Effects of assisted ventilation on the work of breathing: volume-controlled versus pressure-controlled ventilation.
During assisted ventilation, the same tidal volume can be delivered in different ways, with the possibility for the physician to vary the ventilatory target (pressure or volume) and the peak flow setting. We compared the effects on the respiratory work rate of assisted ventilation, delivered either with a square wave flow pattern (assist control ventilation [ACV]) or with a decelerating flow pattern and a constant pressure (assisted pressure-control ventilation [APCV]). In the first part of the study where seven patients were studied, inspiratory time and tidal volume were similar in the two modes of ventilation. High and moderate levels of tidal volume (VT) were studied (12 ml/kg and 8 ml/kg, respectively). To obtain moderate VT, inspiratory time was kept constant and, therefore, mean inspiratory flow was reduced. At high VT, no difference between ACV and APCV was noted for breathing pattern, respiratory drive indexes, respiratory muscle work, or arterial blood gases. All patients exhibited respiratory alkalosis. At moderate VT, normal pH was achieved. In this situation significantly lower levels were observed during APCV than during ACV for the power of breathing (10 +/- 2 versus 19 +/- 5 J/min, p<0.05), transdiaphragmatic pressure swing (7 +/- 1 versus 11 +/- 2 cm H2O, p<0.05), and pressure-time index (252 +/- 43 versus 484 +/- 114 cm H2O.s, p<0.05), even though breathing pattern and gas exchange were similar. In the second part of the study where six additional patients were studied, tidal volume was kept constant at a moderate level (8 ml/kg), and we studied the effect of shortening inspiratory time and increasing mean inspiratory flow. At moderate VT and high inspiratory flow, no significant differences could be found between ACV and APCV, and although pressure-time index tended to be lower during APCV, absolute levels of effort were of small magnitude (56 +/- 55 versus 76 +/- 55 cm H2O.s). We conclude that at moderate VT and low flow rates only, inspiratory assistance delivered at a constant pressure reduces the respiratory work rate more effectively than assist control ventilation.


Comparison of the rate of palatal fistulation after two-flap and four-flap palatoplasty.
We studied 73 repairs of cleft palate (48 cleft lip and palate and 25 isolated cleft palate) done during a 7-year period (January 1996-October 2002) by the same plastic reconstructive surgeon. Two-flap or four-flap palatoplasty techniques were used to provide tension-free, three-layer repairs for patients with cleft palate. Their ages ranged from 10-244 months (mean 27). The postoperative follow-up period ranged from 6 to 60 months (mean 21). There was a palatal fistulation rate of 7% (5/73). There were two fistulas after two-flap palatoplasty (5%, 2/39), and three fistulas after four-flap palatoplasty (9%, 3/34). The mean diameter was 7.8 mm (range 5.1 to 13). There was no significant difference between the two techniques.


The Current State of MPOWER Policies in the Republic of Kazakhstan: Data from the Global Adult Tobacco Survey 2014.
The Global Adult Tobacco Survey (GATS) is a global study to monitor tobacco use, and evaluate current measures and requisite policies on tobacco control. In this study, the key indicators from GATS Kazakhstan that address six tobacco control policies are assessed. GATS Kazakhstan was a nationally representative household survey of the adult population aged 15 yr or older (n=4425, 52.8% females) implemented in 2014, in all regions of Kazakhstan. A multi-stage, geographically clustered sample design was used to obtain the key indicators of tobacco use and tobacco measures in the country. The sampling weights were employed to ensure real national representation. A household and individual questionnaire were administered through electronic devices. The majority of current tobacco users were cigarette smokers 22.2%. Overall, 19.0% of adults were exposed to secondhand smoke while at work. One third of smokers made a quit attempt in the last 12 months. Only, 74.0% of adults believed that breathing other people's smoke causes serious illness in non-smokers. Almost all current smokers (97.6%) noticed pictorial health warnings on cigarette packages. Over half (58.0%) of the current smokers had thought about quitting, having seen pictorial warning labels. Exposure to any cigarette advertisement, sponsorship or promotion had been experienced by 25.7% of adults, with the highest rate of noticing cigarette advertisements being found in stores where cigarettes are sold (14.0%). Cigarettes were largely affordable for the population. The GATS Kazakhstan results identified tobacco use indicators, as well as existing gaps in tobacco control measures.


Initial experiences in endovenous treatment of saphenous vein reflux.
The most common site of venous reflux is the long saphenous vein (LSV). The preferred treatment for reflux in the LSV is surgical stripping of the LSV. However, the complications of surgical stripping are well documented and undesirable. The constant search for treatment options with less morbidity, which are also cosmetically more acceptable, has resulted in the endovenous treatment for primary varicose veins, developed by VNUS Medical Technologies, Inc (Sunnyvale, Calif). We hereby present our first treatment experiences and propose refinements to the procedure. Two types of heat-generating endovenous catheters were used to treat incompetence of the LSV with a diameter of up to 12 mm. The procedure was performed on a blood-empty limb. Twenty-six limbs, in 26 patients, were treated, and the follow-up period was 1 year. The mean preoperative CEAP score was 4, and the postoperative score was 1.26, which was statistically significantly less (P <.0001, with Wilcoxon nonparametric matched pair test). Five patients had postoperative paresthesia of the saphenous nerve, and one patient had a burn from the procedure. The overall complication rate was 23%. All complications occurred in the first half of the studied population (P =.015, with Fisher exact test), indicating the learning curve effect. In one patient (3.8%), was total recanalization of the treated segment occurred, one patient (3.8%) could not be treated at all (technical failure), and one patient (3.8%) had partial recanalization of the LSV. Eight patients (30.8%) had closure of the entire LSV but with persisting reflux in the saphenofemoral junction (SFJ). Two patients had a competent SFJ with occlusion of the LSV. In 13 patients (50%), closure of both the LSV and the SFJ was seen. The LSV was successfully occluded in 88% of the patients. The endovenous catheter should not be used more than 5 to 10 cm below the knee to prevent saphenous nerve damage. Performance of the procedure with bloodlessness is preferable. A result of 88% of successfully treated LSV segments indicates a promising alternative for surgical stripping of the LSV.


Neonatal citrullinemia: comparison of conventional MR, diffusion-weighted, and diffusion tensor findings.
Conventional MR, diffusion-weighted, and diffusion tensor imaging were performed in an 8-day-old girl with citrullinemia. She had severe hyperammonemia for several days. On conventional T2-weighted MR images, symmetric, confluent high signal intensity was found in the bilateral thalami, basal ganglia, cortex, and subcortical white matter. Diffusion-weighted imaging demonstrated decreased apparent diffusion coefficient in these areas, reflecting cytotoxic edema. Follow-up MR imaging at the age of 4 months revealed subcortical cysts, ulegyric changes, and atrophy, which were most prominent in the occipital lobes. Diffusion tensor imaging revealed decreased anisotropy throughout the brain, consistent with diffuse injury to the oligodendro-axonal unit. Diffusion-weighted and diffusion tensor imaging are valuable techniques for the detection of irreversible brain damage and for the characterization of hyperintense lesions on T2-weighted MR images in patients with the neonatal form of citrullinemia.


Management of double system ureterocele.
Thirty eight patients with double system ureterocele are reviewed. More than half presented in infancy, urinary infection being the commonest clinical feature. Urinary tract ultrasound (US) and renal nuclide scan (RNS) were found to be the most useful diagnostic investigations. Whereas there are various surgical options available, an analysis of the results indicates that the primary operation should usually be an upper pole heminephrourterectomy, particularly in infancy. Secondary bladder surgery will be necessary in many infants but in children with disease confined to the ureterocele segment only, bladder surgery may be avoided. In selected cases, usually beyond infancy, total one stage reconstruction with upper pole heminephroureterectomy and bladder surgery may be justified.


Simulation for Milestone Assessment: Use of a Longitudinal Curriculum for Pediatric Residents.
Determining clinical competency on the milestones requires direct observation of residents, which is difficult for faculty members who are also providing patient care. Simulation can potentially represent an effective standardized tool for high-stakes assessment. Using a longitudinal simulation curriculum with formative and summative components, we conducted a pilot investigation to examine whether (1) performance on the formative cases predicted performance on the summative cases and (2) performance on the summative cases correlated with the clinical competency committee's (CCC) milestone placement. We developed 6 formative and 6 matched summative cases for pediatric interns that covered core pediatric topics. The interns progressed through the formative cases in pairs during the course of the academic year and then through the summative cases back to back individually at the end of the year. The interns were evaluated using a competency-based simulation evaluation. We determined the relationship between the formative and summative scores and between the summative scores and those from the CCC. The relationship between formative and summative scores was not statistically significant. There was a statistically significant relationship between summative and CCC scores. Significant methodological limitations preclude definite conclusions about the predictive power of simulation cases for Pediatric Milestones-based assessment. However, our work is an example of how simulation is a potentially useful tool for assessing residents' skill development on the Pediatric Milestones. More rigorous research is needed to determine the extent to which simulation can be used for high-stakes, milestones-based assessment.


Emotion regulation as a mediator of the relation between emotion socialization and deliberate self-harm.
This study examined (a) whether retrospective reports of specific parent responses to sadness (i.e., reward, punishment, neglect, override, magnification) were related to deliberate self-harm (DSH) and (b) whether difficulties regulating emotions (i.e., difficulties monitoring, evaluating, and modifying emotions) mediated those relations. One hundred eighteen college students completed measures of parental emotion socialization, emotion regulation difficulties, and DSH. Parental reward and override of sadness were directly related to lower DSH scores. Parental punishment and neglect of sadness were related to higher DSH scores, and these associations were mediated by difficulties evaluating emotions. In other words, parental punishment and neglect of sadness may place individuals at risk for DSH by fostering negative evaluations of emotional experiences and the belief that nothing can be done to effectively manage emotions.


