Conflicting cues in a dynamic search task are reflected in children's eye movements and search errors.
Three-year-olds were given a search task with conflicting cues about the target's location. A ball rolled behind a transparent screen and stopped behind one of four opaque doors mounted into the screen. A wall that protruded above one door provided a visible cue of blockage in the ball's path, while the transparent screen allowed visual tracking of the ball's progress to its last disappearance. On some trials these cues agreed and on others they conflicted. One group saw the ball appear to pass through the wall, violating its solidity, and another group saw the ball stop early, behind a door before the visual wall. Children's eye movements were recorded with an Applied Science Laboratories eye tracker during these real object events. On congruent trials, children tended to track the ball to the visible barrier and select that door. During conflict trials, children's eye movements and reaching errors reflected the type of conflict they experienced. Our data support Scholl and Leslie's (1999) hypotheses that spatio-temporal and contact mechanical knowledge are based on two separate, distinct mechanisms.


Development and validity of the expectations of physiotherapists questionnaire on practice management software.
Despite the growing trend in the use of digital technologies in physiotherapy, the overall adoption of both, practice management software (PMS) and electronic health records in physiotherapy clinics has been low and slow over time. In order to learn what factors determine the adoption of these technologies by physiotherapists, there is a need to examine the expectations of physiotherapists (EPs) on specific software attributes. The main aims of this study were to develop a questionnaire to measure and describe the EPs towards PMS. The knowledge of these EPs will be useful to guide PMS design in order to improve physiotherapists' satisfaction. Instrument development study with validity and reliability testing. The development of this questionnaire was conducted in three phases: identification of attributes to be explored, development of the items, pilot study, and psychometric testing. The questionnaire was distributed to chartered physiotherapists. A total of 272 participants completed the questionnaire. A series of analysis were conducted to assess item reduction, factor structure of the questionnaire and metric properties of multi-item scales. From the initial 43 attributes, the final version of the questionnaire consisted of 26 items on EPs, grouped in nine scales and two areas (clinical care and administrative activities). As a result, all scores had strong item-scale correlations, excellent item scaling success, and good internal consistency (Cronbach alpha coefficients of >.7). Our study also showed that current EPs were high towards most of the items, only two scales concentrated most of the attributes with the least expectations (monitoring quality of care and digital health interventions). Our study included physiotherapists with and without experience with PMS, and it showed that both groups had a similar pattern of expectations. Our study provides a valuable questionnaire of EP on PMS attributes for clinical care and administrative activities and shows a detailed development process.


The effect of ciprofibrate on flow-mediated dilation and inflammatory markers in patients with combined hyperlipidemia.
Impairment of flow-mediated dilation (FMD) has been shown to be associated with hypercholesterolemia and hypertriglyceridemia and reduction of cholesterol and/or triglyceride levels can improve FMD. In hyperlipidemia the role of inflammatory substances on endothelial function requires further clarification. In patients with combined hyperlipidemia (n = 29), the capacity of FMD was weaker whereas the levels of interleukin (IL)-lalpha, tumor necrosis factor alpha (TNFalpha), soluble intercellular adhesion molecule (sICAM), and fibrinogen were higher compared to normolipemic controls with normal FMD adjusted for age and sex. Patients were randomized to a diet-only or to a ciprofibrate treatment group. After 8 weeks FMD levels rose significantly both in the diet-only (10.2%) and the ciprofibrate treatment (79.4%) groups. In the diet-only group improvement of FMD was significantly associated with the reduction of triglyceride (by 15.9%) and cholesterol (6.9%) levels. The much larger improvement of FMD due to ciprofibrate therapy was accompanied by significant reductions of cholesterol (by 14.4%), fibrinogen, IL-1alpha, and sICAM levels and by significant increase of high-density lipoprotein (HDL) cholesterol concentration, but the change in FMD correlated only with the reduction of the cholesterol level. In line with previous data the authors emphasize that improvement of FMD in patients with combined hyperlipidemia treated with diet and/or ciprofibrate is linked directly to the reduction of cholesterol and triglyceride concentrations rather than to changes in the level of the investigated inflammatory markers.


Structural Characterization and Antimicrobial Activity of a Biosurfactant Obtained From Bacillus pumilus DSVP18 Grown on Potato Peels.
Biosurfactants constitute a structurally diverse group of surface-active compounds derived from microorganisms. They are widely used industrially in various industrial applications such as pharmaceutical and environmental sectors. Major limiting factor in biosurfactant production is their production cost. The aim of this study was to investigate biosurfactant production under laboratory conditions with potato peels as the sole source of carbon source. A biosurfactant-producing bacterial strain (Bacillus pumilus DSVP18, NCBI GenBank accession no. GQ865643) was isolated from motor oil contaminated soil samples. Biochemical characteristics of the purified biosurfactant were determined and its chemical structure was analyzed. Stability studies were performed and biological activity of the biosurfactant was also evaluated. The strain, when grown on modified minimal salt media supplemented with 2% potato peels as the sole carbon source, showed the ability to reduce Surface Tension (ST) value of the medium from 72 to 28.7 mN/m. The isolated biosurfactant (3.2 ± 0.32 g/L) was stable over a wide range of temperatures (20 - 120 ºC), pH (2-12) and salt concentrations (2 - 12%). When characterized using high-performance liquid chromatography (HPLC) and Fourier transform infrared spectroscopy, it was found to be a lipopeptide in nature, which was further confirmed by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (mass peak 1044.60) and nuclear magnetic resonance (NMR) studies. Data showed that the isolated biosurfactant at the concentration range of 30 - 35 µg/ml had strong antimicrobial activity when tested against standard strains of Bacillus cereus, Escherichia coli, Salmonella enteritidis, Staphylococcus aureus and Paenibacillus larvae. Potato peels were proved to be potentially useful substrates for biosurfactant production by B. pumilus DSVP18. The strain possessed a unique property to reduce surface tension of the media from 72 to 28.7 mN/m. In addition, it showed a stable surface activity over a wide range of temperatures, pH, and saline conditions and had strong antimicrobial activity. This potential of the identified biosurfactant can be exploited by pharmaceutical industries for its commercial usage.


Chronic food restriction is associated with subtle dendritic alterations in granule cells of the rat hippocampal formation.
The hippocampal formation undergoes significant morphological and functional changes after prolonged feeding with low-protein diets. In this study we tested whether prolonged food restriction causes deleterious alterations in this brain region as well. It was found that the total number of dentate granule cells and hippocampal CA3 and CA1 pyramidal neurons did not differ between controls and rats submitted to food restriction (40%) for 36 weeks. Likewise, no effects of this dietary regimen have been detected on the morphology of the dendritic trees of hippocampal pyramids, and on the total number of the mossy fiber-CA3 synapses. By contrast, the dendritic arborizations of granule cells were found to have a reduced number of segments in food-restricted rats. However, the spine density on the distal segments of their dendritic trees and the total number of axospinous synapses in the outer molecular layer of the dentate gyrus were increased in these animals. In addition, the total dendritic length of the granule cells and the overall surface area of the active zones of the synapses in the outer molecular layer were preserved, indicating that the capacity of dentate granule cells to process afferent stimuli is likely to be unaffected by this dietary treatment. Supporting this view are the results obtained in the water maze experiment which show that food-restricted rats exhibit unimpaired spatial abilities, which are known to be dependent on the entorhinal drive towards the hippocampal formation. These results show that, among hippocampal neurons, dentate granule cells are selectively vulnerable to food restriction. Nonetheless, the reorganization which takes place in their dendrites and synapses is capable of minimizing the functional impairments that were expected to occur following changes in the hippocampal neuronal circuitry induced by this type of dietary restriction.


Highly Enantioselective, Hydrogen-Bond-Donor Catalyzed Additions to Oxetanes.
A precisely designed chiral squaramide derivative is shown to promote the highly enantioselective addition of trimethylsilyl bromide (TMSBr) to a broad variety of 3-substituted and 3,3-disubstituted oxetanes. The reaction provides direct and general access to synthetically valuable 1,3-bromohydrin building blocks from easily accessed achiral precursors. The products are readily elaborated both by nucleophilic substitution and through transition-metal-catalyzed cross-coupling reactions. The enantioselective catalytic oxetane ring opening was employed as part of a three-step, gram-scale synthesis of pretomanid, a recently approved medication for the treatment of multidrug-resistant tuberculosis. Heavy-atom kinetic isotope effect (KIE) studies are consistent with enantiodetermining delivery of bromide from the H-bond-donor (HBD) catalyst to the activated oxetane. While the nucleophilicity of the bromide ion is expected to be attenuated by association to the HBD, overall rate acceleration is achieved by enhancement of Lewis acidity of the TMSBr reagent through anion abstraction.


[Analysis of the influence on the prognosis and safety of arginine in patients with severe trauma and burns--a multi-center randomized double blinded, placebo controlled, clinical trail in 86 patients].
To observe the influence on prognosis and possible side-effects of arginine in Multi-center clinical trial, randomized double blinded patients with severe trauma and burns. and placebo control methods were employed in the study. Eighty-six patients with severe trauma and burns were randomly divided into control (C, n = 45) and arginine treatment (Arg, n = 41) groups. The patients in Arg group received arginine in dose of 0. 4 g x kg(-1) x d(-1) orally, while those in C group received same dose of placebo (tyrosine) for 7 days. All the patients in both groups were given diet with equal calories and equal nitrogen content. The changes in the wound healing time, hospital stay, and the incidence of side-effects of the medication in both groups of patients were observed and compared before and after the supplementation of arginine. The wound healing time and hospital stay days of severe trauma patient in Arg group (n = 29) were 11. 1+/-2. 8 d and 19+/-6 d, which were all obviously shorter than those in C group (13. 2+/-5. 5 d, 22 +/-6 d, n =33, P <0.05). On the other hand, in severe burn patients there were no significant difference of the wound healing time (20+/-5 d vs 22+/-8 d, n = 12, P > 0. 05) and hospital stay days (28+/-6 d vs 29+/-8 d, n = 12, P >0. 05) between the Arg and C groups. In addition, in C and Arg groups, the occurrence of the side-effects were seldom (2. 44% vs 2. 22% , P = 1. 000) and it disappeared when the supplementation of drugs was stopped. Oral feeding of arginine is beneficial in enhancing wound healing, reduction of hospital stay days in severe trauma patients and with little side-effects, but it is not beneficial to improve the prognosis of severe burn patients. Maybe this is due to inadequate number of case involved in the study.


