Natural history of intracranial atherosclerosis: a critical review.
Intracranial atherosclerosis is responsible for a significant number of strokes. Medical therapy for this condition may fail, leaving patients at high risk for cerebral infarction and death. With advances in endovascular techniques on the horizon, understanding the prognosis of conservative treatment is essential for appropriate patient management. Although several small studies have attempted to address this issue, a comprehensive review regarding the natural history of intracranial atherosclerosis in a vessel-specific manner is lacking. Owing to heterogeneity in vascular anatomy and physiology, atherosclerosis in different vessels may represent diseases with fundamentally distinct courses. Therefore, it is important to distinguish vascular territories when studying the natural history of this condition. To this end, we critically review the literature investigating medical management of patients with intracranial atherosclerosis, segregating our findings by vessel. Analysis by this method suggests that middle cerebral artery atherosclerosis carries a lower mortality rate than stenoses involving other intracranial vessels, and that asymptomatic disease follows a more benign course. In addition, plaque progression and transcranial Doppler-detected microemboli seem to predict outcome according to limited data. This comprehensive review may help guide clinical decision-making and therapeutic developments in this patient population.


Randomized controlled trial comparing ondansetron and placebo for the reduction of spinal anesthesia-induced hypotension during elective cesarean delivery in Egypt.
To evaluate the effect of prophylactic ondansetron on spinal anesthesia-induced hypotension and bradycardia among patients undergoing elective cesarean deliveries. A prospective, double-blind, randomized, placebo-controlled trial enrolled patients aged 20-40years scheduled for elective cesarean delivery under spinal anesthesia between January 1, 2015 and January 31, 2016 at Menoufia University Hospital, Egypt. Patients were randomized to receive intravenous ondansetron 4mg in 10mL of saline or 10mL of saline. Participants and investigators were masked to group assignments. The primary outcomes were systolic and diastolic blood pressure, mean arterial pressure, and heart rate, measured at baseline, 10-minute intervals to 60minutes, and at 2hours. Per-protocol analyses were performed including patients who delivered under spinal anesthesia. The analyses included 50 patients in each group. Decreases in systolic blood pressure were reduced among patients receiving ondansetron at all time points (P<0.05) and diastolic blood pressure did not differ between the groups (P>0.05). Among patients who received ondansetron, mean arterial pressure was higher immediately and 30minutes after spinal anesthesia (P<0.05), higher heart rates were recorded immediately, 20minutes, and 50minutes after anesthesia (P<0.05), and the incidence of nausea (P=0.020) and vomiting (P=0.031) were lower. Prophylactic intravenous ondansetron significantly reduced hypotension and heart-rate fluctuations among patients undergoing elective cesarean deliveries under spinal anesthesia. Pan African Clinical Trials Registry: PACTR 201601001397193.


Utilization of sulfur and other mineral elements by growing dairy heifers treated with bovine somatotropin.
Apparent absorption and retention of Ca, P, Mg, K, Cu, Mn, Zn, and S were determined in Holstein heifers treated with recombinant bovine somatotropin (bST). Six heifers (initial BW averaged 104 kg) were assigned to various doses of bST in a 6 x 6 Latin square design with six consecutive 21-d periods. Treatments were daily i.m. injections of 0, 6.7, 33.3, 66.7, 100, or 200 micrograms of bST/kg of BW on d 8 to 21 of each period. All heifers were fed a hay-concentrate diet, and nutrient digestibilities and balances were determined on d 14 to 20 of each period. Mineral concentrations in feed, water, excreta, and blood plasma were determined with an inductively coupled argon plasma-emission spectrometer. Exogenous bST did not affect apparent absorption or retention of Ca, P, Mg, K, Cu, Mn, or Zn. Plasma CU concentration was greater (P less than .05) in heifers receiving bST (82 micrograms of Cu/dl) than in those receiving excipient (73 micrograms of Cu/dl); plasma concentrations of other elements were not affected by bST. Injection of bST did not affect S absorption, but urinary S excretion decreased (P less than .05) and S retention increased (P less than .05) as dose of bST increased. The amount of S retained (1.5 g/d) when the heifers received the largest dose of bST was approximately 50% greater than the amount retained when heifers received excipient. These results demonstrate that bST affects the postabsorptive metabolism of S. Generally, bST did not affect nutrient digestibilities. Effects of bST on dietary mineral requirements were not determined because of the relatively short (14 d) treatment periods.


Structure characterization and optical properties investigation of the four main components of the classical phenazinium dye Safranin O.
Safranin O is an important and classical phenazinium dye; since the 19th century, it has been extensively used in the academic field as a spectroscopic probe and indicator. Surprisingly, we found that this long-used reagent is without exception a mixture. In this study, the four main components in a Safranin O sample were prepared, and their chemical structures were elucidated for the first time. Optical property investigations showed that the components had somewhat different absorbance properties and markedly different fluorescence properties, and their structure-optical activity relationships were also discussed. It could be inferred that the variation of each component in the content would unavoidably result in inconsistent optical data when using this Safranin O reagent as a spectroscopic probe or indicator. Considering the accurate transfer of measurement results between laboratories, high-purity Safranin O is in urgent demand in the academic field.


Impact of viral drift on vaccination dynamics and patterns of seasonal influenza.
Much research has been devoted to the determination of optimal vaccination strategies for seasonal influenza epidemics. However, less attention has been paid to whether this optimization can be achieved within the context of viral drift. We developed a mathematical model that links different intra-seasonal dynamics of vaccination and infection to investigate the effect of viral drift on optimal vaccination for minimizing the total number of infections. The model was computationally implemented using a seasonal force of infection, with estimated parameters from the published literature. Simulation results show that the pattern of large seasonal epidemics is strongly correlated with the duration of specific cross-protection immunity induced by natural infection. Considering a random vaccination, our simulations suggest that the effect of vaccination on epidemic patterns is largely influenced by the duration of protection induced by strain-specific vaccination. We found that the protection efficacy (i.e., reduction of susceptibility to infection) of vaccine is a parameter that could influence these patterns, particularly when the duration of vaccine-induced cross-protection is lengthened. Given the uncertainty in the timing and nature of antigenically drifted variants, the findings highlight the difficulty in determining optimal vaccination dynamics for seasonal epidemics. Our study suggests that the short- and long-term impacts of vaccination on seasonal epidemics should be evaluated within the context of population-pathogen landscape for influenza evolution.


GC Method Validation for the Analysis of Menthol in Suppository Pharmaceutical Dosage Form.
Menthol is widely used as a fragrance and flavor in the food and cosmetic industries. It is also used in the medical and pharmaceutical fields for its various biological effects. Gas chromatography (GC) is considered to be a sensitive method for the analysis of menthol. GC chromatographic separation was developed using capillary column (VF-624) and a flame ionization detector (FID). The method was validated as per ICH guidelines for various parameters such as precision, linearity, accuracy, solution stability, robustness, limit of detection, and quantification. The tested validation parameters were found to be within acceptable limits. The method was successfully applied for the quantification of menthol in suppositories formulations. Quality control departments and official pharmacopeias can use our developed method in the analysis of menthol in pharmaceutical dosage formulation and raw material.


The Application of Retrograde Intrarenal Surgery to Remove a Single Large Kidney Stone During Pregnancy.
To report the application and outcome of retrograde intrarenal surgery (RIRS) to remove a large kidney stone during pregnancy. A 30-year-old woman presented with an infected kidney stone (3 cm in size) at 4 weeks of pregnancy. We decided to remove the stone due to the possibility of obstruction and infection and chose to carry out this procedure by RIRS. In order to avoid complications associated with anesthetic, the surgery was carried out after the infection had cleared and when the patient had entered the second trimester of pregnancy. First, we used an ureteral access sheath and semi-rigid ureteroscopy to evaluate the ureteral lumen. We confirmed that the ureteral access sheath had been positioned appropriately by direct visualization with a flexible ureterorenoscope. The procedure was then carried out with a radiation-free protocol and without fluoroscopy. Ho-YAG laser lithotripsy was used to fragment the stones, and these fragments were then removed in a stone basket. The patient required three sessions of RIRS to remove the stone in its entirety; during this time, the patient was 18-29 weeks into her pregnancy. During each session, we removed approximately 30% of the stone. The patient developed fever after the first operation but responded fully to antibiotics. There were no perioperative complications, and the patient only remained in hospital for 3 days. The male infant was delivered by caesarian section at 37 weeks of pregnancy without any health complications. We successfully removed a large kidney stone from a pregnant patient using an ureteral access sheath and RIRS without fluoroscopy. There were no complications indicating that this procedure can be carried out safely during pregnancy.


Serological and molecular detection of avian pneumovirus in chickens with respiratory disease in Jordan.
Avian pneumovirus (APV) causes upper respiratory tract infection in chickens and turkeys. There is a serious respiratory disease in chickens, resulting in catastrophic economic losses to chicken farmers in Jordan. The objective of this study was to investigate the role of APV as a factor in the respiratory disease of chickens in Jordan by serological and molecular methods. Thirty-eight chicken flocks were examined by competitive ELISA (23 broilers, 8 layers, and 7 broiler breeders), and 150 chicken flocks were examined by reverse-transcription PCR (133 broiler flocks, 7 layer flocks, and 10 broiler breeder flocks). Avian pneumovirus antibodies were detected in 5 out of 23 broiler flocks (21.7%), 6 out of 8 layer flocks (75%), and 7 out of 7 broiler breeder flocks (100%). Avian pneumovirus nucleic acid was detected in 17 broiler flocks (12.8%) and 3 layer flocks (42.9%). None of the broiler breeder flocks tested by reverse-transcription PCR was positive. All of the 20 detected APV isolates were subtype B. This is the first report of APV infection in Jordan. In conclusion, the Jordanian poultry industry, vaccination programs should be adjusted to include the APV vaccine to aid in the control of this respiratory disease.


