Interval training in patients with severe chronic heart failure: analysis and recommendations for exercise procedures.
This study analyzes a new exercise training procedure, which includes interval exercise training on cycle ergometer (IntCT) (30-s work phases/60-s recovery phases) and on treadmill (60-s work and recovery phases each). Training was applied for 3 wk in 18 patients with severe chronic heart failure (CHF) ((mean +/- SEM) age 52 +/- 2 yr, ejection fraction 21 +/- 1%). Peak VO2 was increased from 12.2 +/- 0.7 to 14.6 +/- 0.7 ml-kg-1 min-1 owing to training (P < 0.001). A specific steep ramp test (work rate increments 25 W.10 s-1) was developed to derive exercise intensity for work phases in IntCT, which was 50% of the maximum work rate achieved. Steep ramp test was performed at the start of the study to determine the initial training work rate, then weekly to readjust it. Since the maximum work rate achieved from this test increased weekly (144 +/- 10 W -->172 +/- 10 W-->200 +/- 11 W; P < 0.001), the training work rate also increased (72 +/- 4 W-->86 +/- 6 W-->100 +/- 7 W; P < 0.001). Physical responses to IntCT were measured. There was no significant change in heart rate, blood pressure, and ratings of perceived exertion (RPE) using a Borg Scale between the first and the third week of training (heart rate 88 +/- 3 b.min-1; blood pressure 115 +/- 4/80 +/- 2 mm Hg; leg fatigue 12 +/- 1; dyspnea 10 +/- 1). Mean lactate concentration (1.70 +/- 0.09 mmol-1-1) indicated an overall aerobic range of training intensity. When compared with the commonly used intensity level of 75% peak VO2 from an ordinary ramp test (work rate increments 12.5 W.min-1), the performed training work rate was more than doubled (240%; P < 0.0001) while cardiac stress was lower (86%; P < 0.01). Values of norepinephrine and epinephrine as well as of RPE corresponded to those measured at 75% peak VO2. Interval exercise training is thus recommended for selected patients with CHF as it allows intense exercise stimuli on peripheral muscles with minimal cardiac strain. Using a steep ramp test, training work rate can be determined and readjusted weekly during initial training period.


The Acinetobacter regulatory UmuDAb protein cleaves in response to DNA damage with chimeric LexA/UmuD characteristics.
In the DNA damage response of most bacteria, UmuD forms part of the error-prone (UmuD'(2) )C polymerase V and is activated for this function by self-cleavage after DNA damage. However, the umuD homolog (umuDAb) present throughout the Acinetobacter genus encodes an extra N-terminal region, and in Acinetobacter baylyi, regulates transcription of DNA damage-induced genes. UmuDAb expressed in cells was correspondingly larger (24 kDa) than the Escherichia coli UmuD (15 kDa). DNA damage from mitomycin C or UV exposure caused UmuDAb cleavage in both E. coli wild-type and ΔumuD cells on a timescale resembling UmuD, but did not require UmuD. Like the self-cleaving serine proteases LexA and UmuD, UmuDAb required RecA for cleavage. This cleavage produced a UmuDAb' fragment of a size consistent with the predicted cleavage site of Ala83-Gly84. Site-directed mutations at Ala83 abolished cleavage, as did mutations at either the Ser119 or Lys156 predicted enzymatic residues. Co-expression of the cleavage site mutant and an enzymatic mutant did not allow cleavage, demonstrating a strictly intramolecular mechanism of cleavage that more closely resembles the LexA-type repressors than UmuD. These data show that UmuDAb undergoes a post-translational, LexA-like cleavage event after DNA damage, possibly to achieve its regulatory action.


[Analysis of Cases of Thrombolytic Therapy Administration for Acute Thrombosis of Mechanical Prosthetic Valves].
Mechanical prosthetic valve thrombosis is a life-threatening complication that in most cases requires urgent re-intervention. A significant risk of intraoperative complications, death and presence of a small fresh thrombus suggest thrombolytic therapy to be an alternative option of treatment because of a relatively low risk of the procedure. This article presents successful experience of systemic thrombolysis in patients with acute thrombosis of mechanical prosthetic valves.


Samples from patients with AML show high concordance in detection of mutations by NGS at local institutions vs central laboratories.
Next-generation sequencing (NGS) to identify pathogenic mutations is an integral part of acute myeloid leukemia (AML) therapeutic decision-making. The concordance in identifying pathogenic mutations among different NGS platforms at different diagnostic laboratories has been studied in solid tumors but not in myeloid malignancies to date. To determine this interlaboratory concordance, we collected a total of 194 AML bone marrow or peripheral blood samples from newly diagnosed patients with AML enrolled in the Beat AML Master Trial (BAMT) at 2 academic institutions. We analyzed the diagnostic samples from patients with AML for the detection of pathogenic myeloid mutations in 8 genes (DNMT3A, FLT3, IDH1, IDH2, NPM1, TET2, TP53, and WT1) locally using the Hematologic Neoplasm Mutation Panel (50-gene myeloid indication filter) (site 1) or the GeneTrails Comprehensive Heme Panel (site 2) at the 2 institutions and compared them with the central results from the diagnostic laboratory for the BAMT, Foundation Medicine, Inc. The overall percent agreement was over 95% each in all 8 genes, with almost perfect agreement (κ > 0.906) in all but WT1, which had substantial agreement (κ = 0.848) when controlling for site. The minimal discrepancies were due to reporting variants of unknown significance (VUS) for the WT1 and TP53 genes. These results indicate that the various NGS methods used to analyze samples from patients with AML enrolled in the BAMT show high concordance, a reassuring finding given the wide use of NGS for therapeutic decision-making in AML.


Prognostic Role of Biomarkers for Pulmonary Arterial Hypertension Associated with Bronchopulmonary Dysplasia in Extremely Premature Infants.
To explore the association of the biochemical markers after birth with BPD-PAH, factors independently predicting BPD-PAH risk were identified by multivariate logistic regression. Cut off values were determined by plotting receiver-operator curve (ROC), for the sake of dichotomizing continuous variables that showed independent relation with BPD-PAH risk. The results show that uric acid (UC) and blood urea nitrogen (BUN) contents markedly increased among infants experiencing BPD-PAH in comparison with those without BPD-PAH (11.6 vs. 9.7 mmol/L, P = 0.006 and 482.0 vs. 249.0 μmol/L, P < 0.001, separately). As shown by multivariate logistic regression, serum BUN levels (OR = 1.143) and uric acid levels (OR = 1.034) were important risk factors for BPD-PAH. Through a lot of experiments, the effectiveness and the advanced nature of the framework proposed in this paper are proved effectively. The framework proposed in this paper can provide some reference and thinking for follow-up research.


Prevalence and serotypes of Listeria monocytogenes contamination in Chinese beef processing plants.
The aim of this work was to study the epidemiology of Listeria spp., particularly Listeria monocytogenes, and to identify the serotypes present in contaminated samples from beef processing plants in China. A total of 439 samples were obtained from bovine feces, hides, and carcasses at three commercial processing plants. A standard protocol (ISO 11290-1) was followed to detect Listeria spp. and L. monocytogenes, and multiplex polymerase chain reaction was used to identify the various L. monocytogenes serotypes. The overall prevalences of Listeria spp. and L. monocytogenes were 65.6% and 26.4%, respectively, and the contamination was highest in the hide samples. The identified L. monocytogenes serotypes were 1/2c and 1/2a. The results of the current study indicate that Listeria spp. contamination is common in Chinese beef processing plants; specific measures should be taken to prevent and/or treat L. monocytogenes contamination of feces and hides in beef slaughter plants. Furthermore, because Listeria spp. contamination was found to be prevalent, it should, therefore, be studied further. The prevention of cases of sporadic listeriosis in China should also be addressed.


In-situ deposition of iron oxide nanoparticles on polyacrylonitrile-based nanofibers by chemico-thermal reduction method.
Polyacrylonitrile (PAN)-based nanocomposite fibers were prepared by co-precipitation of different amounts of Fe(II) and Fe(III) in an alkaline medium to get iron oxide impregnated nanofibers. Nanofibers web were prepared from blend solution of PAN containing different concentrations (1, 2 and 3 wt%) of ferrous (Fe2+)/ferric (Fe3+) solution in the 1:2 molar ratio in an effort to further improvement of the porosity and thereby, electrical properties. Electrospun fibers containing various concentrations of iron salts were then treated with KOH solution to produce nanosized magnetite particles in situ within the PAN nanofibers by precipitating Fe2+ ions or mixture of Fe2+ and Fe3+ ions. Such nanoscale particles homogeneously dispersed in PAN nanofibers to form the three-dimensional network structure. The homogeneously dispersed nanoparticles of iron oxide in and on the PAN carbon nanofibers produced the network structure of reasonably well-aligned configuration. Composite nanofibers morphologies and surface properties were discussed utilizing the combined techniques viz., field emission scanning electron microscope (FE-SEM), particle size analyzer, surface area and pore size distribution measurements.


Structural and Kinetic Visualization of the Protein Corona on Bioceramic Nanoparticles.
Bioceramic nanoparticles exhibit excellent features that enable them to function as an ideal material for hard tissue engineering. However, to fully understand their behavior, it is of crucial importance to understand their behavior within the fluids of the human body. To achieve this goal, we have studied the interaction between hydroxyapatite nanorods (HA) and bovine serum albumin (BSA). First, we describe the surface morphology of the nanoparticle. Then, the main characteristics of the physiological interplay of BSA and the hydroxyapatite nanoparticle are presented by using a battery of techniques: ITC, zeta potential, UV-vis, fluorescence, and CD. Experimental data was analyzed by developing specific approaches to determining important parameters such as rates, affinities, and stochiometries of protein associated with the nanoparticles. ITC has been confirmed as a powerful technique for determining the affinity, binding, and thermodynamics of BSA-nanoparticle interactions. Careful quantitative assessment of the kinetic properties of the adsorption were revealed by UV-vis and fluorescence measurements. Finally, CD measurements highlight the important role of protein flexibility in these kinds of systems.


A case of pheochromocytoma of the urinary bladder in a long-term hemodialysis patient.
The development is reported of a pheochromocytoma of the urinary bladder in a 33-year-old patient with systemic lupus erythematosus who had undergone long-term hemodialysis. A hypertensive episode followed by defecation was demonstrated by the monitoring of blood pressure with a portable automated sphygmomanometer without elevation of plasma catecholamines. The tumor was surgically removed and normalization of the patient's blood pressure followed. Thus, monitoring of blood pressure for 24 h proved useful for the diagnosis of pheochromocytoma and, in particular, of paroxysmal hypertension.