Isolation of locally derived stem/progenitor cells from the peri-infarct area that do not migrate from the lateral ventricle after cortical stroke.
Neurogenesis can arise from neural stem/progenitor cells of the subventricular zone after strokes involving both the cortex and striatum. However, it is controversial whether all types of stroke and strokes of different sizes activate neurogenesis from the subventricular zone niche. In contrast with cortical/striatal strokes, repair and remodeling after mild cortical strokes may involve to a greater extent local cortical stem/progenitor cells and cells from nonneurogenic niches. We compared stem/progenitor cell responses after focal cortical strokes produced by distal middle cerebral artery occlusion and cortical/striatal strokes produced by the intraluminal suture model. To label migrating neuroblasts from the subventricular zone, we injected DiI to the lateral ventricle after distal middle cerebral artery occlusion. By immunohistochemistry, we characterized cells expressing stem/progenitor cell markers in the peri-infarct area. We isolated cortical stem/progenitor cells from the peri-infarct area after distal middle cerebral artery occlusion and assayed their self-renewal and differentiation capacity. In contrast with cortical/striatal strokes, focal cortical strokes did not induce neuroblast migration from the subventricular zone to the infarct zone after distal middle cerebral artery occlusion. By immunohistochemistry, we observed subpopulations of reactive astrocytes in the peri-infarct area that coexpressed radial glial cell markers such as Sox2, Nestin, and RC2. Clonal neural spheres isolated from the peri-infarct area after distal middle cerebral artery occlusion differentiated into neurons, astrocytes, oligodendrocytes, and smooth muscle cells. Notably, neural spheres isolated from the peri-infarct area also expressed RC2 before differentiation. Mild cortical strokes that do not penetrate the striatum activate local cortical stem/progenitor cells but do not induce neuroblast migration from the subventricular zone niche.


Attachment, borderline personality, and romantic relationship dysfunction.
Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25-36. Study 2 consisted of a psychiatric sample (N = 138) aged 21-60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction.


Fatigue and somatic anxiety in patients with major depression.
The objective this study aimed to investigate the independent contribution of somatic anxiety to the severity of depression-related fatigue. Seventy-six patients (85.5% female), aged 23-65 years (mean 48.7±10.6), diagnosed with major depressive disorder and currently in a major depressive episode (ΜΙΝΙ 5.0.0.) with a 17-item Hamilton Depression Rating Scale (HDRS) score ≥17, were studied. Forty-nine patients (64.5%) were concurrently suf fering from anxiety disorder(s). Patients with physical diseases or other fatigue-related conditions were excluded. Reported fatigue was measured with the 14-item Fatigue Questionnaire (FQ). Based on HDRS item 11 (somatic anxiety) scores, patients were divided into those with somatic anxiety (HDRS-11≥2) and those without (HDRS-11≤1). Pearson's (r) and Spearman's (rho) correlations between FQ score, age, gender, inpatient status, HDRS score and somatic anxiety status were calculated. A multiple regression analysis was then performed, with FQ as the dependent variable. Fifty-seven patients (75%) were rated as suffering from somatic anxiety (HDRS-11≥2). Patients with somatic anxiety had significantly higher HDRS and FQ scores. The FQ score significantly correlated with the HDRS score (r=0.36, p=0.001) and somatic anxiety status (rho=0.35, p=0.002). The FQ score was independently predicted by HDRS score and somatic anxiety status, with standardised beta coefficients of 0.259 (p=0.028) and 0.255 (p=0.031), respectively. R2 was 0.185. Both the severity of depression and the presence of somatic anxiety independently correlate with the severity of reported fatigue in patients with major depression. This finding has potential implications for the management of depression-related fatigue.


[Medical treatment of neuropathic pain].
Neuropathic pain represents a diagnostic challenge and is difficult to treat. In recent years, clinical trials have led to the development of a number of new treatment guidelines. The guidelines recommend drugs for the most important types of neuropathic pain and suggest alternatives in the event of lack of effect or intolerable adverse effects. Patients with this condition often suffer from anxiety, depression and insomnia, which influences the choice of drug. This article presents the most important drugs on which these guidelines concur.


Brain protein and alpha-ketoglutarate dehydrogenase complex activity in Alzheimer's disease.
To determine whether the reduction in brain alpha-ketoglutarate dehydrogenase complex activity in Alzheimer's disease (AD) is associated with an abnormality in one of its three constituent enzyme subunits, we measured protein levels of alpha-ketoglutarate dehydrogenase (El), dihydrolipoamide succinyltransferase (E2), and dihydrolipoamide dehydrogenase (E3), in postmortem brain of 29 patients with AD (mean age, 73 years; age range of onset, 50-78 years) and 29 control subjects. In the AD group protein levels of all three subunits were significantly reduced by 23 to 41% in the temporal cortex, whereas in the parietal cortex (El: -28%; E3: -32%) and hippocampus (E3: -33%) significant changes were limited to El and E3. alpha-Ketoglutarate dehydrogenase complex activities were more markedly reduced (by 46-68%) and did not correlate with protein levels, suggesting that decreased enzyme activity cannot be primarily explained by loss of alpha-ketoglutarate dehydrogenase complex protein. We did not find two E2 immunoreactive forms in the brain of any patient, as has been reported in fibroblasts of patients with very-early-onset chromosome 14-linked AD. We conclude that brain protein and activity levels of alpha-ketoglutarate dehydrogenase complex are reduced in patients with AD who have onset after 50 years and suggest that these changes, which are also observed in other human brain disorders, may represent a nonspecific consequence of different neurodegenerative processes. Nevertheless, reduced levels of this rate-limiting enzyme of the Krebs cycle could contribute to the brain neurodegenerative mechanisms of AD.


Chitosan hydrogel as a base for transdermal delivery of berberine and its evaluation in rat skin.
Berberine is the main ingredient of Coptis spp. This study selected berberine as a model drug to design a transdermal delivery system for the treatment of cutaneous leishmaniasis. Berberine was incorporated into chitosan hydrogel to prepare ointments. The physicochemical properties of the ointments and the release profile of berberine were investigated. The results indicated that the viscosity of chitosan hydrogel increased with an increasing amount of lactic acid or EDTA. The effect of EDTA on the viscosity was greater than that of lactic acid. By differential scanning calorimetry (DSC) measurement, no interaction was found to occur between chitosan and the soluble berberine. The release rate of berberine was inversely proportional to ointment viscosity. In in vitro skin perfusion studies, only trace amounts of berberine permeated through the rat skin due to its low oil-water partition coefficient. Surfactants were used as penetration enhancers to increase the percutaneous absorption of berberine. Among the enhancers, benzalkonium chloride was found to be the most efficient. Additionally, Tween 80 could increase the loading amount of berberine in the skin.


Methacholine inhalation challenge in patients with post-Mycoplasma pneumoniae pneumonia.
We studied methacholine bronchial inhalation challenge in 12 patients at 4th week and 12th week after recovered from Mycoplasma pneumoniae pneumonia, compared with 12 healthy subjects as controls. The aerosolized methacholine was produced by an atomized nebulizer of the Provocationtest I, Pari-Starnberg, Germany and the aerosol was kept into a reservoir bag. Then, it was inhaled slowly by a subject. Increasing concentration of methacholine solutions (0, 0.5, 1, 5, 10, and 25 mg/ml) were used. The results revealed that 67% of the patients had bronchial reactivity to methacholine at the first time of challenge with a mean concentration of methacholine producing a fall in FEV1 of 20% from baseline (PC20) of 12.3 +/- 6.44 mg/ml. Fifty percent of the patients were still positive to the test on the second time of challenge with a mean PC20 of 20.1 +/- 6.89 mg/ml. None of the healthy subjects had bronchial hyperreactivity (PC20 > 25 mg/ml). Two patients experienced wheezing and asthmatic attacks requiring bronchodilator therapy during acute phase pneumonia. They were also diagnosed as having bronchial asthma for the first time. Many patients had prolonged coughing during the recovery phase lasting more than 4 weeks. This prolonged coughing seemed to have a correlation with the development of bronchial hyperresponsiveness (BHR). We concluded that M. pneumoniae could induce BHR which may be transient or persistent. The effect of mycoplasma respiratory tract infection may result in airway inflammations and asthmatic attacks.


Angiogenesis, angiogenic factor expression and prognosis of gastric carcinoma.
It is known that the growth and metastasis of malignant tumors depends on neovascularization. It has also been suggested that the degree of tumor angiogenesis is related to clinical outcome in several tumor types. This is true for gastric carcinoma, where tumor angiogenesis is closely correlated with prognosis and hematogenous metastasis. Several types of angiogenic factors have been investigated in gastric cancer. In the current review, the correlation between angiogenesis / angiogenic factor expression and prognosis in gastric cancer is discussed. Moreover, the potential clinical applications of antivascular, anti-angiogenic and angiostatic agents for the treatment of gastric carcinoma are summarized.


Development of a facilitation curriculum to support primary care transformation: the "coach medical home" curriculum.
In an effort to improve patient care, retain high-quality primary care providers, and control costs, primary care practices across the United States are transforming to patient-centered medical homes. This is no small task. Practice facilitation, also called "coaching," is increasingly being used to support system change; however, there is limited guidance for these programs. To develop an evidence-based curriculum to help practice coaches guide broad-scale transformation efforts in primary care. We gathered evidence about effective practice transformation coaching from 25 published programs and 8 expert interviews. Given limited published information, we drew extensively on our experience as leaders and coaches in the Safety Net Medical Home Initiative. Using these data, and with input from a User Group, we identified 6 curricular topics and created learning objectives and curricular content related to these topics. The Coach Medical Home curriculum guides coaches in the following areas: getting started with a practice; recognition and payment; sequencing changes; measurement; learning communities; and sustainability and spread. Coach Medical Home is a publically available web-based curriculum that provides tools, resources, and guidance for practice transformation support programs, including practice facilitators and learning community organizers.


