Geographic information analysis and web-based geoportals to explore malnutrition in Sub-Saharan Africa: a systematic review of approaches.
Childhood malnutrition is a serious challenge in Sub-Saharan Africa (SSA) and a major underlying cause of death. It is the result of a dynamic and complex interaction between political, social, economic, environmental and other factors. As spatially oriented research has been established in health sciences in recent years, developments in Geographic Information Science (GIScience) provide beneficial tools to get an improved understanding of malnutrition. In order to assess the current state of knowledge regarding the use of geoinformation analyses for exploring malnutrition in SSA, a systematic literature review of peer-reviewed literature is conducted using Scopus, ISI Web of Science and PubMed. As a supplement to the review, we carry on to investigate the establishment of web-based geoportals for providing freely accessible malnutrition geodata to a broad community. Based on these findings, we identify current limitations and discuss how new developments in GIScience might help to overcome impending barriers. 563 articles are identified from the searches, from which a total of nine articles and eight geoportals meet inclusion criteria. The review suggests that the spatial dimension of malnutrition is analyzed most often at the regional and national level using geostatistical analysis methods. Therefore, heterogeneous geographic information at different spatial scales and from multiple sources is combined by applying geoinformation analysis methods such as spatial interpolation, aggregation and downscaling techniques. Geocoded malnutrition data from the Demographic and Health Survey Program are the most common information source to quantify the prevalence of malnutrition on a local scale and are frequently combined with regional data on climate, population, agriculture and/or infrastructure. Only aggregated geoinformation about malnutrition prevalence is freely accessible, mostly displayed via web map visualizations or downloadable map images. The lack of detailed geographic data at household and local level is a major limitation for an in-depth assessment of malnutrition and links to potential impact factors. We propose that the combination of malnutrition-related studies with most recent GIScience developments such as crowd-sourced geodata collection, (web-based) interoperable spatial health data infrastructures as well as (dynamic) information fusion approaches are beneficial to deepen the understanding of this complex phenomenon.


Insurance coverage mandates: Impact of physician utilization in moderating colorectal cancer screening rates.
Precision public health requires research that supports innovative systems and health delivery approaches, programs, and policies that are part of this vision. This study estimated the effects of health insurance mandate (HiM) variations and the effects of physician utilization on moderating colorectal cancer (CRC) screening rates. A time-series analysis using a difference-in-difference-in-differences (DDD) approach was conducted on CRC screenings (1997-2014) using a multivariate logistic framework. Key variables of interest were HiM, CRC screening status, and physician utilization. The adjusted average marginal effects from the DDD model indicate that physician utilization increased the probability of being "up-to-date" vs. non-compliance by 9.9% points (p = 0.007), suggesting that an estimated 8.85 million additional age-eligible persons would receive a CRC screening with HiM and routine physician visits. Routine physician visits and mandates that lower out-of-pocket expenses constitute an effective approach to increasing CRC screenings for persons ready to take advantage of such policies.


Evolutionarily conserved BIL4 suppresses the degradation of brassinosteroid receptor BRI1 and regulates cell elongation.
Brassinosteroids (BRs), plant steroid hormones, play important roles in plant cell elongation and differentiation. To investigate the mechanisms of BR signaling, we previously used the BR biosynthesis inhibitor Brz as a chemical biology tool and identified the Brz-insensitive-long hypocotyl4 mutant (bil4). Although the BIL4 gene encodes a seven-transmembrane-domain protein that is evolutionarily conserved in plants and animals, the molecular function of BIL4 in BR signaling has not been elucidated. Here, we demonstrate that BIL4 is expressed in early elongating cells and regulates cell elongation in Arabidopsis. BIL4 also activates BR signaling and interacts with the BR receptor brassinosteroid insensitive 1 (BRI1) in endosomes. BIL4 deficiency increases the localization of BRI1 in the vacuoles. Our results demonstrate that BIL4 regulates cell elongation and BR signaling via the regulation of BRI1 localization.


Gold Nanorod Enhanced Photoacoustic Microscopy and Optical Coherence Tomography of Choroidal Neovascularization.
Visualization and evaluation of choroidal neovascularization (CNV) are major challenges to improve treatment outcomes for patients with age-related macular degeneration (AMD). Limitations of current imaging techniques include the limited penetration depth, spatial resolution, and sensitivity and difficulty visualizing CNV from the healthy microvasculature. In this study, a custom-built multimodal photoacoustic microscopy (PAM) and optical coherence tomography (OCT) system was developed to distinguish the margin of CNV in living rabbits with the assistance of functionalized gold nanorods conjugating with RGD ligands (GNR-RGD). Intravenous administration of GNR-RGD into rabbits in a CNV model resulted in signal enhancements of 27.2-fold in PAM and 171.4% in OCT. This molecular imaging technique of contrast-enhanced PAM and OCT is a promising tool for the precise imaging of CNV as well as the evaluation of the pathophysiology in vivo without destruction of tissue.


Flunarizine (Sibelium) in the prophylaxis of migraine. An open, long-term, multicenter trial.
Sixty-four Spanish neurological centers participated in a study designed to evaluate the efficacy and safety of flunarizine in migraine. One thousand four hundred and thirty-five outpatients (367 [25.6%] males and 1,068 [74.4%] females) fulfilling the criteria proposed by the International Headache Society for the diagnosis of migraine entered the study. Patients were treated with 10 mg of single-dose flunarizine (Sibelium) alone at bedtime in open fashion for 6 months. At the end of this treatment period, flunarizine was withdrawn, but the follow-up of the patients continued for another 6 months. The evaluation criteria used were a rating scale (the GES) based on frequency, duration, intensity, and characteristics of the attacks as well as a checklist of possible side-effects. This clinical assessment was recorded in detail in the patients' rating notebooks at the start and at the end of the third, sixth, ninth, and twelfth month of the study. A mean decrease of 66.9% in the GES was obtained at the end of the treatment period, which implies a good or excellent result in the prophylaxis of migraine attacks in 69.5% of the patients. This improvement was practically unchanged at the end of the follow-up period. Side-effects were moderate, the most frequent ones being drowsiness and weight gain. Their incidence decreased after the first months of treatment.


Mitochondrial oxidative stress and CD95 ligand: a dual mechanism for hepatocyte apoptosis in chronic alcoholism.
Apoptosis plays an important role in the progression of alcohol-induced liver disease to cirrhosis. Oxidative stress is an early event in the development of apoptosis. The major aim of this study was to study the conditions in which oxidative stress occurs in chronic alcoholism and its relationship with apoptosis of hepatocytes. We have found that oxidative stress is associated with chronic ethanol consumption in humans and in rats, in the former independently of the existence of alcohol-induced liver disease. Ethanol or acetaldehyde induces apoptosis in hepatocytes isolated from alcoholic rats, but not in those from control rats. Inhibition of aldehyde dehydrogenase, but not of cytochrome P450 2E1, prevents ethanol-induced cell death. Ethanol-induced apoptosis is caused by increased reactive oxygen species (ROS) driven by increased availability of the reduced form of nicotinamide-adenine dinucleotide (NADH) owing to mitochondrial acetaldehyde metabolism and it is prevented by blocking the opening of mitochondrial permeability transition (MPT) pores with cyclosporine A. Inhibition of nitric oxide (NO) synthase or addition of antioxidant vitamins C and E completely prevented ethanol-induced apoptosis. Mitochondrial oxidative stress, which occurs during chronic alcoholism, renders hepatocytes susceptible to apoptosis. On the other hand, the CD95 ligand expression was up-regulated by acetaldehyde. In conclusion, ethanol induces apoptosis via 2 different pathways: MPT and up-regulation of the expression of CD95-Fas ligand. The overproduction of ROS by mitochondria, driven by acetaldehyde metabolism, is a common trigger of both mechanisms.


Tea consumption and mortality after acute myocardial infarction.
Some studies have suggested that tea consumption may be associated with lower mortality among individuals with cardiovascular disease, but the effects of tea consumption on mortality after acute myocardial infarction are unknown. As part of the Determinants of Myocardial Infarction Onset Study, we performed a prospective cohort study of 1900 patients hospitalized with a confirmed acute myocardial infarction between 1989 and 1994, with a median follow-up of 3.8 years. Trained interviewers assessed self-reported usual weekly caffeinated tea consumption during the year before infarction with a standardized questionnaire. We compared long-term mortality according to tea consumption using Cox proportional hazards regression. Of the 1900 patients, 1019 consumed no tea (nondrinkers), 615 consumed <14 cups per week (moderate tea drinkers), and 266 consumed 14 or more cups per week (heavy tea drinkers). Compared with nondrinkers, age- and sex-adjusted mortality was lower among moderate tea drinkers (hazard ratio, 0.69; 95% CI, 0.53 to 0.89) and heavy tea drinkers (hazard ratio, 0.61; 95% CI, 0.42 to 0.86). Additional adjustment for clinical and sociodemographic characteristics did not appreciably alter this association (hazard ratio, 0.72; 95% CI, 0.55 to 0.94 for moderate tea drinkers; hazard ratio, 0.56; 95% CI, 0.37 to 0.84 for heavy tea drinkers). The association of tea and mortality was similar for total and cardiovascular mortality. Self-reported tea consumption in the year before acute myocardial infarction is associated with lower mortality after infarction.


Transforming growth factor beta 1 and renal injury following subtotal nephrectomy in the rat: role of the renin-angiotensin system.
Transforming growth factor-beta (TGF-beta) and the renin-angiotensin system (RAS) have both been implicated in the pathogenesis of chronic renal disease. The present experiment investigated the chronology of TGF-beta 1 gene expression following subtotal nephrectomy (STNx) in the rat and the effect of blocking the RAS by angiotensin converting enzyme (ACE) inhibition or by angiotensin II receptor (AT1) antagonism. Rats that had undergone subtotal nephrectomy developed hypertension, proteinuria, renal impairement, glomerulosclerosis, tubulointerstitial fibrosis and mononuclear cell infiltration. These changes were associated with a 2.5-fold increase in TGF-beta 1 gene expression during a 16-week time course. In situ hybridization localized TGF-beta 1 mRNA to sclerotic glomeruli, areas of tubuloin-terstitial injury and sites of mononuclear cell infiltration. Administration of the ACE inhibitor ramipril and the AT1 receptor blocker valsartan blunted the increase in TGF-beta 1 mRNA, and attenuated the structural and functional manifestations of injury. These data suggest an interaction between the intrarenal RAS and TGF-beta in the pathogenesis of the glomerular and tubulointerstitial fibrosis that follow a major reduction in renal mass.


