The L-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids.
The L-arginine/nitric oxide (L-Arg/NO) pathway regulates endothelial function and may play an important role in the pathogenesis of Duchenne muscular dystrophy (DMD). Yet, this pathway is poorly investigated in children suffering from DMD. Endothelial dysfunction can affect the perfusion of contracting muscles, thus leading to ischemia and hypoxia. In the present study, we tested the hypothesis that reduced NO production due to elevated synthesis of N (G),N (G)-dimethyl-L-arginine (asymmetric dimethylarginine, ADMA), an endogenous inhibitor of NO synthesis, is a possible pathophysiological mechanism for progressive intramuscular muscle ischemia and disturbed endothelial function in children with DMD. Given the possible antagonistic action of homoarginine (hArg) on ADMA, we also analyzed this amino acid. We investigated 55 male patients with DMD and 54 healthy male controls (HC; aged 11.9 ± 4.8 vs. 11.1 ± 4.9 years, mean ± SD). Urinary creatinine and metabolites of the L-Arg/NO pathway were measured in plasma and urine by GC-MS or GC-MS/MS. Urine levels of ADMA and its major urinary metabolite dimethylamine (DMA), nitrite and nitrate (P < 0.001 for all) and hArg (P = 0.002) were significantly higher in DMD patients compared to HC, while the urinary DMA/ADMA molar ratio was lower (P = 0.002). In plasma, nitrate (P < 0.001), hArg (P = 0.002) and the hArg/ADMA ratio (P < 0.001) were lower in DMD than in HC. In plasma, ADMA (631 ± 119 vs. 595 ± 129 nM, P = 0.149), arginine and nitrite did not differ between DMD and HC. In DMD, positive correlations between ADMA, DMA or nitrate excretion and the stage of disease (according to Vignos and Thompson) were found. In DMD patients on steroid medication, lower concentrations of ADMA in plasma, and of DMA, ADMA, nitrate and hArg in urine were observed compared to non-treated patients. The L-Arg/NO pathway is impaired in DMD patients, with the disease progression being clinically negatively correlated with the extent of impairment. One of the underlying mechanisms in DMD may involve insufficient antagonism of ADMA by hArg. Steroids, but not creatine supplementation, seems to improve the L-Arg/NO pathway in DMD.


[The efficacy of repeated laser trabeculoplasy].
The evaluation of the results of repeated laser trabeculoplasty. Retrospective analysis of cases with open angle glaucoma in eyes with uncontrolled intraocular pressure was carried out. The studied group comprised eyes which had shown a significant and prolonged (for at least 12 months) hypotensive response to initial laser trabeculoplasty. 20 patients (26 eyes) were analyzed. The follow-up period lasted from 12 to 59 months. 91% of eyes demonstrated a sustained and favourable response--intraocular pressure decrease of 5.6 mmHg to 17 mmHg (mean 9.6 mmHg). No significant immediate postoperative pressure increases were observed. Our results show the effectiveness of repeated laser trabeculoplasty in the treatment of chosen types of glaucoma.


Radiation Imagers for Quantitative, Single-particle Digital Autoradiography of Alpha- and Beta-particle Emitters.
Promising therapies are being developed or are in early-stage clinical trials that employ the use of alpha- and beta-emitting radionuclides to cure hematologic malignancies. However, these targeted radionuclide therapies have not yet met their expected potential for cancer treatment. A primary reason is lack of biodistribution, dosimetry, and dose-response information at cellular levels, which are directly related to optimal targeting, achieving a requisite therapeutic dose, and assessing the safety profile in normal organs and tissues. The current set of imaging tools, such as film autoradiography, scintigraphy, and SPECT/CT, available to researchers and clinicians do not allow the effective assessment of radiation absorbed dose distributions at cellular levels because resolutions are poor, measurement and analytical times are long, and the spatial resolutions are low-generally resulting in poor signal-to-noise ratios. Recently, new radiation digital autoradiography imaging tools have been developed that promise to address these challenges. They include scintillation-, gaseous-, and semiconductor-based radiation-detection technologies that localize the emission location of charged particles on an event-by-event basis at resolutions up to 20 µm FWHM for alpha and beta emitters. These imaging systems allow radionuclide activity concentrations to be quantified to unprecedented levels (mBq/µg) and provide real-time imaging and simultaneous imaging capabilities of both high- and low-activity samples without dynamic range limitations that plague traditional autoradiography. Additionally, large-area imagers are available (>20 × 20 cm2) to accommodate high-throughput imaging studies. This article reviews the various detector classes and their associated performance trade-offs to provide researchers with an overview of the current technologies available for selecting an optimal detector configuration to meet imaging requirement needs.


Simultaneous kinetic determinations of lipase, chymotrypsin, trypsin, elastase, and amylase on the same microtiter plate.
Micromethods are described to determine in 10 min the activity of the five most common pancreatic zymogens: amylase, lipase, trypsin, chymotrypsin, and elastase. Progress of the reactions is monitored at 405 nm, allowing the kinetic determination of the five enzymes on a single 96-well microtiter plate. Amylase activity is measured by the release of p-nitrophenol from a chemically defined substrate. Linearity of the assay is from 10 to 360 U/L of amylase, and activities as low as 0.4 U/L can be easily measured by extending the period of incubation up to 24 h. Chymotrypsin, trypsin, and elastase activities are monitored by the release of p-nitroanilide from specific substrates, and activities are from 25 to 6,500, 15 to 260, and 20 to 600 U/L, respectively. Finally, lipase is determined by the clearing of a commercially available stabilized emulsion of triolein. The lipase determination can be performed from 90 to 3,600 U/L. When microplate methods were compared with conventional procedures, a perfect correspondence was found between the two types of procedure. Factors necessary to convert microplate results to those of conventional assays are provided. These microassays make possible the rapid and simultaneous determination of the three main types of pancreatic hydrolases (a glycohydrolase, three proteases, and a lipase) with < 5 microliters of pancreatic juice by kinetic analysis. They could be easily adopted as routine assays in most research laboratories.


[The drug industry: a national issue].
Following up on a letter received from the Mrs. Nicole Fontaine, the Delegate Minister of Industry, requesting recommendations concerning the "serious threats" to the French drug industry, the Academy of Medicine auditioned the five leading French pharmaceutical firms and two foreign firms. Their complains led to proposals for six recommendations: recognize the strategic importance of the drug industry, conclude several years of contracts between the Economic committee on health products and the drug industry, facilitate clinical trails of drugs in France, favor relations between the national drug industry and university research centers, Inserm, Cnrs and the administration, encourage the development of biotechnology firms which represent one of the most promising areas of therapeutic research, propose the creation of an interministerial drug counsel presided by the Prime Minister to establish and implement a common national strategy.


Interstitial chemotherapy plus systemic chemotherapy for glioblastoma patients: improved survival in sequential studies.
We investigated the efficacy of 3 different systemic chemotherapy regimes in 122 patients with histologically confirmed glioblastoma, KPS > 60, age < 65. Locoregional chemotherapy was delivered to 22 patients from all three systemic chemotherapy groups. Chemotherapy was given before and during radiotherapy, which was the same for all patients consisting of unconventional fractionation with a break between courses. Survival (Kaplan-Meier) was significantly longer in the subgroup receiving cisplatinum plus BCNU compared to those receiving cisplatinum plus etoposide or carboplatinum plus BCNU with median survival time 21.5 months, 15 months and 15 months respectively (log rank test p = 0.01). Survival was also significantly longer in patients who received locoregional therapy compared to those who received only systemic chemotherapy (21 vs 15 months, p = 0.01). Univariate analysis showed that age, postoperative Karnofsky status and extent of resection were not predictive of survival in the series, although there were trends to better outcome in younger patients and those undergoing total/subtotal resection. Age, systemic chemotherapy type and interstitial treatment were included in a multivariate analysis, and both locoregional treatment and chemotherapy with cisplatinum plus BCNU were significantly predictive of survival [P = 0.01]. These encouraging preliminary results suggest that further trials with locoregional and systemic therapy prior to radiotherapy are worth pursuing.


Pulmonary disorders and exercise.
The respiratory system rarely limits exercise in the normal subject. In patients with chronic pulmonary processes or in the elite athlete, however, the respiratory system may indeed be the limiting factor. Common respiratory disorders include chest pain syndromes, cough, exercise-induced asthma, and vocal cord dysfunction. Chronic lung diseases such as asthma, COPD, and interstitial lung disease impact exercise capacity and endurance. Exercise testing can be useful to distinguish acute and chronic pulmonary causes of dyspnea during exercise, as well as to differentiate between cardiac and pulmonary causes.


Angiotensin-converting enzyme gene I/D polymorphism and carotid artery disease in renovascular hypertension.
There is evidence linking the activation of the renin-angiotensin system (RAS) with target organ damage in renovascular hypertension (RVH). A genetic association of the DD genotype of the angiotensin-converting enzyme (ACE) gene with cardiovascular complications has been found in various clinical conditions. The aim of our study was to determine whether the insertion/deletion (I/D) polymorphism of the ACE gene is associated with the high prevalence of target organ damage reported in RVH. A total of 65 atherosclerotic patients (age 68.2 +/- 5.2 years) with RVH and 49 atherosclerotic patients (age 68.0 +/- 6.3 years) with essential hypertension (EH) were sequentially enrolled when attending the outpatient clinic for specialist assessment of their vascular disorder. Cardiac, renal, and vascular involvement were assessed in both groups and blood was taken for genetic analysis. Patients with RVH had a higher prevalence of left ventricular hypertrophy (LVH), carotid artery disease, and albuminuria than those with EH. In RVH, but not in EH, the DD genotype was significantly associated with severe arterial disease. In RVH, carotid disease (lumen narrowing >60%) was present in 62% of DD patients versus 25% of the other genotypes (OR = 4.90, 95% CI: 1.70-14.13). Such an association was also present in peripheral vascular disease: 72.4% in DD patients versus 41.6% in the other genotypes (OR = 3.67, 95% CI = 1.29-10.36). Logistic regression analysis showed that the DD genotype was the strongest predictor of risk of severe carotid disease. We conclude that, in atherosclerotic RVH, there is an association of the severity of vascular disease with the DD genotype of the ACE gene.


Livestock improvement: art, science, or industry?
The shift in perspectives about livestock improvement over a 70-yr period is reviewed. The view changes from livestock improvement as an art, through its becoming a science, to its application as a technology in industry. The use of scientific tools in corporate settings for poultry, dairy, and swine breeding usually involves a strong focus on the economics of production, and this focus determines that selection indexes should be used. Such focus has seemed to not have been present in breeding for the extensively managed species and livestock classes but seems needed in order to provide a basis for organization and direction of positive contributions of the breeding segment to the production segment.