SDIX RapidChek Listeria F.A.S.T. environmental test system for the detection of Listeria species on environmental surfaces.
The SDIX RapidChek Listeria F.A.S.T. test system was validated against the U.S. Department of Agriculture-Food Safety and Inspection Service (USDA-FSIS) cultural reference method for the detection of Listeria species on stainless steel, plastic, rubber, and painted concrete. The SDIX method uses a proprietary RapidChek Listeria enrichment media for a one-step, 24-40 h enrichment at 30 degrees C, and detects Listeria on an immunochromatographic lateral flow device in 10 min. Different Listeria species were used to spike each of the environmental surfaces. Environmental surfaces were spiked at levels ranging from 50 to 400 CFU/surface (1 in.2 swabs for painted concrete, 4 in.(2) for sponge). A total of 120 spiked samples were tested by the SDIX method at 24 and 40 h and the cultural reference method. Total confirmed positives were 49, 54, and 48 for the SDIX 24 h method, the SDIX 40 h method, and the USDA-FSIS cultural reference method, respectively. Nonspiked samples from all environmental surfaces were reported as negative for Listeria spp. by all methods. The overall Chi square was 0.017 (P = 0.104) and 0.611 (P= 0.566) after a 24 and 40 h enrichment, respectively, indicating that the test method was equivalent in performance to the reference method at both enrichment times. The SDIX method was evaluated for the detection of 50 Listeria and 35 non-Listeria bacterial strains. All 50 Listeria strains were detected by the method (100% sensitivity). Five out of 35 non-Listeria species gave light test signals when grown in nonselective broth culture and tested undiluted. However, when grown in the RapidChek Listeria F.A.S.T. proprietary media, only one bacterial strain (Staphylococcus aureus) was detected, giving a very low test signal (97% specificity). The method was shown to be robust toward several alterations in testing and storage conditions.


Electronic origin of giant magnetic anisotropy in multiferroic LuFe2O4.
We investigated the orbital anisotropy of LuFe(2)O(4) using the Fe L(2,3)- and O K-edge x-ray absorption spectroscopy (XAS) and cluster model calculations. X-ray magnetic circular dichroism reveals a surprisingly large orbital magnetic moment (m(o) approximately 0.8 micro(B)/f.u.), which originates the giant magnetic anisotropy. The polarization dependent XAS enables us to identify the orbital states and occupations, different from the band calculation predictions. These findings were examined by using the cluster model analysis, which also explains the orbital magnetic moment as well as the total moment (2.9 micro(B)/f.u.). Taking into account the charge order, we also determined the spin structure.


Off pump coronary artery surgery and intraoperative safety-experience at AFIC/NIHD, Rawalpindi.
Coronary Artery Bypass Grafting (CABG) with cardiopulmonary bypass (CPB) on one hand allows controlled haemodynamics with superior graft quality while on the other hand carries inherent risks of CPB which has renewed interest in Off-pump coronary artery bypass (OPCAB). Haemodynamic instability and intraoperative dysrythmias are major procedural complications of OPCAB, threatening conversion to emergency on-pump surgery. The purpose of this study was to compare intraoperative dysrythmias and inotropic use for haemodynamic stabilization during OPCAB surgery against conventional CABG. Consecutive CABG cases operated between 1st June 2003 and 31st May 2006 were included while conversions were excluded. Primary end points were analyzed using chi square and t test and values described in percentages, means and probability (p value). Six hundred and eighty-four cases were divided in group-A (on-pump, n = 574) and B (OPCAB, n = 97). Conversion rate was 11.8%. Intraoperative dysrythmias (A, 3.5%, B, 15%, p < 0.0001) and use of inotropic support was higher in group-B (A, 15.3%, B, 30.3%, p < 0.0001). Actual mortality in group-B was higher than the predictive value (A, 3.8%, B, 3.6%, Predictive value 3-5% and 0-3% respectively). OPCAB leads to higher frequency of dysrythmias and inotropic use intraoperatively, highlighting lower procedural safety over conventional CABG.


An unusual case of pulmonary adenocarcinoma with multiple and extraordinary metastases.
Pulmonary adenocarcinoma is one of the major types of lung cancers in which metastasis is not uncommon. Hereby, we report a case of pulmonary adenocarcinoma with multiple muscular, cutaneous, pancreatic and peritoneal metastases. Actually, all these features occurring in one patient makes it an extraordinary case. A rare anatomic variation, double inferior vena cava (IVCs), was another rare manifestation in this case.


Standardization of assay representation in the Ontology for Biomedical Investigations.
The Ontology for Biomedical Investigations (OBI) underwent a focused review of assay term annotations, logic and hierarchy with a goal to improve and standardize these terms. As a result, inconsistencies in W3C Web Ontology Language (OWL) expressions were identified and corrected, and additionally, standardized design patterns and a formalized template to maintain them were developed. We describe here this informative and productive process to describe the specific benefits and obstacles for OBI and the universal lessons for similar projects.


Accelerated coronary atherosclerosis and H syndrome.
A 12-year-old boy with insulin dependent diabetes mellitus, presented with acute myocardial infarction. Intracoronary thrombolysis with urokinase restored TIMI III flow in the culprit vessel. After stabilisation with medical therapy, unusual clinical findings in the form of cutaneous hyperpigmentation and hypertrichosis, affecting the lower extremities, were appreciated. These and other phenotypic features were consistent with H syndrome, a recently described autosomal recessive genodermatosis, and confirmed by mutation analysis. Despite being on optimal medical therapy for coronary artery disease, the patient presented 3 months thereafter, with unstable angina which was successfully managed with percutaneous coronary intervention. An unusual occurrence of coronary artery disease with accelerated atherosclerosis in a child with H syndrome is presented herein. Identification of further patients with this novel disorder will clarify the possible association, suggested here, with increased risk for coronary or other vascular events.


Atypical and rare cause of myocardial infarction: coronary subclavian steal syndrome (CSSS) treated by a carotid-subclavian bypass in a 71-year-old female patient.
The coronary subclavian steal syndrome (CSSS) is a rare complication after coronary arterial bypass graft operations (CABG) using the left or right internal mammary artery ((L/R)IMA). It results from a retrograde blood flow from the IMA into the subclavian artery (SA) due to a stenosis or occlusion of the SA proximal to the IMA origin. This "steal phenomenon" leads to a decreased blood flow in the IMA and may result in myocardial ischemia (MIS) and even myocardial infarction (MIN). Treatment options include interventional and surgical therapy. We report the case of a 71-year old woman, who suffered from an acute non-ST elevation myocardial infarction (NSTEMI) 11 years after LIMA-CABG surgery and who was treated successfully with a carotid-subclavian bypass (CSB) after failed interventional therapy. CSB may be regarded as a viable treatment option for patients suffering CSSS in the case of MIS and even an acute MIN/NSTEMI, especially in the case of missing or failed interventional therapy attempts. Specialists in cardiothoracic and vascular surgery should be aware of possible CSSS conditions and know about appropriate diagnostic and therapeutic options.


[Design of multifocal visual electrophysiology examining system based on fast m-transform].
The multifocal visual electrophysiology is an objective and non-invasive method to examine visual function. It can examine many tiny areas of retina at the same time and have a particular advantage in diagnosing the early diseases of ocular fundus. This paper introduces the design of multifocal visual electrophysiology examining system. The system uses multidisplay technology exclusively owned by Windows 98 or above operating system to control graphics stimulator which generates specified hexagonal array. The white or black transition of each hexagon controlled by a binary m-sequence stimulates corresponding area of retina. The specified Burian-Allen electrode is used to extract the mixed signal originated from many areas of retina. The signal is amplified and A/D transformed. The computer separates the mixed signal through fast m-transform and gets the response of each area of retina. The fast m-transform is a fast computation of cross-correlations with binary m-sequences and can reduce cross-correlation computation to a single Fast Walsh Transform. So a lot of time can be saved.


Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells.
Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Here, we investigated whether adiponectin regulates angiogenic processes in vitro and in vivo. Adiponectin stimulated the differentiation of human umbilical vein endothelium cells (HUVECs) into capillary-like structures in vitro and functioned as a chemoattractant in migration assays. Adiponectin promoted the phosphorylation of AMP-activated protein kinase (AMPK), protein kinase Akt/protein kinase B, and endothelial nitric oxide synthesis (eNOS) in HUVECs. Transduction with either dominant-negative AMPK or dominant-negative Akt abolished adiponectin-induced eNOS phosphorylation as well as adiponectin-stimulated HUVEC migration and differentiation. Dominant-negative AMPK also inhibited adiponectin-induced Akt phosphorylation, suggesting that AMPK is upstream of Akt. Dominant-negative Akt or the phosphatidylinositol 3-kinase inhibitor LY294002 blocked adiponectin-stimulated Akt and eNOS phosphorylation, migration, and differentiation without altering AMPK phosphorylation. Finally, adiponectin stimulated blood vessel growth in vivo in mouse Matrigel plug implantation and rabbit corneal models of angiogenesis. These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells.


Relationship between Anxiety and Burnout among Chinese Physicians: A Moderated Mediation Model.
The main goal of this research was to investigate the complex relationships among coping styles, personality, burnout, and anxiety using a moderated mediation analysis. A random cluster sampling procedure was used to select a total of 1274 physicians from two tertiary grade A hospitals in Heilongjiang Province, which is located in northeast China. The Zung Self-Rating Anxiety Scale (SAS), Chinese Maslach Burnout Inventory (CMBI), Chinese version of the EPQ-revised Short Scale, and the Trait Coping Style Questionnaire (TCSQ) were used to gather data. Moderated mediation analysis was used in this study; it was executed using the PROCESS macro so that the mediators and moderator could function together in the same model. The prevalence of anxiety symptoms among the physicians was 31%, and there were no differences between the sexes. The results showed that positive and negative coping styles partially mediated the association between burnout and anxiety symptoms in physicians. The mediated effect of positive coping styles was moderated by Eysenck's Psychoticism traits. Personality traits moderate the strength of the relationships between burnout and anxiety mediated by positive coping styles; however, personality traits do not moderate the strength of the relationships between burnout and anxiety mediated by negative coping styles.


