Do Neuromuscular Dentistry-Designed Mouthguards Enhance Dynamic Movement Ability in Competitive Athletes?
The purpose of this study was to examine the effect of a neuromuscular dentistry-designed mouthguard (NMDD) on dynamic movement ability. Forty-two competitive athletes (8 women, 21.9 ± 2.9 years, 66.8 ± 18.8 kg, 1.68 ± 0.11 m; 34 men, 22.8 ± 4.8 years, 77.4 ± 12.7 kg, 1.78 ± 0.08 m) with greater than 2 years' experience in their designated sport were enrolled in the study. Participants completed the Functional Movement Screen (FMS), modified Star Excursion Balance Test (mSEBT), and a single-leg landing (SLL) task. Each subject was tested with 3 separate mouthguard conditions in random order: (a) no mouthguard (NO), (b) over-the-counter boil-and-bite mouthguard (BB; Shockdoctor Gravity, (c) and an NMDD (Pure Power Elite). Data were analyzed using a repeated-measures analysis of variance for each variable. There were no differences between mouthguard conditions in each of the 7 individual components or composite FMS score (p > 0.05). No differences were seen in the anterior, posteromedial, or posterolateral movements of the mSEBT; overall composite score; or time-to-contact measurements (p > 0.05). The BB condition (2.16 Nm·kg) exhibited higher peak knee valgus moments (pKVM) on the right leg only when compared with the NMDD condition (1.95 Nm·kg; p = 0.003) but not the NO condition (2.09 Nm·kg; p = 0.7262) during the SLL task. No differences in pKVM were seen on the left leg (p = 0.324). In conclusion, an NMDD was not effective at enhancing or diminishing measures of dynamic movement ability compared with BB or NO conditions.


A simple educational programme substantially reduces unnecessary use of coagulation screening testing in an acute medical department.
A review suggested that coagulation screening tests (CST) were frequently performed unnecessarily in our Acute Medical Department. We reviewed the records of all patients for whom CST was ordered in one week (n141) before designing and delivering an e-mail, poster and presentation based educational programme to clinicians. We repeated the review of records three weeks after this programme (n79). The proportion of patients in whom CST was ordered was significantly lower (22% versus 32%, p0.0014) and proportion of CSTs sent with a valid indication was significantly higher (87% versus 49%, p 0.0001) in the second review period. This study demonstrates that a simple educational programme substantially reduces unnecessary use of CST in an acute medical department with significant potential efficiency savings.


Quantitative proteomic analysis of Sulfolobus solfataricus membrane proteins.
A quantitative proteomic analysis of the membrane of the archaeon Sulfolobus solfataricus P2 using iTRAQ was successfully demonstrated in this technical note. The estimated number of membrane proteins of this organism is 883 (predicted based on Gravy score), corresponding to 30% of the total number of proteins. Using a modified iTRAQ protocol for membrane protein analysis, of the 284 proteins detected, 246 proteins were identified as membrane proteins, while using an original iTRAQ protocol, 147 proteins were detected with only 133 proteins being identified as membrane proteins. Furthermore, 97.2% of proteins identified in the modified protocol contained more than 2 distinct peptides compared to the original workflow. The successful application of this modified protocol offers a potential technique for quantitatively analyzing membrane-associated proteomes of organisms in the archaeal kingdom. The combination of 3 different iTRAQ experiments resulted in the detection of 395 proteins (>or=2 distinct peptides) of which 373 had predicted membrane properties. Approximately 20% of the quantified proteins were observed to exhibit >or=1.5-fold differential expression at temperatures well below the optimum for growth.


Coordinated interactions between hippocampal ripples and cortical spindles during slow-wave sleep.
Sleep is characterized by a structured combination of neuronal oscillations. In the hippocampus, slow-wave sleep (SWS) is marked by high-frequency network oscillations (approximately 200 Hz "ripples"), whereas neocortical SWS activity is organized into low-frequency delta (1-4 Hz) and spindle (7-14 Hz) oscillations. While these types of hippocampal and cortical oscillations have been studied extensively in isolation, the relationships between them remain unknown. Here, we demonstrate the existence of temporal correlations between hippocampal ripples and cortical spindles that are also reflected in the correlated activity of single neurons within these brain structures. Spindle-ripple episodes may thus constitute an important mechanism of cortico-hippocampal communication during sleep. This coactivation of hippocampal and neocortical pathways may be important for the process of memory consolidation, during which memories are gradually translated from short-term hippocampal to longer-term neocortical stores.


[Diagnosis of Helicobacter pylori by polymerase chain reaction].
The Polymerase Chain Reaction (PCR) is a biotechnological useful tool for the diagnosis of bacteria or viruses with high in vitro growth requirements. Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the upper part of the gastrointestinal tract and its diagnosis is very important since it is associated with chronic gastritis, peptic ulcer, and gastric carcinomas. Because of the difficult growth requirements of the H. pylori, the PCR is being used for its diagnosis in samples of gastric biopsy, gastric juices, feces, saliva and subgingival plaque using specific H. pylori DNA fragments. This paper is a literature review that outlines the use of PCR in the diagnosis of H. pylori, the benefits and future applications of this technique in this area.


Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.
To extend our cDNA project for accumulating basic information on unidentified human genes, we newly determined the sequences of 100 cDNA clones from a set of size-fractionated human adult and fetal brain cDNA libraries, and predicted the coding sequences of the corresponding genes, named KIAA1019 to KIAA1118. The sequencing of these clones revealed that the average size of the inserts and corresponding open reading frames were 5.0 kb and 2.6 kb (880 amino acid residues), respectively. Database search of the predicted amino acid sequences classified 58 predicted gene products into the five functional categories, such as cell signaling/communication, cell structure/motility, nucleic acid management, protein management and cell division. It was also found that, for 34 gene products, homologues were detected in the databases, which were similar in sequence through almost the entire regions. The chromosomal locations of the genes were determined by using human-rodent hybrid panels unless their mapping data were already available in the public databases. The expression profiles of all the genes among 10 human tissues, 8 brain regions (amygdala, corpus callosum, cerebellum, caudate nucleus, hippocampus, substania nigra, subthalamic nucleus, and thalamus), spinal cord, fetal brain and fetal liver were also examined by reverse transcription-coupled polymerase chain reaction, products of which were quantified by enzyme-linked immunosorbent assay.


Total saponins from Trillium tschonoskii Maxim promote neurological recovery in model rats with post-stroke cognitive impairment.
Total saponins from Trillium tschonoskii Maxim (TSTT), a bioactive component of local natural herbs in the Enshi area, China, have been demonstrated to have functions of restoring cognitive capacity and promoting axonal regeneration post-stroke, but the mechanism of this process remains unclear. The hippocampus is a critical tissue for controlling learning and memory capacity, and the sonic hedgehog (Shh) signaling pathway plays a major role in the patterning and synaptic plasticity of hippocampal neural circuits. Therefore, we aimed to investigate whether TSTT could restore learning and cognitive functions by modulating the Shh pathway in rats with post-stroke cognitive impairment (PSCI). The ischemia model was established by permanent middle cerebral artery occlusion (MCAO) in 100 Sprague-Dawley (SD) rats, and the model rats were administered using TSTT (100 mg/kg) or donepezil hydrochloride as the positive control (daily 0.45 mg/kg, DON) for 4 weeks after the operation. As assessed by the Morris water maze test, the cognitive function of PSCI rats was significantly improved upon TSTT treatment. Meanwhile, the cerebral infarct volume reduced with TSTT, as shown by HE and TTC staining, and the number of Nissl bodies and dendritic spine density were significantly increased, as shown by Nissl and Golgi staining. In addition, TSTT upregulated PSD-95, SYN, and GAP-43, and inhibited neuronal apoptosis, as evidenced by increased Bcl-2 levels along with decreased Bax and caspase-3 expression. TSTT could also significantly upregulate Shh, Ptch1, Smo, and Gli1 proteins, indicating the activation of the Shh signaling pathway. Therefore, TSTT can protect PSCI rats by inhibiting apoptosis and promoting neuronal synaptic remodeling. The Shh pathway is also involved.


The Value of Ultrasound in Characterizing and Determining the Etiology of Ascites.
The aim of this study was to assess the role of transabdominal ultrasonography in characterizing and determining the etiology of ascites in comparison with laboratory ascitic fluid analysis and other methods used to establish the final diagnosis. A prospective descriptive study was conducted on 61 patients with ascites attending outpatient department (OPD) or admitted to wards of Tikur Anbesa Specialized Hospital (TASH) and referred to radiology department for imaging from June 2017 to November 2017. Data were collected following the internationally recommended scanning technique in consecutive bases. The data were analyzed using SPSS version 20. The comparison of ultrasound and laboratory findings with final clinical diagnosis was analyzed using Chi-square test (X2). Of 61 patients with ascites enrolled in this study, females were 35(57.4%) with age range of 16 to 75 and mean age of 43.2±14.11. The cause of ascites was established in 59 cases using a combination of clinical, pathological, imaging evidences and tumor markers. However there were two cases who had ascites with indeterminate cause. US suggested the diagnosis in 54(91.5%) patients. Excluding mixed and indeterminate cases, ultrasound characterized ascites correctly as exudate and transudate in 95% cases. Ultrasound has significant accuracy to distinguish transudate and exudate ascites and in suggesting the underlying cause. It can be a valuable method of investigation of ascites in places where CT and MRI are not available, and it is the best complement for laboratory investigations on ascites in suggesting the etiology based on ascitic fluid texture and ancillary findings.


