"There are no band-aids for emotions": The development of thinking about emotional harm.
An understanding of harm is central to social and cognitive development, but harm largely has been conceptualized as physical damage or injury. Less research focuses on children's judgments of harm to others' internal well-being (emotional harms). We asked 5- to 10-year-old children (N = 456, 50% girls, 50% boys; primarily tested in Central New York, with socioeconomic diversity, but limited racial/ethnic or linguistic diversity) to compare emotional and physical harms. In Experiment 1, children compared simple harms (intended and completed) and then scenarios in which the perpetrator's intention did not match the outcome (intended emotional harm, but caused physical harm, or vice-versa). Assessments of the severity of emotional (vs. physical) harm increased with age and depended on the perpetrator's intentions. In Experiment 2, children saw emotional and physical harms that were: Simple (intended and completed); Incomplete (intended, but not completed); or Accidental (not intended, but completed). Children evaluated physical and emotional harms in isolation and then compared the two. Judgments of the relative severity of emotional harm increased with age, but only when intentions and outcomes were both present. This reflected an increase with age in children's perceptions that emotional harm was hurtful, whereas perceptions of physical harm were relatively stable across development. With age, children also increasingly associated emotional harms with longer-term impacts (being remembered and reoccurring). These findings suggest reasoning about the severity, underlying intentions, and duration of emotional harm shifts with age. The results hold implications for moral development, law and psychology, and emotional-harm-related interventions including those addressing bullying. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


[Successful treatment of a patient with internal carotid aneurysm].
Presented herein is a clinical report of the surgical treatment of a female patient with left internal carotid aneurysm. Patient M, aged 58 years was hospitalized to the Department of Vascular Surgery, RSCS RAMS, with complaints of a pulsatile formation in the area of the neck on the left, persistent headaches, frequently occurring dizziness, and multiple episodes of loss of consciousness. The patient has been ailing for 20 years. Examination discovered a rounded pulsatile formation about 3 cm in diameter in the left lateral area of the neck in the internal carotid projection. Duplex scanning revealed aneurysm of the left internal carotid artery measuring 2,3 cm x 3.8 cm. Computerized tomography confirmed aneurysm of the left internal carotid artery. On December 10, 2002 the patient underwent resection of aneurysm of the left internal carotid artery followed by establishment of an end-to-end anastomosis. The immediate postoperative period was uneventful. The patient was discharged home in a satisfactory condition.


Hidden renal dysfunction causes increased in-hospital mortality risk after coronary artery bypass graft surgery.
Preoperative chronic renal dysfunction is an independent predictor of mortality in cardiac surgery. As normal range serum creatinine is not representative of normal renal function, we compared mortality rates, total hospital stay and post-surgical hospital stay for patients who underwent isolated coronary artery bypass surgery with serum creatinine < 1.5mg/dL as to their estimated creatinine clearance, normal or impaired. In 4,765 patients submitted to coronary artery bypass surgery between January/1996 and June/2004, the creatinine clearance was estimated by the Cockroft-Gault equation. Impaired renal function was considered as a creatinine clearance <60 mL/min/1.73 m² (chronic renal disease stage 3 - National Kidney Foundation-USA). In hospital mortality, total hospital stay, and post-surgical hospital stay were compared. 4,688 patients had the required data, and 4,403 presented serum creatinine < 1.5 mg/dL - 3,177 with creatinine clearance > 60 mL/min (Group A), and 1,226 with <60 mL/min (Group B). Group B patients had significantly higher total hospital stay and post-surgical hospital stay than those in Group A (respectively 2.85 and 1.79 more days--P < 0.0001). Relative risk of in-hospital death was 2.09 to Group B (95%CI:1.54-2.84) when compared to Group A. More than one quarter of the patients with serum creatinine <1.5 mg/dL had creatinine clearance <60 mL/min. This expressive number of patients, that would not have their renal dysfunction detected by the serum creatinine parameter alone, had double the risk of death, longer total hospital stay and post-surgical hospital stay than the other patients with serum creatinine < 1.5mg/dL.


HIV-associated mortality in the era of antiretroviral therapy scale-up - Nairobi, Kenya, 2015.
Declines in HIV prevalence and increases in antiretroviral treatment coverage have been documented in Kenya, but population-level mortality associated with HIV has not been directly measured. In urban areas where a majority of deaths pass through mortuaries, mortuary-based studies have the potential to contribute to our understanding of excess mortality among HIV-infected persons. We used results from a cross-sectional mortuary-based HIV surveillance study to estimate the association between HIV and mortality for Nairobi, the capital city of Kenya. HIV seropositivity in cadavers measured at the two largest mortuaries in Nairobi was used to estimate HIV prevalence in adult deaths. Model-based estimates of the HIV-infected and uninfected population for Nairobi were used to calculate a standardized mortality ratio and population-attributable fraction for mortality among the infected versus uninfected population. Monte Carlo simulation was used to assess sensitivity to epidemiological assumptions. When standardized to the age and sex distribution of expected deaths, the estimated HIV positivity among adult deaths aged 15 years and above in Nairobi was 20.9% (95% CI 17.7-24.6%). The standardized mortality ratio of deaths among HIV-infected versus uninfected adults was 4.35 (95% CI 3.67-5.15), while the risk difference was 0.016 (95% CI 0.013-0.019). The HIV population attributable mortality fraction was 0.161 (95% CI 0.131-0.190). Sensitivity analyses demonstrated robustness of results. Although 73.6% of adult PLHIV receive antiretrovirals in Nairobi, their risk of death is four-fold greater than in the uninfected, while 16.1% of all adult deaths in the city can be attributed to HIV infection. In order to further reduce HIV-associated mortality, high-burden countries may need to reach very high levels of diagnosis, treatment coverage, retention in care, and viral suppression.


Association of Maternal Preeclampsia With Offspring Risks of Ischemic Heart Disease and Stroke in Nordic Countries.
An association between maternal preeclampsia and an increased risk of cardiovascular disease in the offspring is plausible, but evidence in this area is limited. To investigate (1) the association between maternal preeclampsia and risks of ischemic heart disease (IHD) and stroke in the offspring, (2) whether the association varies by severity or timing of onset of preeclampsia, and (3) the role of preterm birth and small for gestational age (SGA) birth, both of which are related to preeclampsia and cardiovascular diseases, in this association. This multinational population-based cohort study obtained data from Danish, Finnish, and Swedish national registries. Live singleton births from Denmark (1973-2016), Finland (1987-2014), and Sweden (1973-2014) were followed up until December 31, 2016, in Denmark and December 31, 2014, in Finland and Sweden. Data analyses were performed between September 2020 and September 2022. Preeclampsia and its subtypes, including early onset (<34 gestational weeks) and late onset (≥34 gestational weeks), severe and mild or moderate, and with and without SGA birth. Diagnoses of IHD and stroke were extracted from patient and cause-of-death registers. Cox proportional hazards regression models and flexible parametric survival models were used to analyze the associations. Sibling analyses were conducted to control for unmeasured familial factors. The cohort included of 8 475 819 births (2 668 697 [31.5%] from Denmark, 1 636 116 [19.3%] from Finland, and 4 171 006 [49.2%] from Sweden, comprising 4 350 546 boys [51.3%]). Of these offspring, 188 670 (2.2%) were exposed to maternal preeclampsia, 7446 (0.1%) were diagnosed with IHD, and 10 918 (0.1%) were diagnosed with stroke during the median (IQR) follow-up of 19.3 (9.0-28.1) years. Offspring of individuals with preeclampsia had increased risks of IHD (adjusted hazard ratio [HR], 1.33; 95% CI, 1.12-1.58) and stroke (adjusted HR, 1.34; 95% CI, 1.17-1.52). These associations were largely independent of preterm or SGA birth. Severe forms of preeclampsia were associated with a higher stroke risk than less severe forms (severe vs mild or moderate: adjusted HR, 1.81 [95% CI, 1.41-2.32] vs 1.22 [95% CI, 1.05-1.42]; early vs late onset: adjusted HR, 2.55 [95% CI, 1.97-3.28] vs 1.18 [95% CI, 1.01-1.39]; with vs without SGA birth: adjusted HR, 1.84 [95% CI, 1.44-2.34] vs 1.25 [95% CI, 1.07-1.48]). Sibling analyses suggested that the associations were partially explained by unmeasured familial factors. Results of this study suggest that offspring born to individuals with preeclampsia had increased IHD and stroke risk that were not fully explained by preterm or SGA birth, and that the associated risks for stroke were higher for severe forms of preeclampsia.


Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome.
Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event. The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice. Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, pre-analytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.


Identifying simultaneous matrix metalloproteinases/soluble epoxide hydrolase inhibitors.
Matrix metalloproteinase (MMP) and soluble epoxide hydrolase (sEH) have completely unrelated biological functions; however, their dysregulation produce similar effects on biological systems. Based on the similarity in the reported structural requirements for their inhibition, the current study aimed to identify a simultaneous inhibitor for MMP and sEH. Six compounds were identified as potential simultaneous MMP/sEH inhibitors and tested for their capacity to inhibit MMP and sEH. Inhibition of MMP and sEH activity using their endogenous and exogenous substrates was measured by liquid chromatography/mass spectrometry, spectrophotometry, and zymography. Two compounds, CTK8G1143 and ONO-4817, were identified to inhibit both MMP and sEH activity. CTK8G1143 and ONO-4817 inhibited the recombinant human sEH activity by an average of 67.4% and 55.2%, respectively. The IC50 values for CTK8G1143 and ONO-4817 to inhibit recombinant human sEH were 5.2 and 3.5 µM, respectively, whereas their maximal inhibition values were 71.4% and 42.8%, respectively. Also, MMP and sEH activity of human cardiomyocytes were simultaneously inhibited by CTK8G1143 and ONO-4817. Regarding other compounds, they showed either MMP or sEH inhibitory activity but not both. In conclusion, these two simultaneous inhibitors of MMP and sEH could provide a promising intervention for the prevention and control of several diseases, especially cardiovascular diseases.


