Cluster of cases of massive hemorrhage associated with anticoagulant detection in race horses.
Five horses originating from 4 different California race tracks were submitted to the California Animal Health and Food Safety Laboratory for necropsy and diagnostic workup. The 5 horses had a history of sudden collapse and death during exercise. In all of them, massive hemoperitoneum and hemorrhages in other cavities or organs were observed. The liver from these 5 animals and from 27 horses that had been euthanized due to catastrophic leg injuries (controls) were subjected to a rodenticide anticoagulant screen. Traces of brodifacoum, diphacinone, or bromadiolone were detected in the 5 horses with massive bleeding (5/5), and no traces of rodenticides were detected in control horses (0/27). Other frequent causes of massive hemorrhages in horses were ruled out in 4 of the cases; one of the horses had a pelvic fracture. Although only traces of anticoagulants were found in the livers of these horses and the role of these substances in the massive bleeding remains uncertain, it is speculated that exercise-related increases in blood pressure may have reduced the threshold for toxicity of these anticoagulants.


Management of postoperative pain in Spain: a nationwide survey of practice.
Although the need for structured assessment and management of acute postoperative pain has been recognized, practices and responsibilities vary between and within hospitals and countries. We sought to determine current pain management practices in Spanish hospitals with and without acute pain services (APSs) or acute pain management programmes (APMPs) and compare them to practices reported for 1997-1998. Members of the Spanish Pain Society and APS/APMP heads were asked to respond to a survey. Responses were stratified by hospital size (< 200 or ≥ 200 beds) and APS/APMP presence or not. Categorical variables were described by percentages and the 95% confidence interval and continuous ones by the median and interquartile range. Responses were received from 42.4% of hospitals with ≥ 200 beds (vs. 9.6% of the smaller ones). We fully analysed only data for the larger hospitals, 57.7% of which had an APS or APMP. Full-time pain physicians were on staff in 28.6% of large hospitals; 25% had full-time nurses. Patients received written information about postoperative pain in 34.8% of APS/APMP hospitals, and 72% of them recorded pain assessments routinely. Protocols reflected interdepartmental consensus in 80.8%; training in postoperative pain was organised in 54%. Respondents thought pain was well or very well managed in 46.4%. In APS/APMP hospitals the following results had improved: provision of written information for patients (58.5% vs. 0%), the recording of pain assessments (93% vs. 43.8%), consensus on a pain scale (92.5% vs. 41.9%), use of protocols (99.7% vs. 55.2%), analysis of quality indicators (52.8% vs. 15.4%), training (73% vs. 26.9%), and respondents' satisfaction with pain management in their hospital (68.6% vs. 9.5%). The presence of an APS or APMP is associated with better results on indicators of quality of acute postoperative pain management.


[Comparative pharmacological effects of dl-amphetaminil and dl-amphetamine in the rat].
The present investigation shows that amphetamine and amphetaminil produce identical pharmacological effects (increase in motility and body temperature, anorexia, stereotypic behaviour). There was neither a qualitative difference under "open field" conditions nor a difference in the capacity of modifying the reserpine induced syndrome. In isomolar doses amphetamine was somewhat more effective. Almost the same amounts of amphetamine were found in blood and brain following amphetamine or amphetaminil administration, with exception of somewhat higher peak levels after amphetamine. These results favor the hypothesis that amphetaminil effects are produced by the amphetamine molecule.


Gender Differences in Post-Traumatic Stress.
Acute stress can trigger cardiovascular events and disease. The earthquake is an "ideal" natural experiment for acute and chronic stress, with impact mainly on the cardiovascular system. On May 20th and 29th, 2012, two earthquakes of magnitude 5.9° to 6.4° on the Richter scale, hit the province of Modena and Reggio Emilia, an area of the north-center of Italy never considered at seismic risk. The purpose of our study was to assess whether there were gender-specific differences in stress-induced incidence of cardiovascular events and age of patients who arrived at the Emergency Departments (ED) of the three main teaching hospitals of the University of Modena and Reggio Emilia. Global access of patients, divided in relation to age, gender, and diagnosis was compared with that one detected in the same departments and in the same interval of time in 2010. The data collected were relative to consecutive cases derived by retrospective chart and acute cardiovascular events were classified according to ICD-9 (International Classification of Diseases, ninth revision). A total of 1,401 accesses were recorded in the year of earthquake versus 530 in 2010 (p ≤ 0.05), with no statistically significant differences in number of cases and mean age in relation to gender, despite the number of women exceeded that of men in 2012 (730 vs. 671); the opposite occurred, in 2010 (328 vs. 202). The gender analysis of 2012 showed a prevalence of acute coronary syndromes (ACSs 177 vs. 73, p ≤ 0.03) in men, whereas women presented more strokes and transient ischemic attacks (TIAs) (90 vs. 94, p ≤ 0.05), atrial fibrillation (120 vs. 49, p ≤ 0.05), deep venous thrombosis and pulmonary embolism (DVT/PE; 64 vs. 9, p ≤ 0.05), panic attacks (124 vs. 26, p ≤ 0.03), aspecific chest pain (122 vs. 18, p ≤ 0.05), TakoTsubo cardiomyopathy (10 vs. 0, p ≤ 0.05), and DVT/PE (61 vs. 3, p ≤ 0.03). The gender analysis of 2010 showed no difference in number of accesses and age, with higher incidence of ACS in men (130 vs. 34, p ≤ 0.05) and aspecific chest pain in women (42 vs. 5, p ≤ 0.05). The analysis between 2012 and the standard period (2010) showed women recurring to ED in larger number with more panic attacks (124 vs. 3, p ≤ 0.01), more atrial fibrillation (120 vs. 40, p ≤ 0.01) and, as a possible consequence, more TIAs and strokes (190 vs. 25, p ≤ 0.005), more TakoTsubo (10 vs. 0, p ≤ 0.05), DVT/PE (61 vs. 3, p ≤ 0.05), and aspecific chest pain (122 vs. 5, p ≤ 0.01). The difference between men's accesses to ED was less striking, but in 2012 men reported more panic attacks (26 vs. none, p ≤ 0.05), more atrial fibrillations, TIAs, and strokes (49 vs. 13, p ≤ 0.05 and 94 vs. 18, p ≤ 0.03). In conclusion, clinical (stress induced) events recorded during and immediately after the 2012 earthquakes were quite different between women and men, although the pathophysiological mechanism was probably the same, consisting acute sympathetic nervous activation, with elevation of blood pressure and heart rate, endothelial dysfunction, platelet and hemostatic activation, increased blood viscosity, and hypercoagulation. Women, in our observation, appeared to be more sensitive and responsive to acute stress, although men also appeared to suffer from stress effects when compared with a standard period, which, nevertheless, reflects in our population the most common epidemiology of gender difference in ED accesses for cardiovascular events.


[An immunoenzyme test used for the detection of antibodies to rinderpest: the advantage of using a purified virus cultivated in a cell line].
Two types of in vitro assays (enzyme immunoassay and sero-neutralization test) were compared for their ability to detect antibodies to rinderpest virus in field sera from West African bovines. Purified virus grown on Vero cells (Ag/Vero) or bovine kidney cells (Ag/BK), were tested as antigen in enzyme-linked immunoassays (EIA). The results of the comparative evaluation of the two antigens by EIA, prove that Ag/Vero did enhance the sensitivity and the specificity of the test in comparison to Ag/BK and offers a 94% correspondence with seroneutralization.


Prevalence of udder infections and mastitis in 50 California dairy herds.
The California mastitis test (CMT) and bacteriologic culture were performed on samples of bulk-tank milk and cow-composite milk (n = 23,138 cows) from 50 California dairies, 19 of the 50 with known mastitis problems. Thirty-eight (76.0%) bulk-tank milk samples and 12,334 (53.3%) cows were positive by results of the CMT. Potential mastitis agents were isolated from 5,085 (22%) cows. Staphylococcus aureus was isolated from all 50 herds, Streptococcus agalactiae was isolated from 47 herds, and Mycoplasma sp was isolated from 24 herds. For cow-composite milk samples, the prevalences were 9.3% for Str agalactiae, 9.1% for S aureus, 0.9% for Mycoplasma sp, 1.2% for coliform bacteria, 0.9% for other streptococci, 0.8% for coagulase-negative staphylococci, and 1.3% for other organisms. The relative sensitivity and the relative specificity of the CMT performed on cow-composite milk samples were 83.4% and 55.2%, respectively, and the predictive value of positive CMT results was 34.2%.


Assessment of oral health conditions presented in photographs - is there a difference between dentists and non-dental professional caregivers?
Photographs can help non-dental professional caregivers to identify problems when inspecting the mouth of care-dependent older individuals. This study evaluated whether the assessment of oral health-related conditions presented in photographs differed between dentists and non-dental professional caregivers. One-hundred-and-seventy-nine photographs were taken from long-term care facility residents and from patients at the Department of Dentistry of a University Hospital. The following oral health aspects were depicted: denture hygiene, oral hygiene, teeth, gums, tongue and palate/lips/cheeks. Collection continued until for each oral health aspect a pool of photographs was available that showed conditions from perfect health and hygiene to severe problems. A segmented Visual Analogue Scale was applied to assess the conditions presented in the photographs. Each photograph was assessed by each participant of this study. The benchmark was established by three dentists with academic-clinical expertise in gerodontology, special needs dentistry and periodontology. For each photograph, they provided a collective score after reaching consensus. Photographs were assessed individually by 32 general dentists and by 164 non-dental professional caregivers. Linear mixed effects models and generalized linear mixed effects models were fitted and mean squared errors were computed to quantify differences between both groups. For the different oral health aspects, absolute distances from the benchmark scores were 1.13 (95%CI:1.03-1.23) to 1.51 (95%CI:1.39-1.65) times higher for the caregivers than for the dentists. The odds to overestimate the condition were higher for the caregivers than the dentists for oral hygiene (OR = 0.72, 95%CI = 0.62-0.84) and teeth (OR = 0.74; 95%CI = 0.61-0.88). The odds to underestimate the condition were higher for the caregivers than the dentists for gums (OR = 1.39; 95%CI:1.22-1.59) and palate/lips/cheeks (OR = 1.22; 95%CI = 1.07-1.40). Over all assessments, the variance in caregiver scores was 1.9 (95%CI:1.62-2.23) times higher than that for the dentists. Small but significant differences were found between dentists and non-dental professional caregivers assessing oral health-related conditions presented in photographs. When photographs are used to aid non-dental professional caregivers with the oral health assessment, these visualizations should be complemented with comments to facilitate accurate interpretation.