Medication Related Self- efficacy among Linguistically Diverse Patients with Chronic Illnesses.
This study examines medication-related self-efficacy in a linguistically diverse group of patients with diabetes, hypertension, and elevated cholesterol. A telephone survey of 509 adults conducted in six languages (English, Spanish, Korean, Vietnamese, Mandarin, and Cantonese) was analyzed. Self-efficacy was assessed with the overall Medication Understanding and Use Self-Efficacy (MUSE) score and its two subscale scores on taking medication and learning about medications. Compared with English proficient (EP) patients, patients with limited English proficiency (LEP) had a lower mean learning self-efficacy subscale score (LEP: 14.5, EP: 15.4; p<.001) and no difference in the mean taking self-efficacy subscale score (LEP: 14.4, EP: 14.6; p=.40). Receiving verbal medication information (VMI) from providers modified the relationship between LEP status and learning self-efficacy. In conclusion, among patients with chronic illnesses, LEP patients had lower medication-related self-efficacy scores than EP patients, which may put them at greater risk for medication taking errors and lower adherence.


Porous nanosheet-based ZnO microspheres for the construction of direct electrochemical biosensors.
Nanosheet-based ZnO microsphere with porous nanostructures was synthesized by a facile chemical bath deposition method followed by thermal treatment, which was explored for the construction of electrochemical biosensors. Spectroscopic and electrochemical researches revealed the ZnO-based composite was a biocompatible immobilization matrix for enzymes with good enzymatic stability and bioactivity. With advantages of nanostructured inorganic-organic hybrid materials, a pair of stable and well-defined quasi-reversible redox peaks of hemoglobin was obtained with a formal potential of -0.345 V (vs. Ag/AgCl) in pH 7.0 buffer. Facilitated direct electron transfer of the metalloenzymes with an apparent heterogeneous electron transfer rate constant (k(s)) of 3.2s(-1) was achieved on the ZnO-based enzyme electrode. Comparative studies demonstrated the nanosheet-based ZnO microspheres were more effective in facilitating the electron transfer of immobilized enzyme than solid ZnO microspheres, which may result from the unique nanostructures and larger surface area of the porous ZnO. The prepared biosensor displayed good performance for the detection of H(2)O(2) and NaNO(2) with a wide linear range of 1-410 and 10-2700 microM, respectively. The entrapped hemoglobin exhibits high peroxidase-like activity for the catalytic reduction of H(2)O(2) with an apparent Michaelis-Menten constant (K(M)(app)) of 143 microM. The nanosheet-based ZnO could be a promising matrix for the fabrication of direct electrochemical biosensors, and may find wide potential applications in biomedical detection and environmental analysis.


Site-directed placement of three-dimensional DNA origami.
The combination of lithographic methods with two-dimensional DNA origami self-assembly has led, among others, to the development of photonic crystal cavity arrays and the exploration of sensing nanoarrays where molecular devices are patterned on the sub-micrometre scale. Here we extend this concept to the third dimension by mounting three-dimensional DNA origami onto nanopatterned substrates, followed by silicification to provide hybrid DNA-silica structures exhibiting mechanical and chemical stability and achieving feature sizes in the sub-10-nm regime. Our versatile and scalable method relying on self-assembly at ambient temperatures offers the potential to three-dimensionally position any inorganic and organic components compatible with DNA origami nanoarchitecture, demonstrated here with gold nanoparticles. This way of nanotexturing could provide a route for the low-cost production of complex and three-dimensionally patterned surfaces and integrated devices designed on the molecular level and reaching macroscopic dimensions.


Impairment of executive performance after transcranial magnetic modulation of the left dorsal frontal-striatal circuit.
The dorsal frontal-striatal circuit is implicated in executive functions, such as planning. The Tower of London task, a planning task, in combination with off-line low-frequency repetitive transcranial magnetic stimulation (rTMS), was used to investigate whether interfering with dorsolateral prefrontal function would modulate executive performance, mimicking dorsal frontal-striatal dysfunction as found in neuropsychiatric disorders. Eleven healthy controls (seven females; mean age 25.5 years) were entered in a cross-over design: two single-session treatments of low-frequency (1 Hz) rTMS (vs. sham rTMS) for 20 min on the left dorsolateral prefrontal cortex (DLPFC). Directly following the off-line rTMS treatment, the Tower of London task was performed during MRI measurements. The low-frequency rTMS treatment impaired performance, but only when the subjects had not performed the task before: we found a TMS condition-by-order effect, such that real TMS treatment in the first session led to significantly more errors (P = 0.032), whereas this TMS effect was not present in subjects who received real TMS in the second session. At the neural level, rTMS resulted in decreased activation during the rTMS versus sham condition in prefrontal brain regions (i.e., premotor, dorsolateral prefrontal and anterior prefrontal cortices) and visuospatial brain regions (i.e., precuneus/cuneus and inferior parietal cortex). The results show that low-frequency off-line rTMS on the DLPFC resulted in decreased task-related activations in the frontal and visuospatial regions during the performance of the Tower of London task, with a behavioral effect only when task experience is limited.


Effects of chlorine content and position of chlorinated phenols on their oxidation kinetics by potassium permanganate.
Chlorine content and position of chlorinated phenols have many significant effects on the reactivity of oxido-reduction. The effects of chlorine content and position of chlorinated phenols on their oxidation kinetics by potassium permanganate were evaluated through different kinetics studies. Since chlorine was an electron withdrawing atom, the substitution of chlorine on the aromatic ring decreased the oxidation rate constant by sigma-electron withdrawing conductive effect. The substitution of chlorine at ortho or para position on the aromatic ring increased the oxidation rate constant by pi-electron donating conjugative effect, and the conjugative effect could counteract the negative impact of the conductive effect to some extent. On the other hand, the substitution of chlorine at ortho position on the aromatic ring decreased the oxidation rate constant by steric hindrance effect. The oxidation rate constants of phenol and chlorinated phenol studied decreased as follow order: 4-chlorophenol > 2,4-dichlorophenol > phenol > 2,6-dichlorophenol.


Adolescent rats show cognitive rigidity in a test of attentional set shifting.
As neuropsychiatric disorders such as schizophrenia, attention deficit disorder, and mood disorders all impact executive function and are likely to be diagnosed prior to adulthood, it is important to understand the normal ontogeny of executive function. Previous behavioral research has shown that adolescents' executive function is different than that of adults. In the present study, we use a previously validated cognitive test, the intradimensional/extradimensional (ID/ED) set-shifting task, to assess attentional set shifting and reversal learning in adolescent and adult, male, Long-Evans rats. These data suggest that adolescent rats are more cognitively rigid than adult rats and have impairments in the shifting, but not formation, of an attentional set. Adolescent rats are also more susceptible to distraction than adult rats when an irrelevant stimulus dimension is introduced as part of a complex stimulus. Moreover, we find that attentional set shifting becomes adult-like at an earlier age than reversal learning. As these functions are mediated by distinct prefrontal subregions, that is, the prelimbic and orbitofrontal cortices, respectively, we hypothesize that prefrontal cortical subregions show slightly different developmental trajectories.


Saccharomyces cerevisiae Hrq1 helicase activity is affected by the sequence but not the length of single-stranded DNA.
Mutations in the human RecQ4 DNA helicase are associated with three different diseases characterized by genomic instability. To gain insight into how RecQ4 dysfunction leads to these pathologies, several groups have used the Saccharomyces cerevisiae RecQ4 homolog Hrq1 as an experimental model. Hrq1 displays many of the same functions as RecQ4 in vivo and in vitro. However, there is some disagreement in the literature about the effects of single-stranded DNA (ssDNA) length on Hrq1 helicase activity and the ability of Hrq1 to anneal complementary ssDNA oligonucleotides into duplex DNA. Here, we present a side-by-side comparison of Hrq1 and RecQ4 helicase activity, demonstrating that in both cases, long random-sequence 3' ssDNA tails inhibit DNA unwinding in vitro in a length-dependent manner. This appears to be due to the formation of secondary structures in the random-sequence ssDNA because Hrq1 preferentially unwound poly(dT)-tailed forks independent of ssDNA length. Further, RecQ4 is capable of ssDNA strand annealing and annealing-dependent strand exchange, but Hrq1 lacks these activities. These results establish the importance of DNA sequence in Hrq1 helicase activity, and the absence of Hrq1 strand annealing activity explains the previously identified discrepancies between S. cerevisiae Hrq1 and human RecQ4.


Temporal trends in the burden of chronic kidney disease in the United States.
The public health importance of chronic kidney disease (CKD) has only recently come to be appreciated and careful examination of temporal trends is warranted. The purpose of the present review was to examine existing research on temporal trends for CKD and treated end-stage renal disease (ESRD) in the United States. When the broadly representative National Health and Nutrition Examination Survey (NHANES) datasets were compared in 1988-1994 and 1999-2002, a pronounced increase in the prevalence of abnormally low glomerular filtration rate was observed when serum creatinine was used to estimate glomerular filtration rate. In contrast, glomerular filtration rate findings were almost identical when cystatin C levels were examined. Thus, although the community-wide burden of CKD is already high, uncertainty exists as to the growth rate of this problem. For treated ESRD a dramatic increase in incidence rate occurred in the 1980s and 1990s. Changing burdens of standard risk factors for CKD do not readily explain increased rates of treated ESRD, suggesting that selection criteria for dialysis and transplant programs may underlie these secular trends. If the hypothesis that nonbiological factors are major determinants of rates of treated ESRD is valid, the latter may be a poor surrogate for true ESRD and for understanding its causes and rates of progression. Given its prevalence and prognostic implications, it makes intuitive sense to monitor the burden of CKD over time; the validity of the tools used to generate an answer, however, is at least as important as the direction of the answer.


Obstructive sleep apnea after lateral medullary syndrome.
Sleep apnea occurring in association with neurologic lesions is usually of the central type. We have described a patient in whom obstructive sleep apnea followed a lateral medullary syndrome. We hypothesize that the upper airway obstruction during sleep was due to weakness of the palatal and pharyngeal muscles resulting from the neurologic lesion. The patient initially had reduced respiratory center motor output (mouth occlusion pressure) which increased significantly after tracheostomy. We conclude that obstructive as well as central apnea may follow neurologic lesions. Each patient should be carefully evaluated to provide proper treatment.