Photoluminescence and photoconductivity of ZnS-coated ZnO nanowires.
ZnO nanowires (NWs) with a ZnS coating are synthesized in order to modify the surface without changing the diameter of the NWs. They have the wurtzite ZnO at the core and a cubic ZnS at the outer layer. The NWs show a sharp ultraviolet and a broad visible emission of the photoluminescence spectra. Surface modification has led to a change in the position of the maxima of the visible emission in ZnO-ZnS NWs. The photocarrier relaxation under steady UV illumination occurs in ZnO NW arrays but is absent in ZnO-ZnS NW arrays. The dark current value for both type of NWs are similar, whereas the photocurrent value is much higher in the surface-modified NWs. Higher photocurrent value indicates a transport of the photogenerated carriers from the ZnS layer to ZnO during UV illumination. The carrier transport mechanism is proposed through a model.


An information theory account of late frontoparietal ERP positivities in cognitive control.
ERP research on task switching has revealed distinct transient and sustained positive waveforms (latency circa 300-900 ms) while shifting task rules or stimulus-response (S-R) mappings. However, it remains unclear whether such switch-related positivities show similar scalp topography and index context-updating mechanisms akin to those posed for domain-general (i.e., classic P300) positivities in many task domains. To examine this question, ERPs were recorded from 31 young adults (18-30 years) while they were intermittently cued to switch or repeat their perceptual categorization of Gabor gratings varying in color and thickness (switch task), or else they performed two visually identical control tasks (go/no-go and oddball). Our task cueing paradigm examined two temporarily distinct stages of proactive rule updating and reactive rule execution. A simple information theory model helped us gauge cognitive demands under distinct temporal and task contexts in terms of low-level S-R pathways and higher-order rule updating operations. Task demands modulated domain-general (indexed by classic oddball P3) and switch positivities-indexed by both a cue-locked late positive complex and a sustained positivity ensuing task transitions. Topographic scalp analyses confirmed subtle yet significant split-second changes in the configuration of neural sources for both domain-general P3s and switch positivities as a function of both the temporal and task context. These findings partly meet predictions from information estimates, and are compatible with a family of P3-like potentials indexing functionally distinct neural operations within a common frontoparietal "multiple demand" system during the preparation and execution of simple task rules.


Measurement of Hydrodynamic Growth near Peak Velocity in an Inertial Confinement Fusion Capsule Implosion using a Self-Radiography Technique.
First measurements of hydrodynamic growth near peak implosion velocity in an inertial confinement fusion (ICF) implosion at the National Ignition Facility were obtained using a self-radiographing technique and a preimposed Legendre mode 40, λ=140 μm, sinusoidal perturbation. These are the first measurements of the total growth at the most unstable mode from acceleration Rayleigh-Taylor achieved in any ICF experiment to date, showing growth of the areal density perturbation of ∼7000×. Measurements were made at convergences of ∼5 to ∼10× at both the waist and pole of the capsule, demonstrating simultaneous measurements of the growth factors from both lines of sight. The areal density growth factors are an order of magnitude larger than prior experimental measurements and differed by ∼2× between the waist and the pole, showing asymmetry in the measured growth factors. These new measurements significantly advance our ability to diagnose perturbations detrimental to ICF implosions, uniquely intersecting the change from an accelerating to decelerating shell, with multiple simultaneous angular views.


Early and mid-term results of Tönnis lateral acetabuloplasty for the treatment of developmental dysplasia of the hip.
This study aimed to present the clinical and radiological results of a large patient group operated by Tönnis lateral acetabuloplasty (TLA) for developmental dysplasia of the hip (DDH). The retrospective study was conducted with 66 hips of 41 patients (5 males, 36 females; mean age: 32.3±18 months; range, 11 to 132 months) operated for DDH using the TLA technique in a single center between February 2012 and December 2016. Adductor tenotomy was performed on 52 (79%) hips. There was a need for additional femoral shortening and derotation-varization osteotomy in 14 (21%) hips. Clinical outcomes were evaluated with modified McKay criteria. The acetabular index and lateral migration index for the subluxated hip were calculated, and the femoral head position was evaluated according to Perkin's line and Shenton's line. The Severin classification was used to assess the outcome of the hips. The mean follow-up period was 27±11 months. According to the modified McKay criteria for DDH, 77.3% of hips were classified as excellent, 16.6% as good, and 6.1% as fair. The mean acetabular index decreased from 36.1° preoperatively to 18.6° postoperatively. The mean postoperative improvement for the acetabular index was 17.5±5. The lateral migration index improved from 89.7 to 10.6%. A statistically significant difference was determined between the preoperative and postoperative measurements of the acetabular index and lateral migration index (p<0.001). Tönnis lateral acetabuloplasty was found to be safe and effective with a low learning curve, and successful treatment decreases the duration of follow-up required in patients with DDH.


Movement plans for posture selection do not transfer across hands.
In a sequential task, the grasp postures people select depend on their movement history. This motor hysteresis effect results from the reuse of former movement plans and reduces the cognitive cost of movement planning. Movement plans for hand trajectories not only transfer across successive trials, but also across hands. We therefore asked whether such a transfer would also be found in movement plans for hand postures. To this end, we designed a sequential, continuous posture selection task. Participants had to open a column of drawers with cylindrical knobs in ascending and descending sequences. A hand switch was required in each sequence. Hand pro/supination was analyzed directly before and after the hand switch. Results showed that hysteresis effects were present directly before, but absent directly after the hand switch. This indicates that, in the current study, movement plans for hand postures only transfer across trials, but not across hands.


A Long Survival Woman with Primary Small-Cell Carcinoma of the Gallbladder: Role of Chemotherapy Maintenance.
Gallbladder small-cell carcinoma (SCC) is an extremely rare cancer characterized by early metastases and associated with poor survival outcomes. The therapeutic options are limited in this indication and dedicated prospective trials are difficult to achieve. Maintenance chemotherapy is an evolving concept in medical oncology whose goal is to prolong chemotherapy-induced response. The role of maintenance therapy has been demonstrated especially in many cancers but the results remain controversial in small cell cancer. We report a case of a 49-year-old woman admitted in our institution with biliary colic, postprandial bilious vomiting, right hypochondrial mass, and deteriorated general condition. Abdominal computed tomography (CT) revealed a mass of the gallbladder with lymphadenopathy in the hepatic hilum and multiple liver metastases. CT-guided biopsy was performed that showed small, round cells with high nuclear-to-cytoplasmic ratio, and frequent atypical mitosis, which is consistent with high-grade small cell neuroendocrine carcinoma. Tumor cells were positive for chromogranin A, synaptophysin, and CD56. Ki-67 shows a high proliferation rate with 90% tumor cell staining and the diagnosis of gallbladder SCC was confirmed. The treatment used a combination of carboplatin and etoposide, interrupted by the generalized discomfort and shortness of breath during the second course of the etoposide. Repeated CT scan showed a partial radiological response in the order of 35% and carboplatin monotherapy was maintained with good tolerance and stability of the disease until the 11th cure. Thrombocytopenia at 70,000 per mm3 appeared, and its persistence forced the cessation of this treatment. Five months later, the disease progressed and second-line chemotherapy by irinotecan was given weekly. The death occurred 18 months after initiation of medical treatment due to hepatocellular insufficiency. Maintenance therapy in SCC should be considered as a promising therapeutic option when it is well tolerated.


Global regulatory reforms to promote equitable vaccine access in the next pandemic.
There is broad consensus that the global response to the Covid-19 pandemic was inadequate, leading to unacceptable levels of avoidable morbidity and mortality. Three strategic missteps led to the lack of equitable vaccine access: The heavy reliance on commercial vaccine manufacturers in high-income countries (HICs) versus low- and middle-income countries (LMICs); the emergence of vaccine nationalism restricting and delaying the supply of vaccines to LMICs; and an inadequate support or recognition for LMIC national regulatory authorities. To avoid these inequities in a future pandemic, we focus on three successful vaccine development and technology transfer case studies-the Hepatitis B vaccine produced in South Korea in the 1980s; the Meningitis A vaccine for Africa led by Program for Appropriate Technologies in Health (PATH) and the World Health Organization (WHO) in the 2000s; and a recombinant SARS CoV-2 protein-based vaccine technology from the Texas Children's Hospital transferred to India and to Indonesia. In addition to expanding support for academic or non-profit product development partnerships, our analysis finds that an essential step is the strengthening of selected LMIC regulatory systems to become Stringent Regulatory Authorities (SRAs), together with a re-prioritization of the WHO Prequalification (PQ) system to ensure early vaccine availability in LMICs especially during pandemics. Advancing LMIC National Regulatory Authorities (NRAs) to Stringent Regulatory Authorities (SRAs) status will require substantial resources, but the benefits for future pandemic control and for health in LMIC would be immense. We call on the WHO, United Nation (UN) agencies and SRAs, to collaborate and implement a comprehensive roadmap to support LMIC regulators to achieve stringent status by 2030.


Highly sensitive INHIBIT and XOR logic gates based on ICT and ACQ emission switching of a porphyrin derivative.
Fluorescence-switch-based logic devices are very sensitive compared with most of the reported devices based on UV/Vis absorption systems. Herein, we demonstrate that a simple molecule, 5,10,15,20-tetra-(4-aminophenyl)porphyrin (TAPP), shows protonation-induced multiple emission switches through intramolecular charge transfer and/or aggregation-caused quenching. Highly sensitive INHIBIT and XOR logic gates can be achieved by combining the intermolecular assembly with the intramolecular photoswitching of diprotonated TAPP (TAPPH2(2+)). In addition, molecular simulations have been performed by DFT for a better understanding of the emission-switching processes.


The Saccharomyces cerevisiae VMA7 gene encodes a 14-kDa subunit of the vacuolar H(+)-ATPase catalytic sector.
Yeast vacuoles contain an H(+)-ATPase that acidifies the vacuolar lumen and generates an electrochemical gradient of protons across their membranes. Five polypeptides, denoted as subunits A to E in the order of decreasing molecular masses from 69 to 27 kDa, were identified in the catalytic sector of the enzyme. However, other polypeptides may be necessary for the activity of the enzyme. When a 14-kDa polypeptide was suggested to be a subunit of a specialized V-ATPase in Manduca sexta, and a homologous short sequence was detected downstream of the UGA1 gene in yeast, we cloned this counterpart gene from yeast. The gene VMA7 encodes a protein Vma7p of about 14 kDa. The predicted protein is highly homologous to the above mentioned M. sexta protein. The delta vma7::URA3 null mutant exhibits growth characteristics typical of other VMA disruptant mutants in genes encoding subunits of the catalytic sector. The delta vma7::URA3 null mutants are not able to grow on a medium buffered at pH 7.5, they fail to accumulate quinacrine into their vacuoles and the other subunits of the catalytic sector are not assembled onto the vacuolar membrane in its absence. Epitope-tagged Vma7p was constructed and the proton uptake activity of isolated vacuoles from this yeast strain was markedly inhibited by a monoclonal antibody against the epitope-tag. A cold inactivation experiment demonstrated that Vma7p is a genuine subunit of the catalytic sector of V-ATPase and it is denoted as subunit F.