Mathematical modeling to predict the sub-bandage pressure on a conical limb for multi-layer bandaging.
The effectiveness of the compression treatment by a medical compression bandage is dependent on the pressure generated at the interface between the bandage and the skin. This pressure is called interface pressure or sub-bandage pressure. The performance of a bandage depends upon the level of interface pressure applied by the bandage and the sustenance of this pressure over time. The interface pressure exerted by the bandage depends on several other factors like limb shape or size, application technique, physical and structural properties of the bandage, physical activities taken by the patient, etc. The current understanding of how bandages apply pressure to a limb is based on the Law of Laplace, which states that tension in the walls of a container is dependent on both the pressure of the container's content and its radius. This concept was translated mathematically into equation relating pressure to tension and radius by Thomas. In addition, a modified equation was generated by multiplying the model with a constant that represents the number of bandage layers in order to use the model to estimate the pressure applied by multi-layer bandages. This simple multiplication adjustment was questioned by researchers. They had doubts about the model validity and whether it can be used to predict the sub-bandage pressure applied by pressure garments. One of the questions that were raised regarding the bandage thickness affecting the sub-bandage pressure has been recently explored by Al Khaburi where he used the thin and thick cylinder shell theory to study the effect of Multi Component Bandage's (MCB) thickness on the sub-bandage pressure. The model by Al Khaburi and the earlier models developed for pressure prediction are all based on calculations considering the cylindrical limb shapes although the human limb normally is wider at the calf and reduces in circumference towards the ankle. So in our approach, the bandage is assumed to take a conical shape during application and membrane shell theory is used for developing pressure prediction model for multi-layers of bandage. Both analytical and experimental work showed that the effect of bandage thickness and the geometry of the limb on pressure produced by multi-layers of bandage are significant. The model developed when compared to the data obtained using experimental setup confirmed the validity of the mathematical model for multi-layers of bandage based on conical geometry of the limb.


A generalized network based on multi-scale densely connection and residual attention for sound source localization and detection.
Sound source localization and detection (SSLD) is a joint task of identifying the presence of individual sound events and locating the sound sources in space. However, due to the diversity of sound events and the variability of sound source location, SSLD becomes a tough task. In this paper, we propose a SSLD method based on a multi-scale densely connection (MDC) mechanism and a residual attention (RA) mechanism. We design a MDC block to integrate the information from a very local to exponentially enlarged receptive field within the block. We also explored three kinds of RA blocks that can facilitate the conductivity of information flow among different layers by continuously adding feature maps from the previous layers to the next layer. In order to recalibrate the feature maps after convolutional operation, we design a dual-path attention (DPA) unit that is largely embodied in MDC and RA blocks. We firstly verified the effectiveness of the MDC block, RA block, and DPA unit, respectively. We then compared our proposed method with another four methods on the development dataset; finally, with SELDnet and SELD-TCN on another five datasets, experimental results show the generalization of our proposed method.


Estimation of group means when adjusting for covariates in generalized linear models.
Generalized linear models are commonly used to analyze categorical data such as binary, count, and ordinal outcomes. Adjusting for important prognostic factors or baseline covariates in generalized linear models may improve the estimation efficiency. The model-based mean for a treatment group produced by most software packages estimates the response at the mean covariate, not the mean response for this treatment group for the studied population. Although this is not an issue for linear models, the model-based group mean estimates in generalized linear models could be seriously biased for the true group means. We propose a new method to estimate the group mean consistently with the corresponding variance estimation. Simulation showed the proposed method produces an unbiased estimator for the group means and provided the correct coverage probability. The proposed method was applied to analyze hypoglycemia data from clinical trials in diabetes.


Transcatheter occlusion of a persistent left superior vena cava to the left atrium using the transseptal approach.
A persistent left superior vena cava (LSVC) is a common venous anomaly, occurring in up to 10% of patients with congenital heart defects. Usually, a LSVC drains into the coronary sinus, then to the right atrium. The LSVC can drain directly to the left atrium, resulting in a right-to-left shunt and systemic desaturation. Historically, surgery has been used to address this lesion. Transcatheter occlusion of the LSVC is an alternative to surgery. We report the novel use of the transseptal approach to access the LSVC, and device occlusion using the Amplatzer Vascular Plug-II.


Robust Adaptive Control Scheme for Teleoperation Systems With Delay and Uncertainties.
This paper proposes a robust adaptive algorithm that effectively copes with time-varying delay and uncertainties in Internet-based teleoperation systems. Time-delay induced by the communication network, as a major problem in teleoperation systems, along with uncertainties in modeling of robotic manipulators and remote environment warn the stability and performance of the system. A robust adaptive control algorithm is developed to deal with the system uncertainties and to provide a smooth estimation of delayed reference signals. The proposed control algorithm generates chattering-free torques which is one of the practical considerations for robotic applications. In addition, the achieved input-to-state stability gains do not necessarily require high gain control torques to retain the system's stability. Experimental simulation studies validate the effectiveness of the proposed control strategy on a teleoperation system consisting of a Phantom Omni Haptic device and SimMechanics model of the industrial manipulator UR10. The validation of the proposed control methodology was executed through a real-time Internet-based communication established over 4G mobile networks between Australia and Scotland.


A Mixture Containing Fermented Achyranthes japonica Nakai Ameliorates Osteoarthritis in Knee Joints of Monoiodoacetate-Injected Rats.
We demonstrated the effect of a mixture containing fermented Achyranthes japonica Nakai (FS) in the context of a monosodium iodoacetate (MIA)-induced osteoarthritis animal model. The mineralization, anabolic and catabolic factors, and the amount of cytokines within the articular cartilage of rats were measured after administration of MIA. We found that dietary supplementation with methylsulfonylmethane (positive control) and FS (FS 100 mg/kg body weight [b.w.] and FS 300 mg/kg b.w.) effectively suppressed pathological changes in the knee joint and inhibited changes in the architectural and mineralization parameters. In addition, prostaglandin E2 (PGE2) and proinflammatory cytokines in the serum and catabolic factors, including matrix metalloproteinase (MMP)-3 and MMP-7 in articular cartilage, were decreased by dietary supplementation with FS in MIA-induced osteoarthritis. Based on these findings, we suggest that FS can be used for the development of potential therapies for osteoarthritis.


Synthesis, structures, adsorption behaviour and magnetic properties of a new family of polynuclear iron clusters.
Solvothermal reactions of 1,10-phenanthroline-2,9-dicarbaldehyde dioxime (H(2)phendox) with FeCl(3)·6H(2)O or FeBr(3) under solvothermal conditions yielded two trinuclear iron(III) clusters [Fe(III)(3)(mu(3)-O)(phendox)(3)]X·14H(2)O (X = Cl 1·14H(2)O, Br 2·14H(2)O) and three hexanuclear iron(III) and iron(II) clusters, [Fe(III)(6)(mu(4)-O)(2)(MeO)(6)X(4)(phendox)(2)]·MeOH (X = Cl , Br 4) and (H(3)O)[Fe(II)(6)(mu(6)-Cl)(phenda)(6)]·6H(2)O (5·6H(2)O). The phendox(2-) ligand is very useful in constructing magnetically active and stable high-nuclearity metal clusters in that the phenanthroline rings and the oxime nitrogen atoms grasp the metal ions tightly while the two oxygen atoms on the oximates can link other metal centres in the shortest pairwise magnetic exchange pathway. Adjacent Fe(3)(mu(3)-O)(phendox)(3)(+) motifs in 1 and 2 are packed by off-set pi-pi interactions of the aromatic rings on phendox(2-) to generate a 3D supramolecular architecture in the honeycomb topology and with 1D hexagonal channels in the dimension of 13 x 13 Å along the c-axis. 2 is stable upon the removal of guest molecules and the desolvated compound absorbed considerable amount of N(2), CO(2) and H(2). 3 and 4 are isostructural. Two mu(4)-O(2-) and two phendox(2-) units link four metal atoms into a coplanar butterfly-shaped unit with the mu(4)-O(2-) slightly above and below the plane (+/-0.264 Å). The other two Fe(III) ions are capped on the alternate planes via the three bridging mu(2)-methoxides and accordingly form an unprecedented hexanuclear Fe(III) cluster. Furthermore, the oximes underwent hydrolysis to yield carboxylate groups and the resulted 1,10-phenanthroline-2,9-dicarboxylate link the iron atoms to form a hexanuclear cluster of 5. Magnetic studies show that the antiferromagnetic interactions are present in the Fe(3)O core of 2 and in the (mu(6)-Cl)Fe(6)(mu-O)(12) core of 5.


Investigation of Genetic Dependencies Using CRISPR-Cas9-based Competition Assays.
Gene perturbation studies have been extensively used to investigate the role of individual genes in AML pathogenesis. For achieving complete gene disruption, many of these studies have made use of complex gene knockout models. While these studies with knockout mice offer an elegant and time-tested system for investigating genotype-to-phenotype relationships, a rapid and scalable method for assessing candidate genes that play a role in AML cell proliferation or survival in AML models will help accelerate the parallel interrogation of multiple candidate genes. Recent advances in genome-editing technologies have dramatically enhanced our ability to perform genetic perturbations at an unprecedented scale. One such system of genome editing is the CRISPR-Cas9-based method that can be used to make rapid and efficacious alterations in the target cell genome. The ease and scalability of CRISPR/Cas9-mediated gene-deletion makes it one of the most attractive techniques for the interrogation of a large number of genes in phenotypic assays. Here, we present a simple assay using CRISPR/Cas9 mediated gene-disruption combined with high-throughput flow-cytometry-based competition assays to investigate the role of genes that may play an important role in the proliferation or survival of human and murine AML cell lines.


Behavioral and histopathological consequences of paraquat intoxication in mice: effects of alpha-synuclein over-expression.
Genetic variability in the alpha-synuclein gene and long-term exposure to the pesticide paraquat constitute possible risk factors for sporadic Parkinson's disease. The goal of the present study was to further characterize the effects of paraquat in mice as a model of Parkinson's disease and to determine whether it acted synergistically with alpha-synuclein over-expression to cause nigrostriatal cell death or dysfunction. Paraquat (10 mg/kg i.p.) was administered once a week for 3 weeks to mice over-expressing human alpha-synuclein under the Thy1 promoter and their wild-type littermates. The effect of paraquat on catecholaminergic neurons was reminiscent of that of Parkinson's disease, with preferential loss of dopaminergic neurons in the ventral tier of the substantia nigra pars compacta and loss of tyrosine hydroxylase staining in the locus coeruleus. alpha-Synuclein over-expression did not increase paraquat-induced cell loss, and paraquat did not worsen the behavioral deficits observed in the transgenic mice. However, paraquat markedly increased proteinase-K-resistant alpha-synuclein aggregates in substantia nigra of the transgenic mice. The data further validate the use of paraquat to model Parkinson's disease in mice and show that although paraquat and alpha-synuclein over-expression act synergistically to increase protein aggregation in vivo, this interaction does not result in short-term neuroprotection or increased vulnerability of nigrostriatal neurons.