Mycophenolate mofetil in renal transplantation: 3-year results from the placebo-controlled trial. European Mycophenolate Mofetil Cooperative Study Group.
The European double-blind, placebo(PLA) controlled study of mycophenolate mofetil (MMF) for prevention of acute renal allograft rejection showed that MMF 2 and 3 g when added to a standard double-drug regimen of cyclosporine and corticosteroids significantly reduced the incidence of acute rejection/treatment failure at 6 months. Our study presents 3-year data for patient and graft survival, and safety in the MMF-treated patients. The trial included 491 patients who were randomly assigned to receive PLA (n=166), MMF 2g (n=165), or MMF 3 g (n=160). Patients in the PLA group discontinued taking their PLA medication at 1 year posttransplantation; subsequently, they were followed-up only regarding patient and graft survival and the occurrence of malignancies. The 3-year patient survival was 88.9, 92.7, and 91.8% in the PLA, MMF 2 g, and MMF 3 g groups, respectively. The 3-year graft survival (including death as a cause of graft loss) was 78, 84.8, and 81.2%, respectively. Acute allograft rejection was a principal cause of graft loss in all groups (PLA, 10.8%; MMF 2 g, 4.6%; MMF 3 g, 6.3%). Differences in 3-year graft loss rates (excluding death) and 95% confidence intervals for intent-to-treat comparisons of PLA versus MMF 2 g and 3 g, respectively, were 7.3% (1.1, 14.2) and 3.2% (-3.8, 10.1). This leads to a relative risk of graft loss of 0.55 in the MMF 2 g arm compared with the PLA arm. Acute allograft rejection had a major impact on graft loss at 3 years; 31.5% of patients with biopsy-proven acute rejection within 6 months of transplantation lost their graft by the end of 3 years. In contrast, only 6.6% who had no early acute rejection lost their graft by the end of the 3-year study period. Diarrhea, anemia, and leukopenia were the most common clinically relevant adverse events, occurring predominantly in the MMF 3 g group. Only one patient (MMF 3 g) developed cytomegalovirus tissue-invasive disease after the first year posttransplant. Over the 3-year posttransplant period, 12 patients developed malignancies (5 in the PLA group, 3 in the MMF 2 g group, and 4 in the MMF 3 g group). At 3 years posttransplantation, MMF was associated with 7.6% reduction in the incidence of graft loss (excluding death). These data indicate that MMF treatment not only results in a reduction of the incidence of acute rejections but also leads to reduction of late allograft loss.


Expression of clock proteins in developing tooth.
Morphological and functional changes during ameloblast and odontoblast differentiation suggest that enamel and dentin formation is under circadian control. Circadian rhythms are endogenous self-sustained oscillations with periods of 24h that control diverse physiological and metabolic processes. Mammalian clock genes play a key role in synchronizing circadian functions in many organs. However, close to nothing is known on clock genes expression during tooth development. In this work, we investigated the expression of four clock genes during tooth development. Our results showed that circadian clock genes Bmal1, clock, per1, and per2 mRNAs were detected in teeth by RT-PCR. Immunohistochemistry showed that clock protein expression was first detected in teeth at the bell stage (E17), being expressed in EOE and dental papilla cells. At post-natal day four (PN4), all four clock proteins continued to be expressed in teeth but with different intensities, being strongly expressed within the nucleus of ameloblasts and odontoblasts and down-regulated in dental pulp cells. Interestingly, at PN21 incisor, expression of clock proteins was down-regulated in odontoblasts of the crown-analogue side but expression was persisting in root-analogue side odontoblasts. In contrast, both crown and root odontoblasts were strongly stained for all four clock proteins in first molars at PN21. Within the periodontal ligament (PDL) space, epithelial rests of Malassez (ERM) showed the strongest expression among other PDL cells. Our data suggests that clock genes might be involved in the regulation of ameloblast and odontoblast functions, such as enamel and dentin protein secretion and matrix mineralization.


Co-limitation of photosynthetic capacity by nitrogen and phosphorus in West Africa woodlands.
Photosynthetic leaf traits were determined for savanna and forest ecosystems in West Africa, spanning a large range in precipitation. Standardized major axis fits revealed important differences between our data and reported global relationships. Especially for sites in the drier areas, plants showed higher photosynthetic rates for a given N or P when compared with relationships from the global data set. The best multiple regression for the pooled data set estimated V(cmax) and J(max) from N(DW) and S. However, the best regression for different vegetation types varied, suggesting that the scaling of photosynthesis with leaf traits changed with vegetation types. A new model is presented representing independent constraints by N and P on photosynthesis, which can be evaluated with or without interactions with S. It assumes that limitation of photosynthesis will result from the least abundant nutrient, thereby being less sensitive to the allocation of the non-limiting nutrient to non-photosynthetic pools. The model predicts an optimum proportionality for N and P, which is distinct for V(cmax) and J(max) and inversely proportional to S. Initial tests showed the model to predict V(cmax) and J(max) successfully for other tropical forests characterized by a range of different foliar N and P concentrations.


The Center for Epidemiological Studies-Depression (CES-D) Scale: assessment of depression in the medically ill elderly.
This study examines the use of the Center for Epidemiological Studies-Depression Scale (CES-D) in a sample of elderly, medically ill inpatients. Seventy-six individuals completed the CES-D and a psychiatric interview, from which DSM-III-R diagnoses of depression were obtained. Analyses of sensitivity and specificity indicated that use of an alternative scoring method which more closely approximates current diagnostic criteria for depression may improve the predictive power of the test. Employment of stringent cut-scores was not supported, as sensitivity was compromised. Item analyses demonstrated that seven of the CES-D items failed to discriminate major, minor and nondepressed patients, and that several of these items tapped somatic symptoms. These findings suggest that the validity of the CES-D may be compromised when used with elderly medical patients. and modifications for its use are recommended.


Glassy Behavior of Sticky Spheres: What Lies beyond Experimental Timescales?
We use the swap Monte Carlo algorithm to analyze the glassy behavior of sticky spheres in equilibrium conditions at densities where conventional simulations and experiments fail to reach equilibrium, beyond predicted phase transitions and dynamic singularities. We demonstrate the existence of a unique ergodic region comprising all the distinct phases previously reported, except for a phase-separated region at strong adhesion. All structural and dynamic observables evolve gradually within this ergodic region, the physics evolving smoothly from well-known hard sphere glassy behavior at small adhesions and large densities, to a more complex glassy regime characterized by unusually broad distributions of relaxation timescales and length scales at large adhesions.


Change in peripheral refraction over time in Singapore Chinese children.
PURPOSE. Relative peripheral hyperopia has been associated with central myopia. This study was conducted to determine whether baseline relative peripheral hyperopia is associated with an increased risk of developing myopia or myopia progression in young Singapore Chinese children. METHODS. One hundred eighty-seven children who participated in the Peripheral Refraction in Preschool Children (PREP) Study at baseline underwent a follow-up examination. Autorefraction was performed at five eccentricities with an infrared autorefractor after cycloplegia: central axis and 15° and 30° eccentricities in the nasal and temporal visual fields. The primary outcomes were development of myopia among children who were nonmyopic at baseline, and myopia progression in those who were myopic at baseline. RESULTS. The mean age of the children at baseline was 7.2 ± 3.0 years, and the mean duration of follow-up was 1.26 years. At baseline, 96 children were myopic (mean central spherical equivalent [SE] -2.75 ± 1.72 D) and 91 were nonmyopic (mean central SE 0.76 ± 0.81 D). Baseline relative peripheral hyperopia was not associated with a greater likelihood of becoming myopic or myopia progression. At follow-up, children who remained nonmyopic (n = 24) retained relative peripheral myopia at all eccentricities, whereas those who became myopic (n = 67) developed relative peripheral hyperopia at the nasal (+0.44 ± 0.72 D) and temporal 30° (+0.13 ± 0.74 D). The mean change in central SE was -1.51 ± 0.63 D/y for children who developed myopia, -0.82 ± 0.76 D/y for children who were myopic at baseline, and -1.05 ± 0.80 D/y for all children. CONCLUSIONS. Baseline peripheral refraction did not predict the subsequent onset of myopia or influence the progression of myopia.


A constant compliance force modulation technique for scanning force microscopy (SFM) imaging of polymer surface elasticity.
A new method of force modulation scanning force microscopy (SFM) imaging based on a constant compliance feedback loop is presented. The feedback adjusts the loading force applied by the SFM tip to the surface in order to maintain a constant compliance beneath the tip. The new method, constant compliance force modulation (CCFM), has the advantage of being able to quantify the loading force exerted by the tip onto the sample surface and thus to estimate the elastic modulus of the material probed by the SFM tip. Once the elastic modulus of one region is known, the elastic moduli of other surface regions can be estimated from the spatial map of loading forces using the Hertz model of deformation. Force vs. displacement measurements made on one surface locality could also be used to estimate the local modulus. Several model surfaces, including a rubber-toughened epoxy polymer blend which showed clearly resolved compliant rubber phases within the harder epoxy matrix, were analyzed with the CCFM technique to illustrate the method's application.


Probiotic supplementation attenuates age-related sarcopenia via the gut-muscle axis in SAMP8 mice.
Age-related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age-related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut-muscle axis. However, the effects and mechanisms of probiotics in age-related sarcopenia are currently unknown. In this study, we examined the effects of Lactobacillus casei Shirota (LcS), a probiotic previously reported to improve muscle function in young adult mice. We administered LcS (1 × 108 or 1 × 109 CFU/mouse/day) by oral gavage to senescence-accelerated mouse prone-8 mice for 12 weeks (16- to 28-week-old). Sixteen-week-old and 28-week-old SMAP8 mice were included as non-aged and aged controls, respectively. Muscle condition was evaluated using dual-energy X-ray absorptiometry for muscle mass, holding impulse and grip strength tests for muscle strength, and oxygen consumption rate, gene expressions of mitochondrial biogenesis, and mitochondrial number assays for mitochondria function. Inflammatory cytokines were determined using enzyme-linked immunosorbent assay. Gas chromatography-mass spectrometry was utilized to measure the short-chain fatty acid levels. The gut microbiota was analysed based on the data of 16S rRNA gene sequencing of mouse stool. The LcS supplementation reduced age-related declines in muscle mass (>94.6%, P < 0.04), strength (>66% in holding impulse and >96.3% in grip strength, P < 0.05), and mitochondrial function (P < 0.05). The concentration of short-chain fatty acids (acetic, isobutyric, butyric, penic, and hexanoic acid) was recovered by LcS (>65.9% in the mice given high dose of LcS, P < 0.05) in the aged mice, and LcS attenuated age-related increases in inflammation (P < 0.05) and reactive oxygen species (>89.4%, P < 0.001). The high dose of LcS supplementation was also associated with distinct microbiota composition as indicated by the separation of groups in the beta-diversity analysis (P = 0.027). LcS supplementation altered predicted bacterial functions based on the gut microbiota. Apoptosis (P = 0.026), p53 signalling (P = 0.017), and non-homologous end-joining (P = 0.031) were significantly reduced, whereas DNA repair and recombination proteins (P = 0.043), RNA polymerase (P = 0.008), and aminoacyl-tRNA biosynthesis (P = 0.003) were increased. Finally, the genera enriched by high-dose LcS [linear discriminant analysis (LDA) score > 2.0] were positively correlated with healthy muscle and physiological condition (P < 0.05), while the genera enriched in aged control mice (LDA score > 2.0) were negatively associated with healthy muscle and physiological condition (P < 0.05). Lactobacillus casei Shirota represents an active modulator that regulates the onset and progression of age-related muscle impairment potentially via the gut-muscle axis.