Enhancing an enterprise data warehouse for research with data extracted using natural language processing.
This study aims to develop a generalizable architecture for enhancing an enterprise data warehouse for research (EDW4R) with results from a natural language processing (NLP) model, which allows discrete data derived from clinical notes to be made broadly available for research use without need for NLP expertise. The study also quantifies the additional value that information extracted from clinical narratives brings to EDW4R. Clinical notes written during one month at an academic health center were used to evaluate the performance of an existing NLP model and to quantify its value added to the structured data. Manual review was utilized for performance analysis. The architecture for enhancing the EDW4R is described in detail to enable reproducibility. Two weeks were needed to enhance EDW4R with data from 250 million clinical notes. NLP generated 16 and 39% increase in data availability for two variables. Our architecture is highly generalizable to a new NLP model. The positive predictive value obtained by an independent team showed only slightly lower NLP performance than the values reported by the NLP developers. The NLP showed significant value added to data already available in structured format. Given the value added by data extracted using NLP, it is important to enhance EDW4R with these data to enable research teams without NLP expertise to benefit from value added by NLP models.


[Diagnostic value of middle ear resonant frequency in hydrotympanum].
To investigate the diagnostic value of 226 Hz tympanometry and middle ear resonant frequency (RF) in adults with hydrotympanum. Discuss whether the resonant frequency combined with conventional 226 Hz tympanometry could increase the effectiveness for diagnosis of hydrotympanum. Prospective study was applied to compare the normal hearing group and the test group. The otoscopic findings, pure tone audiometry and GSI-33 middle ear analyzer were considered standard. A 90% range of RF values from normal hearing group was considered standard to distinguish normal from abnormal RF values in test group. The subjects who had type B, C or abnormal tympanograms were performed with tympanocentesis. Hydrotympanum were confirmed when the results were positive. The middle ear resonant frequency in adults range from 900 Hz to 1100 Hz was considered normal. There was found to be a statistically significant decrease in RF values in ears with OME compared to normative data (P<0.01). The positive percentage of tympanocentesis on type "B" tympanograms were 83%, which was significantly higher than that of tympanocentesis on type "C" or abnormal tympanograms (P<0.05). The positive percentage of tympanocentesis was 0 when the resonant frequency was normal. The positive percentage of tympanocentesis which the resonant frequency were less than 500 Hz were significantly higher than the subjects whose resonant frequency were more than 500 Hz. Middle ear resonant frequency testing has very important clinic value for diagnosis of hydrotympanum, especially for those patients with type C or abnormal tympanograms.


Anomalous low temperature ambipolar diffusion and Einstein relation.
The regular Einstein relation, connecting the coefficient of ambipolar diffusion and the Dember field with mobilities, is generalized for the case of an interacting electron-hole plasma. The calculations are presented for a nondegenerate plasma injected by light into semiconductors of silicon and germanium type. The Debye-Huckel correlation and the Wigner-Seitz exchange terms are considered. Corrections to the mobilities of carriers due to the difference between average and acting electric fields within the electron-hole plasma are taken into account. The deviation of the generalized relation from the regular Einstein relation is pronounced at low temperatures and can explain the anomaly of the coefficient of ambipolar diffusion, recently discovered experimentally.


Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors.
The aim of the study was to identify genes that confer susceptibility to coronary artery disease (CAD) in low- or high-risk men or women separately and thereby to assess the genetic risk of CAD in such individuals. The prevention of CAD would be facilitated by the identification of genes that confer susceptibility to this condition independently in low- or high-risk individuals, as defined by conventional risk factors. The study population comprised 1661 unrelated Japanese individuals, including 1011 patients with CAD and 650 control subjects. Among all study subjects, 601 individuals (high-risk subjects) had hypertension, diabetes mellitus, and hypercholesterolemia, and 1060 individuals (low-risk subjects) had none of these risk factors for CAD. The genotypes for 37 polymorphisms of 31 candidate genes were determined by a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis, with adjustment for age, body mass index, and the prevalence of smoking and hyperuricemia, revealed that the -219G-->T polymorphism of the apolipoprotein E gene in low-risk men, the -1171/5A-->6A polymorphism of the stromelysin-1 gene in low-risk women, the 1019C-->T polymorphism of the connexin 37 gene in high-risk men, and the 3932T-->C polymorphism of the apolipoprotein E gene in high-risk women were significantly associated with CAD. A stepwise forward selection procedure revealed that the effects of these polymorphisms on CAD were statistically independent of age or conventional risk factors. Genotyping of these polymorphisms may prove informative for assessment of the genetic risk of CAD in low- or high-risk men or women.


Antipsychotic Polypharmacy Among Patients With Schizophrenia in Africa: A Systematic Review and Meta-Analysis.
In Africa, antipsychotic polypharmacy (APP) is increasing due to a high antipsychotic dose prescribing, repeated psychiatric hospitalization, uncontrolled psychotic symptoms, and greater side effect burden. Therefore, the aim of this review and meta-analysis is to assess the prevalence and correlates of APP among patients with schizophrenia in Africa. A systematic search was performed from August 1 to 31, 2020, on PubMed, MEDLINE, Google Scholar, and Science Direct databases to select articles based on the inclusion criteria. Meta-Analysis of Observational studies in Epidemiology guidelines were employed. Cross-sectional observational studies that reported APP and/or its correlates in schizophrenia patients in English language published in peer-reviewed journals without time limits were included in the review. The quality of included articles was assessed using Newcastle-Ottawa quality assessment tool. Prevalence and correlates of APP were the outcome measures of this review and meta-analysis. Open Meta Analyst and RevMan version 5.3 software were used for meta-analysis. A random effect model was used to synthesize data based on the heterogeneity test. Six studies that involved 2154 schizophrenia patients met the inclusion criteria in this review and meta-analysis. The quality of included studies ranges from 6.5 to 10 based on the Newcastle-Ottawa quality assessment tool. The pooled prevalence of APP among patients with schizophrenia was 40.6% with 95% confidence interval: 27.6% to 53.7%. Depot first-generation antipsychotics and oral first-generation antipsychotics were the most commonly prescribed APP combinations. Socio-demographic, clinical, and antipsychotic treatment characteristics were significantly associated with APP. There was a wide variation in the correlates of APP assessed by studies and the way that association/correlations was determined and reported. APP is common and highly prevalent. Advanced age, male gender, longer duration of schizophrenia, hospital admission, and longer antipsychotic treatment were correlates of APP in Africa.


A refined surgical treatment modality for bromhidrosis: Subcutaneous scissor with micropore.
Axillary bromhidrosis has a strong negative effect on one's social life. A high success rate and few complications are criteria for a surgical treatment. The objective of this study was to evaluate a new surgical treatment modality for bromhidrosis: subcutaneous scissor with micropore. Twenty patients with bromhidrosis were treated. Patients were placed in a supine position with their treated arms abducted to 110°. After injection of 60 mL of tumescent solution into each axilla, one small incision was made at the middle axillary of the hair-bearing area. The whole hair-bearing skin was undermined at the level of the superficial fat to obtain adequate skin eversion. The flaps were everted to offer full exposure of the apocrine glands, and meticulous excision of each gland was performed. Both sides were punctured with scalpel. The micropore was used for drainage, and whose width was just 3 mm. Finally, the incisions were re-approximated, and bulky compressive dressings were applied to the area for 72 hours. Of the 40 axillae (20 patients), 34 (85.0%) showed excellent results, and six (15.0%) had good results. Malodor was significantly decreased. There were no serious complications. This technique can produce excellent results with a lower complication rate than most other surgical modalities and can be performed without costly equipment.


Adiponectin-Secretion-Promoting Phenylethylchromones from the Agarwood of Aquilaria malaccensis.
The therapeutic potential of adiponectin regulation has received interest because of its association with diverse human disease conditions, such as diabetes, obesity, atherosclerosis, and cancer. Phenylethylchromone derivatives from Aquilaria malaccensis-derived agarwood promoted adiponectin secretion during adipogenesis in human bone marrow mesenchymal stem cells, and 5,6-dihydroxy-2-(2-phenylethyl)chromone (1) was identified as a new chromone derivative. A target identification study with the most potent adiponectin-secretion-promoting phenylethylchromones, 6-methoxy-2-(2-phenylethyl)chromone (3) and 7-methoxy-2-(2-phenylethyl)chromone (4), showed that they are PPARγ partial agonists. Therefore, the diverse therapeutic effects of agarwood are associated with a PPARγ-mediated adiponectin-secretion-promoting mechanism.


The insulin secretion of a minced neonatal rat pancreas cultured in a pancreatic chamber, in response to various insulin secretagogues.
The minced pancreas of the neonatal rat was cultured for 35 days in a pancreatic chamber which was constructed of a plastic tube and an ultrafiltration membrane. Insulin and amylase secreted from this pancreatic chamber into the culture medium were measured. During the experiment, the concentration of glucose in the culture medium was changed between 5.5 and 16.5 mM at 2-3 day intervals in order to determine the insulin secretory response of the pancreatic tissue. Insulin secretion was markedly increased in response to 16.5 mM glucose. The ratio of insulin secretion to amylase secretion in the culture medium increased with the advance of culture days although secretions of both insulin and amylase decreased individually. On the 7th culture day, short term incubations were performed to test with various insulin secretagogues; obvious insulin release into the incubation medium was observed. These results show that the pancreatic chamber also in vitro secretes insulin rapidly and significantly in response to various stimuli; that by longer culture of a neonatal rat pancreas in this device, insulin secretory cells without exocrine tissue would be obtained without using digestive enzymes; that application of a pancreatic chamber for a pancreatic transplantation may be feasible.


In vivo manipulation of fluorescently labeled organelles in living cells by multiphoton excitation.
Femtosecond laser pulses in the near-infrared region have potential applications in the imaging and manipulation of intracellular organelles. We report on the manipulation of intracellular organelles by two-photon excitation. The dynamics of green fluorescent protein (GFP)-histone are investigated by two-photon fluorescence recovery after photobleaching (FRAP). Intracellular ablation of fluorescently labeled organelles in living cells is performed by focusing femtosecond laser pulses. We report on the selective marking of individual organelles by using two-photon conversion of a photoconvertible fluorescent protein.