MicroRNA-139 inhibits the proliferation and migration of osteosarcoma cells via targeting forkhead-box P2.
Osteosarcoma (OS) is the most common primary bone malignancy that affects adolescents. Although great attention has been paid to the diagnosis of and therapy for OS, the 5-year survival rate of patients with this disease remains poor. MicroRNAs are small non-coding RNAs involved in pathogenesis and progression of human malignancies. MiR-139 has been implicated in several human cancers. However, the role played by miR-139 in pathogenesis of human OS has remained largely unknown. Realtime PCR was used to detect the expression of miR-139. CCK-8, BrdU-ELISA and ApoTox-Glo™ Triplex assay was employed to detect the proliferation and apoptosis of osteosarcoma cells. Realtime PCR, Western Blotting and luciferase report assays were conducted for the target genes analysis. The expression of miR-139 was reduced while the expression of forkhead-box P2 (FOXP2) was induced in both OS tissue and cell lines. The reduced level of miR-139 was correlated with tumor size, clinical stage and distant metastasis. Overexpression of miR-139 inhibited the expression of FOXP2, which suppressed cell growth, but induced apoptosis. Further, we confirmed that FOXP2 was a direct target of miR-139 by luciferase reporter assay. Knockdown of FOXP2 resulted in reduced levels of cell proliferation, but increased levels of apoptosis in vitro. These findings suggest that miR-139 plays a suppressive role in the regulation of OS cell proliferation and migration via directly targeting FOXP2, which might be a potential clinical diagnostic or predictive biomarker for human OS.


Front-Vehicle Detection in Video Images Based on Temporal and Spatial Characteristics.
Assisted driving and unmanned driving have been areas of focus for both industry and academia. Front-vehicle detection technology, a key component of both types of driving, has also attracted great interest from researchers. In this paper, to achieve front-vehicle detection in unmanned or assisted driving, a vision-based, efficient, and fast front-vehicle detection method based on the spatial and temporal characteristics of the front vehicle is proposed. First, a method to extract the motion vector of the front vehicle is put forward based on Oriented FAST and Rotated BRIEF (ORB) and the spatial position constraint. Then, by analyzing the differences between the motion vectors of the vehicle and those of the background, feature points of the vehicle are extracted. Finally, a feature-point clustering method based on a combination of temporal and spatial characteristics are applied to realize front-vehicle detection. The effectiveness of the proposed algorithm is verified using a large number of videos.


Urinary schistosomiasis with cutaneous lesions.
We report a case of urinary schistosomiasis with simultaneous presence of cutaneous lesions in a white male. The literature is reviewed, and the frequency, characteristics and physiopathology are discussed.


The effects of multidisciplinary team care for acute spinal cord injury patients.
The care of 169 survivors of spinal injury receiving acute treatment at the Hamilton General Hospital in Ontario, Canada, was studied. This paper compares treatment of groups of patients before and after formation of a multidisciplinary Acute Spinal Cord Injury Team. The establishment of multidisciplinary team care for acute spinal cord injury patients in our tertiary referral center correlates with clinically and statistically significant reductions in length of stay in the acute care hospital, alterations in the rate of surgical treatment for them, changes in the use of radiological resources, and reduction in the average number of days febrile. The team also brought stronger representation of allied health professionals to the hospital records of acute spinal cord injury patients. These important changes result from implementation of an effective multidisciplinary medical team without the addition of new funds, personnel, or hospital facilities and without alteration in referral patterns. Our team did not reduce mortality, duration of intensive care unit stay, or work for physicians.


[Comparison of the effect of a selective and a nonselective beta receptor blocker on the ischemic ST segment, lung function and stress-induced decrease in blood glucose].
This study was designed to compare the antihypertensive and anti-ischemic effects of the newly developed cardioselective beta-blocking agent, betaxolol, with the non-selective agent, nadolol, both of which have hydrophilic long acting properties, over a period of 48 hours. Additionally, the study was intended to determine whether betaxolol exerts a lesser influence on pulmonary function and whether beta-1- and beta-2-adrenergic blocking agents also induce a decrease in blood glucose levels during standard bicycle ergometry for three to nine minutes, similar to that reported in association with exercise of longer duration and, if so, whether this effect can be circumvented by the use of a selective agent. Ten patients with angiographically documented CAD, stable exercise angina pectoris and reproducible ST-segment depression of at least 1 mm received on day 1, in a single blind fashion, one tablet of placebo, on day 2 and day 7, in a double-blind, randomized and cross-over fashion, 20 mg betaxolol or 80 mg nadolol, respectively. Bicycle ergometry was performed before, four, 24 and 48 hours after drug with fixed work loads, blood glucose determination before and after ergometry four hours after drug and airway resistance and maximal ventilatory capacity studies were carried out five hours after drug administration. As compared with placebo, betaxolol and nadolol led to reductions of ST-segment depression of 65% (p less than 0.01) and 74% (p less than 0.005) at four hours, of 53% (p less than 0.025) and 56% (p less than 0.01) at 24 hours and 41% (p less than 0.05) and 44% (p less than 0.05) at 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS)


Identifying and controlling emerging foodborne pathogens: research needs.
Systems for managing the risks associated with foodborne pathogens are based on detailed knowledge of the microorganisms and the foods with which they are associated--known hazards. An emerging pathogen, however, is an unknown hazard; therefore, to control it, key data must be acquired to convert the pathogen from an unknown to a known hazard. The types of information required are similar despite the identity of the new agent. The key to rapid control is rapid mobilization of research capabilities targeted at addressing critical knowledge gaps. In addition, longer-term research is needed to improve our ability to respond quickly to new microbial threats and help us become more proactive at anticipating and preventing emergence. The type of contingency planning used by the military in anticipating new threats serves as a useful framework for planning for new emergence.


Clinical utility of the UCSD Performance-Based Skills Assessment-Brief (UPSA-B) in adults living with HIV: Associations with neuropsychological impairment and patient-reported everyday functioning difficulties.
Requiring only 10-15 minutes to complete, the UCSD Performance-Based Skills Assessment (UPSA-B) has high clinical utility as a brief measure of functional capacity. This study aimed to validate the UPSA-B in adults living with HIV/AIDS (HIV+), and identify whether the UPSA-B can be used as an indicator of functional dependence in this population. One hundred and three HIV+ adults and 91 HIV- adults completed a comprehensive neuropsychological and neuromedical battery, including a self-report measure of functional status (IADL Dependence vs. IADL Independence), an objective measure of functional capacity (UPSA-B), and a self-report measure of mood states including a subscale related to cognitive difficulties (Profile of Mood States [POMS]-Confusion/Bewilderment subscale). HIV+ participants had significantly lower UPSA-B scores than their HIV- counterparts (p = 0.02), although this fell to a trend (p = 0.08) when including covariates. Among the HIV+ group, higher UPSA-B scores were related to better neuropsychological ability, but unrelated to self-reported functional independence. Conversely, UPSA-B scores were unrelated to participant-reported cognitive difficulties on the POMS Confusion/Bewilderment subscale. An ROC curve was generated to determine the optimal UPSA-B value for discriminating between normal neuropsychological functioning versus neuropsychological impairment, with results indicating an optimal cutoff of 79. The UPSA-B identified HIV+ persons with cognitive impairment with 70.9% accuracy. The UPSA-B was able to differentiate neuropsychological impairment from no impairment among HIV+ participants and holds promise as a clinical screening tool in this population. However, indicators of functional disability among adults living with HIV is still not well understood and is likely multifactorial in nature. These data highlight the complex interplay between objective functional capacity, neurocognitive ability, subjective cognitive symptoms, and functional dependence.


Electronic determination of root canal length in primary teeth with and without root resorption.
To test an electrical device for determining root canal length in primary teeth in vitro, and to compare it with the radiographic length measurement. Two examiners determined the root canal length of 24 extracted maxillary primary incisors (12 with visible root resorption and 12 without) using an electrical root canal meter (Tri Auto ZX, Morita, Dietzenbach, Germany). The instrument was left in the root canal after the second examination and a radiograph was taken. The whole tooth was cleared by immersion in methylsalicylate and subsequently photographed. Both radiographs and photographs of cleared teeth were measured and compared with the electronic measurements. The evaluation of the radiographs showed a mean distance between the instrument tips and apices of 0.60 (+/- 0.41) mm; evaluation of the cleared teeth showed an equivalent distance of 0.62 (+/- 0.40) mm. The mean distance between instrument tip and acceptable working length (determined with the clearing method) was 0.26 (+/- 0.24) mm in teeth without resorption and 0.29 (+/- 0.30) mm in teeth with resorption. The presence of resorption in primary teeth did not affect the accuracy of electrical measurement of root canal length in vitro. The application of this method in primary teeth should be evaluated further.


Early postoperative oral fluid intake in paediatric day case surgery influences the need for opioids and postoperative vomiting: a controlled randomized trial†.
In children younger than 4 yr, it is difficult to distinguish the cause of postoperative distress, such as thirst, pain, and emergence delirium. This may lead to inappropriate treatment, such as administration of opioids. The aim of this study was to evaluate the influence of early postoperative oral fluid intake on the use of opioid analgesics and the incidence of postoperative vomiting (POV) after paediatric day case surgery. After ethics committee approval and with parental informed consent, planned day surgery patients aged 6 months to 4 yr were randomized to the liberal group (LG), in which apple juice (10 ml kg−1) was offered first if the Face Legs Activity Cry COnsolability (FLACC) score was ≥4 in the PACU, or to the control group (CG), in which children were treated after surgery according to the institutional opioid protocol, and drinking was allowed only upon the return to the ward. Bayesian statistical analysis was used to compare POV incidence and opioid use across groups. Data from 231 patients were analysed. The incidence of POV in the LG and the CG was 11.40 and 23.93%, respectively. An opioid was needed in 14.04% (mean total dose: 0.18 mg kg−1) and 35.89% (mean total dose: 0.20 mg kg−1) of the patients in the LG and the CG. The PACU stay was 53.45 and 65.05 min in the LG and the CG, respectively (all differences were statistically significant). In our paediatric outpatient setting, early postoperative oral fluid intake was associated with a reduction in opioid use and POV incidence. These results deserve confirmation in other settings. NCT02288650.