Abnormal amygdala and prefrontal cortex activation to facial expressions in pediatric bipolar disorder.
Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late phase of activation, suggesting different temporal characteristics of brain responses. A total of 20 euthymic adolescents with familial BD (14 male) and 21 healthy control subjects (13 male) underwent fMRI scanning during presentation of happy, sad, and neutral facial expressions. Whole-brain voxelwise analyses were conducted in SPM5, using a three-way analysis of variance (ANOVA) with factors group (BD and healthy control [HC]), facial expression (happy, sad, and neutral versus scrambled), and phase (early and late, corresponding to the first and second half of each block of faces). There were no significant group differences in task performance, age, gender, or IQ. Significant activation from the main effect of group included greater DLPFC activation in the HC group, and greater amygdala/hippocampal activation in the BD group. The interaction of Group × Phase identified clusters in the superior temporal sulcus/insula and visual cortex, where activation increased from the early to late phase of the block for the BD but not the HC group. These findings are consistent with previous studies that suggest deficient prefrontal cortex regulation of heightened amygdala response to emotional stimuli in pediatric BD. Increasing activation over time in superior temporal and visual cortices suggests difficulty processing or disengaging attention from emotional faces in BD.


Changes in glitazone use among office-based physicians in the U.S., 2003-2009.
Little is known regarding recent changes in glitazone use. Interrupted time series analyses of nationally representative office-visit data using IMS Health's National Disease and Therapeutic Index. From 2003 through 2005, glitazone use increased steadily. From February 2005 to January 2007, rosiglitazone use decreased by 16% (95% CI -20 to -11) annually; pioglitazone use increased at an annual rate of 14% (9-18). During a period of Food and Drug Administration (FDA) advisories, rosiglitazone use declined sharply from 0.42 million monthly treatment visits (February 2007) to 0.13 million monthly visits (May 2008). Pioglitazone use remained stable, accounting for approximately 5.8 million physician visits (77% of all glitazone use) where a treatment was used during the final 12 months of observation. The combined effect of scientific publications, advisories, and media exposure was associated with a substantial decrease in rosiglitazone use. Despite a class-level FDA advisory, pioglitazone use was not similarly affected.


Review: immunomodulatory activity of pregnancy-associated plasma protein-A.
This mini-review highlights the growing number of indications for the immunological importance of pregnancy-associated plasma protein-A (PAPP-A), which is a remote member of the alpha-macroglobulin plasma protein family. PAPP-A can bind a variety of cytokines and specifically cleave a binding protein for insulin-like growth factors, thereby serving as a modulator of cytokine activity. Important immune functions, such as lymphocyte proliferation response to alloantigens and lectins and expression of HLA-DR molecules are predominantly suppressed in vitro by PAPP-A. It is likely that the immunoregulatory properties of PAPP-A are very similar to that of alpha 2-macroglobulin. The experimental data allows us to suppose that PAPP-A serves to prevent the recognition of the fetus by the maternal immune system and to suppress locally the host's immune response to the tumour.


Management of diabetic foot ulcers using topical probiotics in a soybean-based concentrate: a multicentre study.
Diabetic foot ulcer (DFU) is a common complication in people with diabetes. Standard management includes strict glycaemic management, control of the infection, revascularisation, debridement, mechanical offloading and foot care education. This study aimed to evaluate the efficacy of using topical probiotics in a soybean-based concentrate in the management of DFUs. A retrospective, multicentre evaluation of patients with diabetes with non-infected DFUs between October 2020 and October 2021, and who were treated with twice daily topical application of probiotics in a soybean-based concentrate as an adjunct to standard wound care. A total of 22 patients were enrolled into this study, including 16 males and six females, with a mean age of 61 years (range: 31-89 years). Defect size ranged from 1-33.5cm2 (mean: 7.2cm2). The mean number of days until complete healing was 51 (range: 21-112 days). Of the patients, 83% showed complete healing at the end of 16 weeks, 72% showed complete healing at 12 weeks, 56% at eight weeks, and 22% at four weeks. The wounds showed an average decrease in size of 0.59cm2 (9%) per week, calculated using generalised estimating equation. This findings of this study provide a new perspective on the therapeutic potential of probiotics as an effective form of management in patients with small, hard-to-heal (chronic) DFUs.


Stimulus properties of opioids with mixed agonist and antagonist activity.
The discriminative stimulus properties of opioids with mixed agonist and antagonist activity are heterogeneous in contrast to the relative uniformity of the stimulus properties of classical morphinelike agonists. Patterns of stimulus generalization to mixed agonist-antagonists are critically dependent on factors such as the particular drug used for training, dose of the training drug, and species of the experimental subject. Opioids can be divided into three broad categories on the basis of their patterns of stimulus generalization in rats and squirrel monkeys trained to discriminate saline from morphine, cyclazocine, or phenyclidine (PCP), and these categories predict the ease with which their stimulus effects can be blocked by nalozone or naltrexone. 1) Opioids that are generalized completely to morphine; stimulus effects are easily antagonized. 2) Opioids that are generalized completely to cyclazocine; stimulus effects are antagonized with difficulty. 3) Opioids that are generalized completely to cyclazocine and PCP; stimulus effects not antagonized. The diversity of the stimulus properties of opioids is consistent with evidence that multiple populations of receptors subserve the actions of morphinelike agonists and agonist-antagonists. However, the stimulus effects of opioids in group 3 appear to be mediated by the same neuronal substrates that are acted on by PCP rather than by neuronal sites traditionally associated with the activity of opioids.


Fat mass changes during menopause: a metaanalysis.
Data: Fat mass has been shown to increase in aging women; however, the extent to which menopausal status mediates these changes remains unclear. The purpose of this review was to determine (1) how fat mass differs in quantity and distribution between premenopausal and postmenopausal women, (2) whether and how age and/or menopausal status moderates any observed differences, and (3) which type of fat mass measure is best suited to the detection of differences in fat mass between groups. This review with metaanalyses is reported according to Metaanalysis of Observational Studies in Epidemiology guidelines. Studies (published up to May 2018) were identified via PubMed to provide fat mass measures in premenopausal and postmenopausal women. We included 201 cross-sectional studies in the metaanalysis, which provided a combined sample size of 1,049,919 individuals and consisted of 478,734 premenopausal women and 571,185 postmenopausal women. Eleven longitudinal studies were included in the metaanalyses, which provided a combined sample size of 2472 women who were premenopausal at baseline and postmenopausal at follow up. The main findings of this review were that fat mass significantly increased between premenopausal and postmenopausal women across most measures, which included body mass index (1.14 kg/m2; 95% confidence interval, 0.95-1.32 kg/m2), bodyweight (1 kg; 95% confidence interval, 0.44-1.57 kg), body fat percentage (2.88%; 95% confidence interval, 2.13-3.63%), waist circumference (4.63 cm; 95% confidence interval, 3.90-5.35 cm), hip circumference (2.01 cm; 95% confidence interval, 1.36-2.65 cm), waist-hip ratio (0.04; 95% confidence interval, 0.03-0.05), visceral fat (26.90 cm2; 95% confidence interval, 13.12-40.68), and trunk fat percentage (5.49%; 95% confidence interval, 3.91-7.06 cm2). The exception was total leg fat percentage, which significantly decreased (-3.19%; 95% confidence interval, -5.98 to -0.41%). No interactive effects were observed between menopausal status and age across all fat mass measures. The change in fat mass quantity between premenopausal and postmenopausal women was attributable predominantly to increasing age; menopause had no significant additional influence. However, the decrease in total leg fat percentage and increase in measures of central fat are indicative of a possible change in fat mass distribution after menopause. These changes are likely to, at least in part, be due to hormonal shifts that occur during midlife when women have a higher androgen (ie, testosterone) to estradiol ratio after menopause, which has been linked to enhanced central adiposity deposition. Evidently, these findings suggest attention should be paid to the accumulation of central fat after menopause, whereas increases in total fat mass should be monitored consistently across the lifespan.


Interferon-gamma is an autocrine mediator for dendritic cell maturation.
Maturation of dendritic cells (DC) is critical for efficient antigen presentation and initiation of an immune response. Interferon-gamma (IFN-gamma) is an important Th1 cytokine. In this study, we investigated the role of IFN-gamma in DC maturation using either IFN-gamma receptor deficient- or IFN-gamma overexpression-models. We showed that immature DC generated in vitro from bone marrow (BM) progenitor cells produced low level of IFN-gamma. After LPS stimulation, DC produced more IFN-gamma, and IFN-gamma productions were at comparable levels among C57BL/6 mice-derived DC (C57BL/6 DC), wild-type 129 mice-derived DC (129 DC) and IFN-gamma receptor deficient 129 mice-derived DC (IFN-gammaR-/-DC). We found that IFN-gammaR-/-DC exhibited decreased expression of CD54, CD86, reduced capacity to secrete IL-1beta and IL-12p70, and impaired capacity to stimulate alloreactive T cells and to drive Th1 differentiation. Transfection of IFN-gamma gene into DC promoted DC to express higher CD40, CD54, CD80, CD86, CCR7 and I-Ab, secrete more IL-1beta and IL-12p70, and more potently activate both CD4 and CD8 T cells. These data suggest that IFN-gamma signaling pathway is important for the maturation of DC in an autocrine fashion.