Questions surrounding the optimal time for surgical treatment of pelvic organ prolapse.
The purpose of study is to evaluate the recurrence rate of pelvic organ prolapse after surgical treatment and pre- to postoperative changes in sexual function of patients with different stages of pelvic organ prolapse. The presented study was a single-centre observational nonrandomized analysis of an ongoing prospective cohort study evaluating anatomical and clinical outcomes in reproductive aged women scheduled for nature tissue repair of POP staged I-III. Two hundred and ten women were recruited, of whom 120 (57.1%) had the advanced prolapse form (POP-Q III). Women at preoperative POP stage I-II were compared with women at stage III without apical prolapse. The best effectively rate with low recurrence depends on preoperative prolapse stage. The overall objective success rate was about 80% in five years in patients with preoperative stage I-II. Study shows a significant improvement in sexual function in all patients with pelvic organ prolapse in five years after surgery. This study showed that women with advanced POP have a higher risk of recurrence after POP native tissue repair compared with early stages and proved the improvement of sexual function especially in women with advanced prolapse forms. Women with early stage of POP should be advised to postpone surgery until progression of complaints because of the high recurrence risk.


Developmental and reproductive toxicity of soybean isoflavones to immature SD rats.
To investigate the dose-dependent toxic effect of soybean isoflavone extracts (SIE) on reproductive development in immature rats. Growing male and female rats (n = 50 each, 4 weeks) were divided into five groups fed with a standard cereal-based diet and gastrogavaged daily with 0, 30, 150, 300, and 600 mg SIE/kg body weight, respectively, for 12 weeks. Body weight, organ weights, and serum level of estrogen and testosterone were measured. Oral administration of SIE had no effect on food intake but decreased food efficiency ratio (P < 0.01). Suppression on body weight gain by SIE was dose-dependent and the effect was greater on male than on female rats (P < 0.01). SIE at high doses exhibited hepatotoxicity by increasing a relative liver weight, and also caused a smaller uterus but a greater relative ovary in female rats, while leading to larger relative testis and epididymis in male rats. SIE could decrease progesterone concentrations in female rats, whereas in male rats it reduced not only total testosterone level but also sperm count compared with the control group (P < 0.05). SIE at a range of 50-1000 times of human intake level affects not only growth but also development of reproductive system in growing rats.


Contact lens prescriptions: a clinicolegal view.
The release of contact lens prescriptions is regulated by a variety of laws, and optometrists need to be familiar with these requirements to determine when prescriptions must be provided to patients or third parties. We recommend that contact lens prescriptions include the refractive data, lens parameters, lens manufacturer, expiration date, number of permissible refills, the notation "for daily wear only" if the lenses are not intended for extended wear, and other appropriate information intended to ensure that the patient will obtain the lenses prescribed if the prescription is presented to a dispenser.


A rapid, efficient and sensitive plate assay for detection and screening of l-asparaginase-producing microorganisms.
l-Asparaginase-producing microbes are conventionally screened on phenol red l-asparagine-containing plates. However, sometimes the contrast of the zone obtained (between yellow and pink) is not very sharp and distinct. In the present investigation, an improved method for screening of the microorganisms producing extracellular l-asparaginase is reported wherein bromothymol blue (BTB) is incorporated as pH indicator in l-asparagine-containing medium instead of phenol red. Plates containing BTB at acidic pH are yellow and turn dark blue at alkaline pH. Thus, a dense dark blue zone is formed around microbial colonies producing l-asparaginase, differentiating between enzyme producers and non-producers. The present method is more sensitive and accurate than the conventional method for screening of both fungi and bacteria producing extracellular l-asparaginase. Furthermore, BTB gives a transient green colour at neutral pH (7.0) and dark blue colour at higher pH 8.0-9.0, indicating the potency of the microorganism for l-asparaginase production.


E-cadherin adhesion molecule and syndecan-1 expression in various thyroid pathologies.
Cadherins and syndecans are transmembrane glycoproteins implicated in cell-cell and cell-matrix adhesion. Impairment of cadherin and syndecan mediated adhesion is likely to constitute one of the main factors leading to the reduced cell-cell and cell-matrix adhesion characteristics of tumor cells and play a pivotal role in the acquisition of invasive and metastatic proprieties by neoplastic epithelial cells. To elucidate the role and alterations of syndecan-1 expression in comparison with those of E-cadherin in normal and pathological thyroid glands (TG). A total of 55 TG carcinomas, 40 TG adenomas, 40 cases of hyperplastic TG disorders and 20 cases of normal TG autopsy samples, were evaluated by immunohistochemistry. The staining intensity, and localization of syndecan-1 and E-cadherin in sequential sections were examined, and semi-quantified. Immunostaining of syndecan-1 and E-cadherin was strong in normal follicular TG epithelial cells, and located mainly in basolateral membrane. No significant change was seen in either molecule in hyperplastic TG disorders compared with TG adenomas. A significant reduction in expression of both syndecan-1 and E-cadherin was seen in well-differentiated TG carcinomas as compared with normal TG epithelium (p = 0.0001 and p = 0.032, respectively). Similarly, there was a significant reduction of both molecules expression in poorly differentiated and anaplastic TG carcinomas compared to well differentiated tumors (syndecan-1: p = 0.0037; and E-cadherin: p = 0.075). Decreased E-cadherin and syndecan-1 expression along with decreasing cellular differentiation may be involved in the complex mechanism of progression of TG pathology.


Hydrogen-bonded bilayers in 7-benzyl-3-tert-butyl-1-phenyl-4,5,6,7-tetrahydro-1H-spiro[pyrazolo[3,4-b]pyridine-5,2'-indan]-1',3'-dione.
In the title compound, C₃₁H₂₉N₃O₂, the reduced pyridine ring adopts a conformation intermediate between the envelope and half-chair forms. The aryl rings of the benzyl and phenyl substituents are nearly parallel and overlap, indicative of an intramolecular π-π stacking interaction. A combination of two C-H∙∙∙O hydrogen bonds and one C-H∙∙∙N hydrogen bond links the molecules into a bilayer having tert-butyl groups on both faces.


Constructing neural networks for multiclass-discretization based on information entropy.
Cios and Liu (1992) proposed an entropy-based method to generate the architecture of neural networks for supervised two-class discretization. For multiclass discretization, the inter-relationship among classes is reduced to a set of binary relationships, and an independent two-class subnetwork is created for each binary relationship. This two-class-based method ends up with the disability of sharing hidden nodes among different classes and a low recognition rate. We keep the interrelationship among classes when training a neural network. Entropy measure is considered in a global sense, not locally in each independent subnetwork. Consequently, our method allows hidden nodes and layers to be shared among classes, and presents higher recognition rates than the two-class-based method.


Hemorrhagic recurrence of neovascular age-related macular degeneration not predicted by spectral domain optical coherence tomography.
To report a case in which a patient with neovascular age-related macular degeneration developed a large submacular hemorrhage 2 days after spectral domain optical coherence tomography imaging, which revealed no intra- or subretinal fluid. A noninterventional case report. A 93-year-old woman with neovascular age-related macular degeneration was seen for a regular follow-up examination 3 years after treatment with verteporfin photodynamic therapy in which lesion quiescence was achieved. Visual acuity was stable at 20/200, and spectral domain optical coherence tomography scans using 2 different instruments revealed no intra- or subretinal fluid. Two days after clinical examination and imaging, the patient presented with a large submacular hemorrhage and 5/400 vision. Hemorrhagic exudation from choroidal neovascularization in age-related macular degeneration may occur suddenly, even in the absence of fluid detected by spectral domain optical coherence tomography.


Activation of glucagon-like peptide-1 receptor inhibits growth and promotes apoptosis of human pancreatic cancer cells in a cAMP-dependent manner.
Glucagon-like peptide-1 (GLP-1) promotes pancreatic β-cell regeneration through GLP-1 receptor (GLP-1R) activation. However, whether it promotes exocrine pancreas growth and thereby increases the risk of pancreatic cancer has been a topic of debate in recent years. Clinical data and animal studies published so far have been controversial. In the present study, we report that GLP-1R activation with liraglutide inhibited growth and promoted apoptosis in human pancreatic cancer cell lines in vitro and attenuated pancreatic tumor growth in a mouse xenograft model in vivo. These effects of liraglutide were mediated through activation of cAMP production and consequent inhibition of Akt and ERK1/2 signaling pathways in a GLP-1R-dependent manner. Moreover, we examined GLP-1R expression in human pancreatic cancer tissues and found that 43.3% of tumor tissues were GLP-1R-null. In the GLP-1R-positive tumor tissues (56.7%), the level of GLP-1R was lower compared with that in tumor-adjacent normal pancreatic tissues. Furthermore, the GLP-1R-positive tumors were significantly smaller than the GLP-1R-null tumors. Our study shows for the first time that GLP-1R activation has a cytoreductive effect on human pancreatic cancer cells in vitro and in vivo, which may help address safety concerns of GLP-1-based therapies in the context of human pancreatic cancer.


The minimally abnormal Papanicolaou smear.
The Bethesda system has helped to standardize the nomenclature for cervical cytology. Previously used cytologic classification systems failed to define modern histopathologic concepts. The Bethesda system also has dramatically increased the number of Papanicolaou smears classified as minimally abnormal. While high-grade squamous intraepithelial lesions (cervical intraepithelial neoplasia 2 and 3) clearly require colposcopic evaluation, the minimally abnormal Pap smear may not always require colposcopic assessment. Common minimally abnormal cytologic categories include atypical squamous cells of undetermined significance, low-grade intraepithelial lesions and atypical glandular cells. New guidelines propose a conservative and expectant approach for these mild abnormalities. Understanding the meaning of these Pap smear reports and instituting appropriate treatments will improve patients care, reduce clinician anxiety and help ensure the best care for patients.


Oxidation of As(III) by potassium permanganate.
The oxidation of As(III) with potassium permanganate was studied under conditions including pH, initial As(III) concentration and dosage of Mn(VII). The results have shown that potassium permanganate was an effective agent for oxidation of As(III) in a wide pH range. The pH value of tested water was not a significant factor affecting the oxidation of As(III) by Mn(VII). Although theoretical redox analyses suggest that Mn(VII) should have better performance in oxidization of As(III) within lower pH ranges, the experimental results show that the oxidation efficiencies of As(III) under basic and acidic conditions were similar, which may be due to the adsorption of As(III) on the Mn(OH)2 and MnO2 resulting from the oxidation of As(III).


