Use of an ultrasonic Doppler flow detector for determining tissue viability in a dog.
An 8-month-old sexually intact female Boxer was examined because of an almost complete disarticulation of the right thoracic limb at the level of the proximal phalanges. Viability of the tissue distal to the injury was considered questionable. An ultrasonic Doppler flow detector was used to determine that circulation to the portion of the digits distal to the injury had been preserved on the palmar aspect of the foot. Orthopedic repair of the fractures of the third and fourth digits and primary skin closure of the wound was performed. Infection and instability at the fracture sites resulted in pseudoarthrosis and a valgus deformity of the digits distal to the injury. The ultrasonic Doppler flow detector provided a simple noninvasive method for determining tissue viability in the severely traumatized foot of this dog.


Transcriptomic analysis of reduced sensitivity to praziquantel in Schistosoma mansoni.
Schistosomiasis is an intravascular parasitic infection estimated to affect over 206 million people, the majority of whom live in Africa where the trematode worms Schistosoma mansoni and Schistosoma haematobium are the major causative agents. While a number of drugs have been used to treat schistosomiasis, praziquantel (PZQ) is the only one that is widely available, relatively cheap, and easy to use. The reliance on a single drug for the treatment of such a prevalent disease is a cause for concern due to the potential for resistance to render PZQ ineffective. In this study, we examine the transcriptome of three generations of a laboratory strain of S. mansoni (PR1) whose susceptibility to PZQ has been diminished across 9 passages through exposure to increasing sub-lethal doses of the drug. Miracidial susceptibility was significantly reduced after exposure to 2 × 50 mg/Kg PZQ during the first passage. Susceptibility of worms in vivo was first assessed during passage 5 when mice infected with PZQ-selected schistosomes were dosed with a lethal dose of 3 × 300 mg/kg PZQ resulting in only a 10% reduction in worm number compared to control treatment. The emergence of reduced sensitivity was marked by a shift in sex ratio from a predominantly male to a female population, a reduction in the length of females and ultimately the loss of the PZQ-selected line after passage 9. Analysis of differentially regulated transcripts did not suggest that any particular gene product or pathway was associated with drug resistance suggesting either a loss of function mutation to a single gene or an epistatic interaction of multiple gene products as the underlying cause of reduced susceptibility.


Mini-column screening assay for tetracyclines in chicken.
A simple, rapid, reliable and economical mini-column (MC) method for the detection of tetracyclines (TCs) residues in chicken meat was developed. The method employs a commonly available Pasteur pipette which is tightly packed with silica gel and anhydrous sodium sulfate. Clean-up and detection of illegal levels can be achieved on the same column. Viewing the developed MC under an ultraviolet lamp revealed that TCs can be detected as a compact golden yellow fluorescent band at the junction between the anhydrous sodium sulfate and silica gel layers. Comparing the yellow band of control extracts with those fortified (100 ng ml(-1)) showed no overlap between analyte and impurities. The limit of detection (LOD) of the MC assay was 1 ng, indicating that the chicken sample containing 10 µg TCs kg(-1) sample could be easily detected. Moreover, the intensity of the yellow band increased whenever TCs levels in the extract increased. Evaluation utility of the method with blind samples as controls or samples fortified with total TCs at various levels indicated that the total blank and spiked samples at levels equal or below the permissible limits were assessed as accepted. The method can provide an alternative to microbial screening assays and could be used as an effective pre-screening technique in public health laboratories.


Simultaneous determination of benzene, toluene, ethylbenzene, and xylenes in urine by thermal desorption-gas chromatography.
The determination of metabolites of benzene, toluene, ethylbenzene, and xylenes in urine has been used to assess human exposure to these compounds. The analyses of urine samples for these metabolites are tedious and time consuming. The determination of unmetabolized individual compounds in urine has been studied previously with some success. A simultaneous determination of several unmetabolized VOC compounds in urine by thermal desorption-gas chromatography was conducted to assess the exposure of smokers and nonsmokers to these compounds. The method of thermal desorption-GC was sensitive enough to detect a significant difference in exposure levels due to the contribution of light smoking in the environmentally-exposed group.


Gas-phase formation of self-assembled monolayers on MgO for protection against hydration.
The gas-phase adsorption of octyltrichlorosilane onto MgO produces self-assembled monolayers that can provide protection against hydration of the underlying MgO surfaces. MgO thin film has attracted attention for application as a protecting layer of alternating current plasma display panel. On exposure to air, the clean MgO surface interacts with water and quickly hydrates to Mg(OH)2, which reduces the secondary electron emission yield. The gas-phase deposition of octyltrichlorosilane on the clean MgO has produced self-assembled monolayers because of high reactivity of the MgO surface. The ultra-thin organic layer of the octylsiloxane can provide significant protection against hydration to the MgO surface, and improves secondary electron emission yield for the MgO samples. The secondary electron emission coefficient y for the monolayer-coated MgO sample is about 25% higher than that for the clean MgO after 24 hr exposing to air.


Cooverexpression of alanine aminotransferase 1 in Chinese hamster ovary cells overexpressing taurine transporter further stimulates metabolism and enhances product yield.
Innovation in monoclonal antibody (mAb) production continues to be driven by cell engineering strategies to increase yield and improve product quality. In a previous study, to investigate the effectiveness of transporter overexpression strategies, we prepared a taurine transporter-overexpressing host cell line (DXB11/TAUT) that produced a higher proportion of high-mAb-titer strains than did the parent host cell line. In the current study, we selected a single DXB11/TAUT/mAb1 strain that remained viable for longer (up to 1 month) under common fed-batch culture conditions, and the improvement in viability could be attributed to its improved metabolic properties. It was also more productive (up to >100 pg/cell/day) and yielded more mAb1 (up to 8.1 g/L/31 days) than the parent cell line, and the mAb1 it produced was of comparable quality. These results suggested that this host cell engineering strategy has unique potential for the improvement of mAb-producing Chinese hamster ovary (CHO) cells; for example, it may be appropriate for high cell density perfusion culture. TAUT-overexpressing cell lines rapidly accumulated the byproduct alanine, and our challenge in the present study was to apply a strategy for modulating cell metabolism to utilize this byproduct to achieve a high mAb yield in a shorter culture period. To accomplish this, we genetically modified the DXB11/TAUT/mAb1 strain to cooverexpress alanine aminotransferase 1 (ALT1). The resulting DXB11/TAUT/mAb1/ALT1 cooverexpressing strain gave a higher mAb yield in a shorter culture period (5.9 g/L/14 days). It is usually difficult to drive the overexpression of two functional genes while balancing competing goals. However, forced cooverexpression of TAUT and ALT1 in our DXB11/TAUT/mAb1/ALT1 strain resulted in a higher proliferation than the DXB11/TAUT/mAb1 strain, with an ideal balance between cell viability and productivity. Therefore, we have demonstrated a strategy capable of achieving an optimum balance among the goals of cell viability, productivity, and proliferative capacity.


Glycerolipid metabolism and signaling in health and disease.
Maintenance of body temperature is achieved partly by modulating lipolysis by a network of complex regulatory mechanisms. Lipolysis is an integral part of the glycerolipid/free fatty acid (GL/FFA) cycle, which is the focus of this review, and we discuss the significance of this pathway in the regulation of many physiological processes besides thermogenesis. GL/FFA cycle is referred to as a "futile" cycle because it involves continuous formation and hydrolysis of GL with the release of heat, at the expense of ATP. However, we present evidence underscoring the "vital" cellular signaling roles of the GL/FFA cycle for many biological processes. Probably because of its importance in many cellular functions, GL/FFA cycling is under stringent control and is organized as several composite short substrate/product cycles where forward and backward reactions are catalyzed by separate enzymes. We believe that the renaissance of the GL/FFA cycle is timely, considering the emerging view that many of the neutral lipids are in fact key signaling molecules whose production is closely linked to GL/FFA cycling processes. The evidence supporting the view that alterations in GL/FFA cycling are involved in the pathogenesis of "fatal" conditions such as obesity, type 2 diabetes, and cancer is discussed. We also review the different enzymatic and transport steps that encompass the GL/FFA cycle leading to the generation of several metabolic signals possibly implicated in the regulation of biological processes ranging from energy homeostasis, insulin secretion and appetite control to aging and longevity. Finally, we present a perspective of the possible therapeutic implications of targeting this cycling.


Robot-assisted partial nephrectomy in patients with baseline chronic kidney disease: a multi-institutional propensity score-matched analysis.
Robot-assisted partial nephrectomy (RPN) in the setting of chronic kidney disease (CKD) presents additional challenges for the preservation of renal function. To evaluate functional outcomes of RPN in patients with CKD relative to patients undergoing RPN without baseline CKD. A total of 1197 consecutive patients who underwent RPN at five academic institutions between 2007 and 2012 were identified for this descriptive study. A total of 172 patients who underwent RPN with preexisting CKD (estimated glomerular filtration rate [eGFR] of 15-60 ml/min per 1.73 m(2)) were identified. Perioperative results of 121 patients were compared against propensity score-matched controls without CKD (eGFR ≥60 ml/min per 1.73 m(2)). RPN in patients with or without baseline CKD. Descriptive statistics and propensity score-matched operative and functional outcomes. After propensity score matching, patients with baseline CKD had a lower percentage eGFR decrease at first follow-up (-5.1 vs -10.9), which remained significant at a mean follow-up of 12.6 mo (-2.8 vs -9.1, p<0.05), and they had less CKD upstaging (11.8% vs 33.1%). CKD patients were less likely to be discharged in the first two postoperative days (39.7% vs 56.2%, p=0.006) and had a higher rate of surgical complications (21.5% vs 10.7%, p=0.007). The retrospective analysis was the main limitation of this study. RPN in patients with baseline CKD is associated with a smaller decrease in renal function compared with patients without baseline CKD, but a higher risk of surgical complications and a longer hospital stay.


Tendoachilles reconstruction and overlying skin cover with a peroneus brevis flap.
We report a post-traumatic case of tendoachilles injury with an overlying skin defect. Following debridement, tendon reconstruction was done by using vascularised peroneus brevis musculotendinous unit and proximal part of the same muscle provided the skin cover. Postoperative recovery was uneventful. At 2 years follow-up, he had a near-normal gait. The main advantage of this flap is not being only a local flap but also providing a vascularised tendon.


Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction.
The vascular endothelium maintains a relatively vasodilated state via the release of nitric oxide (NO), a process that could be disrupted by hyperhomocysteinaemia. Since endothelial dysfunction is associated with increased systemic vascular resistance that is the hallmark of sustained arterial hypertension, we hypothesised that in patients with both hypertension and coeliac disease with hyperhomocysteinaemia (via malabsorption of essential cofactors), treatment of the latter disease could improve blood pressure (BP) control. A single patient with proven sustained hypertension and newly-diagnosed coeliac disease had baseline and post-treatment BP and endothelial function assessed by ambulatory BP monitoring (ABPM) and brachial artery forearm occlusion plethysmography respectively. This 49 year-old woman had uncomplicated sustained hypertension proven on repeated ABPM carried out 6 weeks apart (daytime mean 151/92 mm Hg and 155/95 mm Hg), and sub-clinical coeliac disease (gluten-sensitive enteropathy). Initial assessments revealed raised homocysteine levels with low normal vitamin B(12) level. It was likely that she had impaired absorption of essential cofactors for normal homocysteine metabolism. She adhered to a gluten-free diet and was give oral iron, folate and B(6) supplementations as well as B(12) injections for 3 months. Her BP had improved by 6 months and normalised by 15 months (daytime ABPM mean 128/80 mm Hg). There was parallel restoration of normal endothelial function with normalisation of her homocysteine levels. These observations suggest that sub-clinical coeliac disease related hyperhomocysteinaemia might cause endothelial dysfunction, potentially giving rise to a reversible form of hypertension. In addition, this case study supports the notion that irrespective of aetiology, endothelial dysfunction may be the precursor of hypertension. This highlights the need to resolve co-existing vascular risk factors in patients with hypertension.


Material-Dependent Effect of Common Printing Parameters on Residual Stress and Warpage Deformation in 3D Printing: A Comprehensive Finite Element Analysis Study.
Additive manufacturing (AM), commonly known as 3D printing, has gained significant popularity for its ability to produce intricate parts with high precision. However, the presence of residual stresses and warpage deformation are common issues affecting the quality and functionality of 3D-printed parts. This study conducts a comprehensive finite element analysis (FEA) to investigate the material-dependent impact of key printing parameters on residual stress and warpage deformation in 3D printing. The research focuses on three distinct materials: polyetherimide (PEI), acrylonitrile butadiene styrene (ABS), and polyamide 6 (PA6). Various printing parameters are systematically varied, including printing temperature, printing speed, bed temperature, infill density, layer thickness, and infill pattern. The study employs the Taguchi L27 orthogonal array and employs the analysis of variance (ANOVA) statistical technique to assess the significance of the input parameters. The obtained results reveal that certain parameters exhibit a greater sensitivity to material differences, whereas the layer thickness parameter demonstrates a relatively lower sensitivity. Notably, infill density and printing temperature play a crucial role in reducing residual stress for PA6, while the infill pattern parameter proves to be a significant contributor to minimizing warpage deformation across all three materials. These findings underscore the importance of conducting material-specific analyses to optimize 3D printing parameters and achieve the desired quality outcomes while mitigating residual stress and warpage deformation.


Evaluation of in vitro culture conditions to demonstrate pregnancy-dependent changes in luteal function in the pig.
This study was designed to evaluate the most effective in vitro culture conditions for study of pregnancy-dependent changes in LH-stimulated steroidogenesis in porcine luteal tissue. Mixed luteal cells recovered from the CL of cyclic (Day 12) and pregnant (Day 12 and 16) pigs were incubated either in Eagle's minimum essential medium (MEM) or in MEM supplemented with different concentrations of porcine or calf serum or BSA, or were incubated in a defined medium (DM) containing 2 micrograms/ml insulin, 40 ng/ml hydrocortisone, 5 micrograms/ml transferrin, and 10(-7) M thyroxine. Cultures were treated with various doses of porcine LH (0.1, 1, 10, 100 ng/ml). Additionally, large and small luteal cells of Day 12 cyclic and pregnant pigs were incubated for 4 h in medium 199 supplemented with 2% porcine serum in the absence or presence of various concentrations of LH. Overall, progesterone production by the luteal cells of Day 12 pregnant pigs was significantly (p < 0.05) higher than that by cells of the cyclic pigs. However, the luteal cells of pregnant Day 16 pigs released significantly (p < 0.05) less progesterone than the other groups. LH had a stimulatory effect (p < 0.001) on progesterone release by mixed luteal cells that was independent of the type of medium supplementation or reproductive status. Porcine serum, calf serum, and BSA (p < 0.001, p < 0.001, and p < 0.05, respectively) also stimulated progesterone production. However, the doses of porcine and calf serum or BSA that stimulated progesterone release were dependent on the reproductive status of the pig.(ABSTRACT TRUNCATED AT 250 WORDS)


Construction and performance test of SGM-TRAIN at UVSOR.
A new spherical-grating monochromator with translational and rotational assembly including a normal-incidence mount (SGM-TRAIN) has been constructed at BL5A of the UVSOR facility. The SGM-TRAIN is an advanced version of a constant-length SGM with the following improvements: (i) a wide energy range of 5-250 eV; (ii) a high resolving power; (iii) use of linear and circular polarization; (iv) reduction of second-order light; (v) two computer-controlled driving modes. Part of the performance tests are reported along with a detailed description of the design.


Improving outcomes in diabetes in pregnancy.
One in 250 pregnancies in the UK involves diabetes. The majority of cases (87.5%) are gestational diabetes, 7.5% are type 1 and 5% are type 2 diabetes. Diabetes in pregnancy is associated with a five fold increase in risk of stillbirth and a two-fold increased risk of congenital defects compared with the general maternity population. Fasting blood glucose levels above 5.3 mmol/L can directly affect organogenesis, particularly of the fetal heart and spine. Hyperglycaemia can cause placental failure and stillbirth and for this reason early delivery is recommended. For women with pre-existing diabetes good blood glucose control prior to conception can minimise pregnancy risks towards levels approaching that of women without diabetes. The recommended glycated haemoglobin (HbA(1c)) target in preparation for pregnancy is 48 mmol/mol (6.5%) if this can be safely achieved. Women with an HbA(1c) 86 mmol/mol should be strongly advised against pregnancy. In normal pregnancy, the increased insulin resistance mediated by placental hormone secretion is compensated by increased maternal insulin secretion to maintain euglycaemia. Gestational diabetes arises from an inability to meet these increased insulin requirements adequately. Lifestyle modification with input from a specialist diabetes dietician is key to the management of gestational diabetes. Women with gestational diabetes have a significant lifetime risk of developing type 2 diabetes, hence diabetes screening must be undertaken on an annual basis in primary care.


[Effectiveness of virtual immersion programmes in patients with Parkinson's disease. A systematic review].
Parkinson disease (PD) is the second most common neurodegenerative disease. Virtual reality (VR) is being used in rehabilitation of neurological patients. To analyze the VR systems' therapeutically effectiveness through PD diagnosed subjects with variables of motor, quality of life and cognition. Electronics database were used to look for articles: Medline, EMBASE, PEDro, CINAHL and Cochrane. The inclusion criteria were: randomized control trial (RCT) performed in PD with at least one VR variable included in the therapeutically treatment and diagnosed PD subjects. Four RCT were chosen showing all good methodology quality. Concordance between evaluators was moderate-high. VR was the main treatment in all of them. VR was more effective in balance improvement in PD subjects than conventional physiotherapy in two RCT. VR was not more effective in balance improvement in PD subjects than conventional physiotherapy in two RCT. Contradictory evidences where showed between the effectiveness of the VR programs versus conventional programs in the effectiveness of balance treatment with PD subjects. Non-motor variables improvement was not greater in subjects with VR treatments versus the ones with conventional physiotherapy in the four RCT. The treatments with VR cannot be assumed as more effectives than conventional physiotherapy through PD subjects in motor and psychosocial variables.


Early motor development and cognitive abilities among Mexican preschoolers.
Psychomotricity plays a very important role in children's development, especially for learning involving reading-writing and mathematical calculations. Evaluate motor development in children 3 years old and its relationship with their cognitive abilities at the age of 5 years. Based on a cohort study, we analyzed the information about motor performance evaluated at 3 years old by Peabody Motor Scale and cognitive abilities at 5 years old. The association was estimated using linear regression models adjusted by mother's intelligence quotient, sex, Bayley mental development index at 18 months, and quality of the environment at home (HOME scale). 148 children whose motor performance was determined at age 3 and was evaluated later at age 5 to determine their cognitive abilities. Cognitive abilities (verbal, quantitative, and memory) measured by McCarthy Scales. Significant positive associations were observed between stationary balance at age 3 with verbal abilities (β = 0.67, p = .04) and memory (β = 0.81, p = .02) at 5 years. Grasping and visual-motor integration were significant and positively associated with quantitative abilities (β = 0.74, p = .005; β = 0.61, p = .01) and memory (β = 2.11, p = .001; β = 1.74, p = .004). The results suggest that early motor performance contributes to the establishment of cognitive abilities at 5 years. Evaluation and early motor stimulation before the child is faced with formal learning likely helps to create neuronal networks that facilitate the acquisition of academic knowledge.


Inappropriate discharges by the implantable cardioverter defibrillator during postoperative testing: implications for intraoperative assessment.
Inappropriate shocks were delivered to a patient while in sinus rhythm by an implantable cardioverter defibrillator (ICD) during routine prehospital discharge testing. This was induced by the standard programmer when the "read" telemetry sequence was initiated. The ICD was removed and found to suffer from electrical artifact that was sensed as ventricular tachycardia during telemetry. To avoid inadvertent telemetry-induced shocks during routine testing, all ICDs should be interrogated, using a standard programmer, intraoperatively, with the unit in "defibrillation on" mode.


Blockage of MLKL prevents myelin damage in experimental diabetic neuropathy.
SignificanceDiabetic neuropathy is a commonly occurring complication of diabetes that affects hundreds of millions of patients worldwide. Patients suffering from diabetic neuropathy experience abnormal sensations and have damage in their peripheral nerve axons as well as myelin, a tightly packed Schwann cell sheath that wraps around axons to provide insulation and increases electrical conductivity along the nerve fibers. The molecular events underlying myelin damage in diabetic neuropathy are largely unknown, and there is no efficacious treatment for the disease. The current study, using a diabetic mouse model and human patient nerve samples, uncovered a molecular mechanism underlying myelin sheath damage in diabetic neuropathy and provides a potential treatment strategy for the disease.