The role of the testa during the establishment of physical dormancy in the pea seed.
A water-impermeable testa acts as a barrier to a seed's imbibition, thereby imposing dormancy. The physical and functional properties of the macrosclereids are thought to be critical determinants of dormancy; however, the mechanisms underlying the maintenance of and release from dormancy in pea are not well understood. Seeds of six pea accessions of contrasting dormancy type were tested for their ability to imbibe and the permeability of their testa was evaluated. Release from dormancy was monitored following temperature oscillation, lipid removal and drying. Histochemical and microscopic approaches were used to characterize the structure of the testa. The strophiole was identified as representing the major site for the entry of water into non-dormant seeds, while water entry into dormant seeds was distributed rather than localized. The major barrier for water uptake in dormant seeds was the upper section of the macrosclereids, referred to as the 'light line'. Dormancy could be released by thermocycling, dehydration or chloroform treatment. Assays based on either periodic acid or ruthenium red were used to visualize penetration through the testa. Lipids were detected within a subcuticular waxy layer in both dormant and non-dormant seeds. The waxy layer and the light line both formed at the same time as the establishment of secondary cell walls at the tip of the macrosclereids. The light line was identified as the major barrier to water penetration in dormant seeds. Its outer border abuts a waxy subcuticular layer, which is consistent with the suggestion that the light line represents the interface between two distinct environments - the waxy subcuticular layer and the cellulose-rich secondary cell wall. The mechanistic basis of dormancy break includes changes in the testa's lipid layer, along with the mechanical disruption induced by oscillation in temperature and by a decreased moisture content of the embryo.


Relationship between caregiver's and child's caries prevalence among disadvantaged African Americans.
To assess the relationship between African-American caregivers' and children's caries levels adjusting for sociodemographic factors. A representative sample of 1021 children (0-5 years) and their caregivers were recruited using a stratified two-stage area probability sample of households in Detroit. The response rate was 73.7%. Caries was measured using the International Caries Detection and Assessment System. Caries was defined as D1S/d1s (noncavitated) or D2S/d2s (cavitated lesions) for both caregivers and children. Sociodemographic data included caregivers' employment status, sex, age, income and education. Negative binomial regression techniques were used for the multivariable analyses because of the highly skewed distribution of caries among the children. 48% of the children were male, 39% had employed caregivers, 46% had caregivers with less than a high school education and 44% had family incomes less than $10,000. A total of 47% of the children had at least one noncavitated lesion and 31% had a cavitated lesion. Younger children (ages 0-3 years) had lower caries rates with 24% having one or more noncavitated lesion,18% having a cavitated lesion and 31% with any lesion compared with 78%, 51% and 81%, respectively, among the 4- to 5-year olds. Because of these differences in prevalence in the age groups, subsequent analyses were conducted separately for the two age groups. Multivariable analyses found that the number of cavitated surfaces among the caregivers was significantly related to the number of cavitated and noncavitated lesions among their children for both age groups. The prevalence of children's caries increased with increasing caregivers' caries score when demographic characteristics of caregivers were controlled. Younger children with family incomes of less than $10,000 had a significantly increased risk of higher caries prevalence compared with children in families with incomes greater than or equal to $20,000. Caregivers' caries levels were modestly correlated with children's caries. However, higher caries prevalence among caregivers significantly increased the risk of caries prevalence among their children. Thus, efforts aimed at improving caregiver's oral health could result in reducing caries risk among their children, regardless of whether the mechanism was biologically or behaviorally based. Efforts also should be aimed directly at reducing caries risk among children by increasing fluoride exposure among children and improving access to preventive dental care. Finally, even the poorest of the poor experienced additional health disadvantages associated with income suggesting even small increases in family income raising families could have a significant effect on reducing caries risk among young children.


Pituitary and adrenals are required for hyperglycemic reflex initiated by stimulation of CBR with cyanide.
We have previously shown that stimulation of carotid body receptors (CBR) with sodium cyanide (NaCN) elicits a rapid hyperglycemic reflex. Here we explore whether the pituitary and adrenals, two glands involved in glucose homeostasis, are necessary for this reflex. Experiments were performed on anesthetized rats that were artificially ventilated. Measurements of hepatic venous-arterial glucose difference indicated that CBR stimulation with a bolus of 5 micrograms/100 g NaCN produced an immediate increase in the output of glucose by the liver. The same dose of NaCN failed to increase hepatic output of glucose in rats with bilateral adrenalectomy or in rats 1 wk after surgical removal of neurohypophysis. Reflex glucose output by the liver was maintained after adenohypophysectomy or in adrenalectomized rats after adrenal autotransplantation to epiploon. Measurements of epinephrine in plasma and in the grafted adrenal tissue showed that the adrenal autograft can store and secrete catecholamines Immunocytochemical observations indicated that the grafted adrenals retain medullary cells. These results indicate that neurohypophysis and adrenals are necessary for the hyperglycemic reflex initiated by CBR stimulation with NaCN and that the participation of these two organs in this reflex is probably humoral.


Dynamic optical activity induction in the N-alkyl-N'-trityl ureas and thioureas.
Considered to be rigid, the urea and thiourea functionalities, often used in material chemistry and in asymmetric organocatalysis, are able to transmit information regarding 3D structure from a permanently chiral inducer part to a dynamically chiral (reporter) part of the molecule. Despite a considerable distance between the inducer and the reporter parts of the molecule, the chirality transfer phenomenon has been demonstrated for a series of secondary N-alkyl-N'-trityl ureas and thioureas. The induction of helicity in a stereodynamic trityl propeller is revealed by rising non-zero Cotton effects in the area of trityl absorption. The information regarding the 3D structure of the inducer is transferred to the reporter part of the system through a set of weak but complementary electrostatic interactions. The presence of two supramolecular motifs in the same molecule, characterized by opposite properties, significantly affected the molecular solid state structure of the thioureas and their abilities to assemble. In the crystalline phase, the model, a chiral N-tert-butyl-thiourea derivative that retains the extended Z,Z conformation of the linker, is prone to form a supramolecular network typical of secondary ureas and thioureas. In contrast, the presence of the hydrophobic trityl group suppresses the thioamide NHS[double bond, length as m-dash]C hydrogen bonds. Therefore, trityl acts as a supramolecular protecting group for thioamide functionality, hampering the formation of hydrogen bonded networks in the solid state.


After the bell: adolescents' organised leisure-time activities and well-being in the context of social and socioeconomic inequalities.
Previous research has linked adolescents' participation in organised leisure-time activities (OLTAs) to better health and well-being. It remains unclear whether these associations can be observed consistently across social and socioeconomic strata and countries. The present study used nine nationally representative samples of adolescents aged 11, 13 and 15 years (total n=55 429) from the 2017/2018 Health Behaviour in School-aged Children survey from Europe and Canada. Regression models with mixed effects to account for nested nature of data were applied to estimate: (1) the associations of social and socioeconomic factors with OLTA participation; (2) strengths of the associations between breadth and pattern of OLTA participation with health and well-being indicators, after adjustment for the social and socioeconomic factors. Rates of OLTA participation varied by age, sex and country of adolescents. Participants from lower socioeconomic classes and non-nuclear families were less likely to participate in OLTAs across each of the nine countries. Moreover, breadth of OLTA participation was associated with higher well-being independent of socioeconomic status or family structure. All of the participation patterns were associated with higher life satisfaction, but sports (either alone or in combination with a non-sport OLTA) were also associated with fewer psychological complaints and excellent self-rated health. Adolescents' engagement in OLTAs was associated with adolescents' subjective well-being regardless of country, age, sex and variance in social and socioeconomic factors. Policies aimed at increasing adolescents' subjective well-being and OLTA participation should focus on adolescents from low socioeconomic classes and non-nuclear families.


Use of biomarkers to assess fruit and vegetable intake.
A high intake of fruit and vegetables (FV) has been associated with reduced risk of a number of chronic diseases, including CVD. The aim of this review is to describe the potential use of biomarkers to assess FV intake. Traditional methods of assessing FV intake have limitations, and this is likely to impact on observed associations with disease outcomes and markers of disease risk. Nutritional biomarkers may offer a more objective and reliable method of assessing dietary FV intake. Some single blood biomarkers, such as plasma vitamin C and serum carotenoids, are well established as indicators of FV intake. Combining potential biomarkers of intake may more accurately predict overall FV intake within intervention studies than the use of any single biomarker. Another promising approach is metabolomic analysis of biological fluids using untargeted approaches to identify potential new biomarkers of FV intake. Using biomarkers to measure FV intake may improve the accuracy of dietary assessment.


Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias.
Diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI have high sensitivity and specificity for Creutzfeldt-Jakob disease (CJD). No studies, however, have demonstrated how MRI can distinguish CJD from nonprion causes of rapidly progressive dementia (npRPD). We sought to determine the diagnostic accuracy of MRI for CJD compared to a cohort of npRPD subjects. Two neuroradiologists blinded to diagnosis assessed DWI and FLAIR images in 90 patients with npRPD (n = 29) or prion disease (sporadic CJD [sCJD], n = 48, or genetic prion disease [familial CJD, n = 6, and Gerstmann-Sträussler-Scheinker, n = 7]). Thirty-one gray matter regions per hemisphere were assessed for abnormal hyperintensities. The likelihood of CJD was assessed using our previously published criteria. Gray matter hyperintensities (DWI > FLAIR) were found in all sCJD cases, with certain regions preferentially involved, but never only in limbic regions, and rarely in the precentral gyrus. In all sCJD cases with basal ganglia or thalamic DWI hyperintensities, there was associated restricted diffusion (apparent diffusion coefficient [ADC] map). This restricted diffusion, however, was not seen in any npRPD cases, in whom isolated limbic hyperintensities (FLAIR > DWI) were common. One reader's sensitivity and specificity for sCJD was 94% and 100%, respectively, the other's was 92% and 72%. After consensus review, the readers' combined MRI sensitivity and specificity for sCJD was 96% and 93%, respectively. Familial CJD had overlapping MRI features with sCJD. The pattern of FLAIR/DWI hyperintensity and restricted diffusion can differentiate sCJD from other RPDs with a high sensitivity and specificity. MRI with DWI and ADC should be included in sCJD diagnostic criteria. New sCJD MRI criteria are proposed.