Risk factors for postoperative pulmonary complications in the treatment of non-degenerative scoliosis by posterior instrumentation and fusion.
The aim of this study was to evaluate the prevalence and risk factors for postoperative pulmonary complications (PPC) after posterior instrumentation and fusion (PIF) in patients with non-degenerative scoliosis. We retrospectively evaluated 703 patients (224 males, 479 females) diagnosed with non-degenerative scoliosis who underwent PIF in our center from January 2010 to January 2018. Preoperative, perioperative, demographic data, surgical methods and radiographic parameters were extracted and analyzed to identify risk factors for PPC. The mean age of the patients was 20.8 ± 9.0 years with the following diagnoses: congenital scoliosis (287/703, 40.8%), idiopathic scoliosis (281/703, 40.0%), neuromuscular scoliosis (103/703, 14.7%) and syndromic scoliosis (32/703, 4.5%). PPC manifested in 82 patients (11.7%) including pleural effusion (39/82, 47.6%), pneumonia (33/82, 40.2%), pneumothorax (3/82, 3.7%), respiratory failure (3/82, 3.7%), hemothorax (2/82, 2.4%), pulmonary edema (1/82, 1.2%) and pulmonary embolism (1/82, 1.2%). Multifactorial regression analysis confirmed that revision surgery [odds ratio (OR) = 2.320, P = 0.030], preoperative respiratory disease (OR = 14.286, P < 0.001), preoperative Cobb angle of main curve > 75° (OR = 1.701, P = 0.046) and thoracoplasty (OR = 4.098 P < 0.001) were risk factors for PPC after PIF in patients with non-degenerative scoliosis. A prevalence of 11.7% PPC was observed after PIF. Risk factors were preoperative Cobb angle of main curve > 75°, preoperative respiratory disease, revision surgery and thoracoplasty. Surgeons should recognize and pay attention to these risk factors and take appropriate preventive measures to prevent severe pulmonary complications. These slides can be retrieved under Electronic Supplementary Material.


[A case of toxic shock syndrome induced by MRSA after sinus surgery].
We present a case of toxic shock syndrome (TSS) induced by MRSA after sinus surgery. The patient was a 64-year-old woman who had undergone sinus surgery because of chronic sinusitis. Nine days after the surgery, she began to have sore throat, fever, and diffuse erythroderma followed by severe hypotension and renal dysfunction. Culture of sputum, nasal discharge and stool showed MRSA. Blood culture was negative. She was treated with intravenous fluids, catecholamines and antibiotics (vancomycin and fosfomycin). Continuous hemodiafiltration was started because of oliguria. Her condition improved gradually and she was discharged about a month after the onset of her illness. We should recognize that TSS can occur as a fatal complication after nasal surgery.


Plasma concentrations of efavirenz are associated with body weight in HIV-positive individuals.
Efavirenz is among the most widely used antiretroviral drugs. Increased efavirenz exposure has been associated with CNS side effects and also with the chance of emergence of resistance upon treatment interruptions. The objective of this study was to evaluate factors associated with efavirenz plasma concentrations in a cohort of HIV-infected individuals. From July 2009 to March 2010, HIV-infected patients with efavirenz as part of antiretroviral therapy (600 mg at night), undetectable viral load for at least 1 year and CD4 cell count >200 cells/mm(3) were consecutively enrolled at the HIV/AIDS ambulatory care unit in southern Brazil. Plasma samples were taken 18-23 h after efavirenz last dose and analysed by validated ultra-performance liquid chromatography. Forty-one subjects were included (21 females). Mean age and weight were 45.4 years and 70.9 kg, respectively. Mean efavirenz plasma concentration was 2.20 ± 2.17 mg/L. Most plasma concentrations (73%) were within the therapeutic window (1-4 mg/L); 17% were below and 10% above the limits. There were no significant associations between efavirenz concentration and age, CD4 cell count, time on antiretroviral treatment and gender. There was significant and inverse correlation between efavirenz concentrations and body weight (P = 0.013) and body mass index (P = 0.001). In this cohort of well-controlled HIV-positive individuals, patients with lower weight or body mass index had a higher chance of presenting elevated plasma concentrations of efavirenz. Therapeutic drug monitoring to adjust dose might be a helpful tool to decrease efavirenz dose in order to minimize costs and adverse effects.


Automatic multilabel detection of ICD10 codes in Dutch cardiology discharge letters using neural networks.
Standard reference terminology of diagnoses and risk factors is crucial for billing, epidemiological studies, and inter/intranational comparisons of diseases. The International Classification of Disease (ICD) is a standardized and widely used method, but the manual classification is an enormously time-consuming endeavor. Natural language processing together with machine learning allows automated structuring of diagnoses using ICD-10 codes, but the limited performance of machine learning models, the necessity of gigantic datasets, and poor reliability of terminal parts of these codes restricted clinical usability. We aimed to create a high performing pipeline for automated classification of reliable ICD-10 codes in the free medical text in cardiology. We focussed on frequently used and well-defined three- and four-digit ICD-10 codes that still have enough granularity to be clinically relevant such as atrial fibrillation (I48), acute myocardial infarction (I21), or dilated cardiomyopathy (I42.0). Our pipeline uses a deep neural network known as a Bidirectional Gated Recurrent Unit Neural Network and was trained and tested with 5548 discharge letters and validated in 5089 discharge and procedural letters. As in clinical practice discharge letters may be labeled with more than one code, we assessed the single- and multilabel performance of main diagnoses and cardiovascular risk factors. We investigated using both the entire body of text and only the summary paragraph, supplemented by age and sex. Given the privacy-sensitive information included in discharge letters, we added a de-identification step. The performance was high, with F1 scores of 0.76-0.99 for three-character and 0.87-0.98 for four-character ICD-10 codes, and was best when using complete discharge letters. Adding variables age/sex did not affect results. For model interpretability, word coefficients were provided and qualitative assessment of classification was manually performed. Because of its high performance, this pipeline can be useful to decrease the administrative burden of classifying discharge diagnoses and may serve as a scaffold for reimbursement and research applications.


Exosomal miRNAs in the plasma of Cynoglossus semilaevis infected with Vibrio harveyi: Pleiotropic regulators and potential biomarkers involved in inflammatory and immune responses.
Exosomes are a class of extracellular vesicles with diameters ranging from ~50 to 150 nm. Incorporating diverse biological substances and being present extensively in biofluids, exosomes are involved in intracellular communication in various physiological and pathological processes and emerging as promising biomarkers for the prognosis and diagnosis of many diseases. Accumulating evidence shows that exosomes also play important roles in the inflammatory and immune responses to bacterial infection. However, the study of exosomes in teleost fish remains scarce. In the present study, we focused on the exosomal microRNAs (miRNAs) in the plasma of Chinese tongue sole (Cynoglossus semilaevis) in response to Vibrio harveyi infection. After bacterial challenge, the plasma was sampled at both the early (6 and 16 h) and late stages. (48, 72, and 96 h) of infection, followed by exosome isolation and exosomal miRNA sequencing. Results showed that the expression profile of 85 exosomal miRNAs was significantly different among the control, early-, and late-infection groups. The predictive genes targeted by exosomal miRNAs were extensively involved in various inflammatory and immune processes by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, suggesting that a series of processes were regulated by exosomal miRNAs in the plasma, including the pathogen invasion and recognition and the activation and regulation of signaling pathways related to cytokine production. Moreover, the spleen was found to be a preference for exosome enrichment and the underlying mechanism of interleukin-6 production regulated by ZC3H12A, ARID5A, and exosomal ssa-miR-146a-5p were probably present in Chinese tongue sole. Additionally, the enhanced levels of ssa-miR-146a-5p and nbr-miR-731 in plasma exosomes and the spleen of the infection groups were identified, indicating their application as biomarkers in favor of the prognosis and diagnosis of V. harveyi infection in Chinese tongue sole. Therefore, the collective results in the present study indicated the pleiotropic roles of exosomal miRNAs in the regulation of inflammatory and immune responses and their potential utilization as biomarkers in teleost fish.


Synovial osteochondromatosis of the temporo-mandibular joint.
A rare case of synovial osteochondromatosis of the temporo-mandibular joint is presented. Important diagnostic information can be obtained by CT, MRI, 99m Tc bone scan and aspiration biopsy. Observation using a light microscope showed mild cellular atypia, but the hallmarks characteristic of chondrosarcoma were not found. Observation using an electron microscope showed the mature chondrocytes contained a well-developed rough endoplasmic reticulum. Histological evaluation indicated that the present case was benign synovial osteochondromatosis in an early stage.


Motor patterns of distal hind limb muscles in walking turtles: Implications for models of limb bone loading.
Previous studies of limb bone loading in walking turtles indicate that the ground reaction force exerts a flexor moment at the ankle during stance, requiring extensor muscle activity to maintain joint equilibrium. Of four proposed ankle extensors in turtles, two (gastrocnemius medialis, pronator profundus) originate on the tibia and fibula, respectively, while the other two (flexor digitorum longus, gastrocnemius lateralis) originate from the distal femur, crossing the flexor aspect of the knee and potentially eliciting compensatory forces from antagonist knee extensor muscles that could contribute to femoral stress. Published bone stress models assume all four proposed ankle extensors are active during stance in turtles. However, if only the ankle extensors that cross the knee were active then femoral stresses might be higher than predicted by published models, whereas if only extensors that do not cross the knee were active then femoral stresses might be lower than predicted. We analyzed synchronized footfall and electromyographic activity patterns in slider turtles (Trachemys scripta) and found that all four proposed ankle extensors were active during at least part of stance phase in most individuals, corroborating bone stress models. However, activation patterns were complex, with multiple bursts in many ankle extensors that frequently persisted into swing phase. In addition, two hypothesized ankle flexors (tibialis anterior, extensor digitorum communis) were frequently active during stance. This might increase the joint moment that ankle extensors must counter, elevating the forces they transfer across the knee joint and, thereby, raising femoral stress. Recognition of these activity patterns may help reconcile differences between evaluations of loads on turtle limbs based on force platform versus in vivo strain studies. Moreover, while some variation in motor patterns for the distal hind limbs of turtles may reflect functional compartmentalization of muscles, it may also indicate flexibility in the control of their limb movements.


Virucidal efficacy of various lens cleaning and disinfecting solutions on HIV-I contaminated contact lenses.
The virucidal efficacy of various commercially available contact lens care cleaning regimens on human immunodeficiency virus (HIV-1) contaminated contact lenses using either cursory or meticulous cleaning with a rubber policeman was evaluated. Levels of infectious HIV-1 remaining on individual contact lenses were determined by cultivating the lenses with target HUT-78 cells and subsequently analyzing the cultures for the production of HIV-1 p24 by antigen capture and for HIV-1 gag gene DNA content by the polymerase chain reaction. The data indicate that most of the lens care regimens tested, when coupled with meticulous rubbing, were capable of safely decontaminating the contact lenses, that is, they reduce the amount of infectious HIV-1 on the lenses by greater than a 10 log concentration (10(-10], relative to standard controls. Most tested lens care regimens, if properly followed, would virtually eliminate any chance of the lens serving as a vector for HIV.