[Antidepressants in oncology: issues and clinical perspectives].
Antidepressants in oncology offer a wide range of applications in everyday supportive care while at the same time, they are often not well known by oncologists. Several recent studies suggest that depressive disorders have a negative impact on the overall survival in oncology. The care of the depressed patient in oncology would therefore request early detection prior to adapted drug treatment and psychotherapy interventions. This requires better knowledge of antidepressants whose effectiveness has been demonstrated in severe major depression. The use of antidepressants should also be part of the therapeutic armaments in the treatment of pain and hot flushes. However, their effectiveness in improving minor depressive disorders and cancer-related fatigue has not been proved yet.


The vocabulary of beginning writers: implications for children with complex communication needs.
One of the greatest challenges facing augmentative and alternative communication (AAC) professionals is providing children with complex communication needs with access to the vocabulary that they need in order to develop mature language and literacy abilities. The purpose of this study was to analyze the vocabulary used by typically developing early-elementary children in the United States and New Zealand when they write about self-selected topics, in order to inform practices with children with complex communication needs. The children's writing samples were compared across school ages and countries. The school age comparisons highlighted the relatively restricted range of vocabulary used by children in the earliest stages of writing development, and the country comparisons revealed differences in core vocabulary. The findings of this study hopefully will assist AAC professionals as they engage in selecting, prioritizing, and organizing vocabulary to support written language development in children with complex communication needs.


PERSPECTIVE: A CRITIQUE OF SEWALL WRIGHT'S SHIFTING BALANCE THEORY OF EVOLUTION.
We evaluate Sewall Wright's three-phase "shifting balance" theory of evolution, examining both the theoretical issues and the relevant data from nature and the laboratory. We conclude that while phases I and II of Wright's theory (the movement of populations from one "adaptive peak" to another via drift and selection) can occur under some conditions, genetic drift is often unnecessary for movement between peaks. Phase III of the shifting balance, in which adaptations spread from particular populations to the entire species, faces two major theoretical obstacles: (1) unlike adaptations favored by simple directional selection, adaptations whose fixation requires some genetic drift are often prevented from spreading by barriers to gene flow; and (2) it is difficult to assemble complex adaptations whose constituent parts arise via peak shifts in different demes. Our review of the data from nature shows that although there is some evidence for individual phases of the shifting balance process, there are few empirical observations explained better by Wright's three-phase mechanism than by simple mass selection. Similarly, artificial selection experiments fail to show that selection in subdivided populations produces greater response than does mass selection in large populations. The complexity of the shifting balance process and the difficulty of establishing that adaptive valleys have been crossed by genetic drift make it impossible to test Wright's claim that adaptations commonly originate by this process. In view of these problems, it seems unreasonable to consider the shifting balance process as an important explanation for the evolution of adaptations.


Joint effects of monomer and stabilizer concentrations on physico-chemical characteristics of poly(butyl 2-cyanoacrylate) nanoparticles.
A rotatable central composite design was applied to the formulation of poly(butyl 2-cyanoacrylate) nanoparticles with the aim of modifying some physico-chemical properties of these carriers in a controlled way. The joint effect of stabilizer concentration and monomer concentration on the mean particle size, on the electrophoretic mobility and on the polymer molecular weight has been investigated. The results demonstrate that the particle size is only dependent on the stabilizer concentration, nevertheless the electrophoretic mobility and the molecular weight distribution were affected simultaneously by the monomer and the stabilizer concentrations. Moreover, using the response surface diagrams it is possible to deduce the experimental conditions to design particles with the desired properties. Finally, the degradation rates for two different molecular weight formulations were compared, showing the relevance of this property.


D-penicillamine capped cadmium telluride quantum dots as a novel fluorometric sensor of copper(II).
D-penicillamine-capped cadmium telluride quantum dots (DPA-capped CdTe QDs) were synthesized as the new fluorescent semiconductor nanocrystal in aqueous solution. Fourier transmission infrared spectroscopy, X-ray diffraction, transmission electron microscopy, ultraviolet-visible and photoluminescence spectroscopy were used for characterization of the QDs. Based on the quenching effect of Cu(2+) ions on the fluorescence intensity of DPA-capped CdTe QDs, a new fluorometric sensor for copper(II) detection was developed that showed good linearity over the concentration range 5 × 10(-9)-3 × 10(-6) M with the detection limit 0.4 × 10(-9) M. Owing to the strong affinity of the DPA to copper(II), the sensor showed appropriate selectivity for copper(II) compared with conventional QDs. The DPA-capped CdTe QDs was successfully applied for determination of Cu(2+) concentration in river, well and tap waters with satisfactory results.


Efficiency of low-contrast detail detectability in fluoroscopic imaging.
The detectability of a static low-contrast detail in the dynamic fluoroscopic image of a homogeneous phantom was assessed by physical measurement of the signal-to-noise ratio (SNR) and by psychophysical measurement of the human observer detectability index d'. The two-alternative forced-choice method was used for human observer tests. The image data consisted of digitally recorded fluoroscopic image sequences which were displayed in a continuous loop of varying length (1-50 frames) at a rate of 25 frames/s. Human detection performance was seen to improve with the SNR in all cases studied: when the signal was made stronger, the image noise lower, or when the SNR in the image sequence was made higher by increasing the length of the image sequence. The results imply that the statistical efficiency of humans decreases slowly when the number of frames in the displayed loop is increased. This decrease of efficiency with loop length was not seen in all test series, however, and it is possible that the phenomenon is partly related to the high d' values found at the greatest loop lengths studied. When the display contrast was high, the statistical efficiency of the human observer was 30%-40% for both static and dynamic images. The efficiency was somewhat lower, 15%-25%, for images that were displayed with a display contrast gain setting more typical of fluoroscopy. The accumulation rate of SNR2 is a suitable quantity for the measurement of fluoroscopic image quality as related to a given static signal detection task. In contrast to this, visibility measurement by determination of the threshold contrast was seen to be unacceptably imprecise if the test is based on only one observer's opinion, as is often the case in practical quality assurance testing. The precision of the threshold contrast measurement could, however, be improved by using several observers and test objects with a smaller step between details than is usual.


Temporal change in Syndecan-1 as a therapeutic target and a biomarker for the severity classification of COVID-19.
Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microembolism or microvascular endothelial injuries. Here, we report that syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury. We analyzed the data of COVID-19 patients for 1 year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with SDC-1 by ELISA. We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P = 0.032, P < 0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, d-dimer, ISTH score; P = 0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p < 0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P = 0.009 and P < 0.0001, respectively). Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.


Noncognitive symptoms in Alzheimer disease and caregivers distress in Chile.
This study describes the profile of noncognitive symptoms in Chilean AD patients and its effects on the caregiver's mental health. In a sample of 26 urban dwelling AD patients, 21 of them women, age range 63-90 years, diagnosed using NINCDS-ADRDA, the intensity and frequency of noncognitive symptoms and caregivers distress was assessed using NPI. Seventeen caregivers were first degree relatives. The most prevalent symptoms were apathy, irritability, and anxiety. The least were euphoria, hallucinations, and disinhibition. The most stressful conditions were disinhibition and agitation: the best well-tolerated were euphoria and anxiety. Caregivers responded most frequently with feelings of concern and depression. Few of them reported to be ashamed. These results may reflect cultural differences and represents the first description of this reality in Chile.


Medication consultation and split treatment during psychotherapy.
In split treatment a patient simultaneously sees both a psychotherapist and a pharmacotherapist. Research indicates that medication and psychotherapy have additive value when used together in the treatment of depression and probably in other disorders as well. However, little is known about the presumably common technique of separate therapists administering these treatments. Complex interpersonal issues arise, reflecting both ideological and transferential attitudes toward medication as well as the intricacies of triangular relationships. Establishing a three-way therapeutic alliance, awareness of competitive countertransference feelings, and recognition of covert issues other than medication in the request for consultation are examples of areas where special attention can help the treatment succeed.


A curcumin-based molecular probe for near-infrared fluorescence imaging of tau fibrils in Alzheimer's disease.
In recent years, there has been growing interest in the near-infrared (NIR) fluorescence imaging of tau fibrils for the early diagnosis of Alzheimer's disease (AD). In order to develop a curcumin-based NIR fluorescent probe for tau fibrils, structural modification of the curcumin scaffold was attempted by combining the following rationales: the curcumin derivative should preserve its binding affinity to tau fibrils, and, upon binding to tau fibrils, the probe should show favorable fluorescence properties. To meet these requirements, we designed a novel curcumin scaffold with various aromatic substituents. Among the series, the curcumin derivative with a (4-dimethylamino-2,6-dimethoxy)phenyl moiety showed a significant change in its fluorescence properties (22.9-fold increase in quantum yield; Kd, 0.77 μM; λem, 620 nm; Φ, 0.32) after binding to tau fibrils. In addition, fluorescence imaging of tau-green fluorescent protein-transfected SHSY-5Y cells with confirmed that detected tau fibrils in live cells.


Synchrotron radiation - early history.
The scientific history of the work that led to the prediction and observation of synchrotron radiation goes back more than a century. This paper is a summary of that history.


Spectral properties of networks with community structure.
In this paper, we discuss the eigenspectra of networks with community structure. It is shown that in many cases, the spectrum of eigenvalues of the adjacency matrix of a network with community structure gives a clear indication of the number of communities in the network. In particular, for a network with N nodes and N_(c) communities, there will typically be N_(c) eigenvalues that are significantly larger than the magnitudes of all the other (N-N_(c)) eigenvalues. We discuss this property as well as its use and limitations for determining N_(c) .


Percutaneous treatment of an injured coronary stent using the looping wire technique.
Drug-eluting stent implantation is an effective treatment for coronary artery disease, yet unexpected serious complications during stent implantation are possible. A 70-year-old man with unstable angina presented with a left main bifurcation lesion. Two drug-eluting stents were successfully deployed at the left main bifurcation lesion by the mini-crush technique under intravascular ultrasound guidance. However, after removal of the wire and intravascular ultrasound catheter, the stent of the proximal left circumflex artery was damaged and shortened at the distal edge. We used a looping wire technique to cross the injured stent and we successfully re-dilated the damaged portion of the stent. Finally, we deployed an additional drug-eluting stent at the left circumflex artery over the damaged stent. Our case illustrates the importance of gentle handling of devices during coronary intervention. Furthermore, interventionists should keep in mind the role of intravascular ultrasound when treating this kind of serious complication.