Antiterminator protein GlpP of Bacillus subtilis binds to glpD leader mRNA.
The Bacillus subtilis glpD gene encodes glycerol-3-phosphate (G3P) dehydrogenase. Expression of glpD is mainly controlled by termination/antitermination of transcription at an inverted repeat in the glpD leader. Antitermination is mediated by the antiterminator protein GlpP in the presence of G3P. In this paper, interaction between GlpP and glpD leader mRNA in vivo and in vitro is reported. In vivo, the antiterminating effect of GlpP can be titrated in a strain carrying the glpD leader on a plasmid. GlpP has been purified and gel shift experiments have shown that it binds to glpD leader mRNA in vitro. GlpP is not similar to other known antiterminator proteins, but database searches have revealed an Escherichia coli ORF which has a high degree of similarity to GlpP.


[A novel view of prophylaxis and treatment of chronic adenoiditis in children].
The present clinical study had the objective to evaluate the role of a hypertonic solution of sterile water from the Adriatic Sea in the prevention and treatment of chronic adenoiditis in children. It included 30 children aged from 2.5 to 15 years. The control group was comprised of 30 children treated by intransal drop infusion of physiological saline followed by irrigation of the nasal cavity with framicetin as recommended by the manufacturer. The study failed to reveal a significant difference (P > 0.05) between dynamics of the symptoms of chronic adenoiditis in the patients of either group assessed based on the 10-point analog visual scale. However, the frequency of relapses of adenoiditis during the observation period (3 months) was significantly lower in the patients treated with the hypertonic solution of sterile seawater. Microbiological investigations of the material from the pharyngonasal cavity showed no difference between the occurrence of tansient bacterial microflora in the patients of the study and control groups.


Tobacco nicotine uptake permease (NUP1) affects alkaloid metabolism.
An effective plant alkaloid chemical defense requires a variety of transport processes, but few alkaloid transporters have been characterized at the molecular level. Previously, a gene fragment encoding a putative plasma membrane proton symporter was isolated, because it was coordinately regulated with several nicotine biosynthetic genes. Here, we show that this gene fragment corresponds to a Nicotiana tabacum gene encoding a nicotine uptake permease (NUP1). NUP1 belongs to a plant-specific class of purine uptake permease-like transporters that originated after the bryophytes but before or within the lycophytes. NUP1 expressed in yeast cells preferentially transported nicotine relative to other pyridine alkaloids, tropane alkaloids, kinetin, and adenine. NUP1-GFP primarily localized to the plasma membrane of tobacco Bright Yellow-2 protoplasts. WT NUP1 transcripts accumulated to high levels in the roots, particularly in root tips. NUP1-RNAi hairy roots had reduced NUP1 mRNA accumulation levels, reduced total nicotine levels, and increased nicotine accumulation in the hairy root culture media. Regenerated NUP1-RNAi plants showed reduced foliar and root nicotine levels as well as increased seedling root elongation rates. Thus, NUP1 affected nicotine metabolism, localization, and root growth.


GAGESIGHT: A Computer Vision System for Automatic Inspection of Instrument Gauges.
GAGESIGHT is a computer vision system recently integrated into production which demonstrates new flexibility in production automation technology. The vision algorithm accommodates significant misregistration in the position and orientation of objects, and adjusts process control parameters accordingly. The GAGESIGHT system is easily reconfigured for inspecting new types of objects by executing a teach program, and responding to a few instructions at an interactive display console. GAGESIGHT, intially intended for the automatic inspection and assembly of pointers and other components to instrument gauges, is finding new applications as well since the approach employed makes few assumptions regarding the objects being viewed.


Expanding the Search for Sperm Transmission Elements in the Mitochondrial Genomes of Bivalve Mollusks.
Doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA) in bivalve mollusks is one of the most notable departures from the paradigm of strict maternal inheritance of mtDNA among metazoans. Recently, work on the Mediterranean mussel Mytilus galloprovincialis suggested that a nucleotide motif in the control region of this species, known as the sperm transmission element (STE), helps protect male-transmitted mitochondria from destruction during spermatogenesis. Subsequent studies found similar, yet divergent, STE motifs in other marine mussels. Here, we extend the in silico search for mtDNA signatures resembling known STEs. This search is carried out for the large unassigned regions of 157 complete mitochondrial genomes from within the Mytiloida, Veneroida, Unionoida, and Ostreoida bivalve orders. Based on a sliding window approach, we present evidence that there are additional putative STE signatures in the large unassigned regions of several marine clams and freshwater mussels with DUI. We discuss the implications of this finding for interpreting the origin of doubly uniparental inheritance in ancestral bivalve mollusks, as well as potential future in vitro and in silico studies that could further refine our understanding of the early evolution of this unusual system of mtDNA inheritance.


Radiation therapy for neoplasms of the brain.
The effectiveness and complications of radiation therapy for brain neoplasms are reviewed. While the available data suggest a favorable influence and outcome, randomized studies are needed to further optimize radiation therapy techniques and to integrate new therapeutic modalities.


Improving the quality of care for patients with advanced epithelial ovarian cancer: Program components, implementation barriers, and recommendations.
The high lethality of ovarian cancer in the United States and associated complexities of the patient journey across the cancer care continuum warrant an assessment of current practices and barriers to quality care in the United States. The objectives of this study were to identify and assess key components in the provision of high-quality care delivery for patients with ovarian cancer, identify challenges in the implementation of best practices, and develop corresponding quality-related recommendations to guide multidisciplinary ovarian cancer programs and practices. This multiphase ovarian cancer quality-care initiative was guided by a multidisciplinary expert steering committee, including gynecologic oncologists, pathologists, a genetic counselor, a nurse navigator, social workers, and cancer center administrators. Key partnerships were also established. A collaborative approach was adopted to develop comprehensive recommendations by identifying ideal quality-of-care program components in advanced epithelial ovarian cancer management. The core program components included: care coordination and patient education, prevention and screening, diagnosis and initial management, treatment planning, disease surveillance, equity in care, and quality of life. Quality-directed recommendations were developed across 7 core program components, with a focus on ensuring high-quality ovarian cancer care delivery for patients through improved patient education and engagement by addressing unmet medical and supportive care needs. Implementation challenges were described, and key recommendations to overcome barriers were provided. The recommendations emerging from this initiative can serve as a comprehensive resource guide for multidisciplinary cancer practices, providers, and other stakeholders working to provide quality-directed cancer care for patients diagnosed with ovarian cancer and their families.


Nurse auxiliaries as providers of intrauterine devices for contraception in Guatemala and Honduras.
Nurse auxiliaries staff the majority of primary health service delivery outlets in low-income countries, particularly in rural areas with high unmet need for contraception. Yet often service delivery guidelines prohibit them from providing contraceptive methods such as the intrauterine device (IUD). Operations research in Guatemala and Honduras in 1997-2005, described in this paper, have shown that nurse auxiliaries can provide IUDs in a safe and clinically appropriate fashion, which can help improve women's choice of methods and decrease costs in health centres with physicians and professional nurses, and health posts. Empowering these health workers requires commitment at the health system and policy levels to a long-term strategy in which small pilot studies are first conducted, followed by phased scaling-up of the strategies, which can require several years. Training can be conducted both in high volume clinics or on-site in health posts. Simple measures such as mentioning the method during counselling and to users of different services and providing women and communities with printed materials have been effective in increasing requests for IUDs. These studies also showed that nurse auxiliaries can take on other reproductive health services, such as contraceptive injections.


Combination chemoimmunotherapy for extensive non-oat cell lung cancer.
In a prospective randomized trial, sc Corynebacterium parvum (C. parvum) immunotherapy did not significantly affect the responses and survival of 49 non-oat cell lung cancer patients receiving isophosphamide and adriamycin chemotherapy. Remissions (tumor regression greater than 50%) were seen in five of 23 patients receiving an intensive C. parvum schedule and in three of 26 patients receiving a nonintensive C. parvum schedule (22% versus 12%). Median survival was 20 weeks for patients given intensive C. parvum and 23 weeks for patients given nonintensive C. parvum. This study did demonstrate the importance of pretherapy immunocompetence, performance status, and weight loss as predictors for survival. Weight loss was the most significant prognostic factor. Performance status was closely associated with weight loss but skin reactivity to dermatophytin predicted independently and was the second most important prognostic characteristic.


Are health inequalities evident at all ages? An ecological study of English mortality records.
Inequalities in mortality are often presumed to exist at all ages. Here we examine whether this is true. We conducted an ecological study of mortality in England for 1997-99 using routinely collected public records. We used a (smoothed) single year of age rate of mortality for males and females by the multiple deprivation quintile of their ward of residence, for all and specific causes to assess if inequalities varied by age. For most ages, a greater mortality risk exists for those living in the most deprived compared with the least deprived quintile of wards. However, during late adolescence there is equality. The equalization occurs at the age of 17-19 years. There is a longer period of 10 years for females and 20 years for males of convergence and then divergence centred on late adolescence and young adulthood. The equalization is driven principally through a heightened exposure to the risk of land transport accidents and a resulting higher than expected rate of mortality for the least deprived rather than a decrease in risk for the most deprived. It seems likely that an increase in risk taking associated with late adolescence combined with exposure to a relatively dangerous transport environment leads to large increases in risk for young people in the least deprived parts of England. As a result mortality inequality disappears at this age.


Killing and replacing queen-laid eggs: low cost of worker policing in the honeybee.
Worker honeybees, Apis mellifera, police each other's reproduction by killing worker-laid eggs. Previous experiments demonstrated that worker policing is effective, killing most (∼98%) worker-laid eggs. However, many queen-laid eggs were also killed (∼50%) suggesting that effective policing may have high costs. In these previous experiments, eggs were transferred using forceps into test cells, mostly into unrelated discriminator colonies. We measured both the survival of unmanipulated queen-laid eggs and the proportion of removal errors that were rectified by the queen laying a new egg. Across 2 days of the 3-day egg stage, only 9.6% of the queen-laid eggs in drone cells and 4.1% in worker cells were removed in error. When queen-laid eggs were removed from cells, 85% from drone cells and 61% from worker cells were replaced within 3 days. Worker policing in the honeybee has a high benefit to policing workers because workers are more related to the queen's sons (brothers, r = 0.25) than sister workers' sons (0.15). This study shows that worker policing also has a low cost in terms of the killing of queen-laid eggs, as only a small proportion of queen-laid eggs are killed, most of which are rapidly replaced.