Evaluation of genetic variation in the international Brown Swiss population.
The international Brown Swiss cattle population pedigree was studied to measure genetic variations and to identify the most influential animals. Twenty-two countries provided pedigree information on 71 497 Brown Swiss bulls used for artificial insemination (AI). The total number of animals with the pedigree is 181 094. The mean inbreeding coefficient for the pedigree population was 0.77%. There was, in most cases, an increase in the mean inbreeding coefficient, with the highest value at 2.89% during the last 5-year period (2000 to 2004). The mean average relatedness for the pedigree population was 1.1%. The effective population size in 2004 was 204. There was notable variation between average generation intervals for the four parental pathways. The longest average generation interval, at 8.73 years, was observed in the sire-son pathway. The average generation interval for the whole population was 6.53 years. Most genetically influential individuals were sires. The highest contributing founder was a sire with a 3.22% contribution, and the highest contributing founder dam made a contribution of 1.75%. The effective number of founders and the effective number of ancestors were 141 and 88, respectively. The study showed that genetic variation within the pedigree population has been decreasing over recent years. Increasing the number of AI bulls with a low individual coefficient of inbreeding could help to maintain a good level of genetic variation in the Brown Swiss population.


Depression and Suicide Risk Among Nursing Staff at a Honduran National Hospital.
Depression and suicide risk among nursing staff have become increasingly concerning, especially given the demanding nature of their profession. The World Health Organization identifies depression as a primary factor contributing to global disability and suicide deaths. A descriptive, non-experimental, cross-sectional cohort study was conducted, encompassing the eligible personnel (n=82) out of a total of 102 nurses at the Mario Catarino Rivas Hospital in San Pedro Sula, Honduras, from October to November 2022. The study utilized the Okasha assessment tool to gauge the prevalence of suicidal risk and the Beck Depression Inventory-II (BDI-II) instrument to analyze the extent and severity of depression. In addition, the participants completed a demographic survey. Results: The average age of participants was 34.91 years, with a majority (86.6%) being female. In terms of work assignments, 54.9% were employed in the inpatient area. Regarding the mental health of the nursing staff, 78% displayed no or minimal depression, 9.7% presented mild depression, 7.3% showed moderate depression, 4.8% displayed severe depression, and 14.6% exhibited a suicide risk. Young adults had the highest prevalence of all three levels of depression, and the emergency department and inpatient area had the most at-risk individuals for suicidal tendencies. The study offers a comprehensive insight into the demographics, work environment, and mental health of the nursing staff at the Honduran National Hospital. The results highlight the importance of specialized measures and strong support systems to safeguard the mental health of nursing staff.


Combating quasiparticle poisoning with multiple Majorana fermions in a periodically-driven quantum wire.
Quasiparticle poisoning has remained one of the main challenges in the implementation of Majorana-based quantum computing. It inevitably occurs when the system hosting Majorana qubits is not completely isolated from its surrounding, thus considerably limiting its computational time. We propose the use of periodic driving to generate multiple Majorana fermions at each end of a single quantum wire, which naturally provides the necessary resources to implement active quantum error corrections with minimal space overhead. In particular, we present a stabilizer code protocol that can specifically detect and correct any single quasiparticle poisoning event. Such a protocol is implementable via existing proximitized semiconducting nanowire proposals, where all of its stabilizer operators can be measured from an appropriate Majorana parity dependent four-terminal conductance.


ASF1B is a Promising Prognostic Biomarker and Correlates With Immunotherapy Efficacy in Hepatocellular Carcinoma.
Background: Anti-silencing function 1B (ASF1B), a histone H3-H4 chaperone, is crucial for S-phase progression and cell proliferation. Recent studies have shown that ASF1B may be used as a new proliferation marker for cancer prognosis. However, the prognostic value and effect of ASF1B on tumor cells and the immune microenvironment in hepatocellular carcinoma (HCC) remain unclear. Methods: We analyzed the expression of ASF1B and its prognostic value using The Cancer Genome Atlas (TCGA) database (as a training set) and other databases, and we validated the findings by immunohistochemistry in our clinical database, containing 141 HCC patients (as a validation set). Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to probe the tumor-associated biological processes of ASF1B in HCC. The interrelationships between ASF1B expression and tumor immunological characteristics were analyzed by multiple databases. The Imvigor210 cohort was retrieved to assess the ability of ASF1B to predict immunotherapy efficacy. Results: ASF1B was highly expressed in tumor tissue compared to paracancerous tissue. High ASF1B expression was associated with worse overall survival (OS) and progression-free survival (PFS) in the training set (p = 0.005, p < 0.001) and validation set (p < 0.001, p < 0.001). Multivariate analysis revealed that ASF1B was an independent prognostic factor associated with OS and PFS. GSEA and GSVA suggested that ASF1B was involved in tumor-associated biological processes, including the cell cycle, DNA replication, base excision repair, mismatch repair, RNA degradation, ubiquitin-mediated proteolysis, and nucleotide excision repair. Further analysis revealed that the levels of ASF1B were positively correlated with the immune cells infiltration of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells. However, ASF1B was positively correlated with Treg cell infiltration and inhibitory immune checkpoints in exhausted T cells. Patients who received anti-PD-L1 immunotherapy with high ASF1B expression had a higher objective response. Conclusion: The ASF1B level is an independent prognostic factor and may serve as a potential immunotherapeutic target.


Differential effects of the soluble fiber inulin in reducing adiposity and altering gut microbiome in aging mice.
Inulin, a soluble dietary fiber, is thought to exert multiple beneficiary effects through promoting growth of bacteria that metabolize the fiber to short-chain fatty acids (SCFAs); however, the effect and efficacy of inulin in aging subjects is unknown. This study aims to systematically evaluate the capacity of SCFAs production and host response in mice of different ages. Male C57BL/6J mice across young (5 months), middle (11 months) and old (26 months) age were subjected to a control diet for 2 weeks, followed by 6 weeks of inulin-containing diet. Inulin-induced increase in fecal butyric acid levels was most prominent in middle-age group compared to other age groups. In addition, inulin-induced increase in fecal propionic acids showed age-dependent decline. Interestingly, the SCFA-producing Roseburia was most abundantly and persistently increased in the middle-age group. Furthermore, inulin intake significantly reduced Firmicutes to Bacteroidetes ratio, and several dysbiotic bacteria associated with pro-inflammatory state. Concomitantly, circulating levels of CXCL1, a chemoattractant for neutrophils, was reduced by inulin intake. Inulin decreased fat mass in all age groups, with middle-aged mice being most responsive to fat-reducing effects of inulin. Moreover, inulin significantly increased energy expenditure and voluntary wheel running in middle-aged mice, but not in old mice. Overall, our data suggest that the efficacy of inulin in altering the microbiome and SCFA production, and the subsequent metabolic response was diminished in old mice, and highlight the importance of including age as a variable in studies determining host-microbe response to diets.


The synchronizing role of multiplexing noise: Exploring Kuramoto oscillators and breathing chimeras.
The synchronization of spatiotemporal patterns in a two-layer multiplex network of identical Kuramoto phase oscillators is studied, where each layer is a non-locally coupled ring. Particular focus is on the role played by a noisy inter-layer communication. It is shown that modulating the inter-layer coupling strength by uncommon noise has a significant impact on the dynamics of the network, in particular, that modulating the interlayer coupling by noise can counter-intuitively induce synchronization in networks. It is further shown that increasing the noise intensity has many other analogous effects to that of increasing the interlayer coupling strength. For example, the noise intensity can also induce state transitions in a similar way, in some cases causing the layers to completely synchronize within themselves. It is discussed how such disturbances may in many cases be beneficial to multilayer systems. These effects are demonstrated both for white noise and for other kinds of colored noise. A "floating" breathing chimera state is also discovered in this system.


Laparoscopy-assisted total gastrectomy for advanced gastric cancer with carcinomatous ascites after S1 plus cisplatin chemotherapy: a case report.
A 29-year-old man with a type 4 tumor, in the lower third of the stomach, and carcinomatous ascites was diagnosed by aspiration cytology of the ascitic fluid. Curative resection was considered impossible, and S1 (120 mg/d) and cisplatin (90 mg/d) were given for 21 days in 1 course. The cancer lesion showed marked remission (partial response), and the ascites completely disappeared after the fourth course. Twenty-five days after completion of the S1 treatment, laparoscopy-assisted total gastrectomy was performed. Histopathological examination showed no remnant cancer cells in the resected specimen and no lymph node metastases. The tumor was replaced with fibrosis having a granulomatous change. The patient's postoperative course was uneventful. The patient was continued with S1 monotherapy after surgery, and no signs of recurrence or metastases have been seen on any examination 12 months after the surgery.


Androgen receptor antagonists in castration-resistant prostate cancer.
Persistent androgen receptor (AR) signaling despite low levels of serum androgens has been identified as a critical target for drug discovery in castration-resistant prostate cancer (CRPC). As proof of principle that the AR remains relevant in CRPC, 2 AR-targeted agents recently approved by the Food and Drug Administration-abiraterone and enzalutamide-have increased overall survival for patients with CRPC in the setting of prior chemotherapy. This review focuses on the AR and 2 direct antagonists, enzalutamide and ARN-509. These next-generation AR antagonists offer great promise for patients with advanced disease. Relative to conventional antiandrogens such as bicalutamide, they bind to the receptor with higher affinity, prevent nuclear translocation and DNA binding, and induce apoptosis without agonist activity in preclinical models. The success of these AR-targeted agents in the clinic has changed the landscape of therapy for patients with CRPC, and further therapeutic options building on this platform are currently in development.