A general palladium-catalyzed method for alkylation of heteroarenes using secondary and tertiary alkyl halides.
A general alkylation of heterocycles using a simple palladium catalyst is reported. Most classes of heterocycles, including indoles and pyridines, efficiently coupled with unactivated secondary and tertiary alkyl halides. An alkyl radical addition to neutral heteroarenes is most likely involved.


Children with reading disorder show modality independent brain abnormalities during semantic tasks.
Neuroimaging studies have suggested that left inferior frontal gyrus, left inferior parietal lobule and left middle temporal gyrus are critical for semantic processing in normal children. The goal of the present functional magnetic resonance imaging (fMRI) study was to determine whether these regions are systematically related to semantic processing in children (9- to 15-year-old) diagnosed with reading disorders (RD). Semantic judgments required participants to indicate whether two words were related in meaning. The strength of semantic association varied continuously from higher association pairs (e.g., king-queen) to lower association pairs (e.g. net-ship). We found that the correlation between association strength and activation was significantly weaker for RD children compared to controls in left middle temporal gyrus and left inferior parietal lobule for both the auditory and the visual modalities and in left inferior frontal gyrus for the visual modality. These results suggest that the RD children have abnormalities in semantic search/retrieval in the inferior frontal gyrus, integration of semantic information in the inferior parietal lobule and semantic lexical representations in the middle temporal gyrus. These deficits appear to be general to the semantic system and independent of modality.


Serum anti-Staphylococcus pseudintermedius IgE and IgG antibodies in dogs with atopic dermatitis and nonatopic dogs.
Dogs and humans with atopic dermatitis (AD) are predisposed to colonization and recurrent infection with Staphylococcus spp. Studies in humans suggest that staphylococcus-specific immunoglobulin E (IgE) plays a key role in disease pathogenesis. Few such studies have been undertaken in dogs. The aim of this study was to compare levels of staphylococcus-specific IgE and immunoglobulin G (IgG) in dogs with AD, nonatopic dogs with staphylococcal pyoderma, and nonatopic and noninfected control dogs. Sera were collected from 108 dogs with AD, 39 nonatopic dogs with staphylococcal pyoderma secondary to different underlying conditions, 67 age-matched nonatopic control dogs, and nine control dogs reared in minimal disease conditions. Serum Staphylococcus pseudintermedius-specific IgE and IgG antibodies were measured by enzyme-linked immunosorbent assay. Dogs with AD had significantly higher levels of anti-staphylococcal IgE than nonatopic dogs with staphylococcal pyoderma and the two groups of control dogs. Levels of anti-staphylococcal IgG were significantly higher in atopic dogs and nonatopic dogs with pyoderma compared with nonatopic control dogs and control dogs reared in minimal disease conditions, but there was no significant difference in levels of anti-staphylococcal IgG between dogs with AD and nonatopic dogs with pyoderma. A significantly increased IgE response to S. pseudintermedius antigens in atopic dogs suggests an immunopathogenic role for anti-staphylococcal IgE. The finding of elevated IgE and IgG in atopic dogs is also important as a prelude to studies on antigenic specificity and possible correlations with disease phenotype.


[Randomly discovered enlargement in the region of sella turcica].
Computer tomography (CT) and magnetic resonance imaging (MRI) quite often detect unexpected cases of enlargement in the hypothalamus-hypophysial region, without the above methods being indicated for clinical manifested symptomatology provoked by the tumour. This is not surprising if we consider that autopsies show the presence of hypophysial adenomas of 10-15% of population on an average. X ray, CT or MRI are indicated in the case of head traumas, lateral nasal cavity inflammations, headaches, strokes, neurological diseases and other disorders. A number of tumours of diverse etiology occur in the hypothalamus-hypophysial region, but hypophysial adenomas are by far the most frequent among all (above 90 %). Among other primary enlargements, the most frequent are craniopharyngeomas and meningeomas, while other enlargements are by fare less common. Such randomly detected tumours are mostly asymptomatic, but targeted anamnesis may show some of the symptoms quite clearly. The symptomatology can be linked with possible slight hormonal overproduction of hypophysial adenomas, a deficit of hypophysial hormones or local manifestations of expansion. Exact assessment of MRI results, of hormonal activity of the enlargement, of the relation to surrounding structures, especially the optic nerves, and the assessment of hypophysial functions are important for the therapeutic decision. Depending on the type and extension of the tumour the options considered are pharmacotherapy (the treatment of choice in the case of prolactinomas), surgery, radiotherapy (today prevailingly using the gamma knife), and if no intervention is necessary, follow up with regular MRI examinations. Tumorous growth is more often observed in "macroadenomas" than in "microadenomas" (up to 10 mm).


Porous acrylic cement: evaluation of a novel implant material.
The preparation and some properties of in situ curing porous acrylic cement, a modification of the traditional bone cement, are described. Through numerous animal experiments, the behavior of the porous cement in a biological environment has been studied. The histological evaluation reveals that hard and soft tissues readily grow into the pores of the cement, thus anchoring the implant to the host tissues. Some inflammatory foci, decreasing in number with residence time, together with varying numbers of multinucleated giant cells were found occasionally in the tissues in and around implants. When implanted in soft tissues, the porous cement behaved favorably with respect to solid acrylic implants because of the immobility of the implants and the absence of ectopic hard tissue formation. The biocompatibility of porous acrylic cement is judged to justify clinical trials in plastic and reconstructive surgery.


Up-regulation of urokinase plasminogen activator messenger ribonucleic acid and protein in hen granulosa cells by transforming growth factor alpha in vitro during follicular development.
The aim of the present study was to examine the regulatory role of transforming growth factor alpha (TGF alpha) on urokinase plasminogen activator (uPA) gene expression and protein levels in hen granulosa cells from different stages of ovarian follicular development in vitro. Granulosa cells from the first (F1), the second and third (F2-3), and the fourth, fifth, and sixth (F4-6) largest preovulatory follicles were cultured for 21 h in the absence and presence of TGF alpha (10 ng/ml). The uPA mRNA abundance and protein content were determined by Northern and Western blot analysis, respectively. Cell-associated and secreted PA activity was measured by a fibrinolysis assay and characterized by zymography. Hen granulosa cells produce a uPA with a molecular mass of about 35 kDa and a transcript size of approximately 2.5 kb. Basal uPA mRNA abundance, protein content, and activity were highest in granulosa cells from F4-6 follicles and decreased with follicular maturation. Granulosa cell uPA mRNA levels, protein content, and activity were increased in the presence of TGF alpha, reaching maximal levels in granulosa cells from less mature follicles, although the percentage of stimulation was higher in cells from late stages of follicular development. These findings clearly demonstrate specific expression of uPA in proliferatively active granulosa cells and responsiveness of uPA to TGF alpha at both transcriptional and translational levels. They support the concept that PA of the urokinase type plays an important role in extracellular matrix remodeling during TGF alpha-induced granulosa cell proliferation and ovarian follicular growth.


The G1-S checkpoint in fission yeast is not a general DNA damage checkpoint.
Inhibitory mechanisms called checkpoints regulate progression of the cell cycle in the presence of DNA damage or when a previous cell-cycle event is not finished. In fission yeast exposed to ultraviolet light the G1-S transition is regulated by a novel checkpoint that depends on the Gcn2 kinase. The molecular mechanisms involved in checkpoint induction and maintenance are not known. Here we characterise the checkpoint further by exposing the cells to a variety of DNA-damaging agents. Exposure to methyl methane sulphonate and hydrogen peroxide induce phosphorylation of eIF2alpha, a known Gcn2 target, and an arrest in G1 phase. By contrast, exposure to psoralen plus long-wavelength ultraviolet light, inducing DNA adducts and crosslinks, or to ionizing radiation induce neither eIF2alpha phosphorylation nor a cell-cycle delay. We conclude that the G1-S checkpoint is not a general DNA-damage checkpoint, in contrast to the one operating at the G2-M transition. The tight correlation between eIF2alpha phosphorylation and the presence of a G1-phase delay suggests that eIF2alpha phosphorylation is required for checkpoint induction. The implications for checkpoint signalling are discussed.


Functional motor innervation of brachial plexus roots. An intraoperative electrophysiological study.
The electrophysiological properties of the normal brachial plexus and functional motor innervation were examined during the operation of transfer of contralateral C7 transfer from the healthy side. Different roots of the brachial plexus were stimulated and maximum amplitudes were recorded. The results showed that functional motor innervation of brachial plexus roots were: C5 mainly forms the axillary nerve to innervate the deltoid muscle; C6 mainly forms the musculocutaneous nerve to innervate biceps; C7 mainly forms the radial nerve to innervate triceps; C8 mainly forms the median nerve to innervate flexor digitorum superficialis and profundus; and T1 mainly forms the ulnar nerve to innervate the intrinsic muscles of the hand.


High performance self-powered photodetector based on van der Waals heterojunction.
Self-powered photodetectors that do not require external power support are expected to play a key role in future photodetectors due to their low power characteristics, but achieving high responsivity remains a challenge. 2D van der Waals heterojunctions are a promising technology for high-performance self-powered photodetectors due to their excellent optical and electrical properties. Here, we fabricate a self-powered photodetector based on In2Se3/WSe2/ReS2van der Waals heterojunction self-powered photodetector. Due to the presence of ReS2layer, photocurrent is enhanced as a result of the increase in light absorption efficiency and the effective region for generating photogenerated carriers. The built-in electric field is enhanced by a negative 'back-gate voltage' along the p-n junction vertical direction generated by the electrons in the photo-generated electrons accumulation layer. Accordingly, the optical responsivity and the photoresponse speed of this heterojunction self-powered photodetector are greatly boosted. The proposed self-powered photodetector based on the In2Se3/WSe2/ReS2heterojunction exhibits a high responsivity of 438 mA W-1, which is 17 times higher compared to the In2Se3/WSe2photodetector, a self-powered current (1.1 nA) that is an order of magnitude higher than that of the In2Se3/WSe2photodetector, and a fast response time that is 250% faster. Thus the self-powered photodetector with a stronger built-in electric field and a wider depletion zone can provide a new technological support for the fabrication of high responsivity, low power consumption and high speed self-powered photodetectors based on van der Waals heterojunctions.