The Current Status of the Ketogenic Diet in Psychiatry.
The ketogenic diet (KD) has been used in treatment-resistant epilepsy since the 1920s. It has been researched in a variety of neurological conditions in both animal models and human trials. The aim of this review is to clarify the potential role of KD in psychiatry. Narrative review of electronic databases PubMED, PsychINFO, and Scopus. The search yielded 15 studies that related the use of KD in mental disorders including anxiety, depression, bipolar disorder, schizophrenia, autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). These studies comprised nine animal models, four case studies, and two open-label studies in humans. In anxiety, exogenous ketone supplementation reduced anxiety-related behaviors in a rat model. In depression, KD significantly reduced depression-like behaviors in rat and mice models in two controlled studies. In bipolar disorder, one case study reported a reduction in symptomatology, while a second case study reported no improvement. In schizophrenia, an open-label study in female patients (n = 10) reported reduced symptoms after 2 weeks of KD, a single case study reported no improvement. In a brief report, 3 weeks of KD in a mouse model normalized pathological behaviors. In ASD, an open-label study in children (n = 30) reported no significant improvement; one case study reported a pronounced and sustained response to KD. In ASD, in four controlled animal studies, KD significantly reduced ASD-related behaviors in mice and rats. In ADHD, in one controlled trial of KD in dogs with comorbid epilepsy, both conditions significantly improved. Despite its long history in neurology, the role of KD in mental disorders is unclear. Half of the published studies are based on animal models of mental disorders with limited generalizability to the analog conditions in humans. The review lists some major limitations including the lack of measuring ketone levels in four studies and the issue of compliance to the rigid diet in humans. Currently, there is insufficient evidence for the use of KD in mental disorders, and it is not a recommended treatment option. Future research should include long-term, prospective, randomized, placebo-controlled crossover dietary trials to examine the effect of KD in various mental disorders.


The natural history of benign thyroid nodules.
Detection of asymptomatic thyroid nodules has increased. Consensus is lacking regarding the optimal follow-up of cytologically proven benign lesions and sonographically nonsuspicious nodules. Current guidelines recommend serial ultrasound examinations and reassessment of cytology if significant growth is observed. To determine the frequency, magnitude, and factors associated with changes in thyroid nodule size. Prospective, multicenter, observational study involving 992 consecutive patients with 1 to 4 asymptomatic, sonographically or cytologically benign thyroid nodules. Patients were recruited from 8 hospital-based thyroid-disease referral centers in Italy between 2006 and 2008. Data collected during the first 5 years of follow-up, through January 2013, were analyzed. Baseline nodule growth (primary end point) was assessed with yearly thyroid ultrasound examinations. Size changes were considered significant for growth if an increase of 20% or more was recorded in at least 2 nodule diameters, with a minimum increase of 2 mm. Baseline factors associated with growth were identified. Secondary end points were the sonographic detection of new nodules and the diagnosis of thyroid cancer during follow-up. Nodule growth occurred in 153 patients (15.4% [95% CI, 14.3%-16.5%]). One hundred seventy-four of the 1567 original nodules (11.1% [95% CI, 10.3%-11.9%]) increased in size, with a mean 5-year largest diameter increase of 4.9 mm (95% CI, 4.2-5.5 mm), from 13.2 mm (95% CI, 12.1-14.2 mm) to 18.1 mm (95% CI, 16.7-19.4 mm). Nodule growth was associated with presence of multiple nodules (OR, 2.2 [95% CI 1.4-3.4] for 2 nodules; OR, 3.2 [95% CI, 1.8-5.6 for 3 nodules; and OR, 8.9 [95% CI, 4.4-18.0] for 4 nodules), main nodule volumes larger than 0.2 mL (OR, 2.9 [95% CI, 1.7-4.9] for volumes >0.2 to <1 mL and OR, 3.0 [95% CI, 1.8-5.1] for volumes ≥1 mL), and male sex (OR, 1.7 [95% CI, 1.1-2.6]), whereas an age of 60 years or older was associated with a lower risk of growth than age younger than 45 years (OR, 0.5 [95% CI 0.3-0.9]). In 184 individuals (18.5% [95% CI, 16.4%-20.9%]), nodules shrank spontaneously. Thyroid cancer was diagnosed in 5 original nodules (0.3% [95% CI, 0.0%-0.6%]). Only 2 had grown. An incidental cancer was found at thyroidectomy in a nonvisualized nodule. New nodules developed in 93 patients (9.3% [95% CI, 7.5%-11.1%]), with detection of one cancer. Among patients with asymptomatic, sonographically or cytologically benign thyroid nodules, the majority of nodules exhibited no significant size increase during 5 years of follow-up and thyroid cancer was rare. These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.


Identification of a novel protein (G210) specific to the Golgi apparatus.
A monoclonal antibody, 3C9, has enabled the detection of a novel Golgi-specific protein in bovine tissues. Immunohistochemical studies at the light microscopic level have detected the 3C9 antigen only in certain cells: exocrine pancreas, gut epithelium, and thymus epithelium. Examination of gut and pancreas by immunoelectron microscopy showed a localization exclusive to the Golgi apparatus. The relative molecular weight of the antigen detected by immunoblotting is 210,000 daltons. The antigen is not extracted from microsomal membranes of bovine gut epithelium by sodium carbonate solutions. Furthermore, the 3C9 antigen enters into the detergent phase when Triton X-114 partitioning methods are used. These data strongly suggest that this novel antigen is an intrinsic membrane protein, resident in the Golgi apparatus of certain cells. Moreover, they enhance the hypothesis that the distribution of enzymes and polypeptides in the Golgi apparatus is cell specific.


A new method for identifying bivariate differential expression in high dimensional microarray data using quadratic discriminant analysis.
One of the drawbacks we face up when analyzing gene to phenotype associations in genomic data is the ugly performance of the designed classifier due to the small sample-high dimensional data structures (n ≪ p) at hand. This is known as the peaking phenomenon, a common situation in the analysis of gene expression data. Highly predictive bivariate gene interactions whose marginals are useless for discrimination are also affected by such phenomenon, so they are commonly discarded by state of the art sequential search algorithms. Such patterns are known as weak/marginal strong bivariate interactions. This paper addresses the problem of uncovering them in high dimensional settings. We propose a new approach which uses the quadratic discriminant analysis (QDA) as a search engine in order to detect such signals. The choice of QDA is justified by a simulation study for a benchmark of classifiers which reveals its appealing properties. The procedure rests on an exhaustive search which explores the feature space in a blockwise manner by dividing it in blocks and by assessing the accuracy of the QDA for the predictors within each pair of blocks; the block size is determined by the resistance of the QDA to peaking. This search highlights chunks of features which are expected to contain the type of subtle interactions we are concerned with; a closer look at this smaller subset of features by means of an exhaustive search guided by the QDA error rate for all the pairwise input combinations within this subset will enable their final detection. The proposed method is applied both to synthetic data and to a public domain microarray data. When applied to gene expression data, it leads to pairs of genes which are not univariate differentially expressed but exhibit subtle patterns of bivariate differential expression. We have proposed a novel approach for identifying weak marginal/strong bivariate interactions. Unlike standard approaches as the top scoring pair (TSP) and the CorScor, our procedure does not assume a specified shape of phenotype separation and may enrich the type of bivariate differential expression patterns that can be uncovered in high dimensional data.


Development of a flexible system for measuring muscle area using ultrasonography.
Muscular strength can be estimated by quantification of muscle area. For this purpose, we developed a flexible measuring system for muscle area using ultrasonography. This method is completely safe and is particularly suitable for elderly people because the subjects are not required to perform any muscular contraction during measurement. The ultrasound probe is installed on a mechanical arm, and continuously scans fragmental images along the body surface. A wide-area cross-sectional image is then constructed using the measured images. The link mechanism is very flexible, enabling the operator to measure images for any body posture and body site. Use of the spatial compounding method reduces speckle and artifact noise in the resultant cross-sectional images. The operator can observe individual muscles (extensor, flexor muscle, etc.) in detail. We conducted experiments to evaluate the performance of the system. In the experiments, the position of the ultrasound probe was calculated with high accuracy according to the link posture. In addition, a high degree of correlation was verified between MR images and those of the developed system. We observed a reduction in noise due to use of the spatial compounding method, and propose a new calibration method for correcting the measured muscle area, which were slightly deformed by the contact pressure of the ultrasound probe. Finally, we examined the relation between muscular area and muscular strength in young and middle-aged subjects. The results of these experiments confirm that the developed system can estimate muscular strength based on muscular area.


Immunohistochemical identification of Campylobacter fetus in natural cases of bovine and ovine abortions.
An immunohistochemistry (IHC) procedure for the detection of Campylobacter fetus antigens using an avidin-biotin complex technique was performed on formalin fixed bovine and ovine fetal tissues from 26 natural cases of Campylobacter spp. abortion (four ovine and 22 bovine). The species of Campylobacter isolated included C. fetus ssp. venerealis from 13 bovine fetuses, C. fetus ssp. fetus from two ovine and one bovine fetus, Campylobacter jejuni from seven bovine fetuses, Campylobacter lari from two ovine fetuses and an unspeciated Campylobacter species in one bovine fetus. Histologic lesions identified in the aborted fetuses included placentitis, serositis, pneumonia, gastroenteritis, hepatitis and encephalitis. Campylobacter fetus antigens were identified by IHC in 13 of 13 bovine fetuses from which C. fetus ssp. venerealis was isolated and in two of two ovine fetuses from which C. fetus ssp. fetus was isolated. The IHC stains were negative in tissues from seven bovine fetuses from which C. jejuni was isolated, one bovine fetus infected with C. fetus ssp. fetus, one bovine fetus infected with the unspeciated Campylobacter and two ovine fetuses infected with C. lari. In positive cases, the IHC stain most frequently identified bacteria in the lung and gastrointestinal tract. The C. fetus IHC procedure performed on formalin fixed tissues is a practical tool for the diagnosis of natural cases of ovine and bovine abortion caused by C. fetus.