The relationship between fundamental movement skill proficiency and physical self-confidence among adolescents.
This study aims to assess fundamental movement skill (FMS) proficiency, physical self-confidence levels, and the relationship between these variables and gender differences among adolescents. Three hundred and ninety five adolescents aged 13.78 years (SD = ±1.2) from 20 schools were involved in this study. The Test of Gross Motor Development-2nd Edition (TGMD), TGMD-2 and Victorian Skills Manual were used to assess 15 FMS. Participants' physical self-confidence was also assessed using a valid skill-specific scale. A significant correlation was observed between FMS proficiency and physical self-confidence for females only (r = 0.305, P < 0.001). Males rated themselves as having significantly higher physical self-confidence levels than females (P = 0.001). Males scored significantly higher than females in FMS proficiency (P < 0.05), and the lowest physical self-confidence group were significantly less proficient at FMS than the medium (P < 0.001) and high physical self-confidence groups (P < 0.05). This information not only highlights those in need of assistance to develop their FMS but will also facilitate in the development of an intervention which aims to improve physical self-confidence and FMS proficiency.


Cervical conization complicated by sepsis with lung and liver abscesses.
Extrapelvic infections complicating cervical conization are exceedingly rare. Seven days after conization, a 44-year-old patient presented with fever and right upper quadrant pain. Pleural effusion and pulmonary and hepatic abscesses were detected. The pathology report of the conization showed microabscesses. Blood cultures grew Fusobacterium necrophorum. Intravenous antibiotics were administered. The pulmonary findings improved but did not completely resolve after drainage of pleural effusions. The patient refused further procedures and was discharged in good clinical condition and with oral antibiotics after 37 days. Extrapelvic abscesses are rare complications of cervical conization. This is the first report in identifying F. necrophorum as a cause of this complication. Appropriate cultures, drainage of abscesses, and antibiotics are the mainstay of diagnosis and treatment.


Sternal closure with resorbable synthetic suture material in children.
The use of resorbable sutures for sternal closure after median sternotomy in children has developed to a clinically routine procedure. Since there is no follow-up study so far about the influence of these synthetic sutures on sternal stability, wound healing, and compatibility in children, we evaluated the use of polydioxanon (PDS) cord in children particularly regarding those properties. In 59 children (weighing up to 30 kg) we could show that the use of synthetic resorbable materials (Vicryl 4/0, PDS) allows a complication-free stability of the sternum, good wound healing, and very good compatibility. It is concluded that the use of PDS cord is a suitable and reliable method for sternal closure with good clinical results.


Cost-effectiveness analysis of the nine-valent HPV vaccine in Italy.
In Italy HPV vaccination with the quadrivalent vaccine (Gardasil®) is offered actively and free of charge to girls aged 12 since 2007. A nine-valent vaccine (Gardasil 9®) received the European market authorization in 2015 to protect, with only 2 doses, against around 90% of all HPV positive cancers, over 80% of high-grade precancerous lesions and 90% of genital warts caused by HPV types 6/11. A dynamic transmission model simulating the natural history of HPV-infections was calibrated to the Italian setting and used to estimate costs and QALYs associated with vaccination strategies. The analyses compared two strategies with the nine-valent vaccine (cervical cancer screening and vaccination in girls only or vaccination in boys and girls) to four alternative strategies (cervical cancer screening and vaccination with quadrialent vaccine in girls only, in both boys and girls, with bivalent vaccine in girls and screening strategy only). The National Health Service perspective was considered. The switch to the nine-valent vaccine in Italy can further reduce the burden associated to cervical cancer and HPV-related diseases and is highly cost-effective. Compared to the current vaccination program with quadrivalent vaccine, the nine-valent vaccine in a programme including girls and boys shows further reductions of 17% in the incidence of cervical cancer, 35 and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new technology is associated with an ICER of 10,463€ per QALY gained in universal vaccination, decreasing to 4483€ when considering the vaccine switch for girls-only.


The importance of hydrogen and formate transfer for syntrophic fatty, aromatic and alicyclic metabolism.
We used a combination of genomic, transcriptional and enzymatic analyses to determine the mechanism of interspecies electron transfer by two model syntrophic microorganisms, Syntrophomonas wolfei and Syntrophus aciditrophicus. Both organisms contain multiple hydrogenase and formate dehydrogenase genes, but lack genes for outer membrane cytochromes and nanowire formation. Syntrophically grown cells and cell-free extracts of S. aciditrophicus and S. wolfei had both hydrogenase and formate dehydrogenase activities. Butyrate metabolism and CH4 production by washed cell suspensions of S. wolfei and Methanospirillum hungatei were inhibited by hydrogenase inhibitors (cyanide and carbon monoxide), but not by a formate dehydrogenase inhibitor (hypophosphite). Syntrophic benzoate oxidation and CH4 production by washed cell suspensions of S. aciditrophicus and M. hungatei were inhibited by hypophosphite, but not cyanide and carbon monoxide. All three inhibitors halted syntrophic cyclohexane-1-carboxylate metabolism. Two hydrogenase genes, hydA1 and hydA2, were more highly expressed when S. wolfei was grown syntrophically. S. aciditrophicus expressed multiple hydrogenase and formate dehydrogenase genes during syntrophic benzoate and cyclohexane-1-carboxylate growth, one of which (fdhA2) was highly differentially expressed during syntrophic benzoate growth. Thus, these syntrophic microorganisms have flexible metabolisms that allow them to use either H2 or formate transfer depending on the substrate involved.


Preparation of anti-ras Mr 21,000 protein monoclonal antibodies and immunohistochemical analyses on expression of ras genes in human stomach and thyroid cancers.
Sixteen clones (RASK-1 to -16) of murine monoclonal antibodies were raised against ras Mr 21,000 protein (p21). The p21 produced by Escherichia coli with inserted v-Ki-ras genes was used as immunogen. RASK-1 was found to be specific for Ki-ras p21, whereas RASK-2 to -16 reacted with the p21s of Ki-, N-, and Ha-ras genes in both enzyme-linked immunosorbent and immunoblotting assays. Binding inhibition assays with biotinylated monoclonal antibodies by enzyme-linked immunosorbent assay showed that the monoclonal antibodies of the 16 clones included those binding to several mutually distinct sites on p21. The expressions of ras p21 in human stomach and thyroid tissues were examined with RASK-3, which reacted with all the Ki-, N-, and Ha-ras p21s immunohistochemically by the avidin-biotin peroxidase complex method. Formalin-fixed, paraffin-embedded tissues of 101 cases of stomach cancer, 53 cases of noncancerous stomach, 74 cases of cancer of the thyroid, and 59 cases of noncancerous thyroid were analyzed. In both the stomach and thyroid, cancer cells expressed p21 predominantly. Cells of cases with various noncancerous disorders as well as certain types of normal cells were also p21 positive. These findings suggest that precaution is required in use of p21 as a cancer marker. Expression of p21 was noted in moderately to well-differentiated stomach cancer, intestinal metaplasia, and atypical hyperplasia. This finding suggests that the appearance of p21 in stomach cancer may be initiated before cytological transformation.


Effects of diluents and plasma on honey bee (Apis mellifera L.) drone frozen-thawed semen fertility.
Cryopreservation is an advanced method used to protect germplasm in liquid nitrogen. Honey bees are of special interest to protect because of their pollination activity and critical role in agriculture. There has been important progress in the cryopreservation of honey bee germplasm in recent years, leading to practical recovery of genetic material for breeding purposes following freezing. However, there remains room for improvement and the goal of the present study was to evaluate the effect of different "extenders" added post-thaw on the fertilization rate of cryopreserved honey bee semen. The purpose of adding extender post-thaw was to dilute the cryoprotectant to remove chemicals after centrifugation because of potential adverse effects. The control consisted of frozen-thawed semen without the addition of an extender; treatment groups included the addition of one of the following extenders: glucose solution, fresh ram semen plasma, fresh honey bee semen plasma, extender solution. All of the above treatments and frozen-thawed control were compared to fresh semen. For each group, 15 virgin queens were instrumentally inseminated with the semen-diluent solution and introduced into nucleus colonies to determine the brood patterns of the queens. Percentages of worker brood produced in the fresh semen, frozen-thawed semen control, glucose, fresh ram semen plasma, fresh honey bee semen plasma, and extender solution supplemented groups were 98.±1.1%, 47.0 ± 0.9%, 3.0 ± 0.8%, 0.3 ± 0.1%, 48.1 ± 4.1% and 40.3 ± 2.4%, respectively. Similiarly, spermatozoa numbers in the spermathecae of the same treatment groups were 3.6 × 106, 1.6 × 106, 7.3 × 105, 4.7 × 105, 8.1 × 105, and 4.6 × 105 spermatozoa for the same treatment, respectively. The differences in both worker brood percentage and sperm count in the spermatheca were statistically significant (P < 0.01) among all treatment groups, except the frozen-thawed control group and fresh drone semen plasma group. We found a positive correlation between sperm count in the spermatheca and the percentage of worker brood (r = 0.91). With the exception of fresh honey bee semen plasma, the fertility rate was reduced following the addition of various plasmas and diluents post-freezing.


[Cenesthetic schizophrenia by Huber: 50 years of a concept].
50 years after the first description of cenesthetic schizophrenia as a concept by Gerd Huber, it can be valued as a starting point of fundamental insights into the course of schizophrenia and also for the development of the concept of basic symptoms assessment. Because patients suffering from cenesthetic schizophrenia are often misdiagnosed, it is still relevant for diagnostic and therapeutic purposes in practise today. Cenesthetic symptoms can be considered as substrate-close because they can be part of idiopathic psychosyndromes and also of organic brain lesions. Therefore they could be allocated as a typical example of the possible phenomenological identity or overlap of neurological and psychopathological symptomatology. The historical, psychopathological methodological and clinical foundations of the concept of cenesthetic schizophrenia will be demonstrated and the importance of this work for today will be emphasized.