Computed tomography lung parenchymal descriptions in routine radiological reporting have diagnostic and prognostic utility in patients with idiopathic pulmonary arterial hypertension and pulmonary hypertension associated with lung disease.
Patients with pulmonary hypertension (PH) and lung disease may pose a diagnostic dilemma between idiopathic pulmonary arterial hypertension (IPAH) and PH associated with lung disease (PH-CLD). The prognostic impact of common computed tomography (CT) parenchymal features is unknown. 660 IPAH and PH-CLD patients assessed between 2001 and 2019 were included. Reports for all CT scans 1 year prior to diagnosis were analysed for common lung parenchymal patterns. Cox regression and Kaplan-Meier analysis were performed. At univariate analysis of the whole cohort, centrilobular ground-glass (CGG) changes (hazard ratio, HR 0.29) and ground-glass opacification (HR 0.53) predicted improved survival, while honeycombing (HR 2.79), emphysema (HR 2.09) and fibrosis (HR 2.38) predicted worse survival (all p<0.001). Fibrosis was an independent predictor after adjusting for baseline demographics, PH severity and diffusing capacity of the lung for carbon monoxide (HR 1.37, p<0.05). Patients with a clinical diagnosis of IPAH who had an absence of reported parenchymal lung disease (IPAH-noLD) demonstrated superior survival to patients diagnosed with either IPAH who had coexistent CT lung disease or PH-CLD (2-year survival of 85%, 60% and 46%, respectively, p<0.05). CGG changes were present in 23.3% of IPAH-noLD and 5.8% of PH-CLD patients. There was no significant difference in survival between IPAH-noLD patients with or without CGG changes. PH-CLD patients with fibrosis had worse survival than those with emphysema. Routine clinical reports of CT lung parenchymal disease identify groups of patients with IPAH and PH-CLD with significantly different prognoses. Isolated CGG changes are not uncommon in IPAH but are not associated with worse survival.


Gender differences in psychopathy in a Swedish offender sample.
In this study we examined gender differences in the PCL:SV employing a variety of statistical methods with two subsets of psychopathic individuals drawn from larger samples of 129 female and 499 male Swedish offenders. The larger samples included forensic psychiatric patients, forensic psychiatric evaluees and criminal offenders. We found gender differences in antisocial behavior, as defined in factor 2 of the PCL:SV, with female psychopaths (PCL:SV>or=18) displaying significantly more lying, deceitfulness and lack of control, while male psychopaths were more antisocial as measured by the PCL:SV. We conclude that it might be meaningful to use gender specific definitions in the assessment of psychopathy or, alternatively, slightly revise the diagnostic tools. Our results support the use of the three-factor model of the PCL-R and PCL:SV introduced by Cooke and Michie (2001) in female populations.


Phytochrome-mediated light regulation of nitrate reductase expression in squash cotyledons.
In etiolated squash (Cucurbita maxima L.) cotyledons, nitrate-inducible NADH:nitrate reductase activity and protein were increased in darkness by red light pulses with red/far-red photoreversibility. Continuous far-red light also led to increased levels of nitrate reductase activity and protein. Poly(A)+RNA, which hybridizes to squash nitrate reductase cDNA, was also increased by light treatments. Thus, we found that after nitrate triggering, nitrate reductase expression appears to be regulated by light via phytochrome.


Maternal resveratrol supplementation ameliorates bisphenol A-induced atherosclerotic lesions formation in adult offspring ApoE-/- mice.
Current evidence suggests that intrauterine bisphenol A (BPA) exposure increases the risk of developing cardiovascular diseases in later stages of life. The beneficial effect of resveratrol (Rsv) on developmental programming of atherosclerosis lesions formation in offspring is seldom reported. Hence, we sought to study the effect of maternal Rsv in ameliorating perinatal BPA exposure-induced atherosclerosis lesions formation in adult offspring using the apolipoprotein E-deficient (ApoE-/-) mice model. The pregnant ApoE-/- mice were allocated into three groups: control, BPA, BPA + resveratrol (BPA + Rsv). The BPA group mice received BPA in their drinking water (1 μg/ml). BPA + Rsv group mice received BPA in their drinking water (1 μg/ml) and were treated orally with Rsv (20 mg kg-1 day-1). All the treatments were continued throughout the gestation and lactation period. Quantitative analysis of Sudan IV-stained aorta revealed a significantly increased area of atherosclerotic lesions in both female (p < 0.01) and male adult offspring mice (p < 0.01) in the BPA group. Supplementation with Rsv significantly reduced the BPA-induced atherosclerotic lesion development in the female offspring mice (p < 0.05). Transmission electron microscopy revealed the presence of a significantly high incidence of autophagic endothelial, smooth muscle, and macrophage cells in the aorta of BPA-exposed mice. Rsv treatment reduced the incidence of autophagic cells in BPA-exposed mice. In conclusion, maternal Rsv supplementation significantly prevents the BPA-induced atherosclerotic lesions formation in a sex-dependent manner potentially by acting as an autophagy modulator. The online version contains supplementary material available at 10.1007/s13205-021-03078-y.


Ascaris-mimicking common bile duct stone: A case report.
In most cases, it is not difficult to differentiate common bile duct (CBD) stone from Ascaris infection because they are different disease entities and have different imaging findings. The two diseases usually demonstrate unique characteristic findings on computed tomography or magnetic resonance cholangiopancreatography. However, we report a rare case from our experience in which a CBD stone mimicked and was misdiagnosed as Ascaris. A 72-year-old male presented with elevated serum liver enzymes. Computed tomography showed a hyper-attenuated, elongated lesion in the CBD lumen and associated biliary inflammation. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography revealed a linear filling defect in the bile duct. Moreover, elongated echogenic material with a central hypoechogenic area was seen on endoscopic ultrasound. Although the imaging findings caused us to suspect infection with the nematode Ascaris, the lesion was revealed to be a dark-brown-colored CBD stone through endoscopic extraction. We report a rare case of a CBD stone that mimicked Ascaris. We also review the literature for side-by-side comparisons of the imaging features of CBD stones and ascariasis.


Study of a benzoylperoxy radical in the gas phase: ultraviolet spectrum and C6H5C(O)O2 + HO2 reaction between 295 and 357 K.
This work reports the ultraviolet absorption spectrum and the kinetic determinations of the reactions 2C(6)H(5)C(O)O(2) → products (I) and C(6)H(5)C(O)O(2) + HO(2) → C(6)H(5)C(O)O(2)H + O(2) (IIa), → C(6)H(5)C(O)OH + O(3) (IIb), → C(6)H(5)C(O)O + OH + O(2) (IIc). Experiments were performed using a laser photolysis technique coupled with UV-visible absorption detection over the pressure range of 80-120 Torr and the temperature range of 293-357 K. The UV spectrum was determined relative to the known cross section of the ethylperoxy radical C(2)H(5)O(2) at 250 nm. Kinetic data were obtained by simulating the temporal behavior of the UV absorption at 245-260 nm. At room temperature, the rate constant value of reaction I (cm(3)·molecule(-1)·s(-1)) was found to be k(I) = (1.5 ± 0.6) × 10(-11). The Arrhenius expression for reaction II is (cm(3)·molecule(-1)·s(-1)) k(II)(T) = (1.10 ± 0.20) × 10(-11) exp(364 ± 200/T). The branching ratios β(O3) and β(OH), respectively, of reactions IIb and IIc are evaluated at different temperatures; β(O3) increases from 0.15 ± 0.05 at room temperature to 0.40 ± 0.05 at 357 K, whereas β(OH) remains constant at 0.20 ± 0.05. To confirm the mechanism of reaction II, a theoretical study was performed at the B3LYP/6-311++G(2d,pd) level of theory followed by CBS-QB3 energy calculations.


Carbon Emission Calculation and Influencing Factor Analysis Based on Industrial Big Data in the "Double Carbon" Era.
The arrival of the "double carbon" era indicates that industrial carbon reduction with high energy consumption and high carbon emission is imperative. From the perspective of carbon emission driving factors, industrial carbon emission is decomposed into five influencing factors: energy intensity, energy structure, industrial structure, economic efficiency, and employee scale. Taking the data of 41 subindustries of industrial industry in Liaoning Province from 2010 to 2019 as the research sample, the carbon emission is calculated. The LMDI model is used to analyze and point out the difference in the driving contribution of carbon emissions of each subindustry. The results show that the total carbon emission of Liaoning province gradually decreases, decreases for the first time in 2014, and gradually turns from flat to upward. Economic efficiency is the only and most important reason to drive the increase of industrial carbon emissions in Liaoning Province, and energy efficiency is the primary factor to curb carbon emissions. High carbon industries play a significant role in promoting the increase of carbon emissions, while the medium and low carbon industries have a better effect on restraining carbon emissions. It provides reference and theoretical basis for the government to adjust the industrial structure, control industrial overcapacity, and realize the "double carbon" goal as soon as possible. It is of great significance for the country to optimize energy layout, ensure energy security, and implement the new energy strategy.


[Traumatic brain injury in children].
We investigated the prognosis of 42 children with traumatic brain injuries. The main etiology was a traffic accident in 46 cases, especially during walking and bicycling, and child abuse in 7 cases. Eighteen cases of acute subdural hematoma 18 cases distributed at all ages, 9 cases of diffuse axonal injury mainly during school age, 4 cases of chronic subdural hematoma under 2 years. These were all caused by child abuse. Fifteen cases showed a good prognosis with independent activities of daily living (ADL). The main type of injury was diffuse axonal injury in this group. Twelve cases showed a bad prognosis with completely dependent ADL. The bad prognostic factors were chronic subdural hematoma caused by child abuse, consciousness loss with Glasgow Coma Scale less than 8 or lasting more than 2 weeks. After rehabilitation in our hospital, 37 cases returned to school: an ordinary class in 20 cases, a special class in an ordinary school in 5 cases and a special class in 12 cases. About half of the cases returned to an ordinary class, although with problems such as learning difficulty, danger and bullying.