Ecology-based evaluation of groundwater ecosystems under intensive agriculture: A combination of community analysis and sentinel exposure.
Ecological criteria are needed for a comprehensive evaluation of groundwater ecosystem health by including biological components with the physical and chemical properties that are already required by European directives. Two methodological approaches to assess the ecological status of groundwater ecosystems were combined in two alluvial plains (the Ariège and Hers Rivers, southwestern France) varying in agriculture intensity (from grassland to crop rotation including maize and sunflower, and to maize monoculture). In the first approach, the composition of invertebrate assemblages (only obligate-groundwater crustaceans, i.e. stygobionts) sampled in 28 wells differing in their land use contexts was analysed. Abundance, species richness, and assemblage composition significantly changed with agricultural land use or urbanization around the wells. In the second approach, we tested an in situ exposure of sentinel organisms to quantify their response to the environmental pressures. The epigean and native amphipod species Gammarus cf. orinos was used as the sentinel species. Amphipods (30 individuals in each of 10 wells) were exposed for one week to the in situ conditions at two seasons with contrasted concentrations of pollutants. The Ecophysiological Index (EPI) synthetizing the survival rates and energetic storage decreased in wells with low oxygen and high nitrate concentrations, but only during the highest contamination period. Atrazine-related compounds negatively impacted sentinel health whatever the season. The combination of these two approaches may have major applications for orientating groundwater ecosystem management.


A genetic screen identifies Crat as a regulator of pancreatic beta-cell insulin secretion.
Glucose-stimulated insulin secretion is a critical function in the regulation of glucose homeostasis, and its deregulation is associated with the development of type 2 diabetes. Here, we performed a genetic screen using islets isolated from the BXD panel of advanced recombinant inbred (RI) lines of mice to search for novel regulators of insulin production and secretion. Pancreatic islets were isolated from 36 RI BXD lines and insulin secretion was measured following exposure to 2.8 or 16.7 mM glucose with or without exendin-4. Islets from the same RI lines were used for RNA extraction and transcript profiling. Quantitative trait loci (QTL) mapping was performed for each secretion condition and combined with transcriptome data to prioritize candidate regulatory genes within the identified QTL regions. Functional studies were performed by mRNA silencing or overexpression in MIN6B1 cells and by studying mice and islets with beta-cell-specific gene inactivation. Insulin secretion under the 16.7 mM glucose plus exendin-4 condition was mapped significantly to a chromosome 2 QTL. Within this QTL, RNA-Seq data prioritized Crat (carnitine O-acetyl transferase) as a strong candidate regulator of the insulin secretion trait. Silencing Crat expression in MIN6B1 cells reduced insulin content and insulin secretion by ∼30%. Conversely, Crat overexpression enhanced insulin content and secretion by ∼30%. When islets from mice with beta-cell-specific Crat inactivation were exposed to high glucose, they displayed a 30% reduction of insulin content as compared to control islets. We further showed that decreased Crat expression in both MIN6B1 cells and pancreatic islets reduced the oxygen consumption rate in a glucose concentration-dependent manner. We identified Crat as a regulator of insulin secretion whose action is mediated by an effect on total cellular insulin content; this effect also depends on the genetic background of the RI mouse lines. These data also show that in the presence of the stimulatory conditions used the insulin secretion rate is directly related to the insulin content.


Pseudoreversion analysis indicates a direct role of cell division genes in polar morphogenesis and differentiation in Caulobacter crescentus.
A pseudoreversion analysis was used to examine the role of cell division genes in polar morphogenesis in Caulobacter crescentus. Extragenic suppressors of temperature sensitive mutations in pleC, a pleiotropic gene required for cell motility, formation of polar phi CbK bacteriophage receptors, and stalk formation, were isolated. These suppressors, which restored motility at 37 degrees C, simultaneously conferred a cold sensitive cell division phenotype and they were mapped to the three new cell division genes divJ, divL and divK. The cold-sensitive mutations in divL, and to a lesser extent divJ, exhibited a relatively narrow range of suppression. The cold-sensitive cell division mutation in divK, by contrast, suppressed all pleC mutations examined and behaved as a classical bypass suppressor. The direct role of this cell division gene in the regulation of motility is suggested by the observation that divK341 mapped to the same locus as pleD301, a pleiotropic mutation that prevents loss of motility and stalk formation. These results provide strong evidence that the cell division and developmental pathways are interconnected and they support our earlier conclusion that cell division is required for the regulation of polar morphogenesis and differentiation in C. crescentus.


Biliary protein output by isolated perfused rat livers. Effects of bile salts.
The output of proteins into bile was studied by using isolated perfused rat livers. Replacement of rat blood with defined perfusion media deprived the liver of rat serum proteins (albumin, immunoglobulin A) and resulted in a rapid decline in the amounts of these proteins in bile. When bovine serum albumin was incorporated into the perfusion medium it appeared in bile within 20 min and the amount in the bile was determined by the concentration of the protein in the perfusion medium. The use of a defined perfusion medium also deprived the livers of bile salts and the amounts of these, and of plasma-membrane enzymes [5'-nucleotidase (EC 184.108.40.206) and phosphodiesterase I], in bile declined rapidly. Introduction of micelle-forming bile salts (taurocholate or glycodeoxycholate) to the perfusion medium 80 min after liver isolation markedly increased the output of plasma-membrane enzymes but had no effect on the other proteins. The magnitude of this response was dependent on the bile salt used and its concentration in bile; there was little effect on plasma-membrane enzyme output until the critical micellar concentration of the bile salt had been exceeded in the bile. A bile salt analogue, taurodehydrocholate, which does not form micelles, did not produce the enhanced output of plasma-membrane enzymes. This work supports the view that the output of plasma-membrane enzymes in bile is a consequence of bile salt output and also provides evidence for mechanisms by which serum proteins enter the bile.


Vaccination with mRNAs encoding tumor-associated antigens and granulocyte-macrophage colony-stimulating factor efficiently primes CTL responses, but is insufficient to overcome tolerance to a model tumor/self antigen.
Immunization of mice with dendritic cells transfected ex vivo with tumor-associated antigen (TAA)-encoding mRNA primes cytotoxic T lymphocytes (CTL) that mediate tumor rejection. Here we investigated whether direct injection of TAA mRNA, encapsulated in cationic liposomes, could function similarly as cancer immunotherapy. Intradermal and intravenous injection of ovalbumin (OVA) mRNA generated specific CTL activity and inhibited the growth of OVA-expressing tumors. Vaccination studies with DNA have demonstrated that co-administration of antigen (Ag)- and cytokine-encoding plasmids potentiate the T cell response; in analogous fashion, the inclusion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA enhanced OVA-specific cytotoxicity. The ability of this GM-CSF-augmented mRNA vaccine to treat an established spontaneous tumor was evaluated in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mouse, using the SV40 large T Ag (TAg) as a model tumor/self Ag. Repeated vaccination elicited vigorous TAg-specific CTL activity in nontransgenic mice, but tumor-bearing TRAMP mice remained tolerant. Adoptive transfer of naïve splenocytes into TRAMP mice prior to the first vaccination restored TAg reactivity, and slowed tumor progression. The data from this study suggests that vaccination with TAA mRNA is a simple and effective means of priming antitumor CTL, and that immunogenicity of the vaccine can be augmented by co-delivery of GM-CSF mRNA. Nonetheless, limitations of such vaccines in overcoming tolerance to tumor/self Ag may mandate prior or simultaneous reconstitution of the autoreactive T cell repertoire for this form of immunization to be effective.


Long-term survival and complications following bladder-preserving brachytherapy in patients with cT1-T2 bladder cancer.
Radical cystectomy (RC) is considered standard treatment for muscle-invasive bladder cancer (BC) and high-risk non-muscle invasive BC. In selected cases, bladder-sparing treatment using brachytherapy can be offered. We examined the outcome after brachytherapy in comparison to RC in terms of survival, complications and bladder preservation in patients with cT1G3-T2N0M0 BC. Between 1988 and 2016, 301 patients underwent brachytherapy in two centres. Overall survival (OS) and disease specific survival (DSS) after brachytherapy and RC were assessed using Kaplan-Meier curves. Cox proportional hazards modelling was used to determine variables associated with OS and DSS. Local recurrences, bladder preservation and salvage cystectomy (SC) after brachytherapy were reported. Complications after brachytherapy, RC and SC were compared using CTCAE criteria. Median follow-up was 9.6 years (95% confidence interval (CI): 8.8-10.4) after brachytherapy and 10.6 years (95% CI: 10.0-11.2) after RC. Five/10-year OS was 66%/49% after brachytherapy and 68%/53% after RC (p = 0.4). Five/10-year DSS was 73%/67% after brachytherapy and 75%/65% after RC (p = 0.8). Intravesical recurrence occurred in 58/259 brachytherapy patients after which salvage cystectomy was performed in 32 patients. In total, 84% of brachytherapy-treated patients preserved their bladder. The brachytherapy cohort experienced less high grade complications than the RC cohort (p = 0.02). In selected patients with solitary, ≤5 cm cT1G3-T2N0M0 bladder tumours brachytherapy is a bladder-sparing therapy with good survival outcome and with a favourable complication rate compared to RC.


Effects of indented interframe cross talk in charge-coupled device detection of discrete displays.
By considering CCD detection as a spatiotemporal sampling process and considering electronically addressed liquid-crystal display's (LCD's) and cathode ray tube (CRT) display's as discrete displays, we investigate the frame-grabbing process for CCD detection of discrete displays by using CRT-CCD and LCD-CCD models. Because of the nature of the timing for pixel addressing in the CRT, line addressing in the LCD, and frame transfer in the CCD, it is found that CCD frames suffer from indented interframe cross talk of the displayed input frames. This indented cross talk occurs regardless of whether a synchronizing signal is utilized. Cross talk typically takes place between two or three input frames. Indented interframe cross talk does not affect CCD detection for frame refreshing. However, cross talk increases as the interframe difference between successive displayed input frames increases.