Knockdown of eIF3a attenuates the pro-fibrogenic response of hepatic stellate cells induced by TGF-β1.
Activation of hepatic stellate cells (HSCs) plays an important role in the development of liver fibrosis. The eukaryotic translation initiation factor (eIF) 3a is the largest subunit of the eIF3 complex and has been involved in pulmonary fibrosis. However, the role of eIF3a in liver fibrosis remains largely unknown. Therefore, in this study, we investigated the role of eIF3a in transforming growth factor-β1 (TGF-β1)-induced HSC activation. Our results demonstrated that the expression of eIF3a was up-regulated in human liver fibrotic tissues and activated HSCs. In addition, knockdown of eIF3a suppressed TGF-β-induced HSC proliferation and the expression of α-smooth muscle actin (α-SMA) and collagen I. Furthermore, knockdown of eIF3a inhibited the expression of p-Smad3 induced by TGF-β1 in HSCs. These results suggest that eIF3a may function as a novel regulator to modulate HSC activation, potentially through inhibiting the TGF-β1/Smad3 signaling pathway.


Metabolic allometric scaling model: combining cellular transportation and heat dissipation constraints.
Living organisms need energy to be 'alive'. Energy is produced by the biochemical processing of nutrients, and the rate of energy production is called the metabolic rate. Metabolism is very important from evolutionary and ecological perspectives, and for organismal development and functioning. It depends on different parameters, of which organism mass is considered to be one of the most important. Simple relationships between the mass of organisms and their metabolic rates were empirically discovered by M. Kleiber in 1932. Such dependence is described by a power function, whose exponent is referred to as the allometric scaling coefficient. With the increase of mass, the metabolic rate usually increases more slowly; if mass increases by two times, the metabolic rate increases less than two times. This fact has far-reaching implications for the organization of life. The fundamental biological and biophysical mechanisms underlying this phenomenon are still not well understood. The present study shows that one such primary mechanism relates to transportation of substances, such as nutrients and waste, at a cellular level. Variations in cell size and associated cellular transportation costs explain the known variance of the allometric exponent. The introduced model also includes heat dissipation constraints. The model agrees with experimental observations and reconciles experimental results across different taxa. It ties metabolic scaling to organismal and environmental characteristics, helps to define perspective directions of future research and allows the prediction of allometric exponents based on characteristics of organisms and the environments they live in.


[Pathophysiology of medial temporal lobe epilepsy: role of cerebral dysgenesis].
We studied the incidence of cerebral dysgenetic lesions(CD) in 39 operated patients with medial temporal lobe epilepsy(MTLE) who had hippocampal sclerosis. Four patients had CD, such as menigocele at the ipsilateral temporal fossa, schizencephaly in the ipsilateral peri-Rolandic area, focal cortical dysplasia in the ipsilateral inferior temporal gyrus and periventricular nodular heterotopia at the bilateral inferior horns of the lateral ventricle. Histological examinations of the resected lateral temporal lobes from 29 MTLE patients revealed the presence of microdysgenesis (microscopic cerebral dysgenesis) in 28 patients, including heterotopic white matter neuron(24 cases), molecular layer neuron(14), oligodendroglial cell cluster(11), dilated perivascular space(10). These findings suggest that the congenital factors, as well as hippocampal sclerosis, may be involved in the development of MTLE.


Effects of Diabetic Ketoacidosis on Executive Function in Children With Type 1 Diabetes: Evidence From Wisconsin Card Sorting Test Performance.
Diabetic ketoacidosis (DKA) in patients with type 1 diabetes mellitus (T1DM) is known to affect memory function, but little is known about its impact on executive function. This study aimed to determine whether a history of DKA was associated with changes in executive function in children with T1DM. The sample consisted of 99 patients with T1DM with histories of DKA, 82 patients with T1DM without DKA, and 100 healthy controls aged 7 to 18 years. Neuropsychological function and emotion assessments were performed in all participants. The Wisconsin Card Sorting Test (WCST) was used to assess executive function. Compared with healthy controls, the DKA group (but not the non-DKA group) had a significantly lower mean intelligence quotient (IQ; p = .006, Cohen d = 0.528) and a significantly higher rate of WCST perseverative errors (p = .006, Cohen d = 0.475). In the DKA group, the age at DKA onset was significantly associated with the IQ (p = .001) and the number of completed WCST categories (p = .046). Higher hemoglobin A1c levels were associated significantly with lower IQ (p < .001), increased rate of WCST perseverative errors (p = .015), and completion of fewer WCST categories (p = .027). DKA has implications for executive function in children with T1DM. These findings emphasize the importance of DKA prevention in patients with known T1DM, especially younger children with newly diagnosed T1DM.


TRPS1 mutation associated with trichorhinophalangeal syndrome type 1 with 15 supernumerary teeth, hypoplastic mandibular condyles with slender condylar necks and unique hair morphology.
Trichorhinophalangeal syndrome type 1 (TRPS1; Online Mendelian Inheritance in Man #190350) is an autosomal dominant disorder caused by mutations in TRPS1. We report a Thai male with TRPS1 who carried a c.1842C>T (p.Arg615Ter) mutation. He had 15 supernumerary teeth, double mental foramina, hypoplastic mandibular condyles with slender condylar necks and unique ultrastructural hair findings. Body hair was absent. The hair in the area of a congenital melanocytic nevus had a greater number of hair cuticles than normal. Occipital hair had abnormal hair follicles and cuticles. The scale edges of the hair cuticles were detached and rolled up. Hypoplastic mandibular condyles with slender condylar necks, double mental foramina and the rolled up edges of hair cuticles have not been reported in patients with TRPS1.


Phase-field model for Marangoni convection in liquid-gas systems with a deformable interface.
We developed a phase-field model for Marangoni convection in a liquid-gas system with a deformable interface, heated from below. In order to describe both Marangoni instabilities (with short and long wavelengths), an additional force component must be considered in the Navier-Stokes equation. This term describes the coupling of the temperature to the velocity field via the phase-field function. It results by minimizing the free-energy functional of the system. For a bidimensional problem in linear approximation we performed a numerical code that successfully computes both Marangoni instabilities. In the limit of sharp and rigid interfaces, our results are compared with the literature.


[Is Stewart's malignant midline granuloma a peripheral T-cell lymphoma? Apropos of 5 cases].
Midline granuloma includes diverse clinicopathological entities, such as Wegener granulomatosis, polymorphic reticulosis, lethal midline granuloma and conventional malignant lymphoma of the nose usually of B-cell origin. The authors describe five patients with LMG clinically and pathologically typical. Using an extensive panel of monoclonal antibodies, they demonstrate an "activate" T-cell phenotype observed on the initial lesion of the face in one patient, similar to that found in two patients with LMG but studied after dissemination in peripheral T-cell lymphoma. Furthermore, many atypical cells were found in LMG, and stained with the Ki-67 monoclonal antibody, a marker of proliferating cells. These findings support the view that LMG is closely related to T-cell malignancies. Two of them were treated with recombinant Interferon alpha 2a followed by a response rapidly objective. Immunohistologic studies are very important for confirming the T-cell origin of such a disease and for selecting patients to be treated with Interferon alpha.


Process to generate a synthetic diagnostic for microwave imaging reflectometry with the full-wave code FWR2D.
A synthetic microwave imaging reflectometer (MIR) diagnostic employing the full-wave reflectometer code (FWR2D) has been developed and is currently being used to guide the design of real systems, such as the one recently installed on DIII-D. The FWR2D code utilizes real plasma profiles as input, and it is combined with optical simulation tools for synthetic diagnostic signal generation. A detailed discussion of FWR2D and the process to generate the synthetic signal are presented in this paper. The synthetic signal is also compared to a prescribed density fluctuation spectrum to quantify the imaging quality. An example is presented with H-mode-like plasma profiles derived from a DIII-D discharge, where the MIR focal is located in the pedestal region. It is shown that MIR is suitable for diagnosing fluctuations with poloidal wavenumber up to 2.0 cm(-1) and fluctuation amplitudes less than 5%.


Stress test of liver function using technetium-99m-mebrofenin hepatobiliary scintigraphy.
Technetium-99m (Tc) mebrofenin hepatobiliary scintigraphy (HBS) enables a quantitative assessment of liver function. This is normally performed in a fasting state and might therefore reflect the resting liver function. We evaluated the change in liver function using HBS after stimulation with an oral metabolic challenge. Healthy volunteers aged 50-60 (n=12) or older than or equal to 75 (n=12) years underwent two sequential HBS. The first scan was performed after an overnight fast and the second scan was performed after the administration of chocolate milk. Hepatic Tc-mebrofenin uptake rate (cMUR) was calculated and the difference was expressed as percentage. cMUR after fasting was 10.9±2.5%/min/m (mean±SD) and increased by 20% to 13.0±3.1%/min/m after stimulation with chocolate milk (P<0.001). cMUR increased markedly after the administration of an oral metabolic challenge in comparison with fasting. This may be a consequence of hepatocyte stimulation, reflecting the hepatic functional reserve capacity.


Water system hardware and management rehabilitation: Qualitative evidence from Ghana, Kenya, and Zambia.
Sufficient, safe, continuously available drinking water is important for human health and development, yet one in three handpumps in sub-Saharan Africa are non-functional at any given time. Community management, coupled with access to external technical expertise and spare parts, is a widely promoted model for rural water supply management. However, there is limited evidence describing how community management can address common hardware and management failures of rural water systems in sub-Saharan Africa. We identified hardware and management rehabilitation pathways using qualitative data from 267 interviews and 57 focus group discussions in Ghana, Kenya, and Zambia. Study participants were water committee members, community members, and local leaders in 18 communities (six in each study country) with water systems managed by a water committee and supported by World Vision (WV), an international non-governmental organization (NGO). Government, WV or private sector employees engaged in supporting the water systems were also interviewed. Inductive analysis was used to allow for pathways to emerge from the data, based on the perspectives and experiences of study participants. Four hardware rehabilitation pathways were identified, based on the types of support used in rehabilitation. Types of support were differentiated as community or external. External support includes financial and/or technical support from government or WV employees. Community actor understanding of who to contact when a hardware breakdown occurs and easy access to technical experts were consistent reasons for rapid rehabilitation for all hardware rehabilitation pathways. Three management rehabilitation pathways were identified. All require the involvement of community leaders and were best carried out when the action was participatory. The rehabilitation pathways show how available resources can be leveraged to restore hardware breakdowns and management failures for rural water systems in sub-Saharan Africa. Governments, NGOs, and private sector actors can better build capacity of community actors by focusing on their role in rehabilitating hardware and management and to ensure that they are able to quickly contact external support actors when needed for rehabilitation. Using qualitative and participatory methods allows for insight into rapid rehabilitation of hardware and management.