States and functions of tyrosine residues in Escherichia coli asparaginase II.
The importance of five tyrosine residues of Escherichia coli asparaginase II (EcA2) for catalysis and protein stability was examined by site-directed mutagenesis, chemical modification of wild-type and variant enzymes, and by thermodynamic studies of protein denaturation. While the tyrosine residue Y25 is directly involved in catalysis, the hydroxyl groups of residues Y181, Y250, Y289 and Y326 are not necessary for EcA2 activity. However, residues Y181 and Y326 are crucial for stabilization of the native EcA2 tetramer. pH titration curves showed that the active-site residue Y25 has a normal pKa while the C-terminal Y326 is unusually acidic. 1H-NMR signals of a peculiar ligand-sensitive tyrosine residue were assigned to Y25. These and other data suggest that a peptide loop (residues 14-27) which shields the active site during catalysis is highly flexible in the free enzyme.


Middle cerebral to umbilical artery Doppler ratio in post-date pregnancies.
To determine which antepartum test is the best predictor of post-date-related adverse outcome among the amniotic fluid index (AFI), nonstress test (NST), biophysical profile, or middle cerebral artery to umbilical artery Doppler ratio. Pregnant women of 41 or more weeks' gestation with singleton fetuses and vertex presentations underwent antepartum testing twice a week. Pulsed Doppler ultrasound was used to obtain the flow velocity waveforms from the umbilical and middle cerebral arteries. Adverse post-date-related outcome was defined as the occurrence of meconium aspiration syndrome, cesarean delivery for fetal distress, or fetal acidosis. The predictive values of an AFI equal to or less than 5 cm, a biophysical profile score equal to or greater than 6, a nonreactive NST, and a middle cerebral artery to umbilical artery ratio less than 1.05 in identifying adverse outcome were compared. Forty-nine women met the inclusion criteria; ten (20.4%) had an adverse outcome. A middle cerebral artery to umbilical artery ratio of less than 1.05 was found to be the best predictor of adverse outcome, with a sensitivity of 80%, specificity of 95%, positive predictive value of 80%, and negative predictive value of 95%. The other three diagnostic tests had sensitivities equal to or less than 40%. The middle cerebral artery to umbilical artery ratio was also a better discriminator of adverse outcome than either the umbilical artery systolic-diastolic (S/D) ratio or the middle cerebral artery S/D ratio. Although the sample size of our study was small, the results suggest that a middle cerebral artery to umbilical artery ratio of less than 1.05 is an accurate method of predicting post-date-related adverse outcome.


Control of Varroa Destructor in Kazakhstan.
Varroa mite is one of the most dangerous bee parasites and causes a lot of damage to the beekeeping industry. Several chemical and herbal medicines have been used to control this mite so far. In this study, the effects of Artemisia absinthium and Hypericum perforatum prescription to control Varroa mite were investigated. To this end, a total of 380 bee colonies in 5 areas in Kazakhstan were considered. The bitter wormwood herbs and Hypericum extracts were mixed in a ratio of 1:1, and then, prepared in a ratio of 1:10 with sugar syrup (100 ml infusion per 1 liter of sugar syrup). An amount of 200 ml of the prepared solution was used for 5-7 days per colony after medical collection and honey pumping. The percentage of mite infestation at the beginning and end of the experimental period, which was spring, summer, and autumn, and the number of worker mites and worker bees were determined daily. At the beginning of the experiment, the percentage of mite infestation in the experimental hives was not significantly different; however, at the end of the experiment, there was a significant difference between the experimental treatments. The use of a mixture of A. absinthium and H. perforatum extract significantly reduced the abundance index of Varroa mite to 0. Due to the adverse effects of chemical drugs and their high cost, it is recommended to use this extract to control Varroa mite contamination.


Characteristics of cases and deaths arising from SARS-CoV-2 infection in Zambia: March 2020 to April 2021.
since March 2020, Zambia has been experiencing a SARS-CoV-2 epidemic. Little data has been reported on cases and deaths arising from COVID-19 in Africa. We described the demographic characteristics of these cases and deaths in Zambia. we analyzed data on all persons testing positive for SARS-CoV-2 from 18th March 2020 to 25th April 2021 in Zambia. COVID-19 cases were identified through port-of-entry surveillance, contact-tracing, health-care-worker testing, health-facility-based and community-based screening and community-death screening. All diagnoses were confirmed using real-time-polymerase-chain-reaction and rapid-antigen-test-kits of nasopharyngeal specimens. We analyzed age, sex, and date-of-reporting according to whether the cases or deaths occurred during the first wave (1st July to 15th September 2020) or the second wave (15th December 2020 to 10th April 2021). We computed Mann-Whitney-U-test to compare medians of continuous variables and chi-square tests to compare differences between proportions using R. a total 1,246 (1.36%) deaths were recorded among 91,378 confirmed cases during March 2020-April 2021 in Zambia. Persons who died were older than those who did not (median age 50 years versus 32.0 years, p< 0.001). Although only 4.7% of cases were among persons aged >60 years, most deaths (31.6%) occurred in this age group (p<0.001). More deaths (83.5%) occurred in the community than in health facilities (p<0.001). during the SARS-CoV-2 epidemic in Zambia, most deaths occurred in the community, indicating potential gaps in public health messaging about COVID-19. Improving health-seeking behaviors for COVID-19 through public messaging campaigns and engaging key community stakeholders in Zambia might reduce avoidable mortality. As the group most impacted by COVID-19 mortality, older persons might need enhanced outreach and linkage to care.


Exploration of a novel physical therapy protocol that uses a sensory substitution device to improve the standing postural balance of children with balance disorders.
To explore if an intensive balance training protocol that incorporated the BrainPort sensory substitution device improves the standing postural balance of children with balance disorders. Eight children with balance disorders received 8-weeks of balance training while using the BrainPort device. Pre- and post-intervention changes in the Bruininks-Oseretsky Test of Motor Proficiency balance subtest (BOT-2) scores, standing duration on an unstable surface, and center of pressure (COP) sway were assessed. Post-intervention, the BOT-2 balance subtest scores increased by 29.6% and demonstrated clinically meaningful improvements. Overall, the standing duration with vision increased. The standing duration on the unstable surface without vision increased significantly from pre- to post-intervention. However, anterior-posterior (AP) and medial-lateral (ML) sway did not change post-intervention. The children also reported new functional activities (i.e. riding a bike, standing on unsteady or narrow surfaces). Balance training with the BrainPort sensory substitution device has the potential to result in clinically relevant improvements in the standing postural balance of children with balance disorders.


Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome.
Phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P(2)] is a signaling phospholipid implicated in a wide variety of cellular functions. At synapses, where normal PtdIns(4,5)P(2) balance is required for proper neurotransmission, the phosphoinositide phosphatase synaptojanin 1 is a key regulator of its metabolism. The underlying gene, SYNJ1, maps to human chromosome 21 and is thus a candidate for involvement in Down's syndrome (DS), a complex disorder resulting from the overexpression of trisomic genes. Here, we show that PtdIns(4,5)P(2) metabolism is altered in the brain of Ts65Dn mice, the most commonly used model of DS. This defect is rescued by restoring Synj1 to disomy in Ts65Dn mice and is recapitulated in transgenic mice overexpressing Synj1 from BAC constructs. These transgenic mice also exhibit deficits in performance of the Morris water maze task, suggesting that PtdIns(4,5)P(2) dyshomeostasis caused by gene dosage imbalance for Synj1 may contribute to brain dysfunction and cognitive disabilities in DS.


Characteristics of stable isotope signature of diet in tissues of captive Japanese macaques as revealed by controlled feeding.
We determined the magnitude of isotopic fractionation of carbon and nitrogen stable isotope ratios (as enrichment factors, Δδ(13)C and Δδ(15)N, respectively) between the tissues and diets of captive Japanese macaques (Macaca fuscata) using a controlled feeding experiment, to provide basic data for reconstructing their feeding habits. The Δδ(13)C and Δδ(15)N values, respectively, were 0.9 ± 0.2 ‰ (mean ± standard deviation, SD) and 3.0 ± 0.3 ‰ for whole blood, 1.3 ± 0.2 ‰ and 4.3 ± 0.3 ‰ for plasma, and 0.8 ± 0.2 ‰ and 3.0 ± 0.2 ‰ for red blood cells. However, the Δδ(13)C and Δδ(15)N values for hair were 2.8 ± 0.3 ‰ and 3.4 ± 0.2 ‰, respectively. No difference was detected in the δ(13)C and δ(15)N values of hair sampled from different parts of the body. We investigated the effects of diet on δ(13)C in growing hair by alternating the diet of the macaques each month between two diets that differed markedly in δ(13)C. Hair regrown after shaving repeatedly recorded the δ(13)C of the diet consumed during the time of hair growth. On the other hand, hair naturally grown during the diet-change experiment did not show a clear pattern. One possible reason is that the hair had grown abnormally under unnatural indoor conditions and showed complicated isotope signatures. To reconstruct the long-term feeding history of Japanese macaques, we need to further clarify the relationships between the stable isotope signature of diet and various body tissues.


Has the optimum time for faecal nematode egg count reduction testing in sheep in New Zealand changed?
To determine what, if any, changes have taken place in the optimum time, for undertaking faecal egg count reduction tests (FECRT) in sheep in New Zealand. A comparison was made between the numbers and types of nematode genera adequately represented for testing purposes (faecal nematode egg count (FEC) of ≥50 epg) in initial FECRT case submissions to a veterinary laboratory in New Zealand, during two 4-year periods, in 1992-1995 and 2006-2009. Although there were some minor differences between them, the seasonal patterns of occurrence remained basically the same for all parasite genera in both datasets, with their individual peak periods of representation occurring during February to May in all instances. Not surprisingly, this period of maximum seasonal occurrence for each parasite genus also coincided with those months of the year when the greatest numbers of worm genera were adequately represented for faecal nematode egg count reduction (FECR) testing. The results of this study indicate that the optimum time for conducting FECRT in sheep in New Zealand continues to be during the late summer-autumn months of February to May. However, they also reaffirmed that even during this optimal period there are still likely to be many occasions when relatively few nematode genera may be sufficiently well represented for satisfactory FECR testing. Accordingly, veterinary practitioners ought to be aware that, in order to obtain a complete picture of the resistance status of all worm genera on a particular property, such testing may need to be carried out on more than one occasion.