Gap junction-mediated communication in the developing and adult cerebral cortex.
Recent cell biological and electrophysiological studies have shown that gap junctional coupling and the proteins that mediate this form of communication are present in the developing cerebral cortex from early in corticogenesis to the later stage of neuronal circuit formation. We have used electron microscopy to visualize gap junctions in the developing rat cerebral cortex, and studied the expression patterns and cellular localizations of connexin26 (Cx26; beta 2), Cx32 (beta 1) and Cx43 (alpha 1), which take part in their formation. We found that these connexins are expressed differentially during development, and their patterns of expression are correlated with important developmental events such as cell proliferation, migration and formation of cortical neuronal circuits. We also observed that gap junctions and their constituent connexins were abundant in the adult cerebral cortex. Junctions were predominantly between glial cells or between neurons and glia. The frequency and distribution of gap junctions varied in different regions of the adult cortex, possibly reflecting differences in the cellular and functional organization of these cortical areas.


The relationship between insulin resistance and dyslipidaemia in cigarette smokers.
Considerable evidence shows that cigarette smokers tend to have the dyslipidemic pattern of high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations, a highly atherogenic lipoprotein profile also typical of the insulin-resistant state even in the absence of cigarette smoking. However, because cigarette smokers are frequently insulin resistant, it is unclear if this dyslipidaemia is secondary to smoking, per se, or simply to the fact that smokers tend to be insulin resistant. The present study was initiated to determine whether this dyslipidaemia prevalent in cigarette smokers and characteristic of insulin-resistant individuals is a function of cigarette smoking or of insulin resistance. As measured using vertical auto profile-II methodology, the lipid and lipoprotein concentrations were compared in 34 cigarette smokers divided into insulin-sensitive and insulin-resistant subgroups. The two groups were similar in age and body mass index, differing only in their insulin-mediated glucose uptake as quantified by the steady-state plasma glucose concentration determined during the insulin suppression test. While levels of TG and very low-density lipoprotein cholesterol (VLDL-C) were significantly elevated in insulin-resistant cigarette smokers, total cholesterol (C), low-density lipoprotein cholesterol (LDL-C), narrow-density (ND) LDL-C, intermediate-density lipoprotein-C (IDL-C), HDL-C and non-HDL-C were not different in the two groups. The insulin-resistant smokers also had a preponderance of small, dense LDL particles, while the reverse was true of the insulin-sensitive cigarette smokers. These data suggest that the dyslipidaemia previously attributed to smoking occurs primarily in those smokers who are also insulin resistant.


Quantitative genetic variation in an island population of the speckled wood butterfly (Pararge aegeria).
Evidence of changes in levels of genetic variation in the field is scarce. Theoretically, selection and a bottleneck may lead to the depletion of additive genetic variance (V(A)) but not of nonadditive, dominance variance (V(D)), although a bottleneck may converse V(D) to V(A). Here we analyse quantitative genetic variation for the Speckled Wood butterfly Pararge aegeria on the island of Madeira about 120 generations after first colonisation. Colonisation of the island involved both a bottleneck and strong natural selection, changing the average value of traits. Several life history and morphological traits with varying levels of change since colonisation were analysed. In accordance with expectations, all traits except one showed relatively low levels of V(A), with an average heritability (h(2)) of 0.078. Levels of V(D) for these traits were relatively high, 20-94% of total variance and on average 80% of V(G). The exception was a morphological trait that probably had not experienced strong natural selection after colonisation, for which a h(2) of 0.27 was found. Another interesting observation is that the population seems resistant to inbreeding effects, which may be the result of purging of deleterious alleles.


Minimally invasive screw plates for surgery of unstable intertrochanteric femoral fractures: a biomechanical comparative study.
This study presents the first biomechanical comparison of two minimal invasive screw plates used in the treatment of intertrochanteric fractures of the femur. Six fresh cadaveric pairs of human femur were included, following dual energy X-ray absorbsiometry analysis to obtain two cohorts of homogenous femurs. In each pair, unstable four-part trochanteric fractures were created and reduced. In each cohort, one femur was randomly selected to undergo instrumentation using one of the two minimal invasive devices, and the other femur was instrumented using the other device (minimally invasive screw system (MISS) or per cutaneous compression plate (PCCP)). Femurs were positioned at 25 degrees of adduction in order to simulate the anatomical loading during one-legged stance. Biomechanical tests were performed using a single vertical compressive load applied on the femoral head. Cycling loading was applied with three-dimensional fracture motions with stereophotogrammetric analysis and global displacement analysis throughout the cyclic test. Intact femurs after cyclic loading were tested to failure. Failure mode was diagnosed with macroscopic or radiographic analysis. Significant difference were detected between PCCP and MISS in sliding of the lag screw. Global vertical displacement of the femoral head during cyclic loading was higher for the PCCP. No statistically significant difference was noted in three-dimensional inter fragmentary displacement and load to failure between these two devices. Failure mode in both devices mainly consisted in fracture impaction, but no cut-out was noted. PCCP and MISS appear to be mechanical devices that may improve clinical outcomes and reduce the risk of co-morbidities associated with unstable trochanteric fractures without increased risk of mechanical failure.


Superficial radial neuropathy.
Isolated neuropathy of the cutaneous branch of the radial nerve is a rarely recognised condition. Five cases were described in 1932 by Wartenberg, who suggested the name cheiralgia paraesthetica. The condition has also been described as Wartenberg's disease. Twelve cases of isolated neuropathy of the cutaneous branch of the radial nerve are described, the literature is reviewed and the clinical picture outlined. In six of the cases the condition subsided without treatment, in two there was a good response to local injection of hydrocortisone, and in four cases a satisfactory result followed resection of the nerve. The course and distribution of the superficial branch of the radial nerve are described. The need to avoid the nerve during operations around the wrist is stressed.


DNA fingerprinting in botany: past, present, future.
Almost three decades ago Alec Jeffreys published his seminal Nature papers on the use of minisatellite probes for DNA fingerprinting of humans (Jeffreys and colleagues Nature 1985, 314:67-73 and Nature 1985, 316:76-79). The new technology was soon adopted for many other organisms including plants, and when Hilde Nybom, Kurt Weising and Alec Jeffreys first met at the very First International Conference on DNA Fingerprinting in Berne, Switzerland, in 1990, everybody was enthusiastic about the novel method that allowed us for the first time to discriminate between humans, animals, plants and fungi on the individual level using DNA markers. A newsletter coined "Fingerprint News" was launched, T-shirts were sold, and the proceedings of the Berne conference filled a first book on "DNA fingerprinting: approaches and applications". Four more conferences were about to follow, one on each continent, and Alec Jeffreys of course was invited to all of them. Since these early days, methodologies have undergone a rapid evolution and diversification. A multitude of techniques have been developed, optimized, and eventually abandoned when novel and more efficient and/or more reliable methods appeared. Despite some overlap between the lifetimes of the different technologies, three phases can be defined that coincide with major technological advances. Whereas the first phase of DNA fingerprinting ("the past") was dominated by restriction fragment analysis in conjunction with Southern blot hybridization, the advent of the PCR in the late 1980s gave way to the development of PCR-based single- or multi-locus profiling techniques in the second phase. Given that many routine applications of plant DNA fingerprinting still rely on PCR-based markers, we here refer to these methods as "DNA fingerprinting in the present", and include numerous examples in the present review. The beginning of the third phase actually dates back to 2005, when several novel, highly parallel DNA sequencing strategies were developed that increased the throughput over current Sanger sequencing technology 1000-fold and more. High-speed DNA sequencing was soon also exploited for DNA fingerprinting in plants, either in terms of facilitated marker development, or directly in the sense of "genotyping-by-sequencing". Whereas these novel approaches are applied at an ever increasing rate also in non-model species, they are still far from routine, and we therefore treat them here as "DNA fingerprinting in the future".


Simultaneous determination of amoxicillin and clavulanic acid in human plasma by HPLC-ESI mass spectrometry.
A simple, fast and sensitive high-performance liquid chromatography (HPLC)-mass spectrometric (MS) method has been developed for simultaneous determination of amoxicillin and clavulanic acid in human plasma using terbutaline as internal standard. After precipitation of the plasma proteins with acetonitrile, the analytes were separated on a C(8) reversed-phase column with formic acid-water-acetonirile (2:1000:100) and detected using electrospray ionization (ESI) mass spectrometry in negative selected ion monitoring (SIM) mode. The method was validated and successfully applied to analysis of amoxicillin and clavulanic acid in clinical studies. The limit of quantitation, 0.12 microg/ml for amoxicillin and 0.062 microg/ml for clavulanic acid, was five times lower than that of the published HPLC-UV method.


Type 1 and type 2 cytokine-producing mouse CD4+ and CD8+ T cells in acute Schistosoma mansoni infection.
CD4+ and CD8+ T cells can be divided based on the cytokines that they secrete into type 1 (Th1, Tc1) and type 2 (Th2, Tc2) subsets. Schistosoma mansoni infection in mice is characterized by a type 2-dominated response. We have used intracellular cytokine staining to demonstrate dramatic changes in the relative numbers of Tc1 and Th2 cells in the spleens of mice during acute schistosome infection. In infected mice prior to egg laying a generalized type 1 response dominated, and was associated with an expansion in the frequency of Tc1 and Th1 cells. By week 7 after infection the cytokine response was of type 2, with an increase in the numbers of Th2 cells and a dramatic reduction in the frequency of Tc1 cells. Following the onset of egg laying there was apoptosis of cells in the spleens of mice, with CD4+ and in particular CD8+ T cells undergoing apoptosis. The loss of CD8+ T cells may in part be attributable to the development of a type 2 environment, following egg laying, with type 2 responses mediating the apoptosis of Tc1 cells. Schistosome regulation of Tc1 during egg laying may be required to prevent type 1 inflammatory responses from exacerbating egg-induced pathology.


Protease immobilization onto polyacrolein microspheres.
Water-insoluble proteases were prepared by immobilizing papain and chymotrypsin onto the surface of polyacrolein microspheres with and without oligoglycines as spacer. The activity of immobilized proteases was found to be still high toward small ester substrates, but very low toward casein, a high-molecular-weight substrate. The relative activity of the immobilized proteases without spacer decreased gradually with the decreasing surface concentration of the immobilized proteases on the microspheres. On the contrary, the immobilized proteases with oligoglycine spacers gave an almost constant activity for the substrate hydrolysis within the surface concentration region studied and gave a much higher relative activity than those without any spacer. With the longer spacer, the immobilized enzymes showed a higher activity toward casein hydrolysis, whereas there was an optimum length for the spacer when hydrolysis was carried out toward the low-molecular-weight substrate. The thermal stability of the immobilized proteases was higher than that of the respective native proteases. The initial enzymatic activity of the immobilized proteases maintained almost unchanged without any elimination and inactivation of proteases, when the batch enzyme reaction was performed repeatedly, indicating the excellent durability.


