresponding online monitoring systems must provide sufficient data. A promising method for fast, large-area, and non-contact monitoring is hyperspectral imaging (HSI), which was used in this paper for the detection and quantification of organic surface contaminations. Depending on the cleaning parameter constellation, different levels of organic residues remained on the surface. Afterwards, the cleanliness was determined by the carbon content in the atom percent on the sample surfaces, characterized by XPS and AES. The HSI data and the XPS measurements were correlated, using machine learning methods, to generate a predictive model for the carbon content of the surface. The regression algorithms elastic net, random forest regression, and support vector machine regression were used. Overall, the developed method was able to quantify organic contaminations on technical surfaces. The best regression model found was a random forest model, which achieved an R2 of 0.7 and an RMSE of 7.65 At.-% C. Due to the easy-to-use measurement and the fast evaluation by machine learning, the method seems suitable for an online monitoring system. However, the results also show that further experiments are necessary to improve the quality of the prediction models.


Regulation of sodium excretion by renal interstitial hydrostatic pressure.
Renal interstitial hydrostatic pressure (RIHP) appears to play a crucial role in linking the renal circulation to the rate of tubular reabsorption of sodium and water. Various physiological and pharmacological maneuvers that increase RIHP are associated with increases in sodium excretion. Renal vasodilators that increase RIHP also increase sodium excretion, whereas the vasodilators that do not alter RIHP do not affect sodium excretion. Preventing increases in RIHP during intrarenal infusion of vasodilators markedly attenuates the normal increase in sodium and water excretion. Techniques that directly increase RIHP by renal interstitial volume expansion increase urinary excretion of sodium and water. RIHP may be an important mediator of renal perfusion pressure (RPP) natriuresis. Experimental evidence suggests that the proximal tubule of deep nephrons may be an important nephron site that is sensitive to changes in RPP.


Effects of sire fertility and daughter stayability on profitability of sire selection.
Holstein sires (n = 340) with milk, milk fat, semen unit fertility, daughter stayability evaluations, and semen price for 1986 were studied. Effects of variation in sire fertility and daughter stayability on profitability of sire selection using the net present value criterion were estimated. The model estimated expected profit from a cow bred to pregnancy from future production and from cattle disposal and replacement after discounting costs and returns to the time of insemination. Effects of semen sexing and semen unit dilution on profitability to determine optimal breeding strategies for dairy herds were examined. Sire profitability increased with herd average conception rate and sire selection intensity. Daughter stayability had a greater impact on profitability than semen unit fertility when profit maximization was computed under the criterion of breeding a cow to pregnancy. Genetic progress for production was compromised when selecting to maximize profit. Dilution of semen units seems profitable only when semen availability is limited for high demand sires. The use of sexed female semen may only be appropriate when it can generate additional income from the sale of surplus heifers.


Fetal and neonatal responses following maternal exposure to mobile phones.
To study fetal and neonatal heart rate (HR) and cardiac output (COP), following acute maternal exposure to electromagnetic fields (EMF) emitted by mobile phones. The present study was carried out at Benha University Hospital and El-Shorouq Hospital, Cairo, Egypt, from October 2003 to March 2004. Ninety women with uncomplicated pregnancies aged 18-33 years, and 30 full term healthy newborn infants were included. The pregnant mothers were exposed to EMF emitted by mobile telephones while on telephone-dialing mode for 10 minutes during pregnancy and after birth. The main outcome were measurements of fetal and neonatal HR and COP. A statistical significant increase in fetal and neonatal HR, and statistical significant decrease in stroke volume and COP before and after use of mobile phone were noted. All these changes are attenuated with increase in gestational age. Exposure of pregnant women to mobile phone significantly increase fetal and neonatal HR, and significantly decreased the COP.