Efflux of organic acids in Penicillium simplicissimum is an energy-spilling process, adjusting the catabolic carbon flow to the nutrient supply and the activity of catabolic pathways.
Continuous cultivation was used to study the effect of glucose, ammonium, nitrate or phosphate limitation on the excretion of tricarboxylic acid (TCA) cycle intermediates by Penicillium simplicissimum. Additionally, the effect of benzoic acid, salicylhydroxamic acid (SHAM) and 2,4-dinitrophenol on TCA cycle intermediates was studied. The physiological state of the fungus was characterized by its glucose and O(2) consumption, its CO(2) production, its intra- and extracellular concentrations of TCA cycle intermediates, as well as by its biomass yield, its maintenance coefficient and its respiratory quotient. The excretion of TCA cycle intermediates was observed during ammonium-, nitrate- and phosphate-limited growth. The highest productivity was found with phosphate-limited growth. The respiratory quotient was 1.3 under ammonium limitation and 0.7 under phosphate limitation. Citrate was always the main excreted intermediate. This justifies calling this excretion an energy-spilling process, because citrate excretion avoids the synthesis of too much NADH. The addition of benzoic acid further increased the excretion of TCA cycle intermediates by ammonium-limited hyphae. A SHAM-sensitive respiration was constitutively present during ammonium-limited growth of the fungus. The sum of the excreted organic acids was negatively correlated with the biomass yield (Y(GlcX)).


Anaesthetic considerations and perioperative features of endoscopic third ventriculostomy in infants: analysis of 57 cases.
Endoscopic third ventriculostomy (ETV) is currently considered the best alternative to shunt systems in the treatment of triventricular hydrocephalus. However, there has been very few published data about the anaesthetic management and the complications of ETV procedure in infants. In this report, we detail our experience with 57 infants, who underwent ETV as an initial treatment for obstructive triventricular hydrocephalus between 2003 and 2010. Anesthesia chart-records were retrospectively investigated and perioperative data were classified according to the stages of the procedure. In this series, mean heart rate values showed a statistically significant difference in the period concerning the balloon dilatation of ventriculostomy orifice. An episode of bradycardia occurred in 2 patients during balloon dilatation. After the deflation of the balloon, bradycardia resolved immediately without administration of any medication. Video recordings of those two patients revealed that one of them had a narrow and opaque tuber cinereum, and the other had a shallow interpeduncular cistern. During ETV procedure in infants, bradycardia may be a serious complication especially when performing balloon dilatation of the ventriculostomy orifice. We believe that close communication between the surgeon and the anaesthetist is extremely essential in this stage of the procedure.


Possible role of autoimmunity to spermatozoa in idiopathic infertility of stallions.
Testicular degeneration is a major cause of subfertility in stallions, although an aetiological diagnosis cannot be made in most cases. In the present study, autoimmune testicular degeneration was induced and evaluated in stallions by immunizing stallions with their own spermatozoa mixed with an adjuvant. The factors evaluated included changes in semen quality and testicular histology. A large decrease in sperm number and quality was observed in response to sperm autoantigens. An ELISA test specific for antisperm antibodies was developed which enabled antibody titres in serum, seminal plasma and accessory sex organs to be measured. Serum antibodies were characterized as being specific for spermatozoa by absorption studies and western blotting. The data obtained and the tests developed in the present study provide a better understanding of the disease in subfertile breeding stallions and the ability to diagnose the disease using ELISA. The results of a clinical trial demonstrate that there is a higher incidence of antisperm antibodies in subfertile stallions compared with fertile stallions. The results of the present study indicate that autoimmunity to spermatozoa plays a role in idiopathic subfertility in stallions. A potentially useful method for tentative diagnosis of autoimmune testicular degeneration in subfertile stallions was also developed.


Onyalai at Rundu, Namibia 1981-1988: age, sex, morbidity, mortality and seasonal variation of 612 hospitalized patients.
Of 51,263 admissions to Rundu State Hospital in Namibia between 1981 and 1988, 612 (1.19%) were diagnosed as onyalai. The annual incidence varied between 0.96% and 1.66% of all admissions. The female to male ratio was 3:2. The mean age at presentation was 24.8 years (range 6 months to 80 years) and the mean hospital stay (and duration of clinical bleeding) for the years 1981 to 1982 and 1985 to 1988 was 7.68 d (range 1-38 d). Although the highest number of cases occurred during the months March, April and May a statistically significant monthly variation was not found. The treatment policy of commencing intravenous fluid on admission and a blood transfusion whenever the haemoglobin dropped below 10 g/dl in patients with active bleeding was associated with a mortality rate of 2.78% compared to 9.8% in cases recorded up to 1981.


[Na, K-ATPase activity in the erythrocyte membrane preparations and kidneys of spontaneously hypertensive rats].
The enzyme activity in the cortex and medulla of the SHR was 1.5-2.0-fold lower than that of the WKY and Wistar rats. The Na, K-ATPase and Ca-ATPase activities were by 25 and 15% lower in the erythrocyte ghosts of the SHR than in normotensive rats. Removal of protein of the membrane skeleton from the erythrocyte membranes abolished the difference in the enzyme activity of normo- and hypertensive rats. The lower Na, K-ATPase activity in the SHR kidney seems to be an etiological factor in development of primary hypertension.


The accuracy of CT staging of small bowel adenocarcinoma: CT/pathologic correlation.
Several studies have documented the use of CT in the evaluation of small bowel neoplasms, but few have addressed the CT staging of adenocarcinoma. We retrospectively correlated CT and pathologic staging to evaluate the accuracy of CT for staging small bowel adenocarcinoma using American Joint Committee on Cancer criteria. The preoperative CT scans of 15 patients with pathologically proven small bowel adenocarcinoma were analyzed. Two blinded readers separately interpreted extent of invasion, presence of lymphadenopathy, and distant metastases. Pathologic and CT staging were compared. The overall accuracy of CT staging was 47% (14/30). The sensitivity of detection of mesenteric infiltration was 88%. The sensitivity and specificity for detection of distant metastases were 58 and 63% and for lymphadenopathy 75 and 20%, respectively. Errors occurred in patients with Crohn disease, adenomas, Peutz-Jegher syndrome, small bowel obstruction, and perforation and on suboptimal studies. The accuracy of CT staging of small bowel adenocarcinoma is 47%. CT is highly sensitive but not specific for the detection of mesenteric infiltration and regional lymphadenopathy. Since spiral CT may offer improved detection of distant metastases and increased accuracy in the evaluation of patients with concomitant bowel disease, further research is needed to determine the maximal utility of CT in the staging of adenocarcinoma of the small bowel.


Using Magnetic Ions to Probe and Induce Magnetism of Pyrophosphates, Bacteria, and Mammalian Cells.
Magnetic isolation using magnetic nanoparticles (MNPs) as trapping probes have been widely used in sample pretreatment to shorten analysis time. Nevertheless, to generate MNPs is time-consuming. Furthermore, the generated MNPs have to be further functionalized to gain the capability of recognizing their target species. Thus, an alternative approach that can impose magnetism to nonmagnetic species by simply using magnetic ions as the probes is developed in this study. That is, we employ magnetic ions (Fe3+, Co2+, and Ni2+) that can interact with nonmagnetic species containing oxygen-containing functional groups as the probes. Pyrophosphate (PPi), bacteria, and mammalian cells were selected as the model samples. Our results show that the as-prepared magnetic ion-PPi conjugates gain sufficient magnetism and can be readily aggregated by applying an external magnetic field. Moreover, the magnetic trapping is reversible. The PPi-containing conjugates can lose their magnetic property simply using ethylenediaminetetraacetic acid or aluminum ions as competing agents to remove or to replace, respectively, the conjugated magnetic ions. In addition, bacteria and mammalian cells that possess abundant oxygen-containing functional groups on their cell surfaces can be selectively probed by magnetic ions and gain sufficient magnetism for magnetic isolation from complex serum samples.


Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting.
For decades, neuroscientists have used enriched preparations of synaptic particles called synaptosomes to study synapse function. However, the interpretation of corresponding data is problematic as synaptosome preparations contain multiple types of synapses and non-synaptic neuronal and glial contaminants. We established a novel Fluorescence Activated Synaptosome Sorting (FASS) method that substantially improves conventional synaptosome enrichment protocols and enables high-resolution biochemical analyses of specific synapse subpopulations. Employing knock-in mice with fluorescent glutamatergic synapses, we show that FASS isolates intact ultrapure synaptosomes composed of a resealed presynaptic terminal and a postsynaptic density as assessed by light and electron microscopy. FASS synaptosomes contain bona fide glutamatergic synapse proteins but are almost devoid of other synapse types and extrasynaptic or glial contaminants. We identified 163 enriched proteins in FASS samples, of which FXYD6 and Tpd52 were validated as new synaptic proteins. FASS purification thus enables high-resolution biochemical analyses of specific synapse subpopulations in health and disease.


1.6 angstroms structure of an NAD+-dependent quinate dehydrogenase from Corynebacterium glutamicum.
To date, three different functional classes of bacterial shikimate/quinate dehydrogenases have been identified and are referred to as AroE, SDH-L and YdiB. The enzyme AroE and the catalytically much slower SDH-L clearly prefer NADP+/NADPH as the cosubstrate and are specific for (dehydro-)shikimate, whereas in YdiB the differences in affinity for NADP+/NADPH versus NAD+/NADH as well as for (dehydro-)shikimate versus (dehydro-)quinate are marginal. These three subclasses have a similar three-dimensional fold and hence all belong to the same structural class of proteins. In this paper, the crystal structure of an enzyme from Corynebacterium glutamicum is presented that clearly prefers NAD+ as a cosubstrate and that demonstrates a higher catalytic efficiency for quinate rather than shikimate. While the kinetic constants for this enzyme clearly differ from those reported for AroE, SDH-L and YdiB, the three-dimensional structure of this protein is similar to members of these three subclasses. Thus, the enzyme described here belongs to a new functional class of the shikimate/quinate dehydrogenase family. The different substrate and cosubstrate specificities of this enzyme relative to all other known bacterial shikimate/quinate dehydrogenases are discussed by means of analyzing the crystal structure and derived models. It is proposed that in contrast to shikimate, quinate forms a hydrogen bond to the NAD+. In addition, it is suggested that the hydroxyl group of a conserved active-site threonine hydrogen bonds to quinate more effectively than to shikimate. Also, the hydroxyl group of a conserved tyrosine approaches the carboxylate group of quinate more closely than it does the carboxylate group of shikimate. Taken together, these factors most likely lead to a lower Michaelis constant and therefore to a higher catalytic efficiency for quinate. The active site of the dehydrogenase reported here is larger than those of other known shikimate/quinate dehydrogenases, which may explain why quinate is easily accommodated within the catalytic cleft.