Amphiphilic Nucleating Agents to Enhance Calcium Phosphate Growth on Polymeric Surfaces.
Poly(ε-caprolactone) (PCL) is an aliphatic polyester widely explored in the preparation of guided bone regeneration (GBR) membranes because of its interesting mechanical properties and biodegradability. However, PCL high hydrophobicity often impairs cell adhesion and proliferation as well as calcium phosphate growth, all of which are crucial to achieving suitable bone-tissue integration. In this work, aimed at achieving less-hydrophobic surfaces, amphiphilic molecules were added at low concentrations to the polymeric dope solutions that generated the GBR membranes. During membrane formation, these molecules migrate to the solution/air interface in such a way that, upon liquid-solid phase transition, the negatively charged heads are exposed while the apolar tails are anchored to the polymer bulk. As a consequence, these molecules became nucleating agents for subsequent calcium phosphate growth using an alternating soaking process. Herein, PCL porous membranes containing different amphiphilic molecules, such as stearic acid and bis(2-ethylhexyl) phosphate, were investigated. This new, simple, and atoxic method to superficially treat polymeric membranes could be extended to a wide range of polymers and applications.


Inhibition effects of Yuxiao San combined with cisplatin on transplanted tumor growths via upregulation of nm-23 and downregulation of K-ras in Lewis lung cancer mice.
Traditional Chinese medicine applied to cancer therapy has a long history. This study aimed to investigate the effect and underlying mechanism of the traditional Chinese medicine, Yuxiao San, in combination with cisplatin, on Lewis lung cancer mice. Lewis lung cancer mouse models were were established in mice, and were randomly divided into model (normal saline + egg white), cisplatin (cisplatin injection + egg white), traditional Chinese medicine (Yuxiao San + egg white) and combined medication (Yuxiao San + cisplatin injection + egg white) groups. The weight and tumor size of mice was measured every 3 days, and the number of lung surface metastasis nodules were calculated after 14 days. Nucleoside diphosphate kinase (nm-23) and K-ras expression levels in tumor tissues were determined by immunohistochemical methods and reverse transcription- quantitative polymerase chain reaction. The results suggested that compared with the model group, cisplatin, traditional Chinese medicine and combined medication groups significantly inhibited growth of transplanted tumors, reduced the number of lung metastasis nodules, increased the inhibition rate of lung metastasis (P<0.05 or P<0.01), significantly increased tumor suppressor gene nm-23 expression and significantly downregulated oncogene K-ras expression. Among all groups, the effect of the combined medication group for inhibiting tumor growth was most favorable (P<0.01). Compared with the cisplatin group, nm-23 expression in the traditional Chinese medicine group and the combined medication group was significantly increased, and K-ras expression in the traditional Chinese medicine and combined medication groups was significantly reduced (P<0.01). To conclude, Yuxiao San and cisplatin injection effectively inhibited growth of the transplanted tumor. The underlying mechanism may be associate with nm-23 upregulation and K-ras downregulation. Therefore, the Yuxiao San and cisplatin injection may become a potential therapeutic strategy for tumor treatment.


Endoscopic variceal sclerotherapy as primary treatment for bleeding esophageal varices.
In this study of 75 patients with bleeding esophageal varices we confirm not only the ability of endoscopic variceal sclerotherapy (EVS) to control acute bleeding episodes but to effect variceal obliteration that confers a significant survival advantage, regardless of initial Child's classification. Survival correlates directly with the degree of hepatic dysfunction, although all patients regardless of Child's status have a statistically significant survival advantage when treated until esophageal variceal obliteration is achieved. All patients treated with EVS should be followed for life, but virtually all follow-up can be done on an outpatient basis. Shunt surgery should be reserved for: (a) patients whose acute bleeding cannot be controlled with EVS at the time of index bleed; and (b) patients who rebleed repeatedly or uncontrollably from gastric or duodenal varices. EVS is more cost-effective than other available treatments. It also effectively stabilizes potential candidates for orthotopic liver transplantation. Despite a progressive increase in the admissions for bleeding varices at our institution, the introduction of EVS has been associated with a significant decline in portosystemic shunt therapy. We believe that EVS is now the first-line treatment for all patients with bleeding esophageal varices.


Biosynthesis of the regulatory oxysterol, 5-cholesten-3beta,25-diol 3-sulfate, in hepatocytes.
Cellular cholesterol homeostasis is maintained through coordinated regulation of cholesterol synthesis, degradation, and secretion. Nuclear receptors for oxygenated cholesterol derivatives (oxysterols) are known to play key roles in the regulation of cholesterol homeostasis. We recently identified a sulfated oxysterol, 5-cholesten-3beta,25-diol 3-sulfate (25HC3S), that is localized to liver nuclei. The present study reports a biosynthetic pathway for 25HC3S in hepatocytes. Assays using mitochondria isolated from rats and sterol 27-hydroxylase (Cyp27A1) gene knockout mice indicated that 25-hydroxycholesterol (25HC) is synthesized by CYP27A1. Incubation of cholesterol or 25HC with mitochondrial and cytosolic fractions in the presence of 3'-phosphoadenosyl 5'-phosphosulfate resulted in the synthesis of 25HC3S. Real-time RT-PCR and Western blot analysis showed the presence of insulin-regulated hydroxycholesterol sulfotransferase 2B1b (SULT2B1b) in hepatocytes. 25HC3S, but not 25HC, decreased SULT2B1b mRNA and protein levels. Specific small interfering RNA decreased SULT2B1b mRNA, protein, and activity levels. These findings demonstrate that mitochondria synthesize 25HC, which is subsequently 3beta-sulfated to form 25HC3S.


Hypomelanosis of Ito: a syndrome requiring a multisystem approach.
Hypomelanosis of Ito can be defined as a syndrome providing a cutaneous epiphenomenon with a peculiar pattern of distribution, usually associated with disorders of the nervous system, skeleton and eyes. Four further patients are reported and the literature reviewed. The diagnostic criteria and the differences with other pigmentary diseases distributed along Blaschko's lines are highlighted. The main histopathological features are reported and the high frequency of the associated abnormalities are emphasized. The chromosomal findings and main genetic hypotheses are discussed. The suggested follow-up aims not only at the knowledge of the natural history of this condition, but also at its better delineation.


Effect of HK2, PKM2 and LDHA on Cetuximab efficacy in metastatic colorectal cancer.
Although hexokinase (HK) 2, pyruvate kinase muscle (PKM) isozyme 2 and lactate dehydrogenase (LDH) A predict the efficacy of medicines in various solid tumors, their ability to predict the efficacy of cetuximab in metastatic colorectal cancer (mCRC) remains unclear. mCRC patients with pathological specimens who received cetuximab and chemotherapy from 2005 to 2015 in the present institution were enrolled. Immunohistochemistry was used to detect HK2, PKM2 and LDHA expression. SPSS20 was used for statistical analysis. A total of 68 patients were included; 33 received cetuximab plus chemotherapy as first-line therapy, and the rest, as second- or later-line therapy. HK2 expression levels were increased in cancer compared with normal tissue (75.4% vs. 40%; P<0.001), however PKM2 (P=0.243) and LDHA (P=0.067) expression levels were not. For progression-free survival (PFS) with first-line cetuximab plus chemotherapy, patients with high HK2 expression exhibited longer PFS compared with those with low HK2 expression (23.9 months vs. 6.9 months; P=0.021). However, this positive association was absent in 35 cases administered first-line chemotherapy alone (13.4 months vs. 13.5 months; P=0.539). LDHA expression was associated with the PFS of patients receiving first-line chemotherapy (18.3 and 10.1 months for high and low expression, respectively; P=0.005), whereas this association was absent in cetuximab plus chemotherapy cases (19.9 months vs. 12 months; P=0.522). Furthermore, high LDHA expression correlated with high overall response rate (ORR) (72.2% vs. 15.4%, P=0.006) for chemotherapy, however not disease control rate (DCR) (P=0.074). Neither DCR nor ORR were associated with HK2 expression. PKM2 expression did not affect PFS, DCR or ORR. LDHA expression (P=0.005), pathological differentiation (P=0.019) and synchronous/metachronous metastasis (P=0.014) were independent predictive factors of PFS for all first-line patients, and tumor differentiation (P=0.002) was associated with overall survival (OS) in multivariate analysis. HK2, PKM2 and LDHA did not impact OS. It was concluded that HK2 expression was increased in colorectal cancer tissue and may predict cetuximab efficacy and LDHA for chemotherapy treatment of mCRC.


Effect of Class I-III obesity on driver seat belt fit.
Approximately 40% of the U.S. adult population are obese. An issue associated with this trend is proper seat belt fit for obese occupants. This study extends previous research, in which few individuals with high BMI (> 40 kg/m2) were included, by examining the relationship between participant and belt factors on belt fit for drivers with Class I-III obesity. Posture and belt fit of 52 men and women with BMI from 31 to 59 kg/m2 (median 38 kg/m2) were measured in a laboratory vehicle mockup. Five seat belt configurations were achieved by manipulating the belt anchorage locations. Body and belt landmark locations were recorded using a three-dimensional coordinate measuring machine. Higher BMI was associated with a lap belt position further forward and higher relative to the pelvis. On average, the lap belt was positioned an additional 32 mm forward and 13 mm above the ASIS with each increasing level of obesity classification. Sex had a small effect after accounting for BMI and stature. The mean fore-aft location of the lap belt was 24 mm more forward for men vs. women and 12 mm higher for women vs. men at the same stature and BMI. On average, women used 50 mm more belt webbing in the lap and 92 mm more in the shoulder vs. men. The results suggest that increasing levels of obesity class effectively introduces slack in the seat belt system by routing the belt further away from the skeleton. Because the belt is designed to engage the pelvis during a frontal crash, belt placements that are higher and further forward may increase injury risk by allowing excursions or submarining. Unique to this cohort, sex had an important effect on belt fit measures after taking into account stature and BMI. The participant and belt factors considered explained only about 40% of the variance in belt fit. The remaining variance may be due to preference or exogenous body shape effects. Further research is needed to assess methods for enhanced seat belt fit for people with obesity, including addressing sex differences in belt routing.