[Clinical manifestations of retinal artery macroaneurysms].
To summarize the clinical characteristics of retinal arterial macroaneurysm and to improve the diagnosis accuracy in order to differentiate it from other fundus diseases. It was a retrospective case series. of fluorescein angiography or indocyanine angiography, associated with ultrasound, OCT and several other examinations were analyzed in 22 patients (22 eyes) with retinal arterial macroaneurysm. There were 6 men and 16 women in the 22 patients. The age of all the patients was from 54 to 82 years, and the mean age was 70 years. In the 22 patients, the patient with a single macroaneurysm was 19, and with two macroaneurysms was 3. All 22 patients were affected unilaterally. Macroaneurysms were found only in the temporal artery branches (16 eyes in superior branch and 6 eyes in inferior branch). All macroaneurysms were located in the branches graded 1 to 3. All patients showed pre-retinal hemorrhage and/or vitreous hemorrhage. Sixteen patients suffered from hypertension and five patients had diabetes mellitus. The patient with best corrected visual acuity < 0.05 was 10, 0.05 to 0.2 was 6, 0.3 to 0.6 was 5 and > or = 0.7 was 1. All patients showed retinal arteriosclerosis. After the treatment, 11 patients were pursued,and the patient with best corrected visual acuity < 0.05 was 1, 0.05 to 0.2 was 4 and > or = 0.7 was 1. Clinical features of retinal arterial macroaneurysm include focal dilation of retinal artery with hemorrhages and exudates, associated with retinal arteriosclerosis. These clinical characteristics can be used to differentiate retinal arterial macroaneurysm from other fundus diseases.


[The second opinion procedure in electrophysiology : Legal aspects for treatment providers and second opinion providers].
Patients with statutory health insurance in Germany have the right to obtain a second opinion at the expense of their health insurance in addition to that of their primary practitioner before certain procedures are carried out. This gives rise to various legal obligations and questions on the part of both the practitioner and the second opinion provider. This article outlines, based on the legal situation, which obligations exist for both practitioners and second opinion providers, and who is suitable to provide a second opinion. Focus is placed on informing patients about the possibility of obtaining a second opinion. On the other hand, it explains which requirements second opinion providers have to fulfill and which duties are incumbent on them.


Polygenic Basis and the Role of Genome Duplication in Adaptation to Similar Selective Environments.
Genetic changes underlying adaptation vary greatly in terms of complexity and, within the same species, genetic responses to similar selective pressures may or may not be the same. We examine both complex (supergene) and simple (SNP) genetic variants occurring in populations of rainbow trout (Oncorhynchus mykiss) independently isolated from ocean access and compared them to each other and to an anadromous below-barrier population representing their ancestral source to search for signatures of both parallel and nonparallel adaptation. All landlocked populations displayed an increased frequency of a large inversion on chromosome Omy05, while 3 of the 4 populations exhibited elevated frequencies of another inversion located on chromosome Omy20. In addition, we identified numerous regions outside these 2 inversions that also show significant shifts in allele frequencies consistent with adaptive evolution. However, there was little concordance among above-barrier populations in these specific genomic regions under selection. In part, the lack of concordance appears to arise from ancestral autopolyploidy in rainbow trout that provides duplicate genomic regions of similar functional composition for selection to act upon. Thus, while selection acting on landlocked populations universally favors the resident ecotype, outside of the major chromosomal inversions, the resulting genetic changes are largely distinct among populations. Our results indicate that selection on standing genetic variation is likely the primary mode of rapid adaptation, and that both supergene complexes and individual loci contribute to adaptive evolution, further highlighting the diversity of adaptive genomic variation involved in complex phenotypic evolution.


Case Analysis and Literature Review of Thirteen Patients with Autoimmune Encephalitis.
To investigate the clinical manifestations, laboratory and imaging examinations, and the treatment outcomes of autoimmune encephalitis (AE). The clinical data of 13 patients with autoimmune encephalitis who were hospitalized in the department of neurology, Liaocheng People's Hospital from July 2016 to August 2018 were retrospectively analyzed. The average age of onset of the 13 patients was 45 years, including 6 cases (46%) of anti-NMDAR encephalitis, 3 cases (23%) of anti-GABAB receptor encephalitis, and 4 cases (30%) of anti-LG11 encephalitis, and 4 of them showed abnormal signals of brain MRI (30%). 13 patients (100%) had cognitive impairment and psychiatric symptoms; seizures occurred in 12 patients (92%); lung cancer was found in 1 patient (7%). One case was given up because of the treatment of lung cancer, the other was controlled obviously in epilepsy, and cognitive impairment and abnormal mental behavior were also significantly improved. Patients with AE still need to be diagnosed early to avoid missed diagnosis and receive early immunosuppressive therapy, which could effectively reduce mortality and morbidity. A detailed history, clinical manifestations, and positive results for specific NSAbs tests can confirm the diagnosis, and the treatment is mainly done by immunosuppressive therapy.


A platform for exploration into chaining of web services for clinical data transformation and reasoning.
The heterogeneity of clinical data is a key problem in the sharing and reuse of Electronic Health Record (EHR) data. We approach this problem through the combined use of EHR standards and semantic web technologies, concretely by means of clinical data transformation applications that convert EHR data in proprietary format, first into clinical information models based on archetypes, and then into RDF/OWL extracts which can be used for automated reasoning. In this paper we describe a proof-of-concept platform to facilitate the (re)configuration of such clinical data transformation applications. The platform is built upon a number of web services dealing with transformations at different levels (such as normalization or abstraction), and relies on a collection of reusable mappings designed to solve specific transformation steps in a particular clinical domain. The platform has been used in the development of two different data transformation applications in the area of colorectal cancer.


Modification of lignin biosynthesis in transgenic Nicotiana through expression of an antisense O-methyltransferase gene from Populus.
An aspen lignin-specific O-methyltransferase (bi-OMT; S-adenosyl-L-methionine: caffeic acid/5-hydroxyferulic acid 3/5-O-methyltransferase, EC 188.8.131.52) antisense sequence in the form of a synthetic gene containing the cauliflower mosaic virus 35S gene sequences for enhancer elements, promoter and terminator was stably integrated into the tobacco genome and inherited in transgenic plants with a normal phenotype. Leaves and stems of the transgenes expressed the antisense RNA and the endogenous tobacco bi-OMT mRNA was suppressed in the stems. Bi-OMT activity of stems was decreased by an average of 29% in the four transgenic plants analyzed. Chemical analysis of woody tissue of stems for lignin building units indicated a reduced content of syringyl units in most of the transgenic plants, which corresponds well with the reduced activity of bi-OMT. Transgenic plants with a suppressed level of syringyl units and a level of guaiacyl units similar to control plants were presumed to have lignins of distinctly different structure than control plants. We concluded that regulation of the level of bi-OMT expression by an antisense mechanism could be a useful tool for genetically engineering plants with modified lignin without altering normal growth and development.


In vitro antitumour activity of orsellinates.
Lichen phenolic compounds exhibit antioxidant, antimicrobial, antiproliferative, and cytotoxic activities. The purpose of this study was to evaluate the anticancer activity of lecanoric acid, a secondary metabolite of the lichen Parmotrema tinctorum, and its derivatives, orsellinates, obtained by structural modification. A cytotoxicity assay was carried out in vitro with sulforhodamine B (SRB) using HEp-2 larynx carcinoma, MCF7 breast carcinoma, 786-0 kidney carcinoma, and B16-F10 murine melanoma cell lines, in addition to a normal (Vero) cell line in order to calculate the selectivity index of the compounds. n-Butyl orsellinate was the most active compound, with IC50 values (the concentration that inhibits 50% of growth) ranging from 7.2 to 14.0 microg/mL, against all the cell lines tested. The compound was more active (IC50 = 11.4 microg/mL) against B16-F10 cells than was cisplatin (12.5 microg/mL). Conversely, lecanoric acid and methyl orsellinate were less active against all cell lines, having an IC50 value higher than 50 microg/mL. Ethyl orsellinate was more active against HEp-2 than against MCF7, 786-0, or B16-F10 cells. The same pattern was observed for n-propyl and n-butyl orsellinates. n-Pentyl orsellinate was less active than n-propyl or n-butyl orsellinates against HEp-2 cells. The orsellinate activity increased with chain elongation (from methyl to n-butyl), a likely consequence of an increase in lipophilicity. The results revealed that the structural modification of lecanoric acid increases the cytotoxic activity of the derivatives tested.


Ultra-low-loss tapered optical fibers with minimal lengths.
We design and fabricate ultra-low-loss tapered optical fibers (TOFs) with minimal lengths. We first optimize variations of the torch scan length using the flame-brush method for fabricating TOFs with taper angles that satisfy the adiabaticity criteria. We accordingly fabricate TOFs with optimal shapes and compare their transmission to TOFs with a constant taper angle and TOFs with an exponential shape. The highest transmission measured for TOFs with an optimal shape is in excess of 99.7% with a total TOF length of only 23 mm, whereas TOFs with a constant taper angle of 2 mrad reach 99.6% transmission for a 63 mm TOF length.


The plasma kallikrein-kinin system: its evolution from contact activation.
The plasma kallikrein-kinin system consists of the proteins factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen. It was first recognized as a surface-activated coagulation system that is activated when blood or plasma interacts with artificial surfaces. Although surface-activated contact activation occurs in vivo in the case of tissue destruction or a developing thrombus, the physiologic basis for the activation and function of this system has not been delineated. New investigations indicate that there is a proteolytic pathway on cells for PK activation independent of FXII. This pathway for PK with subsequent FXII activation indicates physiologic activities. These activities include blood pressure regulation and modulation of thrombosis risk independently of hemostasis. Furthermore, they include regulation of endothelial cell proliferation, angiogenesis and apoptosis through a cellular-based, outside-in signaling system. The present characterizations of this system, which incorrectly had been thought to initiate coagulation, represent an evolution of understanding in this field.


Health services research methods: tools for nurse leaders.
A political competency for leaders is to effectively articulate the evidence behind management best practices. Evidence-based practice requires special skills from the nurse leader, many of which are found in health services research (HSR) methods. This review presents approaches associated with HSR, which can be used by nurse managers for the benefit of their units. HSR methods reviewed are cost analyses, small area analysis, geographic information systems, use of existing databases, quality of care measures, and risk adjustment. This review examines the kind of evidence various HSR methods provide, as well as examples of their use and resources needed to apply them.