[Interstrain differences in changes in 5-nucleotidase activity in mouse macrophages in response to immunostimulation].
The effect of immunostimulants on the activity of 5-nucleotidase in the macrophages of peritoneal exudate (MPE) has been investigated in mice of various strains. It has been demonstrated that in case of subcutaneous introduction of immunostimulants interstrain differences might be observed in the changes of MPE 5-nucleotidase activity. The decrease in the enzymatic activity in MPE was found to be the most pronounced in C57Bl/6 mice, while in AKR mice it was the least marked. CBA and C3 mice revealed no changes in MPE 5-nucleotidase activity in response to immunostimulation.


[Significance of Chlamydia trachomatis for female fertility with special reference to prevalence in the endometrium].
144 patients with longstanding infertility (mean duration of infertility 4.9 years) were screened for endometrial infection with Chlamydia trachomatis by means of endometrial biopsy and McCoy cell-culture. The same day blood was taken for detection of Chlamydia IgG antibodies in serum samples. During a 1 year's period, all new patients of a large infertility clinic without complaints or clinical symptoms of infection of the lower genital tract were consecutively submitted to the study. Elevated titers of IgG antibodies in serum samples (Chlam. AB greater than or equal to 1/256) revealed previous chlamydial infection of 26% of patients, but Chlamydia trachomatis was detected in endometrial biopsies in only 5/144 (3.5%). There was a strong correlation of previous chlamydial infection and reduced tubal patency (p 0.001) and a lower pregnancy rate after 6 months. The results suggested that infections with Chlamydia trachomatis, influenced by demographic and socio-economic aspects, are of minor importance as an actual infection in asymptomatic patients with longstanding infertility. Previous chlamydial infections, however, are of great importance because of their negative influence on tubal function.


Role of estradiol in the rise in follicle-stimulating hormone levels during the luteal-follicular transition.
Follicular recruitment takes place under FSH stimulation at the end of the luteal phase and the beginning of the subsequent follicular phase, the so-called luteal-follicular transition (LFT). Inhibin, a known suppressor of FSH, has been implicated in the onset of the rise in FSH levels, as the fall in its immunoreactive plasma levels after the demise of the corpus luteum has been shown to correlate negatively with the increase in FSH. To analyze the role of estradiol (E2), another inhibitor of FSH secretion in the LFT, we designed an experimental paradigm to dissociate the physiological falls in inhibin and E2. This was achieved by extending the duration of luteal plasma E2 levels with transdermal E2 treatment. Untreated ovulatory cycles in seven healthy female volunteers, aged 28-38 yr, were compared with E2-treated cycles in the same subjects, with treatment starting on the 10th day after the LH surge and continuing through the 4th day of the following menses [either 0.2 mg (n = 6; G1) or 0.1 mg (n = 6; G2) E2 daily]. Blood samples were obtained daily from the LH surge until the 11th day of the next cycle. Immunoreactive plasma inhibin levels reached a nadir on day 2 of menses regardless of whether women received E2. Plasma E2 (mean +/- SEM) levels remained within the normal luteal range (220 +/- 51 to 635 +/- 279 pmol/L) until the end of the treatment period in G2 (range, 253 +/- 40 to 382 +/- 62 pmol/L), but not in G1 (range, 598 +/- 195 to 1835 +/- 1259 pmol/L). However, the onset of the FSH rise was clearly delayed, from a mean of 2 days before menstruation in the controls to day 4 of the cycle in G1 and G2. Peak plasma FSH levels were attained within 6 days in the controls and within 2 or 3 days in both treatment periods. Our data suggest that it is the decrease in plasma E2 rather than inhibin that is the triggering signal for the LFT rise in plasma FSH. The exact roles of inhibin and other gonadal proteins (e.g. activins) in follicular recruitment remain to be determined.


Expanding biological activities of Ts19 Frag-II toxin: Insights into IL-17 production.
Tityus serrulatus (Ts) venom is composed of a mixture of toxins presenting diverse biological functions. However, although this venom has been studied over the past three decades, omics analysis revealed that most of its toxins are not identified or their biological activities are unknown. Ts19 Frag-II is included in this group, which function is still uncertain. This study aimed to expand the biological activities of Ts19 Frag-II through in vivo investigation. Our results demonstrates that mice challenged with Ts19 Frag-II presented biochemical alterations, increasing serum levels of urea, ALT and β-globulin, besides decreasing γ-globulins. Moreover, this toxin was also able to induce immunological alterations, increasing NO, IL-6, TNF-α and IL-17, being considered a proinflammatory toxin. The increase of IL-17 was unprecedented regarding Ts toxins and could be a result of the overall produced-effect of cells of innate immunity cells (neutrophils, monocytes, natural killers and lymphoid tissue inducers - LTis) as well as of adaptive immunity (Th17 cells). This study expanded the biological activities of Ts19 Frag-II, suggesting that this toxin could be contributing to the Ts envenoming through alterations of biochemical parameters as well as triggering the inflammatory response.


Real-time classification of auditory sentences using evoked cortical activity in humans.
Recent research has characterized the anatomical and functional basis of speech perception in the human auditory cortex. These advances have made it possible to decode speech information from activity in brain regions like the superior temporal gyrus, but no published work has demonstrated this ability in real-time, which is necessary for neuroprosthetic brain-computer interfaces. Here, we introduce a real-time neural speech recognition (rtNSR) software package, which was used to classify spoken input from high-resolution electrocorticography signals in real-time. We tested the system with two human subjects implanted with electrode arrays over the lateral brain surface. Subjects listened to multiple repetitions of ten sentences, and rtNSR classified what was heard in real-time from neural activity patterns using direct sentence-level and HMM-based phoneme-level classification schemes. We observed single-trial sentence classification accuracies of [Formula: see text] or higher for each subject with less than 7 minutes of training data, demonstrating the ability of rtNSR to use cortical recordings to perform accurate real-time speech decoding in a limited vocabulary setting. Further development and testing of the package with different speech paradigms could influence the design of future speech neuroprosthetic applications.


A prospective study of reproductive and menstrual factors and colon cancer risk in Japanese women: findings from the JACC study.
The effects of reproductive factors on the etiology of colon cancer in Asian populations remain unexplored. So we examined 38,420 Japanese women aged 40-79 years who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During an average 7.6 years of follow-up, we documented 207 incident colon cancers. Multivariate analysis indicated that colon cancer risk was likely to be lower among parous women than among nulliparous. Women who had two abortions or more had a 72% higher risk of developing colon cancer [relative risk (RR) 1.72; 95% confidence interval (CI) 1.16-2.55; trend P < 0.01] compared with women who never had an abortion. The RR of colon cancer among postmenopausal women significantly decreased with increasing age at menarche (trend P = 0.01). No apparent association between colon cancer and gravida, age at first birth, age at menopause, or duration of menstruation was seen. These prospective data support the hypothesis that female reproductive events modify colon cancer risk, and suggest that reproductive factors, particularly age at menarche and having an abortion, may be of importance in the etiology of colon cancer among Japanese women.


Genetics and Epigenetics of Gastroenteropancreatic Neuroendocrine Neoplasms.
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are heterogeneous regarding site of origin, biological behavior, and malignant potential. There has been a rapid increase in data publication during the last 10 years, mainly driven by high-throughput studies on pancreatic and small intestinal neuroendocrine tumors (NETs). This review summarizes the present knowledge on genetic and epigenetic alterations. We integrated the available information from each compartment to give a pathway-based overview. This provided a summary of the critical alterations sustaining neoplastic cells. It also highlighted similarities and differences across anatomical locations and points that need further investigation. GEP-NENs include well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NENs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, NECs are G3 by definition. The distinction between NETs and NECs is also linked to their genetic background, as TP53 and RB1 inactivation in NECs set them apart from NETs. A large number of genetic and epigenetic alterations have been reported. Recurrent changes have been traced back to a reduced number of core pathways, including DNA damage repair, cell cycle regulation, and phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling. In pancreatic tumors, chromatin remodeling/histone methylation and telomere alteration are also affected. However, also owing to the paucity of disease models, further research is necessary to fully integrate and functionalize data on deregulated pathways to recapitulate the large heterogeneity of behaviors displayed by these tumors. This is expected to impact diagnostics, prognostic stratification, and planning of personalized therapy.


Restless legs symptoms in a patient with above knee amputations: a case of phantom restless legs.
We describe a 78-year-old gentleman who, following bilateral above-knee amputations, developed symptoms of restless legs syndrome in the absent portions of his lower extremities. These symptoms improved with dopamine agonist therapy. In addition, he later developed parkinsonism with prominent rest tremor on metoclopramide. This suggests that this individual had a dopamine-deficient state which predisposed him to both restless legs syndrome and drug-induced or drug-exacerbated parkinsonism. We propose expanding the spectrum of phantom limb phenomena to include phantom restless legs.


Highly Selective Room-Temperature Suzuki-Miyaura Coupling of Bromo-2-sulfonyloxypyridines for Unsymmetrical Diarylpyridines.
A new and mild synthetic approach has been developed for the synthesis of pharmaceutically important unsymmetrical diarylpyridines via chemoselective Suzuki-Miyaura coupling reactions of bromo-2-sulfonyloxypyridines. Most reactions allow for facile access to aryl-2-sulfonyloxypyridines at room temperature in yields of 5-99% with excellent chemoselectivity in the presence of Pd(OAc)2 (2.0 mol %) and Ad2BnP (2.4 mol %). The second arylation of the remaining tosyl or triflyl group in the monoarylpyridine derivatives obtained was successfully accomplished for the synthesis of unsymmetrical 2,3-, 2,4-, 2,5-, and 2,6-diarylpyridine derivatives. Furthermore, a one-pot synthesis of unsymmetrical diarylpyridines starting from bromo-2-sulfonyloxypyridine was accomplished to demonstrate the practical convenience. Finally, with this method, an antibacterial agent, a topoisomerase inhibitor, and etoricoxib, a nonsteroidal anti-inflammatory drug, were successfully synthesized from the corresponding bromo-2-hydroxypyridines in overall yields of 80, 86, and 49%, respectively.


