A fast U-D factorization-based learning algorithm with applications to nonlinear system modeling and identification.
A fast learning algorithm for training multilayer feedforward neural networks (FNN's) by using a fading memory extended Kalman filter (FMEKF) is presented first, along with a technique using a self-adjusting time-varying forgetting factor. Then a U-D factorization-based FMEKF is proposed to further improve the learning rate and accuracy of the FNN. In comparison with the backpropagation (BP) and existing EKF-based learning algorithms, the proposed U-D factorization-based FMEKF algorithm provides much more accurate learning results, using fewer hidden nodes. It has improved convergence rate and numerical stability (robustness). In addition, it is less sensitive to start-up parameters (e.g., initial weights and covariance matrix) and the randomness in the observed data. It also has good generalization ability and needs less training time to achieve a specified learning accuracy. Simulation results in modeling and identification of nonlinear dynamic systems are given to show the effectiveness and efficiency of the proposed algorithm.


Interaction of the dopamine D2 receptor agonist quinpirole with sympathetic vasomotor tone and the central action of rilmenidine in conscious rabbits.
Previous studies in conscious rats have shown that systemic administration of the dopamine D2 receptor agonist quinpirole causes a centrally-mediated increase in blood pressure which is associated with increased plasma levels of noradrenaline and adrenaline. In addition, treatment with quinpirole caused a marked inhibition of the antihypertensive effect of centrally-acting sympatho-inhibitory drugs such as clonidine, rilmenidine and alpha-methyldopa, suggesting an interaction at the level of sympathetic vasomotor tone. The main aim of the present study was investigate in conscious rabbits the effect of quinpirole on renal sympathetic nerve activity. In addition, we studied the effect of pretreatment with quinpirole on responses to additional quinpirole injections or rilmenidine treatment. Quinpirole treatment caused a prolonged dose-dependent increase in blood pressure and heart rate. Additional injection of quinpirole, 30 min after the first treatment, caused a significantly smaller pressor response (7+/-2 vs. 17+/-2 mm Hg). Injection of rilmenidine caused a larger decrease in blood pressure in rabbits which had been pretreated with quinpirole than in controls (-28+/-3 vs. -14+/-3 mm Hg). Total renal sympathetic nerve activity was markedly increased by quinpirole treatment (3.5-fold), an effect which could be attributed to both increased amplitude and increased frequency of the renal nerve signal. After a second injection of quinpirole, 30 min after the first treatment, only total renal sympathetic nerve activity and amplitude were increased and the effects were reduced. These results show marked actions of quinpirole on renal sympathetic nerve activity in conscious rabbits. However, the previously described apparent desensitisation to the antihypertensive effect of rilmenidine could not be observed in rabbits, suggesting marked species differences in the mechanism and site of action of rilmenidine.


Overall survival analysis of adjuvant radiation versus observation in stage I testicular seminoma: a surveillance, epidemiology, and end results (SEER) analysis.
The standard adjuvant treatment for men with stage I testicular seminoma remains controversial within the literature. We analyzed survival rates in men with stage I seminoma who underwent adjuvant radiation therapy (RT) or observation (OB) after orchiectomy. Data were obtained from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute from 1973 to 2003. The primary end points were overall survival (OS) and cause-specific survival (CSS). Multivariate Cox regression models were used to study the significance of clinical variables: age at diagnosis, laterality of primary disease, race, and radiation group. Of 6764 patients eligible for analysis, 5265 were treated with RT and 1499 with OB. After a median follow-up of 7.6 years, the 5-, 10-, and 20-year OS rates for the RT versus OB were 97.9 versus 95.0, 94.8 versus 92.2, and 83.5 versus 84.1 (P=0.0047), respectively. The CSS rates for the same time periods were 99.6 versus 98.7, 99.4 versus 98.7, and 99.2 versus 98.7 (P=0.0015), respectively. Adjuvant RT was associated with improved CSS on multivariate analysis with hazard ratio of 0.37 (confidence interval, 0.20-0.70; P=0.0023). Within this large US population analysis, adjuvant RT was associated with improved OS and CSS compared with OB for men with stage I testicular seminoma. Further studies are needed to determine whether modern RT techniques and field-size reductions may lead to greater improvements in the therapeutic ratio, in light of the trend toward chemotherapy as primary treatment.


[Prevention of epilepsy].
To review the preventive and prophylactic aspects of epilepsy. The description of the prevention of the causes of epilepsy includes the measures to prevent epilepsy and epileptic seizures. The concept of antiepileptogenesis is discussed according to the available information about the role that both the classic and new antiepileptic drugs (AEDs) play in this process. Neuroprotection is discussed in the context of the mechanisms of action of the AEDs and of the mechanisms of neuronal lesion produced by the causes of epilepsy or by the seizures themselves. Among the new therapeutic modalities the current knowledge about the vagus nerve stimulator and the surgical treatment is summarized. The potential future therapeutic modalities include alternative medicine, pharmacologic treatment of the epileptogenic focus, genetic treatment and vaccination. The first step in preventing epilepsy is to avoid the causes or the risk factors. Some classic AEDs have demonstrated to be effective in the prophylaxis of provoked seizures (acute, symptomatic) but not of unprovoked seizures (epileptic). The best knowledge of the pathogenesis and the molecular and biological basis of epileptogenesis secondary to lesional causes, suggest that antioxidant and neuroprotective agents, including the new AEDs, may prevent epilepsy. There is a need to design studies with the goal of demonstrating their antiepileptogenic and/or neuroprotective activity at different ages in life. New and future therapeutic modalities may offer additional preventive options.


Strength training versus robot-assisted gait training after incomplete spinal cord injury: a randomized pilot study in patients depending on walking assistance.
Task-specific locomotor training has been promoted to improve walking-related outcome after incomplete spinal cord injury (iSCI). However, there is also evidence that lower extremity strength training might lead to such improvements. The aim of this randomized cross-over pilot study was to compare changes in a broad spectrum of walking-related outcome measures and pain between robot-assisted gait training (RAGT) and strength training in patients with chronic iSCI, who depended on walking assistance. We hypothesized that task-specific locomotor training would result in better improvements compared to strength training. Nine participants with a chronic iSCI were randomized to group 1 or 2. Group 1 received 16 sessions of RAGT (45 min each) within 4 weeks followed by 16 sessions of strength training (45 min each) within 4 weeks. Group 2 received the same interventions in reversed order. Main outcome measures were the 10 m Walk Test (10MWT) at preferred and maximal speed. Furthermore, we assessed several measures such as walking speed under different conditions, balance, strength, and 2 questionnaires that evaluate risk of falling and pain. Data were collected at baseline, between interventions after 4 weeks, directly after the interventions and at follow-up 6 months after the interventions. Pain was assessed repeatedly throughout the study. There were no significant differences in changes in scores between the 2 interventions, except for maximal walking speed (10MWT), which improved significantly more after strength training than after RAGT. Pain reduced after both interventions. In patients with chronic iSCI dependent on walking assistance, RAGT was not more effective in improving walking-related outcome compared to lower extremity strength training. However, the low sample size limits generalizability and precision of data interpretation. This study was registered at Clinicaltrials.gov (NCT01087918).


Effects of chlorobutanol and bradykinin on myocardial excitation.
The negative inotropic effect of a commonly used formulation of bradykinin (Sandoz BRS-640) was found to be due to chlorobutanol, a constituent of the preparation. Solutions containing up to 100 mug of crystalline bradykinin/ml had no effect on tension or action-potential shape. Chlorobutanol (500 mug/ml) caused a 30% decrease in contraction amplitude and a 20% increase in action-potential duration. Chlorobutanol lowered conduction velocity and induced conduction failure and automaticity within isolated ventricular muscle strips. Chlorobutanol affected neither positive nor negative treppe. We conclude that bradykinin has no direct action on toad, frog, or rat myocardium. However, chlorobutanol does have direct effects on myocardial cells, acting on the cell membrane and decreasing isometric tension produced by the heart.


Near-fatal asthma: a population-based study of risk factors.
The study of near-fatal asthma (NFA) may provide a means to further our understanding of fatal asthma. Studies of NFA often are derived from a single ICU rather than from a defined population. We therefore aimed to identify factors distinguishing NFA patients (cases) from those persons treated in an emergency department (ED) [ED control subjects] and in the community (community control subjects [CCs]). This was a population-based case-control study conducted over 20 months of 45 NFA patients (age range, 5 to 50 years), 197 ED control subjects treated in an ED, and 303 CCs, all of whom were residents of Alberta. The age distribution was similar between NFA patients and control subjects, with the majority being < 22 years of age (NFA patients, 68.9%; ED control subjects, 71.3%; CCs, 60.7%). Those patients with NFA were significantly more likely to have received a diagnosis before 5 years of age (66.6%), compared to ED control subjects (39.6%) and CCs (28.7%). The NFA group was significantly more likely to report moderate-to-severe disease and more frequent symptoms than the other groups. Therapy with bronchodilators was used most frequently by the NFA group compared to the ED control subjects and CCs (p < 0.001), as was therapy with inhaled steroids (p < 0.001) and oral steroids (p < 0.001). NFA patients had higher scores for vulnerability and were most likely to admit to stress as an asthma trigger. All groups had high exposure to cigarette smoke and pets. NFA patients have many modifiable risk factors and many similarities to ED control subjects and CCs with asthma. General measures to improve asthma control and awareness of risks are required in all groups.


Lipids and the ocular lens.
The unusually high levels of saturation and thus order contribute to the uniqueness of human lens membranes. In addition, and unlike in most biomembranes, most of the lens lipids are associated with proteins, thus reducing their mobility. The major phospholipid of the human lens is dihydrosphingomyelin. Found in significant quantities only in primate lenses, particularly human ones, this lipid is so extremely stable that it was reported to be the only lipid remaining in a frozen mammoth 40,000 years after its death. Unusually high levels of cholesterol add peculiarity to the composition of lens membranes. Beyond the lateral segregation of lipids into dynamic domains known as rafts, the high abundance of cholesterol in the human lens leads to the formation of patches of pure cholesterol. Changes in human lens lipid composition with age and disease as well as differences among species are greater than those observed for any other biomembrane. The relationships among lens membrane composition, structure, and lipid conformation reviewed in this article are unique to the mammalian lens and offer exciting insights into lens membrane function. This review focuses on findings reported over the last two decades that demonstrate the uniqueness of mammalian lens membranes regarding their morphology and composition. Because the membranes of human lenses do undergo the most dramatic changes with age and cataractogenesis, the final sections of this review address our current knowledge of the unusual composition and organization of adult human lens membranes with and without opacification. Finally, the questions that still remain to be answered are presented.