Weight loss and low age are associated with intensity of rooting behaviours in newborn infants.
Little is known about the developing breastfeeding behaviour of newborn infants. This study describes infants' prebreastfeeding behaviour during the second day of life and explores possible associations with infant characteristics. We studied 13 mothers and healthy full-term infants after normal births. At 24-48 hours of life, the newborns were placed in skin-to-skin contact with their mothers for breastfeeding and were video-filmed. The order, frequency and duration of predefined infant prefeeding behaviours and suckling were coded and analysed using computer-based video software. Prefeeding behaviours occurred in the following order: rooting, hand to mouth movements, licking of the nipple and hand to breast to mouth movements. The infants started to suckle at a median of one to two minutes. Rooting was the most common behaviour, observed in 12 infants. The duration of rooting movements during the last minute before breastfeeding was inversely related to neonatal age (p ≤ 0.001) and positively related to neonatal weight loss (p = 0.02) after birth. Infants exhibited a distinct sequence of prefeeding behaviours during the second day of life, and our findings suggest that rooting movements were governed by mechanisms involved in the regulation of food intake and weight gain.


Female reproductive biology of the bluemouth Helicolenus dactylopterus dactylopterus: spawning and fecundity.
The bluemouth Helicolenus dactylopterus dactylopterus is a zygoparous species that spawns multiple batches of embryos enclosed within a gelatinous matrix. Oocyte development is asynchronous, and the recruitment of secondary growth oocytes occurs continuously during the developing phase, but stops before the start of the first spawning (i.e. fecundity is determinate). The number of developing oocytes can be estimated as a function of the total length of the fish, its ovary mass and its gonado-somatic index. Only at the onset of spawning, when potential fecundity is determined, does condition also have a significant effect. The low levels of atresia detected during most of the spawning season show that this mechanism does not substantially affect the process. There is variability both in the spawning interval (with a mean of 2 days) and in the number of embryos comprising every single batch (up to 37,000). Expected effect of fisheries on the reproductive traits of this deep-sea species is also discussed.


Attempted immunization of cats against feline infectious peritonitis, using avirulent live virus or sublethal amounts of virulent virus.
Kittens vaccinated with an avirulent biotype of the Black strain of feline infectious peritonitis virus (FIPV; given oronasally) developed both indirect fluorescent and virus-neutralizing antibodies, but were not protected against oronasal challenge exposure with virulent virus. In fact, kittens vaccinated with avirulent virus were more readily infected than were nonvaccinated cats. A proportion of kittens could be immunized to FIPV by giving sublethal amounts of virulent virus. This technique, however, was too inconsistent and hazardous to have clinical relevance. The results of these studies indicated that humoral immunity was not protective in FIPV infection. There was no correlation between fluorescent and virus-neutralizing antibodies and either disease or immunity. Immune serum from FIPV-resistant cats failed to passively protect susceptible animals against virulent virus given intraperitoneally or oronasally, and as expected, actually sensitized them to infection. It was concluded that cell-mediated immunity was probably responsible for protection.


Critical problems in spatial vision.
In recent years the study of spatial vision seems to have come almost full circle. Localized stimuli (such as lines, bars, and edges) were abandoned in favor of textured patterns (such as sinusoidal gratings), a trend that was accelerated by the discovery that gratings of sufficiently different spatial frequencies or orientations (stimuli localized in the Fourier domain) were detected independently. This led to various attempts to model form vision in terms of spatial frequency analysis. More recently there has been a shift toward models that include, once again, the local aspects of spatial processing; this trend is more consistent with both retinal and cortical physiology. (Still surviving is the notion of a complete set of orthonormal basis functions, but not sinusoidal ones.) Other important developments include attempts to model spatiotemporal interaction, and the discovery that spatial processing takes on an entirely different character in the absence of any temporal variation (i.e., when the retinal image is stabilized). We attempt to trace these developments in terms of a selected group of representative studies, which we examine in some depth.


In Defence of Machine Learning: Debunking the Myths of Artificial Intelligence.
There has been much hype, over the past few years, about the recent progress of artificial intelligence (AI), especially through machine learning. If one is to believe many of the headlines that have proliferated in the media, as well as in an increasing number of scientific publications, it would seem that AI is now capable of creating and learning in ways that are starting to resemble what humans can do. And so that we should start to hope - or fear - that the creation of fully cognisant machine might be something we will witness in our life time. However, much of these beliefs are based on deep misconceptions about what AI can do, and how. In this paper, I start with a brief introduction to the principles of AI, machine learning, and neural networks, primarily intended for psychologists and social scientists, who often have much to contribute to the debates surrounding AI but lack a clear understanding of what it can currently do and how it works. I then debunk four common myths associated with AI: 1) it can create, 2) it can learn, 3) it is neutral and objective, and 4) it can solve ethically and/or culturally sensitive problems. In a third and last section, I argue that these misconceptions represent four main dangers: 1) avoiding debate, 2) naturalising our biases, 3) deresponsibilising creators and users, and 4) missing out some of the potential uses of machine learning. I finally conclude on the potential benefits of using machine learning in research, and thus on the need to defend machine learning without romanticising what it can actually do.


Alpha-fetoprotein production by a hepatoid adenocarcinoma of the uterus.
A case of a 62 year old Japanese woman with an endometrial adenocarcinoma producing alpha-fetoprotein (AFP) is described. Microscopically, the tumour was composed of a major medullary portion and a minor tubular adenocarcinoma which had invaded the myometrium, the myometrial lymphatics and blood vessels. Neoplastic cells in the medullary portion were polygonal with glycogen-rich cytoplasm. Vascular permeation by neoplastic cells was prominent. Extensive hepatoma-like features were observed. The tumour cells lacked features suggestive of a diagnosis of embryonal carcinoma or endodermal sinus tumour. The production of AFP by the tumour cells was demonstrated immunohistochemically using the PAP technique. Only two cases of AFP producing endometrial adenocarcinomas have been reported previously.


How early does the selfing syndrome arise? Associations between selfing ability and flower size within populations of the mixed-mater Collinsia verna.
Widespread associations between selfing rate and floral size within and among taxa suggest that these traits may evolve in concert. Does this association develop immediately because of shared genetic and/or developmental control, or stepwise with selection shaping the evolution of one trait following the other? If the former, then association ought to appear within and across selfing populations. We explore this fundamental question in three populations of the mixed-mater Collinsia verna where autonomous selfing (AS) ability has been shown to be under selection by the pollination environment. We grew clonal replicates of C. verna in a controlled environment to characterize broad-sense genetic correlations among traits within populations and to assess whether divergence in mating system and floral traits among these populations is consistent with their previously observed selection pressures. As predicted by their respective pollination environments, we demonstrate significant genetic divergence among populations in AS ability. However, patterns of divergence in floral traits (petal, stamen, and style size, stigmatic receptivity, and stigma-anther distance) were not as expected. Within populations, genetic variation in AS appeared largely independent from floral traits, except for a single weak negative association in one population between flower size and AS rate. Together, these results suggest that associations between selfing rate and floral traits across Collinsia species are not reflected at microevolutionary scales. If C. verna were to continue evolving toward the selfing syndrome, floral trait evolution would likely follow stepwise from mating system evolution.


Seroprevalence of diphtheria toxoid IgG antibodies in children, adolescents and adults in Poland.
Recommendations for diphtheria immunization are to apply an effective primary immunization in infancy and to maintain immunity throughout life. Immunity against diphtheria depends primarily on antibody to the diphtheria toxin. This study evaluated the seroprevalence of IgG diphtheria antitoxin in sera of healthy children, adolescents and adults in Poland. A total of 1387 serum samples collected between 2010 and 2012 from individuals with ages ranging from 1 month to 85 years were investigated. Antibody concentrations were measured with an enzyme-linked immunosorbent assay (Anti-Diphtheria Toxoid ELISA IgG, Euroimmun, Germany). The results showed that among 1387 individuals examined, 547 (39.4%) had anti-diphtheria toxoid IgG antibody levels below 0.1 IU/ml (36.9% ≤ 18 years and 40.5% >18 years old, respectively). The 212 (50.8%) children and 542 (55.9%) adults showed only basic protection (0.1-1.0 IU/ml) and need immediate booster. High levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were found more often in children and adolescent (12.2%) than in adults (3.6%) and this was statistically significant (P < 0.05). The proportion of seronegatives (< 0.1 IU/ml) in children below 2 years old, adolescents and young adults to 25 years old decreased from 53.5% to 17.4%. However, in older individuals the seronegative proportion tended to increase with age, from 22.7% in adults (26-30 years old) to 67.1% in subjects > 60 years old. Characteristically, in individuals > 40 years old high levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were not seen. There were no statistically significant differences in results in relation to gender. The present study showed inadequate immunity levels to diphtheria amongst the Polish population, especially in adults > 40 years old and children ≤ 2 years old. To prevent reemergence of diphtheria an information campaign reminding people about recommendations concerning diphtheria booster vaccination in adults should be conducted. Moreover, the immunogenicity of the DTP vaccine used in Poland should be verified.


Prostaglandin-mediated inhibition of Na+/H+ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine.
Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the porcine ileum through a mechanism involving cAMP-dependent Cl- secretion and inhibition of electroneutral Na+/H+ exchanger (NHE) activity. In the present study, we focused on the role of individual NHE isoforms in the recovery of barrier function. Ischemia-injured porcine ileal mucosa was mounted on Ussing chambers. Short-circuit current (I(sc)), transepithelial electrical resistance (TER), and isotopic fluxes of 22Na were measured in response to PGE2 and selective inhibitors of epithelial NHE isoforms. Immunoassays were used to assess the expression of NHE isoforms. Forty-five minutes of intestinal ischemia resulted in a 45% reduction in TER (P < 0.01). Near-complete restitution occurred within 60 min. Inhibition of NHE2 with HOE-694 (25 microM) added to the mucosal surface of the injured ileum stimulated significant elevations in TER, independent of changes in I(sc) and histological evidence of restitution. Pharmacological inhibition of NHE3 or NHE1 with mucosal S-3226 (20 microM) or serosal cariporide (25 microM), respectively, had no effect. Ischemia-injured tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in mucosal-to-serosal fluxes of 22Na+ (by approximately 35%) compared with nontreated ischemia-injured control tissues (P < 0.05). Intestinal ischemia resulted in increased expression of the cytoplasmic NHE regulatory factor EBP50 in NHE2 but not in NHE3 immunoprecipitates. Selective inhibition of NHE2, and not NHE3, induces recovery of barrier function in the ischemia-injured intestine.