Oridonin effectively reverses the drug resistance of cisplatin involving induction of cell apoptosis and inhibition of MMP expression in human acute myeloid leukemia cells.
Cisplatin is the first generation platinum-based chemotherapy agent. However, the extensive application of cisplatin inevitably causes drug resistance, which is a major obstacle to cancer chemotherapy. Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activity. The aim of our study is to investigate the role of oridonin to reverse the cisplatin-resistance in human acute myeloid leukemia (AML) cells. The effect of oridonin on human AML cell proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in cisplatin-resistant human AML cells. Furthermore, cell apoptosis was examined by flow cytometry. The inhibitive effect of oridonin in vivo was determined using xenografted nude mice. In addition, the expressions of MMP2 and MMP9 were detected by Western blot. There was a synergistic antitumor effect between cisplatin and oridonin on cisplatin-resistant human AML cells in vitro and in vivo. In addition, the combination of cisplatin and oridonin synergistically induced cell apoptosis. Furthermore, the combination treatment not only inhibited AML cell migration and invasion, but more significantly, decreased the expressions of MMP2 and MMP9 proteins. Our results suggest that the synergistic effect between both agents is likely to be driven by the inhibition of MMP expression and the resulting increased apoptosis.


Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma.
To monitor changes in itraconazole susceptibility of isolates from a patient undergoing treatment for pulmonary Aspergillus infection and relate these changes to genotypic/phenotypic alterations. Six Aspergillus fumigatus isolates were serially recovered from the patient. Itraconazole MICs were determined by Etest and NCCLS methodology. Growth characteristics and phenotype were monitored. Molecular analysis included random amplified polymorphic DNA (RAPD) assay and sequencing of the cyp51A gene. The MIC of itraconazole against the first isolate before treatment was 0.25 mg/L; the MIC against the second isolate, recovered after 6 months of itraconazole therapy, was >16 mg/L; and that against the third isolate, obtained 2 months after discontinuation of the therapy, was 0.5 mg/L. The MIC against the last three isolates, acquired after restoration of itraconazole therapy for 4-7 months, was >16 mg/L. The six isolates shared identical band patterns of RAPD assay using four primers and the same sequence in intertranscribed spacers (ITS). Therefore, the six isolates were likely to be the same strain of A. fumigatus, and mutations involving itraconazole resistance possibly occurred in these isolates after prolonged itraconazole therapy. Sequencing of the cyp51A gene in the coding region revealed a mutation of M220I in cytochrome P450 sterol 14-alpha-demethylase in the second resistant isolate and a mutation of G54R in the last three resistant isolates. Expression changes of some pump genes, such as MDR3, may also, in part, be related to the resistance to itraconazole. We conclude that resistance of A. fumigatus to itraconazole occurred in a patient treated with the drug, and the resistance may result from mutations in the cyp51A gene-the gene encoding the target enzyme for itraconazole.


Potential theory method for 3D crack and contact problems of multi-field coupled media: a survey.
This paper presents an overview of the recent progress of potential theory method in the analysis of mixed boundary value problems mainly stemming from three-dimensional crack or contact problems of multi-field coupled media. This method was used to derive a series of exact three dimensional solutions which should be of great theoretical significance because most of them usually cannot be derived by other methods such as the transform method and the trial-and-error method. Further, many solutions are obtained in terms of elementary functions that enable us to treat more complicated problems easily. It is pointed out here that the method is usually only applicable to media characterizing transverse isotropy, from which, however, the results for the isotropic case can be readily obtained.


[Adherence as a result of a "particular relationship". HIV-infected patients about their physician-patient relationship].
This qualitative study examines the relationship between doctors and HIV-infected patients with regard to problems of adherence. Objective hermeneutics was used to analyze the scene of a doctor-patient conversation produced through psychodrama. Specific traits shared by the patients in question were a confused regulation of closeness and distance as well as a non-maintenance of the traditional asymmetry within the doctor-patient relation. The patients faced the doctors on a level of diffuse social relations and showed the tendency to involve the doctor into their community. The conclusion for a model explaining patients' adherence may be: it exist an individual level of the need for being accepted by the doctor as somebody particular. If this level is reached, i. e. individual claims are met and personal desires are satisfied, the patient will follow the physician's advice. Authors discuss whether the model is compatible with the conflict of self-esteem.


[Immunization and preventive care for young people in Switzerland].
Children of foreign origin have better immunization coverage than children of swiss origin. This difference fades as children reach the teenage years and disappears in adulthood. On the other hand migrants have less access to preventive services. In teenagers, school immunization programs are the strongest determinant of good coverage. Immunization is only one aspect of adolescent preventive care but it provides the opportunity for a wider range of preventive activities. Multi-sectoral approaches including national and cantonal policies, school health services, primary care are needed to improve vaccine coverage and preventive opportunities at the same time. This article highlights the benefits of preventive services for young people whatever their origin and offers practical recommendations for immunization catch up in 11-25 year olds'.


Dielectric Relaxation, Local Structure and Lattice Dynamics in Mn-Doped Potassium Tantalate Ceramics.
Alkaline niobate and tantalate perovskites have attracted attention as polar dielectrics for electronics and telecommunications. Here, we studied the polar behaviour, lattice dynamics, and local structure in conventionally processed K0.985Mn0.015TaO3±δ ceramics using a combination of variable-temperature dielectric and Raman spectroscopies, and X-ray absorption fine structure (XAFS) measurements, respectively. Mn doping induces a low-frequency dielectric relaxation in KTaO3 (KT), which follows the Arrhenius law with an activation energy U ≈ 105 meV and the characteristic relaxation time τ0 ≈ 4.6 × 10-14 s. Our XAFS results support preferential Mn occupancy of the cuboctahedral sites as Mn2+, with these cations strongly off-centred in the oversized oxygen cages. Such disordered Mn displacements generate electric dipoles, which are proposed as the source of the observed dielectric relaxation. We show that in Mn-doped ceramics, the low-frequency polar TO1 mode softens on cooling and, at low temperatures, exhibits a higher frequency than in undoped KT. This mode displays no detectable splitting, which contrasts with Li-doped KT that also contains off-centred Li+ species on the cuboctahedral sites. Therefore, we conclude that the coupling between the Mn displacements and the lattice is weaker than in the Li case, and Mn-doped KT therefore exhibits a dielectric relaxation but no ferroelectric transition.


Seroprevalence of antibodies to Sarcocystis neurona in horses residing in Oregon.
To determine seroprevalence of antibodies to Sarcocystis neurona in neurologically normal horses residing in 4 regions of Oregon and to describe the effects of age, gender, breed, and housing on seroprevalence within each region. Prevalence survey. Serum samples from 334 horses systematically selected by practicing veterinarians. Antibodies to S neurona were measured in sera, using a western blot. Information including age, gender, breed, housing, geographic location, and duration of residence was obtained for each horse. Data were analyzed, using descriptive statistics. 45% (149/334) of horses evaluated were seropositive for antibodies to S neurona with significant differences in the percentage of seropositive horses from different regions of the state. Seroprevalances of antibodies to S neurona in horses in regions I and II, west of the Cascade Range, were 65 and 60%, respectively; whereas seroprevalances in central and eastern Oregon, regions III and IV, were 43 and 22%, respectively. Seroprevalence consistently increased with age of horse for each region. Gender, breed, and housing were not associated with significant differences in seroprevalence of antibodies to S neurona in the overall sample population, or in comparisons of samples obtained from horses within a particular region, or among samples obtained from horses residing in different regions. The high seroprevalence of antibodies to S neurona in neurologically normal horses indicates that analysis of serum alone would not be useful for definitive diagnosis of equine protozoal myeloencephalitis in horses in Oregon.


Thanatophoric dysplasia. A report of three cases.
Thanatophoric dysplasia is an osteochondrodysplasia always lethal already in the neonatal period. Three cases, showing the characteristic X-ray picture of the disease, are described. Histopathologically, an abnormality in the endochondral ossification process was observed. In sections from tubular bones the growth zone was found to be irregular with deficient chondrocyte maturation, absence of orderly chondrocyte columns, and the development of coarse bone trabeculae. Moreover, prominent subperiostal bone formation could be demonstrated. A constant finding was also a fibrous band, continuous with the periosteum/perichondrium, and extending into the growth zone. From this fibrous tissue membranous bone formation, directed towards the metaphysis and appearing to add to bone length, was observed. It seems as if direct bone formation predominates in thanatophoric dysplasia.


[Endocrine neoplasm of the stomach. Study of thirteen cases].
A Thirteen patients with primary endocrine neoplasm of the stomach were studied for 20 years. Six patients were male and 7 female with an age range of 33 to 77, mean age 57 years. Nine cases corresponded to well differentiated carcinoids and four to neuroendocrine carcinomas. Of the former, three were sporadic and six were associated with atrophic gastritis. These two forms of neoplasm showed important differences: those associated with atrophic gastritis had hypergastrinemia, all of the multiple small tumors confined to the corpus and fundus were well differentiated carcinoids associated with intestinal metaplasia and G cell hyperplasia in antrum and ECL cell hyperplasia in corpus and fundus. Tumors were clinically benign, with an excellent prognosis. All patients are currently alive with no evidence of neoplasm. In only one of these cases, antiparietal cell antibodies were documented; in three of them, extensive intestinal metaplasia probably due to Helicobacter pylori infection was found. In contrast, sporadic carcinoids were large isolated tumors originating in the antrum or corpus. Two patients died as a consequence of the neoplasm; all of them were moderately differentiated and in none of the cases we found evidence of endocrine hyperplasia. All were positive for generic endocrine markers and were focally positive to some of the specific hormone markers. Al four neuroendocrine carcinomas had a clinical course similar to that of gastric adenocarcinomas and were poorly differentiated large tumors. We conclude that gastric carcinoids associated with atrophic gastritis have an excellent prognosis. On the other hand, neuroendocrine carcinomas have a very poor prognosis with fatal outcome of patients. Sporadic carcinoids have an intermediate prognosis.