Osteoporosis care during the COVID-19 pandemic in the Netherlands: A national survey.
This is a survey study concerning osteoporosis care during the COVID-19 pandemic in the Netherlands. Respondents reported that osteoporosis care stagnated and lower quality of care was provided. This leads to the conclusion that standardization of osteoporosis care delivery in situations of crisis is needed. During the initial phase of the COVID-19 pandemic, there was no guidance of professional societies or guidelines on the organization of osteoporosis care in case of such a crisis, and treatment relied on local ad hoc strategies. Experiences from the current pandemic need to be taken into account for the near future, and therefore, a national multidisciplinary survey was carried out in the Netherlands. A survey of 17 questions concerning the continuation of bone mineral density measurements by Dual Energy X-ray absorptiometry (DXA), outpatient clinic visits, and prescription of medication was sent to physicians, nurses, nurse practitioners, and physician assistants working in the field of osteoporosis. 77 respondents finished the questionnaire, of whom 39 (50.6%) reported a decline in DXA-scanning and 36 (46.8%) no scanning at all during the pandemic. There was an increase in remote consultations for both new and control patient visits (n = 48, 62.3%; n = 62, 81.7% respectively). Lower quality of care regarding fracture prevention was reported by more than half of the respondents (n = 44, 57.1%). Treatment with intravenous bisphosphonates and denosumab was delayed according to 35 (45.4%) and 6 (6.3%) of the respondents, respectively. During the COVID-19 pandemic, osteoporosis care almost completely arrested, especially because of the discontinuation of DXA-scanning and closing of outpatient clinics. More than half of the respondents reported a substantial lower quality of osteoporosis care during the COVID pandemic. To prevent an increase in fracture rates and a decrease in patient motivation, adherence and satisfaction, standardization of osteoporosis care delivery in situations of crisis is needed.


Bleeding disorder due to an isolated platelet factor 3 deficiency.
To determine the clinical and functional characteristics of isolated platelet factor 3 (PF-3) deficiency, platelet function studies were carried out in 316 patients who were suspected of having a bleeding tendency. Although PF-3 abnormality was observed in 69 patients (22%), an isolated PF-3 abnormality was noted in only three patients. The abnormality was congenital in one patient and secondary to Hashimoto's thyroiditis, Ehlers-Danlos syndrome, and chronic myelocytic leukemia in the other two. Further investigations in the patient with congenital abnormality disclosed that PF-3 activity failed to respond to any of the stimuli tested, and there was a clear dissociation between PF-3 availability and platelet aggregation. The abnormality was due to an intrinsic platelet defect caused by a true deficiency of the membrane phospholipid clotting activity. The findings clearly establish that isolated PF-3 deficiency is an entity of qualitative platelet disorders that may be associated with a severe bleeding tendency.


mGlu3 receptor regulates microglial cell reactivity in neonatal rats.
Perinatal inflammation is a key factor of brain vulnerability in neonates born preterm or with intra-uterine growth restriction (IUGR), two leading conditions associated with brain injury and responsible for neurocognitive and behavioral disorders. Systemic inflammation is recognized to activate microglia, known to be the critical modulators of brain vulnerability. Although some evidence supports a role for metabotropic glutamate receptor 3 (mGlu3 receptor) in modulation of neuroinflammation, its functions are still unknown in the developing microglia. We used a double-hit rat model of perinatal brain injury induced by a gestational low-protein diet combined with interleukin-1β injections (LPD/IL-1β), mimicking both IUGR and prematurity-related inflammation. The effect of LPD/IL-1β on mGlu3 receptor expression and the effect of mGlu3 receptor modulation on microglial reactivity were investigated using a combination of pharmacological, histological, and molecular and genetic approaches. Exposure to LPD/IL-1β significantly downregulated Grm3 gene expression in the developing microglia. Both transcriptomic analyses and pharmacological modulation of mGlu3 receptor demonstrated its central role in the control of inflammation in resting and activated microglia. Microglia reactivity to inflammatory challenge induced by LPD/IL-1β exposure was reduced by an mGlu3 receptor agonist. Conversely, both specific pharmacological blockade, siRNA knock-down, and genetic knock-out of mGlu3 receptors mimicked the pro-inflammatory phenotype observed in microglial cells exposed to LPD/IL-1β. Overall, these data show that Grm3 plays a central role in the regulation of microglial reactivity in the immature brain. Selective pharmacological activation of mGlu3 receptors may prevent inflammatory-induced perinatal brain injury.


Cerebellar transcranial current stimulation - An intraindividual comparison of different techniques.
Transcranial current stimulation (tCS) techniques have been shown to induce cortical plasticity. As an important relay in the motor system, the cerebellum is an interesting target for plasticity induction using tCS, aiming to modulate its excitability and connectivity. However, until now it remains unclear, which is the most effective tCS method for inducing plasticity in the cerebellum. Thus, in this study, the effects of anodal transcranial direct current stimulation (tDCS), 50 Hz transcranial alternating current stimulation (50 Hz tACS), and high frequency transcranial random noise stimulation (tRNS) were compared with sham stimulation in 20 healthy subjects in a within-subject design. tCS was applied targeting the cerebellar lobe VIIIA using neuronavigation. We measured corticospinal excitability, short-interval intracortical inhibition (SICI), short-latency afferent inhibition (SAI), and cerebellar brain inhibition (CBI) and performed a sensor-based movement analysis at baseline and three times after the intervention (post1 = 15 min; post2 = 55 min; post3 = 95 min). Corticospinal excitability increased following cerebellar tACS and tRNS compared to sham stimulation. This effect was most pronounced directly after stimulation but lasted for at least 55 min after tACS. Cortico-cortical and cerebello-cortical conditioning protocols, as well as sensor-based movement analyses, did not change. Our findings suggest that cerebellar 50 Hz tACS is the most effective protocol to change corticospinal excitability.


Evaluation of the usefulness of the SAGES Safe Cholecystectomy Program from the viewpoint of the European surgeon.
Common bile duct injury (CBDI) is a severe complication of laparoscopic cholecystectomy (LC). To minimize its occurrence, SAGES established the Safe Cholecystectomy Program (SCP) with 6 rules to follow during surgery. To assess the knowledge of SCP among European surgeons and their opinion on its usefulness. Data were gathered using questionnaires during surgical conferences in Poland and Denmark. The questionnaire asked about the surgeon's experience in cholecystectomy and the number of complications in the form of CBDI. It asked about the surgeon's opinion on the usefulness of SCP rules on a 10-point scale. A comparison between specialists and residents was performed. The study has been registered in the ClinicalTrials.gov - NCT03155321. One hundred eighty-four questionnaires were gathered. One hundred fourteen (61.96%) specialists (72.8% male, mean age: 50 years) and 70 (38.04%) residents (56% male, mean age: 34 years) completed the questionnaire. Mean work experience was 22 years among specialists and 4.5 years among residents. A high percentage of specialists have experienced CBDI (46% vs. 17% of residents, p = 0.014). More specialists are familiar with the SCP than residents (49.3% vs. 21.7%, p = 0.021). Significant differences in the mean usefulness score were observed for three rules: rules 2 and 6 were found more useful by residents (mean score: 7.07 vs. 6.01, p = 0.025 and 8.70 vs. 8.27, p < 0.001), and rule 3 was found more useful by specialists (mean: 8.73 vs. 8.36, p < 0.001). The awareness of the SCP in Europe is low. Participants consider the rules of the SCP to be useful during surgery, although there are differences in the usefulness scores between the groups. An educational program to promote and further implement the SCP should be established.


[Ledipasvir/sofosbuvir combination for chronic hepatitis C infection in children and adolescents].
Hepatitis C virus infection is world health problem. The aim of this study was to assess the safety and efficacy of ledipasvir/sofosbuvir combination in chronic Hepatitis C Virus (HCV) genotype 1 and 4 infection in paediatric patients. Eligible patients to be treated with ledipasvir/sofosbuvir were patients from 6 to 18 years old with a chronic HCV genotype 1 or 4 infection. The duration and doses of antiviral drugs were changed depending on patient age, fibrosis stage, and PEGylated interferon+ribavirin experience status. The primary efficacy endpoint was the percentage of patients with a sustained virological response 12 weeks post-treatment. A total of nine patients (7 males) with a median age of 14.8 years (8.48-17.91) were treated with ledipasvir/sofosbuvir combination. Five patients received previous treatment with PEGylated interferon+ribavirin during a median of 8.5 months (3-12 months). Eight patients had some degree of fibrosis (1 patient presented with F1, three patients F2, 2 patients F3, and 2 patients F4). The median pre-treatment viral load was 6.2 Log [5.9-6.8] with the HCV RNA becoming negative six weeks after starting the treatment in 100% of the patients. All patients maintained a sustained viral response at 12 weeks. Three patients (33.3%) had some type of adverse effect (2 headache and one oral thrush). The median post-treatment follow-up was 24 weeks (12-104). Treatment with ledipasvir/sofosbuvir in paediatric patients with chronic HCV infection genotype 1 and 4 is safe and effective with SVR12 and similar to those reported in adults.


Bioactivities of chicken essence.
The special flavor and health effects of chicken essence are being widely accepted by people. Scientific researches are revealing its truth as a tonic food in traditional health preservation. Chicken essence has been found to possess many bioactivities including relief of stress and fatigue, amelioration of anxiety, promotion of metabolisms and post-partum lactation, improvement on hyperglycemia and hypertension, enhancement of immune, and so on. These activities of chicken essence are suggested to be related with its active components, including proteins, dipeptides (such as carnosine and anserine), polypeptides, minerals, trace elements, and multiple amino acids, and so on. Underlying mechanisms responsible for the bioactivities of chicken essence are mainly related with anti-stress, anti-oxidant, and neural regulation effects. However, the mechanisms are complicated and may be mediated via the combined actions of many active components, more than the action of 1 or 2 components alone.