Dizziness Symptom Type Prevalence and Overlap: A US Nationally Representative Survey.
The traditional approach to dizziness encourages providers to emphasize the type of dizziness. However, symptom types might substantially overlap in individual patients, thus limiting the clinical value of this approach. We aimed to describe the overlap of types of dizziness using a US nationally representative sample. The 2008 US National Health Interview Survey was examined for prevalence and overlap of types of dizziness. The data were also separately examined among people who otherwise had typical features of traditionally vertigo-based disorders (ie, benign paroxysmal positional vertigo and Meniere's disease). Data analysis also included exploratory factor analysis. Twelve-month prevalence of problems with dizziness or balance was 14.8%, representing 33.4 million individuals. The mean number of dizziness symptoms was 2.4 (95% confidence interval [CI], 2.3-2.4), with 61.1% reporting more than one type. Of subjects who otherwise had typical features of traditionally vertigo-based disorders, the mean number of dizziness types was 3.1 (95% CI, 3.0-3.3), and only 24.6% (95% CI, 21.0%-28.7%) reported vertigo as the primary type. Exploratory factor analysis found that symptom types loaded onto a single factor without other clinical or demographic variables. Substantial overlap of dizziness types exists among US adults with dizziness. People otherwise having features of traditionally vertigo-based disorders also typically report multiple dizziness types and do not typically report vertigo as the primary type. Symptom types correlate more strongly with each other than with other clinical or demographic variables. These findings suggest that the traditional emphasis on dizziness types is likely of limited clinical utility.


Simultaneous Reconstruction of the Anterior Cruciate Ligament and Medial Collateral Ligament in Patients With Chronic ACL-MCL Lesions: A Minimum 2-Year Follow-up Study.
In cases of chronic anterior cruciate ligament (ACL)-medial collateral ligament (MCL) lesions, nonoperative treatment of the MCL lesion may lead to chronic valgus instability and rotatory instability. The optimal management for patients who have combined ACL-MCL injuries remains controversial. To present a case series of 21 patients who underwent simultaneous ACL-MCL reconstruction with a 2- to 5-year follow-up. Case series; Level of evidence, 4. From October 2007 to December 2010, a total of 21 patients with chronic ACL-MCL injuries, for which the 2 ligaments were reconstructed during the same surgical procedure, were studied. All patients were available for follow-up for at least 2 years. The International Knee Documentation Committee (IKDC) subjective knee scores, valgus and sagittal stability, anteromedial rotatory stability, range of motion, and complications were assessed both preoperatively and postoperatively. At follow-up, valgus and sagittal laxity were not observed in any of the patients. The mean medial knee opening was significantly reduced to 0.80 ± 0.96 mm (range, -1.2 to 2.6 mm) postoperatively compared with 8.0 ± 1.3 mm (range, 6.1 to 10.7 mm) preoperatively (P < .01). The mean postoperative side-to-side difference measured with the KT-1000 arthrometer was reduced to 0.8 ± 0.9 mm (range, -1.2 to 2.3 mm) compared with 8.4 ± 1.6 mm (range, 6.2 to 13.2 mm) preoperatively (P < .01). Preoperative anteromedial instability was seen in 71% of patients (15/21), whereas none of the patients had anteromedial rotatory instability at the last follow-up. The mean IKDC subjective score improved overall from 45.3 ± 12.0 (range, 28.7-69.0) preoperatively to 87.7 ± 8.2 (range, 65.5-100.0) at the last follow-up (P < .01). Most patients (20/21) had normal or nearly normal range of motion of the knee joint; only 1 patient (5%) had a limitation of flexion of 15° compared with the contralateral knee at the last follow-up. In patients with chronic ACL-MCL lesions, simultaneous reconstruction of the ACL and MCL can significantly improve the medial, sagittal, and rotatory stability of the knee at short-term follow-up.


U.s.-Japanese space relations at a crossroads.
The relations between Japan and the United States in space form a microcosm of the complex, multidimensional interactions between these two powerful societies. Cooperation and competition exist side by side, and the future balance between them is uncertain. The United States needs to develop a strategy with respect to future U.S.-Japanese space relations that balances national security, political, scientific, and economic interests. Crafting such a strategy is particularly difficult while both the United States and Japan debate the goals and content of their future space programs and while the two nations try to assess their broader interests and roles in the rapidly changing geopolitical environment. Essential to a productive approach to U.S.-Japanese space relations is an accurate understanding of the character and content of the Japanese space effort.


In situ distributed diagnostics of flowable electrode systems: resolving spatial and temporal limitations.
In this study, we have developed an in situ distributed diagnostics tool to investigate spatial and temporal effects in electrochemical systems based on flowable electrodes. Specifically, an experimental approach was developed that enables spatially-resolved voltage measurements to be obtained in situ, in real-time. To extract additional data from these distributed measurements, an experimentally-parameterized equivalent circuit model with a new 'flow capacitor' circuit element was developed to predict the distributions of various system parameters during operation. As a case study, this approach was applied to investigate the behavior of the suspension electrodes used in an electrochemical flow capacitor under flowing and static conditions. The volumetric capacitance is reduced from 15.6 F ml(-1) to 1.1 F ml(-1) under flowing conditions. Results indicate that the majority of the charging in suspension electrodes occurs within ∼750 μm of the current collectors during flow, which gives rise to significant state-of-charge gradients across the cell, as well as underutilization of the available active material. The underlying cause of this observation is attributed to the relatively high electrical resistance of the slurry coupled with a stratified charging regime and insufficient residence time. The observations highlight the need to develop more conductive slurries and to design cells with reduced charge transport lengths.


Real-world particle and NOx emissions from hybrid electric vehicles under cold weather conditions.
Hybrid electric vehicle (HEV) technology is critical to reduce the impact of the internal combustion engines on air pollution and greenhouse gases. HEVs have an advantage in market penetration due to their lower cost and higher driving range compared to battery electric vehicles (BEVs). On the other hand, HEVs use an internal combustion engine and still emit air pollutants. It is hypothesized that HEV performance is impacted by the weather conditions as a result of many factors. It was beyond the scope of this work to systematically evaluate all factors so instead we measured emissions from two vehicles driving city and highway routes in Minneapolis, Minnesota in the winter (-5 °C) and looked for major differences in emissions relative to each vehicle and relative to results that would be obtained from a chassis dynamometer in a controlled laboratory setting at a higher temperature approximately 20 °C). The study then looked to associate differences in emissions with the prevailing conditions to gain new insights. Emissions of interest included the total particle number (TPN), solid particle number (SPN), particulate matter mass (PM), and NOx. One key difference in vehicle engine technology was PFI (port fuel injection) versus GDI (gasoline direct injection). We found the frequency at which the Prius hybrid engine reignited was much higher than the Sonata for city and highway driving, although for both vehicles the catalyst temperature remained high and appeared to be unaffected by the reignitions, despite the cold weather. For most conditions, the Prius emitted more NOx but fewer particles than the Sonata. In some cases, NOx and particle emissions exceeded the most comparable laboratory-based emissions standards.


Medical Students' Perspectives on Family Planning and Impact on Specialty Choice.
Physicians are known to delay childbearing compared with nonphysicians and to experience higher rates of age-related pregnancy complications. Delay of childbearing is more pronounced in surgical specialties, and family planning and building goals may influence specialty choice. To assess medical students' perspectives on the development of family planning goals and the timing of family building within a medical career to elucidate how these perceptions impact their choice of specialty. This qualitative study included fourth-year medical students at the University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada, and was conducted between May and August 2021. Participants were purposively sampled to maximize diversity of gender and specialty choice. Interviews were conducted via videoconferencing software that were recorded, transcribed verbatim, and verified for accuracy. Thematic analysis was completed independently by 2 researchers and consensus on final themes was reached through discussion among study investigators. Data were analyzed between September and December 2021. Participants were asked to share their perceptions of personal family planning goals, support currently in place, family planning education in medicine and factors contributing to their choice of specialty and program. Thematic analysis was completed. A total of 34 fourth-year medical students (median [range] age, 26 [24-33] years; 23 females [67.6%]) were interviewed. Four main themes were identified: (1) there is no ideal time to family build in a medical career, (2) family planning is a taboo topic, (3) surgical specialties offer less support for family building, and (4) residents who have children are perceived to place a burden on their colleagues. Medical students considered their family planning while deliberating among specialty choices and their experiences were highly influential in shaping their specialty selection. Results of this qualitative study suggest that medical students perceive that family building during training may have unfavorable implications for team dynamics and relationships with colleagues, and these perceptions may affect specialty choice and family planning goals. Integration of family planning discussions and support for family building into medical curricula is needed along with efforts to improve culture by supporting team dynamics and workload when students take parental leave.


Genetic Dissection of ICP-Detected Nutrient Accumulation in the Whole Seed of Common Bean (Phaseolus vulgaris L.).
Nutrient transport to grain legume seeds is not well studied and can benefit from modern methods of elemental analysis including spectroscopic techniques. Some cations such as potassium (K) and magnesium (Mg) are needed for plant physiological purposes. Meanwhile, some minerals such as copper (Cu), iron (Fe), molybdenum (Mo), and zinc (Zn) are important micronutrients. Phosphorus (P) is rich in legumes, while sulfur (S) concentration is related to essential amino acids. In this research, the goal was to analyze a genetic mapping population of common bean (Phaseolus vulgaris L.) with inductively coupled plasma (ICP) spectrophotometry to determine concentrations of and to discover quantitative trait loci (QTL) for 15 elements in ground flour of whole seeds. The population was grown in randomized complete block design experiments that had been used before to analyze Fe and Zn. A total of 21 QTL were identified for nine additional elements, of which four QTL were found for Cu followed by three each for Mg, Mn, and P. Fewer QTL were found for K, Na and S. Boron (B) and calcium (Ca) had only one QTL each. The utility of the QTL for breeding adaptation to element deficient soils and association with previously discovered nutritional loci are discussed.