Ethical policies on animal experiments are not compromised by whether a journal is freely accessible or charges for publication.
The advent of the open access (OA) movement in publishing has been instrumental in causing a shift in the accessibility of research findings published in academic journals. The adoption of OA and other online publication models means that the results of scientific research published in journals using a free access (FA) framework are now available, free of charge, to anyone with access to the Internet. FA journals typically require a payment from the authors of a manuscript, which has raised concerns about the quality of work published in them; accepting payment from an author may compromise a journal's acceptance criteria. This study addresses whether journal policy on the treatment of animals is influenced by whether a journal follows a FA publishing model, and whether a requirement to pay for publication has an influence. A random sample of 332 biomedical journals listed in the ISI Web of Knowledge and Directory of Open Access Journals databases were assessed for whether they had an ethical policy on publishing animal studies, and what form of publication framework they used (103 of the journals followed a FA framework; 101 charged in some way for publication). Only 135 (40.7%) of the journals surveyed demanded that submissions comply with a pre-defined ethical stance. FA journals are just as likely to have an ethical policy on the treatment and presentation of animal studies as 'traditional', non-FA journals (significance of there being a difference: P = 0.98), and there is no relationship between policy and whether an author is required to pay for publication (significance of there being a difference: P = 0.57). Older journals are more likely to have an ethical policy (P = 0.03). There is, therefore, no obvious compromise shown by FA journals in the explicit policies on reporting studies involving animals. However, since anyone can read published FA studies online, FA journals that do not have an explicit policy about publishing animal research are urged to consider adopting one.


Climatic implications of an 8000-year hydrogen isotope time series from bristlecone pine trees.
Tree rings from three dendrochronologically dated bristlecone pines were analyzed for stable hydrogen isotopic composition. These trees give a continuous time series from 8000 years ago to the present that indicates the presence of a postglacial climate optimum 6800 years ago and a continuous cooling since then. The qualitative agreement between this record and records from other sources, such as ice cores, pollen, and treeline fluctuations, indicates that these climate changes were global. This record can serve as a reference for other climate indicators throughout the past 8000 years.


Ultrasonography as a complementary exam in the diagnosis of oral arteriovenous malformation.
The Doppler ultrasonography (DU) in cases of arteriovenous malformations (AVMs) is not widely use by dentists and there are a lack of information on the topic in the literature. AVM is common in the region of the head and neck and are commonly confused with hemangiomas (congenital). Appropriate classification is essential for therapeutic decision. The diferential diagnosis is based on clinical history, diascopy, and, if necessary, diagnostic imaging. This article present two cases of oral AVM in which DU was crucial in detecting a venous and/or arterial component in purplish lesions in the tongue and buccal mucosa, with positive diascopy. In our cases, after DU, we found a predominance of blood component within the lesion and therefore both patients were referred to the head and neck surgeon for surgical removal of the lesion. Only in the presence of a venous component does outpatient treatment become feasible. Given the predominance of the arterial component, outpatient procedures are contraindicated. Therefore DU is an important supplementary test, being of great importance in the clinical decision and treatment plan for oral AVMs and should become a routine part of the dentist front of vascular lesions of medium to large size.


Effect of early mobilisation on grip strength, pinch strength and work of hand muscles in cases of closed diaphyseal fracture radius-ulna treated with dynamic compression plating.
The purpose of the study was to objectively determine the effects of early mobilisation in terms of grip strength and work of hand muscles in cases of closed diaphyseal fracture radius - ulna treated with dynamic compression plating. Fifty normal subjects and Twenty-one patients, (Eleven patients treated with early active and resistive goal directed mobilisation and Ten control group) were assessed for pinch strength and grip strength on Pinch Dynamometer and Jamar Dynamometer and work of hand muscles on Ergograph. Standardised positions of the equipments and patients were maintained throughout the study. Results showed highly significant reduction in performance in patients treated with early mobilisation as compared to normal subjects in their first assessment (Fourth week post operatively). These patients showed significant improvement in successive assessments (sixth & eighth post operative week) on exercising in between these assessments. There are significant effects on grip strength and work of hand muscles in patients treated with that early active and resistive goal directed mobilisation.


Reduction of aflatoxin production by Aspergillus flavus and Aspergillus parasiticus in interaction with Streptomyces.
The aim of this study is to investigate aflatoxin gene expression during Streptomyces-Aspergillus interaction. Aflatoxins are carcinogenic compounds produced mainly by Aspergillus flavus and Aspergillus parasiticus. A previous study has shown that Streptomyces-A. flavus interaction can reduce aflatoxin content in vitro. Here, we first validated this same effect in the interaction with A. parasiticus. Moreover, we showed that growth reduction and aflatoxin content were correlated in A. parasiticus but not in A. flavus. Secondly, we investigated the mechanisms of action by reverse-transcriptase quantitative PCR. As microbial interaction can lead to variations in expression of household genes, the most stable [act1, βtub (and cox5 for A. parasiticus)] were chosen using geNorm software. To shed light on the mechanisms involved, we studied during the interaction the expression of five genes (aflD, aflM, aflP, aflR and aflS). Overall, the results of aflatoxin gene expression showed that Streptomyces repressed gene expression to a greater level in A. parasiticus than in A. flavus. Expression of aflR and aflS was generally repressed in both Aspergillus species. Expression of aflM was repressed and was correlated with aflatoxin B1 content. The results suggest that aflM expression could be a potential aflatoxin indicator in Streptomyces species interactions. Therefore, we demonstrate that Streptomyces can reduce aflatoxin production by both Aspergillus species and that this effect can be correlated with the repression of aflM expression.


Is the food-entrainable circadian oscillator in the digestive system?
Food-anticipatory activity (FAA) is the increase in locomotion and core body temperature that precedes a daily scheduled meal. It is driven by a circadian oscillator but is independent of the suprachiasmatic nuclei. Recent results that reveal meal-entrained clock gene expression in rat and mouse peripheral organs raise the intriguing possibility that the digestive system is the site of the feeding-entrained oscillator (FEO) that underlies FAA. We tested this possibility by comparing FAA and Per1 rhythmicity in the digestive system of the Per1-luciferase transgenic rat. First, rats were entrained to daytime restricted feeding (RF, 10 days), then fed ad libitum (AL, 10 days), then food deprived (FD, 2 days). As expected FAA was evident during RF and disappeared during subsequent AL feeding, but returned at the correct phase during deprivation. The phase of Per1 in liver, stomach and colon shifted from a nocturnal to a diurnal peak during RF, but shifted back to nocturnal phase during the subsequent AL and remained nocturnal during food deprivation periods. Second, rats were entrained to two daily meals at zeitgeber time (ZT) 0400 and ZT 1600. FAA to both meals emerged after about 10days of dual RF. However, all tissues studied (all five liver lobes, esophagus, antral stomach, body of stomach, colon) showed entrainment consistent with only the night-time meal. These two results are inconsistent with the hypothesis that FAA arises as an output of rhythms in the gastrointestinal (GI) system. The results also highlight an interesting diversity among peripheral oscillators in their ability to entrain to meals and the direction of the phase shift after RF ends.


The structure of a cyanobacterial sucrose-phosphatase reveals the sugar tongs that release free sucrose in the cell.
Sucrose-phosphatase (SPP) catalyzes the final step in the pathway of sucrose biosynthesis in both plants and cyanobacteria, and the SPPs from these two groups of organisms are closely related. We have crystallized the enzyme from the cyanobacterium Synechocystis sp PCC 6803 and determined its crystal structure alone and in complex with various ligands. The protein consists of a core domain containing the catalytic site and a smaller cap domain that contains a glucose binding site. Two flexible hinge loops link the two domains, forming a structure that resembles a pair of sugar tongs. The glucose binding site plays a major role in determining the enzyme's remarkable substrate specificity and is also important for its inhibition by sucrose and glucose. It is proposed that the catalytic reaction is initiated by nucleophilic attack on the substrate by Asp9 and involves formation of a covalent phospho-Asp9-enzyme intermediate. From modeling based on the SPP structure, we predict that the noncatalytic SPP-like domain of the Synechocystis sucrose-phosphate synthase could bind sucrose-6(F)-phosphate and propose that this domain might be involved in metabolite channeling between the last two enzymes in the pathway of sucrose synthesis.


A fine line between macrophage activation syndrome and multisystem inflammatory syndrome in children - literature review based on two case reports.
Multisystem inflammatory syndrome in children is a newly described condition temporarily associated with severe acute respiratory syndrome coronavirus 2. The primary observations indicated coronavirus disease 2019 infection in children to be mild. However, recent reports have revealed a correlation between multisystem inflammatory symptoms and coronavirus infection. The manifestation of the disease is similar to Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. Treatment includes intravenous corticosteroids, immunoglobulin and biological therapy (anakinra, tocilizumab, infliximab). In this article we compare world reports of multisystem inflammatory syndrome in children to case reports of two patients who were hospitalized recently at the Department of Paediatric Cardiology and Rheumatology. In the course of diagnostics they presented numerous symptoms which required differentiation from multisystem inflammatory syndrome in children.


Half-molar sodium-lactate solution has a beneficial effect in patients after coronary artery bypass grafting.
To compare two solutions for fluid resuscitation in post-coronary artery bypass grafting (CABG) surgery patients: Ringer's lactate (RL) versus a new solution containing half-molar sodium-lactate (HL). Prospective randomized open label study. The first 12 h post-CABG surgery in an intensive care unit (ICU). There were 230 patients enrolled in the study: 208 were analyzed, with 109 from the HL group and 99 from the RL group. Patients received over the first 12 h post-CABG 10 ml kg BW(-1) HL solution in the HL group versus 30 ml kg BW(-1) of RL solution in the RL group. Hemodynamic status, body fluid balance and inotrope utilization were compared in the two groups. Post-operative cardiac index increase was significantly higher in HL than in RL (P = 0.02), while mean arterial pressure and other hemodynamic parameters were comparable together with urinary output, indicating similar tissue perfusion in both the groups despite a much lower fluid infusion in the HL group. Therefore, a significant negative fluid balance was achieved in the HL but not in the RL group (-790 +/- 71 vs. +43 +/- 115 mL 12 h(-1), P < 0.0001 for HL and RL, respectively). None of the enrolled patients exhibited side effects related to the treatment. Half-molar lactate solution is effective for fluid resuscitation in post-CABG patients. Compared to Ringer's Lactate, its use results in a significantly higher cardiac index with less volume being infused, resulting in a very negative post-operative body fluid balance.