Organization of the primary projections of the lateral line nerves in the lamprey Lampetra japonica.
The lateral line sensory system of Lampetra japonica is innervated by the anterior and posterior lateral line nerves. The anterior lateral line nerve innervates all electroreceptors throughout the body and mechanoreceptors of the head. The posterior lateral line nerve innervates trunk mechanoreceptors. The anterior lateral line nerve consists of two ganglia (anterior lateral line and intracapsular) and four major peripheral branches (superficial ophthalmic, buccal, hyomandibular, and recurrent nerves). The posterior lateral line nerve has one posterior lateral line ganglion and one peripheral branch. The location and central projection patterns of the primary sensory neurons of these branches of the lateral line nerves were studied with the aid of horseradish peroxidase labeling. The ganglion cells of the buccal nerve were found in the rostral half, and those of the hyomandibular nerve were found in the caudal half of the medial part of the anterior lateral line ganglion. The lateral part of the anterior lateral line ganglion contains ganglion cells of the recurrent nerve and the superficial ophthalmic nerve. The rostral half of the intracapsular ganglion contains ganglion cells of the recurrent, hyomandibular, and buccal nerves. The ganglion cells of the posterior lateral line nerve were found in the posterior lateral line ganglion. The buccal nerve afferents terminated mainly in the lateral part of the ipsilateral mechanoreceptive medial nucleus. The peripheral part of the electroreceptive dorsal nucleus also received several afferents. The hyomandibular afferents terminated ipsilaterally in the central part of the medial nucleus and in the dorsolateral part of the dorsal nucleus. Some afferents of the hyomandibular nerve ascended and descended in the descending nucleus of the trigeminal nerve near its dorsal margin. The ventral nucleus, the primary nucleus of the VIIIth nerve, received a few fibers of the buccal and hyomandibular nerves. In the recurrent nerve, the fibers of the lateral part of the anterior lateral line ganglion terminated throughout the entire dorsal nucleus, and the fibers of the intracapsular ganglion projected to the dorsolateral part of the nucleus. The afferents of the posterior lateral line nerve terminated in the medial part of the ipsilateral medial nucleus and in the lateral part of the contralateral medial nucleus. In the cerebellar area, afferents of the anterior lateral line nerve were located laterally to those of the posterior lateral line nerve. Several fibers terminated in some branchiomotor nuclei, the cerebellar crest, and the dorsal gray near the obex level. No efferent cell bodies were found in the place where efferent neurons of the VIIIth nerve have been previously reported.


Post-renal transplantation weight gain: its causes and its consequences.
A tendency to increased body mass index (BMI) occurs after renal transplantation. The objective of this study was to analyze the causes and consequences of this weight gain. Two hundred twelve renal transplant recipients were divided into 3 groups according to the evolution of their BMI: BMI loss (group 1); BMI increase <10% (group 2); and BMI increase >10% (group 3). The mean BMI gain was 6.2%, weight gain was 3.9 kg, and BMI gain was 1.4 kg/m(2). The patients in group 3 were younger, but there were no other significant differences in gender, preoperative diabetes, acute rejection, or prior BMI. Blood pressure was similar in all 3 groups, but more group 3 patients needed antihypertensive treatment. A progressive increase in total and low-density lipoprotein (LDL)-cholesterol was also observed as patients showed increased BMI. No differences were observed regarding carbohydrate metabolism. Groups 1 and 3 showed a more unfavorable micro-inflammatory profile. The creatinine clearance level was better in group 3 compared with group 1. We found no differences regarding the number of nonfatal postoperative cardiovascular events.


[Persons living with HIV/AIDS: ethnic and sociocultural differences in Chile].
The association between ethnicity and HIV/AIDS is an emerging and unexplored issue in Chile. To determine the profile of patients with HIV/AIDS by ethnicity and socioeconomic factors associated with diagnostic-therapeutic opportunity in the Araucania and Metropolitan regions. Cross-sectional study with 558 patients from two centers of HIV/AIDS in Chile. Data were collected using a questionnaire with clinical and sociocultural data obtained under informed consent. Descriptive analysis raw and stratified associations for each variable was performed. Mapuche patients were mostly male, heterosexual (53.1%), lower average age (36.7 years), educational and income level lower than no Mapuche patients. The median of CD4(+) lymphocytes from Mapuche patients was the lowest in the sample, less than 51 cells/mm3, under 25 percentile (CI 38-123). Lifestyle variables indicated that drug use, number of sexual partners, and relationships between men were associated with higher levels of income, education and no Mapuche ethnicity. There are differences between Mapuche and non Mapuche patients regarding their sociocultural and clinical status, which generates health inequalities.


The contribution of nuclear medicine and ultrasounds in cardiac surgery.
The constant progress in surgical techniques during the last few years have prepared the way for important developments in the field of noninvasive cardiac exploration. Their non-traumatic character, appreciable in diagnostic and preoperative examinations, become indipensable whenever there is a need to repeat the examination in order to evaluate the effects of a treatment or to monitor progress both in the short and long term. In order that such methods be adopted in cardiac surgery it is important that not only must they be without risk but also that the results obtained be clearly presented, if possible in the form of images, and allow a quantitative interpretation. It is necessary also that the results can be justified both by clinical experience and also by comparison with other examinations. No procedure, not even radiologic, can at the same time explore the myocardium and its perfusion, the central circulation and the cardiac haemodynamics. By reason of their respective principles, radioisotopic methods and ultrasounds tackle cardiac problems in different ways and facilitate, by appropriate choice of methods, the selection of one diagnostic response from among several. This paper contains first of all, a resume of the principal nuclear and ultrasonic techniques used together with their basic principles. Next we try to show how these non-invasive techniques, most with dynamic imaging, can assist cardiac surgery. For this, we successively look at the different pathologies, working from the exterior (pericardium) towards the interior (intracardiac structures and central circulation) and covering the different aspects of the myocardial pathology. In each case the mutual contributions of physical techniques is specified as well as the preference for either isotopic or ultrasonic methods.


[Type III procollagen N-terminal aminopeptide and type IV collagen 7S in pleural effusion fluid].
The mechanism of pleural fibrosis in malignant and inflammatory pleural effusion remains unclear. We measured the levels of type III procollagen N-terminal amino peptide (PIIIP) and type IV collagen 7S in patients who had pleural effusion and lung carcinoma, and in others who had inflammatory diseases (parapneumonic and tuberculous pleuritis). The PIIIP level and the PIIIP/type IV collagen 7S ratio in patients with malignant pleural effusion were significantly lower than those in patients with inflammatory pleural effusion (p < 0.01), but the levels of type IV collagen 7S did not differ. The ratio of PIIIP to type IV collagen 7S was higher in patients with tuberculous pleuritis than in those with parapneumonic pleuritis (p < 0.05). These data indicate that pleural fibrotic adhesion may be accelerated in inflammatory pleural effusion because of elevated production of type III collagen; basement membrane injury in malignant and inflammatory pleural effusion may be caused by similar damage. We conclude that a high level of PIIIP and a high PIIIP/type IV collagen 7S ratio may indicate the presence of inflammatory pleuritis, and that the latter may indicate the presence of tuberculous pleuritis.


A tuberculosis model with seasonality.
The statistical data of tuberculosis (TB) cases show seasonal fluctuations in many countries. A TB model incorporating seasonality is developed and the basic reproduction ratio R(0) is defined. It is shown that the disease-free equilibrium is globally asymptotically stable and the disease eventually disappears if R(0)<1, and there exists at least one positive periodic solution and the disease is uniformly persistent if R(0)>1. Numerical simulations indicate that there may be a unique positive periodic solution which is globally asymptotically stable if R(0)>1. Parameter values of the model are estimated according to demographic and epidemiological data in China. The simulation results are in good accordance with the seasonal variation of the reported cases of active TB in China.


[The treatment of elderly and senile patients with venous trophic ulcers and type 2 diabetes mellitus.]
The effectiveness of the inclusion of sulodexide in the pharmacotherapy of complex treatment of patients (n=52) elderly and senile with a combination of chronic diseases of the veins complicated by refractory trophic ulcers of the lower extremities, and type 2 diabetes mellitus was studied. Patients were randomly randomized in the 1st (n=26) and the 2nd (n=26) groups, the statistical differences between them in age (t1-2=0,2, p1-2=0,833), sex (χ21-2=0,008, p1-2=0,991), nosology (χ21-2=0,004, р1-2=0,993); the anamnesis of chronic diseases of veins (t1-2=0,14, p1-2=0,893); duration of trophic ulcers (t1-2=0,21, p1-2=0,827); planimetric parameters of trophic ulcers (t1-2=0,18, p1-2=0,865) were not recorded. Patients of the 1st group received treatment with sulodexide according to the standard schedule for 50 days. The primary outcome of the study is the complete closure of the trophic ulcer after 1 month. Secondary outcomes are epithelization after 2 months and dynamic planimetric indices within 12 months. The effectiveness of the use of sulodexide was assessed according to the VCSS scale, dynamic changes in the malleolar volume and changes in planimetric parameters. A statistically significant improvement in the overall VSCC score was observed in both the 1st (p=0,002) and the 2nd (p=0,0016) groups in all study outcomes. At the same time, a statistically significant improvement in the VSCC scores was more pronounced in the 1st group (p<0,05). After 2 and 6 months, a statistically significant decrease in the malleolar volume of the affected lower extremity was recorded both in the 1st (t=4,17, p=0,001) and in the 2nd (t=2,4, p=0,37) groups. Clinically and statistically significant decrease in malleolar volume was more pronounced in the 1st group (p<0,05). After 30 days, trophic ulcers were closed in 9 (34,6%) cases in the 1st group and in 5 (19,2%) patients in the 2nd group (p<0,05). On day 60 epithelization was achieved in 22 (84,6%) and 12 (46,1%) patients, respectively. The time of complete epithelization in patients of the 1st and the 2nd groups was 51,2±1,6 and 78,4±2,6 days (p<0,05). The conclusion is made that sulodexide is an effective and pathogenetically grounded pharmacological preparation for the treatment of patients of elderly and senile age with chronic clinical disease C6 of clinical class and type 2 diabetes mellitus.