BioRAT: extracting biological information from full-length papers.
Converting the vast quantity of free-format text found in journals into a concise, structured format makes the researcher's quest for information easier. Recently, several information extraction systems have been developed that attempt to simplify the retrieval and analysis of biological and medical data. Most of this work has used the abstract alone, owing to the convenience of access and the quality of data. Abstracts are generally available through central collections with easy direct access (e.g. PubMed). The full-text papers contain more information, but are distributed across many locations (e.g. publishers' web sites, journal web sites and local repositories), making access more difficult. In this paper, we present BioRAT, a new information extraction (IE) tool, specifically designed to perform biomedical IE, and which is able to locate and analyse both abstracts and full-length papers. BioRAT is a Biological Research Assistant for Text mining, and incorporates a document search ability with domain-specific IE. We show first, that BioRAT performs as well as existing systems, when applied to abstracts; and second, that significantly more information is available to BioRAT through the full-length papers than via the abstracts alone. Typically, less than half of the available information is extracted from the abstract, with the majority coming from the body of each paper. Overall, BioRAT recalled 20.31% of the target facts from the abstracts with 55.07% precision, and achieved 43.6% recall with 51.25% precision on full-length papers.


Norepinephrine and cerebral blood flow regulation in patients with arteriovenous malformations.
To test the hypothesis that the sympathetic nervous system plays a role in cerebral blood flow regulation in patients with arteriovenous malformations (AVM). Cortical interstitial norepinephrine was measured by means of microdialysis, regional cerebral blood flow was measured by a thermal diffusion technique, and regional oxygen saturation (SO2) was measured by microspectrophotometry in 12 patients harboring cerebral AVMs (AVM group) and in 15 patients with deep-seated nonvascular lesions (control group) before and after resection. Measurements were compared according to groups and times of measurements. All values are given as means +/- standard deviation. Cortical regional SO2 increased significantly (P < 0.05) in both groups after surgery (AVM group: presurgery 52.4 +/- 12.5% SO2, postsurgery 71.4 +/- 7.4% SO2; control group: presurgery 57.1 +/- 8.4% SO2, postsurgery 69.9 +/- 8.7% SO2), whereas regional cerebral blood flow increased only in the AVM group (AVM group: presurgery 18.9 +/- 6.6 ml/100 g/min, postsurgery 26.2 +/- 6.9 ml/100 g/min; control group: presurgery 20.1 +/- 7.6 ml/100 g/min, postsurgery 19.4 +/- 7.8 ml/100 g/min). Norepinephrine concentrations were significantly lower in the AVM group as compared with the control group before surgery. Although there was no significant difference between pre- and postsurgery conditions in the AVM group, the norepinephrine level of the control group was significantly lower after surgery (AVM group: presurgery 3.3 +/- 1.2 nmol/L, postsurgery 2.9 +/- 1.7 nmol/L; control group: presurgery 5.4 +/- 1.4 nmol/L, postsurgery 4.2 +/- 1.1 nmol/L). Chronically lowered perfusion pressure seems to induce the hypothesized adaptive down-regulation of sympathetic nervous system activity, yet protective up-regulation after a sudden elevation of cerebral perfusion pressure after AVM excision could not be shown in this study.


Congenital tumors of the retrorectal space in the adult: report of two cases and review of the literature.
To describe and discuss, on the basis of the authors' experience and a review of the literature, the main aspects regarding the etiology, diagnosis, treatment and prognosis of congenital tumors of the retrorectal space. We present 2 cases of congenital retrorectal tumors, a sacrococcygeal teratoma and a dermoid cyst, which represent, from the pathogenetic point of view, the most frequent presentation of the rare tumors of the retrorectal space. The reported cases are typical. The teratoma presented as an encapsulated, mixed mass located in the pelvic cavity behind the rectum and the vaginal canal, without signs of sacral involvement. The dermoid cyst appeared as a unilocular lesion filled with sebum and hair, which extended laterally to the iliopubic branch, medially to the urethra and anal canal, and posteriorly to the adipose tissue of the right buttock. Pelvic MRI produced a precise picture of the extension of the lesion and of the relationship between the mass and the pelvic organs and surrounding bony structures. Both lesions were completely removed via the perineal approach without coccygectomy. No recurrences were observed at 2 years of follow-up. Congenital retrorectal tumors are rare. MRI is crucial for diagnosis and preoperative planning. Complete surgical removal is the treatment of choice. Resection of the coccyx is necessary only in case of its involvement by the neoplastic mass or suspected malignant transformation.


Ultrastructural immunohistochemical study of interstitial collagenous components of the healthy human keratinized mucosa surrounding implants.
The aim of this study was to investigate the ultrastructural and immunohistochemical organization of the main collagenous components of healthy human keratinized mucosa surrounding endosseous implants. Eight patients with completely edentulous mandibles were selected. Four endosseous implants were placed in the mandible of each patient, connected with a bar to support a complete overdenture, and loaded 4 months later. Two years after placement, biopsies of surrounding soft tissue, including the sulcular and junctional epithelium with the underlying and supracrestal connective tissue, were routinely prepared for standard electron microscopy and for ultrastructural immunolabeling of Types I, III, and IV collagen. The connective tissue located under the junctional epithelium comprised Types I and III collagen, whereas the supracrestal connective tissue was composed mainly of Type I collagen. Type IV collagen was located exclusively in the basement membrane of the junctional epithelium.


Factors that may influence the postural health of schoolchildren (K-12).
Ergonomic seating and proper positioning during the performance of activities is a major focus in the adult workplace. This focus, however, is typically ignored in classrooms where our youngest workers spend the majority of their time. A review of the literature was done to determine the effects of school furniture design on the postural health of schoolchildren (K-12). The review indicated that the adjustability of school furniture is an important design feature if children are to have equal educational opportunity, increased comfort, and decreased incidences of musculoskeletal symptoms. The effectiveness of ergonomic school furniture on schoolchildren has been demonstrated in only one study reviewed in this paper. The other studies are reviewed in an effort to identify: (1) the variation of anthropometric measures of children; (2) the performance of activities exposing children to various postures; and (3) the physical design features of school furniture as three factors which influence the postural health of schoolchildren.


Endoscopic ultrasound-guided through-the-needle microforceps biopsy in the evaluation of pancreatic cystic lesions: a multicenter study.
Background and study aims Accurate diagnosis and classification of pancreatic cysts (PCs) remains a challenge. The aims of this study were to: (1) evaluate the safety and technical success of a novel microforceps for EUS-guided through-the-needle biopsy (TTNB) of PCs; and (2) assess its diagnostic yield for mucinous PCs when compared to FNA cyst fluid analysis and cytology. Patients and methods This was a multicenter retrospective analysis of 47 patients who underwent EUS-FNA and TTNB for PCs between January 2014 and June 2017. Technical success was defined as acquisition of a specimen adequate for cytologic or histological evaluation. Cyst fluid carcinoembryonic antigen (CEA) was used to initially categorize cysts as non-mucinous (CEA < 192 ng/mL) or mucinous (CEA ≥ 192 ng/mL). Final diagnosis was based on identifiable mucinous pancreatic cystic epithelium on cytology, microforceps histology and/or surgical histology when available. Results Forty-seven patients with PCs (mean size 30.7 mm) were included. TTNB was successfully performed in 46 of 47 (97.9 %). Technical success was significantly lower with FNA (48.9 %) compared to TTNB (85.1 %) ( P < .001). For cysts with insufficient amount of fluid for CEA (n = 19) or CEA < 192 ng/mL, the cumulative incremental diagnostic yield of a mucinous PC was significantly higher with TTNB vs. FNA (52.6 % vs 18.4 %; P = .004). TTNB alone (34.4 %) diagnosed more mucinous PCs than either CEA ≥ 192 ng/mL alone (6.3 %) or when combined with FNA cytology (9.4 %). One episode of self-limited bleeding (2.1 %) and one of pancreatitis (2.1 %) occurred. Conclusions EUS-TTNB is safe and effective for evaluating PCs. TTNB may help increase the diagnostic yield of mucinous PCs.


PREVALENCE OF BODY DYSMORPHIC DISORDER AMONG ATTENDANCES SEEKING FACIAL COSMETIC PROCEDURES IN BAGHDAD.
Aim: To find out the prevalence of body dysmorphic disorder among patients seeking facial cosmetic procedures, find out association of social demographic (age, gender, occupation, marital status, friends relationship, and dating status) ampatientsient with body dysmorphic disorder. Materials and Methods: A cross-sectional study was done on a sample of 100 patients from Al-waste Hospital and Ghazy Al-Hariri Hospital for surgical specialties in Baghdad by using a body dysmorphic disorder questionnaire to diagnose a probable case and then a semi-structured questionnaire based on DSM5 criteria to diagnose body dysmorphic disorder during the period extended from beginning of January 2019 to the end of April 2019. Results: The chi-square test proved the association between female gender and body dysmorphic disorder is significant P=0.026. Significant associations were also noticed between single patients and body dysmorphic disorder 76.8% in comparison with married 37.8, and divorced or widowed 42.9% (P=0.001). It was found that 68.6% of unemployed patients think that they need to correct their body dysmorphic disorder so they attended the hospital while only 40% of employed persons did so P=0.008. The mean age of patients exposed to a second operation was significantly higher than the mean age of other patients P=0.022. Conclusions: High prevalence of body dysmorphic disorder among patients seeking plastic surgery which is about 60%. Body dysmorphic disorder is more common among single and unemployment and among young adults and gender female. There is no significant association between the mean age of male and female patients of body dysmorphic disorder group.


Coexistence of three benign and a borderline tumor in the ovaries of a 52-year-old woman.
In this paper, the authors describe a rare case of four simultaneous ovarian tumors. A 52-year-old postmenopausal woman underwent total hysterectomy and bilateral salpingo-ophorectomy. Multiple slides from the ovaries were examined. Histological examination revealed the presence of three ovarian tumors on the right ovary, of the following types: cystadenoma, mucinous borderline ovarian tumor and mature teratoma, and also a benign Brenner tumor on the left ovary. Pathologists must examine multiple sections of both ovaries, regardless of the macroscopic or clinical specimen's appearance, in order to exclude the presence of malignancy, which could alter the surgical approach. Particular attention should also be paid to the frozen section of the contralateral ovary, as depending on the result, it could change the surgical approach. From the surgeon's perspective, bilateral salpingo-ophorectomy with total hysterectomy should be the treatment of choice in postmenopausal women with multiple ovarian tumors. The diagnosis of a malignant or borderline tumor on a normal-appearing ovary changes the radicality of the surgical approach. In such a case, staging surgery, including omentectomy, multiple peritoneal biopsies, and washes are required.