Predicting ligand-dependent tumors from multi-dimensional signaling features.
Targeted therapies have shown significant patient benefit in about 5-10% of solid tumors that are addicted to a single oncogene. Here, we explore the idea of ligand addiction as a driver of tumor growth. High ligand levels in tumors have been shown to be associated with impaired patient survival, but targeted therapies have not yet shown great benefit in unselected patient populations. Using an approach of applying Bagged Decision Trees (BDT) to high-dimensional signaling features derived from a computational model, we can predict ligand dependent proliferation across a set of 58 cell lines. This mechanistic, multi-pathway model that features receptor heterodimerization, was trained on seven cancer cell lines and can predict signaling across two independent cell lines by adjusting only the receptor expression levels for each cell line. Interestingly, for patient samples the predicted tumor growth response correlates with high growth factor expression in the tumor microenvironment, which argues for a co-evolution of both factors in vivo.


[Value of the detection of serum thyroglobin and I-131 scintigraphy in the follow-up of differentiated thyroid cancer].
The objective of this work has been to know the sensitivity of serum thyroglobulin and I-131 scintigraphy in the detection of thyroid remnants or metastases, and to evaluate the predictive value of serum thyroglobulin in the follow-up of differentiated thyroid cancer patients. We have carried out a retrospective study of 218 patients with differentiated thyroid cancer, with detection of serum thyroglobulin levels and I-131 scintigraphy in clinical status of hypothyroidism, after to perform thyroidectomy and between six and nine months later. We have rejected 16 and 14 patients who have had presented high serum levels of thyroglobulin, or an incomplete follow-up. Our results showed a good correlation of both parameters (92%). The sensitivity of TG and I-131 scan was 85% and 90% respectively, and superior to 90% for both procedures in the diagnosis of the osseous and lung metastases. The sensitivity of I-131 scan and TG was 100% and less to 70% in the detection of thyroid remnants and regional lymphatic nodes. The positive and negative value of TG was 99% and 91%, respectively, with a total of 24 false negative results. Considering this study, we believe that both techniques are complementary, with a lower sensitivity of serum TG in the detection of thyroid remnants and regional lymphatic involvement, and a negative predictive value that does not permit to accomplish the follow-up of differentiated thyroid cancer patients, considering exclusively the results of this tumoral marker.


Characterization of nanoporous gold electrodes for bioelectrochemical applications.
The high surface areas of nanostructured electrodes can provide for significantly enhanced surface loadings of electroactive materials. The fabrication and characterization of nanoporous gold (np-Au) substrates as electrodes for bioelectrochemical applications is described. Robust np-Au electrodes were prepared by sputtering a gold-silver alloy onto a glass support and subsequent dealloying of the silver component. Alloy layers were prepared with either a uniform or nonuniform distribution of silver and, post dealloying, showed clear differences in morphology on characterization with scanning electron microscopy. Redox reactions under kinetic control, in particular measurement of the charge required to strip a gold oxide layer, provided the most accurate measurements of the total electrochemically addressable electrode surface area, A(real). Values of A(real) up to 28 times that of the geometric electrode surface area, A(geo), were obtained. For diffusion-controlled reactions, overlapping diffusion zones between adjacent nanopores established limiting semi-infinite linear diffusion fields where the maximum current density was dependent on A(geo). The importance of measuring the surface area available for the immobilization was determined using the redox protein, cyt c. The area accessible to modification by a biological macromolecule, A(macro), such as cyt c was reduced by up to 40% compared to A(real), demonstrating that the confines of some nanopores were inaccessible to large macromolecules due to steric hindrances. Preliminary studies on the preparation of np-Au electrodes modified with osmium redox polymer hydrogels and Myrothecium verrucaria bilirubin oxidase (MvBOD) as a biocathode were performed; current densities of 500 μA cm(-2) were obtained in unstirred solutions.


Associations between genetic and epigenetic variations in cytokine genes and mild persistent breast pain in women following breast cancer surgery.
Persistent pain following breast cancer surgery is a significant problem. Both inherited and acquired mechanisms of inflammation appear to play a role in the development and maintenance of persistent pain. In this longitudinal study, growth mixture modeling was used to identify persistent breast pain phenotypes based on pain assessments obtained prior to and monthly for 6months following breast cancer surgery. Associations between the "no pain" and "mild pain" phenotypes and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. The methylation status of the CpG sites found in the promoters of genes associated with pain group membership was determined using bisulfite sequencing. In the multivariate analysis, three SNPs (i.e., interleukin 6 (IL6) rs2069840, C-X-C motif chemokine ligand 8 (CXCL8) rs4073, tumor necrosis factor (TNF) rs1800610) and two TNF CpG sites (i.e., c.-350C, c.-344C) were associated with pain group membership. These findings suggest that variations in IL6, CXCL8, and TNF are associated with the development and maintenance of mild persistent breast pain. CpG methylation within the TNF promoter may provide an additional mechanism through which TNF alters the risk for mild persistent breast pain after breast cancer surgery. These genetic and epigenetic variations may help to identify individuals who are predisposed to the development of mild levels of persistent breast pain following breast cancer surgery.


Laparoscopic abdominal cervical cerclage before conception--case report.
Cervical incompetence is characterized by painless cervical dilation in the second or early in the third trimester with prolapsed membranes and expulsion of an immature fetus. Cervical cerclage performed during pregnancy is a typical and effective treatment of cervical incompetence. In case of previously failed cervical cerclages or other cervix malformations the procedure of abdominal cerclage in prepregnancy period can be considered as an option to help keep a pregnancy. In the following work we present two cases in which laparoscopic abdominal cervical cerclage was performed before conception. Laparoscopic cervical cerclage is a less invasive technique with acceptable outcome, that could replace the traditional laparotomy technique.


Multiple session early psychological interventions for the prevention of post-traumatic stress disorder.
The prevention of long-term psychological distress following traumatic events is a major concern. Systematic reviews have suggested that individual psychological debriefing is not an effective intervention at preventing post-traumatic stress disorder (PTSD). Over the past 20 years, other forms of intervention have been developed with the aim of preventing PTSD. To examine the efficacy of psychological interventions aimed at preventing PTSD in individuals exposed to a traumatic event but not identified as experiencing any specific psychological difficulties, in comparison with control conditions (e.g. usual care, waiting list and no treatment) and other psychological interventions. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and ProQuest's Published International Literature On Traumatic Stress (PILOTS) database to 3 March 2018. An earlier search of CENTRAL and the Ovid databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to May 2016). We handsearched reference lists of relevant guidelines, systematic reviews and included study reports. Identified studies were shared with key experts in the field.We conducted an update search (15 March 2019) and placed any new trials in the 'awaiting classification' section. These will be incorporated into the next version of this review, as appropriate. We searched for randomised controlled trials of any multiple session (two or more sessions) early psychological intervention or treatment designed to prevent symptoms of PTSD. We excluded single session individual/group psychological interventions. Comparator interventions included waiting list/usual care and active control condition. We included studies of adults who experienced a traumatic event which met the criterion A1 according to the Diagnostic and Statistical Manual (DSM-IV) for PTSD. We entered data into Review Manager 5 software. We analysed categorical outcomes as risk ratios (RRs), and continuous outcomes as mean differences (MD) or standardised mean differences (SMDs), with 95% confidence intervals (CI). We pooled data with a fixed-effect meta-analysis, except where there was heterogeneity, in which case we used a random-effects model. Two review authors independently assessed the included studies for risk of bias and discussed any conflicts with a third review author. This is an update of a previous review.We included 27 studies with 3963 participants. The meta-analysis included 21 studies of 2721 participants. Seventeen studies compared multiple session early psychological intervention versus treatment as usual and four studies compared a multiple session early psychological intervention with active control condition.Low-certainty evidence indicated that multiple session early psychological interventions may be more effective than usual care in reducing PTSD diagnosis at three to six months' follow-up (RR 0.62, 95% CI 0.41 to 0.93; I2 = 34%; studies = 5; participants = 758). However, there was no statistically significant difference post-treatment (RR 1.06, 95% CI 0.85 to 1.32; I2 = 0%; studies = 5; participants = 556; very low-certainty evidence) or at seven to 12 months (RR 0.94, 95% CI 0.20 to 4.49; studies = 1; participants = 132; very low-certainty evidence). Meta-analysis indicated that there was no statistical difference in dropouts compared with usual care (RR 1.34, 95% CI 0.91 to 1.95; I2 = 34%; studies = 11; participants = 1154; low-certainty evidence) .At the primary endpoint of three to six months, low-certainty evidence indicated no statistical difference between groups in reducing severity of PTSD (SMD -0.10, 95% CI -0.22 to 0.02; I2 = 34%; studies = 15; participants = 1921), depression (SMD -0.04, 95% CI -0.19 to 0.10; I2 = 6%; studies = 7; participants = 1009) or anxiety symptoms (SMD -0.05, 95% CI -0.19 to 0.10; I2 = 2%; studies = 6; participants = 945).No studies comparing an intervention and active control reported outcomes for PTSD diagnosis. Low-certainty evidence showed that interventions may be associated with a higher dropout rate than active control condition (RR 1.61, 95% CI 1.11 to 2.34; studies = 2; participants = 425). At three to six months, low-certainty evidence indicated no statistical difference between interventions in terms of severity of PTSD symptoms (SMD -0.02, 95% CI -0.31 to 0.26; I2 = 43%; studies = 4; participants = 465), depression (SMD 0.04, 95% CI -0.16 to 0.23; I2 = 0%; studies = 2; participants = 409), anxiety (SMD 0.00, 95% CI -0.19 to 0.19; I2 = 0%; studies = 2; participants = 414) or quality of life (MD -0.03, 95% CI -0.06 to 0.00; studies = 1; participants = 239).None of the included studies reported on adverse events or use of health-related resources. While the review found some beneficial effects of multiple session early psychological interventions in the prevention of PTSD, the certainty of the evidence was low due to the high risk of bias in the included trials. The clear practice implication of this is that, at present, multiple session interventions aimed at everyone exposed to traumatic events cannot be recommended. There are a number of ongoing studies, demonstrating that this is a fast moving field of research. Future updates of this review will integrate the results of these new studies.


