In vitro induction of infection-related hyphal structures in plant pathogenic fungi.
In recent years, a voluminous amount of genomic data has been generated for several plant pathogenic fungi. Multiple studies have utilized these genomic data to advance our knowledge about the molecular mechanisms of plant pathogenesis. However, not all plant pathogenic fungi share the same infection strategies, and several genes have been identified that are crucial for plant pathogenesis in one fungus, but dispensable in others. In order for data on biological relevance to keep pace with accumulating genomic data, new biological assays need to be developed for several pathogenic fungi. Accordingly, we have developed an in vitro assay that allows us to monitor morphological changes in hyphal development as the head blight pathogen Fusarium graminearum infects wheat. Using previously frozen detached wheat glumes, we are able to monitor both subcuticular and intercellular hyphal development of F. graminearum. The method described takes only 3-5 days from inoculation to microscopic observation (depending on time point) and does not require any elaborate laboratory equipment or supplies. This method could be adapted for different necrotrophic or hemi-biotrophic pathogens, on their host tissue types, in order to characterize their hyphal differentiation in vitro.


Autologous transplant remains the preferred therapy for relapsed APL in CR2.
Despite their favorable prognosis, 10-20% of acute promyelocytic leukemia (APL) patients relapse. Reinduction therapy is often followed by autologous hematopoietic cell transplantation (auto-HCT). Arsenic trioxide (ATO) has become part of standard reinduction and is often followed by auto-HCT. Data on patients in CR2 were collected from two large transplant registries (Center for International Blood and Marrow Transplant Research (CIBMTR) and European Group for Blood and Marrow Transplant (EBMT)) and two specialty referral centers. The outcome of patients in CR2 who received only ATO-based therapy as reinduction was retrospectively compared with those who got an auto-HCT, with or without ATO. Prognostic factors included age, disease risk, extramedullary disease and duration of CR1. Of 207 evaluable patients, the median age was 31.5 years, 15.3% had extramedullary disease and median WBC at diagnosis was 4.8 × 10(9)/L. Sixty-seven patients received ATO alone and 140 underwent auto-HCT. The groups were comparable for age, gender, extramedullary disease, risk group and duration of CR1. At 5 years, overall survival (OS) was 42% and 78% for the ATO-only and auto-HCT groups, respectively (P<0.001). In addition, OS was associated with longer duration of CR1 (P=0.002), but not with disease risk at diagnosis. These data suggest that auto-HCT for APL patients in CR2 results in better OS than ATO-based therapy alone.


[Lower dyspeptic syndrome. Recommended diagnostic and therapeutic procedures for general practitioners 2006].
Lower dyspeptic syndrome is a bowel disease manifesting namely with pain or sensation of abdominal discomfort and bowel movement problems (changes in the frequency and stool consistency). Symptoms include sensation of intraabdominal pressure and fullness, diarrhoea (with or without pain), sensation of incomplete defecation, constipation or bowel movement problems (with or without pain), irregular stool, collywobbles and bowel content flow (borborygia with spasms), meteorism, flatulency. Prevalence of the Irritable Bowel Syndrome in the European population is estimated to be 5 to 25 %. In the Czech Republic the total prevalence of dyspepsias is about 13 %. To the pathogenesis of the lower dyspeptic syndrome contribute: 1. abnormal motility, 2. abnormal visceral perception, 3. psychosocial factors, 4. luminal factors, 5. imbalance of neurotransmitters and/or intestinal bacteria and 6. possible inflammatory changes of the intestinal mucosa. Infectious diarrhoea is one of the causes. Functional bowel defects represent various combinations of chronic and recurrent symptoms from the digestive tract which cannot be explained by structural or biochemical abnormalities. Irritable bowel syndrome is a functional defect manifesting with abdominal pain, intestinal dyspepsia and compulsive defecations. Subtypes with typical symptomatology are characterized by circumstances which bring about pain and compulsive defecations (morning fractional defecation, postprandial defecation, debacles). Functional diarrhoea manifests with diarrhoea without intensive pain. Spastic obstipation manifests by abdominal pain, obstipation, compulsive defecations are absent, stool is cloddish, fragmented by spastic haustration, or it has a ribbon-form. Changes in the intestinal chemism include fermentative and putrefactive dyspepsia. Among the incomplete and atypical forms the isolated meteorism, irregular defecation, flatulency, abdominal pain--syndrome of the left or right epigastium or the syndrome of the right hypogastrium can be included. In patients with typical set of symptoms the working diagnose of the lower dyspeptic syndrome can be done by general practitioner. Complete history of the disease can reveal possible extra abdominal cause of dyspepsia, recognise alarming symptoms and consider circumstances elevating or lowering the probability of functional problems. Functional bowel problems have usually long-term character and represent clinically demanding challenge. Only few therapeutic regimens are successful and the therapy aimed at the abolishment of one symptom need not bring general improvement. For the clinical studies of the therapy of functional bowel problems significant placebo effect is typical. Quoad vitam prognosis is good, quoad sanationem it is rather doubtful.