Forming the Hematology-Oncology Collaborative Videoconferencing (CO-VID) Learning Initiative: Experiential Lessons Learned From a Novel Trainee-Led Multidisciplinary Virtual Learning Platform.
COVID-19 challenged medical practice and graduate medical education. Building on previous initiatives, we describe and reflect on the formative process and goals of the Hematology-Oncology Collaborative Videoconferencing Learning Initiative, a trainee-led multi-institutional virtual COVID-19 learning model. Clinical fellows and faculty from 13 US training institutions developed consensus needs, goals, and objectives, recruited presenters, and generated a multidisciplinary COVID-19 curriculum. Weekly Zoom conferences consisted of two trainee-led instructional segments and a trainee-moderated faculty Q&A panel. Hematology-oncology training program faculty and trainees were the targeted audience. Leadership evaluations consisted of anonymized baseline and concluding mixed methods surveys. Presenter evaluations consisted of session debriefs and two structured focus groups. Conference evaluations consisted of attendance, demographics, and pre- or postmultiple-choice questions on topic learning objectives. In 6 weeks, the initiative produced five conferences: antivirals, anticoagulation, pulmonology, provider resilience, and resource scarcity ethics. The average attendance was 100 (range 57-185). Among attendees providing both pre- and postconference data, group-level knowledge appeared to increase: antiviral (n = 46) pre-/postcorrect 82.6%/97.8% and incorrect 10.9%/2.2%, anticoagulation (n = 60) pre-/postcorrect 75%/93.3% and incorrect 15%/6.7%, and pulmonary (n = 21) pre-/postcorrect 66.7%/95.2% and incorrect 33.3%/4.8%. Although pulmonary management comfort appeared to increase, comfort managing of antivirals and anticoagulation was unchanged. At the conclusion of the pilot, leadership trainees reported improved self-confidence organizing multi-institutional collaborations, median (interquartile range) 58.5 (50-64) compared with baseline 34 (26-39), but did not report improved confidence in other educational or leadership skills. During crisis, trainees built a multi-institutional virtual education platform for the purposes of sharing pandemic experiences and knowledge. Accomplishment of initiative goals was mixed. Lessons learned from the process and goals may improve future disaster educational initiatives.


Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial.
To evaluate the clinical outcome of a hydrogel-based autologous chondrocyte implantation (ACI) for large articular cartilage defects in the knee joint. Prospective, multicenter, single-arm, phase III clinical trial. ACI was performed in 100 patients with focal full-thickness cartilage defects ranging from 4 to 12 cm2 in size. The primary outcome measure was the responder rate at 2 years using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Two years after ACI treatment, 93% of patients were KOOS responders having improved by ≥10 points compared with their pre-operative level. The primary endpoint of the study was met and demonstrated that the KOOS response rate is markedly greater than 40% with a lower 95% CI (confidence interval) of 86.1, more than twice the pre-specified no-effect level. KOOS improvement (least squares mean) was 42.0 ± 1.8 points (95% CI between 38.4 and 45.7). Mean changes from baseline were significant in the overall KOOS and in all 5 KOOS subscores from Month 3 (first measurement) to Month 24 (inclusive) (P < 0.0001). The mean MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score after 24 months reached 80.0 points (95% CI: 70.0-90.0 points) and 92.1 points in lesions ≤ 5 cm2. Overall, hydrogel-based ACI proved to be a valuable treatment option for patients with large cartilage defects in the knee as demonstrated by early, statistically significant, and clinically meaningful improvement up to 2 years follow-up. Parallel to the clinical improvements, MRI analyses suggested increasing maturation, re-organization, and integration of the repair tissue. NCT03319797; EudraCT No.: 2016-002817-22.


Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment aspects.
Mantle cell lymphoma (MCL) is a lymphoproliferative disorder comprising about 6-10% of all B cell lymphoma cases. Ibrutinib is an inhibitor of Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. Although treatment with ibrutinib has significantly improved the outcome of MCL patients, approximately one-third of the patients have primary drug resistance while others appear to develop acquired resistance. Understanding the molecular events leading to the primary and acquired resistance to ibrutinib is essential for achieving better outcomes in patients with MCL. In this review, we describe the biology of the BCR signalling pathway and summarize the landmark clinical trials that have led to the approval of ibrutinib. We review the molecular mechanisms underlying primary and acquired ibrutinib resistance as well as recent studies dealing with overcoming ibrutinib resistance.


Key Structural Features of Azanaphthoquinone Annelated Pyrrole Derivative as Anticancer Agents Based on the Rational Drug Design Approaches.
Azanaphthoquinone annelated pyrrole derivatives have been developed and synthesized with a continuous attempt to develop novel DNA intercalating agents as anti-cancer compounds with lower organ toxicity. With the remarkable antiproliferative activity of synthesized azanaphthoquinone annelated pyrrole derivatives, a structurally novel scaffold of these compounds is appropriated for further development of novel anti-cancer agents. Therefore, in the present study, 3D QSAR study (CoMSIA) was applied on 28 azanaphthoquinone annelated pyrrole derivatives to evaluate the structural requirement of these compounds. The resulting CoMSIA model is satisfied with r(2) of 0.99 and q(2) of 0.65. The interpretation of CoMSIA contours reveals the significant importance of steric, electrostatic, hydrophobic and hydrogen acceptor descriptors on the activities of azanaphthoquinone annelated pyrrole derivatives. Remarkably, the structural requirement of six substituent positions on the azanaphthoquinone annelated pyrrole scaffold was elucidated here. This result is the useful concept for design of new and more active azanaphthoquinone annelated pyrrole derivatives. Moreover, MD simulations using AMBER program were performed to model the binding of azanaphthoquinone annelated pyrrole derivatives in the intercalation site of the DNA duplex. Based on MD simulations, the information in terms of ligand-DNA interaction, complex structure and binding free energy was provided in this work. Therefore, the integrated results are informative for further modification of azanaphthoquinone annelated pyrrole scaffold leading to gain novel azanaphthoquinone annelated pyrrole derivatives possessing better antiproliferative activity.


[Factors influencing the diagnose on causes of dyspepsia in central area of Shaanxi province].
To investigate the proportions of functional dyspepsia (FD) and structural diseases within the dyspeptic outpatients in hospitals of different ranking in central area Shaanxi province, and to explore the safety in adopting "symptom and treatment" algorithm used in Western countries. A clinical epidemiology survey was carried out by means of a stratified sample of 3 019 dyspeptic outpatients through standardized questionnaire. All of the patients were followed for 4 - 24 weeks, and finally received their diagnoses through a consistent criteria. Proportionally, FD in all the outpatients took up 44.8% with 44.7% benign organic causes and 10.5% malignant diseases. In the patients who had marked alarm symptoms, the proportion of benign and malignant diseases rose to 52.1% and 29.2%, respectively. They were significantly higher than those without alarm symptoms (39.2%, 2.9%) (P < 0.01). All of the dyspeptic patients were divided into 7 groups according to different ages. 64.5% of FD patients were younger than 25 years and the rate of FD declined with age. It was found that only four patients below 35 years old had malignance. The number of cases increased significantly in age 35 - 45 group and reached 30.8% in 65 - 74 group. There were some differences noticed within dyspeptic patterns between local area in China and Western countries, and the "symptom and treatment" approach was not entirely suitable to the local area in China.


Association of apolipoprotein E and B polymorphisms with serum lipids.
Genetic polymorphism of apolipoprotein E (apoE) and the Xbal restriction-fragment-length polymorphisms (RFLP) of the gene for apolipoprotein B (apoB) have both been shown to be associated with plasma lipid concentration. We studied the combined effect of these gene polymorphisms on serum cholesterol concentrations in 300 subjects aged nine to 18 years. In three way ANOVA, there was a statistically significant interaction between the effects of apoE phenotype and gender on serum cholesterol (P = 0.009). Therefore, males and females were analysed separately by two way ANOVA: there was no interaction between the effects of apoE phenotype and apoB Xbal polymorphism in either gender. In females, there were independent effects of both the apoE phenotype (P = 0.020) and the apoB Xbal genotype (P = 0.037) on serum cholesterol, but in males these effects were not statistically significant. These data suggest that variations at the apolipoprotein B and E gene locus play a role in the determination of serum cholesterol concentration in young female Finns.


Correlation of the gait speed with the quality of life and the quality of life classified according to speed-based community ambulation in Thai stroke survivors.
Gait abnormality commonly resulted from stroke which affected patients living and probably quality of life (QOL). To assess the relationship between gait speed and the QOL in Thai stroke patients and to compare the QOL among three patient groups that were categorized by gait speed: i) household ambulators <0.4 m/s, ii) limited community ambulators 0.4-0.8 m/s and iii) community ambulators >0.8 m/s. This was a cross-sectional descriptive research study. The demographic data of 92 stroke patients at Songklanagarind Hospital in Thailand were collected. The gait speed was calculated by the 10 meter walk test. The Thai version of the Stroke Impact Scale (SIS) 3.0 evaluated the QOL of the patients. The gait speed was correlated with the SIS score (r = 0.64, p < 0.001). The relationship between the gait speed and most domains of the SIS (i.e., strength, mobility, hand function, activities of daily living [ADL], emotion, social participation and thinking of recovery) were also statistically significant. The community ambulators had a higher total SIS score (729.8) than the limited community (600.8) or household ambulators (478.8) (p < 0.001). For each SIS domain mentioned above, there were significant mean scores except for emotion in the community ambulators compared with the others. The gait speed was significantly correlated with the physical domains of the QOL in stroke patients. The community ambulators had the highest QOL among the three groups.


Donor Site Morbidity after Lumbar Artery Perforator Flap Breast Reconstruction.
The lumbar artery perforator flap is a second-choice flap in autologous breast reconstruction whenever a deep inferior epigastric artery perforator (DIEP) flap is not possible. Ideal candidates are pear-shaped women who do not have enough bulk on the abdomen or thighs. Patient-reported "satisfaction with breasts" is excellent but we were curious about the donor site morbidity. We performed a retrospective study of all lumbar flap breast reconstructions performed between 2010 and 2019. Patients were invited by e-mail and telephone to take part in a BREAST-Q survey. One hundred fifty-four flaps were performed in 110 patients. Sixty-three patients filled out the BREAST-Q questionnaire. The most frequently observed donor site complications are seroma (35.1%), dehiscence (8.4%), and hematoma (3.2%). Correction of the donor site scar was performed in 31.8% of patients, lipofilling of the donor flank in 5.2%, and liposuction of the contralateral flank in 18.3% of patients. Body mass index (BMI) was the only significant risk factor for donor site complications. Patient-reported "satisfaction with donor site appearance" was good but significantly lower for primary reconstructions compared with secondary and tertiary procedures. Flap weight significantly influences patient-reported "physical wellbeing of the donor site." Ninety-seven percent of patients would recommend the surgery to someone in a similar position and would do it all over. The lumbar artery perforator flap is a good alternative for breast reconstruction in selected patients. The donor site issues consist mainly of seromas, prolonged discomfort, and a scar that might be noticeable to others, but patient-reported satisfaction is very high.