Spatiotemporal patterns of cortical fiber density in developing infants, and their relationship with cortical thickness.
The intrinsic relationship between the convoluted cortical folding and the underlying complex whiter matter fiber connections has received increasing attention in current neuroscience studies. Recently, the axonal pushing hypothesis of cortical folding has been proposed to explain the finding that the axonal fibers (derived from diffusion tensor images) connecting to gyri are significantly denser than those connecting to sulci in both adult human and non-human primate brains. However, it is still unclear about the spatiotemporal patterns of the fiber density on the cortical surface of the developing infant brains from birth to 2 years of age, which is the most dynamic phase of postnatal brain development. In this paper, for the first time, we systemically characterized the spatial distributions and longitudinal developmental trajectories of the cortical fiber density in the first 2 postnatal years, via joint analysis of longitudinal structural and diffusion tensor imaging from 33 healthy infants. We found that the cortical fiber density increases dramatically in the first year and then keeps relatively stable in the second year. Moreover, we revealed that the cortical fiber density on gyral regions was significantly higher at 0, 1, and 2 years of age than that on sulcal regions in the frontal, temporal, and parietal lobes. Meanwhile, the cortical fiber density was strongly positively correlated with cortical thickness at several three-hinge junction regions of gyri. These results significantly advanced our understanding of the intrinsic relationship between the cortical folding, cortical thickness and axonal wiring during early postnatal stages.


Considering Image Information and Self-Similarity: A Compositional Denoising Network.
Recently, convolutional neural networks (CNNs) have been widely used in image denoising, and their performance has been enhanced through residual learning. However, previous research mostly focused on optimizing the network architecture of CNNs, ignoring the limitations of the commonly used residual learning. This paper identifies two of its limitations, which are the neglect of image information and the lack of effective consideration of image self-similarity. To solve these limitations, this paper proposes a compositional denoising network (CDN), which contains two sub-paths, the image information path (IIP) and the noise estimation path (NEP), respectively. IIP is trained via an image-to-image method to extract image information. For NEP, it utilizes image self-similarity from the perspective of training. This similarity-based training method constrains NEP to output similar estimated noise distributions for different image patches with a specific kind of noise. Finally, image information and noise distribution information are comprehensively considered for image denoising. Experimental results indicate that CDN outperforms other CNN-based methods in both synthetic and real-world image denoising, achieving state-of-the-art performance.


Neural organization of afferent pathways from the stomatopod compound eye.
Crustaceans and insects share many similarities of brain organization suggesting that their common ancestor possessed some components of those shared features. Stomatopods (mantis shrimps) are basal eumalacostracan crustaceans famous for their elaborate visual system, the most complex of which possesses 12 types of color photoreceptors and the ability to detect both linearly and circularly polarized light. Here, using a palette of histological methods we describe neurons and their neuropils most immediately associated with the stomatopod retina. We first provide a general overview of the major neuropil structures in the eyestalks lateral protocerebrum, with respect to the optical pathways originating from the six rows of specialized ommatidia in the stomatopod's eye, termed the midband. We then focus on the structure and neuronal types of the lamina, the first optic neuropil in the stomatopod visual system. Using Golgi impregnations to resolve single neurons we identify cells in different parts of the lamina corresponding to the three different regions of the stomatopod eye (midband and the upper and lower eye halves). While the optic cartridges relating to the spectral and polarization sensitive midband ommatidia show some specializations not found in the lamina serving the upper and lower eye halves, the general morphology of the midband lamina reflects cell types elsewhere in the lamina and cell types described for other species of Eumalacostraca.


Age differences and protected first heterosexual intercourse in Ghana.
Age differences between partners, where females are relatively younger than their male partners, can negatively affect power dynamics and subsequent negotiations for safe sex practices with implications on unplanned pregnancies and STIs transmission. This paper examines the effects of age differentials on condom use at first sex. Using a weighted sample of 925 women drawn from the fifth round of Ghana Demographic and Health Survey and applying complementary log-log model, the probability of first sex being protected vis-a-vis partner age differences are estimated. The results suggest that females' being ten or more years younger than their male partners at first sex was a significant indicator of non-protection while at age intervals 1-4 and 5-9 years, the probability of protected sex inflates significantly. The results demonstrate that large age disparities between partners pose a significant barrier to protection during first sex and strategies have to be developed to altering wrong perceptions associated with intergenerational sex, particularly, in settings such as Africa where gerontocratic tendencies pervade not only social relationships but sexual as well.


[Efficacy and safety of bulevirtide in patients with chronic hepatitis D and compensated cirrhosis].
To study the efficacy and safety of bulevirtide, the HBV and HDV entry inhibitor. Analysis of the results of using bulevirtide in randomized controlled open-label comparative studies MYR202 and MYR203 in 56 patients with chronic hepatitis D and compensated cirrhosis, in monotherapy and combination with pegylated interferon alpha-2a (PEG-IFN). Monotherapy with bulevirtide for 24 weeks in the MYR202 study in 46 patients with compensated liver cirrhosis demonstrated: 1) a high rate of virological (100%) and biochemical response (alanine aminotransferase normalization rate 45.7%), 2) superiority of bulevirtide in efficacy over the control group (tenofovir), 3) comparability of treatment efficacy in patients with and without cirrhosis, 4) no progression of liver fibrosis with elastometry in most patients. Treatment with bulevirtide in monotherapy and combination with PEG-IFN for 48 weeks in 10 patients with compensated liver cirrhosis in the MYR203 study was accompanied by a high rate of virological response (80%) and normalization of alanine aminotransferase (70%). Bulevirtide was well tolerated, there was no deterioration in tolerability compared with patients without cirrhosis, there were no serious adverse events and cases of treatment cancellation due to adverse events. Bulevirtide is recommended as the first line of treatment for chronic hepatitis D in patients with compensated cirrhosis in monotherapy and combination with PEG-IFN.


Clofarabine-based combination chemotherapy for relapse and refractory childhood acute lymphoblastic leukemia.
Clofarabine, one of the key treatment agents for refractory and relapsed acute lymphoblastic leukemia (ALL), achieves a remission rate of approximately 30% with single-agent clofarabine induction chemotherapy. However, a remission rate of approximately 50% was reported with a combination chemotherapy regimen consisting of clofarabine, etoposide, and cyclophosphamide. We treated two cases with refractory and relapsed ALL with combination chemotherapy including clofarabine; one was an induction failure but the other achieved remission. Both cases developed an infectious complication (NCI-CTCAE grade 3) and body pain with infusion. Prophylactic antibiotic and opioid infusions facilitated avoiding septic shock and pain. Further investigation of such cases is required.


GPR88 in A2A receptor-expressing neurons modulates locomotor response to dopamine agonists but not sensorimotor gating.
The orphan receptor, GPR88, is emerging as a key player in the pathophysiology of several neuropsychiatric diseases, including psychotic disorders. Knockout (KO) mice lacking GPR88 throughout the brain exhibit many abnormalities relevant to schizophrenia including locomotor hyperactivity, behavioural hypersensitivity to dopaminergic psychostimulants and deficient sensorimotor gating. Here, we used conditional knockout (cKO) mice lacking GPR88 selectively in striatal medium spiny neurons expressing A2A receptor to determine neuronal circuits underlying these phenotypes. We first studied locomotor responses of A2A R-Gpr88 KO mice and their control littermates to psychotomimetic, amphetamine, and to selective D1 and D2 receptor agonists, SKF-81297 and quinpirole, respectively. To assess sensorimotor gating performance, mice were submitted to acoustic and visual prepulse inhibition (PPI) paradigms. Total knockout GPR88 mice were also studied for comparison. Like total GPR88 KO mice, A2A R-Gpr88 KO mice displayed a heightened sensitivity to locomotor stimulant effects of amphetamine and SKF-81297. They also exhibited enhanced locomotor activity to quinpirole, which tended to suppress locomotion in control mice. By contrast, they had normal acoustic and visual PPI, unlike total GPR88 KO mice that show impairments across different sensory modalities. Finally, none of the genetic manipulations altered central auditory temporal processing assessed by gap-PPI. Together, these findings support the role of GPR88 in the pathophysiology of schizophrenia and show that GPR88 in A2A receptor-expressing neurons modulates psychomotor behaviour but not sensorimotor gating.


Primary Renal Mesenchymal Neoplasms in Nephrectomy Specimens: A 16-Year Survey of Primary and Incidental Cases From a Single Institution.
Context. Primary renal mesenchymal neoplasms are rare but diverse. Several neoplasms of mesenchymal derivation can arise as a primary renal mass; however, incidental tumors are identified in nephrectomies performed for end-stage renal disease or other malignant epithelial renal neoplasms. In this article, we document their frequencies with demographic information in nephrectomy specimens. Design. We retrospectively searched our database for nephrectomy specimens from the year 2000 to 2016. Results. A total of 224 cases were identified with an incidence rate of 4.4% (224/5128). One hundred ninety (85%) neoplasms were benign, 27 (12%) were malignant, and 7 (3%) were of intermediate biologic behavior. The majority of cases occurred in adults (93%, 208/224), and 39% of cases represented an incidental finding. The most common neoplasms were angiomyolipoma (58%) and renomedullary interstitial cell tumor (17%). Malignant mesenchymal kidney tumors are rare (0.39% of nephrectomy specimens). The most common adults' malignant tumors in our survey were synovial sarcoma and Ewing's sarcoma. Conclusion. Primary renal mesenchymal tumors are rare and are mostly benign in nature with many incidentally identified lesions. They arise in different age groups with malignant lesions usually presenting at a younger mean age.