Transient oscillations induced by delayed growth response in the chemostat.
In this paper, in order to try to account for the transient oscillations observed in chemostat experiments, we consider a model of single species growth in a chemostat that involves delayed growth response. The time delay models the lag involved in the nutrient conversion process. Both monotone response functions and nonmonotone response functions are considered. The nonmonotone response function models the inhibitory effects of growth response of certain nutrients when concentrations are too high. By applying local and global Hopf bifurcation theorems, we prove that the model has unstable periodic solutions that bifurcate from unstable nonnegative equilibria as the parameter measuring the delay passes through certain critical values and that these local periodic solutions can persist, even if the delay parameter moves far from the critical (local) bifurcation values. When there are two positive equilibria, then positive periodic solutions can exist. When there is a unique positive equilibrium, the model does not have positive periodic oscillations and the unique positive equilibrium is globally asymptotically stable. However, the model can have periodic solutions that change sign. Although these solutions are not biologically meaningful, provided the initial data starts close enough to the unstable manifold of one of these periodic solutions they may still help to account for the transient oscillations that have been frequently observed in chemostat experiments. Numerical simulations are provided to illustrate that the model has varying degrees of transient oscillatory behaviour that can be controlled by the choice of the initial data.


Accounting for population structure in selective cow genotyping strategies.
The objective of the present study was to investigate the impact of considering population structure in cow genotyping strategies over the accuracy and bias of genomic predictions. A small dairy cattle population was simulated to address these objectives. Based on four main traditional designs (random, top-yield, extreme-yield and top-accuracy cows), different numbers (1,000; 2,000 and 5,000) of cows were sampled and included in the reference population. Traditional designs were replicated considering or not population structure and compared among and with a reference population containing only bulls. The inclusion of cows increased accuracy in all scenarios compared with using only bulls. Scenarios accounting for population structure when choosing cows to the reference population slightly outperformed their traditional versions by yielding higher accuracy and lower bias in genomic predictions. Building a cow-based reference population from groups of related individuals considering the frequency of individuals from those same groups in the validation population yielded promising results with applications on selection for expensive- or difficult-to-measure traits. Methods here presented may be easily implemented in both new or already established breeding programs, as they improved prediction and reduced bias in genomic evaluations while demanding no additional costs.