[Assisting the assessment of rehabilitation need by a self-administered questionnaire: problems and solutions].
Rehabilitation in Germany is an important sector of the medical system. Rehabilitation need of insurees who claim rehabilitation benefits is assessed by the financially responsible agency (mostly pension funds). Legal regulations allow little time for this decision so insurers aim at making decisions from the records only. Information on the specific case often is however insufficient. Self-administered questionnaires have been employed in the past to remedy that problem. In this article typical problems are illustrated which arise when administering additional questionnaires to assist the assessment, and solutions for these problems are shown. Important questions concern the instruments that should be used, technical problems of computer-aided assessment and processing of the data, and possible legal objections. Also, general problems and limitations of the approach are discussed.


Biology and cytotoxicity of dental materials: an in vitro study.
The purpose of the experiment was to determine the degree of biocompatibility of a sealer (RO, laboratory made product) dental material in terms of cytotoxicity and animal tests. In the present study, the biological compatibility of eight experimental composite materials was examined by in vitro methods. The bio-composites used for the cytotoxicity test were placed into direct contact with normal human fibroblasts in a cell-culture dish. After fibroblast bioassay was performed, a duplicate sample of biomaterial was placed in each well, and then the fibroblasts were incubated for 48 hours at 37°C and 5% carbon dioxide. Local reactions after the implantation of the material regarding preclinical evaluation have been carried out within the Biobase Laboratory of the "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. The biocompatibility was studied using the tolerance test by the subcutaneous and intramuscular implantation of the cured specimens. The sealant C3 scored the highest value to the cell viability. The results of the present study showed that different dental materials had different effects on cells. The resin monomer TEGDMA, present in the sealer's composition, increased the amount of intracellular reactive oxygen species. Resin-based composites are cytotoxic before polymerization and immediately thereafter, whereas already set specimens cause almost no reaction. The test of tolerance showed that the composite materials do not contain any toxic, irritant substances or destructive ones for the living cells or tissues. The tests with experimental composite materials revealed that they are not cytotoxic for the living cells, in all versions of the materials used. All the samples of composite materials have maintained their integrity during the experiment, allowing the testing together with the embedded cells, which proved good viability, so they are suitable for dentistry use.


Intra-articular injection of human meniscus stem/progenitor cells promotes meniscus regeneration and ameliorates osteoarthritis through stromal cell-derived factor-1/CXCR4-mediated homing.
Meniscus injury is frequently encountered in clinical practice. Current surgical therapy involving partial or complete meniscectomy relieves pain in the short-term but often leads to osteoarthritis (OA) in the long-term. In this study, we report a new strategy of articular cartilage protection by intra-articular injection of novel human meniscus stem/progenitor cells (hMeSPCs). We found that hMeSPCs displayed both mesenchymal stem cell characteristics and high expression levels of collagen II. In the rat meniscus injury model, hMeSPC transplantation not only led to more neo-tissue formation and better-defined shape but also resulted in more rounded cells and matured extracellular matrix. Stromal cell-derived factor-1 (SDF-1) enhanced the migration of hMeSPCs, whereas AMD3100 abolished the chemotactic effects of SDF-1 on hMeSPCs, both in vitro and in vivo. In an experimental OA model, transplantation of hMeSPCs effectively protected articular cartilage, as evidenced by reduced expression of OA markers such as collagen I, collagen X, and hypoxia-inducible factor 2α but increased expression of collagen II. Our study demonstrated for the first time that intra-articular injection of hMeSPCs enhanced meniscus regeneration through the SDF-1/CXCR4 axis. Our study highlights a new strategy of intra-articular injection of hMeSPCs for meniscus regeneration.


Histologic conversion in the non-Hodgkin's lymphomas.
Between July 1, 1971 and December 31, 1978, 150 patients with favorable subtypes of non-Hodgkin's lymphoma [nodular poorly differentiated lymphocytic (NLPD), nodular mixed, or diffuse well differentiated lymphocytic] were entered into prospective randomized clinical trials at Stanford University. Treatments included involved field, total lymphoid, or whole body irradiation, single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine and prednisone (CVP) or with cyclophosphamide, vincristine, procarbazine, and prednisone (C-MOPP), or various combinations of chemotherapy and irradiation. The initial complete response rate (CR) was 79%. Among patients who achieved a CR, 31% later relapsed. There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed. Histologic conversion (change from initially favorable to an unfavorable subtype of non-Hodgkin's lymphoma) was documented in 22/78 patients (28%). However, the actuarial risk for conversion was actually much greater (60% at 8 yr). The median time to documentation of conversion was 51 mo. The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma. Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma, and the median survival after conversion was less than 1 yr. However, those patients who achieved a CR after conversion had a more favorable outcome (actuarial survival 75% at 5 yr). No specific risk factors predictive of histologic conversion could be identified.


Ballet injuries: injury incidence and severity over 1 year.
Prospective, descriptive single-cohort study. To assess the incidence and severity of injuries to a professional ballet company over 1 year. Data for an elite-level ballet company of 52 professional dancers were collected by an in-house medical team using a time-loss injury definition. A total of 355 injuries were recorded, with an overall injury incidence of 4.4 injuries per 1000 hours (female, 4.1; male, 4.8; P>.05) and a mean of 6.8 injuries per dancer (female, 6.3; male, 7.3; P>.05). Mean injury severity was 7 days (female, 4; male, 9; P<.05). Most injuries were classified as overuse (64%; female, 68%; male, 60%; P>.05); mean severity of injury was 3 days for females and 9 days for males (P<.05). The percentage of traumatic injuries was 32% for females and 40% for males (P<.05); the corresponding severity was 6 and 10 days, respectively (P<.05). The relatively high number of injuries reported and the resulting loss of dance time support the need to introduce interventions to reduce the risk of injury in professional dancers.J Orthop Sports Phys Ther 2012;42(9):781-790. Epub 19 July 2012. doi:10.2519/jospt.2012.3893.


Fibre type composition in the lumbar perivertebral muscles of primates: implications for the evolution of orthogrady in hominoids.
The axial musculoskeletal system is important for the static and dynamic control of the body during both locomotor and non-locomotor behaviour. As a consequence, major evolutionary changes in the positional habits of a species are reflected by morpho-functional adaptations of the axial system. Because of the remarkable phenotypic plasticity of muscle tissue, a close relationship exists between muscle morphology and function. One way to explore major evolutionary transitions in muscle function is therefore by comparative analysis of fibre type composition. In this study, the three-dimensional distribution of slow and fast muscle fibres was analysed in the lumbar perivertebral muscles of two lemuriform (mouse lemur, brown lemur) and four hominoid primate species (white-handed gibbon, orangutan, bonobo, chimpanzee) in order to develop a plausible scenario for the evolution of the contractile properties of the axial muscles in hominoids and to discern possible changes in muscle physiology that were associated with the evolution of orthogrady. Similar to all previously studied quadrupedal mammals, the lemuriform primates in this study exhibited a morpho-functional dichotomy between deep slow contracting local stabilizer muscles and superficial fast contracting global mobilizers and stabilizers and thus retained the fibre distribution pattern typical for quadrupedal non-primates. In contrast, the hominoid primates showed no regionalization of the fibre types, similar to previous observations in Homo. We suggest that this homogeneous fibre composition is associated with the high functional versatility of the axial musculature that was brought about by the evolution of orthograde behaviours and reflects the broad range of mechanical demands acting on the trunk in orthograde hominoids. Because orthogrady is a derived character of euhominoids, the uniform fibre type distribution is hypothesized to coincide with the evolution of orthograde behaviours.


Antiangiogenic and antitumoral activity of phenyl-3-(2-chloroethyl)ureas: a class of soft alkylating agents disrupting microtubules that are unaffected by cell adhesion-mediated drug resistance.
The development of new anticancer agents with lower toxicity, higher therapeutic index, and weaker tendency to induce resistant phenotypes in tumor cells is a continuous challenge for the scientific community. Toward that end, we showed previously that a new class of soft alkylating agents designed as phenyl-3-(2-chloroethyl)ureas (CEUs) inhibits tumor cell growth in vitro and that their efficiency is not altered by clinically relevant mechanisms of resistance such as overexpression of multidrug resistance proteins, increase in intracellular concentration of glutathione and/or glutathione S-transferase activity, alteration of topoisomerase II, and increased DNA repair. Mechanistic studies have showed recently that the cytotoxic activity of several CEUs was mainly related to the disruption of microtubules. Here, we present results supporting our assumption that 4-tert-butyl-[3-(2-chloroethyl)ureido]phenyl (tBCEU) (and its bioisosteric derivative 4-iodo-[3-(2-chloroethyl)ureido]phenyl (ICEU) are potent antimicrotubule agents both in vitro and in vivo. They covalently bind to beta-tubulin, leading to a microtubule depolymerization phenotype, consequently disrupting the actin cytoskeleton and altering the nuclear morphology. Accordingly, tBCEU and ICEU also inhibited the migration and proliferation of endothelial and tumor cells in vitro in a dose-dependent manner. It is noteworthy that ICEU efficiently blocked angiogenesis and tumor growth in three distinct animal models: (a) the Matrigel plug angiogenesis assay; (b) the CT-26 tumor growth assay in mice; and (c) the chick chorioallantoic membrane tumor assay. In addition, we present evidence that CEU cytotoxicity is unaffected by additional resistance mechanisms impeding tumor response to DNA alkylating agents such as cisplatin, namely the cell adhesion mediated-drug resistance mechanism, which failed to influence the cytocidal activity of CEUs. On the basis of the apparent innocuousness of CEUs, on their ability to circumvent many classical and recently described tumor cell resistance mechanisms, and on their specific biodistribution to organs of the gastrointestinal tract, our results suggest that CEUs represent a promising new class of anticancer agents.