A mixed generalized ordered response model for examining pedestrian and bicyclist injury severity level in traffic crashes.
This paper proposes an econometric structure for injury severity analysis at the level of individual accidents that recognizes the ordinal nature of the categories in which injury severity are recorded, while also allowing flexibility in capturing the effects of explanatory variables on each ordinal category and allowing heterogeneity in the effects of contributing factors due to the moderating influence of unobserved factors. The model developed here, referred to as the mixed generalized ordered response logit (MGORL) model, generalizes the standard ordered response models used in the extant literature for injury severity analysis. To our knowledge, this is the first such formulation to be proposed and applied in the econometric literature in general, and in the safety analysis literature in particular. The MGORL model is applied to examine non-motorist injury severity in accidents in the USA, using the 2004 General Estimates System (GES) database. The empirical findings emphasize the inconsistent results obtained from the standard ordered response model. An important policy result from our analysis is that the general pattern and relative magnitude of elasticity effects of injury severity determinants are similar for pedestrians and bicyclists. The analysis also suggests that the most important variables influencing non-motorist injury severity are the age of the individual (the elderly are more injury-prone), the speed limit on the roadway (higher speed limits lead to higher injury severity levels), location of crashes (those at signalized intersections are less severe than those elsewhere), and time-of-day (darker periods lead to higher injury severity).


Subcellular imaging mass spectrometry of brain tissue.
Imaging mass spectrometry provides both chemical information and the spatial distribution of each analyte detected. Here it is demonstrated how imaging mass spectrometry of tissue at subcellular resolution can be achieved by combining the high spatial resolution of secondary ion mass spectrometry (SIMS) with the sample preparation protocols of matrix-assisted laser desorption/ionization (MALDI). Despite mechanistic differences and sampling 10(5) times less material, matrix-enhanced (ME)-SIMS of tissue samples yields similar results to MALDI (up to m/z 2500), in agreement with previous studies on standard compounds. In this regard ME-SIMS represents an attractive alternative to polyatomic primary ions for increasing the molecular ion yield. ME-SIMS of whole organs and thin sections of the cerebral ganglia of Lymnaea stagnalis demonstrate the advantages of ME-SIMS for chemical imaging mass spectrometry. Subcellular distributions of cellular analytes are clearly obtained, and the matrix provides an in situ height map of the tissue, allowing the user to identify rapidly regions prone to topographical artifacts and to deconvolute topographical losses in mass resolution and signal-to-noise ratio.


Accurate and precise determination of isotopic ratios by MC-ICP-MS: a review.
For many decades the accurate and precise determination of isotope ratios has remained a very strong interest to many researchers due to its important applications in earth, environmental, biological, archeological, and medical sciences. Traditionally, thermal ionization mass spectrometry (TIMS) has been the technique of choice for achieving the highest accuracy and precision. However, recent developments in multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) have brought a new dimension to this field. In addition to its simple and robust sample introduction, high sample throughput, and high mass resolution, the flat-topped peaks generated by this technique provide for accurate and precise determination of isotope ratios with precision reaching 0.001%, comparable to that achieved with TIMS. These features, in combination with the ability of the ICP source to ionize nearly all elements in the periodic table, have resulted in an increased use of MC-ICP-MS for such measurements in various sample matrices. To determine accurate and precise isotope ratios with MC-ICP-MS, utmost care must be exercised during sample preparation, optimization of the instrument, and mass bias corrections. Unfortunately, there are inconsistencies and errors evident in many MC-ICP-MS publications, including errors in mass bias correction models. This review examines "state-of-the-art" methodologies presented in the literature for achievement of precise and accurate determinations of isotope ratios by MC-ICP-MS. Some general rules for such accurate and precise measurements are suggested, and calculations of combined uncertainty of the data using a few common mass bias correction models are outlined.


[Mutagenic and antimutagenic activities of human whole blood, plasma and albumin].
The seeds of Crepis capillaris were used to examine the mutagenic und antimutagenic properties of human whole blood, plasma, serum albumin and gamma-globulin by recording chromosomal and chromatid aberrations. The antimutagenic activity was determined by preliminary, simultaneous, and subsequent biosubstrate treatments of the seeds. The whole and twice-diluted blood, as well as plasma, induced aberrations exceeding the level of self-arbitrary mutagenesis by 3.7-5.3 and 2.6-3.1 times, respectively. When the blood was diluted to its 20% concentration, the antimutagenic efficiency of biological fluids was recorded. Human serum albumin and gamma-globulin were found to have an antimutagenic effect. In the dilutions having no antimutagenic effect, blood, plasma, and albumin showed their ability to be effectively decrease the level of induced aberrations.


Standardizing global gene expression analysis between laboratories and across platforms.
To facilitate collaborative research efforts between multi-investigator teams using DNA microarrays, we identified sources of error and data variability between laboratories and across microarray platforms, and methods to accommodate this variability. RNA expression data were generated in seven laboratories, which compared two standard RNA samples using 12 microarray platforms. At least two standard microarray types (one spotted, one commercial) were used by all laboratories. Reproducibility for most platforms within any laboratory was typically good, but reproducibility between platforms and across laboratories was generally poor. Reproducibility between laboratories increased markedly when standardized protocols were implemented for RNA labeling, hybridization, microarray processing, data acquisition and data normalization. Reproducibility was highest when analysis was based on biological themes defined by enriched Gene Ontology (GO) categories. These findings indicate that microarray results can be comparable across multiple laboratories, especially when a common platform and set of procedures are used.


Genetic polymorphism of hOGG1 and risk of pterygium in Chinese.
Ultraviolet irradiation is known to cause oxidative DNA damage and is thought to be a major factor implicated in the pathogenesis of pterygium. The highly mutagenic 8-hydroxy-2'-deoxyguanosine, a marker for the evaluation of photo-oxidative DNA damage, can be repaired by human 8-oxoguanine glycosylase I (hOGG1). A transition of C to G at nucleotide position 1245 in exon 7 of the hOGG1 gene is associated with the substitution of cysteine for serine at codon 326. In this study, we investigated the association of the hOGG1 Ser326Cys polymorphism with pterygium in a Chinese population. In all, 70 patients and 86 controls were enrolled in this study. The Ser326Cys polymorphism was determined by the polymerase chain reaction-restriction fragment-length polymorphism analysis. The association between this genetic polymorphism and risk of pterygium was examined by chi(2)-test and logistic regression. The allelic frequencies for the Ser and Cys variants of hOGG1 gene were not significantly different between the two groups. However, when compared with Ser/Ser and Ser/Cys genotypes combined, we found that the homozygous Cys/Cys genotype was more prevalent in pterygium patients than controls (P=0.024) with the odds ratio being 2.2 (95% CI: 1.1-4.5). In the pterygium group, the mean age of patients with the Cys/Cys genotype was younger than those with the other two genotypes (P=0.025). Our findings suggest that the 1245C --> G transition in exon 7 of the hOGG1 gene, which results in Ser326Cys substitution of the enzyme, might play a role in the susceptibility of humans to pterygium.


Contact lens care products effect on corneal sensitivity and patient comfort.
To evaluate the possible effect of two leading soft contact lens care products on corneal sensitivity, relative comfort, and superficial corneal staining in adapted disposable soft contact lens wearers. Eight disposable soft contact lens wearers equally divided between habitual users of OPTI-FREE Express Lasting Comfort No Rub formula (Alcon Laboratories, Fort Worth, TX) and ReNu MultiPlus (Bausch & Lomb, Rochester, NY) were enrolled in this crossover study. The habitual lens care product was designated the first crossover period. Patients completed a visual analog scale rating of midday and end-of-day comfort, underwent slitlamp examination for staining, and had corneal sensitivity measured by Cochet-Bonnet esthesiometry before and after being switched to the alternative lens care product. The lens care product used was masked from the investigator. Patients habitually using OPTI-FREE Express reported higher comfort ratings than did patients using ReNu MultiPlus. On crossover, patients who initially used ReNu MultiPlus experienced similar comfort when using OPTI-FREE Express, but OPTI-FREE Express users experienced a substantial decrease in comfort when switched to ReNu MultiPlus. Esthesiometry showed significant differences in average sensitivity in favor of OPTI-FREE Express (P=0.0041). Statistical trends supported observed increases in corneal sensitivity when switching to OPTI-FREE Express and decreased corneal sensitivity when switching to ReNu MultiPlus. ReNu MultiPlus was also associated with slightly more corneal staining. ReNu MultiPlus, a biguanide-based contact lens care product, was associated with decreased comfort during midday and end-of-day periods. ReNu MultiPlus was also associated with significant reduction in relative corneal sensitivity compared to Polyquad-based OPTI-FREE Express. Disturbance to normal corneal sensitivity may play a role in contact lens-related dry eye and discomfort. Further investigation is warranted.


Solanum torvum inhibits Helicobacter pylori growth and mediates apoptosis in human gastric epithelial cells.
Helicobacter pylori infection is associated with an increased risk for development of duodenal ulcers, gastric ulcers, gastric adenocarcinomas and gastric lymphomas. However, resistant strains have developed because of antibiotic treatment. In this study, the water, acetone, chloroform and methanol extracts of two Solancaceae plants, Solanum erianthum and Solanum torvum (ST), were tested for their anti-H. pylori activity. All of ST extracts were able to inhibit the growth of H. pylori and showed better activities against antibiotic strains than the reference strain. Among them, chloroform extract of ST (ST-C) possessed the strongest ability to inhibit H. pylori growth. Association assay was performed by the ST-C showing that ST-C was able to interrupt the association of bacteria to host cells. Furthermore, H. pylori-induced apoptosis could also be efficiently suppressed by the ST-C. It was able to interfere with the interaction between bacteria and host cells and also target H. pylori-induced gastric injury by suppressing apoptosis. Therefore, ST-C may offer a new approach for the treatment of H. pylori. Further studies on the elucidation of the molecular mechanisms of the growth inhibition on H. pylori by ST-C, and to identify active compounds in the plants are in progress.


Vertical profiles of phosphorus fractions in the sediment in a chain of reservoirs in North China: Implications for pollution source, bioavailability, and eutrophication.
The level of eutrophication in reservoirs is dependent on their internal and external P loads. Identifying the P pollution characteristics and its fractional composition in sediments is therefore necessary to determine the potential bioavailability and dominant sources of P for effective water pollution control. In this study, we investigated the P pollution characteristics in the overlying water and sediment in a chain of reservoirs (the Panjiakou (PJK), Daheiting (DHT) and Yuqiao (YQ) Reservoirs) in North China. Our results showed that the P concentrations in the overlying water of the YQ Reservoir was higher than that of the PJK and DHT Reservoirs, but the sediment P loading and P bio-availability were lower than the PJK and DHT Reservoirs. However, the sediment P release risk in the YQ Reservoir was higher than the DHT and PJK Reservoirs. The YQ Reservoir was mainly polluted by internal sediment P release and external sources predominantly derived from the inflowing polluted Sha River Basin. Various forms of P in the DHT Reservoir decreased with depth, and the P in the overlying water column was mainly sourced from internal P release due to sediment accumulation of excess P from human activities. In recent years, the proportion of bio-available P (BAP) in the PJK and YQ Reservoirs had increased, and the proportion of the more inert Al-P and Ca-P in the PJK Reservoir decreased. Ca-P in the YQ Reservoir had also decreased, indicating that inert P has been gradually transformed into active P in the PJK and YQ Reservoirs in recent years. The observed differences in P loading and sedimentary P fractions indicate different pollution characteristics and sources between the three reservoirs. We therefore recommend site-specific remediation strategies for effective control on P pollution in the three eutrophic reservoirs.