Plasminogen activators and matrix metalloproteinases in angiogenesis.
In the initial stages of capillary formation (angiogenesis) microvascular endothelial cells of preexisting blood vessels locally degrade the underlying basal lamina and invade into the stroma of the tissue to be vascularized. A consistent body of experimental evidence has shown that this process requires a wide array of dedradative enzymes. Components of the plasminogen activator (PA)-plasmin system and of the matrix metalloproteinase (MMP) family play important roles. PAs trigger a proteinase cascade that results is the generation of high local concentrations of plasmin and active MMPs. This increase in proteolytic activity has three major consequences: it permits endothelial cell degradation and invasion of the vessel basal lamina, generates extracellular matrix (ECM) degradation products that are chemotactic for endothelial cells, and activates and mobilizes growth factors localized in the ECM. In addition, urokinase-type PA modulates some endothelial cell functions, including proliferation and migration, with a mechanism independent of proteolytic activity. PA and MMP activities are modulated in endothelial cells by complex mechanisms, including transcriptional regulation by a variety of growth factors and cytokines with angiogenic activity, extracellular control of the proteolytic activities by tissue inhibitors, and interaction with binding sites on the cell membrane and ECM.


The modified Burton-Pellegrini method for the treatment of trapeziometacarpal arthritis. Medium-term results.
An original modification in the Burton-Pellegrini technique was used to treat 20 cases of trapeziometacarpal arthritis between 1992 and 2001. A retrospective evaluation concerned 13 cases and was based on functional and radiographic criteria measuring the height of the column of the thumb at rest and under stress. Mean follow-up was 54.2 months (range 24-144). The height of the column of the thumb was decreased in relation to that of healthy hands and shortening under stress was significantly correlated with an increase in pain under stress (R2 = 44.7; p = 0.012). The observation of hyperextension of the MP (> 20 degrees) at follow-up was correlated with worse functional results. The method proposed has proven to be reliable, safe, capable of guaranteeing greater force as compared to other surgical methods described in the literature. The study emphasizes the need for a careful preoperative evaluation and possible treatment of MP joint hyperextension.


Hydrogen and Deuterium Molecular Escape from Clathrate Hydrates: "Leaky" Microsecond-Molecular-Dynamics Predictions.
It is predicted herewith that the leakage of both hydrogen (H2) and deuterium (D2) from sII clathrate hydrates, borne of guest chemical-potential equalization driving enhanced nonequilibrium intercage hopping, should be observable experimentally. To this end, we have designed simulations to realize and study this process by microsecond molecular dynamics within the temperature range of 150-180 K-for which the hydrate lattice was found to be stable. In this pursuit, we considered initial large-cage (51264) guest occupancies of 1-4, with single occupation of 512 cavities. Examining transient, nonequilibrium intercage hopping, we present a lattice-escape activation energy for the four nominal large-cage occupancies (1-4), by fitting to the hydrate-leakage rate. The intercage hopping of H2 and D2 was studied using Markov-chain models and expressed at different temperatures and large-cage occupancies. The free energy of guest "binding" in the large and small cages was also computed for all of the occupancies. Toward equilibrium, following the majority of H2/D2 escape via leakage, the percentage of occupancies was calculated for both H2 and D2 for all of the systems for all initial nominal large-cage occupancies; here, not unexpectedly, double occupancies occurred more favorably in large cages and single occupancies dominated in small cages.


Adolescent correlates of adult physical activity: a 26-year follow-up.
It is hypothesized that adolescent physical activity, fitness, anthropometric dimensions, fatness, biological maturity, and family characteristics contribute to the variation in physical activity at 40 yr of age, and that these associations vary with age. Subjects were 166 males followed from 1969 to 1996, between the ages of 14 and 40 yr from the Leuven Longitudinal Study on Lifestyle, Fitness and Health. Sports participation, fitness, anthropometric dimensions, fatness, and biological maturity were observed during the growth period. Also, sociocultural characteristics of the family were examined. The work, leisure time, and sport activity index of the Baecke Questionnaire and activity counts of a triaxial accelerometer were used as outcome variables at 40 yr. When upper and lower activity groups (quintiles) at 40 yr were contrasted, moderate associations were found (R2c varied between 0.1419 and 0.3736). No or low associations were found with the leisure time index. Body dimensions, fitness scores, sports practice, and family characteristics contributed to the explained variance in work, sport index, and activity counts. Multiple correlations were low (R2 = 0.037-0.085) for the work and leisure time activities, and were somewhat higher (R2 = 0.06-0.156) for the sport index and the activity counts in the total sample. Adolescent somatic dimensions, fitness, sports participation, parental sociocultural characteristics, and sport participation contributed to a small-to-moderate extent to the contrast between high and low active adults.


There is no evidence for a 'no overt subject' stage in early child Spanish: a note on Grinstead (2000).
Grinstead (2000) argues that there is a stage in both Spanish and Catalan children's grammatical development when they are restricted to using verbs without overt subjects. However, the evidence for a 'no overt subjects' stage in early child Spanish is based on very thin data from a single child: Juan between the ages of 1;7 and 2;1. In the present note we reanalyse the data from Juan and compare it with data from another child María at 1;7 and 1;8. Our results show that Juan produces his first overt subject during the same session as his first non-imperative verb form, and that María produces a relatively high proportion of verbs with overt subjects in both of her first two transcripts. They thus provide no support for the claim that there is a 'no overt subject' stage in early child Spanish.


Target Molecular Size and Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis Analysis of the ATP-and Pyrophosphate-Dependent Proton Pumps from Maize Root Tonoplast.
Tonoplast-enriched membranes were prepared from maize (Zea mays L. cv LG 11) primary roots, using sucrose nonlinear gradients. The functional molecular size of the tonoplast ATP-and PPi-dependent proton pumps were analyzed by radiation inactivation. Glucose-6-phosphate dehydrogenase (G6PDH) was added as an internal standard. Frozen samples (-196 degrees C) of the membranes were irradiated with (60)Co for different periods of time. After thawing the samples, the activities of G6PDH, ATPase, and PPase were tested. By applying target theory, the functional sizes of the ATPase and PPase in situ were found to be around 540 and 160 kilodaltons, respectively. The two activities were solubilized and separated by gel filtration chromatography. The different polypeptides copurifying with the two pumps were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two bands (around 59 and 65 kilodaltons) were associated with the ATPase activity, whereas a double band (around 40 kilodaltons) was recovered with the PPase activity.


[Interpretation of visual field with Humphrey Zeiss Analyser].
In the beginning of the article where are defined the notions of the soft of automated perimetry: threshold, kind of tests, the strategy of automated perimetry. Then are shown the steps of automated perimetry interpretation: kind of test and strategy, evaluation of patient reliability, interpretation of the visual field defects (artifacts or no) and statistical analysis.


Localization of endogenous sugar-binding proteins (lectins) in tumors of the central and peripheral nervous system by biotinylated neoglycoproteins.
The carbohydrate part of cellular glycoconjugates - glycoproteins, glycoproteins, glycolipids and proteoglycans - and specific endogenous sugar receptors, i.e. lectins, can establish a system of biological recognition based on protein-sugar interactions on the cellular and subcellular levels. To gain insight into the role of proteins in this type of interaction, sections of surgically removed tumor specimens of central and peripheral nervous tissue were analyzed glycohistochemically, using biotinylated neoglycoproteins with different sugar part. A specific staining with this type of probe, exposing different sugar moieties as ligands, indicated the presence of sugar receptors in different types of meningiomas, glioblastomas, gangliocytomas, anaplastic and well-differentiated oligodendrogliomas and ependymomas as well as in neurinomas and neurofibromas of peripheral nerves. In comparison to the well-differentiated ependymomas, the anaplastic form of this tumor exhibited a generally higher capacity to specifically bind the neoglycoproteins, containing alpha- or beta-glucosides. Inverse intensity of the glycohistochemical reaction was observed with galactose-6-phosphate-, galactose-beta(1.3)-N-acetylglucosamine-N-acetyl-D-glucosamine- and mannose- (BSA- biotin), respectively, when anaplastic and differentiated oligodendrogliomas were compared with each other. Tumorously dedifferentiated neurons, i.e. in gangliocytomas, showed a changed spectrum of endogenous sugar receptors in comparison to neurons of normal cerebral cortex. Qualitative and quantitative differences of sugar receptors were observed among the distinct subtypes of meningiomas. Receptors for N-acetyl-D-galactosamine were present only in the anaplastic form, while glucuronic acid-specific receptors were only found in the meningotheliomatous meningiomas. Distinctions in binding spectrum of neoglycoproteins suggest the presence of a possible additional subtype of meningiomas, called submalignant meningioma. Analysis of the spectrum of endogenous sugar receptors can serve to distinguish between different cell populations composing a given tumor, as shown in neurofibromas in the cases of Schwann cells and fibroblastoid cells stained with N-acetyl-D-glucosamine-(BSA-biotin). The analysis of expression of endogenous sugar receptors, as part of an intercellular information code system, may represent a further way of studying the mechanism of tumor differentiation and propagation.


The tomato nia gene complements a Nicotiana plumbaginifolia nitrate reductase-deficient mutant and is properly regulated.
A nitrate reductase (NR) deficient mutant of Nicotiana plumbaginifolia totally impaired in the production of functional nia transcript and protein was restored for NR activity by transformation with a cloned tomato nia gene. The transgenic plants expressed from undetectable to 17% of the control NR activity in their leaves. Restoration of growth rates comparable to the wild type was obtained for transgenic plants expressing as little as 10% of the wild-type activity showing that nitrate reduction is not a growth-limiting factor in the wild-type plant. The analysis of the transgene expression showed that the tomato nia gene transcription was regulated by light, nitrate and a circadian rhythm as in tomato plants. These results suggest that all the cis-acting sequences involved in these regulations are contained in the 3 kb upstream region of the tomato nia gene and are still functional in transgenic N. plumbaginifolia plants. The amount of NR transcript synthesized from the tomato nia gene was reduced when a functional N. plumbaginifolia nia locus was introduced by sexual crosses. These data support the hypothesis that nitrate reduction is regulated by nitrate-derived metabolites as demonstrated in fungi.