Effects of dopaminergic modulation on the integrative properties of the ventral striatal medium spiny neuron.
Dopaminergic modulation produces a variety of functional changes in the principal cell of the striatum, the medium spiny neuron (MSN). Using a 189-compartment computational model of a ventral striatal MSN, we simulated whole cell D1- and D2-receptor-mediated modulation of both intrinsic (sodium, calcium, and potassium) and synaptic currents (AMPA and NMDA). Dopamine (DA) modulations in the model were based on a review of published experiments in both ventral and dorsal striatum. To objectively assess the net effects of DA modulation, we combined reported individual channel modulations into either D1- or D2-receptor modulation conditions and studied them separately. Contrary to previous suggestions, we found that D1 modulation had no effect on MSN nonlinearity and could not induce bistability. In agreement with previous suggestions, we found that dopaminergic modulation leads to changes in input filtering and neuronal excitability. Importantly, the changes in neuronal excitability agree with the classical model of basal ganglia function. We also found that DA modulation can alter the integration time window of the MSN. Interestingly, the effects of DA modulation of synaptic properties opposed the effects of DA modulation of intrinsic properties, with the synaptic modulations generally dominating the net effect. We interpret this lack of synergy to suggest that the regulation of whole cell integrative properties is not the primary functional purpose of DA. We suggest that D1 modulation might instead primarily regulate calcium influx to dendritic spines through NMDA and L-type calcium channels, by both direct and indirect mechanisms.


Mental Health Care Gap: The Case of the Slovak Republic.
This study explored unmet mental health and social care needs in the Slovak Republic and their adverse human rights consequences. We estimated treatment gap for persons aged 15-64 years in year 2015 affected by depressive, anxiety, substance use and schizophrenic disorders by comparing local treated prevalence rates with population estimated rates for Europe. Two-thirds of people with depressive disorders and over 80% of those with anxiety disorders and alcohol dependence were not receiving treatment. There was no treatment gap for persons with schizophrenia. Fifty-one percent of those eligible for disability pension on the grounds of mental disorders failed to receive it. We discuss the implications of the estimated gaps in mental health and social care and consequent human rights violations that may result from the current system of mental health care in Slovakia.


Warm Needling Therapy and Acupuncture at Meridian-Sinew Sites Based on the Meridian-Sinew Theory: Hemiplegic Shoulder Pain.
This study was performed to evaluate the effectiveness and safety of warm needling acupuncture at meridian-sinew sites based on the meridian-sinew theory in the treatment of hemiplegic shoulder pain (HSP) after stroke. In total, 124 subjects were randomized into a treatment group and control group. In the treatment group, warm needling therapy and acupuncture at meridian-sinew sites based on the meridian-sinew theory were performed. In the control group, usual care therapy was applied. The visual analog scale (VAS) score, range of motion (ROM), and Barthel index (BI) were used to evaluate treatment effectiveness. At 2 weeks of treatment, the VAS score, ROM, and BI had obviously changed from baseline in the two groups (P < 0.01). The changes in the VAS score and ROM in the treatment group were significantly greater than those in the control group (P < 0.01). At the 3-month follow-up after treatment, the changes in the treatment group were significantly greater than those in the control group (P < 0.01). This study indicates that warm needling therapy with acupuncture at meridian-sinew sites based on the meridian-sinew theory is effective for HSP.


The concept of clinical leadership.
This paper examines the concept of clinical leadership and finds that the concept has been used in a number of ways within the nursing literature. The paper argues that in a nursing practice setting the concept of clinical leadership is an appropriate one. In the clinical setting the nurse leader often has followers in the health care team, patients and their relatives. Thus it is argued that clinical leadership can be defined as the expert nurse who leads patients to better health care.


Laparoscopic Roux-en-Y Gastric bypass after failed vertical banded gastroplasty: a multicenter experience with 203 patients.
Vertical banded gastroplasty (VBG) has long been the main restrictive procedure for morbid obesity but has many long-term complications for which conversion to Roux-en-Y gastric bypass (RYGBP) is often considered the best option. This series regroups patients operated on by three different surgeons in four different centers. All data were collected prospectively, then pooled and analyzed retrospectively. Out of 2,522 RYGBP performed between 1998 and 2010, 538 were reoperations, including 203 laparoscopic RYGBP after VBG. There were 175 women and 28 men. The mean BMI before VBG was 43.2 ± 6.3, and the mean BMI before reoperation was 37.4 ± 8.3. Most patients had more than one indication for reoperation and/or had regained significant weight. There was no conversion to open surgery. A total of 24 patients (11.8 %) developed complications, including nine (4.5 %) who required reoperation and one death. With a follow-up of 88.9 % after 8 years, the mean BMI after 1, 3, 5, 7, and 9 years was 29.1, 28.8, 28.7, 29.9, and 28.8, respectively. On the basis of this experience, the largest with laparoscopic reoperative RYGBP after failed VBG, we conclude that this procedure can safely be performed in experienced hands, with weight loss results similar to those observed after primary RYGBP. In patients with too difficult an anatomy below the cardia, dividing the esophagus just above the esophago-gastric junction and performing an esophagojejunostomy may be a safe alternative to converting to a Scopinaro-type BPD, obviating the additional long-term risks associated with malabsorption.


Validity and intra- and interobserver reliability of an indirect volume measurements in patients with upper extremity lymphedema.
We investigated a method of indirect volume measurement that utilized surface measurements and a simplified formula derived from the formula for a frustum (Sitzia's method) to determine limb volumes in patients with breast cancer-related lymphedema of the upper extremity. Repeated measurements of upper-extremity limb volume were obtained by two observers on both upper extremities of 30 women with unilateral lymphedema. Volume was calculated using a simplified formula and compared with water displacement method as a gold standard. Indirect volume determination using Sitzia's method is comparable with the water displacement method, has comparable intra- and interobserver reliabilities, and can be used for diagnosis and follow up measurements of lymphedema. Indirect volume determination using surface measurements at 8 cm intervals is only suitable for follow up measurements. The methods should not be used interchangeably.


Altered Carbon Partitioning Enhances CO2 to Terpene Conversion in Cyanobacteria.
Photosynthetic terpene production represents one of the most carbon and energy-efficient routes for converting CO2 into hydrocarbon. In photosynthetic organisms, metabolic engineering has led to limited success in enhancing terpene productivity, partially due to the low carbon partitioning. In this study, we employed systems biology analysis to reveal the strong competition for carbon substrates between primary metabolism (e.g., sucrose, glycogen, and protein synthesis) and terpene biosynthesis in Synechococcus elongatus PCC 7942. We then engineered key "source" and "sink" enzymes. The "source" limitation was overcome by knocking out either sucrose or glycogen biosynthesis to significantly enhance limonene production via altered carbon partitioning. Moreover, a fusion enzyme complex with geranyl diphosphate synthase (GPPS) and limonene synthase (LS) was designed to further improve pathway kinetics and substrate channeling. The synergy between "source" and "sink" achieved a limonene titer of 21.0 mg/L. Overall, the study demonstrates that balancing carbon flux between primary and secondary metabolism can be an effective approach to enhance terpene bioproduction in cyanobacteria. The design of "source" and "sink" synergy has significant potential in improving natural product yield in photosynthetic species.


Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4.
Dengue virus (DENV) is responsible for the most prevalent arthropod-borne viral infection in humans. Events decisive for disease development occur in the skin after virus inoculation by the mosquito. Yet, the role of human dermis-resident immune cells in dengue infection and disease remains elusive. Here we investigated how dermal dendritic cells (dDCs) and macrophages (dMs) react to DENV and impact on immunopathology. We show that both CD1c(+) and CD14(+) dDC subsets were infected, but viral load greatly increased in CD14(+) dDCs upon IL-4 stimulation, which correlated with upregulation of virus-binding lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN/CD209) and mannose receptor (CD206). IL-4 also enhanced T-cell activation by dDCs, which was further increased upon dengue infection. dMs purified from digested dermis were initially poorly infected but actively replicated the virus and produced TNF-α upon lectin upregulation in response to IL-4. DC-SIGN(+) cells are abundant in inflammatory skin with scabies infection or Th2-type dermatitis, suggesting that skin reactions to mosquito bites heighten the risk of infection and subsequent immunopathology. Our data identify dDCs and dMs as primary arbovirus target cells in humans and suggest that dDCs initiate a potent virus-directed T-cell response, whereas dMs fuel the inflammatory cascade characteristic of dengue fever.


RNA trafficking and subcellular localization-a review of mechanisms, experimental and predictive methodologies.
RNA localization is essential for regulating spatial translation, where RNAs are trafficked to their target locations via various biological mechanisms. In this review, we discuss RNA localization in the context of molecular mechanisms, experimental techniques and machine learning-based prediction tools. Three main types of molecular mechanisms that control the localization of RNA to distinct cellular compartments are reviewed, including directed transport, protection from mRNA degradation, as well as diffusion and local entrapment. Advances in experimental methods, both image and sequence based, provide substantial data resources, which allow for the design of powerful machine learning models to predict RNA localizations. We review the publicly available predictive tools to serve as a guide for users and inspire developers to build more effective prediction models. Finally, we provide an overview of multimodal learning, which may provide a new avenue for the prediction of RNA localization.


[Reasons for lumbar syndromes after disc operations (author's transl)].
This investigation presents the findings in 105 patients after disc operations who required renewed in-patient treatment mainly because of their resistance to therapy and/or recurrence of the lumbar syndrome. A number of factors were found to be implicated in providing a reason for unsatisfactory results after operations for prolapsed lumbar intervertebral discs. It must be postulated that interfering factors like ligamental pain, restricted movement, participation of the hip, psychological aspects, polyneuropathics and focal occurrence have to be taken into consideration already preoperatively in the diagnosis, indication for operation and therapy. Also with post-operative complaints special alteration must be paid during rehabilitation to those factors quoted above, as well as to direct post-operative complications like inflammation and scar.


Modelizing home safety as experienced by people with mental illness.
As more individuals with mental disorders now live in the community and as the custodial care housing model has shifted to supported housing, home safety has become a rising issue, however, not well documented. To describe the phenomenon of home safety for people with a mental disorder as well as its contributing factors. A descriptive qualitative design was used. Individual interviews were conducted with persons with a mental disorder (n = 8), while focus groups were conducted with relatives, health and social service providers and community stakeholders (n = 21). The data were analyzed with the grounded theory analysis as described by Paillé (1994). Findings suggest that home safety implies risk and protective factors, which are associated with (1) the person's characteristics; (2) the quality of the home environment; (3) the nature of the activities in which the individual engages. These dimensions are interrelated so that home incidents arise from a dynamic interaction between risk and protective factors. Home incidents therefore occur when the interaction between these dimensions is altered. Considering this situation, Occupational Therapists are well positioned to play a leading role and act as key contributors in the area of home safety in people with mental disorders.