Neurally adjusted ventilatory assist improves patient-ventilator interaction.
To determine if, compared with pressure support (PS), neurally adjusted ventilatory assist (NAVA) reduces trigger delay, inspiratory time in excess, and the number of patient-ventilator asynchronies in intubated patients. Prospective interventional study in spontaneously breathing patients intubated for acute respiratory failure. Three consecutive periods of ventilation were applied: (1) PS1, (2) NAVA, (3) PS2. Airway pressure, flow, and transesophageal diaphragmatic electromyography were continuously recorded. All results are reported as median (interquartile range, IQR). Twenty-two patients were included, 36.4% (8/22) having obstructive pulmonary disease. NAVA reduced trigger delay (ms): NAVA, 69 (57-85); PS1, 178 (139-245); PS2, 199 (135-256). NAVA improved expiratory synchrony: inspiratory time in excess (ms): NAVA, 126 (111-136); PS1, 204 (117-345); PS2, 220 (127-366). Total asynchrony events were reduced with NAVA (events/min): NAVA, 1.21 (0.54-3.36); PS1, 3.15 (1.18-6.40); PS2, 3.04 (1.22-5.31). The number of patients with asynchrony index (AI) >10% was reduced by 50% with NAVA. In contrast to PS, no ineffective effort or late cycling was observed with NAVA. There was less premature cycling with NAVA (events/min): NAVA, 0.00 (0.00-0.00); PS1, 0.14 (0.00-0.41); PS2, 0.00 (0.00-0.48). More double triggering was seen with NAVA, 0.78 (0.46-2.42); PS1, 0.00 (0.00-0.04); PS2, 0.00 (0.00-0.00). Compared with standard PS, NAVA can improve patient-ventilator synchrony in intubated spontaneously breathing intensive care patients. Further studies should aim to determine the clinical impact of this improved synchrony.


[Study of the pelvic lymph nodes in urology].
The lymph nodes of genito-urinary cancers are discussed and the topography of the pelvic lymph nodes is described. The various staging methods are described including imaging modality, examination by operative biopsy, showing the specificity, sensitivity and accuracy of these methods. According to the author, these two methods complement each other.


Rebuilding the R&D engine in big pharma.
From December 2000 to February 2008, the top 15 companies in the pharmaceutical industry lost roughly $850 billion in shareholder value. Although a number of factors--including the rise of generics, pricing pressures, regulatory requirements, and legal entanglements--are to blame, Garnier, the CEO of GlaxoSmithKline, believes that declining R&D productivity is his industry's primary problem. The way to solve it, he says, is to return power to the scientists--by reorganizing R&D into highly focused groups headed by inspirational leaders, seeking the best science outside as well as inside a company, fixing broken processes, and promoting a strong culture of innovation and passion for excellence. GSK has replaced its organizational pyramid with 12 "centers of excellence. The company has worked to untangle the quest for breakthrough drugs from the effort to develop best-in-class offerings and has overhauled incentives for the scientists who actually make discoveries. It has also pursued contractual relationships with academia and biotech companies in a bid to secure the best science, wherever it may reside. When the company began a sweeping reengineering of its R&D, it had only two products in late-stage development. Today it has 34--the most in the industry. But much more remains to be done, the author says. Significant cost efficiencies could be achieved by offshoring clinical trials. Development of new blockbuster drugs could be simplified and accelerated if researchers targeted only a limited segment of the potential patient population and then expanded to others over time. The innovation malaise in pharmaceuticals is not unique, Garnier says. Many other industries face the same challenges. A cultural revolution and a broad transformation of the organization are necessary first steps to rebuilding the R&D engine.


Speech movements do not scale by orofacial structure size.
The potential role of a size-scaling principle in orofacial movements for speech was examined by using between-group (adults vs. 5-yr-old children) as well as within-group correlational analyses. Movements of the lower lip and jaw were recorded during speech production, and anthropometric measures of orofacial structures were made. Adult women produced speech movements of equal amplitude and velocity to those of adult men. The children produced speech movement amplitudes equal to those of adults, but they had significantly lower peak velocities of orofacial movement. Thus we found no evidence supporting a size-scaling principle for orofacial speech movements. Young children have a relatively large-amplitude, low-velocity movement strategy for speech production compared with young adults. This strategy may reflect the need for more time to plan speech movement sequences and an increased reliance on sensory feedback as young children develop speech motor control processes.


Significant premaxillary augmentation.
Substantial premaxillary augmentation is necessary as an adjunctive treatment in most cleft rhinoplasties and in those patients exhibiting an acute nasolabial angle due to retrusion of the premaxila. We describe our technique of evaluation and treatment of this condition using a custom-carved piece of material made from a woven combination of Teflon and organic fibers (Proplast). Detailed technical illustrations as well as patient results are demonstrated. We have found this technique in our hands to be a simple, safe, and effective means of correction of significant premaxillary retrusion.


Scavenging free radicals improves endothelial dysfunction in human coronary arteries in vivo.
The effect of a novel free radical scavenger, edaravone, on coronary endothelial dysfunction was examined in patients who had no significant stenosis of coronary arteries, to elucidate the role of free radicals on coronary endothelial dysfunction. The coronary blood flow (CBF) responses to acetylcholine (ACh) were measured by quantitative coronary arteriography and the intracoronary Doppler technique before and after the administration of edaravone. Twenty-four patients were divided into two groups on the basis of CBF responses to ACh; those with "attenuated" (%Delta CBF < 300%, n = 12) and "normal" (%Delta CBF > 300%, n = 12) flow responses. An intracoronary infusion of edaravone significantly improved ACh-induced increases in CBF in patients with attenuated flow responses; however, edaravone had no effect in those with normal flow responses (36.8% +/- 7.3% vs 0.0% +/- 5.1%, P < 0.01). The plasma levels of nitric oxide compounds (NOx) in the attenuated response group were lower than those in the normal group (35.7 +/- 2.3 vs 49.4 +/- 6.2 muM, P < 0.01) and correlated with the magnitude of CBF improvement by edaravone (r = 0.566, P < 0.01). The plasma level of malondialdehyde and 4-hydroxynonenal, which indicates the level of oxidative stress, in the attenuated group was higher than that in the normal group (6.9 +/- 0.9 vs 3.3 +/- 0.5 muM, P < 0.01) and correlated with the magnitude of CBF improvement by edaravone (r = 0.854, P < 0.01). A free radical scavenger improved the ACh-induced CBF response in patients with coronary atherosclerosis in vivo. Therefore, the current results suggest that scavenging free radicals has a beneficial effect for patients with coronary endothelial dysfunction.


Outcomes of multidisciplinary treatment for posterior cerebral artery aneurysms.
Posterior cerebral artery (PCA) aneurysms are rare and often challenging to manage. Since Drake's historical report regarding PCA aneurysms, there has been limited additional information on recent advancements in either microsurgical or endovascular tools. We report a series of 25 consecutive cases and attempt to extrapolate useful information for managing PCA aneurysms. A total of 25 cases of PCA aneurysm that were treated either by microsurgical or endovascular methods were selected and retrospectively reviewed. The clinical data, radiographic findings, and outcomes associated with the treatment modality were analysed. The case series included 13 women and 12 men with a mean age of 52 years, ranging from 11 to 75 years. Fourteen aneurysms were ruptured, 7 aneurysms caused a direct mass effect, and the remaining 4 aneurysms were found incidentally. Most aneurysms were located in the P1 through P2A segment of the PCA (19 aneurysms, 76%). Seven aneurysms (28%) were large-giant in size (>20 mm), 4 of which had a thrombosed sac. Microsurgical treatment was the primary treatment in 15 aneurysms, including 9 successful direct clip ligations, 3 aneurysms that were surgically trapped without a bypass, and 2 wrapped aneurysms. One giant thrombosed aneurysm was incompletely clipped; subsequently, the large remnant was coil-embolised. Endovascular coil embolisation was performed for 6 aneurysms, stent-assisted coil embolisation was performed for 2 aneurysms, and 2 aneurysms were treated by endovascular occlusion of the parent artery. Permanent deficits acquired after treatment included limb weakness, palsy of the third cranial nerve, and hemianopsia in 5 cases (20%). There was no mortality. Overall, 22 patients (88%) showed favourable clinical outcomes according to the modified Rankin Scale Score (≤2) at the mean clinical follow-up period of 43.2 months (range: 2-130 months). The present case series suggests that treating PCA aneurysms with microsurgical or endovascular options can achieve a comparable outcome when a judicious decision is made. Endovascular treatment had excellent anatomical and clinical outcomes for non-mass compressing, non-giant, saccular aneurysms. Given the propensity for the large-giant, dysplastic nature of PCA aneurysms to develop in younger patients, microsurgical competence should be maintained. Along with careful evaluation of the anatomic collaterals over the PCA territory, therapeutic parent artery sacrifice may be an appropriate option without adding bypass.


Measurement of DNA damage in rat urinary bladder transitional cells: improved selective harvest of transitional cells and detailed Comet assay protocols.
Urinary bladder transitional epithelium is the main site of bladder cancer, and the use of transitional cells to study carcinogenesis/genotoxicity is recommended over the use of whole bladders. Because the transitional epithelium is only a small fraction of the whole bladder, the alkaline single cell gel electrophoresis assay (Comet assay), which requires only a small number of cells per sample, is especially suitable for measuring DNA damage in transitional cells. However, existed procedures of cell collection did not yield transitional cells with a high purity, and pooling of samples was needed for Comet assay. The goal of this study was to develop an optimized protocol to evaluate DNA damage in the urinary bladder transitional epithelium. This was achieved by an enzymatic stripping method (trypsin-EDTA incubation plus gentle scraping) to selectively harvest transitional cells from rat bladders, and the use of the alkaline Comet assay to detect DNA strand breaks, alkaline labile sites, and DNA-protein crosslinks. Step by step procedures are reported here. Cells collected from a single rat bladder were sufficient for multiple Comet assays. With this new protocol, increases in DNA damage were detected in transitional cells after in vitro exposure to the positive control agents, hydrogen peroxide or formaldehyde. Repair of the induced DNA damage occurred within 4h. This indicated the capacity for DNA repair was maintained in the harvested cells. The new protocol provides a simple and inexpensive method to detect various types of DNA damage and to measure DNA damage repair in urinary bladder transitional cells.