Delineating parameter unidentifiabilities in complex models.
Scientists use mathematical modeling as a tool for understanding and predicting the properties of complex physical systems. In highly parametrized models there often exist relationships between parameters over which model predictions are identical, or nearly identical. These are known as structural or practical unidentifiabilities, respectively. They are hard to diagnose and make reliable parameter estimation from data impossible. They furthermore imply the existence of an underlying model simplification. We describe a scalable method for detecting unidentifiabilities, as well as the functional relations defining them, for generic models. This allows for model simplification, and appreciation of which parameters (or functions thereof) cannot be estimated from data. Our algorithm can identify features such as redundant mechanisms and fast time-scale subsystems, as well as the regimes in parameter space over which such approximations are valid. We base our algorithm on a quantification of regional parametric sensitivity that we call 'multiscale sloppiness'. Traditionally, the link between parametric sensitivity and the conditioning of the parameter estimation problem is made locally, through the Fisher information matrix. This is valid in the regime of infinitesimal measurement uncertainty. We demonstrate the duality between multiscale sloppiness and the geometry of confidence regions surrounding parameter estimates made where measurement uncertainty is non-negligible. Further theoretical relationships are provided linking multiscale sloppiness to the likelihood-ratio test. From this, we show that a local sensitivity analysis (as typically done) is insufficient for determining the reliability of parameter estimation, even with simple (non)linear systems. Our algorithm can provide a tractable alternative. We finally apply our methods to a large-scale, benchmark systems biology model of necrosis factor (NF)-κB, uncovering unidentifiabilities.


Pleural effusions in febrile medical ICU patients: chest ultrasound study.
To assess the necessity of thoracentesis in febrile medical ICU (MICU) patients, and to evaluate the efficiency and reliability of sonographic effusion patterns for diagnosing empyema. A prospective, 1-year, tertiary-care hospital study of febrile MICU patients with physical, radiographic, and ultrasonographic evidence of pleural effusion. During this study period, we screened 1,640 patients who had been admitted to the MICU; of these, 94 patients had a temperature > 38 degrees C for > 8 h with evidence of pleural effusion proven by chest radiography and ultrasound. Routine thoracentesis and pleural effusion cultures were performed in 94 febrile patients under portable chest ultrasound guidance. Three days later, if the first pleural effusion culture was inconclusive and the patient still had persistent fever of > 38 degrees C, we repeated the diagnostic thoracentesis and pleural effusion culture. In total, 118 procedures were performed in those 94 febrile patients. In all, 58 patients (62%) had infectious exudates (parapneumonic, n = 36; empyema, n = 15; urosepsis, n = 3; liver abscess, n = 2; deep neck infection, n = 1; and wound infection, n = 1), 28 patients (30%) had transudates, and 8 patients (8%) had noninfectious exudates. The prevalence of empyema in febrile patients admitted to the MICU was 16% (15 of 94 patients). Analyses of the sonographic patterns of the 15 patients with empyema out of the 118 thoracenteses performed showed the following: anechoic pattern, 0% (0 of 47 procedures); complex nonseptated and relatively nonhyperechoic pattern, 0% (0 of 36 procedures); complex nonseptated and relatively hyperechoic pattern, 100% (2 of 2 procedures); complex septated pattern, 35% (11 of 31 procedures); and homogeneously echogenic pattern, 100% (2 of 2 procedures). Hemothorax was the only complication, and it occurred in two patients (2%). Both patients had a favorable outcome after drainage. Portable chest ultrasound examination and ultrasound-guided thoracentesis in febrile MICU patients are safe, feasible, and useful methods for diagnosing thoracic empyema. Our results suggest that only some sonographic patterns of pleural effusion (homogeneously echogenic, complex nonseptated and relatively hyperechoic, and complex septated) deserve aggressive assessment and rapid management.


Factors Related to the Probable PTSD after the 9/11 World Trade Center Attack among Asian Americans.
Despite the fact that Asians constituted a sizeable proportion of those exposed to the World Trade Center attack on September 11, 2001 due to its proximity to Chinatown and many South Asians working in the nearby buildings, no study had focused on examining the mental health impact of the attack in this group. Based on data collected by the World Trade Center Health Registry from a sample of 4721 Asians 2-3 years after the disaster, this study provides a baseline investigation for the prevalence and the risk and protective factors for PTSD among Asian Americans directly exposed to the attack and compared this population against 42,862 non-Hispanic Whites. We found that Asians had a higher prevalence of PTSD compared to Whites (14.6 vs 11.7%). "Race-specific factors" significantly associated to PTSD in the multivariate analyses were noted among sociodemographics: higher education was protective for Whites but a risk factor for Asians; being employed was protective for Whites but had no effect for Asians; and being an immigrant was a risk factor for Whites but had no effect for Asians. However, income was a protective factor for both races. Other "universal factors" significantly increased the odds of PTSD symptoms but showed no racial differences, including exposure to the disaster and the presence of lower respiratory symptoms which intensified odds of PTSD by the greatest magnitude (3.6-3.9 times). Targeted effort to reach out to Asians is essential for prevention and follow up treatment given this group's striking history of underutilization of mental health services.


The CDC2-related kinase PITALRE is the catalytic subunit of active multimeric protein complexes.
PITALRE is a human protein kinase identified by means of its partial sequence identity to the cell division cycle regulatory kinase CDC2. Immunopurified PITALRE protein complexes exhibit an in vitro kinase activity that phosphorylates the retinoblastoma protein, suggesting that PITALRE catalyses this phosphorylation reaction. However, the presence of other kinases in the immunopurified complex could not be ruled out. In the present work, an inactive mutant of the PITALRE kinase has been used to demonstrate that PITALRE is the catalytic subunit responsible for the PITALRE-complex-associated kinase activity, Ectopic overexpression of PITALRE did not increase the total PITALRE kinase activity in the cell, suggesting that PITALRE is regulated by limiting cellular factor(s). Characterization of the PITALRE-containing protein complexes indicated that most of the cellular PITALRE protein exists as a subunit in at least two different active multimeric complexes. Although monomeric PITALRE is also active in vitro, PITALRE present in multimeric complexes exhibits several-fold higher activity than monomeric PITALRE. In addition, overexpression of PITALRE demonstrated the existence of two new associated proteins of approx. 48 and 98 kDa. Altogether these results suggest that, in contrast to the situation with cyclin-dependent kinases, monomeric PITALRE is active, and that association with other proteins modulates its activity and/or its ability to recognize substrates in vivo.


Predictive values of time-dense SARS-CoV-2 wastewater analysis in university campus buildings.
Wastewater-based SARS-CoV-2 surveillance on college campuses has the ability to detect individual clinical COVID-19 cases at the building-level. High concordance of wastewater results and clinical cases has been observed when calculated over a time window of four days or longer and in settings with high incidence of infection. At Duke University, twice a week clinical surveillance of all resident undergraduates was carried out in the spring 2021 semester. We conducted simultaneous wastewater surveillance with daily frequency on selected residence halls to assess wastewater as an early warning tool during times of low transmission with the hope of scaling down clinical test frequency. We evaluated the temporal relationship of the two time-dense data sets, wastewater and clinical, and sought a strategy to achieve the highest wastewater predictive values using the shortest time window to enable timely intervention. There were 11 days with clinical cases in the residence halls (80-120 occupants) under wastewater surveillance with 5 instances of a single clinical case and 3 instances of two clinical cases which also corresponded to a positive wastewater SARS-CoV-2 signal. While the majority (71%) of our wastewater samples were negative for SARS-CoV-2, 29% resulted in at least one positive PCR signal, some of which did not correlate with an identified clinical case. Using a criteria of two consecutive days of positive wastewater signals, we obtained a positive predictive value (PPV) of 75% and a negative predictive value of 87% using a short 2 day time window for agreement. A conventional concordance over a much longer 4 day time window resulted in PPV of only 60%. Our data indicated that daily wastewater collection and using a criteria of two consecutive days of positive wastewater signals was the most predictive approach to timely early warning of COVID-19 cases at the building level.


Investigational drugs in phase I and phase II clinical trials for the treatment of community-acquired pneumonia.
Community acquired pneumonia is one of the main infections, remaining as a global cause of considerable morbidity and mortality. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely pathogens and the severity of disease. Although antibiotic resistance is increasing and pharmaceutical companies continue to debate the profitability of introducing new antibacterial agents, an encouraging number of new molecules have recently been unveiled which target multidrug-resistant bacteria. Areas covered: Herein, the authors summarize the actual situation of novel antibiotics for CAP in phase I & II of development. For each set of compounds, the medical significance and possible clinical placement are discussed. Current treatment options from the most important international guidelines are also reviewed. Expert opinion: Our review shows that the new antibiotics in the pipeline belong to existing antibiotic classes as β-lactams, macrolides, quinolones, oxazolidinones, tetracyclines, lipoglycopeptides, and cyclic lipopeptides and a few with a narrow spectrum of activity are novel compounds directed against novel targets. With rising outpatient antibiotic resistance in pneumonia, some of the compounds discussed are being considered for more rapid advancement in the pipeline, helping to increase the number of agents in later stages of development.