Early pregnancy signals in domestic animals.
Large early embryonic death losses occur in all domestic animals and these losses are temporally related to early pregnancy recognition signals. Binucleate trophoblastic cells, which migrate to the endometrial endothelium, are a potential vehicle for early (day 15-20) communication between the mother and the embryo in ruminant animals. In cattle, the first pregnancy recognition signal, which results in increased progesterone secretion by the corpus luteum as early as day 10, appears to be a small (less than 10,000 Mr) heat-labile lipid-soluble molecule that can be adsorbed by dextran-coated charcoal. Although this substance has not yet been identified, there is a possibility that it is embryo-derived platelet-activating factor (EDPAF). EDPAF appears to influence progesterone synthesis by causing the release of luteotropic factors (arachidonic acid metabolites and serotonin) from activated platelets. The second pregnancy recognition factor in cattle and sheep appears to be a trophoblastic peptide having a molecular weight of 22,000-24,000 daltons (bTP-1, cattle) or 17,000 daltons (oTP-1, sheep). These compounds do not have direct luteotropic effects, but are thought to exert their antiluteolytic effects by inhibiting the production of luteolytic eicosanoids (PGF2 alpha) by the endometrium. A third early pregnancy signal in cattle is an hCG-like protein that appears in allantoic fluid on day 25, just after the disappearance of bTP-1. There is as yet no clear evidence that steroids produced by the conceptus act as early pregnancy signals in ruminants. However, estrogens appear to provide the essential early signal for corpus luteum maintenance in the pig.


Anorexia and bulimia nervosa.
Anorexia and bulimia nervosa are eating disorders characterised by abnormal eating behaviour, a morbid concern over body weight and a distorted perception of body size. It commonly occurs in young postpubertal girls in developed societies. Aetiological factors are a complex interplay of biological, psychological and social factors. Bizarre eating patterns can lead to life-threatening medical situations which require urgent in-hospital care. Comprehensive management should be effected by a multi-disciplinary team with contributions from the internist, the psychiatrist, the nurse, the psychologist, the social worker and the teacher. There is significant psychiatric morbidity and mortality in the outcome of these eating disorders.


Neural and humoral mechanisms of angiotensin-dependent hypertension.
We examined whether neural or humoral mechanisms mediate the acute versus chronic phases of angiotensin II (ANG II)-dependent hypertension in rabbits. ANG II was administered intravenously at 50 ng.kg-1.min-1 for 10 days. This dose of ANG II elevated mean arterial pressure (MAP) from 76 +/- 2 to 98 +/- 2 mmHg on day 1 and sustained the hypertension throughout the infusion period. Heart rate (226 +/- 7 beats/min) was not altered. The depressor response to ganglionic blockade (-38 +/- 2 mmHg) was significantly blunted on day 1 (-22 +/- 3 mmHg) and was significantly enhanced on days 5 (-52 +/- 4 mmHg) and 7 (-52 +/- 6 mmHg). In contrast, plasma norepinephrine (PNE) and renal sympathetic nerve activity (RSNA) levels were acutely reduced to approximately one-third of control (day 1 of ANG II) and chronically rose to an intermediate level (2-9 days of ANG II). However, the pressor effect of resetting PNE and RSNA may be magnified by an augmented pressor responsiveness to alpha-agonists after chronic ANG II. In animals with the area postrema removed, PNE, RSNA, and heart rate were acutely reduced and remained chronically depressed. In addition, area postrema lesion blocked the chronic, but not the acute hypertensive response, to infusing ANG II. Thus the direct vasoconstrictor actions of ANG II appear to acutely predominate, whereas neurogenic vasomotor tone appears to chronically predominate. This shift appears to be mediated by changes in vascular sensitivity, as well as the area postrema allowing resetting of the baroreflex.


Acute kidney injury in late pregnancy in developing countries.
The data directly evaluating acute renal failure (ARF) in third trimester of pregnancy from Indian subcontinent are scanty. This study analyzes the clinical spectrum of ARF with respect to total birth in third trimester of pregnancy. All pregnant women after the 28th week of pregnancy or in early postpartum period (up to 7 days) admitted to our hospital between August 2006 and August 2008 were screened for clinical evidence of ARF. Pregnant women with clinical diagnosis of ARF in third trimester were included in this study. Of the 4758 pregnant women in third trimester, ARF developed in 85 cases (1 in 56 births). Preeclampsia, puerperal sepsis, and intrauterine death were responsible for ARF in 35.29, 24.7, and 16.67% of cases, respectively. Postpartum hemorrhage and antepartum hemorrhage were the causes of ARF in 10.59 and 8.29% of patients, respectively. Acute fatty liver of pregnancy was noted in one patient. Complicated preeclampsia (hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, eclampsia, and uterine hemorrhage) was associated and higher incidence of ARF. Live birth occurred in 61.2% of patients with vaginal delivery in 70% cases. Renal cortical necrosis was diagnosed in two cases. Overall, mortality was 20%. The puerperal sepsis contributed 41% of total death. ARF complicated 1.78% of total delivery in third trimester of pregnancy. Preeclampsia was the most common cause of ARF followed by puerperal sepsis. In contrast to the developed countries, incidence of ARF is still very high in late pregnancy in the developing countries. Overall mortality was 20% with highest (33%) mortality in puerperal sepsis group.


Development of a speed breeding protocol with flowering gene investigation in pepper (Capsicum annuum).
Pepper (Capsicum spp.) is a vegetable and spice crop in the Solanaceae family with many nutritional benefits for human health. During several decades, horticultural traits, including disease resistance, yield, and fruit quality, have been improved through conventional breeding methods. Nevertheless, cultivar development is a time-consuming process because of the long generation time of pepper. Recently, speed breeding has been introduced as a solution for shorting the breeding cycle in long-day or day-neutral field crops, but there have been only a few studies on speed breeding in vegetable crops. In this study, a speed breeding protocol for pepper was developed by controlling the photoperiod and light quality. Under the condition of a low red (R) to far-red (FR) ratio of 0.3 with an extended photoperiod (Epp) of 20 h (95 ± 0 DAT), the time to first harvest was shortened by 75 days after transplant (DAT) compared to that of the control treatment (170 ± 2 DAT), suggesting that Epp with FR light is an essential factor for flowering in pepper. In addition, we established the speed breeding system in a greenhouse with a 20 h photoperiod and a 3.8 R:FR ratio and promoted the breeding cycle of C. annuum for 110 days from seed to seed. To explain the accelerated flowering response to the Epp and supplemented FR light, genome-wide association study (GWAS) and gene expression analysis were performed. As a result of the GWAS, we identified a new flowering gene locus for pepper and suggested four candidate genes for flowering (APETALA2 (AP2), WUSCHEL-RELATED HOMEOBOX4 (WOX4), FLOWERING LOCUS T (FT), and GIGANTEA (GI)). Through expression analysis with the candidate genes, it appeared that Epp and FR induced flowering by up-regulating the flowering-promoting gene GI and down-regulating FT. The results demonstrate the effect of a combination of Epp and FR light by genetic analysis of flowering gene expression. This is the first study that verifies gene expression patterns associated with the flowering responses of pepper in a speed breeding system. Overall, this study demonstrates that speed breeding can shorten the breeding cycle and accelerate genetic research in pepper through reduced generation time.


Liesegang-like rings in fine needle aspirates of renal/perirenal hemorrhagic cysts.
Periodic structures with equally spaced radial striations, identified as Liesegang-like rings, were encountered in fine needle aspirates of two patients' hemorrhagic renal/perirenal cysts. The patients, one 60 and the other 39 years old, had acute right-flank pain; both underwent nephrectomy. The ring structures ranged in size from 8 microns to 200 microns in diameter and had regularly striated double walls. Histochemical and immunoperoxidase tests for iron, calcium, mucopolysaccharides, amyloid, keratin and hemoglobin performed on the tissue sections of the resected specimens gave negative results. With electron microscopy, the ring structures of one of the cases displayed a fine fibrillary composition. Since these Liesegang-like structures may be mistaken for parasites or necrotic tissue, pathologists should be aware of them. To our knowledge, this is the first report of Liesegang-like rings in the cytology literature.


There Is a "U" in Clutter: Evidence for Robust Sparse Codes Underlying Clutter Tolerance in Human Vision.
The ability to recognize objects in clutter is crucial for human vision, yet the underlying neural computations remain poorly understood. Previous single-unit electrophysiology recordings in inferotemporal cortex in monkeys and fMRI studies of object-selective cortex in humans have shown that the responses to pairs of objects can sometimes be well described as a weighted average of the responses to the constituent objects. Yet, from a computational standpoint, it is not clear how the challenge of object recognition in clutter can be solved if downstream areas must disentangle the identity of an unknown number of individual objects from the confounded average neuronal responses. An alternative idea is that recognition is based on a subpopulation of neurons that are robust to clutter, i.e., that do not show response averaging, but rather robust object-selective responses in the presence of clutter. Here we show that simulations using the HMAX model of object recognition in cortex can fit the aforementioned single-unit and fMRI data, showing that the averaging-like responses can be understood as the result of responses of object-selective neurons to suboptimal stimuli. Moreover, the model shows how object recognition can be achieved by a sparse readout of neurons whose selectivity is robust to clutter. Finally, the model provides a novel prediction about human object recognition performance, namely, that target recognition ability should show a U-shaped dependency on the similarity of simultaneously presented clutter objects. This prediction is confirmed experimentally, supporting a simple, unifying model of how the brain performs object recognition in clutter. The neural mechanisms underlying object recognition in cluttered scenes (i.e., containing more than one object) remain poorly understood. Studies have suggested that neural responses to multiple objects correspond to an average of the responses to the constituent objects. Yet, it is unclear how the identities of an unknown number of objects could be disentangled from a confounded average response. Here, we use a popular computational biological vision model to show that averaging-like responses can result from responses of clutter-tolerant neurons to suboptimal stimuli. The model also provides a novel prediction, that human detection ability should show a U-shaped dependency on target-clutter similarity, which is confirmed experimentally, supporting a simple, unifying account of how the brain performs object recognition in clutter.


Recent advances in gut immunology.
In recent years, there have been significant advances in our understanding of the mucosal immune system. In addition to unravelling some of the complexities of this system, including the discovery of completely new cells types, further insights into the three-way interactions between mucosal immune cells, the intestinal epithelium and the microbial communities colonizing the GI tract promise to redefine our understanding of how intestinal homeostasis is maintained, but also how dysregulation of these highly integrated interactions conspires to cause disease. In this review, we will discuss major recent advances in the role of key immune players in the gut, including innate lymphoid cells (ILCs), mucosa-associated invariant T cells (MAIT cells) and cells of the mononuclear phagocyte system (MPS), including how these cells interact with the intestinal epithelial and their crosstalk with components of the intestinal microbiota, and how these interactions shape host health.