Systematic conservation planning for groundwater ecosystems using phylogenetic diversity.
Aquifer ecosystems provide a range of important services including clean drinking water. These ecosystems, which are largely inaccessible to humans, comprise a distinct invertebrate fauna (stygofauna), which is characterized by narrow distributions, high levels of endemism and cryptic species. Although being under enormous anthropogenic pressure, aquifers have rarely been included in conservation planning because of the general lack of knowledge of species diversity and distribution. Here we use molecular sequence data and phylogenetic diversity as surrogates for stygofauna diversity in aquifers of New South Wales, Australia. We demonstrate how to incorporate these data as conservation features in the systematic conservation planning software Marxan. We designated each branch of the phylogenetic tree as a conservation feature, with the branch length as a surrogate for the number of distinct characters represented by each branch. Two molecular markers (nuclear 18S ribosomal DNA and mitochondrial cytochrome oxidase subunit I) were used to evaluate how marker variability and the resulting tree topology affected the site-selection process. We found that the sites containing the deepest phylogenetic branches were deemed the most irreplaceable by Marxan. By integrating phylogenetic data, we provide a method for including taxonomically undescribed groundwater fauna in systematic conservation planning.


The structural basis for the mutagenicity of O(6)-methyl-guanine lesions.
Methylating agents are widespread environmental carcinogens that generate a broad spectrum of DNA damage. Methylation at the guanine O(6) position confers the greatest mutagenic and carcinogenic potential. DNA polymerases insert cytosine and thymine with similar efficiency opposite O(6)-methyl-guanine (O6MeG). We combined pre-steady-state kinetic analysis and a series of nine x-ray crystal structures to contrast the reaction pathways of accurate and mutagenic replication of O6MeG in a high-fidelity DNA polymerase from Bacillus stearothermophilus. Polymerases achieve substrate specificity by selecting for nucleotides with shape and hydrogen-bonding patterns that complement a canonical DNA template. Our structures reveal that both thymine and cytosine O6MeG base pairs evade proofreading by mimicking the essential molecular features of canonical substrates. The steric mimicry depends on stabilization of a rare cytosine tautomer in C.O6MeG-polymerase complexes. An unusual electrostatic interaction between O-methyl protons and a thymine carbonyl oxygen helps stabilize T.O6MeG pairs bound to DNA polymerase. Because DNA methylators constitute an important class of chemotherapeutic agents, the molecular mechanisms of replication of these DNA lesions are important for our understanding of both the genesis and treatment of cancer.


Controllable decomposition of Ca(BH4)2 for reversible hydrogen storage.
Ca(BH4)2 could reversibly store 9.6 wt% hydrogen based on the overall reaction of Ca(BH4)2 → 1/3CaB6 + 2/3CaH2 + 10/3H2. Formation of CaB6 instead of elemental boron and/or high boranes (e.g. CaB12H12) in the dehydrogenation process is crucial for rehydrogenation. Here, we reported two experimental protocols regarding how to form CaB6 from the decomposition of Ca(BH4)2: (1) decomposition below the melting point, e.g. 350 °C via CaB2H6 to CaB6 and (2) decomposition above the melting point, e.g. 400 °C via elemental boron to CaB6.


Rapidly detecting the carcinogen acetaldehyde: preparation and application of a flower-like MoS2 cataluminescence sensor at low working temperature.
In this paper, a cataluminescence (CTL) gas sensor based on flower-like molybdenum disulfide (MoS2) is developed. The experimental results show that it has high sensitivity and selectivity to acetaldehyde. The CTL sensor has the advantage of fast response; the response time is about 3 s and the recovery time is about 40 s. The optimal working temperature of this sensor is 174 °C, which is lower than that of the CTL sensors used for acetaldehyde detection in many other reports. Under the optimized conditions, the CTL signal intensity shows a good linear relationship with acetaldehyde concentration (R2 = 0.9991) within the concentration range of 40-2000 ppm, and the detection limit (LOD) is 3.75 ppm. The selectivity experiment results show that the sensor has an obvious response to acetaldehyde and a very weak response to acetic acid, and has no response to many other VOCs (ether, cyclohexane, butyl ether, carbon tetrachloride, ethanol, toluene, formaldehyde, glycerol, trichloromethane and xylene). After 8 repeated measurements for four weeks, the relative standard deviation (RSD) of the CTL sensor is 1.03%, indicating that it has good reproducibility and stability, which shows that the CTL sensor has a promising prospect for the detection of acetaldehyde.


Inside epoxyeicosatrienoic acids and cardiovascular disease.
Epoxyeicosatrienoic acids (EETs) generated from arachidonic acid through cytochrome P450 (CYP) epoxygenases have many biological functions. Importantly, CYP epoxygenase-derived EETs are involved in the maintenance of cardiovascular homeostasis. In fact, in addition to their potent vasodilating effect, EETs have potent anti-inflammatory properties, inhibit platelet aggregation, promote fibrinolysis, and reduce vascular smooth muscle cell proliferation. All EETs are metabolized to the less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Numerous evidences support the role of altered EET biosynthesis in the pathophysiology of hypertension and suggest the utility of antihypertensive strategies that increase CYP-derived EET or EET analogs. Indeed, a number of studies have demonstrated that EET analogs and sEH inhibitors induce vasodilation, lower blood pressure and decrease inflammation. Some of these agents are currently under evaluation in clinical trials for treatment of hypertension and diabetes. However, the role of CYP epoxygenases and of the metabolites generated in cancer progression may limit the use of these drugs in humans.


Cell-cycle perturbations suppress the slow-growth defect of spt10Δ mutants in Saccharomyces cerevisiae.
Spt10 is a putative acetyltransferase of Saccharomyces cerevisiae that directly activates the transcription of histone genes. Deletion of SPT10 causes a severe slow growth phenotype, showing that Spt10 is critical for normal cell division. To gain insight into the function of Spt10, we identified mutations that impair or improve the growth of spt10 null (spt10Δ) mutants. Mutations that cause lethality in combination with spt10Δ include particular components of the SAGA complex as well as asf1Δ and hir1Δ. Partial suppressors of the spt10Δ growth defect include mutations that perturb cell-cycle progression through the G1/S transition, S phase, and G2/M. Consistent with these results, slowing of cell-cycle progression by treatment with hydroxyurea or growth on medium containing glycerol as the carbon source also partially suppresses the spt10Δ slow-growth defect. In addition, mutations that impair the Lsm1-7-Pat1 complex, which regulates decapping of polyadenylated mRNAs, also partially suppress the spt10Δ growth defect. Interestingly, suppression of the spt10Δ growth defect is not accompanied by a restoration of normal histone mRNA levels. These findings suggest that Spt10 has multiple roles during cell division.


Water discharge affects Atlantic salmon Salmo salar smolt production: a 27 year study in the River Orkla, Norway.
A model that explains 48% of the annual variation in Atlantic salmon Salmo salar smolt production in the River Orkla, Norway, has been established. This variation could be explained by egg deposition, minimum daily discharge during the previous winter and minimum weekly discharge during the summer 3 years before smolt migration. All coefficients in the model were positive, which indicates that more eggs and higher minimum discharge levels during the winter before smolt migration and the summer after hatching benefit smolt production. Hence, when the spawning target of the river is reached, the minimum levels of river discharge, in both winter and summer, are the main bottlenecks for the parr survival, and hence for smolt production. The River Orkla was developed for hydropower production in the early 1980s by the construction of four reservoirs upstream of the river stretch accessible to S. salar. Although no water has been removed from the catchment, the dynamics of water flow has been altered, mainly by increasing discharges during winter and reducing spring floods. In spite of the higher than natural winter discharges, minimum winter discharge is still a determinant of smolt production. Hence, in regulated rivers, the maintenance of discharges to ensure that they are as high as possible during dry periods is an important means of securing high S. salar smolt production.


Within-individual hematocrit variations and self-monitoring of blood glucose.
Many self-monitoring of blood glucose (SMBG) systems have generated artefactually increased glucose results in low-hematocrit patients (e.g., intensive care unit and renal failure patients); conversely, these devices could produce artefactually decreased glucose results in high-hematocrit patients (e.g., neonates). The introduction of hematocrit-independent SMBG systems permits more accurate testing in anemic or polycythemic individuals. In this issue of Journal of Diabetes Science and Technology, Ramljak and coauthors have created glucose bias graphs for 19 common SMBG devices and declared certain systems to be optimally accurate because of insensitivity to hematocrit variation over a broad hematocrit range. Luckily, the average within-individual variation of hematocrit is low (between 2.9 and 3.3%). As such, a larger spectrum of SMBG devices can be regarded as optimally hematocrit independent.


Influence of drinking method on tooth-surface pH in relation to dental erosion.
The aim of this investigation was to study the intraoral pH response on tooth surfaces in relation to dental erosion during and after drinking a sugar-free cola-type soft drink. Six different methods of drinking were tested in a randomized order: holding; short-sipping; long-sipping; gulping; nipping; and sucking. Two methods of pH measurement were used in two series of individuals. In the first series, pH was measured by using the microtouch method in 12 healthy adults at three dental erosion-prone sites: 11 palatally; 11 buccally; and at the mesiobuccal cusp tip of 16. In the second series, pH was measured by using the telemetric method in 6 healthy individuals, producing continuous recordings of pH by means of a glass electrode in a specified approximal area. The two series showed similar results, although the telemetric method generally recorded larger pH falls. Holding the drink in the mouth before swallowing led to the most pronounced pH drop, followed by the long-sipping method. Gulping resulted in only a small decrease of pH. No differences among the three intraoral sites were found when analyzed by using the microtouch method. The conclusion from this study is that the drinking method strongly affects tooth-surface pH and thereby the risk for dental erosion. It therefore seems appropriate to include advice on the method of drinking in dietary counseling related to dental erosion.