[Generic drugs and legal incentives: which impact?].
The dispositions that regulate generic substitution in Switzerland have been recently revised, and impose definite incentives on prescribers. The benefits and drawbacks associated with the prescription of generic drugs are reviewed, considering the viewpoints of patients, practitioners and third party payers. While the initial prescription of a generic drug raises no specific concerns, the generic switch during long-term treatment may require some caution. The advantages of using International Nonproprietary Names (INN) for drug prescription are discussed. A renewal of prescription habits would be welcomed however several practical issues would have to find rational solutions.


Inhibition of HIV-1 replication in human monocyte-derived macrophages by parasite Trypanosoma cruzi.
Cells of monocyte/macrophage lineage are one of the major targets of HIV-1 infection and serve as reservoirs for viral persistence in vivo. These cells are also the target of the protozoa Trypanosoma cruzi, the causative agent of Chagas disease, being one of the most important endemic protozoonoses in Latin America. It has been demonstrated in vitro that co-infection with other pathogens can modulate HIV replication. However, no studies at cellular level have suggested an interaction between T. cruzi and HIV-1 to date. By using a fully replicative wild-type virus, our study showed that T. cruzi inhibits HIV-1 antigen production by nearly 100% (p<0.001) in monocyte-derived macrophages (MDM). In different infection schemes with luciferase-reporter VSV-G or BaL pseudotyped HIV-1 and trypomastigotes, T. cruzi induced a significant reduction of luciferase level for both pseudotypes in all the infection schemes (p<0.001), T. cruzi-HIV (>99%) being stronger than HIV-T. cruzi (approximately 90% for BaL and approximately 85% for VSV-G) infection. In MDM with established HIV-1 infection, T. cruzi significantly inhibited luciferate activity (p<0.01). By quantifying R-U5 and U5-gag transcripts by real time PCR, our study showed the expression of both transcripts significantly diminished in the presence of trypomastigotes (p<0.05). Thus, T. cruzi inhibits viral post-integration steps, early post-entry steps and entry into MDM. Trypomastigotes also caused a approximately 60-70% decrease of surface CCR5 expression on MDM. Multiplication of T. cruzi inside the MDM does not seem to be required for inhibiting HIV-1 replication since soluble factors secreted by trypomastigotes have shown similar effects. Moreover, the major parasite antigen cruzipain, which is secreted by the trypomastigote form, was able to inhibit viral production in MDM over 90% (p<0.01). Our study showed that T. cruzi inhibits HIV-1 replication at several replication stages in macrophages, a major cell target for both pathogens.


Colon cancer screening update and management of the malignant polyp.
Colorectal carcinoma is common, but screening for this cancer has found less acceptance with the public than screening for breast, prostate, and cervical cancer. Available methods include fecal occult blood tests (FOBTs), flexible sigmoidoscopy (FOS), double-contrast barium enema, colonoscopy, computed tomographic colography, and fecal DNA. Evaluation of these options demonstrates that colonoscopy at ages 55 and 65 offers the best combination of reduction in colorectal cancer at the lowest cost. However, when compliance with screening recommendations is very high, costs are high, and the proportion of cancers arising from adenomas is low, the combination of FOS and FOBT is most cost effective. Malignant polyps look friable and irregular and feel hard. Sessile malignant polyps need to be treated by formal resection. Patients with pedunculated polyps with favorable histology (clear margin, well or moderately differentiated, no lymphovascular invasion) can be observed, and those whose polyps show unfavorable histology should have the polyp-bearing segment of colon resected along with its draining lymph nodes.


Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.
The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg · mL(-1) Pentostam compared with the control passage group (38.5 μg · mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is.


Approach to a child with monoarthritis.
Arthritis in childhood is common. The pattern, presentation and duration of arthritis help differentiate between the various possible diagnoses. When only one joint is involved, i.e., monoarthritis, it may be difficult to make a diagnosis as there are many possibilities both acute and chronic in nature. A detailed history and clinical examination is important to reach a correct diagnosis and the single most important investigation when a child presents acutely is a joint aspiration to rule out septic arthritis that may destroy the joint in hours. Inflammatory markers, antinuclear antibody testing, test for tuberculosis and imaging (in specific cases) play an important role in the diagnosis of a child that presents with a chronic monoarthritis. In this article we provide a clinical approach to the diagnosis of monoarthritis in a child.


Family members' experiences living with members with depression.
Using interview data from 11 family members and grounded theory methods, this study describes family members' experiences in living with a member with depression. Findings suggest that this process can be described as family transformations. In the first stage of this process--acknowledging the strangers within--family members described observing the metamorphosis of the person and other family members, finding socially acceptable explanations, living two lives, searching for reasons and solutions, and hoping for what was. In the second stage--fighting the battle--family members alternated between the strategies of holding our ground (protective) and of moving forward (coercive) to counteract the metamorphosis, and the strategy of working the system to get help for their ill member. In the third and final stage, family members described gaining a new perspective and identified preserving oneself, refocusing on others, redesigning the relationship, and becoming hopeful as strategies used in this stage.


Investigation of a 2D two-point maximum entropy regularization method for signal-to-noise ratio enhancement: application to CT polymer gel dosimetry.
This study presents a new method of image signal-to-noise ratio (SNR) enhancement by utilizing a newly developed 2D two-point maximum entropy regularization method (TPMEM). When utilized as an image filter, it is shown that 2D TPMEM offers unsurpassed flexibility in its ability to balance the complementary requirements of image smoothness and fidelity. The technique is evaluated for use in the enhancement of x-ray computed tomography (CT) images of irradiated polymer gels used in radiation dosimetry. We utilize a range of statistical parameters (e.g. root-mean square error, correlation coefficient, error histograms, Fourier data) to characterize the performance of TPMEM applied to a series of synthetic images of varying initial SNR. These images are designed to mimic a range of dose intensity patterns that would occur in x-ray CT polymer gel radiation dosimetry. Analysis is extended to a CT image of a polymer gel dosimeter irradiated with a stereotactic radiation therapy dose distribution. Results indicate that TPMEM performs strikingly well on radiation dosimetry data, significantly enhancing the SNR of noise-corrupted images (SNR enhancement factors >15 are possible) while minimally distorting the original image detail (as shown by the error histograms and Fourier data). It is also noted that application of this new TPMEM filter is not restricted exclusively to x-ray CT polymer gel dosimetry image data but can in future be extended to a wide range of radiation dosimetry data.


Endothelin binding to receptors and endothelin production by human thyroid follicular cells: effects of transforming growth factor-beta and thyrotropin.
Measurable endothelin (ET) was found in serum-free medium of cultured primary thyroid cells derived from human thyroid tissues after 3 days incubation at levels ranging from undetectable to 35 fmol/100,000 cells. Out of 12 thyroid glands studied, 2 responded to transforming growth factor-beta (TGF-beta) treatment with increased ET secretion into medium. Detailed study of cells derived from one of these thyroids showed TGF-beta at 1 ng/ml stimulated ET secretion from 13.7 to 33.3 fmol/100,000 cells after 3 days incubation. Although TSH alone did not significantly modulate ET release into medium, TSH enhanced the stimulatory effect of TGF-beta. A combination of TSH at 1 mU/ml and TGF-beta at 1 ng/ml stimulated ET secretion to 63.8 fmol/100,000 cells after 3 days incubation. Immunostaining studies demonstrated the presence of intracellular immunoreactive ET, largely localized in perinuclear regions, which was greatly stimulated by TSH but not by TGF-beta. These observations suggest that TSH may stimulate only ET synthesis, whereas TGF-beta may stimulate both synthesis and secretion. Binding of [125I]ET-1 to receptor on thyroid cells was dose-dependently stimulated by TGF-beta (0-10 ng/ml) pretreatment for 3 days. Scatchard analysis of competitive binding data from TGF-beta (1 ng/ml)-treated cells indicated that increased binding was the result of increased receptor number and not increased receptor affinity. TSH (0-10 mU/ml), though not as potent as TGF-beta, also dose-dependently stimulated ET binding. Treatment of thyrocytes with 1 mU/ml TSH for 3 days did not significantly affect ET receptor number or binding affinity. These results illuminate aspects of a possible autocrine regulation of ET in the thyroid gland.


Asialoglycoprotein receptor and hepatic blood flow using technetium-99m-DTPA-galactosyl human serum albumin.
Asialoglycoprotein receptor (ASGP-R) amount and hepatic blood flow were quantitatively measured by using a newly developed kinetic model of 99mTc-labeled diethylenetriaminepentaacetic acid-galactosyl human serum albumin (99mTc-GSA) in which receptor-mediated endocytosis and receptor recycling were considered. Five healthy volunteers were intravenously injected 3-mg and 9-mg 99mTc-GSA doses. The absolute amounts of 99mTc-GSA in the liver and extrahepatic blood were estimated from the time-activity curves for the liver, heart and lung. The metabolic process was represented by five differential equations with 10 parameters as variables. To estimate total receptor amount (Rtotal), hepatic plasma flow (Q) and hepatic plasma volume (Vh), other parameters were fixed and estimated by analyzing their data with the least-squares method. Nineteen patients with liver diseases were given a 3-mg dose, and the data were analyzed to estimate Rtotal, Q and Vh. The values of the fixed parameters were estimated as follows: dissociation constant, 0.032 microM; rate constant for internalization, 0.604 min(-1); and ratio of surface receptors to total receptors, 6.1%. The fitted liver uptake curve corresponded well to the measured data. The simulated liver uptake curve was significantly influenced by Rtotal and Q in cases with normal receptor amounts. Analysis in patients with normal livers, chronic hepatitis and liver cirrhosis showed statistically significant differences in their Rtotal values, but not in their Q or Vh values. The s.e. values of Rtotal, Q and Vh for normal livers were small, and the s.e. values of Q and Vh were high for cirrhotic livers. This method is useful for measuring ASGP-R amount and hepatic blood flow simultaneously based on dynamic images, without the need for blood sampling, and reflects the cellular transport of asialoglycoproteins and the ASGP-R recycling mechanism.