Triggered Crosslinking of Main-Chain Enediyne Polyurethanes via Bergman Cyclization.
Crosslinking chemistries occupy an important position in polymer modification with a particular importance when triggered in response to external stimuli. Enediyne (EDY) moieties are used as functional entities in this work, known to undergo a pericyclic Bergman cyclization (BC) to induce a triggered crosslinking of polyurethanes (PU) via the intermediately formed diradicals. Diamino-EDYs, where the distance between the enyne-moieties is known to be critical to induce a BC, are placed repetitively as main-chain structural elements in isophorone-based PUs to induce reinforcement upon heating, compression, or stretching. A 7-day compression under room temperature results in a ≈69% activation of the BC, together with the observation of an increase in tensile strength by 62% after 25 stretching cycles. The occurrence of BC is further proven by the decreased exothermic values in differential scanning calorimetry, together with characteristic peaks of the formed benzene moieties via IR spectroscopy. Purely heat-induced crosslinking contributes to 191% of the maximum tensile strength in comparison to the virgin PU. The BC herein forms an excellent crosslinking strategy, triggered by heat or force in PU materials.


Space-variant video compression and processing in digital holographic microscopy sensor networks with application to potable water monitoring.
Water-related diseases affect societies in all parts of the world. Online sensors are considered a solution to the problems associated with laboratory testing in potable water. One of the most active research areas of such online sensors has been within optics. Digital holographic microscopy (DHM) has the potential to rival state-of-the-art techniques such as advanced turbidity measurement. However, its use as an online sensor is limited by the large data requirements typical for digital holographic video. In this paper, we provide a solution that permits DHM to be applied to a whole class of online remote sensor networks, of which potable water analysis is one example. The designed sensors incorporate a novel space-variant quantization algorithm to preprocess each frame of a video sequence before transmission over a network. The system satisfies the generally accepted requirements of an online system: automated, near real-time, and operating in a real environment. To verify the effectiveness of the design, we implemented and evaluated it in an active potable water facility.


Embryonic signaling in melanoma: potential for diagnosis and therapy.
As the frequency of melanoma diagnosis increases, current treatment strategies are still struggling to significantly impact patient survival. Some promise has been shown in treating certain melanomas by targeting activated signaling pathways resulting from specific mutations in proteins, such as BRAF and NRAS. Recently, the identification of embryonic signaling pathways in melanoma has helped us better understand certain biological characteristics, such as cellular heterogeneity and phenotypic plasticity, and has provided novel insight pertinent to diagnosis and therapy. For instance, our studies have shown that the TGF-β family member, Nodal, is expressed in melanoma and is responsible, at least in part, for tumor cell plasticity and aggressiveness. Since the majority of normal adult tissues do not express Nodal, we reason that this embryonic morphogen could be used to identify and target aggressive melanoma cells. We have also identified that molecular cross-talk between the Notch and Nodal pathways may represent a mechanism responsible for the overexpression of Nodal in melanoma. Further exploitation of the relationship between embryonic signaling pathways and cancer pathogenesis could lead to novel approaches for diagnosis and therapy in cancers, such as melanoma.


Inhibitors of protein kinases abolish ECM-mediated promotion of neuronal polarity.
Different extracellular matrix (ECM) molecules, when presented to hippocampal neurons in culture in a substrate-bound form, exert strikingly similar effects on the establishment of neuronal polarity, i.e., the growth of axon-like major neurites is favored, whereas extension of dendrite-like minor neurites is inhibited. To gain insight into the underlying signal transduction processes, we have investigated the effects of modulators of protein kinase activity on the morphology of neurons cultured on tenascin-R, tenascin-C, and laminin-entactin substrates. We found differential effects of broad-spectrum protein kinase inhibitors: H-7 promoted the growth of minor neurites, whereas H-8 reduced the growth of major neurites on ECM but not control substrates. In contrast, chelerythrine, a specific inhibitor of protein kinase C, selectively affected growth of both minor and major neurites on control, but not on ECM substrates. Finally, reagents which elevate intracellular cAMP levels facilitated growth of minor neurites and inhibited growth of major neurites and thus interfered with the establishment of a polarized phenotype on both ECM and control substrates. Our results suggest that protein kinases mediate the effects of ECM molecules on neuronal polarity and that different kinases control extension of axons and dendrites.


Incremental value of the measures of arterial stiffness in cardiovascular risk assessment.
Predicting the occurrence of organ damage and future cardiovascular events is critical to improving patient prognosis through early personalized treatment. Although many tools have been developed and used for individuals' cardiovascular risk, they have limitations and unmet needs for improved risk stratification. For this purpose, arterial stiffness information can be practical. Arterial walls stiffen with age or prolonged exposure to various noxious stimuli such as high blood pressure, hyperglycemia, inflammation and oxidative stress. Differently from several methods of measuring arterial stiffness, pulse wave velocity (PWV) is most widely used for its non-invasive and easy measurement. It is well authorized that information on arterial stiffness is associated with the development of future cardiovascular events, independent from traditional cardiovascular risk factors, in various patient groups with specific diseases along with the general population. Moreover, when this information of arterial stiffness is associated with other risk stratification tools, it is possible to predict individuals' cardiovascular risk easier. Herein, we will review the incremental value of the measurement of arterial stiffness in cardiovascular risk assessment when combined with other risk factors such as traditional risk factors, biomarkers, other vascular testing and non-invasive cardiac imaging.


Future directions in drug abuse prevention research.
For most youth, substance use appears to be the result, in large part, of social influences. Thus, teaching youth to resist these influences appears to be a reasonable approach to the prevention of use. However, it is not realistic to assume that all youth use for the same reason or respond to the same prevention approach. Moreover, identification of factors that act to promote or deter the transition from experimental or occasional use to abuse has not been addressed by these studies. While the social inoculation and social skills approaches appear to hold considerable promise for many youth, the research results indicate that a sizeable number of youth initiate and escalate use in spite of these programs. It appears that those youth who are most at risk for compulsive drug use are those who use drugs for reasons other than social influences (Robins and Przybeck 1985). Thus there is a need not to focus on any single prevention approach, but to explore multiple strategies. Identifying effective prevention approaches also requires the ability to target programs--to identify which types of individuals are effectively reached with a specific approach. Alternative programs, such as the cognitive-developmental approach described by Glynn, Leventhal, and Hirschman, warrant additional attention. A host of areas needing further research have been identified above. While the RAUS review participants did not establish priorities among areas, some attempt to do so is necessary since funds available for research are limited.(ABSTRACT TRUNCATED AT 250 WORDS)


A Head-to-head Comparison of De Novo Sirolimus or Everolimus Plus Reduced-dose Tacrolimus in Kidney Transplant Recipients: A Prospective and Randomized Trial.
Mammalian target of rapamycin inhibitors (mTORi), sirolimus (SRL) and everolimus (EVR), have distinct pharmacokinetic/pharmacodynamics properties. There are no studies comparing the efficacy and safety of de novo use of SRL versus EVR in combination with reduced-dose calcineurin inhibitor. This single-center prospective, randomized study included first kidney transplant recipients receiving a single 3 mg/kg antithymocyte globulin dose, tacrolimus, and prednisone, without cytomegalovirus (CMV) pharmacological prophylaxis. Patients were randomized into 3 groups: SRL, EVR, or mycophenolate sodium (MPS). Doses of SRL and EVR were adjusted to maintain whole blood concentrations between 4 and 8 ng/mL. The primary endpoint was the 12-mo incidence of the first CMV infection/disease. There were 266 patients (SRL, n = 86; EVR, n = 90; MPS, n = 90). The incidence of the first CMV event was lower in the mTORi versus MPS groups (10.5% versus 7.8% versus 43.3%, P < 0.0001). There were no differences in the incidence of BK polyomavirus viremia (8.2% versus 10.1% versus 15.1%, P = 0.360). There were no differences in survival-free from treatment failure (87.8% versus 88.8% versus 93.3%, P = 0.421) and incidence of donor-specific antibodies. At 12 mo, there were no differences in kidney function (75 ± 23 versus 78 ± 24 versus 77 ± 24 mL/min/1.73 m2, P = 0.736), proteinuria, and histology in protocol biopsies. Treatment discontinuation was higher among patients receiving SRL or EVR (18.6% versus 15.6% versus 6.7%, P = 0.054). De novo use of SRL or EVR, targeting similar therapeutic blood concentrations, shows comparable efficacy and safety. The reduced incidence of CMV infection/disease and distinct safety profile of mTORi versus mycophenolate were confirmed in this study.


History of traumatic brain injury in prison populations: A systematic review.
Traumatic brain injury (TBI) can lead to cognitive, behavioural and social impairments. The relationship between criminality and a history of TBI has been addressed on several occasions. The objective of this review was to present an update on current knowledge concerning the existence of a history of TBI in prison populations. PubMed and PsycINFO databases were searched for relevant papers, using the PRISMA guidelines. We selected papers describing TBI prevalence among incarcerated individuals and some that also discussed the validity of such studies. Thirty-three papers were selected. The majority of the papers were on prison populations in Australia (3/33), Europe (5/33) and the USA (22/33). The selected studies found prevalence rates of the history of TBI ranging from 9.7% and 100%, with an average of 46% (calculated on a total population of 9342). However, the level of evidence provided by the literature was poor according to the French national health authority scale. The majority of the prisoners were males with an average age of 37. In most of the papers (25/33), prevalence was evaluated using a questionnaire. The influence of TBI severity on criminality could not be analysed because of a lack of data in the majority of papers. Twelve papers mentioned that several comorbidities (mental health problems, use of alcohol…) were frequently found among prisoners with a history of TBI. Two papers established the validity of the use of questionnaires to screen for a history of TBI. These results confirmed the high prevalence of a history of TBI in prison populations. However, they do not allow conclusions to be drawn about a possible link between criminality and TBI. Specific surveys need to be performed to study this issue. The authors suggest ways of improving the screening and healthcare made available to these patients.