Regional Changes in Choroidal Thickness Associated With Accommodation.
To characterize the changes occurring in choroidal thickness (ChT) across the posterior pole during accommodation using enhanced-depth imaging optical coherence tomography (OCT). Forty participants (mean age 21 ± 2 years) had measures of ChT and ocular biometry taken during accommodation to 0, 3, and 6 diopter (D) stimuli, with the Spectralis OCT and Lenstar biometer. A Badal optometer and cold mirror system was mounted on both instruments, allowing measurement collection while subjects viewed an external fixation target at varying accommodative demands. The choroid exhibited significant thinning during accommodation to the 6 D stimulus in both subfoveal (mean change, -5 ± 7 μm) and parafoveal regions (P < 0.001). The magnitude of these changes varied by parafoveal meridian, with the largest changes seen in the temporal (-9 ± 12 μm) and inferotemporal (-8 ± 8 μm) meridians (P < 0.001). Axial length increased with accommodation (mean change, +5 ± 11 μm at 3 D, +14 ± 13 μm at 6 D), and these changes were weakly negatively associated with the choroidal changes (r2 = 0.114, P < 0.05). A small, but significant thinning of the choroid was observed at the 6 D accommodation demand, which was greatest in the temporal and inferotemporal parafoveal choroid, and increased with increasing eccentricity from the fovea. The regional variation in the parafoveal thinning corresponds to the distribution of the nonvascular smooth muscle within the uvea, which may implicate these cells as the potential mechanism by which the choroid thins during accommodation.


A pilot study of oral physostigmine plus yohimbine in patients with Alzheimer disease.
Effective symptomatic treatment of Alzheimer's disease (AD) may require a combination of agents that augment cholinergic as well as noradrenergic neurotransmission. We conducted a pilot study of physostigmine plus oral yohimbine challenge in AD. Ten patients were enrolled in a 12-day double-blind protocol. Each patient received placebo q2h while awake for 5 days, followed by physostigmine 2 mg q2h while awake for 7 days. During each of these drug conditions, yohimbine challenges were administered at oral doses of 10 and 20 mg in a placebo-controlled manner. There was no significant improvement in Alzheimer's Disease Assessment Scale test performance for six patients for whom complete cognitive data were obtained for the 6 challenge days. Nine patients tolerated the protocol with no clinically significant changes in blood pressure, pulse, or electrocardiogram (ECG), and no cardiovascular, gastrointestinal, or autonomic toxicity. One patient complained of chest discomfort associated with tachycardia, a modest rise in blood pressure, and had t-wave inversion in a single precordial lead. These signs and symptoms resolved within a few hours. Serial ECG tracings and cardiac enzymes revealed no evidence of myocardial injury. This pilot study did not reveal major cognitive improvement with this regimen, but underscores the importance of careful cardiovascular monitoring during future combined cholinergic-noradrenergic therapies in AD.


Peptides derived from the Mycobacterium tuberculosis Rv1490 surface protein implicated in inhibition of epithelial cell entry: potential vaccine candidates?
This study reports the Rv1490 gene presence and transcription in members of the Mycobacterium tuberculosis complex, and characterises the encoded Rv1490 putative membrane protein in M. tuberculosis H37Rv. Rv1490 derived peptides were synthesised and their A549 and U937 cell binding ability was tested, finding five high activity binding peptides (HABPs) for A549 and five for U937. Only two HABPs (11060 and 11073) were shared by both cell lines, both of which affected M. tuberculosis' invading ability to target cells, thus indicating an important role for these sequences in M. tuberculosis entry to A549 alveolar epithelial cells and supporting their inclusion in further studies on the development of a subunit-based multi-epitopic, chemically synthesised anti-tuberculosis vaccine.


Sodium Butyrate Attenuates Taurocholate-Induced Acute Pancreatitis by Maintaining Colonic Barrier and Regulating Gut Microorganisms in Mice.
Acute pancreatitis (AP) damages the intestinal barrier, which aggravates AP. Butyrate exhibits anti-inflammatory effects in AP, but it is unknown if such a protective effect is associated with the regulation of gut microorganisms. We aim to investigate the effects of sodium butyrate (SB) on pancreatic inflammation, colonic barrier, and gut microorganisms. C57BL/6 mice were divided into groups of sham operation (Sham), AP, 200 mg/kg SB intervention (SB-200), and 500 mg/kg SB intervention group (SB-500). Samples were harvested 24 h after the model was established. The gut microbiota was analyzed using 16S rRNA gene sequencing. Pancreatic infiltration of neutrophils, macrophages, and M2-type macrophages was significantly reduced in the SB-500 intervention group. Supplementation of SB-500 improved colon mucosal histology and the expression of ZO-1 and occluding. The relative abundance of Alloprevotella and Muribaculaceae was increased and that of Akkermansia was decreased in the SB-500 group compared with the AP group. Ruminococcaceae was the most significantly increased species and Prevotellaceae was the most significantly decreased species in the SB-500 group compared with the AP group. High dose of SB inhibits pancreatic inflammation probably by maintaining the intestinal barrier and regulating gut microbiota in mice with AP.


The effects of transdermal scopolamine on simulated ship navigation and attention/reaction time.
Transdermal scopolamine is commonly used by mariners to prevent or treat seasickness. Most studies indicate that scopolamine administered transdermally via an adhesive patch does not impair performance of skills required to navigate a vessel, but trials have not been conducted testing navigation and ship handling under realistic conditions. The aim of this study was to test the effects of transdermal scopolamine on performance using training simulators to assess complex vessel navigation and rough-weather ship handling abilities. A randomized double-blind crossover study assessed 32 Swedish maritime cadets under transdermal scopolamine and placebo conditions on simulated navigation and ship handling performance, sleepiness, and subjective measures of fitness and performance. There were no significant differences on occupational outcomes by medication condition, but sustained reaction time was significantly increased under transdermal scopolamine, relative to placebo. We conclude that the transdermal scopolamine patch does not impair simulated ship handling.


Use of approximate inference in an index of completeness of biological inventories.
To assess the completeness of a floristic or faunal inventory, one may use the ratio of the observed number of species to the "true number" of species (C). If the inventory is complete, C =1. The estimate of the true number can be obtained from accumulation curves, nonparametric methods, or other techniques. We devised a simple method for computing confidence intervals (CI) for C and for evaluating the null hypothesis that the inventory is complete. The method is based on the assumptions that an estimate of the variance of the true number of species is known and that the distribution of the estimator of the true number of species is approximately normal. We applied our method to bird inventories in the Balsas Basin of Mexico. The completeness index for subtransects were lower (84.0, 85.4, and 89.9%) than for the whole transect (91.6%) (all significantly different from 100%). Thus, these particular inventories were incomplete at 2 spatial resolutions. Our method of estimating CI for C can be used to estimate species richness obtained from databases of different sites or to test the null hypothesis that an inventory derived from a database is complete.


Growth hormone therapy improves bone mineral density in children with cerebral palsy: a preliminary pilot study.
Cerebral palsy is associated with osteopenia, increased fracture risk, short stature, and decreased muscle mass, whereas GH therapy is associated with increased bone mineral density (BMD) and linear growth and improvement in body composition. We conducted a pilot study to evaluate the effect of 18 months of GH therapy on spinal BMD, linear growth, biochemical markers, and functional measures in children with cerebral palsy. The study was a randomized control trial, conducted from 2002-2005 at the University of California, Los Angeles, Orthopedic Hospital's Center for Cerebral Palsy. Patients included 12 males with cerebral palsy, ages 4.5-15.4 yr. We compared 18 months of GH (50 microg daily) vs. no treatment. Spinal BMD (dual-energy x-ray absorptiometry scan), height, growth factors, and bone markers were assessed. Ten subjects (five in each group) completed the study. Pre- and post-average height z-scores were -1.47 +/- 0.23 and 0.8 +/- 0.2 (GH-treated group) vs. -1.35 +/- 1.26 and -1.36 +/- 1.27 (control group) (Delta SD score, 0.67 vs. -0.01; P = 0.01). Average change in spinal BMD z-score (Delta SD score corrected for height) was 1.169 +/- 0.614 vs. 0.24 +/- 0.25 in the treated and control groups, respectively (P = 0.03). Osteocalcin, IGF-I, and IGF-binding protein 3 levels increased during GH therapy. There was no change in quality of life scores as measured by the Pediatric Orthopedic Disability Inventory. This small pilot study suggests that 18 months of GH therapy is associated with statistically significant improvement in spinal BMD and linear growth.


Rare pancreatic neoplasm: MDCT and MRI features of a typical solid pseudopapillary tumor.
Solid pseudopapillary tumor of the pancreas is a rare neoplasm, predominantly observed in young women and with greatest incidence in the second and third decade. It has clinically good behavior, although large at the time of diagnosis. We report the case of a thirty-year-old woman with a giant mass in the pancreas, incidentally discovered during an abdominal ultrasonography. The mass was later investigated by multidetector computed tomography and magnetic resonance imaging. The cystic-solid appearance of the encapsulated lesion suggested to radiologists the possibility of a solid pseudopapillary tumor. Imaging features of this pancreatic neoplasm and differential diagnosis from other cystic pancreatic tumors are discussed in our report, in order to help radiologists and clinicians achieve correct diagnosis and management.


[Dumping syndrome: a case after Nissen's operation].
We report on a case of dumping syndrome 1 month after Nissen fundoplication in a 5 month-old infant presenting with symptoms of late hypoglycemia. Blood glucose levels in pre- and post-prandial periods, oral glucose tolerance test and isotopic gastric emptying study confirmed the diagnosis. All symptoms resolved with diet therapy which could be stopped 8 months later. Dumping syndrome is not a so rare complication of gastric surgery and should be considered in patients with non specific symptoms.


Hydatid cyst of head of pancreas mimicking choledochal cyst.
A 5-year-old girl presented with abdominal pain, intermittent jaundice and a gall bladder lump. Clinical examination and preoperative imaging suggested the diagnosis of a type I choledochal cyst (CDC). During surgery, this was found to be a hydatid cyst (HC) occupying the head of pancreas causing obstruction to the common bile duct (CBD). A pancreatic HC mimicking a CDC and presenting with CBD obstruction is unusual.