Outcomes of Transferring a Healthy Motor Fascicle From the Radial Nerve to a Branch for the Triceps to Recover Elbow Extension in Partial Brachial Plexus Palsy.
Triceps reinnervation is an important objective to pursue when repairing the brachial plexus for cases with upper roots injuries, and a number of different techniques have been developed in order to restore elbow extension in such cases. To demonstrate the surgical outcomes associated with the technique of transferring a single healthy motor fascicle from the radial nerve of the affected arm to a branch innervating 1 of the 3 heads of the triceps. A retrospective study of 13 adult patients sustaining an upper trunk syndrome associated with total elbow extension palsy who underwent the proposed technique as part of the surgical planning for reconstruction of the brachial plexus. Outcomes scored as M4 for elbow extension were noted in 9 cases (70%), M3 in 3 (23%), and M1 in 1 subject (7%). No patient considered the postoperative strength for carpal or finger extension as impaired. There were no differences in outcomes by using a fascicle activating carpal or finger extension as donor, as well as regarding the use of the branch to the medial or lateral head of the triceps as the recipient. The technique of transferring a healthy motor fascicle from the radial nerve of the affected side to one of its nonfunctional motor branches to the triceps is an effective and safe procedure for recovering elbow extension function in patients sustaining partial injuries of the brachial plexus.


Brugada phenocopy in a patient with acute pulmonary embolism presenting with recurrent syncope.
Brugada phenocopy (BrP) refers to a group of clinical conditions that have etiologies distinct from Brugada syndrome (BrS). Although both demonstrate features of ST-segment elevation in the right precordial leads on the electrocardiogram (ECG), one must be distinguished from the other as their treatment options are different. We report a male patient who presented with recurrent syncope with a Brugada and a S1Q3T3 pattern on the ECG. Acute pulmonary embolism (APE) complicated by BrS was suspected. Twenty-four hours Holter monitoring did not demonstrate any evidence of ventricular arrhythmias. Computed tomography pulmonary angiogram confirmed the presence of an APE. He was treated with low molecular weight heparin and a repeat ECG taken the next day showed resolution of the Brugada and S1Q3T3 patterns. This case report illustrates that APE and BrS can present with similar clinical and electrocardiographic features of recurrent syncope and Brugada pattern, respectively.


Soft tissue vibration dynamics after an unexpected impact.
It has been proposed that during walking and running the body has strategies to minimize the soft tissue vibrations. The concept of muscle tuning suggests that muscle activity changes in response to the input signal to modify the frequency and damping of such vibrations. Although it has been demonstrated for continuous vibrations and single impacts, the adaptations dynamics are still unclear. The purpose of this study was to determine (1) if the neuromuscular adaptation to repeated single impacts is immediate, (2) what are the adaptation mechanisms, and (3) if there are functional groups defined by different adaptation strategies. Twenty-one subjects performed two sets of knee curl on a dynamometer with a custom-made appliance that supported the foot and heel. The first set was for familiarization with a 90° range of movement and 400°/sec velocity. The second set had 15 repetitions with a 55° range and the same angular velocity. The subjects were not notified of the change; therefore the first impact was unexpected. A pair of electrodes and a three-dimensional accelerometer were placed on the gastrocnemius medialis. Damping coefficient, natural frequency, and EMG characteristics were measured. All the participants adapted to the vibrations and showed changes in the damping coefficient and or the natural frequency. Apart from the immediate adaptation, a subgroup showed a progressive adaptation after the first immediate change. Three functional groups were identified using support vector machine, correlations with anthropometric values suggest that muscle mass could affect the adaptation strategy used.


Ionic Liquid-Assisted 3D Printing of Self-Polarized β-PVDF for Flexible Piezoelectric Energy Harvesting.
Three-dimensional (3D) printing technologies have unparalleled advantages in constructing piezoelectric devices with three-dimensional structures, which are conducive to improving the efficiency of energy harvesting. Among them, fused deposition modeling (FDM) is the most widely used thanks to its low cost and wide range of molding materials. However, as the best piezoelectric polymer, a high electroactive β-phase poly(vinylidene fluoride) (PVDF) piezoelectric device cannot be directly obtained by FDM printing because the β-crystal is unstable at the molten state. Herein, we develop for the first time ionic liquid (IL)-assisted FDM for direct printing of β-PVDF piezoelectric devices. An IL can induce and maintain β crystals during melt extrusion and FDM printing, ensuring that the β-crystal in the printed PVDF device is as high as 98.3%, which is the highest in 3D-printed PVDF as far as we know. Furthermore, the shearing force provided by the FDM facilitates the directional arrangement of the dipoles, resulting in the printed PVDF device having self-polarization characteristics without poling. Finally, the piezoelectric output voltage of the 3D-printed PVDF device is 4.7 times that of the flat PVDF device, and its area current density (17.5 nA cm-2) is more than that of the reported 3D-printed PVDF piezoelectric device in the literature by two orders of magnitude. The one-step 3D printing strategy proposed in this paper can realize the rapid preparation of complex-shaped and lightweight self-polarized β-PVDF-based piezoelectric devices for energy harvesting.


[Immediate and early reinterventions in the surgery of colorectal cancer].
Out of 584 cases submitted to colorectal surgery 461 (78.92%) were performed for cancer. Thirty-three patients (7.16%) necessitated immediate (1) or precocious reinterventions for bleeding, fistulae, peritoneal infections, bowel occlusion, necrosis or stenosis of the iliac anus. We are out the technical procedures chosen for each class of complications asking for reintervention. We registered 4 deaths, in aged patients with hard associated morbidity, with emergency reinterventions. We appreciate that a correct preoperative preparation reduces the rate of reintervention and an early reintervention reduces the post-operative mortality.


Mutation of Isocitrate Dehydrogenase 1 in Cholangiocarcinoma Impairs Tumor Progression by Inhibiting Isocitrate Metabolism.
Aim: Isocitrate dehydrogenase 1 (IDH1) is key enzyme involved in cellular metabolism and DNA repair. Mutations in IDH1 occur in up to 25% of cholangiocarcinomas. The present study aimed to explore the features of cellosaurus REB cells with mutant and wide-type IDH1. Methods: To compare the features of IDH1 knockout and mutation in cholangiocarcinoma, we firstly constructed the IDH1 knockout and IDH1 mutation cell lines. We then evaluated the viability of these cell lines using the cell count assay and MTT assay. Next, we determined cell migration and invasion using the Transwell assay. Additionally, to evaluate the effects of IDH1 on cellular metabolism, the levels of α-ketoglutarate (α-KG) and nicotinamide adenine dinucleotide phosphate (NADPH) were determined using enzyme-linked immunosorbent assay. We then applied ChIPbase dataset to explore the genes that were regulated by IDH1. Results: High frequency of mutated IDH1 was observed in the cholangiocarcinoma and IDH1 R132C was presented in more than 80% of mutations. The results showed that IDH1 knockout decreased cell proliferation, migration and invasion, whereas the overexpression of IDH1 in IDH1 knockout cell line recovered its proliferation, migration and invasion capacities. Additionally, IDH1 mutation reduced the levels of NADPH and α-KG. Furthermore, investigation into the underlying mechanisms revealed that IDH1 overexpression induced the expression of aldehyde dehydrogenase 1 thereby promoting cell proliferation, migration and invasion. Conclusion:IDH1 plays an important role in cholangiocarcinoma and its mutation impairs tumor progression in part by inhibition of isocitrate metabolism.


Baicalin Attenuates Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury by Modulating the BDNF-TrkB/PI3K/Akt and MAPK/Erk1/2 Signaling Axes in Neuron-Astrocyte Cocultures.
Background: Baicalin (BCL), a candidate drug for ischemic stroke, has been indicated to protect neurons by promoting brain-derived neurotrophic factor (BDNF). However, the cellular source of BDNF release promoted by baicalin and its detailed protective mechanism after ischemia/reperfusion remains to be studied. The aim of this study was to investigate the neuroprotective mechanisms of baicalin against oxygen-glucose deprivation/reoxygenation (OGD/R) in a neuron-astrocyte coculture system and to explore whether the BDNF-TrkB pathway is involved. Methods and Results: A neuron-astrocyte coculture system was established to elucidate the role of astrocytes in neurons under OGD/R conditions. The results demonstrated that astrocytes became reactive astrocytes and released more BDNF in the coculture system to attenuate neuronal apoptosis and injury after OGD/R. BCL maintained the characteristics of reactive astrocytes and obviously increased the expression of cyclic AMP response element-binding protein (CREB) and the levels of BDNF in the coculture system after OGD/R. To further verify whether BDNF binding to its receptor tyrosine kinase receptor B (TrkB) was required for the neuroprotective effect of baicalin, we examined the effect of ANA-12, an antagonist of TrkB, on NA system injury, including oxidative stress, inflammation, and apoptosis induced by OGD/R. The results showed that treatment of NA systems with ANA-12 significantly attenuated the neuroprotection of BCL. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways are two important downstream cascades of signaling pathways activated by BDNF binding to TrkB. We investigated the expressions of TrkB, PI3K, Akt, MAPK, and ERK. The results demonstrated that baicalin significantly increased the expressions of TrkB, PI3K/AKT, and MAPK/ERK. Conclusion: The neuroprotective effects of baicalin against oxidative stress, inflammation, and apoptosis were improved by astrocytes, mainly mediated by increasing the release of BDNF and its associated receptor TrkB and downstream signaling regulators PI3K/Akt and MAPK/ERK1/2.


Which Functional Outcomes Can be Measured in Low Back Pain Trials and Therapies?: A Prospective 2-Year Factor-, Cluster-, and Reliability-Multicenter Analysis on 42 Variables in 1049 Individuals.
Prospective 2-year factor-, cluster-, and reliability-multicenter analysis. To provide evidence on the uniqueness and usefulness of a set of potential relevant functional outcomes. A very high number of functional outcomes that can be utilized as variables in low back pain (LBP) trials exists. Participants (n = 1049) with and without current LBP were included. At 7 visits (baseline, 4 wk, 3 mo, 6 mo, 9 mo, 1 yr, and 2 yr), 42 different functional outcomes were assessed. Two exploratory factor analyses (for baseline-values and for changes scores to 3 mo post-baseline) were calculated (maximum likelihood extraction, varimax factor rotation). The strongest factor-loading outcomes were selected for the following hierarchical cluster analyses (average linkage, Euclidean distance measure). For each cluster, time point, and outcome, reliability analyses were subsequently calculated using intraclass correlation coefficients, standard error of measurements and coefficients of variation. The factor analysis for the cross-sectional values revealed 9 factors with a cumulative variance explanation of 61.7% and 13 unique ones. The change-score factor analysis revealed nine factors with a total variance explanation of 61.8%, seven outcomes were unique. Ten outcomes were important for both cross-sectional and change-score analyses, 11 were most valuable for cross-sectional and four for the change scores. Patients with pain grades 1 to 3 show comparable patterns (cluster 2). Grade 0 (cluster 1) and grade 4 (cluster 3) are unique and cannot be cumulated with other grades. Most biomechanical outcomes were highly reliable and display low measurement errors. We found 25 potentially meaningful functional outcomes in the context of objective functional measurements (such as trunk range of motion, dynamic and static balance, strength, and muscle fatigue resistance) and body characteristics. The present framework may help to select appropriate functional outcomes and rate effects beyond the known core set of outcomes.Level of Evidence: 1.