Echocardiography Population Study in Russian Federation for 4P Medicine Using Machine Learning.
This article describes the study results of echocardiographic (ECHO) test data for 4P medicine applied to cardiovascular patients. Data from more than 145,000 echocardiographic tests were analyzed. One of the objectives of the study is the possibility to identify patterns and relationships in patient characteristics for more accurate appointment procedures based on the history of the disease and the individual characteristics of the patient. This is achieved by using classifications models based on machine learning methods. Early detection of disease risks and "accurate" appointment of diagnostic procedures makes a significant contribution to value-based medicine. Moreover, it was also possible to identify the classes and characteristics of patients for whom repeated diagnostic procedures are well founded. Calculation of personal risks from empirical retrospective data helps to detect the disease in early stages. Identifying patients with high risk of disease complications allow physicians to make right decisions about timely treatment, which can significantly improve the quality of treatment, and help to avoid diseases complications, optimize costs and improve the quality of medical care.


Collagen Functionalized With Graphene Oxide Enhanced Biomimetic Mineralization and in Situ Bone Defect Repair.
Biomimetic mineralization using simulated body fluid (SBF) can form a bonelike apatite (Ap) on the natural polymers and enhance osteoconductivity and biocompatibility, and reduce immunological rejection. Nevertheless, the coating efficiency of the bonelike apatite layer on natural polymers still needs to be improved. Graphene oxide (GO) is rich in functional groups, such as carbonyls (-COOH) and hydroxyls (-OH), which can provide more active sites for biomimetic mineralization and improve the proliferation of the rat bone marrow stromal cells (r-BMSCs). In this study, we introduced 0%, 0.05%, 0.1%, and 0.2% w/v concentrations of GO into collagen (Col) scaffolds and immersed the fabricated scaffolds into SBF for 1, 7, and 14 days. In vitro environment scanning electron microscopy (ESEM), energy-dispersive spectrometry (EDS), thermogravimetric analysis (TGA), micro-CT, calcium quantitative analysis, and cellular analysis were used to evaluate the formation of bonelike apatite on the scaffolds. In vivo implantation of the scaffolds into the rat cranial defect was used to analyze the bone regeneration ability. The resulting GO-Col-Ap scaffolds exhibited a porous and interconnected structure coated with a homogeneous distribution of bonelike apatite on their surfaces. The Ca/P ratio of 0.1% GO-Col-Ap group was equal to that of natural bone tissue on the basis of EDS analysis. More apatites were observed in the 0.1% GO-Col-Ap group through TGA analysis, micro-CT evaluation, and calcium quantitative analysis. Furthermore, the 0.1% GO-Col-Ap group showed significantly higher r-BMSCs adhesion and proliferation in vitro and more than 2-fold higher bone formation than the Col-Ap group in vivo. Our study provides a new approach of introducing graphene oxide into bone tissue engineering scaffolds to enhance biomimetic mineralization.


Quadriceps Insufficiency following Repair of the Anterior Cruciate Ligament*.
This study was originally presented at the American College of Sports Medicine annual meeting in San Diego, CA, 1984. Following repair of the anterior cruciate ligament, it is fairly typical for a patient to return to activity at approximately 12 months postsurgery. The purpose of the study was to quantify quadriceps size and function at 1 year postsurgery. Bilateral isokinetic torque measurements, tomographic scans, muscle biopsies, and anthropometrics were performed on 13 patients (3 females, 10 males) at 13 months post-surgery. The operative leg was 3% smaller in circumference, 10% smaller in total muscle area, 12% smaller in quadriceps area (all p < 0.05) and had a 9% larger subcutaneous fat area (p = 0.06). No difference in hamstrings area was seen. Isokinetic torques for the quadriceps were reduced by 11-15% in the operative leg (p < .05) with no difference seen between the hamstrings torques. Types I and II fibers were clinically smaller in both legs with the type II fibers being significantly (p < 0.05) reduced in the operative leg. It was concluded that 1) leg circumference was a poor indicator of muscle size due to the selective fat deposition in the operative leg, 2) the cross-sectional area of muscle was proportional to isokinetic torque at 240/sec, and 3) there were clinically and statistically significant isokinetic torque differences between quadriceps 13 months post-surgery.J Orthop Sports Phys Ther 1988;9(7):245-249.


Recognition of binding sites on Candida albicans by monoclonal antibodies to human leukocyte antigens.
Candida albicans exhibits examples of human molecular mimicry, including receptors resembling human steroid receptors and human complement receptor (CR)-like receptors that bind the complement fragments C3d and iC3b. To further characterize the epitopes of the Candida human CR-like molecules, a panel of monoclonal antibodies (MAbs) against epitopes within the human CR3 was used. MAbs Mo1, M1/70HL, and 7C3 bound to the germ tube, as assessed by immunofluorescence. MAbs Leu15, 60.1, and 95G8 did not bind. Miscellaneous MAbs against other antigens on human leukocytes (B2, 3D9, and OKT4) did not bind. However, MY9, which recognizes a monocyte antigen, bound extensively to the germ tube. The binding of certain anti-CR3 MAbs suggested limited identity between the Candida CR3-like receptor and the human CR3. The binding of MY9 identified an antigen recognized by a MAb to a human cell antigen not previously known to exist on C. albicans.


[Health and functional status among elderly individuals living in nursing homes in Madrid].
Epidemiologic studies on probabilistic samples of the institutionalized elderly in Spain are very scarce. The aim of this study was to describe the health and functional status of a population of older people living in nursing homes. A cross-sectional epidemiologic study was carried out. A sample of 800 subjects living in 19 public and 26 private nursing homes in Madrid was obtained through a stratified cluster method. Residents, main caregivers, doctors and nurses were interviewed. Cognitive status, perceived health, depression, pain, functional capacity, chronic illnesses, pressure ulcers, urinary and fecal incontinence, drug consumption and hospitalizations were assessed. Seventy-five percent of the sample were women. The mean age was 83.4 (standard deviation, 7.3) years. Forty-four percent had some degree of cognitive impairment. Forty-six percent were independent or mildly dependent in basic activities of daily living. Fifty-five percent reported very good or good perceived health. Thirty percent had depressive symptoms. Thirty-one percent had experienced daily pain in the previous 7 days. Three percent had pressure ulcers. The most prevalent illnesses were hypertension (45%), osteoarthritis (34%), dementia (33%) and anxiety (27%). The prevalence of Alzheimer's disease was 14%. Fifty-three percent had urinary incontinence and 26% had fecal incontinence. Twenty-six percent had been transferred to an emergency unit in the previous year. The estimates of the main variables, such as cognitive impairment and functional status, were in general more favorable than those in other populations of nursing home residents in Europe and North America. This is partly explained by the greater proportion of persons with a low need for care in the nursing homes in Madrid.


Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation.
Mitochondrial dysfunction is a major factor in heart failure (HF). A pronounced variability of mitochondrial electron transport chain (ETC) defects is reported to occur in severe acquired cardiomyopathies without a consistent trend for depressed activity or expression. The aim of this study was to define the defect in the integrative function of cardiac mitochondria in coronary microembolization-induced HF. Studies were performed in the canine coronary microembolization-induced HF model of moderate severity. Oxidative phosphorylation was assessed as the integrative function of mitochondria, using a comprehensive variety of substrates in order to investigate mitochondrial membrane transport, dehydrogenase activity and electron-transport coupled to ATP synthesis. The supramolecular organization of the mitochondrial ETC also was investigated by native gel electrophoresis. We found a dramatic decrease in ADP-stimulated respiration that was not relieved by an uncoupler. Moreover, the ADP/O ratio was normal, indicating no defect in the phosphorylation apparatus. The data point to a defect in oxidative phosphorylation within the ETC. However, the individual activities of ETC complexes were normal. The amount of the supercomplex consisting of complex I/complex III dimer/complex IV, the major form of respirasome considered essential for oxidative phosphorylation, was decreased. We propose that the mitochondrial defect lies in the supermolecular assembly rather than in the individual components of the ETC.


Reassessing specimen number and diagnostic yield of ultrasound guided breast core biopsy.
To reassess the minimum number of specimens required for an accurate diagnosis compared to the standard acquisition of five specimens. A total of 190 consecutive breast mass biopsies were performed using a 14-gauge core biopsy needle under ultrasound guidance. Two to six specimens were obtained from each mass and placed in sequential containers. Each specimen was evaluated by a pathologist in the order it was obtained and was labeled as "diagnostic' or 'non-diagnostic'. During the biopsy procedure, the radiologist indicated after which number biopsy he was confident that an adequate diagnostic specimen had been obtained. This was based upon real-time visualization of the needle passing through the lesion and whether the specimen sank or floated in formalin. These observations were compared with the pathologic diagnostic yield according to specimen number. Fifty-eight lesions (30.5%) were malignant, four (2.1%) were atypical, and 128 (67.4%) were benign. Histologic diagnosis was obtained after the first specimen in 157 (82.6%) lesions, the second specimen in 172 (90.5%) lesions, the third specimen in 186 (97.9%) lesions, the fourth specimen in 188 (98.9%) lesions, and the fifth specimen in 190 (100%) lesions. A histologic diagnosis was made in 90% of the malignant lesions after the first biopsy pass, 95% after the second pass, 98% after the third pass, and 100% after the fourth and fifth passes. Nine (4.7%) lesions showed discrepancy between the radiologist's confidence of diagnosis and pathologic diagnostic yield. Of these lesions, seven were benign and two were malignant. A diagnostic yield of 95% was obtained based on operator estimate of the minimum number of required core biopsies. A high diagnostic yield of 98% was achieved after three biopsy passes and 100% after five passes.