Fundamental frequency during phonetically governed devoicing in normal young and aged speakers.
Age-related changes in the laryngeal system can be perceived as altered vocal pitch and increased pitch variability. However, reports vary as to the nature and extent of an age effect on fundamental frequency (F0) for analyses taken over long segments of connected speech. Analysis of F0 across a smaller time frame may be more informative. Young speakers show an increase in F0 associated with phonetically governed devoicing gestures that is likely mediated by increased vocal fold stiffness. Anatomic and neurophysiologic changes in the aged larynx may limit the role of increased vocal fold stiffness in the devoicing gesture. This study tests the hypothesis that aged speakers show a smaller increase in F0 in association with the devoicing gesture for production of an intervocalic voiceless obstruent than do young speakers. Normal young and aged speakers produced a short sentence containing an intervocalic voiceless obstruent. Measures of F0 were obtained for ten cycles before voice offset and ten cycles after voice onset. Young speakers showed a small increase in F0 during devoicing whereas aged speakers showed a decrease in F0 during devoicing. Aged speakers seem to rely more on vocal fold abduction rather than a combination of abduction and tensing to achieve devoicing.


Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5).
On the basis of the drug-repositioning and redeveloping strategy, first-generation dual-target inhibitors of acetylcholinesterase (AChE) and phosphodiesterase 5 (PDE5) have been recently reported as a potentially novel therapeutic method for the treatment of Alzheimer's disease (AD), and the lead compound 2 has proven this method was feasible in AD mouse models. In this study, our work focused on exploring alternative novel tadalafil derivatives (3a-s). Among the 19 analogues, compound 3c exhibited good selective dual-target AChE/PDE5 inhibition and good blood-brain barrier (BBB) permeability. Moreover, its citrate (3c·Cit) possessed improved water solubility and good effects against scopolamine-induced cognitive impairment with inhibition of cortical AChE activities and enhancement of cAMP response element-binding protein (CREB) phosphorylation ex vivo.


Hydroxysafflor yellow A promotes α-synuclein clearance via regulating autophagy in rotenone-induced Parkinson's disease mice.
Autophagy is an intracellular degradation process that is involved in α-synuclein (α-syn) homeostasis and Parkinson's disease (PD). The purpose of this study was to investigate whether hydroxysafflor yellow A (HSYA) could promote α-syn clearance via regulating autophagy in PD mice. Male C57BL/6 mice were intraperitoneally treated with HSYA. Thirty minutes later, they were intragastrically administered with rotenone at a dose of 30 mg/kg. The hanging wire test was performed at 14 and 28 days. Then, autophagosomes and ultrastructural changes were examined by transmission electron microscopy. The expression of tyrosine hydroxylase (TH), α-syn, JNK1, p-JNK1, Bcl-2, p-Bcl-2, Beclin1, autophagy-related proteins (Atg) 7 and 12-5, and the LC3-II/LC3-I ratio were investigated by western blot. The hanging time of HSYA-treated PD mice was significantly increased compared with that of rotenone-induced PD mice (p < 0.05 or p < 0.01). Compared with rotenone-induced PD mice, treatment with HSYA augmented the formation of autophagosomes. The expression of TH, p-JNK1/JNK1, Beclin1, Atg7, Atg12-5, p-Bcl-2/Bcl-2, and the LC3-II/LC3-I ratio were significantly increased, whereas the expression of α-syn was reduced in the rotenone plus HSYA group. These results indicate that HSYA promoted α-syn clearance via regulating autophagy in rotenone-induced PD mice.


Radiation therapy for hemangioendothelioma: the university of Florida experience.
The benefit of radiotherapy (RT) for unresectable hemangioendotheliomas or patients with a high risk of local recurrence is unclear. This single-institution report describes the long-term effectiveness of RT for hemangioendothelioma. From 1976 to 2009, 14 patients with nonmetastatic hemangioendothelioma were treated with RT at our institution. Median patient age was 45 years (range, 20 to 71 y). Nine patients had hemangioendothelioma of the extremities and 5 had spinal tumors. Eleven tumors originated from bone. Most tumors (n=12) were ≤5 cm in diameter. Nine patients had multifocal tumors. Four patients underwent surgery and postoperative RT, whereas 10 had RT alone. All 4 operative patients had microscopic negative margins. Median RT dose was 52.2 Gy (range, 45 to 60 Gy) for RT alone and 62.2 Gy (range, 60 to 64.8 Gy) for postoperative patients. Seven patients received 1.5-2 Gy once daily and 7 patients received 1.2 Gy twice daily. The median follow-up was 10.3 years (range, 0.1 to 28.0 y). The 10-year local control, cause-specific survival, and overall survival rates were 100%, 86%, and 73%, respectively. Two patients experienced a distant metastasis and died within 3 months of starting definitive RT. Three patients died of intercurrent illness at a median of 10.5 years after treatment. Nine patients had no evidence of disease at most recent follow-up. No patients experienced greater than grade 1 acute or late toxicity from RT. With no local recurrences and minimal risk of toxicity, our data suggest that RT can effectively manage this disease and radical surgery compromising function or cosmesis may be safely avoided with moderate-dose RT.


Cytokines are increased in the rat hippocampus after serotonergic neuron degeneration and upregulate the expression of GDH, an enzyme involved in glutamate detoxification.
The degeneration of serotonergic neurons increases the expression of glutamate dehydrogenase (GDH) in hippocampal astrocytes. This process was demonstrated to be independent of the serotonin level. At the same time, upregulation of tumor necrosis factor (TNF) alpha and interleukin (IL)-1 alpha mRNA were observed, whereas levels of transforming growth factor (TGF) beta 1 mRNA remained unchanged. The level of GDH mRNA was increased in primary cultures of hippocampal astrocytes treated with TNF alpha and IL-1 alpha suggesting that these cytokines act on the GDH metabolism. TNF alpha and IL-1 alpha induced an increase in GDH promoter activity in C8S (an astrocytic cell line) transfected with constructs containing 5' flanking genomic sequences of GDH driving the expression of a reporter gene. These observations suggest that cytokines may be signals that upregulate the astrocytic GDH expression in response to the degeneration of serotonergic terminals in the hippocampus.


Interaction between early maternal smoking and variants in TNF and GSTP1 in childhood wheezing.
Children exposed to tobacco smoke early in life have a higher risk of wheeze. Individual susceptibility may depend on genetic factors. We studied whether variations in single nucleotide polymorphisms (SNPs) in the TNF, glutathione S transferase P1 (GSTP1) and beta2-adrenoreceptor (ADRB2) genes modify the effect of early maternal smoking on the development of childhood asthma, wheeze and allergic sensitization. In the Swedish prospective birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) (n=4089), data collection included questionnaires to measure tobacco smoke exposure and clinical outcomes up to age 4 and medical examinations with blood sampling for specific IgE measurements and genotyping. We defined early maternal smoking as daily smoking by the mother during pregnancy and/or postnatally. We investigated five TNF, six GSTP1 and three ADRB2 SNPs in 982 selected wheezers and non-wheezers. An interaction with early maternal smoking was found for three TNF SNPs (-857C/T, Intron 1, Intron 3) with respect to early wheeze (up to 2 years of age). For example, the odds ratio (OR) for developing early wheeze related to early maternal smoking was 2.4 [95% confidence interval (CI) 1.6-3.7] in children with a wild-type CC homozygote genotype of the TNF-857 SNP, while no tobacco-related risk was seen in children carrying the rare T allele. A clear dose response was observed in children with the CC genotype, with an OR of 1.3 (95% CI 1.1-1.5) per each additional pack per week smoked by the mother during pregnancy. A suggestive interaction with early maternal smoking was also seen for three GSTP1 SNPs (Intron 5, Intron 6 and Ile105Val) with respect to transient wheeze, but not for ADRB2 and wheeze phenotypes. No effect modifications were observed for allergic sensitization. Our results suggest that the risk of early childhood wheeze associated with early maternal smoking may be modified by TNF and GSTP1 polymorphisms.


Investigation of the chemical conversion of hydroperoxyeicosatetraenoate to leukotriene epoxide using stereospecifically labeled arachidonic acid. Comparison with the enzymatic reaction.
A series of stereospecifically labeled polyunsaturated fatty acids were prepared by biosynthesis from [8-DR-3H]- and [8-LS-3H]stearic acids. The labeled stearic acids were synthesized by a novel scheme employing readily available alkyne and aldehyde starting materials. The stereochemical purity of the prochiral tritium labels was judged to be greater than 99%, as determined by analysis of the octadec-1-yn-8(R)- and 8(S)-ol intermediates in the synthesis. Previously, the labeled arachidonic acids were used to investigate the stereoselectivity of hydrogen abstraction in the biosynthesis of leukotriene epoxides. We have now investigated the selectivity of hydrogen abstraction in a chemical synthesis of 14,15-leukotriene (LT) A4 from mixtures of [3-14C]- and either [10-DR-3H]- or [10-LS-3H]15(S)-HPETE methyl esters. Reaction with either chirally labeled precursor led to 70-95% retention of 3H relative to 14C in the 14,15-LTA4 and 10-Z-14,15-LTA4 products after purification by high performance liquid chromatography. The 15-dienone obtained from this reaction was consistently enriched in 3H relative to 14C after isolation and purification. Evidence was obtained to indicate that the majority of the 3H in the products was retained in its original location and configuration. These results indicate that the biomimetic chemical reaction is stereo-random with respect to hydrogen loss from carbon 10 and that, in contrast to the reaction as it occurs in leukocytes and platelets, in the chemical model the reaction begins by decomposition of the hydroperoxide group, with hydrogen loss from carbon 10 occurring as a late or final step.