CXCL12-CXCR4 axis in angiogenesis, metastasis and stem cell mobilization.
Chemokines are key players in the attraction and activation of leukocytes and are thus implicated in the recruitment of immune cells at sites of infection and/or inflammation. They exert their action by binding to seven-transmembrane G protein-coupled receptors. The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 represents the single natural ligand for the chemokine receptor CXCR4. CXCL12 possesses angiogenic properties and is involved in the outgrowth and metastasis of CXCR4-expressing tumors and in certain inflammatory autoimmune disorders, such as rheumatoid arthritis. CXCR4 expression on tumor cells is upregulated by hypoxia and angiogenic factors, such as vascular endothelial growth factor (VEGF). CXCR4 also acts as a co-receptor for entry of human immunodeficiency virus (HIV) in CD4(+) T cells. Finally, CXCL12/CXCR4 interactions were shown to play an important role in the migration of hematopoietic stem cells and their progenitors from, and their retention within, the bone marrow, a site characterized by high CXCL12 expression. As such, CXCR4 inhibitors may be utilized to inhibit HIV-1 infection, tumor growth and metastasis and to mobilize hematopoietic stem cells from the bone marrow in the circulation, where they can be collected for autologous stem cell transplantation. Here, we discuss the different aspects of CXCL12/CXCR4 biology as well as the development and anti-cancer/stem cell mobilizing activity of CXCR4 antagonists.


Defining response and remission in anxiety disorders: toward an integrated approach.
Response and remission rates are commonly used to evaluate the efficacy of treatments for anxiety disorders and other psychiatric illnesses. Response is generally regarded as a clinically meaningful improvement in symptoms, while remission, the goal of treatment, is generally thought of as the absence or near absence of symptoms following illness, accompanied by a return to premorbid levels of functioning. Response and remission are often defined using psychiatric rating scales, based on score cutoffs or the magnitude of score changes from baseline. While no universally accepted criteria exist, a commonly used threshold for response is a >50% improvement in the total score, while for remission, various cutoff points have been used. Comparison of cutoffs or change scores for disease-specific scales with Clinical Global Impressions ratings is a useful way of evaluating response and remission criteria across disorders. To illustrate the use of disease-specific and global measures, this article summarizes data from randomized, placebo-controlled studies of adult patients with generalized anxiety disorder, social anxiety disorder, or panic disorder treated with the serotonin norepinephrine reuptake inhibitor venlafaxine extended release, for which acute-phase data are available (a total of 13 trials).


In vitro studies of the characteristics of the release of prostaglandins from viscous solutions.
The diffusion rates of prostaglandin E2 in different viscous solutions used in clinical practice for inducing abortion and term labour have been studied in the laboratory. The results indicate that of those currently in use, solutions of Dextran might be more appropriate for the purposes. By increasing the viscosity of solutions in use at present, clinical results may be further improved by aiding retention in the vagina or uterus while producing a slow sustained linear release of prostaglandin.


Interim report of the SENTIS trial: cerebral perfusion augmentation via partial aortic occlusion in acute ischemic stroke.
The aim of this paper was to present the interim results of the the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial. The SENTIS study is a phase III, multi-center randomized prospective study to evaluate cerebral perfusion augmentation with partial aortic occlusion in acute ischemic stroke. The trial was designed to compare conventional management of stroke patients with stroke patients treated by partial occlusion of the abdominal aorta by the NeuroFlo device. Follow up was at 24 hours and 90 days. Of the 100 patients enrolled, 53 were randomized to treatment and 47 to control. Six patients enrolled to treatment were found to have specific exclusion criteria and were excluded. Therefore, 97 validated patients, 47 treated patients and 47 control patients were included in the analysis. Adverse events were evenly distributed, among the two cohorts of patients with 16 patients or 34% in each group, including fatal and non-fatal adverse events. However, the mortality was significantly lower for the treated population (6.4%) versus the control population (14.9%), with more stroke progression (8.5%) and hemorrhagic transformation of the stroke area (4.3%) in the control population. The SENTIS trial was designed to test the hypothesis that the NeuroFlo system is safe to be used in humans and able to produce cerebral perfusion augmentation, based on imaging and neurological assessment at 24 hours and at 90 days. The preliminary data yielded by the interim analysis showed that the population enrolled in the trial was rather homogeneous regarding age, baseline NIHSS scores, and other risk factors, suggesting that the treated and control cohorts were similar. The analysis also showed that the adverse events were rather comparable between the two groups, suggesting the treatment procedure to be safe enough for continuation of the trial. The NeuroFlo system so far proved to be safe enough for clinical use and seems to be promising in improving survival in the acute stroke population.


Coordinated reset stimulation in a large-scale model of the STN-GPe circuit.
Synchronization of populations of neurons is a hallmark of several brain diseases. Coordinated reset (CR) stimulation is a model-based stimulation technique which specifically counteracts abnormal synchrony by desynchronization. Electrical CR stimulation, e.g., for the treatment of Parkinson's disease (PD), is administered via depth electrodes. In order to get a deeper understanding of this technique, we extended the top-down approach of previous studies and constructed a large-scale computational model of the respective brain areas. Furthermore, we took into account the spatial anatomical properties of the simulated brain structures and incorporated a detailed numerical representation of 2 · 10(4) simulated neurons. We simulated the subthalamic nucleus (STN) and the globus pallidus externus (GPe). Connections within the STN were governed by spike-timing dependent plasticity (STDP). In this way, we modeled the physiological and pathological activity of the considered brain structures. In particular, we investigated how plasticity could be exploited and how the model could be shifted from strongly synchronized (pathological) activity to strongly desynchronized (healthy) activity of the neuronal populations via CR stimulation of the STN neurons. Furthermore, we investigated the impact of specific stimulation parameters especially the electrode position on the stimulation outcome. Our model provides a step forward toward a biophysically realistic model of the brain areas relevant to the emergence of pathological neuronal activity in PD. Furthermore, our model constitutes a test bench for the optimization of both stimulation parameters and novel electrode geometries for efficient CR stimulation.


The Effectiveness of a Dark Septate Endophytic Fungus, Cladophialophora chaetospira SK51, to Mitigate Strawberry Fusarium Wilt Disease and With Growth Promotion Activities.
Strawberry Fusarium wilt, caused by the virulent fungus Fusarium oxysporum formae speciales fragariae (Fof) is a devastating soil-borne disease that causes severe production losses worldwide, including Japan. Fof is one of the top 10 fungal pathogens that threaten global crop security, and a method to effectively control this pathogen has yet to be found. This study aimed to investigate the effectiveness of dark septate endophytic (DSE) fungi against Fof to develop an efficient, effective, and environmentally friendly approach to improve plant health and fitness. A total of 19 fungal isolates were assessed, out of which three (SK47, SK48, and SK51) were selected based on their effectiveness in disease suppression in controlled growth chamber conditions using a soil system. Isolates SK47, SK48, and SK51 suppressed disease severity by 85.71, 61.90, and 90.48%, respectively. Molecular identification based on highly conserved small subunit (SSU), internal transcribed spacer (ITS), and large subunit (LSU) nrRNA regions identified these isolates as DSE Exophiala sp., Exophiala pisciphila, and Cladophialophora chaetospira, respectively. The sequences were deposited under accession numbers MN811693-MN811695 in the GenBank database. Notably, our results revealed that isolate C. chaetospira SK51 possessed superior growth promotion activities as well as disease suppression by significantly increased plant growth parameters (shoot and root dry mass, chlorophyll content, flower bud initiation, and number of fruit) in comparison to control plants and other two fungal candidates. Root colonization by C. chaetospira SK51 was visualized, and it was confirmed that the symbiosis with strawberry plants occurred successfully. Our results provide new insights in the application of DSE fungus C. chaetospira SK51 as a biocontrol agent on strawberry plants could promote plant growth, flower bud initiation, and fruit formation. C. chaetospira SK51 exhibited remarkable beneficial traits for the host plant, and it can potentially be applied in the development of new, safe, and effective treatments as an alternative to chemical fertilizers and fungicides for sustainable crop protection.


Growth and immobilization of tripterygium wilfordii cultured cells.
The plant Tripterygium wilfordii produces di- and triterpenes of interest for male contraception and treatment of arthritis and skin disorders. Cell line TRP4a obtained form this plant in 1981 was reported to produce these valuable compounds at yields ( approximately 0.04% of the biomass dry weight) higher than found in the plant (0.001%). In order to improve this production, studies were carried out to determine the feasibility of eliminating the troublesome component of coconut milk originally used to culture this cell line. A defined formulation suitable for growth ad maintenance has been developed. This medium consisted of Gamborg's PRL4 or B5 medium supplemented with 2 mg L(-1) 2,4-dichlorophenoxyacetic acid and 20 g L(-1) sucrose. Furthermore, monitoring of carbohydrate uptake revealed that T. wilfordii cells, contrary to many plant cell species, did not hydrolyze sucrose extra-cellularly before uptake. Replacement of this disaccharide by glucose or fructose increased specific growth rate from 0.15 to 0.25 day(-1). As tripdiolide is reported to be present in broth extract in significant amounts, plant cell immobilization technology offers a promising alternative to suspension cultures, especially in view to on line harvesting of the product. Surface immobilized T. wilfordii cell cultures were successfully carried out in 2-L bioreactors. Their biomass production and carbohydrate uptake were comparable to those observed for shake flask grown suspension cultures. Higher nitrate and ammonium uptake were found in immobilized cultures.