Residential greenspace and major depression among older adults living in urban and suburban areas with different climates across the United States.
Residential greenspace could alleviate depression - a leading cause of disability. Fewer studies of depression and greenspace have considered major depression, and, to our knowledge, none have considered how climate, which determines vegetation abundance and type, may change the impacts of greenspace. Our aim was to investigate whether residential greenspace is associated with major depression among older adults and explore effect modification by climate. We used biennial interviews between 2008 and 2016 from the Health and Retirement Study. We calculated greenness within walking distance of home addresses as the maximum NDVI for the year of each participant interview averaged within a 1 km buffer. Reflecting clinical criteria, a score of ≥5 on the CIDI-SF indicated major depression in the preceding 12-months. We characterized climate using Köppen-Geiger classifications. To estimate prevalence ratios, we used Poisson regression. Our models adjusted for sociodemographic characteristics, geography, annual sunshine, and bluespace. The 21,611 eligible participants were 65 ± 10 years old on average, 55% female, 81% White, 12% Black, 10% Hispanic/Latino, and 31% had at least a 4-year college degree. The 12-month prevalence of a major depression was 8%. In adjusted models, more residential greenspace was associated with a lower prevalence of major depression (prevalence ratio per IQR, 0.91; 95% CI, 0.84 to 0.98). There was evidence of effect modification by climate (P-interaction, 0.062). We observed stronger associations in tropical (prevalence ratio per IQR 0.69; 95% CI, 0.47 to 1.01) and cold (prevalence ratio per IQR, 0.83; 95% CI, 0.74 to 0.93) climates compared to arid (prevalence ratio per IQR 0.99; 95% CI, 0.90 to 1.09) and temperate (prevalence ratio per IQR 0.98; 95% CI, 0.86 to 1.11) climates. Residential greenspace may help reduce major depression. However, climate may influence how people benefit from greenspace.


The social parasite wasp Polistes atrimandibularis does not form host races.
Parasites that exploit the parental behaviour of several host species may be selected to form distinct host-specific genetic lineages. This process is well documented in bird brood parasites, but not in insect social parasites. Polistes atrimandibularis is the only paper-wasp social parasite known to exploit four host species. It does not form genetically distinct host races according to analyses based on microsatellite loci. Also, there were no size-matching between parasites and host species. Instead, P. atrimandibularis queens seemed to be successful as parasites in this population only when they originated from nests of P. dominulus, the largest species. The other host species are a sink for P. atrimandibularis since adult females emerging from those nests appear too small to usurp colonies themselves. Traits that may help P. atrimandibularis infiltrate multiple species may include its nonaggressive usurpation tactics and its ability to acquire host cuticular hydrocarbon recognition labels.


Utilization of phosphinoamide ligands in homobimetallic Fe and Mn complexes: the effect of disparate coordination environments on metal-metal interactions and magnetic and redox properties.
A series of homobimetallic phosphinoamide-bridged diiron and dimanganese complexes in which the two metals maintain different coordination environments have been synthesized. Systematic variation of the steric and electronic properties of the phosphinoamide phosphorus and nitrogen substituents leads to structurally different complexes. Reaction of [(i)PrNKPPh(2)] (1) with MCl(2) (M = Mn, Fe) affords the phosphinoamide-bridged bimetallic complexes [Mn((i)PrNPPh(2))(3)Mn((i)PrNPPh(2))] (3) and [Fe((i)PrNPPh(2))(3)Fe((i)PrNPPh(2))] (4). Complexes 3 and 4 are iso-structural, with one metal center preferentially binding to the three amide ligands in a trigonal planar arrangement while the second metal center is ligated by three phosphine donors. A fourth phosphinoamide ligand caps the tetrahedral coordination sphere of the phosphine-ligated metal center. Mössbauer spectroscopy of complex 4 suggests that the metals in these complexes are best described as Fe(II) centers. In contrast, treatment of MnCl(2) or FeI(2) with [MesNKP(i)Pr(2)] (2) leads to the formation of the halide-bridged species [(THF)Mn(μ-Cl)(MesNP(i)Pr(2))(2)Mn(MesNP(i)Pr(2))] (5) and [(THF)Fe(μ-I)(MesNP(i)Pr(2))(2)FeI (7), respectively. Utilization of FeCl(2) in place of FeI(2), however, leads exclusively to the C(3)-symmetric complex [Fe(MesNP(i)Pr(2))(3)FeCl] (6), structurally similar to 4 but with a halide bound to the phosphine-ligated Fe center. The Mössbauer spectrum of 6 is also consistent with high spin Fe(II) centers. Thus, in the case of the [(i)PrNPPh(2)](-) and [MesNP(i)Pr(2)](-) ligands, zwitterionic complexes with the two metals in disparate coordination environments are preferentially formed. In the case of the more electron-rich ligand [(i)PrNP(i)Pr(2)](-), complexes with a 2:1 mixed donor ligand arrangement, in which one of the ligand arms has reversed orientation relative to the previous examples, are formed exclusively when [(i)PrNLiP(i)Pr(2)] (generated in situ) is treated with MCl(2) (M = Mn, Fe): (THF)(3)LiCl[Mn(N(i)PrP(i)Pr(2))(2)(P(i)Pr(2)N(i)Pr)MnCl] (8) and [Fe(N(i)PrP(i)Pr(2))(2)(P(i)Pr(2)N(i)Pr)FeCl] (9). Bimetallic complexes 3-9 have been structurally characterized using X-ray crystallography, revealing Fe-Fe interatomic distances indicative of metal-metal bonding in complexes 6 and 9 (and perhaps 4, to a lesser extent). All of the complexes appear to adopt high spin electron configurations, and magnetic measurements indicate significant antiferromagnetic interactions in Mn(2) complexes 5 and 8 and no discernible magnetic superexchange in Fe(2) complex 4. The redox behavior of complexes 3-9 has also been investigated using cyclic voltammetry, and theoretical investigations (DFT) were performed to gain insight into the metal-metal interactions in these unique asymmetric complexes.


[Mapping of the motor-sensory cortex by functional magnetic resonance tomography in frontoparietal tumors].
The potentialities of functional magnetic resonance imaging (FM-RI) in the preoperative mapping of the motor-sensory cortex of the brain in 24 patients with frontoparietal tumors and 5 healthy volunteers were studied. A good reproducibility of results was achieved while using a simple irritation paradigm as finger flexion-extension. The obtained activation maps were projected to the region of anterior and posterior central gyri and to the central sulcus. Imposition of the maps of motor-sensory cortical activation with routine T1-weighed images allows a surgeon to gain an insight into the mutual location of a tumor and a functionally significant portion of the cortex, by reducing the intraoperative risk of damage to this area. The intraoperative determination of the central sulcus by the evoked potential method in 4 patients confirmed the results obtained after FMRI. The relationship of the obtained activation maps to the presence of venous structures in the area concerned requires further studies on the modes of clarifying the site of functionally significant cortical areas in the brain.


Separation of rare earth elements from mixed-metal feedstocks by micelle enhanced ultrafiltration with sodium dodecyl sulfate.
Micelle enhanced ultrafiltration (MEUF) is a surfactant-based membrane separation process that may be used to separate target ions from mixed metal aqueous solutions, such as leachates of coal ash and other geological wastewaters. The ability of MEUF to separate rare earth elements (REEs) was evaluated using sodium dodecyl sulfate (SDS) as the sorbent in surfactant micelle phase, which was subsequently separated using ultrafiltration, acidification, and ferricyanide precipitation. Separation experiments were performed with a synthetic coal ash leachate feedstock as an example mixed-metal feedstock. Experiments tested the influence of surfactant concentration, pH, and co-existing competitive ions on REE recoveries, and also tested methods for SDS recovery and reuse. Membrane rejection efficiencies of REEs were 97% and 71% respectively for synthetic and real leachate under optimized operating conditions. A two-step process of precipitation with CaCl2 and Na2CO3 following membrane separation was the best for recovering SDS with a yield of 99.7%.


Efficacy of retinal spikes in driving cortical responses.
How does a single retinal ganglion cell (RGC) affect the firing of simple cells in the visual cortex? Although much is known of the functional connections between the retina and the lateral geniculate nucleus (LGN) and between LGN and visual cortex, it is hard to infer the effect of disynaptic connections from retina to visual cortex. Most importantly, there is considerable divergence from retina to LGN, so cortical neurons might be influenced by ganglion cells through multiple feedforward pathways. We recorded simultaneously from ganglion cells in the retina and cortical simple cells in the striate cortex with overlapping receptive fields and evaluated disynaptic connections with cross-correlation analysis. In all disynaptically connected pairs, the retinal receptive field center and overlapping cortical subregion always shared the same sign (either both ON or both OFF). Connected pairs were similar in other respects, such as relative position and timing of their receptive fields, and thus obeyed the same rules of connectivity found previously for retinothalamic and thalamocortical connections. We found that a single RGC directly contributed on average to approximately 3% of the activity of its cortical target. The relative timing of pairs of spikes from the retinal cell affected their efficacy in driving the cortical cell. When two retinal spikes were closely spaced (<10 msec), the second spike was several times more likely to drive the cortical target. The relative magnitude of this disynaptic paired spike enhancement was considerably larger than has been found previously for retinogeniculate and geniculocortical connections. The amplified paired spike enhancement from retina to cortex ensures that signal transmission from retina to cortex is particularly effective when the retina fires a series of closely spaced action potentials.


Comparison of the static structure factor at long wavelengths for a dusty plasma liquid and other liquids.
Especially small values of the static structure factor S(k) at long wavelengths, i.e., small k, were obtained in an analysis of experimental data, for a two-dimensional dusty plasma in its liquid state. For comparison, an analysis of S(k) data was carried out for many previously published experiments with other liquids. The latter analysis indicates that the magnitude of S(k) at small k is typically in a range 0.02-0.13. In contrast, the corresponding value for a dusty plasma liquid was found to be as small as 0.0139. Another basic finding for the dusty plasma liquid is that S(k) at small k generally increases with temperature, with its lowest value, noted above, occurring near the melting point. Simulations were carried out for the dusty plasma liquid, and their results are generally consistent with the experiment. Since a dusty plasma has a soft interparticle interaction, our findings support earlier theoretical suggestions that a useful design strategy for creating materials having exceptionally low values of S(0), so-called hyperuniform materials, is the use of a condensed material composed of particles that interact softly at their periphery.