Affective response during physical activity: Within-subject differences across phases of behavior change.
Affective response during physical activity may be a key factor reinforcing future behavior. However, little is known about how affective responses during physical activity may differ across phases of behavior change. This study used real-time Ecological Momentary Assessment (EMA) to examine within-subject differences in affective response during physical activity in daily life as individuals transitioned across phases of behavior change. A sample of 115 adults (M = 41.0 years, 74% female) participated in an intensive longitudinal study with measurement bursts at 0, 6, and 12-months. Each burst consisted of 8 randomly-prompted EMA occasions per day across 4 days. EMA self-report items assessed current activity level (i.e., physical activity or nonphysical activity), and positive and negative affect. Questionnaires measured phase of behavior change (e.g., preaction [no regular physical activity], action [regular physical activity <6 months], and maintenance [regular physical activity ≥6 months]) at each burst. Three-level (Level-1 = occasion, Level-2 = burst, Level-3 = person) linear regression models tested Phase of Change (Level-2, within-subject) × Physical Activity Level (Level-1, within-subject) interactions controlling for day of week, time of day, and sex. Positive affective response during physical activity (vs. nonphysical activity) was higher when individuals were in preaction phases (vs. action). Negative affective response during physical activity (vs. nonphysical activity) was lower when individuals were in the maintenance phase (vs. action). Long-term maintenance of physical activity may be particularly challenging, given the lack of positive reinforcement that is thought to be needed to sustain behavior. (PsycINFO Database Record


Selective dendritic transport of RNA in hippocampal neurons in culture.
Typical neurons of the central nervous system (CNS) elaborate tens of thousands of membrane specializations at sites of synaptic contacts on their dendrites. To construct, maintain, and modify these specializations, neurons must produce and deliver the appropriate molecular constituents to particular synaptic sites. Previous studies have revealed that polyribosomes are selectively positioned beneath postsynaptic sites, suggesting that in neurons, as in other cell types, protein synthetic machinery is located at or near the sites where particular proteins are needed. The mechanisms that deliver ribosomes and messenger RNA to their specific destinations in cells are therefore of considerable interest. Here we describe a system for RNA transport in dendrites that could provide a mechanism for the delivery of ribosomes and mRNA to synaptic sites in dendrites. Hippocampal neurons grown in culture incorporate 3H-uridine in the nucleus, then selectively transport the newly synthesized RNA into dendrites at a rate of about 0.5 mm day-1. The transport is inhibited by metabolic poisons, suggesting that it is an active, energy-dependent process. The RNA may be transported in association with the cytoskeleton.


Relative risk regression analysis of epidemiologic data.
Relative risk regression methods are described. These methods provide a unified approach to a range of data analysis problems in environmental risk assessment and in the study of disease risk factors more generally. Relative risk regression methods are most readily viewed as an outgrowth of Cox's regression and life model. They can also be viewed as a regression generalization of more classical epidemiologic procedures, such as that due to Mantel and Haenszel. In the context of an epidemiologic cohort study, relative risk regression methods extend conventional survival data methods and binary response (e.g., logistic) regression models by taking explicit account of the time to disease occurrence while allowing arbitrary baseline disease rates, general censorship, and time-varying risk factors. This latter feature is particularly relevant to many environmental risk assessment problems wherein one wishes to relate disease rates at a particular point in time to aspects of a preceding risk factor history. Relative risk regression methods also adapt readily to time-matched case-control studies and to certain less standard designs. The uses of relative risk regression methods are illustrated and the state of development of these procedures is discussed. It is argued that asymptotic partial likelihood estimation techniques are now well developed in the important special case in which the disease rates of interest have interpretations as counting process intensity functions. Estimation of relative risks processes corresponding to disease rates falling outside this class has, however, received limited attention. The general area of relative risk regression model criticism has, as yet, not been thoroughly studied, though a number of statistical groups are studying such features as tests of fit, residuals, diagnostics and graphical procedures. Most such studies have been restricted to exponential form relative risks as have simulation studies of relative risk estimation procedures with moderate numbers of disease events.


Prediction of 3D Cardiovascular hemodynamics before and after coronary artery bypass surgery via deep learning.
The clinical treatment planning of coronary heart disease requires hemodynamic parameters to provide proper guidance. Computational fluid dynamics (CFD) is gradually used in the simulation of cardiovascular hemodynamics. However, for the patient-specific model, the complex operation and high computational cost of CFD hinder its clinical application. To deal with these problems, we develop cardiovascular hemodynamic point datasets and a dual sampling channel deep learning network, which can analyze and reproduce the relationship between the cardiovascular geometry and internal hemodynamics. The statistical analysis shows that the hemodynamic prediction results of deep learning are in agreement with the conventional CFD method, but the calculation time is reduced 600-fold. In terms of over 2 million nodes, prediction accuracy of around 90%, computational efficiency to predict cardiovascular hemodynamics within 1 second, and universality for evaluating complex arterial system, our deep learning method can meet the needs of most situations.


Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis.
Androgen/androgen receptor (AR) signaling plays important roles in normal liver function and in progression of liver diseases. In studies of noncancerous liver diseases, AR knockout mouse models of liver disease have revealed that androgen/AR signaling suppresses the development of steatosis, virus-related hepatitis, and cirrhosis. In addition, studies have shown that targeting AR in bone marrow-derived mesenchymal stem cells (BM-MSCs) improves their self-renewal and migration potentials, thereby increasing the efficacy of BM-MSC transplantation as a way to control the progression of cirrhosis. Androgen/AR signaling is known to be involved in the initiation of carcinogen- or hepatitis B virus-related hepatocellular carcinoma (HCC). However, studies have demonstrated that AR, rather than androgen, plays the dominant role in cancer initiation. Therefore, targeting AR might be an appropriate therapy for patients with early-stage HCC. In contrast, androgen/AR signaling has been shown to suppress metastasis of HCC in patients with late-stage disease. In addition, there is evidence that therapy comprising Sorafenib and agents that enhance the functional expression of AR may suppress the progression of late-stage HCC.


[Association between DNA antibodies levels in the blood of patients with multiple sclerosis and clinical presentation of the disease].
Multiple sclerosis (MS) as an autoimmune disease is characterized by occurrence of high titres of antibodies (AB) to cell structures and autoantigens. Various AB-mediated effector mechanisms can participate directly in the pathogenesis of demyelinisation damaging myelin, oligodendrocytes and nervous fibres. Antinuclear AB, including anti-DNA AB are an example of activation of humoral immunity in MS. Pathogenetic and clinical value of these AB is investigated insufficiently. The aim of this study was estimation of the AB titers in MS patients from two populations of Russia in relation to clinical features of MS. Results of examination of 83 patients with definite MS from Novosibirsk and Moscow (49 and 34 patients) are analyzed. Groups of comparison consisted of healthy donors and patients with SLE of the same age. Use of identical methods in the analysis of the data received in two various populations made the data objective as much as possible and revealed the strongest clinico-biochemical associations. Levels of AB to both native and denaturated DNA were studied. Comparison of several test-systems showed that the system produced by "Specialized scientific Labs" Company has the best sensitivity. In two populations of MS patients the levels of AB in plasma were similar and associated between each other, higher than in donors, but lower than in SLE patients. In both groups MS patients with secondary progressive MS had higher percent of samples of plasma with average and high levels of AB. In the Novosibirsk group associations of levels of AB with parameters of disease severety (EDSS and a number of FS scales) were seen. In the Moscow group levels of AB to DNA were significantly associated with time from the disease onset to certain level of disability (EDSS 3); both the analysis of average values and the correlation analysis showed a weak association of AB to DNA level and MS duration. The data testify that AB to DNA play a more important role in MS pathogenesis than was considered earlier. Catalytic AB as a part of anti-DNA AB may play a special role.


Complete genomes of Pasteurella multocida isolates from porcine, bovine, and cervine samples found in New Zealand farms.
Here, we present complete genome assemblies of Pasteurella multocida strains isolated from porcine, bovine, and cervine farms as part of bacteriology incursion investigations to identify pathogens that might present a sanitary risk to New Zealand.


[Carrier-mediated uptake of L-leucine at the points of growth separated from potato tubers].
The uptake of 14C-L-leucine by the points of growth separated from potato tubers was studied. The pH optimum of the process was about 7.0. The leucine transport over a wide concentration range was biphasic. For descriptive convenience the isotherm was divided into two segments, both of which obeyed the Michaelis-Menten kinetics. The Km value for the high affinity transport was within the range of 7.0 x 10(-6) mM, while that for the low affinity transport was within the range of 5 x 10(-4) mM. The maximum velocities were 3 x 10(-8) mM/g of dry weight/hour and 3.8 x 10(-7) mM/g of dry weight/hour, respectively. Cycloheximide and 2.4-dinitroftorphenol caused a considerable inhibition of net transport of L-leucine, while actinomycin D had no such effect. The uptake of L-leucine was unaffected by phenylalanine and isoleucine, but was strongly inhibited by D-leucine. The results obtained are indicative of a biphasic carrier-mediated uptake system with a high affinity and high substrate specificity for leucine.


N-Chlorotaurine shows high in vitro activity against promastigotes and amastigotes of Leishmania species.
Protozoan parasites of the genus Leishmania are the causative agents of life-threatening visceral as well as cutaneous and mucocutaneous leishmaniasis. First-line drugs are antimonials, but toxicity and resistance in some endemic areas cause serious problems. In the current study, the antileishmanial activity of the weak oxidant N-chlorotaurine (NCT) was investigated. NCT is a derivative of the amino acid taurine produced by granulocytes and monocytes during oxidative burst, but can also be synthesized chemically and used topically as an antiseptic at a concentration of 1 % (55 mM) in vivo. NCT susceptibility tests were performed in vitro with promastigotes and amastigotes of Leishmania infantum and Leishmania donovani. As NH(4)Cl is known to increase the activity of NCT by the formation of monochloramine (NH(2)Cl), co-treatment assays were included in the study. Mean EC(50) values after 1 h of treatment were 5.94 mM for L. infantum and 9.8 mM for L. donovani promastigotes. Co-treatment with 5.5 mM NCT plus 19 mM NH(4)Cl led to complete killing of promastigotes of both strains within 15 min. Amastigotes were inactivated by treatment with 2 mM NCT alone. The results of this study indicate a high potential of NCT against Leishmania species.


Coded-GFDM for Reliable Communication in Underwater Acoustic Channels.
The performance of the coded generalized frequency division multiplexing (GFDM) transceiver has been evaluated in a shallow underwater acoustic channel (UAC). Acoustic transmission is the scheme of choice for communication in UAC since radio waves suffer from absorption and light waves scatter. Although orthogonal frequency division multiplexing (OFDM) has found its ground for multicarrier acoustic underwater communication, it suffers from high peak to average power ratio (PAPR) and out of band (OOB) emissions. We propose a coded-GFDM based multicarrier system since GFDM has a higher spectral efficiency compared to a traditional OFDM system. In doing so, we assess two block codes, namely Bose, Chaudari, and Hocquenghem (BCH) codes, Reed-Solomon (RS) codes, and several convolutional codes. We present the error performances of these codes when used with GFDM. Furthermore, we evaluate the performance of the proposed system using two equalizers: Matched Filter (MF) and Zero-Forcing (ZF). Simulation results show that among the various block coding schemes that we tested, BCH (31,6) and RS (15,3) give the best error performance. Among the convolutional codes that we tested, rate 1/4 convolutional codes give the best performance. However, the performance of BCH and RS codes is much better than the convolutional codes. Moreover, the performance of the ZF equalizer is marginally better than the MF equalizer. In conclusion, using the channel coding schemes with GFDM improves error performance manifolds thereby increasing the reliability of the GFDM system despite slightly higher complexity.