Unraveling the Selectivity Patterns in Phosphine-Catalyzed Annulations of Azomethine Imines and Allenoates.
The mechanism and selectivity of phosphine-catalyzed [3 + 2] and [3 + 3] annulations of azomethine imines and allenoates have been computationally studied. Exploration of the potential energy surface reveals that the cyclization step is a key step controlling the selectivity of the process. This contrasts with previous studies on related transformations where the initial nucleophilic addition involving the activated allenoate was found to exclusively control the regioselectivity of the transformation. Among the possible reaction pathways, the energetically low-lying reaction channel involves an intramolecular Michael addition leading to the experimentally observed [3 + 2] product. The factors controlling the observed regioselectivity have been quantitatively rationalized by means of state-of-the-art computational methods, namely, the activation strain model of reactivity in combination with the energy decomposition analysis.


Effect of Lower and Upper Body High Intensity Training on Genes Associated with Cellular Stress Response.
This study aimed to compare the effect of upper and lower body high intensity exercise (HIE) on select gene expression in athletes. Fourteen elite male artistic gymnasts (age 20.9 ± 2.6 years; weight 68.6 ± 7.2 kg; fat free mass 63.6 ± 6.7 kg; height 1.70 ± 0.04 m) performed lower and upper body 30 s Wingate Tests (WAnTs) before and after eight weeks of specific HIIT. Two milliliters of blood was collected before and after (5, 30 min, resp.) lower and upper body WAnTs, and select gene expression was determined by PCR. Eight weeks of HIIT caused a significant increase in maximal power (722 to 751 Wat), relative peak power in the lower body WAnTs (10.1 to 11 W/kg), mean power (444 to 464 W), and relative mean power (6.5 to 6.8 W/kg). No significant differences in lower versus upper body gene expression were detected after HIIT, and a significant decrease in the IL6/IL10 ratio was observed after lower (-2∧0.57 p = 0.0019) and upper (-2∧0.5 p = 0.03) WAnTs following eight weeks of HIIT. It is hypothesized that a similar adaptive response to exercise may be obtained by lower and upper body exercise.


Differentiation of Potato virus Y strains using improved sets of diagnostic PCR-primers.
Potato virus Y (PVY) is one of the most important viruses of potato world-wide, several strain groups are recognized. In the past two decades, novel PVY variants have appeared causing necrotic symptoms on potato tubers. Implicated are two groups of recombinant strains: PVY(N)W and PVY(NTN), and NA-PVY(NTN). While the first two are recombinants between PVY-N- and O-strains the latter is a recombinant between an N-strain and an unknown PVY strain or other Potyvirus. Available biological and molecular data on PVY suggest that classification of PVY strains has to be revised. Some drawbacks have been found with recently published primers used in RT-PCR based differentiation of PVY strains as some defined isolates could not be identified correctly. Consequently we developed new primers using both recently available sequences and newly generated complete sequences of PVY strains. The reliability of these newly developed primers and procedures was successfully demonstrated on nearly 100 biologically and serologically characterised PVY isolates.


Proliferating trichilemmal cyst: report of two cases, one benign and the other malignant.
Proliferating trichilemmal cyst (PTC) is a rare but morphologically distinct tumor that usually arises on the scalp of elderly women. We report two cases of PTC, one benign and the other malignant. PTCs are well circumscribed, subepidermal lesions and demonstrate a uniform histologic pattern with varying degrees of cytological atypia. Malignant proliferating trichilemmal cyst (MPTC) has features in common with benign proliferating trichilemmal cyst (BPTC), including a central area of abrupt keratinization and hyperplastic squamous epithelium forming solid areas. The diagnosis of MPTC is essentially based on histological features. The presence of a high mitotic rate, atypical mitosis, severe nuclear pleomorphism, and tumor invasion of the adjacent tissues are the essential histological features of malignancy in these unusual tumors. The therapeutic approach in malignant cases is the same as that in the treatment of BPTC: surgical removal with a wide clear margin. However, even with adequate resection, both tumors tend to recur locally.


Endosonography--is it sound for the masses?
Endoscopic ultrasound (EUS), a relatively new addition to the endoscopist's diagnostic armamentarium, provides detailed images of the gut wall layers and surrounding organs. Endosonography is highly accurate in the staging of gastrointestinal neoplasms and may provide information that is invaluable in treatment planning, such as evidence of unresectability. EUS also has particular utility in the evaluation of submucosal lesions of the gastrointestinal tract and the preoperative localization of States, Olympus and Pentax manufacture two different endosonography systems, each with unique advantages and disadvantages. Recently, EUS-directed biopsy has enhanced the diagnostic potential of the procedure. With the recent approval of CPT codes and reimbursement values, interest in the procedure is likely to expand. Adequate training in EUS is essential for the successful performance of the procedure; a period of proctored training with an experienced endosonographer is recommended.


Blood pressure, plasma catecholamine and renin responses to caffeine in elderly hypertensives.
In young hypertensive patients, after a short period of abstention, caffeine ingestion has a significant pressor effect, although the acute cardiovascular responses have not been reported in elderly hypertensives. This study assessed the acute changes in BP, pulse rate, plasma renin activity (PRA) and arterialised plasma catecholamines after 250 mg of caffeine and matching placebo following 12 and 48 hours of caffeine abstention. After 48 hours caffeine abstention supine SBP was higher over the 120 minute study period following acute caffeine loading than following placebo (10 mmHg; 95% Cl 3-17 mmHg, P = 0.016) although the overall post-caffeine rise from baseline values was small (2 mmHg; -3 to 8 mmHg, P = 0.30). Similar differences were seen for supine DBP and standing SBP and DBP although pulse rate was unchanged throughout. After 12 hours abstention no acute pressor effect of caffeine was seen, in fact SBP fell over the study period (-5 mmHg; -10 to 0 mmHg, P = 0.05), and there was no difference between the caffeine and placebo phases. No change in plasma catecholamines or PRA values was found during any of the phases. These results suggest that in elderly hypertensives the pressor effect of caffeine (the equivalent of two to three cups of coffee) is small even after prolonged abstention. After the shorter abstention period, of the duration likely to be seen in clinical practice, no pressor response to caffeine was demonstrated. It is unlikely that acute caffeine ingestion has a significant effect on clinic BP measurements in elderly hypertensives who are regular caffeine consumers.


Staphylococcus epidermidis recovered from indwelling catheters exhibit enhanced biofilm dispersal and "self-renewal" through downregulation of agr.
In recent years, Staphylococcus epidermidis ( Se) has become a major nosocomial pathogen and the most common cause of infections of implanted prostheses and other indwelling devices. This is due in part to avid biofilm formation by Se on device surfaces. However, it still remains unknown that how the process of Se biofilm development is associated with relapsed infection in such patients. We have identified clinical Se isolates displaying enhanced biofilm dispersal and self-renewal relative to reference strain. These isolates also exhibit enhanced initial cell attachment, extracellular DNA release, cell autolysis and thicker microcolonies during biofilm development relative to reference strain. Our genetic analyses suggest that these clinical isolates exhibit significant downregulation of RNAIII, the effector molecule of the agr quorum sensing system, and upregulation of the autolysin gene atlE. Isogenic deletion of the agr system in Se 1457 confirmed that agr negatively regulating atlE resulted in enhanced initial cell attachment, extracellular DNA release, cell autolysis and biofilm formation abilities. In contrast, double deletion of agr and atlE significantly abolished these features. Collectively, these data reveal the role of agr system in long-term biofilm development and pathogenesis during Se caused indwelling devices-related relapsed infection.


Predicting the Necessity for Extracorporeal Circulation During Lung Transplantation: A Feasibility Study.
The factors leading to the implementation of unplanned extracorporeal circulation during lung transplantation are poorly defined. Consequently, the authors aimed to identify patients at risk for unplanned extracorporeal circulation during lung transplantation. Retrospective data analysis. Single-center university hospital. A development data set of 170 consecutive patients and an independent validation cohort of 52 patients undergoing lung transplantation. The authors investigated a cohort of 170 consecutive patients undergoing single or sequential bilateral lung transplantation without a priori indication for extracorporeal circulation and evaluated the predictive capability of distinct preoperative and intraoperative variables by using automated model building techniques at three clinically relevant time points (preoperatively, after endotracheal intubation, and after establishing single-lung ventilation). Preoperative mean pulmonary arterial pressure was the strongest predictor for unplanned extracorporeal circulation. A logistic regression model based on preoperative mean pulmonary arterial pressure and lung allocation score achieved an area under the receiver operating characteristic curve of 0.85. Consequently, the authors developed a novel 3-point scoring system based on preoperative mean pulmonary arterial pressure and lung allocation score, which identified patients at risk for unplanned extracorporeal circulation and validated this score in an independent cohort of 52 patients undergoing lung transplantation. The authors showed that patients at risk for unplanned extracorporeal circulation during lung transplantation could be identified by their novel 3-point score.


Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients.
Acute administration of nicotine patches produced rapid eye movement sleep (REM) increases in non-smoking major depressed patients as well as clinical improvement in mood. Antidepressant effect was also observed after four continuous days of nicotine administration. The main goal of the present study was to observe the relationship between changes in REM sleep variables and mood in non-smoking major depressed patients. Fifteen major depressed patients (DSM-III-R) were studied under the following sleep laboratory conditions: habituation, two all-night polysomnography recordings, the first one was baseline and the second one was nicotine patch (17.5 mg) night. Patients should had a HAMD-21 punctuation equal or above 18 points for to be admitted in the study. A short HAMD (10 items), and side effect scale was used daily during the two recording nights. A significant increase in REM sleep time and reduction in sleep stage II was observed when patients were on nicotine patches. Ten patients improved (reduction of 30% in the HAMD of 10 items), the morning after nicotine. All of them also increased REM sleep time above their baseline. Eight patients from the one with significant improvement had a short REM sleep latency below 60 minutes at baseline. The hypersensitivity of the cholinergic system may be related to the REM sleep enhancement effect observed in some of the patients when received nicotine and also related to the clinical improvement. The role of the acetylcholine in depression could be explored with the administration of transdermal nicotine patches.