A feature fusion deep-projection convolution neural network for vehicle detection in aerial images.
With the rapid development of Unmanned Aerial Vehicles, vehicle detection in aerial images plays an important role in different applications. Comparing with general object detection problems, vehicle detection in aerial images is still a challenging research topic since it is plagued by various unique factors, e.g. different camera angle, small vehicle size and complex background. In this paper, a Feature Fusion Deep-Projection Convolution Neural Network is proposed to enhance the ability to detect small vehicles in aerial images. The backbone of the proposed framework utilizes a novel residual block named stepwise res-block to explore high-level semantic features as well as conserve low-level detail features at the same time. A specially designed feature fusion module is adopted in the proposed framework to further balance the features obtained from different levels of the backbone. A deep-projection deconvolution module is used to minimize the impact of the information contamination introduced by down-sampling/up-sampling processes. The proposed framework has been evaluated by UCAS-AOD, VEDAI, and DOTA datasets. According to the evaluation results, the proposed framework outperforms other state-of-the-art vehicle detection algorithms for aerial images.


Performance of an indigenous integrated slurry photocatalytic membrane reactor (PMR) on the removal of aqueous phenanthrene (PHE).
In this study, a slurry photocatalytic membrane reactor (PMR) was developed and evaluated for the degradation of aqueous phenanthrene (PHE). During continuous process with a hydraulic retention time (HRT) of 140 min, the maximum PHE degradation and total organic carbon (TOC) removal efficiencies were found to be 97% and 79%, respectively. The reuse and recovery potential of TiO2 was studied with continuous recycling. The major intermediates during photodegradation of PHE were found to be phenanthrenequinone, phenanthenol and fluorine. This study also includes an investigation of membrane fouling caused by hydrophilic nano TiO2. The cake layer observed on the membrane surface was characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM) and energy dispersive spectroscopy (EDS). In addition, the effect of operating parameters such as pH and permeate flux on membrane fouling were also investigated. Low permeate flux and alkaline conditions reduced membrane fouling.


Altered immune responses in interleukin 10 transgenic mice.
Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of immune parameters including T helper cell type 1 (Th1) cytokine production, antigen presentation, and antigen-specific T cell proliferation. To understand the consequences of altered expression of IL-10 in immune models of autoimmune disease, the response to infectious agents, and the response to tumors, we developed transgenic mice expressing IL-10 under the control of the IL-2 promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-gamma than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels. Transfer of normally pathogenic CD4(+) CD45RBhigh splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4(+) CD45RBhigh T cells from control mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immune responses were not globally suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs restored in vivo antitumor responses in the transgenic mice. These results demonstrate that a single alteration in the T cell cytokine profile can lead to dramatic changes in immune responses in a manner that is stimulus dependent. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.


Effects of a Specific Pre- and Probiotic Combination and Parent Stock Vaccination on Performance and Bacterial Communities in Broilers Challenged with a Multidrug-Resistant Escherichia coli.
Antibiotic resistance poses a risk for human and animal health, leading to a growing demand for effective alternatives. Combining nutritional tools and parent stock vaccination could be an approach to achieve sufficient protection against bacterial infections in poultry. In an Escherichia coli O1/O18 challenge trial, we investigated the protective effects of feeding diets containing Enterococcus faecium DSM 7134 and fructooligosaccharides (FOS) combined with specific parent stock vaccination in 225 ROSS 308 broilers. Data on performance parameters, intestinal microbial composition and metabolites, and antibiotic resistance genes (sul1-3, dhfr1a, SHV-12) were obtained. E. faecium and FOS combined with parent stock vaccination led to the highest body weights, which were significantly higher than those of controls throughout the experiment and decreased the relative abundance of Proteobacteria in the crop digesta compared to that in the positive control. However, cumulative feed conversation remained unaffected by the strategies. Birds receiving the pre-/probiotic combination showed lower cecal pH levels and higher crop L-lactate concentrations than the controls, whereas copy numbers of dhfr1a (trimethoprim resistance) and SHV-12 (extended-spectrum beta-lactamase) genes were only decreased in broilers from vaccinated hens compared to those in the challenged control. In conclusion, prophylactic administration of E. faecium and FOS in combination with parent stock vaccination can have complementary effects by improving broiler weight gain and stimulating intestinal bacterial metabolism, which may be beneficial for maintaining gut health in terms of Escherichia coli infection.