The Evolution of Sagittal Spinal Alignment in Sitting Position During Childhood.
This is a cross-sectional descriptive study. The purposes of this study are to describe normative data of the sagittal plane in the sitting position within the pediatric population and document the evolution of sagittal alignment during the growth. Surgical procedures addressing the deformity aim to make the maximal correction on the coronal and transverse planes and to restore the physiological curves on the sagittal plane. Prerequisite for sagittal plane reconstruction is to know the physiological values. Children between 3 and 17 years of age, followed by pediatrics unit for nonskeleton disease with lateral radiographs of the entire spine and pelvis on sitting positions, were included to the study. Children with history of surgery or disease that may affect spine development were excluded. Children were evaluated in 4 age groups (3-6, 7-9, 10-12, and 13-17 yr) in terms of spinal sagittal alignment on sitting position. Of the screened, 124 children (49 girls, 75 boys) were included. Descriptive statistics of all possible segmental angles were summarized. Thoracic kyphosis and lumbar lordosis values were lower on sitting position than on standing position. Thoracic segmental angulations steadily increased from T1-T2 to midthoracic segments and then decreased in caudal direction. Moreover, lumbar segmental angulations steadily increased in cephalocaudal direction. Sacral slope, L4-S1 angulation, and T1-T12 and T1-S1 distance tend to increase as the age increases. Sagittal spinal alignment in the sitting position is different than that in the standing position and it changes as the child grows. There is a statistically significant difference between different age groups, especially at the cervicothoracic, thoracolumbar, and lumbosacral junctions. These findings should be taken into consideration for young nonambulatory patients who require spinal instrumentation and/or fusion. 2.


Deciphering the Multisite Interactions of a Protein and Its Ligand at Atomic Resolution by Using Sensitive Paramagnetic Effects.
Quantitative analysis of multisite interactions between a protein and its binding partner at atomic resolution is complicated because locating the binding sites is difficult and differentiating the flexibility of each binding site is even more elusive. Introduction of a paramagnetic metal center close to the binding pocket greatly attenuates the signals in the NMR spectrum upon binding. Herein, the multisite binding of hen egg white lysozyme (HEWL) with lanthanide complexes [Ln(DPA)3 ]3- (DPA=dipicolinic acid) was analyzed with sensitive paramagnetic NMR spectroscopy. Paramagnetic relaxation enhancement (PRE) revealed that HEWL interacts with [Ln(DPA)3 ]3- at four major binding sites in aqueous solution, which is in contrast to a previous X-ray structural analysis. The varied binding affinities for the ligands and different flexibilities at each binding site were in good agreement with atomistic molecular dynamics (MD) simulations. The present work demonstrates that a combination of paramagnetic NMR spectroscopy and MD simulations is a powerful tool to delineate the multisite interactions of a protein with its binding partner at atomic resolution, in terms of both affinity and flexibility.


Lesion-by-lesion correlation between uptake at FDG PET and the Ki67 proliferation index in resected pancreatic neuroendocrine tumors.
Ki67 proliferation index and tumor uptake on 18fluorodeoxyglucose positron-emitting tomography (FDG-PET) could be correlated in pancreatic neuroendocrine tumors (PanNET), but the evaluation of the former is subject to tumor heterogeneity. Explore the correlation between Ki67 and FDG-PET uptake at the lesion scale in PanNET. We identified target lesions ≥10 mm in patients operated on for a PanNET and/or associated metastases with preoperative FDG-PET and without neoadjuvant treatment. We assessed the lesion-by-lesion correlation between Ki67 and the tumor-to-liver SUVmax ratio (SUVmax T/L), and between pathological grade (G) and metabolic grade (mG) (mG1, SUVmax T/L ≤ 1, mG2, SUVmax T/L 1-2.3 and mG3, SUVmax T/L > 2.3). Twenty-one patients underwent pancreatic (n = 12), liver (n = 2) or combined surgery (n = 7). Overall, 36 target lesions (21 primary PanNET, 13 liver metastases and 2 lymph-node metastases) were identified, of median Ki67 4%. Ki67 correlated with SUVmax T/L (r = 0.55, p < 0.001). Median SUVmax T/L was 0.76, 1.41 and 2.67 for lesions G1, G2 and G3, respectively (p = 0.005). Median Ki67 was 1, 4 and 25 for lesions mG1, mG2 and mG3, respectively (p = 0.005). Uptake on FDG-PET could predict the pathological grade of PanNET lesions. Hence, FDG-PET could supplement pathological evaluation of tumor biological aggressiveness and could guide the choice of the most relevant lesions to biopsy.


Measurement of phase retardation of waveplate online based on laser feedback.
Polarization flipping accompanying with intensity transfer between two eigenstates of one laser mode happens when waveplate is placed in external cavity. The position of polarization flipping of two eigenstates is a function of phase retardation of waveplate. Phase retardation of waveplate is measured through analyzing the position of polarization flipping of two eigenstates. The measurement accuracy of phase retardation is 0.22°. A new structure of optical cement tray which can eliminate stress birefringence from optical cement process is invented. The accuracy of waveplate manufacture can be improved greatly based on the work of this article.


[Cardiovascular risk and metabolic profile in obese children and adolescents with low insulin sensitivity].
Infantile obesity is associated with metabolic disturbances (hyperinsulinism, impaired glucose, dyslipidemia) that determine a higher risk of type 2 diabetes, high blood pressure and atherosclerotic vascular disease in adulthood. Insulin resistance is a central mechanism of complications of obesity and is associated to body fat mass. To investigate insulin sensitivity and its association with anthropometric and metabolic variables in obese children. We studied 314 children aged 6 to 15 years. Of these, 235 had a body mass index (BMI) over the 95 percentile for age and sex (classified as obese) and 79 had a normal body mass index; 161 were pre-pubescent and 153 were pubescent. Weight, height, percentage of total body fat (% TBF) using the sum of 4 skinfolds, blood pressure (BP), waist circumference (WC), basal glucose (Glu) and insulin (Ins) were measured. Insulin sensitivity (IS) was calculated with the homeostasis model assessment (HOMA) and QUICKI index. Serum lipids, postprandial Glu and Ins were measured only in obese children. BMI, WC and % TBF had an inverse and significant correlation with basal IS (p <0.001). Obese children had higher BP, basal Ins, and HOMA and a lower QUICKI index, compared to normal weight children. A low basal IS was present in 58% of obese children. Obese children with low IS had higher WC, % TBF, triglycerides, total/HDL-cholesterol ratio, basal and 2-h post glucose Gli and Ins and lower HDL-cholesterol than obese children with normal IS. In prepubescent children, the risk of a low IS was 2.43 times higher with a TBF over 33%. In pubescent children, it was 2.92 times higher with a TBF over 37%. Low IS in prepubescent and pubescent obese children is associated with central obesity and a higher cardiovascular.


Stereospecific radioimmunoassays for l-ephedrine and d-ephedrine in human plasma.
Haptens were prepared by the reaction of d-ephedrine or l-ephedrine with methyl acrylate and subsequent alkaline hydrolysis of the methyl ester groups. The haptens were coupled to bovine serum albumin by a mixed anhydride method, and the resulting drug-protein conjugates were used to immunize rabbits. Antisera raised to these conjugates were highly stereospecific. Neither antiserum cross-reacted with the optical antipode of its substrate nor with racemic pseudoephedrine. Separate radioimmunoassays (RIAs), developed for d-ephedrine and l-ephedrine, were used to measure the concentrations of the enantiomers of ephedrine in the blood of two volunteers dosed with racemic ephedrine. The RIAs were validated by comparing the sum of the concentrations of the enantiomers, determined by RIA, with total ephedrine concentrations determined by a nonstereoselective GLC-ECD method.


Recent advances in the development of anticancer drugs that act against signalling pathways.
Cancer can be considered a disease of deranged intracellular signalling. The intracellular signalling pathways that mediate the effects of oncogenes on cell growth and transformation present attractive targets for the development of new classes of drugs for the prevention and treatment of cancer. This is a new approach to developing anticancer drugs and the potential, as well as some of the problems, inherent in the approach are discussed. Anticancer drugs that produce their effects by disrupting signalling pathways are already in clinical trial. Some properties of these drugs, as well as other inhibitors of signalling pathways under development as potential anticancer drugs, are reviewed.


Abnormalities of mitochondrial functioning can partly explain the metabolic disorders encountered in sarcopenic gastrocnemius.
Aging triggers several abnormalities in muscle glycolytic fibers including increased proteolysis, reactive oxygen species (ROS) production and apoptosis. Since the mitochondria are the main site of substrate oxidation, ROS production and programmed cell death, we tried to know whether the cellular disorders encountered in sarcopenia are due to abnormal mitochondrial functioning. Gastrocnemius mitochondria were extracted from adult (6 months) and aged (21 months) male Wistar rats. Respiration parameters, opening of the permeability transition pore and ROS production, with either glutamate (amino acid metabolism) or pyruvate (glucose metabolism) as a respiration substrate, were evaluated at different matrix calcium concentrations. Pyruvate dehydrogenase and respiratory complex activities as well as their contents measured by Western blotting analysis were determined. Furthermore, the fatty acid profile of mitochondrial phospholipids was also measured. At physiological calcium concentration, state III respiration rate was lowered by aging in pyruvate conditions (-22%), but not with glutamate. The reduction of pyruvate oxidation resulted from a calcium-dependent inactivation of the pyruvate dehydrogenase system and could provide for the well-known proteolysis encountered during sarcopenia. Matrix calcium loading and aging increased ROS production. They also reduced the oxidative phosphorylation. This was associated with lower calcium retention capacities, suggesting that sarcopenic fibers are more prone to programmed cell death. Aging was also associated with a reduced mitochondrial superoxide dismutase activity, which does not intervene in toxic ROS overproduction but could explain the lower calcium retention capacities. Despite a lower content, cytochrome c oxidase displayed an increased activity associated with an increased n-6/n-3 polyunsaturated fatty acid ratio of mitochondrial phospholipids. In conclusion, we propose that mitochondria obtained from aged muscle fibers display several functional abnormalities explaining the increased proteolysis, ROS overproduction and vulnerability to apoptosis exhibited by sarcopenic muscle. These changes appear to be related to modifications of the fatty acid profile of mitochondrial lipids.