In vitro activity of linezolid against clinical isolates of methicillin resistant Staphylococcus.
Staphylococcus is responsible for a variety of medical problems, including skin and soft-tissue infections (SSTIs), surgical site infections (SSIs), endocarditis and hospital acquired bacteraemia. Methicillin resistance in staphylococcus has become a global problem limiting the treatment modalities to a large extent. The aim of this study was to evaluate the in vitro activity of linezolid and other antibiotics against clinical isolates of methicillin resistant staphylococcus (n = 163); including 105 methicillin resistant Staphylococcus aureus and 58 methicillin resistant coagulase negative staphylococci. Antibiogram of these isolates was determined by the Kirby-Bauer disc diffusion method and minimum inhibitory concentration of linezolid was determined by standard agar dilution method. Overall methicillin resistant S. aureus showed high multi-drug resistance. ATCC 25923 Staphylococcus aureus and ATCC 29213 Staphylococcus aureus were used as the standard control strains. MIC90 of linezolid was comparable for methicillin resistant coagulase negative staphylococci and methicillin resistant S. Aureus (4.0 mg/L); however at MIC50 linezolid was two fold more active against methicillin resistant coagulase negative staphylococci (1 mg/L) than methicillin resistant S. aureus (2 mg/L). It is concluded that linezolid has excellent activity against methicillin resistant staphylococci including multidrug resistant strains.


Extracorporeal membrane oxygenation with continuous renal replacement therapy to treat metformin-associated lactic acidosis: A case report.
Metformin-associated lactic acidosis (MALA) is rarely encountered, but has a high mortality rate, Conventional treatments include hemodialysis or continuous renal replacement therapy (CRRT); however, when the disease progresses to end-stage, cardiac function is significantly inhibited, circulation cannot be maintained, CRRT cannot be tolerated, V-A extracorporeal membrane oxygenation (ECMO) may be the last treatment. The study report a rare case of MALA in an elderly female patient at the age of 72 who was admitted to hospital because of nausea for 2 days, complicated with systemic fatigue. MALA was cofirmed because of patient have increased lactic acid levels, blood pH <7.2, and a history of oral metformin intake. Venoarterial ECMO (V-A ECMO) combined with CRRT was initiated when circulation was still not hold after intravenous fluids and 5% sodium bicarbonate were prescribed. V-A ECMO was then terminated after 48 hours when circulation was perserved, CRRT was discontinued when PH and lactic acid level were normal limited. etformin-associated lactic acidosis did not recur during 6 months follow-up. The incidence of MALA is low, but mortality is very high. Intermittent hemodialysis or CRRT should be performed if the lactic acid level is persistently elevated. When severe circulatory dysfunction occurs and cardiac function is inhibited, V-A ECMO support should be performed immediately to maintain circulation, followed by CRRT, which may be the final measure to treat refractory MALA.


[Quantitative measurement and clinical analysis of serum levels of immunosuppressive acidic protein (IAP) in hematopoietic malignancies].
Serum levels of immunosuppressive acidic protein (IAP) in 105 patients with hematopoietic malignancies, there were 12 cases of acute myeloblastic leukemia, 1 acute monocytic leukemia, 13 myelomonocytic leukemia, 4 acute promyelocytic leukemia, 26 chronic myelogenous leukemia, 22 non-Hodgkin's lymphoma, 5 Hodgkin's disease, 6 adult T-cell leukemia, 5 acute lymphoblastic leukemia, 3 chronic lymphocytic leukemia, and 8 multiple myeloma. High levels of serum IAP were detected in all of the patients except chronic phase of CML, malignant lymphoma in stage I and II, and multiple myeloma. In the cases of malignant lymphoma, serum IAP levels in stage III and IV were higher with statistical significance (p less than 0.01) than those in stage I and II. Serum IAP levels in the patients with CML in blastic crisis were higher than in the chronic phase, so serum IAP levels are useful as one diagnostic parameters in blastic crisis. However, in patients with ANLL in relapse, serum IAP levels showed normal values. Serum IAP levels paralleled those of acute phase reactants such as alpha 1-acid glycoprotein , C-reactive protein, alpha 2-globulin, and alpha 1-antitrypsin, and had inverse correlations with PPD and PHA skin test.


Microbiota separation and C-reactive protein elevation in treatment-naïve pediatric granulomatous Crohn disease.
In patients with inflammatory bowel diseases (IBDs), the presence of noncaseating mucosal granuloma is sufficient for diagnosing Crohn disease (CD) and may represent a specific immune response or microbial-host interaction. The cause of granulomas in CD is unknown and their association with the intestinal microbiota has not been addressed with high-throughput methodologies. The mucosal microbiota from 3 different pediatric centers was studied with 454 pyrosequencing of the bacterial 16S rRNA gene and the fungal small subunit (SSU) ribosomal region in transverse colonic biopsy specimens from 26 controls and 15 treatment-naïve pediatric CD cases. Mycobacterium avium subspecies paratuberculosis (MAP) was tested with real-time polymerase chain reaction. The correlation of granulomatous inflammation with C-reactive protein was expanded to 86 treatment-naïve CD cases. The CD microbiota separated from controls by distance-based redundancy analysis (P = 0.035). Mucosal granulomata found in any portion of the intestinal tract associated with an augmented colonic bacterial microbiota divergence (P = 0.013). The granuloma-based microbiota separation persisted even when research center bias was eliminated (P = 0.04). Decreased Roseburia and Ruminococcus in granulomatous CD were important in this separation; however, principal coordinates analysis did not reveal partitioning of the groups. CRP levels >1 mg/dL predicted the presence of mucosal granulomata (odds ratio 28 [6-134.32]; 73% sensitivity, 91% specificity). Granulomatous CD associates with microbiota separation and C-reactive protein elevation in treatment-naïve children; however, overall dysbiosis in pediatric CD appears rather limited. Geographical/center bias should be accounted for in future multicenter microbiota studies.


Triazavirin might be the new hope to fight Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
Since the beginning of the outbreak, a large number of clinical trials have been registered worldwide, and thousands of drugs have been investigated to face new health emergency of highly contagious COVID-19 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Drug repurposing, i.e., utilizing an approved drug for a different indication, offers a time- and cost-efficient alternative for making new (relevant) therapies available to physicians and patients. Considering given strategy, many approved and investigational antiviral compounds, alone or in various relevant combinations, used in the past to fight Severe Acute Respiratory Syndrome Coronavirus-1, Middle East Respiratory Syndrome Coronavirus, Human Immunodeficiency Virus type 1, or Influenza viruses are being evaluated against the SARS-CoV-2. Triazavirin (TZV), a non-toxic broad--spectrum antiviral compound, is efficient against various strains of the Influenza A virus (Influenza Virus A, Orthomyxoviridae), i.e., swine flu (H1N1, or H3N2), avian influenza (H5N1, H5N2, H9N2, or highly pathogenic H7N3 strain), Influenza B virus (Influenza Virus B, Orthomyxoviridae), Respiratory Syncytial Virus (Orthopneumovirus, Pneumoviridae), Tick-Borne Encephalitis Virus (known as Forest-Spring Encephalitis Virus; Flavivirus, Flaviviridae), West Nile Virus (Flavivirus, Flavaviridae), Rift Valley Fever Virus (Phlebovirus, Bunyaviridae), and Herpes viruses (Simplexviruses, Herpesviridae) as well. In regard to COVID-19, the molecule probably reduced inflammatory reactions, thus limiting the damage to vital organs and reducing the need for therapeutic support, respectively. In addition, in silico computational methods indicated relatively satisfactory binding affinities of the TZV ligand to both structural (E)- and (S)-proteins, non-structural 3-chymotrypsin-like protease (3-CLpro) of SARS-CoV-2 as well as human angiotensin-I converting enzyme-2 (ACE-2). The interactions between TZV and given viral structures or the ACE-2 receptor for SARS-CoV-2 might effectively block both the entry of the pathogen into a host cell and its replication. Promising treatment patterns of COVID-19 positive patients might be also based on a suitable combination of a membrane fusion inhibitor (umifenovir, for example) with viral RNA synthesis and replication inhibitor (TZV).


Fluoride ion encapsulation by Mg2+ ions and phosphates in a fluoride riboswitch.
Significant advances in our understanding of RNA architecture, folding and recognition have emerged from structure-function studies on riboswitches, non-coding RNAs whose sensing domains bind small ligands and whose adjacent expression platforms contain RNA elements involved in the control of gene regulation. We now report on the ligand-bound structure of the Thermotoga petrophila fluoride riboswitch, which adopts a higher-order RNA architecture stabilized by pseudoknot and long-range reversed Watson-Crick and Hoogsteen A•U pair formation. The bound fluoride ion is encapsulated within the junctional architecture, anchored in place through direct coordination to three Mg(2+) ions, which in turn are octahedrally coordinated to water molecules and five inwardly pointing backbone phosphates. Our structure of the fluoride riboswitch in the bound state shows how RNA can form a binding pocket selective for fluoride, while discriminating against larger halide ions. The T. petrophila fluoride riboswitch probably functions in gene regulation through a transcription termination mechanism.


Undue inducement, or unfair exclusion: considering a case study of pregnancy in an HIV prevention trial.
In their recent paper'Undue inducement: a case study in CAPRISA 008', Mngadi et al conclude that a participant in an HIV prevention study who deliberately concealed her pregnancy was not 'unduly induced' to participate by the offer of an experimental product. This paper argues that while the authors' conclusion is sound, the framing of this case study is consistent with the preoccupation in research ethics with the concept of undue inducement, coupled with a highly risk-averse attitude to pregnancy (regardless of whether those risks may be willingly assumed by pregnant women themselves). We suggest that the critical research ethics question raised by Mngadi et al's case study is not 'undue inducement', but the exclusion of pregnant women from research studies where the risks are acceptable to the potential participant, and benefits likely. We also suggest that current regulatory paradigms regarding pregnancy are both overly paternalistic and value the fetus over the mother. In order to ensure timely provision of new HIV prevention agents, we argue that there is a need for expeditious testing of proven effective agents in pregnancy, with due consideration given to situations where preliminary efficacy data exist but fall short of licensure standards. This requires a paradigm shift from researchers, funders, regulators and ethical review bodies towards practices that critically examine the legitimacy of the exclusion of pregnant women on a study-by-study basis.


Synthesis, electrochemical properties, and crystal packing of perfluororubrene.
A synthesis of perfluorinated rubrene is reported. Electrochemical analysis revealed the significantly increased electron affinity of perfluororubrene compared with non-modified rubrene. Crystallographic investigation revealed two polymorphs and a solvate, each displaying twisted backbone conformations of perfluororubrene. Taken together, these results suggest perfluororubrene will find applications as a new n-type semiconductor.