Monochromatic waves induced by large-scale parametric forcing.
We study the formation and stability of monochromatic waves induced by large-scale modulations in the framework of the complex Ginzburg-Landau equation with parametric nonresonant forcing dependent on the spatial coordinate. In the limiting case of forcing with very large characteristic length scale, analytical solutions for the equation are found and conditions of their existence are outlined. Stability analysis indicates that the interval of existence of a monochromatic wave can contain a subinterval where the wave is stable. We discuss potential applications of the model in rheology, fluid dynamics, and optics.


Equine infectious anemia virus transactivator is a homeodomain-type protein.
Lentiviral transactivator (Tat) proteins are essential for viral replication. Tat proteins of human immunodeficiency virus type 1 and bovine immunodeficiency virus form complexes with their respective RNA targets (Tat responsive element, TAR), and specific binding of the equine anemia virus (EIAV) Tat protein to a target TAR RNA is suggested by mutational analysis of the TAR RNA. Structural data on equine infectious anemia virus Tat protein reveal a helix-loop-helix-turn-helix limit structure very similar to homeobox domains that are known to bind specifically to DNA. Here we report results of gel-shift and footprinting analysis as well as fluorescence and nuclear magnetic resonance spectroscopy experiments that clearly show that EIAV Tat protein binds to DNA specifically at the long terminal repeat Pu.1 (GTTCCTGTTTT) and AP-1 (TGACGCG) sites, and thus suggest a common mechanism for the action of some of the known lentiviral Tat proteins via the AP-1 initiator site. Complex formation with DNA induces specific shifts of the proton NMR resonances originating from amino acids in the core and basic domains of the protein.


Do Obstetric Patients Opt to Undergo General Anaesthesia to Avoid Being Conscious Despite Safer Alternatives?
There are various modes of anaesthesia available in the community today. This gives anaesthesiologists the freedom to select those that are safe, efficacious and most suitable for patients. However, patients may not always agree with their anaesthesiologist on the preferred mode of anaesthesia because they may have a different set of priorities, with many of them electing to have the lack of intraoperative awareness as the primary objective. Hence, disagreements between anaesthesiologists and patients may arise and could potentially disrupt doctor-patient relationship. This paper attempts to explore the possible reasons for obstetric patients championing for certain modes of anaesthesia and to provide an insight into the need for adequate patient education.


Developing a Generic Risk Assessment Simulation Modelling Software Tool for Assessing the Risk of Foot and Mouth Virus Introduction.
Foot and Mouth disease (FMD) is a highly contagious viral disease that affects all cloven-hoofed animals. Because of its devastating effects on the agricultural industry, many countries take measures to stop the introduction of FMD virus into their countries. Decision makers at multiple levels of the United States Department of Agriculture (USDA) use Risk Assessments (RAs) (both quantitative and qualitative) to make better and more informed scientifically based decisions to prevent the accidental or intentional introduction of the disease. There is a need for a generic RA that can be applied to any country (whether FMD free or non-FMD free) and for any product (FMD infected animals and animal products). We developed a user-friendly generic RA tool (software) that can be used to conduct and examine different scenarios of quantitative/qualitative risk assessments for the different countries with their varying FMD statuses in relation to reintroduction of FMD virus into the USA. The program was written in Microsoft Visual Basic 6.0 (Microsoft Corporation, Redmond, Washington, USA). The @Risk 6.1 Developer Kit (RDK) and @Risk 6.1 Best Fit Kit library (Palisade Corporation, Newfield, NY.USA) was used to build Monte Carlo simulation models. Microsoft Access 2000 (Microsoft Corporation, Redmond, Washington, USA) was used and SQL to query the data. Different input probability distributions can be selected for the nodes in the scenario tree and different output for each end-state of the simulation is given in different graphical formats and statistical values are used in describing the likelihood of FMD virus introduction. Sensitivity Analysis in determining which input factor has more effect on the total risk outputs is also given. The developed generic RA tools can be eventually extended and modified to conduct RAs for other animal diseases and animal products.


GRP78 silencing enhances hyperoxia-induced alveolar epithelial cell apoptosis via CHOP pathway.
Hyperoxia is one of the primary causes of bronchopulmonary dysplasia, which may occur in premature infants following supplemental oxygen therapy. Glucose regulated protein 78 (GRP78), which is a molecular chaperone located in the lumen of the endoplasmic reticulum (ER), has been reported to regulate hyperoxia‑associated ER stress. The role of GRP78 in lung epithelial cells during hyperoxia remains to be elucidated. In the present study, the A549 cultured human lung epithelial cell line was exposed to hyperoxic conditions, and then transfected with short interfering (si)RNA targeted to GRP78. siRNA or pEGFP‑N1 plasmid were used to knockdown or overexpress specific genes, reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect RNA and protein levels of gene expression, and flow cytometry was used to detect apoptosis. The expression levels of ER stress‑associated genes were determined, and a significant increase in C/EBP homologous protein (CHOP) expression and apoptosis of A549 cells was observed, following GRP78 knockdown. The overexpression of CHOP downregulated B‑cell lymphoma (Bcl)‑2 expression levels, upregulated BCL2 associated X (Bax), and increased apoptosis of A549 cells under conditions of hyperoxia. CHOP knockdown demonstrated the opposite effect on Bcl‑2 and Bax expression levels. These results suggested that GRP78 silencing promoted lung epithelial cell apoptosis during hyperoxia, via regulation of the CHOP pathway.


Ocular trauma in an iron forging industry in the eastern province, Saudi Arabia.
Occupational accidents occur in industry worldwide, and the Kingdom of Saudi Arabia (KSA) is no exception. However, accidents are not routinely analyzed in this country and therefore their extent and types remain unknown. The aim of this study was to calculate the rates of ocular injuries in an iron forging factory in the Eastern Province of the KSA. It also aimed at identifying the main causes of injury and the groups at risk. All ocular and non-ocular injuries that occurred during 1991 were reviewed. Data sources were the company's accident report and the employees' medical files. A total of 193 injuries were reported. Seventy-seven (39.9%) of these affected the eyes. The incident rate for ocular injuries was 111.8 per 1,000 men exposed. The age group 33-42 had the highest prevalence rate (55.8%) and 67.5% of the eye injuries involved employees with job experience of 11 months or less. Use of pneumatic chisels was among the most hazardous activities. Projectile foreign bodies were responsible for 76.6% of the incidents. More than a third of the injured were not wearing eye protection. Avoidable factors, such as negligence, were major contributory factors. A training programme concerning safety has much to commend it, and pneumatic chisels should be replaced by other safer means.


Netrin-4 Mediates Corneal Hemangiogenesis but Not Lymphangiogenesis in the Mouse-Model of Suture-Induced Neovascularization.
Netrin-4, a secreted protein, is found in the basement membrane of blood vessels and acts as a key regulator of angiogenesis. Here we investigated the role of Netrin-4 in the mouse-model of suture-induced corneal hem- and lymphangiogenesis. Corneal hem- and lymphangiogenesis were induced in Netrin-4-deficient (Ntn4-/-) and wild-type (WT) mice by placing three 11-0 nylon sutures intrastromally. Fourteen days after suturing, the vascularized area was analyzed via corneal flat mount immunohistochemistry. Messenger RNA levels for VEGF-A, VEGF-C, Lyve-1, Netrin-4, Unc5H2, "deleted in colon cancer" receptor, and Neogenin in treated and nontreated mouse corneas, cultured human corneal keratocytes (HCK) and epithelial cells (HCEC+HCET) were analyzed by quantitative PCR. In wild-type mice, Netrin-4 mRNA expression in the cornea decreased in growing corneal neovascularization after suturing. Correspondingly, Ntn4-/- mice showed an increased vascularized area compared to that in WT mice. Expression of VEGF-A mRNA was higher in Ntn4-/- versus WT mice. There was no Netrin-4 expression in lymphatic vessels and the area of lymphatic vascularization did not differ between Ntn4-/- and WT mice, nor did expression of VEGF-C and Lyve-1 mRNA. Human corneal epithelial cells showed mainly Netrin-4 mRNA expression, which increased after stimulation, while HCK demonstrated Unc5H2 mRNA expression. Expression of VEGF-A, Netrin-4, Unc5H2, and Neogenin mRNA in HCEC and HCK did not differ significantly between the serum-free condition and VEGF-A or Netrin-4 stimulation. Absence of Netrin-4 increased corneal hemangiogenesis but not lymphangiogenesis in the mouse-model of suture-induced neovascularization. Netrin-4 acted as an antiangiogenic factor in the cornea, with which the healthy cornea is enriched via its expression by corneal epithelial cells.


Effect of P-deficiency on photoassimilate partitioning and rhythmic changes in fruit and stem diameter of tomato (Lycopersicon esculentum) during fruit growth.
Tomato (Lycopersicon esculentum) plants were grown in liquid culture inside the greenhouse of Hiroshima University, Japan. At the first fruiting stage, P was withdrawn from the rooting medium for a period of 19 d and its effect was studied on photosynthesis, stomatal conductance, transpiration, partitioning of 13C and 15N, P contents of various organs, and changes in stem and fruit diameter of the plant in order to identify the mechanism of resource management on the part of the plant at low P. Compared to the control, P-deficiency treatment decreased biomass growth of all organs except the roots. The treatment also depressed leaf photosynthesis, stomatal conductance and diameter of fruit and stem after a lag period of about 1 week. The stem diameter of the plant shrank during daytime and expanded during the night; the adverse effect of P-deficiency on stem diameter change was more evident during the night than the day. The circadian rhythm in fluctuations of diameter was less manifested in the fruit compared with the stem. P-deficiency induced daytime shrinkage and reduced night expansion of fruit. However, within the plant, P-deficiency encouraged partitioning of 13C, 15N and P into the fruit at the cost of autotrophic organs such as leaves and the upper parts of the stem. The results were discussed in the light of a plausible effect of P-deficiency on water relations of the plant. It is concluded that, in spite of the preference in partitioning of C and N received within the plant parts, assimilate flow into the fruit is limited at low-P compared with the control, owing to the restriction in fruit expansion.