The benefits, risks and costs of privacy: patient preferences and willingness to pay.
Multiple surveys show that patients want medical privacy; however, there are costs to maintaining privacy. There are also risks if information is not shared. A review of previous surveys found that most surveys asked questions about patient's privacy concerns and willingness to share their medical information. We found only one study that asked about sharing medical information for better care and no survey that asked patients about the risk, cost or comparison between medical privacy and privacy in other areas. To fill this gap, we designed a survey to: (1) compare medical privacy preferences to privacy preferences in other areas; (2) measure willingness to pay the cost of additional privacy measures; and (3) measure willingness to accept the risks of not sharing information. A total of 834 patients attending physician offices at 14 sites completed all or part of an anonymous questionnaire. Over 95% of patients were willing to share all their medical information with their treating physicians. There was no difference in willingness to share between primary care and specialty sites including psychiatry and an HIV clinic. In our survey, there was no difference in sharing preference between standard medical information and information with additional legal protections including genetic testing, drug/alcohol treatment and HIV results. Medical privacy was ranked lower than sharing social security and credit card numbers, but was deemed more private than other information including tax returns and handgun purchases. There was no statistical difference for any questions by site except for HIV/AIDS clinic patients ranking privacy of the medical record more important than reducing high medical costs and risk of medical errors (p < .05). Most patients were willing to spend a modest amount of additional time for privacy, but few were willing to pay more for additional medical privacy. Most patients were unwilling to take on additional risks to keep medical information hidden. Patients were very willing to share medical information with their providers. They were able to see the importance of sharing medical information to provide the best possible care. They were unwilling to hide information from providers if there was increased medical risk. Patients were willing to spend additional time for privacy, but most were unwilling to spend extra money. Sixty-eight percent of patients favored reducing medical costs over privacy.


IDENTIFICATION AND CLASSIFICATION OF MACULAR MORPHOLOGIC BIOMARKERS RELATED TO VISUAL ACUITY IN RADIATION MACULOPATHY: A Multimodal Imaging Study.
To identify and classify, by a multimodal imaging approach, the most relevant macular morphologic biomarkers related to visual acuity in patients affected by radiation maculopathy secondary to brachytherapy. Fifty-one consecutive patients previously treated with Iodine-125 brachytherapy because of uveal melanoma were enrolled. Each patient underwent full ophthalmologic examination including best-corrected visual acuity and multimodal macular imaging analysis. Macular morphological parameters were processed by a stepwise selection analysis. Three macular parameters were identified as the most relevant macular morphologic biomarkers of poor visual acuity: the vertical thickness of the thickest macular cyst (P = 0.0001), the presence of foveal inner segment/outer segment (IS/OS) layer disruption (P = 0.0054), and the presence of foveal retinal pigment epithelium atrophy (0.0884). The intergrader agreement for these morphologic biomarkers was 0.98, 0.92, and 0.92, respectively (interclass correlation coefficient). The vertical thickness of the thickest macular cyst, the presence of foveal retinal pigment epithelium atrophy, and IS/OS layer disruption can be used to clinically characterize radiation maculopathy. These parameters allow for separation of the edematous component of radiation maculopathy, which is potentially treatable in early disease stages, from late onset atrophic components, which are theoretically irreversible.


Phylogenomics reveals surprising sets of essential and dispensable clades of MIKC(c)-group MADS-box genes in flowering plants.
MIKC(C)-group MADS-box genes are involved in the control of many developmental processes in flowering plants. All of these genes are members of one of 17 clades that had already been established in the most recent common ancestor (MRCA) of extant angiosperms. These clades trace back to 11 seed plant-specific superclades that were present in the MRCA of extant seed plants. Due to their important role in plant development and evolution, the origin of the clades of MIKC(C)-group genes has been studied in great detail. In contrast, whether any of these ancestral clades has ever been lost completely in any species has not been investigated so far. Here, we determined the presence of these clades by BLAST, PSI-BLAST, and Hidden Markov Model searches and by phylogenetic methods in the whole genomes of 27 flowering plants. Our data suggest that there are only three superclades of which all members have been lost in at least one of the investigated flowering plant species, and only few additional losses of angiosperm-specific MIKC(C)-group gene clades could be identified. Remarkably, for one seed plant superclade (TM8-like genes) and one angiosperm clade (FLC-like genes), multiple losses were identified, suggesting that the function of these genes is dispensable or that gene loss might have even been adaptive. The clades of MIKC(C)-group genes that have never been wiped out in any of the investigated species comprises, in addition to the expected floral organ identity genes, also TM3-like (SOC1-like), StMADS11-like (SVP-like), AGL17-like and GGM13-like (Bsister) genes, suggesting that these genes are more important for angiosperm development and evolution than has previously been appreciated.


Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells.
Delta(9)-tetrahydrocannabinol (THC) exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial. Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Estrogenic effects of THC were analyzed in vitro by measuring the proliferation of estrogen-sensitive MCF7 cells. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. In contrast to 17beta-estradiol, included as positive control with an EC50 value (concentration required for 50% of maximal 17beta-estradiol-induced proliferation) of 1.00 x 10(-12) M, THC failed to induce cell proliferation in the MCF7 cell line at concentrations between 10(-13) and 10(-4) M. THC inhibited 17beta-estradiol-induced proliferation in wild-type MCF7 and MCF7-AR1 cells, with an IC50 value of 2.6 x 10(-5) M and 9 x 10(-6) M, respectively. THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level.


Enhancing the tensile properties of continuous millimeter-scale carbon nanotube fibers by densification.
This work presents a study of the tensile mechanical properties of millimeter-long fibers comprising carbon nanotubes (CNTs). These CNT fibers are made of aligned, loosely packed parallel networks of CNTs that are grown in and harvested from CNT forests without drawing or spinning. Unlike typical CNT yarn, the present fibers contain a large fraction of CNTs that span the fibers' entire gauge length. The fibers are densified after growth and network formation to study how increasing the degree of interaction among CNTs in a network by various methods influences and limits the mechanical behavior of macroscopic CNT materials, particularly for the case in which the continuity of a large fraction of CNTs across the gauge length prevents failure purely by slip. Densification is carried out using various combinations of capillary-driven densification, mechanical pressure, and twisting. All methods of densification increase the fiber density and modify the nanoscale order of the CNTs. The highest strength and stiffness values (1.8 and 88.7 N tex(-1), respectively) are observed for capillary-densified fibers, whereas the highest toughness values (94 J g(-1)) and maximum reversible energy density (1.35 kJ kg(-1) or 677 kJ m(-3)) are observed for fibers densified by mechanical pressure. The results suggest that the path to higher performance CNT materials may lie not only in the use of continuous and long CNTs but also in controlling their density and nanoscale ordering through modification of the as-grown networks, such as by capillary-driven densification.


Tubulin and CRMP-2 complex is transported via Kinesin-1.
The transport of tubulin and microtubules in a growing axon is essential for axonal growth and maintenance. However, the molecular mechanism underlying the linkage of tubulin and microtubules to motor proteins is not yet clear. Collapsin response mediator protein-2 (CRMP-2) is enriched at the distal part of growing axons in primary hippocampal neurons and plays a critical role in axon differentiation through its interaction with tubulin dimer and Numb. In this study, we show that CRMP-2 regulates tubulin transport by linking tubulin and Kinesin-1. The C-terminal region of CRMP-2 directly binds to the tetratricopeptide repeat domain of kinesin light chain 1 (KLC1). Soluble tubulin binds to the middle of CRMP-2 and forms a trimeric complex with CRMP-2/KLC1. Furthermore, the movement of GFP-tubulin in the photobleached area is weakened by knockdown of KLCs or CRMP-2. These results indicate that the CRMP-2/Kinesin-1 complex regulates soluble tubulin transport to the distal part of the growing axon.


The evolution of suture anchors in arthroscopic rotator cuff repair.
The advancement of suture anchor design and technology has fostered the transition from open to arthroscopic rotator cuff repair. Current suture-bridging constructs have greatly surpassed the biomechanical strength parameters of transosseous repairs and have shown impressive healing rates after arthroscopic rotator cuff repair. This review describes this evolution and discusses the important characteristics of suture anchors.


Binding of apoB-containing lipoproteins from unfractionated human blood sera to immobilized LDL receptor.
Binding of apoB-containing lipoproteins from unfractionated human blood sera to the immobilized bovine receptor of low density lipoproteins (LDL receptor) was studied. Peroxidase-labeled anti-human apoB antibodies were used to evaluate the lipoprotein binding. The equilibrium dissociation constant (Kd) of the interaction between apoB-containing lipoproteins from unfractionated human sera from healthy donors and the immobilized LDL receptor varied from 1 to 20 microg apoB/ml. To describe the binding of lipoproteins to the LDL receptor, a parameter of relative binding affinity (RBA) was used. RBA is inversely related to value of Kd and equal to unity for the standard serum. The RBA values for the binding of apoB-containing lipoproteins from unfractionated sera to the immobilized LDL receptor were found to correlate with the RBA values for the binding of isolated VLDL (r = 0.76, p < 0.001) and fail to correlate with the RBA values for the binding of isolated LDL. The RBA values for the binding of apoB-containing lipoproteins from unfractionated sera correlated with the RBA values for the binding of apoE-containing lipoproteins from unfractionated sera (r = 0.92, p < 0.001) and with values of triglyceride concentration in the sera (r = 0.93, p < 0.001). The RBA values for the binding of apoB-containing lipoproteins from sera of patients with FDB whose LDL were unable to bind to the LDL receptor did not significantly differ from the RBA values for the normal sera. However, the removal of VLDL from the normal sera significantly decreased the RBA values for the binding of apoB-containing lipoproteins from unfractionated sera. The results indicate that the different binding of apoB-containing lipoproteins to the immobilized LDL receptor mainly depended on the different binding of VLDL and not of LDL.


Trace element storage capacity of sediments in dead Posidonia oceanica mat from a chronically contaminated marine ecosystem.
Posidonia oceanica mat is considered a long-term bioindicator of contamination. Storage and sequestration of trace elements and organic carbon (Corg ) were assessed in dead P. oceanica mat and bare sediments from a highly polluted coastal marine area (Augusta Bay, central Mediterranean). Sediment elemental composition and sources of organic matter have been altered since the 1950s. Dead P. oceanica mat displayed a greater ability to bury and store trace elements and Corg than nearby bare sediments, acting as a long-term contaminant sink over the past 120 yr. Trace elements, probably associated with the mineral fraction, were stabilized and trapped despite die-off of the overlying P. oceanica meadow. Mat deposits registered historic contamination phases well, confirming their role as natural archives for recording trace element trends in marine coastal environments. This sediment typology is enriched with seagrass-derived refractory organic matter, which acts mainly as a diluent of trace elements. Bare sediments showed evidence of inwash of contaminated sediments via reworking; more rapid and irregular sediment accumulation; and, because of the high proportions of labile organic matter, a greater capacity to store trace elements. Through different processes, both sediment typologies represent a repository for chemicals and may pose a risk to the marine ecosystem as a secondary source of contaminants in the case of sediment dredging or erosion. Environ Toxicol Chem 2017;36:49-58. © 2016 SETAC.