The spectrum of renal tubular acidosis in paediatric Sjögren syndrome.
Renal tubular acidosis (RTA) is a well-recognized extraglandular complication of adult Sjögren syndrome (SS) but has been reported only rarely in paediatric SS. We wished to describe the natural history of RTA in paediatric SS. We performed a chart and literature review. Inclusion criteria were primary or secondary SS with onset before 18 yr of age, complicated by RTA before 18 yr of age. Twelve cases were identified: two from chart review and 10 from the literature. RTA was mostly associated with primary SS. RTA was detected at the onset of SS or up to 9 yr later. The clinical spectrum ranged from nearly silent to life-threatening, with plasma pH and serum potassium as low as 7.0 and 1.2 mEq/l, respectively. Hypokalaemia was present in 92%. Half the patients presented with profound weakness or paralysis, most likely from hypokalaemia. Proximal, distal and mixed RTA were detected, reflecting a diffuse 'tubulopathy' from interstitial nephritis, which was the predominant histopathological finding. Diabetes insipidus was the most frequent renal comorbidity. The RTA stabilized in 82% of the cases and resolved in one case. Only one patient had long-term unstable RTA. RTA is an under-recognized complication of paediatric SS. It can be life-threatening in the acute phase but generally has a good long-term renal outcome. SS should be considered in the older child with otherwise unexplained RTA. Likewise, RTA should be excluded in children and adolescents with SS who develop weakness, fatigue or growth failure. Early recognition would reduce long-term complications such as growth failure.


Depressive symptoms during pregnancy in relation to fish consumption and intake of n-3 polyunsaturated fatty acids.
An inverse association between depression and the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), primarily obtained from fish consumption, is observed in both observational and experimental research and is biologically plausible. Study objectives were to examine whether prenatal depressive symptoms were associated with lower intakes of fish or EPA+DHA. Pregnant women (n = 2394) completed a telephone interview between 10 and 22 weeks' gestation in London, Ontario, 2002-05. Depressive symptoms were measured using the Center for Epidemiologic Studies - Depression Scale (CES-D). Intakes of fish and EPA+DHA were measured using a validated food-frequency questionnaire. Sequential multiple regression was used to examine associations of depressive symptoms with intake of fish and EPA+DHA, respectively, while controlling for sociodemographic, health and lifestyle variables. The mean CES-D score was 9.9 (SD 8.0). Intake of EPA+DHA was dichotomised at the median value of 85 mg/day. Fish consumption and intake of EPA+DHA were not associated with prenatal depressive symptoms after adjustment for confounders; however, depressive symptoms were significantly higher for lower intakes of EPA+DHA among current smokers and women of single/separated/divorced marital status. The adjusted difference in CES-D scores between intake categories of EPA+DHA was -2.4 [95% CI -4.2, -0.4] for current smokers and -2.8 [95% CI -5.2, -0.4] for women of single marital status. Although pregnant women may be at risk for low concentrations of EPA and DHA, an association between low intakes of EPA+DHA and increased depressive symptoms was only observed among current smokers and women of single marital status.


Biomechanical considerations in patellofemoral joint rehabilitation.
Patellofemoral joint biomechanics during leg press and leg extension exercises were compared in 20 normal subjects (10 men, 10 women) aged 18 to 45 years. Knee moment, patellofemoral joint reaction force, and patellofemoral joint stress were calculated for each subject at four knee flexion angles (0 degree, 30 degrees, 60 degrees, and 90 degrees) during leg press and leg extension exercises. All three parameters (knee moment, patellofemoral joint reaction force, and patellofemoral joint stress) were significantly greater in leg extension exercise than leg press exercise at 0 degree and 30 degrees of knee flexion (P < 0.001). At 60 degrees and 90 degrees of knee flexion, all three parameters were significantly greater in leg press exercise than leg extension exercise (P < 0.001). Patellofemoral joint stresses for leg press and leg extension exercises intersected at 48 degrees of knee flexion. This study demonstrates that patients with patellofemoral joint arthritis may tolerate rehabilitation with leg press exercise better than with leg extension exercise in functional ranges of motion because of lower patellofemoral joint stresses.


[Growth and puberty in children after treatment of acute lymphoblastic leukemia].
Growth retardation and other endocrine abnormalities were recognized as sequelae of therapy of acute lymphoblastic leukemia (ALL), especially when chemotherapy was combined with cranial irradiation. The aim of our study was to establish growth and pubertal development in the group of children who had been previously successfully treated for ALL. 58 children (30 F, 28 M, age 8-18 y.) in complete initial remission lasting 4-15 y. (m 8 y.) after standard antileukemic therapy (including cranial irradiation) completed 2-9 y. ago (m 3 including y.) were studied. Standard deviation score (SDS) of standing height (SH) to chronological age (CA) and to genetic target height (GTH), index of body proportionality and timing of puberty were followed up. The final height attained 21 girls and 3 boys. The height of the boys differed neither from the average for our men, nor from their GTH. Girls: SH 148 cm-169 cm, SH of 7 girls > or = -1.5 SDS, 8 girls > or = -1.5 SDS to their GTH. The final height didn't reach yet 23 boys and 9 girls. Their SH to CA as well as SH to GTH didn't substantially differ from average. Index of body proportionality > or = 1.5 SDS in 12/30 girls and 6/28 boys. Menarche was already reached in 25 girls in age ranging from 10-15 y. (mean 11.3 y.), what was less than average for our population (13.3 y.). Even the height of prepubertal children under study didn't differ from average, the final height of girls (boys could not be evaluated because of small numbers) was significantly lower as could be expected. We suppose the early ending of puberty as a contributing factor of short stature in girls. Clear tendency to obesity especially among older girls was observed. Children who underwent antileukemic therapy deserve careful endocrinological follow-up.


The role of Helicobacter pylori infection in the pathogenesis of gastritis.
We conducted a prospective study to evaluate the relationship between H. pylori infection and gastritis in a Japanese population. The study population consisted of 92 patients with endoscopically proven gastritis. Biopsy specimens were taken from the gastric mucosa from the corpus and antrum according to the Sydney system for the new classification of gastritis. H. pylori was histologically found in 84.3% of patients for mononuclear (MN) cell infiltration and in 88.1% of those positive for polymorphonuclear (PMN) cells. H. pylori was not found in any of nine patients without MN cell infiltration (P < 0.001), while 68.8% of patients without PMN cell infiltration were positive for H. pylori (P < 0.03). The frequency of MN cell infiltration in H. pylori-positive patients was significantly higher than that in H. pylori-negative patients (100% vs 65.4%; P < 0.001). The frequency of PMN cell infiltration in H. pylori-positive patients was also significantly higher than that in H. pylori-negative patients (54.5% vs 23.1%; P < 0.01). The incidence of MN cell infiltration in the antrum was significantly higher than that in the gastric corpus in H. pylori-positive gastritis patients (93.2% vs 65.1%; P < 0.001). The incidence of PMN cell infiltration was also higher in the antrum than in the corpus in H. pylori-positive gastritis patients, although the difference was not significant (42.0% vs 31.7%).(ABSTRACT TRUNCATED AT 250 WORDS)


Diversity of Thrips Species and Vectors of Tomato Spotted Wilt Virus in Tomato Production Systems in Kenya.
Thrips have been recognized as primary vectors of tomato spotted wilt virus (TSWV) with Frankliniella occidentalis (Pergande) reported as the most important and efficient vector, while other species such as Thrips tabaci Lindeman also include populations that can vector the virus. A study was undertaken to establish the diversity of thrips and presence of vectors for TSWV in four major tomato production areas in Kenya. The cytochrome oxidase 1 (CO1) gene was used to generate sequences from thrips samples collected from tomatoes and weeds, and phylogenetic analysis done to establish the variation within potential vector populations. Ceratothripoides brunneus Bagnall was the predominant species of thrips in all areas. F. occidentalis and T. tabaci were abundant in Nakuru, Kirinyaga, and Loitokitok but not detected at Bungoma. Other vectors of tospoviruses identified in low numbers were Frankliniella schultzei (Trybom) and Scirtothrips dorsalis Hood. Variation was observed in T. tabaci, F. occidentalis, and F. schultzei. Kenyan specimens of T. tabaci from tomato belonged to the arrhenotokous group, while those of F. occidentalis clustered with the Western flower thrips G group. The detection of RNA of TSWV in both of these species of thrips supported the role they play as vectors. The study has demonstrated the high diversity of thrips species in tomato production and the occurrence of important vectors of TSWV and other tospoviruses.


Minimum Residual Disease in Patients Post Radical Prostatectomy for Prostate Cancer: Theoretical Considerations, Clinical Implications and Treatment Outcome
Introduction: Minimal residual disease (MRD) remaining after curative therapy for prostate cancer has the potential for growth and can result in metastasis. Circulating prostate cells (CPCs) and bone marrow micro-metastasis (mM) could represent different types of MRD. We here determined; biochemical failure free survival rates; time to BF after 10 years follow-up; and the presence of CPCs and mM in patients treated with radical prostatectomy (RP) for prostate cancer. Methods and Patients: One month after RP, blood and bone marrow were sampled for assessment of CPCs and mM. Cases were classified as: group A, CPC negative and mM negative; group B, CPC negative and mM positive; Group C, CPC positive and mM negative; and Group D, CPC positive and mM positive. Subjects were followed with serial determination of PSA levels, recording the time at which BF occurred defined as a serum PSA >0.2ng/ml. After ten years of follow-up Kaplan-Meier survival curves were generated and the restricted mean survival time (RMST) for each group calculated. Results: A total of 321 men participated, 140 in group A with survival of 92.7% (86.3 to 96.2), 39 in group B with 55.8% (37.2 to 70.9); 54 in group C with 6.41% (1.19 to 18.21) and 88 in group D with 4.96%(1.64 to 11.13%. The RMST (in years) were: group A, 9.47 (9.24 to 9.69); group B, 9.23 (8.87 to 9.58); group C, 4.62 (4.46 to 4.77); and group D, 3.57 (3.52 and 3.63) (p-value<0.001 between groups: A versus C and D, B versus C and D). Conclusions: CPC positive men have more aggressive disease, with increased early failure; men who are only positive for mM are at greater risk of late failure. These two forms of MRD represent different clinical entities with respect to biochemical failure and could be used to guide clinical treatment decisions.


A neural network approach to the early detection of cancer.
Early detection of some cancers (especially of the colon) may be achieved by nuclear magnetic resonance (NMR) spectroscopy applied to whole blood samples. Analysis by conventional Fourier signal processing techniques of the data so obtained has proved to be unreliable because of noise within the associated spectrum. This paper describes a neural network approach to analysis of the NMR data. At the present time, this method has proved to be highly reliable in differentiating between patients with an without colon cancer.


Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus).
Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of FGR on the vasoactive and biomechanical properties of umbilical and systemic vessels in fetal guinea pigs. Methods: FGR was induced by implanting ameroid occluders at mid-gestation in uterine arteries of pregnant guinea pigs, whilst the control group was exposed to simulated surgery. At the term of gestation, systemic arteries (aorta, carotid and femoral) and umbilical vessels were isolated to determine ex vivo contractile and biomechanical responses (stretch-stress until rupture) on a wire myograph, as well as opening angle and residual stresses. Histological characteristics in tissue samples were measured by van Gieson staining. Results: Aorta and femoral arteries from FGR showed an increased in biomechanical markers of stiffness (p < 0.01), contractile capacity (p < 0.05) and relative media thickness (p < 0.01), but a reduced internal diameter (p < 0.001), compared with controls. There were no differences in the biomechanical properties of carotid and umbilical from control and FGR fetuses, but FGR umbilical arteries had a decreased contractile response to KCl (p < 0.05) along with a reduced relative media thickness (p < 0.05). Conclusion: Altogether, these changes in functional, mechanical and morphological properties suggest that FGR is associated with a heterogeneous pro-constrictive vascular remodeling affecting mainly the lower body fetal arteries. These effects would be set during a pathologic pregnancy in order to sustain the fetal blood redistribution in the FGR and may persist up to adulthood increasing the risk of a cardiovascular disease.


Solid-phase synthesis and modification of Thiazole Orange and its derivatives and their spectral properties.
A new solid-phase synthesis is shown to be effective in the preparation of cyanine dye Thiazole Orange (TO) and its derivatives, which can be obtained as a traceless cleavage of the Merrifield resin method. The influence of different solvents, substitutional groups, introduced to benzothiazole such as chlorine, methyl, and nitro was extensively studied. The changes of the special characteristic and fluorescence intensity of the TO derivatives were described. The phenomenon of the synergetic effect was also depicted after modifying the TO molecule with chitosan oligosaccharide (CTS) at the end of the alkyl, which can effectively improve the sensitivity of the fluorescent probe.


Localization without recurrence and pseudo-Bloch oscillations in optics.
Dynamical localization, i.e., the absence of secular spreading of a quantum or classical wave packet, is usually associated with Hamiltonians by the pure point spectrum, i.e., with a normalizable and complete set of eigenstates. Such systems always show quasi-periodic dynamics (recurrence). Here, we show, rather counter-intuitively, that dynamical localization can be observed in Hamiltonians with an absolutely continuous spectrum, where recurrence effects are forbidden. An optical realization of such a Hamiltonian is proposed based on beam propagation in a self-imaging optical resonator with a phase grating. Localization without recurrence in this system is explained in terms of pseudo-Bloch optical oscillations.


Use of S-100B, NSE, CRP and ESR to predict neurological outcomes in patients with return of spontaneous circulation and treated with hypothermia.
With the introduction of therapeutic hypothermia (TH), the prediction of neurological outcomes in cardiac arrest (CA) survivors is challenging. Early, accurate determination of prognosis by emergency physicians is important to avoid unnecessarily prolonged critical care with a likely poor neurological outcome. This prospective observational study included patients with non-traumatic CA and return of spontaneous circulation (ROSC) between March 2009 and May 2012 at a tertiary academic hospital. Unconscious patients with ROSC were treated with mild TH (32°C-34°C) for 24 hours. Blood samples were collected for S-100B, neuron-specific enolase (NSE), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at 0, 24 and 48 hours post-ROSC. Neurological outcomes were evaluated at hospital discharge and dichotomised as good (cerebral performance category (CPC) 1 or 2) or poor (CPC 3, 4 or 5). Of the 119 patients (68.1% male, 53±15.6 years old) who underwent TH, 46 patients had a good outcome (38.9%). Poor neurological outcomes were predicted using receiver operating characteristic analyses at cut-off values of 0.12 g/L for S-100B at 24 hours post-ROSC (sensitivity, 95.0%; specificity, 75.6%; area under the curve (AUC) 0.916; 95% CI of AUC: 0.846 to 0.961), 31.03 ng/mL for NSE at 48 hours post-ROSC (sensitivity, 83.9%; specificity, 96.9%; AUC 0.929; 95% CI of AUC: 0.836 to 0.979) and 11.2 mg/dL for CRP at 48 hours post-ROSC (sensitivity, 69.4%; specificity, 75.0%; AUC 0.731; 95% CI of AUC: 0.617 to 0.827). ESR was not significant. Among the biomarkers, S-100B at 24 hours and NSE at 48 hours post-ROSC were highly predictive of neurological outcomes in patients treated with TH after CA.


Spontaneous emergence of long-range shape symmetry.
Self-organization of matter is essential for natural pattern formation, chemical synthesis, as well as modern material science. Here we show that isovolumetric reactions of a single organometallic precursor allow symmetry breaking events from iron nuclei to the creation of different symmetric carbon structures: microspheres, nanotubes, and mirrored spiraling microcones. A mathematical model, based on mass conservation and chemical composition, quantitatively explains the shape growth. The genesis of such could have significant implications for material design.


DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancer.
Tumor metastasis is the main contributor to high recurrence and mortality in colorectal cancer (CRC). In a previous study, we found that DJ-1 plays an important role in CRC metastasis, and is the main target in Ciclopirox olamine (CPX)-treated CRC. However, the mechanism underlying DJ-1-induced CRC metastasis remains elusive. In the present study, our results showed that DJ-1 could activate Wnt signaling resulting in enhanced invasive potential and epithelial-to-mesenchymal transition (EMT) in CRC cells. RNA-seq and bioinformatics analysis reveals that the DJ-1/Wnt signaling pathway may promote CRC cells' EMT by regulating fibroblast growth factor 9 (FGF9) expression. Molecular validation showed that expression of FGF9 was upregulated by the DJ-1/Wnt signaling pathway and decreasing FGF9-expression impeded DJ-1-induced CRC invasive ability and EMT, suggesting that FGF9 is involved in DJ-1-enhanced CRC metastasis. In addition, we show that FGF9 was overexpressed in CRC human specimens and was significantly associated with tumor differentiation. High FGF9 expression was correlated with worse overall survival, and a correlation exhibited between FGF9 and EMT markers (E-cadherin and Vimentin) in CRC samples. Together, our results determined that FGF9 was involved in DJ-1-induced invasion and EMT in CRC cells, and may represent a promising therapeutic candidate for CRC anti-metastatic strategies.


Circulating endothelial cells as a prognostic marker in thrombotic microangiopathy.
Circulating endothelial cells (CECs) are a reliable marker of disease activity in a variety of vascular disorders. Damage to microvascular endothelial cells is a hallmark of thrombotic microangiopathy (TMA). The aim of this study is to identify and count CECs during the course of TMA and evaluate whether cell numbers may serve as a prognostic marker in patients undergoing plasma exchange. Fifteen patients (8 women, 7 men) aged 31 to 66 years with TMA of different causes were studied before and after 4 sessions of plasma exchange. CECs were isolated by using anti-CD146-driven immunomagnetic isolation and counted after staining with Ulex Europaeus lectin-1. Numbers of CECs were markedly elevated in all patients before treatment (64 to 672 CEC/mL; mean, 320 +/- 205 CEC/mL) compared with healthy controls (0 to 16 CEC/mL; mean, 6.4 +/- 4.2 CEC/mL; P < 0.001). Patients with a favorable outcome had significantly greater initial CEC levels (mean, 426 +/- 175 CEC/mL; P < 0.001), and cell numbers decreased significantly after 4 treatments of plasma exchange (mean, 101 +/- 53 CEC/mL; P = 0.001). Patients with disease unresponsive to plasma exchange presented with lower initial CEC levels (mean, 108 +/- 36 CEC/mL), and numbers failed to decrease after plasma exchange (mean, 114 +/- 57 CEC/mL; P = 0.827). Markedly elevated numbers of CECs reflect severe and widespread endothelial damage in patients with TMA. Cell numbers at presentation and their degree of decrease after 4 sessions of plasma exchange could provide important prognostic clues.


mTORC1 Signaling Contributes to Drinking But Not Blood Pressure Responses to Brain Angiotensin II.
Mechanistic target of rapamycin complex 1 (mTORC1) is a molecular node that couples extracellular cues to a wide range of cellular events controlling various physiological processes. Here, we identified mTORC1 signaling as a critical mediator of angiotensin II (Ang II) action in the brain. In neuronal GT1-7 cells, we show that Ang II stimulates neuronal mTORC1 signaling in an Ang II type 1 receptor-dependent manner. In mice, a single intracerebroventricular (ICV) injection or chronic sc infusion of Ang II activated mTORC1 signaling in the subfornical organ, a critical brain region in cardiovascular control and fluid balance. Moreover, transgenic sRA mice with brain-specific overproduction of Ang II displayed increased mTORC1 signaling in the subfornical organ. To test the functional role of brain mTORC1 in mediating the action of Ang II, we examined the consequence of mTORC1 inhibition with rapamycin on Ang II-induced increase in water intake and arterial pressure. ICV pretreatment with rapamycin blocked ICV Ang II-mediated increases in the frequency, duration, and amount of water intake but did not interfere with the pressor response evoked by Ang II. In addition, ICV delivery of rapamycin significantly reduced polydipsia, but not hypertension, of sRA mice. These results demonstrate that mTORC1 is a novel downstream pathway of Ang II type 1 receptor signaling in the brain and selectively mediates the effect of Ang II on drinking behavior.


Surrogate assessment of coronary artery disease patients' functional capacity.
An investigation of the surrogate assessment of coronary artery disease (CAD) patients' functional capacity was conducted using 193 patient and surrogate rater dyads. Mean age of patients and surrogate raters were 60.4 and 54.4 years, respectively. Patients and surrogates independently completed a brief questionnaire that assessed health and psychosocial factors. The Duke Activity Status Index (DASI) was contained in the patients' questionnaire, while a similar form modified to assess patients' functional capacity was imbedded in the surrogates' questionnaire. Results indicated similar psychometric characteristics and clinical validity for patients' self-report and surrogates' ratings, suggesting that the Surrogate Rating Form of the Duke Activity Status Index (DASI-SRF) is a reliable and valid proxy method of assessing patient's functional capacity when this information may not be obtained directly from the patient. Further, while there were no effects of surrogates' health and psychological characteristics on their ratings of patients' functional capacity, in comparison with other surrogates, spouses were more likely to rate patients higher in functional capacity. Exploration of the patient/care provider relationship via concurrent use of the DASI and DASI-SRF is discussed.