Project Management of Randomized Clinical Trials: A Narrative Review.
A well-structured protocol for a clinical trial may be able to answer clinical questions, but it cannot be deemed enough to ensure success in the face of incompetent management of time as well as human and economic resources. To address this problem, in this article, we present our literature review on evidence as to how a good knowledge of proper management among researchers can enhance the likelihood of the success of clinical trial projects. Using multiple search strategies, we conducted a literature review on published studies in the English language from 2002 to 2012 by searching the Cochrane Database of Systematic Reviews, MEDLINE, Google Scholar, and EMBASE. Our review suggests that a successful trial requires a work plan or work scope as well as a timeline. The trial manager should subsequently manage the study in accordance with the plan and the timeline. Many research units have called for a clinical project manager with scientific background and regulatory skills to effect coordination among various aspects of a clinical trial. Project management may benefit both the managerial and scientific aspects of medical projects and reduce fund waste. However, little has been written to date on project management in the context of clinical research. The suggestions represent the views of the individual authors. To provide a high level of evidence in this regard, we recommend that a randomized controlled trial be performed to compare trial projects progressed with and without the use of project management.


Characterization and functional analyses of a novel chicken CD8α variant X1 (CD8α1).
We provide the first description of cloning and of structural and functional analysis of a novel variant in the chicken cluster of differentiation 8 alpha (CD8a) family, termed the CD8α X1 (CD8α1) gene. Multiple alignments of CD8α1 with known CD8α and CD8β sequences of other species revealed relatively low conservation of AA residues involved in the specific and unique structural domains among CD8α genes. For example, cysteine residues that are involved in disulfide bonding to form the V domain are conserved. In contrast, the O-linked glycosylation sites (XPXX motif) are not found in the chicken CD8α1 sequence, and the A β strand and complementarity-determining region 1 and 2 sequences are poorly conserved between chicken CD8α1 and avian CD8α. Furthermore, the alignment showed that the transmembrane regions show relatively high sequence similarity, whereas the cytoplasmic regions show relatively low similarity, indicating poor conservation. Moreover, the motif (CXCP) that is thought to be responsible for binding the p56 lymphocyte cell kinase subunit (p56) is missing in the CD8α1 sequence. The chicken CD8α1 genomic structure is similar to that of chicken CD8α, but their protein structures differ. Phylogenetic analysis showed that chicken CD8α1 grouped with known avian CD8α sequences but was somewhat distantly related to the CD8α molecules of other species. Moreover, we analyzed the signal transduction and cytokine response to CD8α1 treatment to determine the specific biological functions of chicken CD8α1 in immune cells. The results showed that chicken CD8α1 is a key regulator of the expression of genes that are associated and cooperate with transcription factors in the major histocompatibility complex class I and II promoter regions and activates Janus kinase (JAK) 1/2, signal transducer and activator of transcription (STAT), and suppressor of cytokine signaling (SOCS) 1 signaling-related genes. Immune cells that express functional CD8α1 induce proinflammatory cytokines as well as innate immune responses. Therefore, our data indicate that CD8α1 may have immunoregulatory activity by regulating the expression of proinflammatory or anti-inflammatory cytokines via its effect on immune cells.


Confined collective excitations of self-standing and supported planar periodic particle arrays.
We find the conditions for the existence of trapped modes in planar periodic particle arrays. Confined excitations of TE and TM symmetry are observed in symmetric environments, originating in lattice resonances that are signalled by the onset of new diffraction beams. This mechanism of mode formation is shown to be inhibited by the presence of a dielectric interface in an asymmetric configuration. Modes can still exist above a threshold finite distance from the interface. Both rigorous numerical simulation and analytical modeling are used to elucidate the origin and systematics of this unexpected difference in the behavior of trapped modes in self-standing and supported particle arrays.


Disease Comanagement: A Case Study of HIV/AIDS and Cancer Care in Sub-Saharan Africa
Cancer care is increasingly complicated worldwide by its management with concurrent acute and chronic illness states. In low- and middle-income countries, including those in sub-Saharan Africa, this results in lower overall survival rates and a higher burden of cancer deaths. A case study is presented to highlight the challenges patients with cancer in Zambia-many of whom are also positive for HIV or AIDS-face in relationship to access to care and comanagement of disease states.


The beer and biofuels laboratory: A report on implementing and supporting a large, interdisciplinary, yeast-focused course-based undergraduate research experience.
Course-integrated Undergraduate Research Experiences (CUREs) involve large numbers of students in real research. We describe a late-year microbiology CURE in which students use yeast to address a research question around beer brewing or synthesizing biofuel; the interdisciplinary student-designed project incorporates genetics, bioinformatics, biochemistry, analytical chemistry, and microbiology. Students perceived significant learning gains around multiple technical and "becoming a scientist" aspects of the project. The project is demanding for both the students and the academic implementers. We examine the rich landscape of support and interaction that this CURE both encourages and requires while also considering how we can support the exercise better and more sustainably. The findings from this study provide a picture of a CURE implementation that has begun to reach the limits of both the students' and the academics' capacities to complete it. © 2018 by The International Union of Biochemistry and Molecular Biology, 46(3):213-222, 2018.


Engineered Bacterial Cellulose Nanostructured Matrix for Incubation and Release of Drug-Loaded Oil in Water Nanoemulsion.
Bacterial cellulose (BC) is a highly pure form of cellulose produced by bacteria, which possesses numerous advantages such as good mechanical properties, high chemical flexibility, and the ability to assemble in nanostructures. Thanks to these features, it achieved a key role in the biomedical field and in drug delivery applications. BC showed its ability to modulate the release of several drugs and biomolecules to the skin, thus improving their clinical outcomes. This work displays the loading of a 3D BC nanonetwork with an innovative drug delivery nanoemulsion system. BC was optimized by static culture of SCOBY (symbiotic colony of bacteria and yeast) and characterized by morphological and ultrastructural analyses, which indicate a cellulose fiber diameter range of 30-50 nm. BC layers were then incubated at different time points with a nanocarrier based on a secondary nanoemulsion (SNE) previously loaded with a well-known antioxidant and anti-inflammatory agent, namely, coenzyme-Q10 (Co-Q10). Incubation of Co-Q10-SNE in the BC nanonetwork and its release were analyzed by fluorescence spectroscopy.


Bidirectional Association between Hypertension and NAFLD: A Systematic Review and Meta-Analysis of Observational Studies.
An increasing body of evidence connects non-alcoholic fatty liver disease (NAFLD) to hypertension. The objective of this systematic review and meta-analysis was to estimate the nature and magnitude of the association between NAFLD and hypertension. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for observational studies published up to May 1, 2021. Cohort studies that reported data on the association between NAFLD and incident hypertension or between hypertension and incident NAFLD were included. We used random-effects models to conduct meta-analysis on the measures of association from individual studies. A total of 11 studies were eligible for inclusion, among which 4 studies including 25,260 participants reported the association between hypertension and new-onset NAFLD. The presence of hypertension was significantly associated with an increased risk of incident NAFLD (HR 1.63, 95% CI: 1.41-1.88; I 2 = 37.6%). On the other hand, 9 studies with data on 46,487 participants analyzed the effects of NAFLD on incident hypertension. Pooled analysis showed that the presence of NAFLD was significantly associated with an increased incidence of hypertension (HR 1.55, 95% CI: 1.29-1.87; I 2 = 80.5%). There was significant heterogeneity among the studies in this analysis (p < 0.01). Sensitivity analyses showed that the magnitude of the association was significantly different in subgroups stratified by a mean age of participants and geographical location, which explains part of the heterogeneity. In conclusion, this meta-analysis indicates the existence of a bidirectional relationship between NAFLD and hypertension independent of traditional cardiometabolic risk factors.


Endocrine changes in male HIV patients.
To determine the frequency of adrenal, thyroid and gonadal dysfunction in HIV positive male patients and to evaluate the endocrine function at different level of CD4 cell counts. A total of 150 male HIV positive subjects were included in study. The patients were divided in three groups on the basis of CD4 cell counts. "Group A": HIV positive with CD4 count<200/mm "Group B": HIV positive with CD4 count 200-350/mm3 and "Group C": HIV positive with CD4 count>350/mm3. In "group A" (n=50) 2 patients had basal cortisol<5 microg/dl while 23 patients had basal cortisol>25 microg/ dl. 15 patients had subclinical hypothyroidism while 11 patients had overt hypothyroidism. 25 patients in this group had gonadal dysfunction: majority of them (24) had primary gonadal dysfunction (elevated LH). None of the patients in "group B" (n=50) had hypocortisolism while 11 patients had elevated cortisol; 18 had subclinical hypothyroidism while 4 had overt hypothyroidism while 17 patients were hypogonad, all having elevated LH. In "group C" (n=50) 2 patients had hypocortisolism and 5 had elevated cortisol; 12 patients had subclinical and one had overt hypothyroidism; 7 patients had primary hypogonadism and one had secondary hypogonadism. Overall 4(2.66%) had hypocortisolism while 39 (26%) had elevated cortisol; 45 (30%) had subclinical hypothyroidism while 16(10.66%) had overt hypothyroidism. Gonadal dysfunction was observed in 50 patients (33%) majority of them (48) had primary hypogonadism. On analysis of Pearson's correlation coefficient CD4 count has strong inverse correlation with basal cortisol (r=-0.301, p<0.0001), TSH (r=-0.257, p=0.002) and LH (r=-0.228, p=0.006), while there was a direct correlation with serum testosterone (r=0.175, p=0.037). This pilot study has demonstrated a high incidence of endocrine dysfunction in HIV infected patient in this part of country. High incidence of thyroid and gonadal dysfunction may contribute to morbidity of the patients and have a bearing on quality of life of the HIV infected patients. Hypocortisolism was not that common but high level of cortisol may be a marker of stress due to HIV per se or due to associated infection. Many of these dysfunctions might be transient and a large longitudinal study should be undertaken to substantiate the finding of the present study.