CD200 promotes immunosuppression in the pancreatic tumor microenvironment.
A significant challenge to overcome in pancreatic ductal adenocarcinoma (PDAC) is the profound systemic immunosuppression that renders this disease non-responsive to immunotherapy. Our supporting data provide evidence that CD200, a regulator of myeloid cell activity, is expressed in the PDAC microenvironment. Additionally, myeloid-derived suppressor cells (MDSC) isolated from patients with PDAC express elevated levels of the CD200 receptor (CD200R). Thus, we hypothesize that CD200 expression in the PDAC microenvironment limits responses to immunotherapy by promoting expansion and activity of MDSC. Immunofluorescent staining was used to determine expression of CD200 in murine and human PDAC tissue. Flow cytometry was utilized to test for CD200R expression by immune populations in patient blood samples. In vivo antibody blocking of CD200 was conducted in subcutaneous MT-5 tumor-bearing mice and in a genetically engineered PDAC model (KPC-Brca2 mice). Peripheral blood mononuclear cells (PBMC) from patients with PDAC were analyzed by single-cell RNA sequencing. MDSC expansion assays were completed using healthy donor PBMC stimulated with IL-6/GM-CSF in the presence of recombinant CD200 protein. We found expression of CD200 by human pancreatic cell lines (BxPC3, MiaPaca2, and PANC-1) as well as on primary epithelial pancreatic tumor cells and smooth muscle actin+ stromal cells. CD200R expression was found to be elevated on CD11b+CD33+HLA-DRlo/- MDSC immune populations from patients with PDAC (p=0.0106). Higher expression levels of CD200R were observed in CD15+ MDSC compared with CD14+ MDSC (p<0.001). In vivo studies demonstrated that CD200 antibody blockade limited tumor progression in MT-5 subcutaneous tumor-bearing and in KPC-Brca2 mice (p<0.05). The percentage of intratumoral MDSC was significantly reduced in anti-CD200 treated mice compared with controls. Additionally, in vivo blockade of CD200 can also significantly enhance the efficacy of PD-1 checkpoint antibodies compared with single antibody therapies (p<0.05). Single-cell RNA sequencing of PBMC from patients revealed that CD200R+ MDSC expressed genes involved in cytokine signaling and MDSC expansion. Further, in vitro cytokine-driven expansion and the suppressive activity of human MDSC was enhanced when cocultured with recombinant CD200 protein. These results indicate that CD200 expression in the PDAC microenvironment may regulate MDSC expansion and that targeting CD200 may enhance activity of checkpoint immunotherapy.


Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner.
Severe infections during pregnancy are one of the major risk factors for cognitive impairment in the offspring. It has been suggested that maternal inflammation leads to dysfunction of cortical GABAergic interneurons that in turn underlies cognitive impairment of the affected offspring. However, the evidence comes largely from studies of adult or mature brains and how the impairment of inhibitory circuits arises upon maternal inflammation is unknown. Here we show that maternal inflammation affects multiple steps of cortical GABAergic interneuron development, i.e., proliferation of precursor cells, migration and positioning of neuroblasts, as well as neuronal maturation. Importantly, the development of distinct subtypes of cortical GABAergic interneurons was discretely impaired as a result of maternal inflammation. This translated into a reduction in cell numbers, redistribution across cortical regions and layers, and changes in morphology and cellular properties. Furthermore, selective vulnerability of GABAergic interneuron subtypes was associated with the stage of brain development. Thus, we propose that maternally derived insults have developmental stage-dependent effects, which contribute to the complex etiology of cognitive impairment in the affected offspring.


Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory.
Of the 110 dentists who had presented seroconversion 50 days after the intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine against hepatitis B (HB), administered eight years before at an interval of one month between the 1st and 2nd doses and of five months between the 2nd and 3rd doses, 51 were included for the assessment of the persistence of immunity. None of the dentists had hepatitis or had received HB vaccine during this period. All subjects were submitted to serological tests for the detection of the following markers of hepatitis B virus (HBV) infection: HBsAg, anti-HBc, HBeAg, anti-HBe, and anti-HBs, with no HBsAg, anti-HBc, HBeAg or anti-HBe being detected. A microparticle enzyme immunoassay (MEIA) revealed the presence of anti-HBs at protective titers (> or = 10 mIU/ml) in 42 dentists (82.4%), with the anti-HBs titer being higher than 100 mIU/ml in 36 of them (70.6%) (good responders), between 10 and 100 mIU/ml in 6 (11.8%) (poor responders), and lower than 10 mIU/ml in 9 (17.6%) (non-responders). According to clinical data and serological tests, none of the dentists had presented disease or latent HBV infection during the eight years following the first vaccination. A 2 micrograms booster dose was administered intradermally to eight dentists with anti-HBs titers lower than 10 mIU/ml (non-responders) and to six dentists with titers ranging from 10 to 100 mIU/ml (poor responders); the determination of anti-HBs one month later demonstrated the occurrence of seroconversion in the eight non-responders and an increase in anti-HBs titer in the six poor responders. In summary, the present results demonstrated the prolonged persistence of protection against HBV infection and the development of immunologic memory provided by vaccination against HB--with intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine at 0, 1, and 6 months--carried out eight years before in 51 dentists.


The ATP-sensitive potassium (KATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman.
The homeobox transcription factor Tinman plays an important role in the initiation of heart development. Later functions of Tinman, including the target genes involved in cardiac physiology, are less well studied. We focused on the dSUR gene, which encodes an ATP-binding cassette transmembrane protein that is expressed in the heart. Mammalian SUR genes are associated with K(ATP) (ATP-sensitive potassium) channels, which are involved in metabolic homeostasis. We provide experimental evidence that Tinman directly regulates dSUR expression in the developing heart. We identified a cis-regulatory element in the first intron of dSUR, which contains Tinman consensus binding sites and is sufficient for faithful dSUR expression in the fly's myocardium. Site-directed mutagenesis of this element shows that these Tinman sites are critical to dSUR expression, and further genetic manipulations suggest that the GATA transcription factor Pannier is synergistically involved in cardiac-restricted dSUR expression in vivo. Physiological analysis of dSUR knock-down flies supports the idea that dSUR plays a protective role against hypoxic stress and pacing-induced heart failure. Because dSUR expression dramatically decreases with age, it is likely to be a factor involved in the cardiac aging phenotype of Drosophila. dSUR provides a model for addressing how embryonic regulators of myocardial cell commitment can contribute to the establishment and maintenance of cardiac performance.


Can dynamic consent facilitate the protection of biomedical big data in biobanking in Malaysia?
As with many other countries, Malaysia is also developing and promoting biomedical research to increase the understanding of human diseases and possible interventions. To facilitate this development, there is a significant growth of biobanks in the country to ensure continuous collection of biological samples for future research, which contain extremely important personal information and health data of the participants involved. Given the vast amount of samples and data accumulated by biobanks, they can be considered as reservoirs of precious biomedical big data. It is therefore imperative for biobanks to have in place regulatory measures to ensure ethical use of the biomedical big data. Malaysia has yet to introduce specific legislation for the field of biobanking. However, it can be argued that its existing Personal Data Protection Act 2010 (PDPA) has laid down legal principles that can be enforced to protect biomedical big data generated by the biobanks. Consent is a mechanism to enable data subjects to exercise their autonomy by determining how their data can be used and ensure compliance with legal principles. However, there are two main concerns surrounding the current practice of consent in biomedical big data in Malaysia. First, it is uncertain that the current practice would be able to respect the underlying notion of autonomy, and second, it is not in accordance with the legal principles of the PDPA. Scholars have deliberated on different strategies of informed consent, and a more interactive approach has recently been introduced: dynamic consent. It is argued that a dynamic consent approach would be able to address these concerns.


Aliphatic acetogenin constituents of avocado fruits inhibit human oral cancer cell proliferation by targeting the EGFR/RAS/RAF/MEK/ERK1/2 pathway.
Avocado (Persea americana) fruits are consumed as part of the human diet and extracts have shown growth inhibitory effects in various types of human cancer cells, although the effectiveness of individual components and their underlying mechanism are poorly understood. Using activity-guided fractionation of the flesh of avocado fruits, a chloroform-soluble extract (D003) was identified that exhibited high efficacy towards premalignant and malignant human oral cancer cell lines. From this extract, two aliphatic acetogenins of previously known structure were isolated, compounds 1 [(2S,4S)-2,4-dihydroxyheptadec-16-enyl acetate] and 2 [(2S,4S)-2,4-dihydroxyheptadec-16-ynyl acetate]. In this study, we show for the first time that the growth inhibitory efficacy of this chloroform extract is due to blocking the phosphorylation of EGFR (Tyr1173), c-RAF (Ser338), and ERK1/2 (Thr202/Tyr204) in the EGFR/RAS/RAF/MEK/ERK1/2 cancer pathway. Compounds 1 and 2 both inhibited phosphorylation of c-RAF (Ser338) and ERK1/2 (Thr202/Tyr204). Compound 2, but not compound 1, prevented EGF-induced activation of the EGFR (Tyr1173). When compounds 1 and 2 were combined they synergistically inhibited c-RAF (Ser338) and ERK1/2 (Thr202/Tyr204) phosphorylation, and human oral cancer cell proliferation. The present data suggest that the potential anticancer activity of avocado fruits is due to a combination of specific aliphatic acetogenins that target two key components of the EGFR/RAS/RAF/MEK/ERK1/2 cancer pathway.


[Monozygotic twins with Williams-Beuren or 'elfen-face' syndrome].
Monozygotic male twins with the Williams-Beuren or 'elfin-face' syndrome are described. One twin showed the typical signs of supravalvular aortic stenosis, which is consistent with the cardiovascular symptoms usually found in this syndrome. The somatic and genetic aspects of the syndrome are discussed by reviewing the literature.