Physical Confirmation and Comparative Genomics of the Rat Mammary carcinoma susceptibility 3 Quantitative Trait Locus.
Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map rat Mammary carcinoma susceptibility 3 (Mcs3)-a mammary cancer resistance allele previously predicted at Rattus norvegicus chromosome 1 (RNO1). The mammary cancer susceptible Wistar Furth (WF) strain was the recipient, and the mammary cancer resistant Copenhagen (Cop) strain was the RNO1-segment donor for congenics. Inbred WF females averaged 6.3 carcinogen-induced mammary carcinomas per rat. Two WF.Cop congenic strains averaged 2.8 and 3.4 mammary carcinomas per rat, which confirmed Mcs3 as an independently acting allele. Two other WF.Cop congenic strains averaged 6.6 and 8.1 mammary carcinomas per rat, and, thus, did not contain Mcs3 Rat Mcs3 was delimited to 27.8 Mb of RNO1 from rs8149408 to rs105131702 (RNO1:143700228-171517317 of RGSC 6.0/rn6). Human genetic variants with p values for association to breast cancer risk below 10-7 had not been reported for Mcs3 orthologous loci; however, human variants located in Mcs3-orthologous regions with potential association to risk (10-7 < p < 10-3) were listed in some population-based studies. Further, rat Mcs3 contains sequence orthologous to human 11q13/14-a region frequently amplified in female breast cancer. We conclude that Mcs3 is an independently acting mammary carcinoma resistance allele. Human population-based, genome-targeted association studies interrogating Mcs3 orthologous loci may yield novel breast cancer risk associated variants and genes.


Exercise Intolerance, Mortality, and Organ System Impairment in Adult Survivors of Childhood Cancer.
Exercise intolerance, associated with heart failure and death in general populations, is not well studied in survivors of childhood cancer. We examined prevalence of exercise intolerance in survivors exposed or not to cardiotoxic therapy, and associations among organ system function, exercise intolerance, and mortality. Participants consisted of 1,041 people who had survived cancer ≥ 10 years (and had or did not have exposure to anthracyclines and/or chest-directed radiation) and 285 control subjects. Exercise intolerance was defined as peak oxygen uptake < 85% predicted from maximal cardiopulmonary exercise testing; organ functions were ascertained with imaging or clinical testing. Multivariable regression of the data was performed to compare exercise capacity between survivors exposed or unexposed to cardiotoxic therapy and control subjects, and to evaluate associations between treatment and organ function, and organ function and exercise intolerance. Propensity score methods in time-to-event analyses evaluated associations between exercise intolerance and mortality. Survivors (mean age ± standard deviation [SD], 35.6 ± 8.8 years) had lower mean (± SD) peak oxygen uptake (exposed: 25.74 ± 8.36 mL/kg/min; unexposed: 26.82 ± 8.36 mL/kg/min) than did control subjects (32.69 ± 7.75 mL/kg/min; P for all < .001). Exercise intolerance was present in 63.8% (95% CI, 62.0% to 65.8%) of exposed survivors, 55.7% (95% CI, 53.2% to 58.2%) of unexposed survivors, and 26.3% (95% CI, 24.0% to 28.3%) of control subjects, and was associated with mortality (hazard ratio, 3.9; 95% CI, 1.09 to 14.14). Global longitudinal strain (odds ratio [OR], 1.71; 95% CI, 1.11 to 2.63), chronotropic incompetence (OR, 3.58; 95% CI, 1.75 to 7.31); forced expiratory volume in 1 second < 80% (OR, 2.59; 95% CI, 1.65 to 4.09), and 1 SD decrease in quadriceps strength (OR, 1.49; 95% CI, 1.23 to 1.82) were associated with exercise intolerance. Ejection fraction < 53% was not associated with exercise intolerance. Exercise intolerance is prevalent among childhood cancer survivors and associated with all-cause mortality. Treatment-related cardiac (detected by global longitudinal strain), autonomic, pulmonary, and muscular impairments increased risk. Survivors with impairments may require referral to trained specialists to learn to accommodate specific deficits when engaging in exercise.


Proteinuria can predict prognosis after liver transplantation.
Proteinuria is a manifestation of renal dysfunction and it has been demonstrated to be a significant prognostic factor in various clinical situations. The study was designed to analyze prognosis of patients receiving liver transplantation as well as to determine predictive performance of perioperative proteinuria. We retrospectively reviewed data of patients who had received a liver transplant in a medical center between 2002 and 2010. Demographic information and clinical characteristic parameters were recorded on the day of intensive care unit admission before operation and on postoperative days 1, 7, and 14. Among a total of 323 patients, in-hospital mortality and 90-day mortality rates were 13.0 % (42/323) and 14.2 % (46/323), respectively. Patients with proteinuria on admission had higher rates of acute kidney injury (26.8 % vs. 8.8 %, p < 0.001), severe infection episodes (48.8 % vs. 30.7 %, p = 0.023), hospital death (31.1 % vs. 10.1 %, p < 0.001), and 90-day mortality (37.7 % vs. 10.9 %, p < 0.001). Multivariate analysis showed that proteinuria on admission and Sequential Organ Failure Assessment (SOFA) score were independent predictors of in-hospital mortality. The discriminatory ability of proteinuria plus SOFA was even better than that of SOFA alone, especially on postoperative day 1. The presence of proteinuria before liver transplantation is supposed to be recognized as a negative predictor for in-hospital survival. Moreover, the presence of proteinuria after liver transplantation can assist in the early prediction of poor short-term prognosis for patients receiving liver transplantation.


Pharmacological modulation of caspase-8 in thymus-related medical conditions.
The thymus is a lymphoid organ that governs the development of a diverse T-cell repertoire capable of defending against nonself-antigens and avoiding autoimmunity. However, the thymus can also succumb to different diseases. Hypertrophic diseases, such as thymomas, are typically associated with impairment of negative selection, which leads to autoimmune disease, or disruption of positive selection, which results in immunodeficiency. Hypotrophic diseases of the thymus can manifest during acute infections, cancer, allogeneic bone marrow transplantation, or with aging. This condition leads to decreased immune function and can be treated by either replacing lost thymic tissue or by preventing thymic tissue death. Studies have demonstrated the critical role of caspase-8 in regulating apoptosis in the thymus. In this review, we discuss how pharmacological activation and inhibition of caspase-8 can be used to treat hypertrophic and hypotrophic diseases of the thymus, respectively, to improve its function.


Climbing social media in medicine's hierarchy of needs.
The social media and medicine landscape is evolving rapidly. Early research, social media policies, and educational efforts focused on risk avoidance, while more current efforts have encouraged reflection and explored opportunities. This trajectory has affirmed physicians' professional commitment to maintaining public trust in the face of new challenges in the digital age. In this Commentary, the authors propose viewing physicians' social media use as a hierarchy of needs, similar to Maslow's psychological theory which posits that more basic levels of needs must be met before higher, aspirational levels can be fully attained. The three levels in the social media in medicine's hierarchy of needs are Security, Reflection, and Discovery. Critical to this model is respecting the essential need for Security in order to move towards Reflection and into Discovery. The social media in medicine hierarchy of needs pyramid rests on a foundation of Public Trust. How physicians as a profession have responded to past--and continue to respond to present and future--social media challenges to professionalism reveals what matters most: maintaining public trust and honoring the physicians' contract with society. A victory for online professionalism would be providing trainees with the tools and guidance needed to ascend to Discovery, while ensuring that their basic social media needs are first met. To do this, physician educators need to continue increasing trainees' awareness through designing relevant curricula, encouraging reflection, and providing positive role modeling and effective mentorship.


The acute inflammatory response to copper(II)-doped biphasic calcium phosphates.
Infection and inflammation are two key features to consider to avoid septic or aseptic loosening of bone-implanted biomaterials. In this context, various approaches to fine-tune the biomaterial's properties have been studied in order to modulate the crosstalk between immune and skeletal cells. Cation-doping strategies for tuning of calcium phosphates properties has been evidenced as a promising way to control the biomaterial-induced inflammatory process, and thus improving their osteoimmunomodulatory properties. Copper(II) ions are recognized for their antibacterial potential, but the literature on their impact on particulate material-induced acute inflammation is scarce. We synthesized copper(II) ions-doped biphasic calcium phosphate (BCP), intended to exhibit osteoimmunomodulatory properties. We addressed in vitro, for the first time, the inflammatory response of human primary polymorphonuclear neutrophils (PMNs) to copper(II) ions-doped or undoped (BCP) powders, synthesized by an original and robust wet method, in the presence or absence of LPS as a costimulant to mimic an infectious environment. ELISA and zymography allowed us to evidence, in vitro, a specific increase in IL-8 and GRO-α secretion but not MIP-1β, TNF-α, or MMP-9, by PMNs. To assess in vivo relevance of these findings, we used a mouse air pouch model. Thanks to flow cytometry analysis, we highlighted an increased PMN recruitment with the copper(II) ions-doped samples compared to undoped samples. The immunomodulatory effect of copper(II) ions-doped BCP powders and the consequent induced moderate level of inflammation may promote bacterial clearance by PMNs in addition to the antimicrobial potential of the material. Copper(II) doping provides new insights into calcium phosphate (CaP)-based biomaterials for prosthesis coating or bone reconstruction by effectively modulating the inflammatory environment.


[Current use of electronic cigarettes among never smoker high school students].
To test whether electronic cigarettes use among secondary school students in Spain is associated with initiating nicotine use. Secondary analysis of the ESTUDES 2019 survey, a cross-sectional study conducted on a representative sample of students aged 14-18 years and selected students who had never smoked (n=16,705). We computed the prevalence and estimated the factors associated with current electronic cigarettes use (at least once in the month before the interview), with and without nicotine. The prevalence of current electronic cigarettes use among students who have never smoked is 2.5% (95% confidence interval [95%CI]: 2.2-2.9). 0.1% (95%CI: 0.08-0.2) declared using liquids with nicotine at least sometimes and 2.4% (95%CI: 2.1-2.8) using liquids always without nicotine. Being male and under 17 years of age, reporting binge drinking behavior, and having regular friends who use cannabis, increases the probability of current use of electronic cigarettes. The latter two variables seem to act as contextual variables associated with electronic cigarettes use. The percentage of Spanish never smoker students who currently use electronic cigarettes is lower than in neighboring countries, except for the United Kingdom. Only one in every 1000 Spanish students between 14 and 18 years old who have never smoked initiates the current use of nicotine with an electronic cigarette. However, we must monitor the evolution of this indicator.