Microbial assessment of water, sanitation, and hygiene (WaSH) in temporary and permanent settlements two years after Nepal 2015 earthquake.
Disaster-induced displacement often causes people to live in temporary settlements that have limited infrastructure and access to water, sanitation, and hygiene (WaSH). Reducing the risk of diarrheal diseases in such situations requires knowing how housing influences the presence of pathogens in water and the interaction between human settlements and exposure to pathogens. A cross-sectional study was conducted in May 2017 in two communities hard-hit by the Nepal 2015 earthquake: one recovered with newly reconstructed houses, and one recovered with residents still living in sheet metal temporary shelters constructed after the earthquake. We collected 60 water (30 drinking water and 30 cleaning water), 30 hand rinse, and 90 environmental swab samples (30 toilet handles, 30 utensils, and 30 water vessels) from selected households in each location and quantified 22 bacterial pathogens using microfluidic quantitative polymerase chain reaction (mfqPCR). A total of 59 samples were randomly selected for amplicon-based sequencing of the 16S rRNA, and it identified bacterial community profiles between these two settlements and their association with target genes of pathogenic bacteria. Target genes like uidA of Escherichia coli and the mip gene of Legionella pnuemophila showed significantly high frequency in specific sample types in temporary settlements than in permanent settlements. A significantly high concentration was observed in temporary settlements for Enterococcus spp. and S. typhimurium, specifically in swab samples. There was a sharp distinction of microbial community profiles between water and hand rinse samples with environmental swab samples, with a large abundance of potentially pathogenic bacteria in swab samples in both settlements. This observation highlighted that fomite could be an important transmission route for pathogens in rural settings and designing key interventions to target different stages of transmission pathways is essential. Overall findings from this study suggest that the recovered settlement with higher quality housing may be less impacted by fecal contamination than recovering settlements and that interventions should be designed to disrupt multiple transmission pathways to reduce pathogen exposure.


Biofuel blending reduces particle emissions from aircraft engines at cruise conditions.
Aviation-related aerosol emissions contribute to the formation of contrail cirrus clouds that can alter upper tropospheric radiation and water budgets, and therefore climate. The magnitude of air-traffic-related aerosol-cloud interactions and the ways in which these interactions might change in the future remain uncertain. Modelling studies of the present and future effects of aviation on climate require detailed information about the number of aerosol particles emitted per kilogram of fuel burned and the microphysical properties of those aerosols that are relevant for cloud formation. However, previous observational data at cruise altitudes are sparse for engines burning conventional fuels, and no data have previously been reported for biofuel use in-flight. Here we report observations from research aircraft that sampled the exhaust of engines onboard a NASA DC-8 aircraft as they burned conventional Jet A fuel and a 50:50 (by volume) blend of Jet A fuel and a biofuel derived from Camelina oil. We show that, compared to using conventional fuels, biofuel blending reduces particle number and mass emissions immediately behind the aircraft by 50 to 70 per cent. Our observations quantify the impact of biofuel blending on aerosol emissions at cruise conditions and provide key microphysical parameters, which will be useful to assess the potential of biofuel use in aviation as a viable strategy to mitigate climate change.


Apoptosis of nurse cells at the late stages of oogenesis of Drosophila melanogaster.
In Drosophila a remarkable feature of oogenesis is the regression of the nurse cells after dumping their cytoplasmic contents into the oocyte. We have studied the nature of this process at the late stages of egg chamber development. In egg chambers DAPI staining shows highly condensed chromatin from stage 12 and TUNEL labelling shows DNA fragmentation up to stage 14. Gel electrophoresis of the end-labelled DNA, extracted from isolated egg chambers at the same stages of development, shows a ladder typical of apoptotic nuclei. This provides evidence that, during Drosophila oogenesis, the nurse cells undergo apoptosis. Apoptotic nuclei have also been detected in dumping-defective egg chambers, indicating that the cytoplasmic depletion of nurse cells is concurrent with but apparently not the cause of the process.


[Bleeding Risk Score in Patients with Crimean-Congo Hemorrhagic Fever].
Bleeding is considered to be an indicator of poor prognosis in Crimean-Congo hemorrhagic fever (CCHF) disease. In the prehemorrhagic period, clinical signs are usually non-specific. The hemorrhagic period usually begins 3 to 5 days after the onset of the disease. The aim of this study was to build a risk score to predict bleeding status in CCHF patients with clinical and laboratory findings. This methodological study was carried out in one of the largest centers which is located in the east part of Turkey and CCHF-endemic region between April 2014-October 2019 with 450 CCHF patients' data. Risk score was created with univariate and multivariate logistic regression analyzes with the data of 80% of the patients, and the diagnostic power of the created score was determined by ROC analysis. The data of the remaining 20% were used as the verification data set and the created score was tested by ROC analysis. The patients had a mean age of 47.83 ± 17.46 years (median 48; min-max: 16-90 years) and 209 (59.7%) were male. Hemorrhage was detected in 93 patients (26.6%). Of the hemorrhagic patients, 83 (23.7%) had multiple hemorrhage sites. In univariate analyzes, time between the onset of symptom and admission to the hospital (≥4 days), aspartate aminotransferase (≥228 U/L), alanine aminotransferase (≥143.5 U/L), lactate dehydrogenase (≥641 U/L), creatine kinase (≥227 U/L), white blood cell count (≤1810 × 106/L), platelet count (≤38385 × 106/L), activated partial thromboplastin time (≥38.5 s) and fibrinogen value (≤227 mg/dl) were found to be an independent risk factor for bleeding. As a result of multivariate analysis, the time between the onset of symptoms and admission to the hospital, white blood cell count, platelet count, aspartate aminotransferase, creatine kinase and fibrinogen values were included in the risk scoring. The area under the curve of the generated score is 0.875; sensitivity was 80.6% and specificity was 80.5%. Platelet count responsible for hemostasis, affected in terms of number and function in CCHF disease, LDH, AST and aPTT values used as indicators of liver functions that are the target of the virus can be used with high diagnostic prediction for bleeding. However, the predictive power of the generated score on bleeding is higher than the effect of each variable alone. In addition, it can be easily calculated during patient follow-up and can guide the treatment process.


NtGRAS1, a novel stress-induced member of the GRAS family in tobacco, localizes to the nucleus.
We report the isolation and initial characterization of a new member of the GRAS gene family from tobacco, NtGRAS1. Analysis of the predicted amino acid sequence shows that NtGRAS1 shares the highly conserved carboxy-terminal motifs common to all members of the GRAS family. NtGRAS1 expression was strongly induced in tobacco (BY-2) suspension cells by antimycin A, H(2)O(2), salicylic acid, and L-cysteine which were all found to raise intracellular reactive oxygen levels. An increase in NtGRAS1 expression was also triggered by treating cells with the nitric oxide donor sodium nitroprusside. By employing inhibitors of protein kinase and phosphatase action, we show that reversible phosphorylation is required for the stress-induced induction of NtGRAS1 and that reactive oxygen as well as NO-dependent signaling pathways probably share key intracellular components. Interestingly, in soil-grown plants, high constitutive expression of NtGRAS1 was found only in roots while expression was strongly induced in leaf tissue upon antimycin A treatment or following Pseudomonas syringae infection. Many members of the GRAS family are implicated in regulating transcription and this function for NtGRAS1 is supported by our finding that an NtGRAS1-GFP fusion protein localizes to the nucleus of onion epidermal cells. Our data suggest that NtGRAS1 may represent an important transcriptional regulator involved in the plant stress response.


Crop Loss Relationships and Economic Injury Levels for Ferrisia gilli (Hemiptera: Pseudococcidae) Infesting Pistachio in California.
Ferrisia gilli Gullan (Hemiptera: Pseudococcidae) is a new pest in California pistachios, Pistacea vera L. We conducted a 3-yr field study to determine the type and amount of damage caused by F. gilli. Using pesticides, we established gradients of F. gilli densities in a commercial pistachio orchard near Tipton, CA, from 2005 to 2007. Each year, mealybug densities on pistachio clusters were recorded from May through September and cumulative mealybug-days were determined. At harvest time, nut yield per tree (5% dried weight) was determined, and subsamples of nuts were evaluated for market quality. Linear regression analysis of cumulative mealybug-days against fruit yield and nut quality measurements showed no relationships in 2005 and 2006, when mealybug densities were moderate. However, in 2007, when mealybug densities were very high, there was a negative correlation with yield (for every 1,000 mealybug-days, there was a decrease in total dry weight per tree of 0.105 kg) and percentage of split unstained nuts (for every 1,000 mealybug-days, there was a decrease in the percentage of split unstained of 0.560%), and a positive correlation between the percentage of closed kernel and closed blank nuts (for every 1,000 mealybug-days, there is an increase in the percentage of closed kernel and closed blank of 0.176 and 0.283%, respectively). The data were used to determine economic injury levels, showing that for each mealybug per cluster in May there was a 4.73% reduction in crop value associated with quality and a 0.866 kg reduction in yield per tree (4.75%).


Relation of pulmonary lymphangio-leiomyomatosis to use of the oral contraceptive pill and fertility in the UK: a national case control study.
Pulmonary lymphangioleiomyomatosis is a rare progressive disease of unknown aetiology affecting premenopausal women. Since the oral contraceptive pill has been implicated in its pathogenesis, a case control study was carried out to determine whether women with the disease were more likely to have taken the oral contraceptive pill, and whether the disease was associated with other conditions related to sex hormones including pregnancy, parity, and fibroids. All chest physicians in the UK were asked for details of all live patients with pulmonary lymphangioleiomyomatosis; the patient's family doctor was then asked for four age and sex matched control subjects from their patient register. Details of lifetime use of the oral contraceptive pill, pregnancy, parity, history of fibroids, and smoking were obtained from cases and controls. Relative odds of exposure to potential risk factors were estimated by conditional logistic regression. Medical details were obtained from all 23 cases of lymphangioleiomyomatosis identified; questionnaires were completed by 21 cases (one by proxy) and by 46 matched controls of mean (SD) age 43 (10) and 44 (11) years, respectively. The patients had a mean age of 34 (9) years at onset of symptoms and a median (range) time of 2 (0-29) years from onset of symptoms to diagnosis. Compared with control subjects, cases did not differ in the use of the oral contraceptive pill (odds ratio (OR) 0.39, 95% CI 0.09 to 1.68), diagnosis of fibroids (OR 3.12; 95% CI 0.52 to 18.7), age of menarche, menstrual history, or lifetime smoking. They were, however, less likely to have been pregnant (OR 0.14, 95% CI 0.03 to 0.71) or to have had children (OR 0.13, 95% CI 0.03 to 0.67). More pregnancies had ended in spontaneous abortion (28% v 8%) but the proportion of women undergoing spontaneous abortion was similar in cases and controls (OR 2.13, 95% CI 0.47 to 9.3). This study does not support the hypothesis that use of the oral contraceptive pill is causally associated with the development of pulmonary lymphangioleiomyomatosis. Sex hormones may be involved, however, since patients were less likely to have been pregnant or to have had children, and tended to have had more spontaneous abortions and an increased incidence of fibroids.