The initial feasibility of a computer-based motivational intervention for adherence for youth newly recommended to start antiretroviral treatment.
Young people represent the largest number of new HIV infections, thus youth living with HIV (YLH) are likely to be the largest group to initiate antiretroviral treatment (ART). Adherence patterns for behaviorally infected YLH are not adequate to effectively manage the disease; therefore, novel interventions are needed to improve medication adherence. The purpose of the current study, which will precede a randomized controlled trial, was to assess the initial feasibility of an individually tailored computer-based two-session interactive motivational interviewing (MI) intervention for YLH newly recommended to start ART. Intervention development occurred in collaboration with three youth advisory groups. Ten youth (ages 18-24) were recruited to participate in this study. Participants completed the intervention online. Intervention components focused on medication adherence (rating perceived importance and confidence, and goal setting). Retention was 100% for both intervention sessions. All participants (n=10) felt medication adherence was important, but 80% felt confident they could manage their adherence to HIV medications. Ninety percent of participants set the goal of taking their HIV medications exactly as prescribed and reported success achieving this goal at follow-up. Additionally, participants were satisfied with the quality of the sessions and the amount of assistance they received for managing their adherence to HIV medications (90% participants for Session 1; 89% for Session 2). Per exit interview responses, participants felt that the intervention made them think more about their health and was a motivator for them to take better care of their health. In conclusion, the intervention was feasible for YLH enrolled in the study.


Effects of varying the dietary nitrogen to carbohydrate ratio upon the biological performance of adult Dacus oleae. (Diptera Tephritidae).
By varying the dietary proportions of nitrogen to carbohydrate in a chemically defined diet, it was found that the olive fruit adult fly cannot utilize amino nitrogen as an energy source, while the most critical ingredient for prolonged survival was the carbohydrate part of the diet. Increase of the nitrogen contents above 2.6%, up to 6.4%, shortened adult life span by 50%. The best reproduction rate was scored under a N/C ratio of 1.6/40, while higher nitrogen contents reduced egg deposition. Fertility was adversely affected by low sucrose concentrations as well as by total absence of amino nitrogen, while higher nitrogen concentrations proved also detrimental egg hatchability.


Reevaluation of SNP heritability in complex human traits.
SNP heritability, the proportion of phenotypic variance explained by SNPs, has been reported for many hundreds of traits. Its estimation requires strong prior assumptions about the distribution of heritability across the genome, but current assumptions have not been thoroughly tested. By analyzing imputed data for a large number of human traits, we empirically derive a model that more accurately describes how heritability varies with minor allele frequency (MAF), linkage disequilibrium (LD) and genotype certainty. Across 19 traits, our improved model leads to estimates of common SNP heritability on average 43% (s.d. 3%) higher than those obtained from the widely used software GCTA and 25% (s.d. 2%) higher than those from the recently proposed extension GCTA-LDMS. Previously, DNase I hypersensitivity sites were reported to explain 79% of SNP heritability; using our improved heritability model, their estimated contribution is only 24%.


Open-set speech perception in congenitally deaf children using cochlear implants.
To assess and document the development of open-set speech recognition in congenitally deaf children implanted with the Nucleus multichannel cochlear prosthesis at < 5 years of age. The study group consisted of 38 consecutively chosen children in whom the decision to proceed with implantation had already been made. Congenitally profoundly deaf children were implanted with the Nucleus multichannel cochlear implant at < 5 years of age and followed at NYU Medical Center for a period of 1-5 years. Open-set speech perception was evaluated preoperatively and postoperatively using the following: the Glendonald Auditory Screening Procedure (GASP) word subset, the GASP sentence subtest, Phonetically Balanced Kindergarten monosyllabic word lists, Common Phrases test, Multisyllabic Lexical Neighborhood test, and Lexical Neighborhood test. Correlation coefficients were calculated between scores at each interval and age at implantation; one-way analyses of variance were performed independently. Results showed that all subjects had significant open-set speech recognition at the time of the last postoperative evaluation. Thirty-seven of the children use oral language as their sole means of communication. Multichannel cochlear implants provide significant and usable open-set speech perception in congenitally deaf children given implants at < 5 years of age.


Harmful algal bloom species and phosphate-processing effluent: field and laboratory studies.
In 2002, the Florida Department of Environmental Protection began discharging phosphate-processing effluent into Bishop Harbor, an estuary within Tampa Bay. Because of concerns that the effluent would serve as a nutrient source for blooms of the toxic dinoflagellate Karenia brevis, a field monitoring program was established and laboratory bioassays were conducted. Several harmful algal bloom (HAB) species, including Prorocentrum minimum and Heterosigma akashiwo, were observed in bloom concentrations adjacent to the effluent discharge site. Blooms of diatoms were widespread throughout Bishop Harbor. K. brevis was observed with cell concentrations decreasing with increasing proximity to the effluent discharge site. Bioassays using effluent as a nutrient source for K. brevis resulted in decreased cell yields, increased growth rates, and increased time to log-phase growth. The responses of HAB species within Bishop Harbor and of K. brevis to effluent in bioassays suggested that HAB species differ in their response to phosphate-processing effluent.


Electron-transfer chain in respiratory complex I.
Complex I is a part of the respiration energy chain converting the redox energy into the cross-membrane proton gradient. The electron-transfer chain of iron-sulfur cofactors within the water-soluble peripheral part of the complex is responsible for the delivery of electrons to the proton pumping subunit. The protein is porous to water penetration and the hydration level of the cofactors changes when the electron is transferred along the chain. High reaction barriers and trapping of the electrons at the iron-sulfur cofactors are prevented by the combination of intense electrostatic noise produced by the protein-water interface with the high density of quantum states in the iron-sulfur clusters caused by spin interactions between paramagnetic iron atoms. The combination of these factors substantially lowers the activation barrier for electron transfer compared to the prediction of the Marcus theory, bringing the rate to the experimentally established range. The unique role of iron-sulfur clusters as electron-transfer cofactors is in merging protein-water fluctuations with quantum-state multiplicity to allow low activation barriers and robust operation. Water plays a vital role in electron transport energetics by electrowetting the cofactors in the chain upon arrival of the electron. A general property of a protein is to violate the fluctuation-dissipation relation through nonergodic sampling of its landscape. High functional efficiency of redox enzymes is a direct consequence of nonergodicity.


[Problems of food absorption with reference to age and obesity].
In 1,000 obese persons and 250 persons with normal weight detailed nutrition anamneses concerning the average daily intake of calories, carbohydrates, protein, fats, cholesterol, saturated and repeatedly unsaturated fatty acids were made. Obese persons took less food than persons with normal weight--findings which are to be explained by the different habits of eating in the dynamic (the hyperalimentation takes place above all here) and in the static phase of obesity. There were no age tendencies in women, whereas in men, beginning with the 4th decade of life, all the nutrients were taken in a smaller quantity than in adolescence.


Alkylation of the O6 of guanine is only one of many chemical events that may initiate carcinogenesis.
The original hypothesis that chemical alteration of DNA can ultimately lead to carcinogenesis had been extended to a concept that the presence and persistence (lack of removal) of O6-alkyl G in an organ or cell population is the important requirement for tumorigenesis by alkylating agents. There are, however, many examples given in the text in which the organ specificity does not correlate with the amount of O6-alkyl G, and indeed, in some instances, no tumors result even though it can be shown that the DNA of many organs contains O6-alkyl G and that cell proliferation occurs. In some cases, there are clearly genetic factors. For example, the brain tumor incidence in two mouse strains differ but O6-alkyl G persistence is the same. Differing amounts or repair capability of O6-alkyl G in species, organs, or cells is not sufficient to explain variations in tumor incidence. Consideration must be given to other alkyl derivatives formed by alkylating carcinogens since at least six derivatives can lead to mispairing. Additionally, depurination has profound biological effects and evidence is emerging that bulky carcinogens such as aflatoxin and N-hydroxy-acetylaminofluorene cause rapid depurination (42). The role of phosphotriesters is as yet unknown. In attempting to come to a conclusion concerning the mode of tumor initiation by alkylating agents, we must not ignore the differences between alkyl groups. Dr. Pegg's paper focuses mainly on methylation, while my arguments stress ethylation. When the number of O6-methylguanines greatly exceeds that of O-methyl-pyrimidines, the former is more likely to be the initiating event. However, ethylation is generally more carcinogenic than methylation, if one considers that much less total alkylation is necessary for tumor development. The O-ethylpyrimidines produced by N-nitroso ethylating agents are more numerous than the O6-ethylguanines and they appear to be more persistent; that is, poorly repaired. Table 3 in Dr. Pegg's paper gives strong support to the potential initiation efficiency of the O4-ethylthymine and perhaps even to the idea that some yet-unidentified event is responsible for the carcinogenicity of diethylnitrosamine.(ABSTRACT TRUNCATED AT 400 WORDS)


Inhibition of T-cell proliferation by a MYB antisense oligomer is accompanied by selective down-regulation of DNA polymerase alpha expression.
We recently found that inhibition of MYB protein synthesis in human peripheral blood mononuclear cells (PBMC) exposed to human c-myb (designated MYB) antisense oligodeoxynucleotides prevents entry into S phase and cell proliferation. To determine the mechanism(s) by which down-regulation of human c-myb protein (MYB) synthesis interferes with DNA synthesis, we analyzed mRNA levels of DNA polymerase alpha and proliferating cell nuclear antigen (PCNA), transcripts of two genes required for DNA synthesis, in normal and leukemic T lymphocytes exposed to MYB antisense oligodeoxynucleotides. Expression of DNA polymerase alpha was inhibited both in normal T lymphocytes progressing from G0 to S phase and in exponentially growing CCRF-CEM leukemic cells, whereas expression of PCNA was inhibited only in mitogen-stimulated PBMC and remained essentially unaffected in the leukemia T-cell line. The functional link between expression of MYB and DNA polymerase alpha mRNAs was further demonstrated by analyzing DNA polymerase alpha mRNA levels in a temperature-sensitive (ts) fibroblast cell line (TK-ts13; TK is thymidine kinase) constitutively expressing human MYB mRNA driven by the simian virus 40 (SV40) promoter. In the MYB-expressing TK-ts13 cells, DNA polymerase alpha mRNA levels were unaffected following shift to the nonpermissive temperature of 39.6 degrees C, whereas in the parental line, DNA polymerase alpha mRNA levels were readily down-regulated. These findings indicate that the expression of MYB is related to that of DNA polymerase alpha in cells expressing MYB at high levels and suggest that there is a functional link between c-myb and DNA polymerase alpha mRNA expression during cell cycle progression of normal T lymphocytes.