Health Professionals' Readiness and Its Associated Factors to Implement Electronic Medical Record System in Four Selected Primary Hospitals in Ethiopia.
Incorporating electronic medical record systems (EMRs) into the healthcare system is not only about modernizing the health system, but is about saving lives by facilitating communication and practicing evidence-based decision. Globally, more than 50% of EMR projects fail before they reach their target. Even though EMRs are an essential tool for health care, their adoption and utilization remains low in developing countries including Ethiopia. The aim of this study was to determine health professionals' readiness and associated factors toward the implementation of EMRs in four selected primary hospitals in Ethiopia. An institutionbased cross-sectional study supplemented with a qualitative approach was conducted on 414 health professionals from March 2 to May 5, 2018 in four selected primary hospitals in Ethiopia. A self-administered questionnaire was used to collect the quantitative data and in-depth interviews were employed for the qualitative data. The data were analyzed using SPSS version 20 software. Descriptive statistics, bivariable, and multivariable logistic regression analyses were done. An adjusted odds ratio (AOR) with 95% CI was used to determine the association between the determinants and the outcome variable. More than half (258; 62.3%) of health professionals were ready to use the electronic medical recording system. EMR knowledge (AOR = 2.64; 95% CI: [1.62, 4.29]), attitude (AOR = 1.63; 95% CI: [1.01, 2.63]), computer literacy (AOR = 3.30; 95% CI: [2.05, 5.31]), and EMR training (AOR = 3.63, ;5% CI: [1.69, 5.80]) were significantly associated with EMR readiness. In general, the overall readiness of health professionals for EMR implementation was found to be low. Comprehensive packages of capacity-building are crucial to raise the level of knowledge, attitude, and computer skill among health workers.


Fabrication of patterned multicomponent protein gradients and gradient arrays using microfluidic depletion.
We demonstrate that depletion effects in the fluids used to fill a poly(dimethylsiloxane) microfluidic device can be used in conjunction with its design rules to generate patterned protein gradients. The linear portions of these structures can be designed to present gradients of bound protein coverage-varying from near-saturation to effectively zero-over distances ranging from a few hundred micrometers to more than 1 cm by design. Such patterns can be developed in a simple, single-channel form as well as in a multichannel gradient array of more complex design. The patterning protocols also support the use of multiple protein sources, and we demonstrate an assembly process mediated by a protein that inhibits adsorption to generate a gradient array in pixel form. We describe examples of multiple protein gradient patterns along with simple immunoassays to illustrate the scope of the methodology, the activity of the patterned proteins, and their recognition in gradient form on a surface. These gradients should prove useful to studies in biosensor and bioassay development and as substrates for cell culture to study growth and motility.


N-ethylmaleimide effects on synaptic transmission in frog sympathetic ganglion.
In the isolated bullfrog sympathetic ganglion N-ethylmaleimide (NEM) produced time- and concentration-dependent effects that were irreversible by bathing in drug-free Ringer's solution. Initially, synaptic transmission was facilitated; this was evident as augmented action potential amplitude, repetitive synaptic firing and partial reversal of low [Ca++] transmission failure. Subsequently, transmission was depressed progressively to the point of complete block. Conduction in B and C fiber groups of the preganglionic nerve trunk was also blocked by NEM, without initial facilitation, but at a rate slower than the block of synaptic transmission. NEM had no effect on the amplitude of ganglion cell membrane depolarization produced by acetylcholine, suggesting that its effects were not exerted on postsynaptic nicotinic receptors. None of the effects of NEM were produced by the saturated analog N-ethylsuccinimide. Facilitatory effects of NEM may be attributable to inhibition of Na+ inactivation, or to increased entry of Ca++, at presynaptic nerve terminals. Because the late depressant stages of NEM action involve multiple sites (presynaptic, postsynaptic and axonal), the clarification of possible mechanisms will be a difficult experimental problem.


Alzheimer's Disease Is Associated with Increased Network Assortativity: Evidence from Metabolic Connectivity.
Introduction: Unraveling the network pathobiology in neurodegenerative disorders is a popular and promising field in research. We use a relatively newer network measure of assortativity in metabolic connectivity to understand network differences in patients with Alzheimer's Disease (AD), compared with those with mild cognitive impairment (MCI). Methods: Eighty-three demographically matched patients with dementia (56 AD and 27 MCI) who underwent positron emission tomography-magnetic resonance imaging (PET-MRI) study were recruited for this exploratory study. Global and nodal network measures obtained using the BRain Analysis using graPH theory toolbox were used to derive group-level differences (corrected p < 0.05). The methods were validated in age, and gender-matched 23 cognitively normal, 25 MCI, and 53 AD patients from the publicly available Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Regions that revealed significant differences were correlated with the Addenbrooke's Cognitive Examination-III (ACE-III) scores. Results: Patients with AD revealed significantly increased global assortativity compared with the MCI group. In addition, they also revealed increased modularity and decreased participation coefficient. These findings were validated in the ADNI data. We also found that the regional standard uptake values of the right superior parietal and left superior temporal lobes were proportional to the ACE-III memory subdomain scores. Conclusion: Global errors associated with network assortativity are found in patients with AD, making the networks more regular and less resilient. Since the regional measures of these network errors were proportional to memory deficits, these measures could be useful in understanding the network pathobiology in AD.


Cyclosporine-induced immune suppression alters establishment of HTLV-1 infection in a rabbit model.
Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia and several lymphocyte-mediated inflammatory diseases. Persistent HTLV-1 infection is determined by a balance between host immune responses and virus spread. Immunomodulatory therapy involving HTLV-1-infected patients occurs in a variety of clinical settings. Knowledge of how these treatments influence host-virus relationships is not understood. In this study, we examined the effects of cyclosporine A (CsA)-induced immune suppression during early infection of HTLV-1. Twenty-four New Zealand white rabbits were split into 4 groups. Three groups were treated with either 10 or 20 mg/kg CsA or saline before infection. The fourth group was treated with 20 mg/kg CsA 1 week after infection. Immune suppression, plasma CsA concentration, ex vivo lymphocyte HTLV-1 p19 production, anti-HTLV-1 serologic responses, and proviral load levels were measured during infection. Our data indicated that CsA treatment before HTLV-1 infection enhanced early viral expression compared with untreated HTLV-1-infected rabbits, and altered long-term viral expression parameters. However, CsA treatment 1 week after infection diminished HTLV-1 expression throughout the 10-week study course. Collectively, these data indicate immunologic control is a key determinant of early HTLV-1 spread and have important implications for therapeutic intervention during HTLV-1-associated diseases.


Partial dentures incorporating onlays in the treatment of a complete anterior overbite.
Incorporating onlays onto partial dentures, that is occlusal or incisal rests extended to cover the entire occlusal or incisal edges, can be used successfully to treat overbite. This case study describes its use in a patient with a complete anterior overbite together with severe tilting of some of the maxillary molar teeth. Early tooth loss, which had not been restored, was probably a significant aetiological factor in the patient's condition.


Timing Training in Female Soccer Players: Effects on Skilled Movement Performance and Brain Responses.
Although trainers and athletes consider "good timing skills" critical for optimal sport performance, little is known in regard to how sport-specific skills may benefit from timing training. Accordingly, this study investigated the effects of timing training on soccer skill performance and the associated changes in functional brain response in elite- and sub-elite female soccer players. Twenty-five players (mean age 19.5 years; active in the highest or second highest divisions in Sweden), were randomly assigned to either an experimental- or a control group. The experimental group (n = 12) was subjected to a 4-week program (12 sessions) of synchronized metronome training (SMT). We evaluated effects on accuracy and variability in a soccer cross-pass task. The associated brain response was captured by functional magnetic resonance imaging (fMRI) while watching videos with soccer-specific actions. SMT improved soccer cross-pass performance, with a significant increase in outcome accuracy, combined with a decrease in outcome variability. SMT further induced changes in the underlying brain response associated with observing a highly familiar soccer-specific action, denoted as decreased activation in the cerebellum post SMT. Finally, decreased cerebellar activation was associated with improved cross-pass performance and sensorimotor synchronization. These findings suggest a more efficient neural recruitment during action observation after SMT. To our knowledge, this is the first controlled study providing behavioral and neurophysiological evidence that timing training may positively influence soccer-skill, while strengthening the action-perception coupling via enhanced sensorimotor synchronization abilities, and thus influencing the underlying brain responses.


A Comparison of Critical Speed and Critical Power in Runners Using Stryd Running Power.
Although running traditionally relies on critical speed (CS) as an indicator of critical intensity, portable inertial measurement units offer a potential solution for estimating running mechanical power to assess critical power (CP) in runners. The purpose of this study was to determine whether CS and CP differ when assessed using the Stryd device, a portable inertial measurement unit, and if 2 running bouts are sufficient to determine CS and CP. On an outdoor running track, 10 trained runners (V˙O2max, 59.0 [4.2] mL·kg-1·min-1) performed 3 running time trials (TT) between 1200 and 4400 m on separate days. CS and CP were derived from 2-parameter hyperbolic speed-time and power-time models, respectively, using 2 (CS2TT and CP2TT) and 3 (CS3TT and CP3TT) TTs. Subsequently, runners performed constant-intensity running for 800 m at their calculated CS3TT and CP3TT. Running at the calculated CS3TT speed (3.88 [0.44] m·s-1) elicited an average Stryd running power (271 [28] W) not different from the calculated CP3TT (270 [28]; P = .940; d = 0.02), with excellent agreement between the 2 values (intraclass correlation coefficient = .980). The CS2TT (3.97 [0.42] m·s-1) was not higher than CS3TT (3.89 [0.44] m·s-1; P = .178; d = 0.46); however, CP2TT (278 [29] W) was greater than CP3TT (P = .041; d = 0.75). The running intensities at CS and CP were similar, supporting the use of running power (Stryd) as a metric of aerobic fitness and exercise prescription, and 2 trials provided a reasonable, albeit higher, estimate of CS and CP.