Long-term follow-up of large flat colorectal tumors resected endoscopically.
When a large flat colorectal tumor is excised by piecemeal endoscopic resection, it is not possible to obtain suitable specimens for histopathological examination to assess whether the resection has been complete. We prospectively analysed follow-up colonoscopy examinations of endoscopic polypectomy resection sites for residual lesions. A total of 24 patients with large flat colorectal tumors were treated using an endoscopic submucosal saline injection technique. The resection site was prospectively examined for residual lesions using a magnifying colonoscope, at 3, 6, 12 and 24 months postoperatively. None of the 5 patients who underwent en bloc resection exhibited residual lesions postoperatively. Of the 19 patients who underwent piecemeal resection, one died of an asthma attack and 18 were followed up. Residual lesions were detected in four of these 18 patients (three adenomas and one cancer), which were resected endoscopically. When the tumor was resected endoscopically en bloc and was judged histologically to be completely resected, residual lesions were not detected at follow-up. However, residual lesions were detected in 22.2 % of patients 3 months after initial resection when polyps were resected piecemeal. After treatment, residual lesions were detected in two patients (11.1 %) at 24 months. After piecemeal endoscopic resection for large flat colorectal tumors, it is necessary to follow-up and remove residual lesions endoscopically every 3 months until they all are removed.


Single-shot cryoablation of an epicardial inferoparaseptal accessory pathway: a case report.
Catheter ablation (CA) of epicardial accessory pathways (APs) can be performed via the coronary sinus (CS) system. Variable CS anatomy with complications of former CA procedures inside the CS venous system may require using alternative CA approach and technology. We report the case of a 23-year-old man with Wolff-Parkinson-White syndrome and history of aborted sudden cardiac death (SCD) and unsuccessful previous AP radiofrequency ablation (RFA). CS venography during the redo procedure revealed an early CS trifurcation with cardiac veins stenosis, thus with difficulties in maintaining cardiac veins' access and catheter manoeuvring inside CS venous system. The last office visit with electrocardiogram (ECG) performance was in 3 months after the CA. Neither delta wave on the ECG nor any complaints/adverse health effects was detected at that time. Successful CA of epicardial AP in patients with a high risk of SCD is essential. However, CS complex anatomy and changes after former RFA inside it may lead to CS venous system access limitations. Alternative CA approach and technology should be considered to ensure CS venous system cannulation and epicardial AP CA performance.


Gleaning multicomponent T1 and T2 information from steady-state imaging data.
The driven-equilibrium single-pulse observation of T(1) (DESPOT1) and T(2) (DESPOT2) are rapid, accurate, and precise methods for voxelwise determination of the longitudinal and transverse relaxation times. A limitation of the methods, however, is the inherent assumption of single-component relaxation. In a variety of biological tissues, in particular human white matter (WM) and gray matter (GM), the relaxation has been shown to be more completely characterized by a summation of two or more relaxation components, or species, each believed to be associated with unique microanatomical domains or water pools. Unfortunately, characterization of these components on a voxelwise, whole-brain basis has traditionally been hindered by impractical acquisition times. In this work we extend the conventional DESPOT1 and DESPOT2 approaches to include multicomponent relaxation analysis. Following numerical analysis of the new technique, renamed multicomponent driven equilibrium single pulse observation of T(1)/T(2) (mcDESPOT), whole-brain multicomponent T(1) and T(2) quantification is demonstrated in vivo with clinically realistic times of between 16 and 30 min. Results obtained from four healthy individuals and two primary progressive multiple sclerosis (MS) patients demonstrate the future potential of the approach for identifying and assessing tissue changes associated with several neurodegenerative conditions, in particular those associated with WM.


Defect Effects on TiO2 Nanosheets: Stabilizing Single Atomic Site Au and Promoting Catalytic Properties.
Isolated single atomic site catalysts have attracted great interest due to their remarkable catalytic properties. Because of their high surface energy, single atoms are highly mobile and tend to form aggregate during synthetic and catalytic processes. Therefore, it is a significant challenge to fabricate isolated single atomic site catalysts with good stability. Herein, a gentle method to stabilize single atomic site metal by constructing defects on the surface of supports is presented. As a proof of concept, single atomic site Au supported on defective TiO2 nanosheets is prepared and it is discovered that (1) the surface defects on TiO2 nanosheets can effectively stabilize Au single atomic sites through forming the Ti-Au-Ti structure; and (2) the Ti-Au-Ti structure can also promote the catalytic properties through reducing the energy barrier and relieving the competitive adsorption on isolated Au atomic sites. It is believed that this work paves a way to design stable and active single atomic site catalysts on oxide supports.


WNT3-WNT14B and WNT3A-WNT14 gene clusters (Review).
WNT signals are transduced to beta-catenin - TCF pathway, JNK pathway, or Ca2+-releasing pathway through WNT receptors. FRAT1, FRAT2, and PAR-1 are positive regulators of WNT - beta-catenin pathway. APC, AXIN, NKD1, NKD2, and Strabismus (STB1, STB2) are negative regulators of WNT - beta-catenin pathway. Here, biological significance of WNT3-WNT14B/WNT15 gene cluster (human chromosome 17q21) and WNT3A-WNT14 gene cluster (human chromosome 1q42) will be reviewed. Total-amino-acid identity between WNT3 and WNT3A is 84.2%, and that between WNT14 and WNT14B is 61.4%. WNT3A and WNT14B show reciprocal regulation by all-trans retinoic acid in NT2 cells and by beta-estradiol in MCF-7 cells. Exon-intron structures are well conserved between WNT3-WNT14B gene cluster and WNT3A-WNT14 gene cluster, except for the existence of an additional intron in 3'-UTR of WNT3. Capicua pseudogene and AK024248-related sequence are located within intergenic region of human WNT3A-WNT14 gene cluster, but not within intergenic regions of human WNT3-WNT14B gene cluster and mouse Wnt3a-Wnt14 gene cluster. Integration of mouse mammary tumor virus (MMTV) into mouse Wnt3-Wnt14b gene cluster leads to carcinogenesis. Because these WNT gene clusters might be fragile sites in the human genome, implication of WNT3 or WNT3A in cancer as well as implication of WNT14 or WNT14B in connective tissue disease and congenital joint malformation should be elucidated in the future. WNT3, WNT3A, WNT14, and WNT14B might be applicable to tissue engineering of neuron and joint in the field of regenerative medicine, and as an early diagnostic marker in the field of clinical oncology.


Decreased peroxynitrite inhibitory activity in induced sputum in patients with bronchial asthma.
The production of peroxynitrite, an extremely potent oxidant, is increased in inflammatory lung disease. It is therefore important to measure antioxidant activity against peroxynitrite in epithelial lining fluid to examine the physiological effects of peroxynitrite in the airways of patients with asthma. This study was designed to determine whether peroxynitrite inhibitory activity in induced sputum is correlated with clinical characteristics and airway inflammatory indices in asthmatic patients. Inflammatory indices were measured in induced sputum from 25 patients with asthma and 12 normal control subjects. Peroxynitrite inhibitory activity was also measured by monitoring rhodamine formation in sputum samples. Peroxynitrite inhibitory activity in induced sputum was significantly lower in asthmatic patients (52.4 (24.5)%) than in normal control subjects (92.1 (3.9)%, p<0.0001). Its activity was significantly correlated with forced expiratory volume in 1 second (FEV(1)) % predicted (r=0.774, p<0.0001) and bronchial hyperreactivity to methacholine (r=0.464, p=0.023). There was a significant negative correlation between peroxynitrite inhibitory activity and the degree of eosinophilic airway inflammation (% eosinophils, r=-0.758, p<0.0001; eosinophil cationic protein, r=-0.780, p<0.0001). Decreased peroxynitrite inhibitory activity occurs in induced sputum of asthmatic patients. Since even in patients with stable asthma the airway lining fluid lacks peroxynitrite inhibitory activity, large amounts of peroxynitrite, which are further increased during an acute asthma attack, would not be completely inactivated and asthmatic airways might have markedly increased susceptibility to peroxynitrite induced airway injury.


The impact of badminton on health markers in untrained females.
The purpose of the study was to examine the health effects of 8 weeks of recreational badminton in untrained women. Participants were matched for maximal oxygen uptake (V̇O2max) and body fat percentage and assigned to either a badminton (n = 14), running (n = 14) or control group (n = 8). Assessments were conducted pre- and post-intervention with physiological, anthropometric, motivation to exercise and physical self-esteem data collected. Post-intervention, V̇O2max increased (P < 0.05) by 16% and 14% in the badminton and running groups, respectively, and time to exhaustion increased (P < 0.05) by 19% for both interventions. Maximal power output was increased (P < 0.05) by 13% in the badminton group only. Blood pressure, resting heart rate and heart rate during submaximal running were lower (P < 0.05) in both interventions. Perceptions of physical conditioning increased (P < 0.05) in both interventions. There were increases (P < 0.05) in enjoyment and ill health motives in the running group only, whilst affiliation motives were higher (P < 0.05) for the badminton group only. Findings suggest that badminton should be considered a strategy to improving the health and well-being of untrained females who are currently not meeting physical activity guidelines.


The placebo effect and its clinical associations in gambling disorder.
Although gambling disorder is prevalent and functionally impairing, no FDA-approved medications exist for its treatment. The ability of clinical trials to detect the benefits of active treatment has been hindered by an unusually high placebo response. Virtually nothing is known about baseline clinical characteristics that might predict placebo response in those with gambling disorder. Participants (N = 152) assigned to placebo were pooled from multiple double-blind trials of gambling disorder. Participants were classified as placebo responders or non-responders based on a cut-off of 35% reduction in symptom severity on the Gambling Symptom Assessment Scale. Baseline group differences were characterized using t tests and equivalent non-parametric tests as appropriate. Fifty-one percent of individuals assigned to placebo showed a significant clinical response. Compared with non-responders, placebo responders remained in treatment for significantly longer, were more likely to report "enjoyment" as a trigger for gambling, and were less likely to state that "boredom" or "loneliness" triggered their gambling. Placebo responders and non-responders did not differ significantly in age, sex, age at symptom onset, baseline symptom severity, comorbidities, or likelihood of having received a previous treatment. Predictors of placebo response for gambling disorder appear markedly different from those reported for other mental illnesses.