Susceptibility of North-American and European crickets to Acheta domesticus densovirus (AdDNV) and associated epizootics.
The European house cricket, Acheta domesticus L., is highly susceptible to A. domesticus densovirus (AdDNV). Commercial rearings of crickets in Europe are frequently decimated by this pathogen. Mortality was predominant in the last larval stage and young adults. Infected A. domesticus were smaller, less active, did not jump as high, and the adult females seldom lived more than 10-14 days. The most obvious pathological change was the completely empty digestive caecae. Infected tissues included adipose tissue, midgut, epidermis, and Malpighian tubules. Sudden AdDNV epizootics have decimated commercial mass rearings in widely separated parts of North America since the autumn of 2009. Facilities that are producing disease-free crickets have avoided the importation of crickets and other non-cricket species (or nonliving material). Five isolates from different areas in North America contained identical sequences as did AdDNV present in non-cricket species collected from these facilities. The North American AdDNVs differed slightly from sequences of European AdDNV isolates obtained in 1977, 2004, 2006, 2007 and 2009 and an American isolate from 1988. The substitution rate of the 1977 AdDNV 5kb genome was about two nucleotides per year, about half of the substitutions being synonymous. The American and European AdDNV strains are estimated to have diverged in 2006. The lepidopterans Spodoptera littoralis and Galleria mellonella could not be infected with AdDNV. The Jamaican cricket, Gryllus assimilis, and the European field cricket, Gryllus bimaculatus, were also found to be resistant to AdDNV.


Endogenously expressed HIV-1 nef down-regulates antigen-presenting molecules, not only class I MHC but also CD1a, in immature dendritic cells.
The effects of Nef molecules on immature dendritic cells (iDCs) were analyzed using recombinant human immunodeficiency virus type 1 (HIV-1) with intact nef gene, pseudotyped with vesicular stomatitis virus glycoprotein, HIV/VSV-G/+Nef. When iDCs were infected with HIV/VSV-G/+Nef, the surface expression of CD1a, a molecule for presenting glycolipid/lipid antigens, was selectively down-regulated among CD1 molecules (CD1a, -b, -c, and -d) as well as class I MHC. Moreover, the CD1a molecules were also down-modulated and co-localized with DsRed2-tagged-Nef in CD1a-transfected cells. Their co-localization was dependent upon CD1a cytoplasmic tail and the CD1a was redistributed from cell surface to LAMP-1+ late endosomal/lysosomal compartment. These findings reveal that the HIV-1-Nef interferes with the intracellular trafficking of CD1a, and suggest the involvement of CD1a-restricted immune effectors in the protective immunity against HIV-1 infection, which implicates the feasibility of virus-derived glycolipid/lipid antigens together with epitope peptides for the vaccine development.


BCR-ABL1(+) acute myeloid leukemia: clonal selection of a BCR-ABL1(-) subclone as a cause of refractory disease with nilotinib treatment.
The presence of a Philadelphia chromosome with a corresponding BCR-ABL1 rearrangement is the hallmark of chronic myeloid leukemia, but is considered a very rare event in de novo acute myeloid leukemia (AML). Here, we report the first case in which a dominant Philadelphia chromosome-positive subclone was detected upon relapse in a formerly Philadelphia chromosome-negative MLL-AF6(+) AML. Due to refractory disease under salvage chemotherapy, the patient was started on nilotinib treatment. As a result, the Philadelphia chromosome-positive subclone was eradicated within 1 month; however, disease progressed and was again dominated by the Philadelphia chromosome-negative founding clone, demonstrating rapid clonal expansion under nilotinib-induced selection pressure.


The breast-feeding conversation: a philosophic exploration of support.
Nurses play a vital role in mothers' early experiences with breast-feeding. Literature enumerates both supportive and nonsupportive behaviors, as well as the "interpersonal" aspect of breast-feeding support, although little direction is given to nurses about how to facilitate the relationship. This article conceptualizes breast-feeding support within Gadamerian hermeneutics as a conversation among nurses, mothers, and their newborns. Hermeneutically, breast-feeding conversation encompasses a text (a particular feeding at the breast), conversational partners (a mother, her newborn, and a nurse), and a dialogue that facilitates effective breast-feeding and maternal breast-feeding confidence through interpretation or understanding of the text. History and language are essential as a partnership is formed.


Unexplained haemorrhagic fever in Rural Ethiopia.
This case study was written based on events of an outbreak investigation of an unfamiliar disease in Ethiopia during October-December 2012. Ethiopia did not have reports of similar cases in the 50 years prior to this outbreak. In this case study, we recapitulate and analyse this outbreak investigation based on data gathered from the community, health facility, and laboratory systems. It can be used to teach: 1) the outbreak investigation process; 2) selection of appropriate epidemiological design for the investigation process, 3) basic statistical analysis of surveillance data, and 4) principals of disease control. The target audiences for this case study are officials working in public health and public health trainees. It will take at most 3.5 hours to complete this case study. At the end of the case study, participants should be able to apply the principals of outbreak investigation and use surveillance data to respond to an outbreak in their country-specific context.


Effects of residual water on microtensile bond strength of one-bottle dentin adhesive systems with different solvent bases.
The wet-bonding technique is recommended for the one-bottle dentin adhesive systems, but the moisture concept varies widely among the instructions of manufacturers as well as among investigators. The aim of this study was to evaluate the effects of different dentin surface moisture on the microtensile bond strength(s) of an ethanol/water-based adhesive system and an acetone-based system to dentin. Forty intact human premolars extracted for orthodontic reasons were used. Superficial occlusal flat dentin surfaces of these premolars were exposed, finished with wet 600-grit silicon carbide paper. Under four wet and dry conditions (overwet, blot dry, one-second dry and desiccated), resin composite was bonded to dentin by using Single Bond (SB) or Prime & Bond NT (PB) according to the manufacturers' instructions. The teeth were longitudinally sectioned in the "x" and "y" directions to obtain bonded beams with a cross-sectional area of 0.81 mm(2) with a slow-speed diamond saw. The bonded specimens were tested in tension at a crosshead speed of 1 mm/min until failure of the bonds. Failure modes were observed with a scanning electron microscope. The mean bond strengths were analyzed by one-way ANOVA and Turkey's test. The bond strength of the overwet/SB, blot dry/SB, one-second dry/SB and desiccated/SB groups was 10.87 MPa, 22.47 MPa, 24.91 MPa and 12.99 MPa, respectively. The bond strength of the overwet/PB, blot dry/PB, one-second dry/PB and desiccated/PB groups was 10.02 MPa, 20.67 MPa, 21.82 MPa and 10.09 MPa, respectively. For both SB and PB, the blot dry group and one-second dry group revealed significantly higher bond strengths than the overwet and desiccated groups (P < 0.05). In order to achieve the highest bond strength to dentin, keeping the dentin surface in an appropriately moist condition is critical for the one-bottle dentin adhesive systems with ethanol/water or acetone solvent.


Polyamines in bacteriophage R17 and its RNA.
Bacteriophage R17 and its RNA were found to contain significant amounts of spermidine but not of putrescine. When isolated at 0.01 M KCl, up to 1,000 molecules of spermidine were associated with the virion. The phage RNA isolated with phenol plus sodium lauryl sulfate contained approximately 70 to 90 molecules of spermidine. The association appeared to be ionic because the bound spermidine could be dissociated by KCl, MgCl2, or both. Effects of polyamines on in vitro translation were studied using both poly(U) and phage R17-RNA as mRNA. Addition of spermidine to the system at suboptimal concentrations of Mg2+ resulted in marked stimulations of the rate of protein synthesis. Putrescine alone had no effect but stimulated the incorporation in the presence of suboptimal concentrations of spermidine plus Mg2+. The isolated amino acid-incorporating system contained suboptimal soluble and bound polyamines. A comparison of incorporation was made in this system using R17-RNA with and without bound spermidine. No effects of these bound cations were detected on the rate or extent of incorporation of valine. The ratio of incorporation of histidine (present in non-coat proteins) to valine (total protein) revealed little difference as a functions of cation in the system or a function of the spermidine present in R17-RNA.


Synergistic toxic interactions between CYP2E1, LPS/TNFα, and JNK/p38 MAP kinase and their implications in alcohol-induced liver injury.
The mechanisms by which alcohol causes cell injury are not clear. Many pathways have been suggested to play a role in how alcohol induces oxidative stress. Considerable attention has been given to alcohol-elevated production of lipopolysaccharide (LPS) and TNFα and to alcohol induction of CYP2E1. These two pathways are not exclusive of each other; however, associations and interactions between them, especially in vivo, have not been extensively evaluated. We have shown that increased oxidative stress from induction of CYP2E1 in vivo sensitizes hepatocytes to LPS and TNFα toxicity and that oxidative stress, activation of p38 and JNK MAP kinases, and mitochondrial dysfunction are downstream mediators of this CYP2E1-LPS/TNFα potentiated hepatotoxicity. This Review will summarize studies showing potentiated interactions between these two risk factors in promoting liver injury and the mechanisms involved including activation of the mitogen-activated kinase kinase kinase ASK-1 as a result of CYP2E1-derived reactive oxygen intermediates promoting dissociation of the inhibitory thioredoxin from ASK-1. This activation of ASK-1 is followed by activation of the mitogen-activated kinase kinases MKK3/MKK6 and MKK4/MMK7 and subsequently p38 and JNK MAP kinases. Synergistic toxicity occurs between CYP2E1 and the JNK1 but not the JNK2 isoform as JNK1 knockout mice are completely protected against CYP2E1 plus TNFα toxicity, elevated oxidative stress, and mitochondrial dysfunction. We hypothesize that similar interactions occur as a result of ethanol induction of CYP2E1 and TNFα.


Experimental Insights into the Interplay between Histone Modifiers and p53 in Regulating Gene Expression.
Chromatin structure plays a fundamental role in regulating gene expression, with histone modifiers shaping the structure of chromatin by adding or removing chemical changes to histone proteins. The p53 transcription factor controls gene expression, binds target genes, and regulates their activity. While p53 has been extensively studied in cancer research, specifically in relation to fundamental cellular processes, including gene transcription, apoptosis, and cell cycle progression, its association with histone modifiers has received limited attention. This review explores the interplay between histone modifiers and p53 in regulating gene expression. We discuss how histone modifications can influence how p53 binds to target genes and how this interplay can be disrupted in cancer cells. This review provides insights into the complex mechanisms underlying gene regulation and their implications for potential cancer therapy.