The risk of esophageal resection after esophagomyotomy for achalasia.
Esophagomyotomy is the mainstay of treatment for achalasia with proven long-term success. However, in patients with a significantly dilated esophagus, many advocate esophageal resection thus forgoing an esophagomyotomy. The purpose of this study is to determine the esophagomyotomy failure rate in patients with achalasia. A retrospective review of all patients with achalasia who underwent an esophagomyotomy from 1996 to 2006; 272 patients were divided into three groups based on their preoperative degree of esophageal dilation for comparison. The endpoint for esophagomyotomy failure was persistent symptoms requiring any intervention. The preoperative characteristics were comparable except for the severely dilated esophagus patients who had a longer duration of preoperative symptoms. Group I (mild dilatation) had 162 patients with 7 failures requiring intervention. Group II (moderate dilatation) had 74 patients with 4 failures and group III (severe dilatation) had 36 patients with 5 patients requiring intervention. For the entire cohort, median follow-up was 37 months (range, 8 to 144 months). There was no statistically significant difference among the groups in the number of patients requiring reintervention. The overall esophagectomy rate was only 2%. However, there was a significantly higher (p = 0.02) esophagectomy rate in the severely dilated patients. The degree of esophageal dilatation associated with achalasia does not influence the success of an esophagomyotomy. Of the entire patient population in this study, only 6 patients required an esophagectomy. The majority of patients with the most severely dilated esophagus did not require an esophagectomy. Esophagomyotomy should be the first treatment option for patients with achalasia no matter what the degree of esophageal dilatation.


Pyruvate orthophosphate dikinase in wheat leaves.
Pyruvate orthophosphate dikinase (PPDK) was found in wheat (Triticum aestivum L. cv Cheyenne [CI 8885]) leaves both by activity assays and by the protein blot method. The specific activity of the wheat enzyme is comparable to that of PPDK from maize leaves. Of the total soluble protein in wheat leaves, about 0.05% was PPDK, comparable to the amount in the immature wheat seed and about 1/70th the amount found in mesophyll cells of maize. Immunoprecipitation of wheat PPDK with maize enzyme antiserum indicates partial identity, and the apparent subunit molecular weight is the same based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis.


Development of 124I immuno-PET targeting tumor vascular TEM1/endosialin.
Tumor endothelial marker 1 (TEM1/endosialin) is a tumor vascular marker highly overexpressed in multiple human cancers with minimal expression in normal adult tissue. In this study, we report the preparation and evaluation of (124)I-MORAb-004, a humanized monoclonal antibody targeting an extracellular epitope of human TEM1 (hTEM1), for its ability to specifically and sensitively detect vascular cells expressing hTEM1 in vivo. MORAb-004 was directly iodinated with (125)I and (124)I, and in vitro binding and internalization parameters were characterized. The in vivo behavior of radioiodinated MORAb-004 was characterized in mice bearing subcutaneous ID8 tumors enriched with mouse endothelial cells expressing hTEM1 and by biodistribution and small-animal immuno-PET studies. MORAb-004 was radiolabeled with high efficiency and isolated in high purity. In vitro studies demonstrated specific and sensitive binding of MORAb-004 to MS1 mouse endothelial cells expressing hTEM1, with no binding to control MS1 cells. (125)I-MORAb-004 and (124)I-MORAb-004 both had an immunoreactivity of approximately 90%. In vivo biodistribution experiments revealed rapid, highly specific and sensitive uptake of MORAb-004 in MS1-TEM1 tumors at 4 h (153.2 ± 22.2 percentage injected dose per gram [%ID/g]), 24 h (127.1 ± 42.9 %ID/g), 48 h (130.3 ± 32.4 %ID/g), 72 h (160.9 ± 32.1 %ID/g), and 6 d (10.7 ± 1.8 %ID/g). Excellent image contrast was observed with (124)I-immuno-PET. MORAb-004 uptake was statistically higher in TEM1-positive tumors than in control tumors. Binding specificity was confirmed by blocking studies using excess nonlabeled MORAb-004. In our preclinical model, with hTEM1 exclusively expressed on engineered murine endothelial cells that integrate into the tumor vasculature, (124)I-MORAb-004 displays high tumor-to-background tissue contrast for detection of hTEM1 in easily accessible tumor vascular compartments. These studies strongly suggest the clinical utility of (124)I-MORAb-004 immuno-PET in assessing TEM1 tumor-status.


[New perspectives in life-event history analysis].
"In the last decade, life-event history analysis, also called failure time data analysis or survival analysis, has been widely adopted by demographers. This methodology in demography allows [us] to overcome major hurdles especially when analyzing longitudinal survey data. This paper describes the new perspectives opened to research in that field, and is illustrated by new results and examples of research projects. The authors concentrate on four issues: the analysis of incorrect and imperfect data, the analysis based on more complex data and lastly the study of interaction between phenomena." (SUMMARY IN ENG AND SPA)


Pre-operative computed tomography in abdominal aortic aneurysms.
Major additional pathology, in the abdomen or directly related to the aneurysm itself, which influenced surgical management was demonstrated in 39 (34.5%) of 113 patients with suspected abdominal aortic aneurysm who had undergone pre-operative assessment with computed tomography (CT). Major additional pathology within the abdomen was shown in 11 (9.7%) and related to the aneurysm itself in 26 (23%). Therefore, CT has a significant impact on operative management of such patients and should be routine in the pre-operative evaluation of abdominal aortic aneurysms. The current roles of CT angiography and magnetic resonance angiography are discussed.


[The use of bevacizumab in refractory peritoneal dissemination of gastric cancer with malignant ascites-two case reports].
Vascular endothelial growth factor (VEGF) plays an important role in proliferation of cancer cells, angiogenesis and vascular permeability in peritoneal dissemination. In addition, the release of VEGF by tumor cells has been identified as a main factor promoting the intraperitoneal secretion of fluid. Accordingly, recent evidence suggests that targeting VEGF may have the potential to suspend the ascites production resulting from peritoneal metastasis. We previously reported the effects of bevacizumab (BEV) on the growth inhabitation of peritoneal nodules and the reduction of ascites in peritoneal metastatic models. Here we present two cases of women (62 and 42 years old) with refractory peritoneal dissemination of scirrhous gastric cancer and server symptomatic ascites. They required frequent paracenteses for ascites which was resistant to systemic and intraperitoneal chemotherapy of S-1 and taxane. We treated them with intravenous BEV (5-10 mg/kg) with dramatic improvement in their ascites. BEV may have a role in the management of malignant ascites in the patient with refractory gastric cancer which should be confirmed in a larger series of well selected patients.


Single-Chain Mechanical Properties of Gelatin: A Single-Molecule Study.
Gelatin is an important natural biological resource with a wide range of applications in the pharmaceutical, industrial and food industries. We investigated the single-chain behaviors of gelatin by atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS), and found that gelatin exists as long chains by fitting with the M-FJC model. By comparing the single-chain elasticity in a nonpolar organic solvent (nonane) and DI water, it was surprising to find that there was almost no difference in the single-chain elasticity of gelatin in nonane and DI water. Considering the specificity of gelatin solubility and the solvent size effect of nonane molecules, when a single gelatin chain is pulled into loose nonane, dehydration does not occur due to strong binding water interactions. Gelatin chains can only interact with water molecules at high temperatures; therefore, no further interaction of single gelatin chains with water molecules occurred at the experimental temperature. This eventually led to almost no difference in the single-chain F-E curves under the two conditions. It is expected that our study will enable the deep exploration of the interaction between water molecules and gelatin and provide a theoretical basis and experimental foundation for the design of gelatin-based materials with more functionalities.


[Asbestos, danger and invisibility: perception of environmental risks and health of the residents of Bom Jesus da Serra/Bahia state].
It is important for society as a whole to know how environmentally exposed populations understand and respond to technological chemical risks. This study aimed to analyze the perception of environmental risks and health of the residents of BJS/BA, which is an area especially subjected to environmental exposure to asbestos in Brazil. Mixed questionnaires were used on residents who attend the "Family Health Program" of this city. The subjects of the study were selected according to the following characteristics: specific age groups--one group from 20 to 35 and the other group over 60; sex; length of time and location of dwelling. The intentional sample reached comprised 83 individuals. The results showed that there was general concern about contamination by dust in the air, but general denial of the environmental risks related to asbestos. With respect to health risks, there was lack of visibility by the majority of informants regarding greater risk of getting cancer and pulmonary diseases, mainly for the group of the residents close to the mine and elderly ex-workers.


Correlation of Performance Status and Neutrophil-Lymphocyte Ratio with Efficacy in Radioiodine-Refractory Differentiated Thyroid Cancer Treated with Lenvatinib.
Background: Radioiodine-refractory differentiated thyroid cancer (RR-DTC) has a low 10-year patient-survival rate and is challenging to treat. Lenvatinib is a multikinase inhibitor approved for the treatment of RR-DTC. This study aims to assess Eastern Cooperative Oncology Group performance status (ECOG PS) and neutrophil-to-lymphocyte ratio (NLR) as prognostic markers for patients with RR-DTC treated with lenvatinib. Methods: In this retrospective analysis of the Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT), patients randomly assigned to receive lenvatinib were classified according to baseline ECOG PS (0 or 1) or baseline NLR (≤3 or >3). The effects of baseline ECOG PS and NLR on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated. In addition, the effects of baseline ECOG PS on the change in diameter of target lesions and correlations between baseline NLR and the sums of the diameters of target lesions were calculated. Results: Among patients who received lenvatinib, patients with a baseline ECOG PS of 0 had statistically improved PFS (hazard ratio [HR] 0.52; 95% confidence interval [CI 0.35-0.77]; p = 0.001), OS (HR 0.42 [CI 0.26-0.69]; p = 0.0004), and ORR (odds ratio [OR] 3.51 [CI 2.02-6.10]; p < 0.0001) compared with patients with a baseline ECOG PS of 1. Patients who received lenvatinib with a baseline NLR ≤3 also had improved PFS (HR 0.43 [CI 0.29-0.65]; p < 0.0001) and OS (HR 0.48 [CI 0.29-0.78]; p = 0.0029) versus patients with a baseline NLR >3. Moreover, patients with a baseline NLR ≤3 had a trend toward increased ORR (OR 1.57 [CI 0.94-2.64]; p = 0.08) compared with patients with a baseline NLR >3. Treatment-emergent adverse events were generally similar among patients who received lenvatinib, irrespective of patients' ECOG PS at baseline. Conclusion: Lower ECOG PS and NLR may provide prognostic value for improved efficacy in patients with RR-DTC. ClinicalTrials.gov no. NCT01321554.