Large scale homing in honeybees.
Honeybee foragers frequently fly several kilometres to and from vital resources, and communicate those locations to their nest mates by a symbolic dance language. Research has shown that they achieve this feat by memorizing landmarks and the skyline panorama, using the sun and polarized skylight as compasses and by integrating their outbound flight paths. In order to investigate the capacity of the honeybees' homing abilities, we artificially displaced foragers to novel release spots at various distances up to 13 km in the four cardinal directions. Returning bees were individually registered by a radio frequency identification (RFID) system at the hive entrance. We found that homing rate, homing speed and the maximum homing distance depend on the release direction. Bees released in the east were more likely to find their way back home, and returned faster than bees released in any other direction, due to the familiarity of global landmarks seen from the hive. Our findings suggest that such large scale homing is facilitated by global landmarks acting as beacons, and possibly the entire skyline panorama.


CD8+ T-cell Immune Surveillance against a Tumor Antigen Encoded by the Oncogenic Long Noncoding RNA PVT1.
CD8+ T cells recognize peptides displayed by HLA class I molecules on cell surfaces, monitoring pathologic conditions such as cancer. Advances in proteogenomic analysis of HLA ligandomes have demonstrated that cells present a subset of cryptic peptides derived from noncoding regions of the genome; however, the roles of cryptic HLA ligands in tumor immunity remain unknown. In the current study, we comprehensively and quantitatively investigated the HLA class I ligandome of a set of human colorectal cancer and matched normal tissues, showing that cryptic translation products accounted for approximately 5% of the HLA class I ligandome. We also found that a peptide encoded by the long noncoding RNA (lncRNA) PVT1 was predominantly enriched in multiple colorectal cancer tissues. The PVT1 gene is located downstream of the MYC gene in the genome and is aberrantly overexpressed across a variety of cancers, reflecting its oncogenic property. The PVT1 peptide was recognized by patient CD8+ tumor-infiltrating lymphocytes, as well as peripheral blood mononuclear cells, suggesting the presence of patient immune surveillance. Our findings show that peptides can be translated from lncRNAs and presented by HLA class I and that cancer patient T cells are capable of sensing aberrations in noncoding regions of the genome.


Assessment of potassium current in Royan B(1) stem cell derived cardiomyocytes by patch-clamp technique.
Embryonic stem cells are capable of differentiating to variety of cell tissues including cardiomyocytes. This developmental change is accompanied with a great deal of ion channel expression and functions. Mouse stem cell derived cardiomyocytes were prepared and separated to yield isolated single cell suspension for cell current recording. In the present study some properties of the K(+)-current in Royan B(1) stem cell derived cardiomyocytes were investigated using whole cell patch-clamp technique. When the holding potential was - 60 mV, in some cells a major outward current was elicited by square depolarizing pulses from -60 mV to +50 mV. This outward current was sustained for the duration of 300 ms test pulse. The sustained outward K(+) current was inhibited by tetraethylammonium (10 mM) indicating the activity of Ca(2+) activated K(+) channel in these cells. In some of the cells with 0.2 mM 3,ethylene glycol-bis (β-aminoethyl ether) N,N,N(`),N(`)-tetraacetic acid in the pipette, only a very small outward current was recorded which suggests that in these cells the voltage activated K(+) channels is either absent or if existed it is not fully functional. Other cells were in far between, indicating that voltage activated K(+) channels are developing in these cells but it is not yet fully functional. In conclusion, we have identified functional large conductance Ca(2+) activated K(+) channel in Royan B(1) stem cell derived cardiomyocytes.


[The course of flavivirus infections in mice in the presence of the graft versus host reaction under conditions of 2-way incompatibility].
The graft versus host reaction (GVHR) under conditions of two-way incompatibility was shown to increase average longevity (AL) of mice with experimental tick-borne encephalitis (TBE) and to activate asymptomatic infection caused by Langat virus. Experiments with TBE virus demonstrated participation of viable T lymphocytes in GVHR. Inhibition of function of both humoral and cellular immunity was shown to occur in GVHR. The assumption that the increase in the average longevity in TBE is associated with the inhibition of the damaging function of cellular immunity is experimentally substantiated.


Missing methane emissions from urban sewer networks.
Methane emissions from sewer networks are an important source of anthropogenic greenhouse gases (GHGs) but are not currently reflected in the national GHG inventory. We found significant CH4 emissions of approximately 573 [395-831] CH4 t y-1 from sewer networks in the old residential and commercial areas of Seoul (Gwanak district) using an electric vehicle-based atmospheric GHG monitoring platform. The majority of ethane-to-methane ratios (<0.005) from the observations further suggest that distinctive CH4 emissions from sewer networks are likely related to microbial activity rather than to simple natural gas leakage. Because over 90% of the sewer network in Seoul is a gravity drain type of combined sewer network, where both wastewater and stormwater flow through the same pipes, resulting in the generation of methane emissions from the microbial activity and the manholes and rain gutters, which are directly connected to the combined sewer networks are major sources of atmospheric methane emissions. This study suggests that appropriate treatment of sewer networks can mitigate missing methane emissions in cities that were not originally included in GHG inventory of South Korea.


A decision tree system for finding genes in DNA.
MORGAN is an integrated system for finding genes in vertebrate DNA sequences. MORGAN uses a variety of techniques to accomplish this task, the most distinctive of which is a decision tree classifier. The decision tree system is combined with new methods for identifying start codons, donor sites, and acceptor sites, and these are brought together in a frame-sensitive dynamic programming algorithm that finds the optimal segmentation of a DNA sequence into coding and noncoding regions (exons and introns). The optimal segmentation is dependent on a separate scoring function that takes a subsequence and assigns to it a score reflecting the probability that the sequence is an exon. The scoring functions in MORGAN are sets of decision trees that are combined to give a probability estimate. Experimental results on a database of 570 vertebrate DNA sequences show that MORGAN has excellent performance by many different measures. On a separate test set, it achieves an overall accuracy of 95 %, with a correlation coefficient of 0.78, and a sensitivity and specificity for coding bases of 83 % and 79%. In addition, MORGAN identifies 58% of coding exons exactly; i.e., both the beginning and end of the coding regions are predicted correctly. This paper describes the MORGAN system, including its decision tree routines and the algorithms for site recognition, and its performance on a benchmark database of vertebrate DNA.


Biopsy of the breast for mammographically detected lesions.
We prospectively studied 718 women who underwent biopsy of the breast for suspicious, mammographically detected mammary lesions in an attempt to identify key clinical risk factors, as well as roentgenographic characteristics associated with the appearance of early carcinoma of the breast. Patients with a benign outcome had an average age of 55 years versus 63 years for patients with carcinoma of the breast. Seventy-six per cent of these patients had no previous history of mammary problems, 20 per cent had a positive family history for carcinoma of the breast, 58 per cent were premenopausal and 21 per cent had used birth control pills. Except for age (p less than 0.001), the distribution of clinical risk factors was equal among patients with benign or malignant outcomes. Suspicious mammographic findings included mass lesions (53 per cent), calcifications (36 per cent) and the association of both (11 per cent). The predominant Wolfe pattern on mammography was P1 (36 per cent). No relationship was observed between Wolfe pattern and malignant conditions. In this group of patients, mammography was poorly specific; however, the positive predictive value increased with age and is related to the age-specific prevalence of carcinoma of the breast. Eight hundred and twenty-five lesions were removed. Twenty-five per cent (n = 203) of the specimens taken at biopsy contained carcinoma. Stellate mass lesions were highly suggestive of a malignant growth (p less than 0.0001). No relationship between the size of the suspicious mammographic mass and the malignant lesion was observed. A marked correlation (chi-square test with Yate's correction) was observed between malignant tumor and lesions with a linear or branching pattern, more than 15 calcifications, or small sized calcifications. The presence of a mass with calcifications was associated with carcinoma in 34 per cent. The incidence of invasive carcinoma was much higher for mass lesions (81 per cent) than for suspicious calcifications (56 per cent) (p less than 0.0001).


Selective adherence as a determinant of the host tropisms of certain indigenous and pathogenic bacteria.
The relationship between the selective abilities of bacteria to adhere and their predilections for colonizing different mammalian hosts was investigated by using bacteria indigenous to the tongue dorsum of humans and rats as models. Streptococcus salivarius and S. sanguis averaged 22.6 and 2.8%, respectively, of the cultivable bacteria recovered from swab samples of the tonges of five humans, but these organisms were not indigenous on the tongues of rats (Charles River strain). S. faecalis and serum-requiring diphtheroids were consistently prominant on the tongues of rats, but they were not detected on the tongues of the humans examined. The ability of these organisms to adhere to the tongue surface of the hosts was compared by introducing mixtures of streptomycin-resistant strains into the mouths of human volunteers and rats. S. salivarius adhered in higher proportions to the dorsal tongue surface of humans than did strains of S. faecalis and the serum-requiring diphtheroid. S. sanguis also adhered to human tongues better than the serum-requiring diphtheroid. However, S. faecalis and the serum-requiring diphtheroid sorbed in higher proportions to the tongues of rats. In an in vivo assay, human strains of S. pyogenes and S. salivarius attached in higher numbers to buccal epithelial cells derived from humans than to those obtained from rats, whereas the reverse was observed with a serum-requiring diphtheroid derived from rats. Collectively, these studies show that bacteria sorb with a high degree of specificity to the tissues of different mammalian hosts, and the relative adherence of the organisms studied correlated with their natural host tropisms. The selective adherence of S. salvarius and S. faecalis was similar to the tongues of conventional and germ-free rats, suggesting that the presence of an indigenous bacterial flora did not significantly influence their attachment selectivity. Moreover, the ability of these organisms to colonize the tongues of gnotobiotic rats lacking an indigenous flora paralleled their adherence selectivity. Direct scanning microscopic observations indicated that the tongue dorsum of conventional rats is highly papillated but contains relatively sparse bacterial populations. Indigenous organisms colonized the bases of papillae on the anterior tip and lateral edges of the tongue as discrete microcolonies, but bacteria were rarely observed on other papillae. This localized and restricted pattern of colonization and the spatial distribution of the microcolonies of indigenous bacteria present also suggest that antagonistic interactions are unlikely to account for the bacterial tropisms observed for colonization of the tongues of rats.


The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment.
Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2-3years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment. 6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase (TPMT), nudix hydrolase 15 (NUDT15), and potentially inosine triphosphatase (ITPA), which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1) and dihydrofolate reductase (DHFR). Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1 (SLC19A1) and thymidylate synthetase (TYMS), but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.