Haunting Expectations of Hospital Births Challenged by Traditional Midwives.
In Balochistan, Pakistan, hospitals are not the desired location for childbirth, but an affective economy of obstetric care, deceit, and clinical tactics of control has emerged, redirecting women away from midwives toward biomedical obstetrics. This economy manifests in forms such as coercing expectant mothers to deliver in the clinic rather than the home by generating fear in them and their kin through a narrative of imminent maternal and child harm. Drawing from ethnographic research, I show why Baloch midwives' ethical expertise and affective responses to iatrogenically induced emergencies haunt the postcolonial state and constrain biomedicine's haunting expectations of hospital/clinical births.


Acute liver injury in two workers exposed to chloroform in cleanrooms: a case report.
We report 2 cases of hepatotoxicity in cleanroom workers due to high retained chloroform air concentrations. The women, aged 34 and 41 years, who had been working in a medical endoscopic device manufacturer as cleanroom workers for approximately 40-45 days suffered severe liver damage. Two measured time-weighted averages of the chloroform concentration in the air in the cleanroom were 82.74 and 64.24 ppm, which are more than 6 times the legal occupational exposure limit in Korea. Only 7% of the cleanroom air was newly introduced from outside. The clinical courses of these cases and workplace inspection, led us to conclude that both cases of hepatotoxicity were caused by chloroform exposure.


Parallel analysis of finite element model controlled trial and retrospective case control study on percutaneous internal fixation for vertical sacral fractures.
Although percutaneous posterior-ring tension-band metallic plate and percutaneous iliosacral screws are used to fix unstable posterior pelvic ring fractures, the biomechanical stability and compatibility of both internal fixation techniques for the treatment of Denis I, II and III type vertical sacral fractures remain unclear. Using CT and MR images of the second generation of Chinese Digitized Human "male No. 23", two groups of finite element models were developed for Denis I, II and III type vertical sacral fractures with ipsilateral superior and inferior pubic ramus fractures treated with either a percutaneous metallic plate or a percutaneous screw. Accordingly, two groups of clinical cases that were fixed using the above-mentioned two internal fixation techniques were retrospectively evaluated to compare postoperative effect and function. Parallel analysis was performed with a finite element model controlled trial and a case control study. The difference of the postoperative Majeed standards and outcome rates between two case groups was no statistically significant (P > 0.05). Accordingly, the high values of the maximum displacements/stresses of the plate-fixation model group approximated those of the screw-fixation model group. However, further simulation of Denis I, II and III type fractures in each group of models found that the biomechanics of the plate-fixation models became increasingly stable and compatible, whereas the biomechanics of the screw-fixation models maintained tiny fluctuations. When treating Denis III fractures, the biomechanical effects of the pelvic ring of the plate-fixation model were better than the screw-fixation model. Percutaneous plate and screw fixations are both appropriate for the treatment of Denis I and II type vertical sacral fractures; whereas percutaneous plate fixation appears be superior to percutaneous screw fixation for Denis III type vertical sacral fracture. Biomechanical evidence of finite element evaluations combined with clinical evidence will contribute to our ability to distinguish between indications that require plate or screw fixation for vertical sacral fractures.


[Effect of the protonophore carbonylcyanide-m-chlorophenylhydrazone on the localization of secreted alkaline phosphatase in E. coli].
It was shown that the total amount of synthesized alkaline phosphatase as well as the value of enzymatic activity in E. coli cells decrease in the presence of the protonophore, carbonylcyanide-m-chlorophenylhydrazone. The enzyme content in the periplasm also decreases, while the amount of the enzyme bound to the spheroplasts increases. This effect is enhanced with a rise in the protonophore concentration. An electron cytochemical analysis showed that in the presence of the protonophore, alkaline phosphatase is partly localized in the cytoplasm and on the inner surface of the cytoplasmic membrane, which is unobserved in control cells. It was assumed that carbonylcyanide-m-chlorophenylhydrazone suppresses the translocation of alkaline phosphatase across the cytoplasmic membrane and enzyme biosynthesis, on the whole.


Wheat Protein-Induced Enterocolitis Syndrome Complicated With Wheezing: An Approach to Diagnosis and Wheat Reintroduction.
An 11-month-old Japanese girl was diagnosed with food protein-induced enterocolitis syndrome (FPIES) after presenting with vomiting approximately two hours after wheat intake. She showed positive results on the first wheat oral food challenge (OFC) at nine months of age, although serum wheat- and ω-5 gliadin-specific immunoglobulin E (IgE) were not detected. The second wheat OFC, performed at age 13 months, induced wheezing (usually an IgE-mediated symptom) 4.5 hours after ingestion, probably owing to gastroesophageal reflux caused by repetitive vomiting. The third wheat OFC, performed at age 25 months, did not trigger reactions. Therefore, gradual low-dose wheat was reintroduced at home. The fourth wheat OFC performed at age 30 months induced no response either; thus, the patient was deemed to have developed tolerance to wheat. This case report, therefore, demonstrates that careful assessment of natural history and physician-supervised OFCs are necessary for adequate diagnosis and the successful management of reintroduction in wheat-induced FPIES.


Submucosal gland differentiation and implications in esophageal basaloid squamous cell carcinomas.
Esophageal basaloid squamous cell carcinoma (BSCC) is a heterogenous entity with multilineage differentiation. It lacks systematical analysis on submucosal gland differentiation (SGD) due to the histological diversity and low incidence of esophageal BSCC. This study aims to find the correlation of SGD and clinicopathological features. A total of 152 esophageal BSCCs were separated into three histological groups: pure, mixed, and borderline group. The clinicopathological features were compared between different groups. The prevalence of SGD was also compared between cases of different groups. A panel of antibodies were used to identify SGD. The pure group differed from the mixed and borderline groups in many aspects, lymph node metastasis (LNM), cancer embolus, perineural invasion, and advanced stage occurred less frequently in the pure group (P<0.01). The pure group had a better but statistically insignificant overall survival (P=0.097). The squamous cell carcinoma (SCC) component or focal squamous differentiation was present in metastatic lymph node in almost all mixed BSCCs (95.7%, 22/23) with LNM. The LNM rate of superficial (T1b) BSCCs (17.6%, 6/34) was comparable to that of superficial (T1b) SCCs (18.5%, 57/308). However, LNM exclusively occurred in superficial mixed (3/5) and borderline (3/10) BSCCs. The IHC results demonstrated a prevalence of SGD in pure group (77%, 43/56). SGD is considered to be a favorable factor, while the squamous differentiation or invasive SCC component is an adverse factor in esophageal BSCCs. Refinement of classification is a promising way to improve patient management.


Limited cleavage of cellular fibronectin by plasminogen activator purified from transformed cells.
The substrate specificity and direct catalytic activity of plasminogen activator (PA) was examined under conditions where its natural substrate, plasminogen, was missing or inhibited. PA, purified from cultures of transformed chicken fibroblasts, was incubated with purified preparations of potential substrates. The adhesive glycoprotein fibronectin, isolated from normal chicken fibroblast extracellular matrix, underwent limited but specific cleavage by PA in the absence of plasminogen. Analysis of the cleavage products by polyacrylamide gels under both reducing and nonreducing conditions indicated that PA-mediated cleavage occurred near the carboxyl terminus of fibronectin but on the amino-terminal side of the interchain disulfide bridge, thus disrupting the native dimeric fibronectin molecule. Under the identical conditions, chicken ovalbumin was not cleaved while the established substrate, chicken plasminogen, was extensively converted to plasmin. A monoclonal antibody, directed against avian PA and shown to inhibit plasminogen-free, cell-mediated matrix degradation, specifically inhibited the fibronectin cleavage. A human PA, urokinase, also cleaved fibronectin under plasminogen-free conditions yielding a limited number of high molecular weight cleavage products.


The role of mitochondria in leaf nitrogen metabolism.
For optimal plant growth and development, cellular nitrogen (N) metabolism must be closely coordinated with other metabolic pathways, and mitochondria are thought to play a central role in this process. Recent studies using genetically modified plants have provided insight into the role of mitochondria in N metabolism. Mitochondrial metabolism is linked with N assimilation by amino acid, carbon (C) and redox metabolism. Mitochondria are not only an important source of C skeletons for N incorporation, they also produce other necessary metabolites and energy used in N remobilization processes. Nitric oxide of mitochondrial origin regulates respiration and influences primary N metabolism. Here, we discuss the changes in mitochondrial metabolism during ammonium or nitrate nutrition and under low N conditions. We also describe the involvement of mitochondria in the redistribution of N during senescence. The aim of this review was to demonstrate the role of mitochondria as an integration point of N cellular metabolism.


Mapping of serological testing and SARS-CoV-2 seroprevalence studies performed in 20 European countries, March-June 2020.
The SARS-CoV-2 pandemic spread across Europe from February 2020. While robust SARS-CoV-2 serological assays were quickly developed, only limited information on applied serological testing is available. We describe the extent and nature of SARS-CoV-2 serological testing used in Europe and assess the links between epidemiology, mitigation strategies applied and seroprevalence. An online questionnaire on SARS-CoV-2 serology was sent to the European Society of Clinical Virology and European Non-Polio Enterovirus Network members in September 2020. Data were analysed by comparing mitigation approaches, serological methods and seroprevalance studies performed. About 100 000 laboratory confirmed cases identified between March and June 2020 were reported by 36 participating laboratories from 20 countries. All responders experienced mitigation strategies including lockdowns and other closures. All except one participant had introduced serological testing; most had validated their assays (n = 29), but some had had difficulties in obtaining reference material. Most used commercial assays (n = 35), measuring IgG response against the spike antigen. Serology was used primarily for diagnostic purposes (n = 22) but also for convalescent plasma (n = 13) and research studies (n = 30). Seroprevalence studies targeted mainly health care workers (n = 20; seroprevalance 5% to 22%) and general population (n = 16; seroprevalance 0.88% to 5.6%). Basic demographic and clinical information were collected by most laboratories (n = 28), whereas data on long-term outcomes were rarely collected. This is first study gathering systematic information on serological testing approaches implemented during the first pandemic wave in Europe.