Pimozide and pancreatic cancer in diabetic chorea: a case report.
Diabetic chorea is a rare movement disorder associated with diabetes mellitus. We report the case of a patient that benefited from pimozide and died of pancreatic cancer. A 70-year-old woman presented with pollakiuria and involuntary movements of left limbs since three months. Laboratory tests revealed high serum levels of glycemia and glycated haemoglobin. She was admitted to internal medicine department and discharged one week later: insulin was administered with normalization of blood glucose levels and the involuntary movements gradually disappeared. Three weeks later she was admitted to neurological department due to the recurrence of the involuntary movements. Glycemia and other routine laboratory tests were normal. Neurological examination showed choreic movements involving left limbs. MRI showed a hyperintensity on T1- and T2-weighted sequences of right putamen and caudate nucleus head. Haloperidol was administered without improvement, it was successively substituted with tetrabenazine and the patient was discharged with an unvaried clinical picture. Two months later tetrabenazine was discontinued because of inefficacy and pimozide was started. The choreic movements considerably diminished after few days. Four months later, a pancreatic cancer was diagnosed and the patient died in the same month. Clinical and radiological features were suggestive of diabetic chorea. Our patient benefited exclusively from pimozide, it could be reasonable to use pimozide in resistant form and also propose it as first choice treatment. Another important element is the diagnosis of pancreatic cancer some months after chorea onset: a causal link could exist.


An integrated university emergency medicine - trauma program.
Systems for prehospital care, emergency medical care, and trauma care clearly overlap educationally, medically, financially, and politically. Most systems have not accomplished separation of this interdisciplinary tangle. To solve this dilemma we have customized an Emergency Medicine and Trauma Service (EM & TS) at a regional trauma medical center. The program (annually): 1)treats 32,000 patients (11,330 are trauma); 2) educates 140 paramedics, residents, students. Physician personnel: Members are fully trained in Internal Medicine, Surgery, or Pediatrics; are members of other academic departments. Each is approved by three chairman: Emergency Department, The physician's specialty, and Surgery, Structure: Board-qualified trauma surgeon always present; other faculty supplement surgical manpower; physicians are salaried; each is responsible to Director of EM & TS; trainees are not included as patient-care manpower. Organization: Academically, EM & TS is a Section of the Department of Surgery; the Section Chief is Director of EM & TS, and is responsible for Emergency Department, prehospital care, and trauma admissions. A vertical responsibility structure to this multidisciplinary system has provided a successful solution and may be tailored to other systems.


Acid phosphatases from the liver of Labeo rohita: purification and characterization.
Low molecular weight acid phosphatase (LM-ACP) peak 2 (the isoenzyme corresponding to isoform 2, IF-2) from the liver of fish Rahu (Labeo rohita) was purified to homogeneity. 900 times purification resulted with specific activity of 35 U/mg of protein and recovery of 0.2%. The enzyme was found homogeneous on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Molecular weight of 18 killo Daltons (kDa) was obtained. The peak 1 isoenzyme corresponding to isoform1 (IF-1) was partially purified about 160 times with specific activity of 7 U/mg of protein. Major protein band corresponding to 18 kDa was seen along with other protein faint bands. High molecular weight acid phosphatase (HM-ACP) was also partially purified. The molecular weight was estimated to be a 100 kDa by gel filtration on Sephadex G-100. LM-ACP isoenzymes and HM-ACP enzyme were studied for their substrate specificity, sensitivity to inhibitors or activators and other kinetic parameters. LM-ACP isoenzymes were not inhibited by tartrate and fluoride but were inhibited by sulfhydryl reagent whereas high molecular weight enzyme was strongly inhibited by fluoride and tartrate. Phosphate vanadate and molybdate inhibited both types of enzymes competitively, but their action was more pronounced in HM-ACP enzyme. LM-ACP was effectively activated by purine compounds whereas HM-ACP was not. LM-ACP showed strict substrate specificity while HM-ACP showed broad substrate specificity. The two types of acid phosphatases also differed in their rate of hydrolysis of alpha-naphthyl phosphate and beta-glyerophosphate.