[Adjuvant methadone or fentanyl in spinal anesthesia with bupivacaine: a randomized, double-blind, placebo-controlled trial].
To compare the effect of combining spinal bupivacaine with either of 2 lipophilic opioids (fentanyl or methadone), testing the hypothesis that methadone would give longer-lasting analgesia. Randomized, double-blind, placebo-controlled trial enrolling 69 women undergoing vaginal hysterectomy under spinal anesthesia (13 mg of 0.5% bupivacaine). The patients were randomized to 3 groups for use of different adjuvants: normal saline (placebo), 15 μg [DOSAGE ERROR CORRECTED] of fentanyl, or 3 mg of methadone. The main outcome was duration of analgesic effect measured as time elapsing until need for the first analgesic dose. The characteristics of the spinal blocks and adverse events were secondary outcome variables. Methadone significantly prolonged the duration of analgesia in comparison with the other adjuvants; with methadone, the effect was 1.9 times longer than in the placebo group and 1.5 times longer than in the fentanyl group. Duration of the sensory-motor block was significantly shorter in the methadone group (mean difference, 30 minutes). No differences in the incidences of adverse events were observed between the 2 opioid groups. No signs or symptoms suggestive of direct neurologic toxic effects were observed. The addition of methadone to bupivacaine significantly prolonged the postoperative analgesic effect of spinal anesthesia and shortened sensory-motor block duration, enhancing patient comfort after surgery.


Protein methylation as a marker of aspartate damage in glucose-6-phosphate dehydrogenase-deficient erythrocytes: role of oxidative stress.
The 'Mediterranean' variant of glucose-6-phosphate dehydrogenase (G6PD) deficiency is due to the C563CT point mutation, leading to replacement of Ser with Phe at position 188, resulting in acute haemolysis triggered by oxidants. Previous work has shown increased formation of altered aspartate residues in membrane proteins during cell ageing and in response to oxidative stress in normal erythrocytes. These abnormal residues are specifically recognized by the repair enzyme L-isoaspartate (d-aspartate) protein O-methyltransferase (PCMT; EC 126.96.36.199). The aim of this work was to study the possible involvement of protein aspartate damage in the mechanism linking the G6PD defect and erythrocyte injury, through oxidative stress. Patients affected by G6PD deficiency (Mediterranean variant) were selected. In situ methylation assays were performed by incubating intact erythrocytes in the presence of methyl-labelled methionine. Altered aspartate residues were detected in membrane proteins by methyl ester quantification. We present here evidence that, in G6PD-deficient erythrocytes, damaged residues are significantly increased in membrane proteins, in parallel with the decay of pyruvate kinase activity, used as a cell age marker. Erythrocytes from patients were subjected to oxidative stress in vitro, by treatment with t-butylhydroperoxide, monitored by a rise in concentration of both methaemoglobin and thiobarbituric acid-reactive substances. L-Isoaspartate residues increased dramatically in G6PD-deficient erythrocytes in response to such treatment, compared with baseline conditions. The increased susceptibility of G6PD-deficient erythrocytes to membrane protein aspartate damage in response to oxidative stress suggests the involvement of protein deamidation/isomerization in the mechanisms of cell injury and haemolysis.


Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract.
The majority of new HIV infections occur in women as a result of heterosexual intercourse, overcoming multiple innate barriers to infection within the mucosa. However, the avenues through which infection is established, and the nature of bottlenecks to transmission, have been the source of considerable investigation and contention. Using a high dose of a single round non-replicating SIV-based vector containing a novel dual reporter system, we determined the sites of infection by the inoculum using the rhesus macaque vaginal transmission model. Here we show that the entire female reproductive tract (FRT), including the vagina, ecto- and endocervix, along with ovaries and local draining lymph nodes can contain transduced cells only 48 hours after inoculation. The distribution of infection shows that virions quickly disseminate after exposure and can access target cells throughout the FRT, with an apparent preference for infection in squamous vaginal and ectocervical mucosa. JRFL enveloped virions infect diverse CD4 expressing cell types, with T cells resident throughout the FRT representing the primary target. These findings establish a new perspective that the entire FRT is susceptible and virus can reach as far as the ovary and local draining lymph nodes. Based on these findings, it is essential that protective mechanisms for prevention of HIV acquisition must be present at protective levels throughout the entire FRT to provide complete protection.


Insecticide resistance: challenge to pest management and basic research.
The agricultural use of synthetic insecticides usually protects crops but imposes strong selection pressures that can result in the development of resistance. The most important resistance mechanisms are enhancement of the capacity to metabolically detoxify insecticides and alterations in target sites that prevent insecticides from binding to them. Insect control methods must incorporate strategies to minimize resistance development and preserve the utility of the insecticides. The most promising approach, integrated pest management, includes the use of chemical insecticides in combination with improved cultural and biologically based techniques.


Therapeutic apheresis rescue mission: recurrent focal segmental glomerulosclerosis in renal allografts.
Recurrent idiopathic focal segmental glomerulosclerosis (FSGS) after renal transplantation can lead to a rapid failure of the allograft. A circulating, nonimmunoglobulin factor appears to be important in the pathogenesis of this complication in many cases. Between 30% and 50% of transplant recipients with FSGS develop recurrent disease. Three major risk factors for recurrence have been identified: short duration of native kidney disease, history of recurrence with previous kidney transplant, and pediatric aged recipients. Although no properly controlled trials have been conducted, plasmapheresis has emerged as one of the important treatment modalities for this entity. Retrospective studies prior to the routine use of plasmapheresis showed graft loss rates as high as 80%, a rate much higher than that seen in more recent series managed with plasmapheresis. Duration and intensity of treatment of plasmaphersis have not been studied rigorously, but in most case series, plasmapheresis was continued until a clear diminution of proteinuria was seen. The benefit of other adjuvant therapies for this condition remains unclear, but also may play a role in the treatment of this entity.


[Toxicological and hygienic studies of a new polymer glue to be used in shoe-making industry].
Toxico-hygienic studies have been carried out of a new polymeric glue to be used in the shoe-making industry. As a result of studies the use of the glue is recommended in the shoe-making industry, conditions of its safe use and the way to maintain current sanitary supervision have been suggested.


BEMER Therapy Combined with Physiotherapy in Patients with Musculoskeletal Diseases: A Randomised, Controlled Double Blind Follow-Up Pilot Study.
Background. This study evaluates the effect of adjuvant BEMER therapy in patients with knee arthrosis and chronic low back pain in a randomized double blind design. Methods. A total of 50 patients with chronic low back pain and 50 patients with osteoarthritis of knee took part in this study and were randomized into 4 groups. Hospitalized patients received a standardized physiotherapy package for 3 weeks followed by BEMER therapy or placebo. Results. In patients with low back pain, the comparison of the results obtained at the first and second visit showed a significant improvement in resting VAS scores and Fatigue Scale scores. The Oswestry scores and Quality of Life Scale scores showed no change. In patients with knee arthrosis, the comparison of the first and second measurements showed no significant improvement in the abovementioned parameters, while the comparison of the first and third scores revealed a significant improvement in the Fatigue Scale scores and in the vitality test on the Quality of Life Scale. Conclusions. Our study showed that BEMER physical vascular therapy reduced pain and fatigue in the short term in patients with chronic low back pain, while long-term therapy appears to be beneficial in patients with osteoarthritis of knee.


Evaluation of protein kinase CK2 as a therapeutic target for squamous cell carcinoma of cats.
OBJECTIVE To investigate protein kinase CK2 (CK2) expression in squamous cell carcinoma (SCC) of cats and to examine effects of CK2 downregulation on in vitro apoptosis and viability in SCC. SAMPLE Biopsy specimens of oral mucosa and testis and blood samples from clinically normal cats, biopsy specimens of oral SCC from cats, and feline SCC (SCCF1) and mammary gland carcinoma (K12) cell lines. PROCEDURES Immunohistochemical labeling for CK2α was performed on biopsy specimens. Sequences of the CK2α subunit gene and CK2α' subunit gene in feline blood and feline cancer cell lines were determined by use of PCR and reverse-transcription PCR assays followed by direct Sanger sequencing. Specific small interfering RNAs (siRNAs) were developed for feline CK2α and CK2α'. The SCCF1 cells were treated with siRNA and assessed 72 hours later for CK2α and CK2α' expression and markers of apoptosis (via western blot analysis) and for viability (via 3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium assays). RESULTS CK2α was expressed in all feline oral mucosa samples and 7 of 8 oral SCC samples. Expression of CK2α and CK2α' was successfully downregulated in SCCF1 cells by use of siRNAs, which resulted in decreased viability and induction of apoptosis. CONCLUSIONS AND CLINICAL RELEVANCE In this study, CK2 appeared to be a promising therapeutic target for SCCs of cats. A possible treatment strategy for SCCs of cats would be RNA interference that targets CK2.


Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone.
Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associated with bone metastases in prostate and breast cancer patients, and is known to occur in ES. Here we investigated the effects of Cad-11 on bone metastases of ES. Human ES cell lines RD-ES, SK-ES-1, SK-N-MC, and TC-71 cells were transduced with lentivirus containing Cad-11 shRNA or control shRNA (ES/Cad-11 and ES/Ctr). RD-ES and TC-71 were infected with a lentivirus luciferase vector. Adhesion assays were performed using these cells and recombinant Cad-11-Fc chimera or mouse osteoblast cell line MC3T3-E1. Cell motility was investigated via wound-healing assay. Intracardiac injection of RD-ES/Cad-11 and RD-ES/Ctr was used to create a mouse model of experimental bone metastasis. The association between Cad-11 expression and bone metastases and clinical prognosis in ES patients was analyzed by immunohistochemistry. We found knockdown of Cad-11 in ES cells resulted in reduced attachment ability and cell motility. In a mouse model of metastasis, RD-ES/Cad-11 cells caused fewer metastases than RD-ES/Ctr cells. The expression of Cad-11 in ES patients was significantly related to bone metastases (P < 0.05, logistic regression) and poorer overall survival (P < 0.05, log-rank test). These findings may explain that Cad-11 in ES cells may be essential for cell adhesion and motility, and is a promising molecular target for patients with ES.