Bilateral CMUT Cells and Arrays: Equivalent Circuits, Diffraction Constants, and Substrate Impedance.
We introduce the large-signal and small-signal equivalent circuit models for a capacitive micromachined ultrasonic transducer (CMUT) cell, which has radiating plates on both sides. We present the diffraction coefficient of baffled and unbaffled CMUT cells. We show that the substrate can be modeled as a very thick radiating plate on one side, which can be readily incorporated in the introduced model. In the limiting case, the reactance of this backing impedance is entirely compliant for substrate materials with a Poisson's ratio less than 1/3. We assess the dependence of the radiation performance of the front plate on the thickness of the back plate by simulating an array of bilateral CMUT cells. We find that the small-signal linear model is sufficiently accurate for large-signal excitation, for the purpose of the determining the fundamental component. To determine harmonic distortion, the large-signal model must be used with harmonic balance analysis. Rayleigh-Bloch waves are excited at the front and back surfaces similar to conventional CMUT arrays.


Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure.
Mechanical ventilation is used to sustain life in patients with acute respiratory failure. A major concern in mechanically ventilated patients is the risk of ventilator-induced lung injury, which is partially prevented by lung-protective ventilation. Spontaneously breathing, nonintubated patients with acute respiratory failure may have a high respiratory drive and breathe with large tidal volumes and potentially injurious transpulmonary pressure swings. In patients with existing lung injury, regional forces generated by the respiratory muscles may lead to injurious effects on a regional level. In addition, the increase in transmural pulmonary vascular pressure swings caused by inspiratory effort may worsen vascular leakage. Recent data suggest that these patients may develop lung injury that is similar to the ventilator-induced lung injury observed in mechanically ventilated patients. As such, we argue that application of a lung-protective ventilation, today best applied with sedation and endotracheal intubation, might be considered a prophylactic therapy, rather than just a supportive therapy, to minimize the progression of lung injury from a form of patient self-inflicted lung injury. This has important implications for the management of these patients.


Lipopolysaccharides up-regulate Kir6.1/SUR2B channel expression and enhance vascular KATP channel activity via NF-kappaB-dependent signaling.
Sepsis is a severe medical condition causing a large number of deaths worldwide. Recent studies indicate that the septic susceptibility is attributable to the vascular ATP-sensitive K(+) (K(ATP)) channel. However, the mechanisms underlying the channel modulation in sepsis are still unclear. Here we show evidence for the modulation of vascular K(ATP) channel by septic pathogen lipopolysaccharides (LPS). In isolated mesenteric arterial rings, phenylephrine (PE) produced concentration-dependent vasoconstriction that was relaxed by pinacidil, a selective K(ATP) channel opener. The PE response was disrupted with a LPS treatment. In acutely dissociated aortic smooth myocytes the LPS treatment augmented K(ATP) channel activity, and hyperpolarized the cells. Quantitative PCR analysis showed that LPS raised Kir6.1 and SUR2B transcripts in a concentration-dependent manner, which was suppressed by transcriptional inhibition. Consistently, the same LPS treatment did not affect Kir6.1/SUR2B channels in a heterologous expression system. The LPS effect on Kir6.1 and SUR2B expression was abolished in the presence of NF-kappaB inhibitors. Several other Toll-like receptor ligands also stimulated Kir6.1 and SUR2B expression to a similar degree as LPS. Thus, the effect of LPS on vasodilation involves up-regulation of K(ATP) channel expression, in which the NF-kappaB-dependent signaling plays an important role.


Role of grooming in biological control of ticks.
Although many species of wild bovids live in tick infested environments, tick loads are usually kept to very low levels, primarily by frequent self grooming. Evidence from numerous studies on antelope in Africa strongly support the concept that the delivery of bouts of grooming reflects programmed grooming rather than stimulus driven or reactive grooming. In other words, grooming occurs in response to an endogenous generator that produces grooming bouts at periodic intervals, resulting in removal of ticks before they attach and begin to feed. In the same tick exposure environment, animals that groom most have the fewest ticks. The rate of programmed grooming is modulated by a number of interspecific and intraspecific determinants. Interspecific determinants include adult body size and whether or not the evolutionary habitat is tick dense or tick sparse. Intraspecific determinants include developmental stage of growth, gender (e.g., territorial male vs. female), ectoparasite exposure, and stage of arousal. Some of the intraspecific determinants appear to be mediated by systemic physiological influences suggesting there may be ways to improve grooming activity in weak groomers, such as cattle.


Cleavage furrow positioning in dividing Dictyostelium cells.
Accurate placement of the cleavage furrow is crucial for successful cell division. Recent advancements have revealed that diverse mechanisms have evolved across different branches of the phylogenetic tree. Here, we employed Dictyostelium cells to validate previous models. We observed that during metaphase and early anaphase, mitotic spindles exhibited random rotary movements which ceased when the spindle elongated by approximately 7 μm. At this point, astral microtubules reached the polar cell cortex and fixed the spindle axis, causing cells to elongate by extending polar pseudopods and divide along the spindle axis. Therefore, the position of the furrow is determined when the spindle orientation is fixed. The distal ends of astral microtubules stimulate the extension of pseudopods at the polar cortex. One signal for pseudopod extension may be phosphatidylinositol trisphosphate in the cell membrane, but there appears to be another unknown signal. At the onset of polar pseudopod extension, cortical flow began from both poles toward the equator. We suggest that polar stimulation by astral microtubules determines the furrow position, induces polar pseudopod extension and cortical flow, and accumulates the elements necessary for the construction of the contractile ring.


Opioid receptor blockade improves mesenteric responsiveness in biliary cirrhosis.
Arterial vasodilation with concomitant hyperdynamic circulation is a common finding in cirrhotic subjects. Elevated levels of plasma endogenous opioid peptides have been reported in cholestasis and cirrhosis. Increased opioid peptides contribute to different manifestations of chronic liver disease such as pruritus, ascitis, and hepatic encephalopathy. In this study the potential role of opioid system in cirrhosis-induced vascular hyporesponsiveness was investigated. Bile duct ligated and sham operated animals received daily subcutaneous administration of naltrexone, an opioid receptor antagonist (20 mg/kg/day), or saline for 28 days. After 4 weeks the superior mesenteric artery was cannulated and was perfused according to McGregor method and then phenylephrine vasoconstrictor response of mesenteric vessels (10(-10) to 10(-6 )mol) was examined. In order to evaluate the effects of acute opioid receptor blockade, additional groups of animals were treated by acute single intraperitoneal naltrexone injection (20 mg/kg). Plasma level of nitrite/nitrate as an indicator for nitric oxide production was measured. Biliary cirrhosis was accompanied with a decrease in baseline perfusion pressure in mesenteric vascular bed (P < 0.01). Chronic opioid receptor blockade significantly increased this parameter (P < 0.01). The maximum pressure response to phenylephrine was decreased significantly in cirrhosis while chronic naltrexone treatment completely improved it (P < 0.01). Acute single injection of naltrexone could not influence the understudied homodynamic parameters. Chronic opioid receptor blockade did not modulate the increased nitrite/nitrate levels following cholestasis. This study provided evidence on the contribution of endogenous opioid system to vascular hyporesponsiveness in cirrhosis which is not directly correlated to high plasma NO levels.


Electron dynamics in MoS2-graphite heterostructures.
The electron dynamics in heterostructures formed by multilayer graphite and monolayer or bulk MoS2 were studied by femtosecond transient absorption measurements. Samples of monolayer MoS2-multilayer graphite and bulk MoS2-multilayer graphite were fabricated by exfoliation and dry transfer techniques. Ultrafast laser pulses were used to inject electron-hole pairs into monolayer or bulk MoS2. The transfer of these photocarriers to the adjacent multilayer graphite was time resolved by measuring the differential reflection of a probe pulse. We found that photocarriers injected into monolayer MoS2 transfer to graphite on an ultrafast time scale shorter than 400 fs. Such an efficient charge transfer is key to the development of high performance optoelectronic devices with MoS2 as the light absorbing layer and graphite as electrodes. The absorption coefficient of monolayer MoS2 can be controlled by the carriers in graphite. This process can be used for interlayer coupling and control. In a bulk MoS2-graphite heterostructure, the photocarrier transfer time is about 220 ps, due to the inefficient interlayer charge transport in bulk MoS2. These results provide useful information for developing optoelectronic devices based on MoS2-graphite heterostructures.


Quantitative phase-flow MR imaging in dogs by using standard sequences: comparison with in vivo flow-meter measurements.
For evaluation of the feasibility and clinical potential of using the phase data from standard MR imaging sequences to measure blood flow, 11 vessels with diameters of 4 to 7 mm were imaged in seven dogs. The flow in either the superior mesenteric vein or the inferior vena cava was measured first at laparotomy (in ml/min) with electromagnetic flow meters. Immediately thereafter, these vessels were imaged by MR in 25-mm thick sections by using a standard spin echo (SE) 750/30 sequence with a Philips 0.5-T imager. Previous phase-flow calibration of the imager and sequence allowed calculation of the blood flow rates from the phase images that were used to measure the vessels' cross-sectional areas and blood phase values. Comparison of the measurements obtained with each technique showed a significant correlation (r = .977, p less than .05) between MR-imaging values and flow-meter measurements when the blood velocity was less than approximately 40 cm/sec, the known upper limit of the flow dynamic range for the MR hardware and sequence used. There was no correlation for blood velocities greater than 40 cm/sec. However, the range of blood flow velocities in dogs and man extends to more than 100 cm/sec. Thus, these results suggest that this technique might yield valuable adjunctive flow data in routine clinical imaging provided that improvements in hardware and software permit a larger dynamic range.