Functional phosphoproteomic mass spectrometry-based approaches.
Mass Spectrometry (MS)-based phosphoproteomics tools are crucial for understanding the structure and dynamics of signaling networks. Approaches such as affinity purification followed by MS have also been used to elucidate relevant biological questions in health and disease.The study of proteomes and phosphoproteomes as linked systems, rather than research studies of individual proteins, are necessary to understand the functions of phosphorylated and un-phosphorylated proteins under spatial and temporal conditions. Phosphoproteome studies also facilitate drug target protein identification which may be clinically useful in the near future.Here, we provide an overview of general principles of signaling pathways versus phosphorylation. Likewise, we detail chemical phosphoproteomic tools, including pros and cons with examples where these methods have been applied. In addition, basic clues of electrospray ionization and collision induced dissociation fragmentation are detailed in a simple manner for successful phosphoproteomic clinical studies.


COVID-19 Guidance for Triage of Operations for Thoracic Malignancies: A Consensus Statement From Thoracic Surgery Outcomes Research Network.
The extraordinary demands of managing the COVID-19 pandemic has disrupted the world's ability to care for patients with thoracic malignancies. As a hospital's COVID-19 population increases and hospital resources are depleted, the ability to provide surgical care is progressively restricted, forcing surgeons to prioritize among their cancer populations. Representatives from multiple cancer, surgical, and research organizations have come together to provide a guide for triaging patients with thoracic malignancies as the impact of COVID-19 evolves as each hospital.


Multiview tiling light sheet microscopy for 3D high-resolution live imaging.
Light-sheet or selective plane illumination microscopy (SPIM) is ideally suited for in toto imaging of living specimens at high temporal-spatial resolution. In SPIM, the light scattering that occurs during imaging of opaque specimens brings about limitations in terms of resolution and the imaging field of view. To ameliorate this shortcoming, the illumination beam can be engineered into a highly confined light sheet over a large field of view and multi-view imaging can be performed by applying multiple lenses combined with mechanical rotation of the sample. Here, we present a Multiview tiling SPIM (MT-SPIM) that combines the Multi-view SPIM (M-SPIM) with a confined, multi-tiled light sheet. The MT-SPIM provides high-resolution, robust and rotation-free imaging of living specimens. We applied the MT-SPIM to image nuclei and Myosin II from the cellular to subcellular spatial scale in early Drosophila embryogenesis. We show that the MT-SPIM improves the axial-resolution relative to the conventional M-SPIM by a factor of two. We further demonstrate that this axial resolution enhancement improves the automated segmentation of Myosin II distribution and of nuclear volumes and shapes.


Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study.
Methylphenidate is the most frequently used medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in Europe. Following concerns about its safety, the European Commission called for research into the long-term effects of methylphenidate on children and adolescents with ADHD. The Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) research programme was designed to address this call. At the heart of this programme is a 2-year longitudinal naturalistic pharmacovigilance study being conducted in 27 European sites. 3 cohorts of children and adolescents (aged 6-17) living in the UK, Germany, Italy and Hungary are being recruited:Group 1 (Medicated ADHD): 800 ADHD medication-naive children and adolescents with a clinical diagnosis of ADHD about to start methylphenidate treatment for the first time.Group 2 (Unmedicated ADHD): 400 children and adolescents with a clinical diagnosis of ADHD who have never been treated with ADHD medication and have no intention of beginning medication.Group 3 (Non-ADHD): 400 children and adolescents without ADHD who are siblings of individuals in either group 1 or 2.All participants will be assessed 5 times during their 2-year follow-up period for growth and development, psychiatric, neurological and cardiovascular health. The primary outcome measure will be the height velocity SD score. Ethical approval for the study has been granted by the East of Scotland Research Ethics Service. Following this approval, patient information leaflets and consent forms were translated as necessary and submissions made by lead sites in each of the other 3 countries to their own ethics committees. Following ethical approval in each country, local ethical permissions at each site were sought and obtained as needed. The study's website (http://www.adhd-adduce.org/page/view/2/Home) provides information for researchers, participants and the general public. NCT01470261.