[Prognostic analysis of cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma].
To analyze the prognostic factors of cervical lymph node metastasis (CLN) in thoracic esophageal squamous cell carcinoma (TESCC), and to probe and verify the esophageal carcinoma staging of the 7th edition of American Joint Committee on Cancer (AJCC) TNM staging system. A total of 1 715 TESCC patients underwent radical esophagectomy plus three-field lymph node dissection at Fujian Provincial Cancer Hospital between January 1993 and March 2007. 547 patients had pathological metastasis of CLN, and 296 patients received surgery only (S group) and 251 patients received postoperative radiotherapy (S+R group). The prognostic factors were analyzed and the pattern of recurrence and metastases was studied according to the esophageal carcinoma staging criteria of the 7th edition of AJCC TNM staging system. The metastasis rate of CLN was 31.9% for the entire group, 44.2%, 31.5% and 14.4% for the upper, middle and lower TESCC, respectively (P < 0.001). The 5-year overall survival rate of the patients with metastatic CLN was 27.7%, and the median overall survival time was 27.5 months. The 5-year survival rate was 21.3% in the S group and 34.2% in the S+R group, and the median survival time was 21.9 months in the S group and 35.4 months in the S+R group (P < 0.001). Multivariate analysis showed that gender, lesion length in X-ray, N stage, AJCC stage and treatment modality were independent prognostic factors of CLN metastasis in TESCC. Independent prognostic factors for S group included the primary tumor site, pT stage, N stage and AJCC stage, and N stage was an independent prognostic factor for the S+R group. TESCC with CLN metastasis have a better prognosis after surgery. It supports that cervical lymph nodes belong to regional lymph nodes classified in the 7th edition of AJCC TNM staging system.


Selective homonuclear decoupling in 1H NMR: application to visualization of enantiomers in chiral aligning medium and simplified analyses of spectra in isotropic solutions.
The proton NMR spectral complexity arising due to severe overlap of peaks hampers their analyses in diverse situations, even by the application of two-dimensional experiments. The selective or complete removal of the couplings and retention of only the chemical shift interactions in indirect dimension aids in the simplification of the spectrum to a large extent with little investment of the instrument time. The present study provides precise enantiodiscrimination employing more anisotropic NMR parameters in the chiral liquid crystalline medium and differentiates the overlapped peaks of many organic molecules and peptides dissolved in isotropic solvents.


Migration modelling from food-contact plastics into foodstuffs as a new tool for consumer exposure estimation.
One important aspect within the European Union's public healthcare is the exposure of consumers to undesirable chemicals in the diet. Food-contact materials (FCM) are one potential contamination source and therefore of particular interest for food exposure assessment. On the other hand, scientific investigations concerning the migration potential and behaviour of food-packaging materials have demonstrated that diffusion in and migration from FCM are foreseeable physical and, in principle, mathematically describable processes. Because of this situation and the current state-of-the-art in migration science, a research project was initiated within the 5th Framework Programme of the European Commission. This project, with the acronym 'FOODMIGROSURE' (European Union Contract No. 'QLK1-CT2002-2390') started on 1 March 2003, was due to last 3 years and had the participation of nine European project partners (see the project website: www.foodmigrosure.org). The aim of the project was to extend currently existing migration models (which have been demonstrated to be applicable for less complex matrices such as food simulants) to foodstuffs themselves. In this way, the project aims to provide a novel and economic tool for estimation of consumer exposure to chemicals migrating from food-contact plastic materials under any actual contact conditions. In addition, the project aims to increase knowledge of the mechanisms of diffusion of organic compounds in foodstuffs and provide data on the partitioning effects between FCM and foods. Today the latter aspect is increasingly regarded as a fundamental influence parameter for migration into foods. Based on the project achievements, a much better scientific basis is available to allow scientifically appropriate amendments of European Union Directive 85/572/EEC as well as to support further developments with the so-called Plastics Directive 2002/72/EC. The paper introduces the project and presents an overview of the project work progress.


Odorant receptor-derived cAMP signals direct axonal targeting.
In mammals, odorant receptors (ORs) direct the axons of olfactory sensory neurons (OSNs) toward targets in the olfactory bulb. We show that cyclic adenosine monophosphate (cAMP) signals that regulate the expression of axon guidance molecules are essential for the OR-instructed axonal projection. Genetic manipulations of ORs, stimulatory G protein, cAMP-dependent protein kinase, and cAMP response element-binding protein shifted the axonal projection sites along the anteriorposterior axis in the olfactory bulb. Thus, it is the OR-derived cAMP signals, rather than direct action of OR molecules, that determine the target destinations of OSNs.


The Difference between Cartilaginous and Bony Sulcus Angles for Patients with or without Patellofemoral Instability: A Systematic Review and Meta-Analysis.
The cartilaginous sulcus angle and bony sulcus angle have been widely used to evaluate trochlea dysplasia. The current review aims to evaluate (1) whether there is a difference in measurement for cartilaginous and bony sulcus angles, (2) whether both the cartilaginous and bony sulcus angles could be used to differentiate between patients with or without trochlear dysplasia, and (3) whether the same cut-off of 145 degrees, originally used for radiographs, can be applied for the cartilaginous and bony sulcus angles measured on CT and MRI. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRSIMA) guidelines. A total of 11 publications with 1204 patients were included. All publications reported the sulcus angle to be greater in patients with patellofemoral instability. All publications reported the cartilaginous sulcus angle to be greater than the bony sulcus angle (MD 7.27 degrees; 95% CI: 5.67 - 8.87). The mean cartilaginous sulcus angle for the control group was 141.83 degrees (95% CI: 139.90 - 143.76) while the mean cartilaginous sulcus angle for patients with patellofemoral instability was 156.24 degrees (95% CI: 153.71 - 158.77). The mean bony sulcus angle for the control group was noted to be 133.69 degrees (95% CI: 131.23 - 136.15) while the mean bony sulcus angle for patients with patellofemoral instability was 148.42 (95% CI: 144.02 - 152.82). Both the cartilaginous and bony sulcus angles measured on CT and MRI could therefore be used to differentiate between patients with and without trochlear dysplasia. However, the cartilaginous sulcus angles are significantly higher than that of bony sulcus angles. Different cut off values should therefore be used.


What Parents and Their Gay and Bisexual Sons Say About HIV Prevention.
Despite ongoing prevention efforts, young gay and bisexual men (YGBM) accounted for more than three fourths of all recent HIV infections. Furthermore, they continue to engage in high-risk sexual behaviors at alarming rates. Nowadays, families are beginning to emerge as important resources for these youth. However, the viewpoints of YGBM and their families are largely missing from HIV prevention research and intervention development. To address this gap, we solicited the opinions of YGBM and their parents as to why YGBM engage in unsafe sex and what might be done to help them avoid HIV. Participants discussed youth's sense of invulnerability, sexual arousal, parental disapproval, and lack of societal acceptance as contributors to unsafe sex. Participants called for gay-sensitive sex education and community programming as well as increased societal acceptance. Overall, respondents recommended interpersonal and structural-level interventions that emphasized the importance of reducing stigma as a key component of HIV prevention.


Blood β-hydroxybutyrate vs. urine acetoacetate testing for the prevention and management of ketoacidosis in Type 1 diabetes: a systematic review.
Diabetic ketoacidosis is a life-threatening complication of Type 1 diabetes. Blood β-hydroxybutyrate testing is now widely available as an alternative to urine acetoacetate testing for detecting ketosis. The aim of this study was to review the effectiveness of capillary or serum β-hydroxybutyrate compared with urine acetoacetate testing in prevention and management of diabetic ketoacidosis. MEDLINE, EMBASE, EBM Reviews, The Cochrane Library and CINAHL (until April 2012, no language restrictions, studies in humans) were searched for experimental and observational studies comparing the effectiveness of blood β-hydroxybutyrate and urine acetoacetate testing. Outcomes examined were prevention of diabetic ketoacidosis, time to recovery from diabetic ketoacidosis, healthcare costs and patient or caregiver satisfaction. Additional sources included reference lists, conference proceedings and contact with experts in the field. Four studies (two randomized controlled trials and two cohort studies) met eligibility criteria, including 299 participants across 11 centres. Risk of bias was low to moderate. Blood ketone testing compared with urine testing was associated with reduced frequency of hospitalization (one study), reduced time to recovery from diabetic ketoacidosis (three studies), cost benefits (one study) and greater satisfaction (one study, intervention group only). No study assessed prevention of diabetic ketoacidosis. Meta-analysis could not be performed because of heterogeneity in study design and published data. There is evidence suggesting that blood β-hydroxybutyrate testing is more effective than urine acetoacetate testing in reducing emergency department assessment, hospitalization and time to recovery from diabetic ketoacidosis, as well as potentially lowering healthcare expenditure. Further research in both young people and adults is needed.


[Effect of ethirazol and parmidine ofn the development of experimental atherosclerosis in rabbits].
Experiments on rabbits which received cholesterol in food for 3-4 months showed an inhibitory effect of ethirazol (bis-methylamide-1-ethyl-pyrazol-3,4-bicarbonic acid) and parmidine (piridinolcarbamate, 2,6-bis-hydroxymethylpiridine bis-n-methylcarbamate) on the development of experimental atherosclerosis: there proved to be a reduction of accumulation of total cholesterol in the aorta and of its atherosclerotic affection. At the same time the blood serum cholesterol, triglycerids and phospholipid content was not significantly changed by these drugs.


[A case report: ovarian carcinoma IVth can become complete remission by immunochemotherapy].
A patient with navel metastasis from ovarian carcinoma was treated by immunotherapy and neo-adjuvant intraarterial infusion chemotherapy (OK-432 i.c., VP-16 25 mg/body x 10 days po, CDDP 100 mg/m2 iA, CPM 200 mg x 3 days/body i.v., THP 50 mg/m2 iA). Maximal blood concentration of THP was 1.081 micrograms/ml at 1 hour intraarterially and 0.091 microgram/ml at 2 hour intravenously. THP concentration of arteria is ten times higher than that of venous. And the area under the curve (AUC) of THP is 3.46 micrograms/ml/hr intraarterially and 0.43 microgram/ml/hr at intravenous. Two courses of the neo-adjuvant intraarterial chemotherapy were done. One month after, the first operation was performed. Each tissue platina concentration is 9.72 micrograms/ml is 9.72 micrograms/cm3 uterus cervix, 7.10 micrograms/cm3 uterus corporis, 5.72 micrograms/cm3 left ovarium, 2.64 micrograms/cm3 right ovarium, 0.52 microgram/cm3 paraaortic lymph node. After the immuno-chemotherapy, the metastatic tumor appeared remarkably smaller and the main tumor regained normal size and we achieved the optimal operation successfully. This patient was treated with double platina chemotherapy by intraperitoneal infusion using implantable reservoir access after the first operation (VP-16 200 mg/m2 i.p. D1, CDDP 100 mg/m2 ip D1, CBDCA 300 mg/m2 i.v. D3). This patient can keep the state of cytological complete remission for more than four months after the second look operation. Now she continues maintenance immuno-chemotherapy from a home doctor.