No apparent benefits of allonursing for recipient offspring and mothers in the cooperatively breeding meerkat.
Cooperative behaviours by definition are those that provide some benefit to another individual. Allonursing, the nursing of non-descendent young, is often considered a cooperative behaviour and is assumed to provide benefits to recipient offspring in terms of growth and survival, and to their mothers, by enabling them to share the lactation load. However, these proposed benefits are not well understood, in part because maternal and litter traits and other ecological and social variables are not independent of one another, making patterns hard to discern using standard univariate analyses. Here, we investigate the potential benefits of allonursing in the cooperatively breeding Kalahari meerkat, where socially subordinate females allonurse the young of a dominant pair without having young of their own. We use structural equation modelling to allow us to account for the interdependence of maternal traits, litter traits and environmental factors. We find no evidence that allonursing provides benefits to pups or mothers. Pups that received allonursing were not heavier at emergence and did not have a higher survival rate than pups that did not receive allonursing. Mothers whose litters were allonursed were not in better physical condition, did not reconceive faster and did not reduce their own nursing investment compared to mothers who nursed their litters alone. These patterns were not significantly influenced by whether mothers were in relatively good, or poor, condition. We suggest that allonursing may persist in this species because the costs to allonurses may be low. Alternatively, allonursing may confer other, more cryptic, benefits to pups or allonurses, such as immunological or social benefits.


Motivation for a health-literate health care system--does socioeconomic status play a substantial role? Implications for an Irish health policymaker.
In this article, the authors argue that the association between socioeconomic status and motivation for a health-literate health care system has implications for health policymakers. As Ireland now undergoes health care reform, the authors pose the question, "Should policymakers invest in health literacy as predominately a health inequalities or a public health issue?" Data from 2 cohorts of the Survey of Lifestyle, Attitudes and Nutrition (1998 and 2002) were used to construct a motivation for a health-literate health care system variable. Multivariate logistic regressions and concentration curves were used in the analyses of this variable. Of the 12,513 pooled respondents, 46% sought at least 1 attribute on a health-literate health care system. No discernible trend emerged from the main independent variables-social class grouping, medical card eligibility, level of education, and employment-in the regression analyses. The concentration curve, for 2002 data, graphically showed that the motivation for a health-literate health care system is spread equally across the income distribution. This analysis and more recent data suggest that health literacy in Ireland should be viewed predominately as a public health issue with a policy focus at a system level.


Phytoavailability of cadmium in long-term biosolids-amended soils.
Agronomic use of biosolids has raised concern that plant availability of biosolids-Cd will increase with time after cessation of biosolids application. It has been demonstrated that chemical extractability of Cd is persistently decreased in biosolids-amended soils. This study was conducted to determine if Cd phytoavailability in long-term biosolids-amended soils was also persistently decreased. Paired control and biosolids-amended soils were collected from three experimental sites where large cumulative rates of biosolids were applied about 20 yr ago. The pH of all soils [in 0.01 mol L(-1) Ca(NO(3))(2)] was adjusted to 6.5 +/- 0.2. Increasing rates of Cd-nitrate (from 0 to 10.0 mg Cd kg(-1) soil) enriched in (111)Cd stable isotope were added to all soils, and Romaine lettuce (Lactuca sativa L. var. longifolia Lam.) was grown in pots to bioassay phytoavailable Cd. After harvest, Cd concentrations in shoots and labile pool of Cd (Cd(L)) in soils were determined. The relationship between added salt-Cd and Cd concentrations in lettuce shoots was linear for all soils tested. Ratios of (shoot Cd):(soil Cd) slopes were highest in the control soils. Biosolids amendment decreased (shoot Cd):(soil Cd) slopes to varied extent depending on biosolids source, properties, and application rate. The decrease in slope in comparison to the control was an indication of the lower phytoavailability of Cd in biosolids-amended soils. A significant negative correlation existed between Cd uptake slopes and soil organic matter, free and amorphous Fe and Al oxides, Bray-P, and soil and plant Zn. Biosolids-Cd was highly labile (%L 80-95) except for Fulton County soil (%L = 61).


Mutations in the focal adhesion targeting region of deleted in liver cancer-1 attenuate their expression and function.
Deleted in liver cancer-1 (DLC-1) is a RhoGTPase-activating protein (RhoGAP) domain containing tumor suppressor that is often down-regulated in various cancer types. Previously, we have shown that DLC-1 is recruited to focal adhesions by binding to the Src homology 2 domains of tensins and the focal adhesion localization is critical for the tumor suppression activity of DLC-1. To investigate whether mutations in the focal adhesion targeting (FAT) region might occur and attenuate the expression, localization, and function of DLC-1, we have first mapped the FAT region to the amino acid residues from 201 to 500, and then sequenced cDNAs and genomic DNAs encoding the FAT region from cancer patients. Several missense and nonsense mutations were detected. All missense mutations were further examined for the potential effect on the function of DLC-1. Although these mutations did not seem to affect the focal adhesion localization of DLC-1, the activities of suppressing tumor cell growth were impaired in two mutants: T301K and S308I. Consistent with the fact that the RhoGAP activity of DLC-1 is essential for inhibiting tumor cell growth, the RhoGAP activities were significantly reduced in these mutants, suggesting that the FAT region also contains a regulatory element for its COOH-terminal RhoGAP domain. Our studies have shown that mutations in DLC-1 may lead to loss of function and contribute to the tumorigenesis, and have revealed an allosteric regulation site for its RhoGAP activity.


[Placental fatty acids in the guinea pig during pregnancy].
Prostaglandins are involved in different stages of reproduction. In respect to the placental metabolism of prostaglandins in the Guinea pig, we have studied the composition of Guinea pig placenta in free and total fatty acids. The arachidonic and dihomo-gamma-linolenic acids, precursors of prostaglandins of series 2 and 1, and the linoleic acid were quantified at different gestational ages using a gas-chromatography capillary column technique. Only the linoleic acid shows a significant increase at the end of gestation.


Long-Term Efficacy and Safety of Superficial Radiation Therapy in Subjects With Nonmelanoma Skin Cancer: A Retrospective Registry Study
Background: Low-dose superficial radiation therapy (SRT) effectively treats nonmelanoma skin cancer (NMSC) without requiring invasive excision. SRT is especially safe and effective among the elderly who comprise most patients with basal cell and squamous cell carcinomas (BCCs and SCCs). Objective: To demonstrate the long-term safety and efficacy of SRT for treating NMSC with a new generation device. Methods: A retrospective chart review was performed at four clinical study sites. The study population included male and female patients (N=516) treated with SRT for NMSC (N=776) including BCCs (n=448) and SCCs (n=328) prior to January 2015 with long-term follow-up records. Results: The overall mean (SD) total treatment dosage was 4652.33 (366.34) cGy (range, 3636.6 to 5455 cGy) administered over a mean of 12.3 (1.85) sessions. The overall Kaplan-Meier survival probability estimate (95% CI) was 0.989 (0.980, 0.998) at 24 months, 0.989 (0.969, 1.000) at 60 months, and 0.989 (0.942, 1.000) at 85 months. There were six recurrences of BCCs (n=4) and SCCs (n=2). The most common adverse event was hypopigmentation. Limitations: Retrospective study design and some incomplete data. Conclusion: It is estimated that 98.9% of nonmelanoma skin cancers will not recur after 85 months following superficial radiation therapy. J Drugs Dermatol. 2020;19(2)163-168. doi:10.36849/JDD.2020.4647


NDE application of ultrasonic tomography to a full-scale concrete structure.
Newly developed ultrasonic imaging technology for large concrete elements, based on tomographic reconstruction, is presented. The developed 3-D internal images (velocity tomograms) are used to detect internal defects (polystyrene foam and pre-cracked concrete prisms) that represent structural damage within a large steel reinforced concrete element. A hybrid air-coupled/contact transducer system is deployed. Electrostatic air-coupled transducers are used to generate ultrasonic energy and contact accelerometers are attached on the opposing side of the concrete element to detect the ultrasonic pulses. The developed hybrid testing setup enables collection of a large amount of high-quality, through-thickness ultrasonic data without surface preparation to the concrete. The algebraic reconstruction technique is used to reconstruct p-wave velocity tomograms from the obtained time signal data. A comparison with a one-sided ultrasonic imaging method is presented for the same specimen. Through-thickness tomography shows some benefit over one-sided imaging for highly reinforced concrete elements. The results demonstrate that the proposed through-thickness ultrasonic technique shows great potential for evaluation of full-scale concrete structures in the field.


Visits to specialists under Medicare: socioeconomic advantage and access to care.
This study examines the relationship between socioeconomic advantage and the likelihood of receiving specialty care in a nationally representative sample of older Americans participating in fee-for-service Medicare. In 1992, 62.9 percent of Americans aged 65 and older visited a specialist physician at least once. Being white, having more education, and having a higher income were each independently associated with a higher likelihood of visiting a specialist. Having insurance to supplement basic Medicare coverage was also independently associated with an increased likelihood of visiting a specialist; disadvantaged elders are less likely to have such supplemental insurance. Therefore, based both upon socioeconomic disadvantage and a lack of insurance to supplement the basic Medicare benefit, black, less educated and low-income elders are less likely to receive specialty services under fee-for-service Medicare. As the program evolves, it will be important to continue to monitor access to specialty care in vulnerable, socioeconomically disadvantaged populations.


Retrospective family study of childhood medulloblastoma.
Medulloblastoma is the most common malignant central nervous system tumor of childhood and can occur sporadically or in association with inherited cancer susceptibility syndromes such as the nevoid basal cell carcinoma syndrome (NBCCS). To determine whether an association existed between the risk of developing medulloblastoma and undiagnosed syndromes, we retrospectively reviewed clinical data on 33 patients with medulloblastoma from a single institution and compared them with their unaffected relatives (n = 46). Six patients had tumors showing desmoplastic histology. Two of the six met diagnostic criteria for NBCCS. One NBCCS patient had a missense mutation of patched-1 (PTCH1); the other had no identifiable PTCH1 mutation. Two patients with isolated desmoplastic medulloblastoma had an insertion and splice site mutation, respectively, in suppressor of fused (SUFU). All patients with nondesmoplastic medulloblastoma histology received molecular testing for SUFU. None of these patients had an identifiable mutation in PTCH1 or SUFU. We performed a clinical evaluation for Greig cephalopolysyndactyly syndrome (GCPS) in four medulloblastoma families, who exhibited macrocephaly as the only finding consistent with the diagnosis of GCPS. Molecular analysis of GLI3 in these four families was negative. There was a paucity of clinical findings among the majority of medulloblastoma patients in this study group to suggest a definable cancer genetic syndrome. We conclude that clinically recognizable syndromes are uncommon among patients with medulloblastoma, however, PTCH1 and SUFU mutations are present at a low but significant frequency.