Deconvolution of BIL-SFG and DL-SFG spectroscopic signals reveals order/disorder of water at the elusive aqueous silica interface.
Through the prism of the rather controversial and elusive silica/water interface, ab initio DFT-based molecular dynamics simulations of the structure and non-linear SFG spectroscopy of the interface are analysed. Following our recent work [Phys. Chem. Chem. Phys., 2018, 20, 5190-5199], we show that once the interfacial water is decomposed into BIL (Binding Interfacial Layer) and DL (Diffuse Layer) interfacial regions, the SFG signals can be deconvolved and unambiguously interpreted, and a global microscopic understanding on silica/water interfaces can be obtained. By comparing crystalline quartz/water and amorphous (fused) silica/water interfaces, the dependence of interfacial structural and spectroscopic properties on the degree of surface crystallinity is established, while by adding KCl electrolytes at the quartz/water interface, the chaotropic effect of ions on the interfacial molecular arrangement is unveiled. The evolution of structure and SFG spectra of silica/water interfaces with respect to increasing surface deprotonation, i.e., with respect to pH conditions, is also evaluated. Spectroscopic BIL-SFG markers that experimentally allow one detect the water order/disorder in the BIL as a function of surface hydroxylation and ion concentration are revealed, while the pH-induced modulations in the experimentally recorded SFG spectra are rationalized in terms of changes in both BIL and DL SFG signatures.


Gynecologic Oncologist Perspective About ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer.
ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer was simultaneously published in 3 prestigious journals and is sure to have a huge impact on the clinical practice of gynecologic oncology community and other gynecologic cancer care providers.It is a tremendous report representative of great effort. Hovewer, as practicing gynecologic oncologists, endometrial carcinoma is the most common clinical entity encountered in our routine daily practice; as such, we find some of the report confusing and object to some of its findings, as detailed in this brief report.We also attempted to summarize the differences between the well-known NCCN guidelines and the ESMO-ESGO-ESTRO Consensus Conference guidelines and try to give the point of view of gynecologic oncologic perspective. It is obvious that differences in the management of endometrial carcinomas will continue to be debated by the scientific community.


Image Translation by Ad CycleGAN for COVID-19 X-Ray Images: A New Approach for Controllable GAN.
We propose a new generative model named adaptive cycle-consistent generative adversarial network, or Ad CycleGAN to perform image translation between normal and COVID-19 positive chest X-ray images. An independent pre-trained criterion is added to the conventional Cycle GAN architecture to exert adaptive control on image translation. The performance of Ad CycleGAN is compared with the Cycle GAN without the external criterion. The quality of the synthetic images is evaluated by quantitative metrics including Mean Squared Error (MSE), Root Mean Squared Error (RMSE), Peak Signal-to-Noise Ratio (PSNR), Universal Image Quality Index (UIQI), visual information fidelity (VIF), Frechet Inception Distance (FID), and translation accuracy. The experimental results indicate that the synthetic images generated either by the Cycle GAN or by the Ad CycleGAN have lower MSE and RMSE, and higher scores in PSNR, UIQI, and VIF in homogenous image translation (i.e., Y → Y) compared to the heterogenous image translation process (i.e., X → Y). The synthetic images by Ad CycleGAN through the heterogeneous image translation have significantly higher FID score compared to Cycle GAN (p < 0.01). The image translation accuracy of Ad CycleGAN is higher than that of Cycle GAN when normal images are converted to COVID-19 positive images (p < 0.01). Therefore, we conclude that the Ad CycleGAN with the independent criterion can improve the accuracy of GAN image translation. The new architecture has more control on image synthesis and can help address the common class imbalance issue in machine learning methods and artificial intelligence applications with medical images.


Strong reciprocity, human cooperation, and the enforcement of social norms.
This paper provides strong evidence challenging the self-interest assumption that dominates the behavioral sciences and much evolutionary thinking. The evidence indicates that many people have a tendency to voluntarily cooperate, if treated fairly, and to punish noncooperators. We call this behavioral propensity "strong reciprocity" and show empirically that it can lead to almost universal cooperation in circumstances in which purely self-interested behavior would cause a complete breakdown of cooperation. In addition, we show that people are willing to punish those who behaved unfairly towards a third person or who defected in a Prisoner's Dilemma game with a third person. This suggests that strong reciprocity is a powerful device for the enforcement of social norms involving, for example, food sharing or collective action. Strong reciprocity cannot be rationalized as an adaptive trait by the leading evolutionary theories of human cooperation (in other words, kin selection, reciprocal altruism, indirect reciprocity, and costly signaling theory). However, multilevel selection theories of cultural evolution are consistent with strong reciprocity.