Disease activity and fatigue in juvenile idiopathic arthritis.
To examine the association between parent/proxy- and child-reported fatigue and disease activity in children with polyarticular, extended oligoarticular, and persistent oligoarticular juvenile idiopathic arthritis (JIA). We enrolled a cross-sectional cohort of 309 children recruited from the Seattle Children's Hospital rheumatology clinic from 2009-2011. Parents and children completed the PedsQL Multidimensional Fatigue Scales. The parent/proxy, child, and/or physician provided additional disease activity data at each clinic visit, including active joint count, pain, and the Childhood Health Assessment Questionnaire (C-HAQ). Disease activity was dichotomized as active or inactive using the American College of Rheumatology provisional criteria for clinically inactive disease. The Juvenile Arthritis Disease Activity Score (JADAS) was also calculated. Linear regression was used to examine the associations between fatigue and disease activity. Associations among fatigue, clinically inactive disease, and the JADAS were not statistically significant after controlling for pain. In the multivariable models of fatigue, the C-HAQ and parent/child-reported disease activity were significantly associated with fatigue; however, only the C-HAQ remained significantly associated after adjustment for pain. The C-HAQ and parent/child-reported disease activity explained 17% and 30% of the variance in fatigue for the parent/proxy- and child-reported multivariable models, respectively. In this cohort, functional ability, as measured by the C-HAQ, was significantly associated with fatigue. Child- and parent/proxy-reported pain were important confounders of the relationship between fatigue and disease activity. Routinely incorporating pain and fatigue into interventional and observational trials of JIA will enable better delineation of the relationships between these variables.


S K-edge NEXAFS spectra of model systems for SO2 on TiO2 (110): a TDDFT simulation.
The time dependent density functional theory approach has been employed to simulate the S K edge absorption spectra of model systems for the adsorption of SO(2) on TiO(2) (110) regular surface, employing cluster models to mimic the rutile surface. The spectra calculated for the adsorbate models are compared with the spectrum of the free SO(2) in order to discuss the nature of the adsorbate-substrate interaction in terms of the differences in the core excitation spectra. The comparison with the experimental NEXAFS spectra, measured at different temperatures, is satisfactory at low temperature while it reveals the difficulty of reproducing the complex experimental situations induced by the temperature increase with an adsorption model based on a perfect TiO(2) surface.


From Perugino to Picasso revisited: Electrophysiological responses to faces in paintings from different art styles.
Behavioral research (Ventura, et al., 2023) suggested that pictorial representations of faces varying along a realism-distortion spectrum elicit holistic processing as natural faces. Whether holistic face neural responses are engaged similarly remains, however, underexplored. In the present study, we evaluated the neural correlates of naturalist and artistic face processing, by exploring electrophysiological responses to faces in photographs versus in four major painting styles. The N170 response to faces in photographs was indistinguishable from that elicited by faces in the renaissance art style (depicting the most realistic faces), whilst both categories elicited larger N170 than faces in other art styles (post-impressionism, expressionism, and cubism), with a gradation in brain activity. The present evidence suggest that visual processing may become finer grained the more the realistic nature of the face. Despite behavioral equivalence, the neural mechanisms for holistic processing of natural faces and faces in diverse art styles are not equivalent.


[Synthesis, spectra, nonlinear optical properties and theoretical calculations of metal complexes containing phenothiazine ligand].
A new ligand, S-benzyl-(-N-[10-ethylphenothiazinyl-3yl]-methylene] dithiocarbazate (abbreviated as HL), and its complexes ML2 (M=Co and Hg) have been synthesized and fully characterized by elemental analyses, EI-MS, 1H NMR, IR, UV-Vis spectra, and photoluminescence measurement. All of the compounds emit an olivine color in DMF solution. The emission maximum (lambdamax(em)), and fluorescence quantum (phif) of each compound were measured. Nonlinear Optical properties of the HL and ML2 were studied by z-scan technique. Nonlinear absorption coefficient beta were measured to be 0.71, 0.19 and 0.395 cm x GW(-1). Theoretical calculations (RHF/PM3) were consistent with the experimental results.


Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1.
The contribution of neuronal dysfunction to neurodegeneration is studied in a mouse model of spinocerebellar ataxia type 1 (SCA1) displaying impaired motor performance ahead of loss or atrophy of cerebellar Purkinje cells. Presymptomatic SCA1 mice show a reduction in the firing rate of Purkinje cells (both in vivo and in slices) associated with a reduction in the efficiency of the main glutamatergic synapse onto Purkinje cells and with increased A-type potassium current. The A-type potassium channel Kv4.3 appears to be internalized in response to glutamatergic stimulation in Purkinje cells and accumulates in presymptomatic SCA1 mice. SCA1 mice are treated with aminopyridines, acting as potassium channel blockers to test whether the treatment could improve neuronal dysfunction, motor behavior, and neurodegeneration. In acutely treated young SCA1 mice, aminopyridines normalize the firing rate of Purkinje cells and the motor behavior of the animals. In chronically treated old SCA1 mice, 3,4-diaminopyridine improves the firing rate of Purkinje cells, the motor behavior of the animals, and partially protects against cell atrophy. Chronic treatment with 3,4-diaminopyridine is associated with increased cerebellar levels of BDNF, suggesting that partial protection against atrophy of Purkinje cells is possibly provided by an increased production of growth factors secondary to the reincrease in electrical activity. Our data suggest that aminopyridines might have symptomatic and/or neuroprotective beneficial effects in SCA1, that reduction in the firing rate of Purkinje cells can cause cerebellar ataxia, and that treatment of early neuronal dysfunction is relevant in neurodegenerative disorders such as SCA1.


[Basal insulin glargine using a basal-bolus regimen in a common clinical practice: observational, non-interventional, multicenter, national project LINDA (Lantus in daily practice - safety and efficacy in basal bolus regimen)].
To evaluate the safety and efficacy of basal insulin glargine using a basal-bolus regimen in a common clinical practice setting in the Czech Republic. The LINDA project was a non-interventional, multicenter (n = 255), national, observational project. A total of 4,998 patients with Type 1 and 2 diabetes mellitus (T1DM, T2DM) with predominantly insulin therapy (99,7 %), after switch on insulin glargine at basal-bolus regimen, were enrolled in this project. The patients were followed up for 6 months after initiation of the therapy with insulin glargine. The primary objective of the project was to investigate the incidence of severe hypoglycemic episodes during the treatment with basal insulin analogue glargine (Lantus®) in a common clinical practice setting. The se-condary endpoints were changes in glycosylated hemoglobin (HbA1c) levels, fasting plasma glucose (FPG), body weight, insulin dose, change of number of hypoglycemic episodes in comparison the previous therapy and the frequency of adverse effects. Severe hypoglycaemia were observed during treatment with insulin glargine at 0.8 % patients. When comparing the incidence of hypoglycemia with the previous therapy, we demonstrated a clinically and statistically significant reduction in their frequencies. The percentage of patients with hypoglycemic episodes (17.6 %), severe hypoglycemia (0.8 %) and severe nocturnal hypoglycemia (0.3 %) over the last month of treatment with insulin glargine using the basal-bolus regimen was consistently lower compared to the last month of treatment before initiation of this therapy (42.5 %, 17.6 %, and 13.8 % of the patients, respectively). In patients with T1DM, the incidence of hypoglycemia decreased from 37.80 ± 15.95 episodes/patient/year to 8.76 ± 4.38 epi-sodes/patient/year (p < 0.001) for all hypoglycemic episodes; from 5.64 ± 3.27 episodes/patient/year to 0.0396 ± 0.012 episodes/patient/year (p < 0.001) for severe hypoglycemia; and from 3.84 ± 2.04 episodes/patient/year to 0.0096 ± 0.003 episodes/patient/year (p < 0.001) for severe nocturnal hypoglycemia. In patients with T2DM, the incidence of hypoglycemia decreased from 12.48 ± 7.57 episodes/patient/year to 1.68 ± 0.78 episodes/patient/year (p < 0.001) for all hypoglycemic episodes; from 2.04 ± 0.94 episodes/patient/year to 0.0132 ± 0.005 episodes/patient/year (p < 0.001) for severe hypoglycemia; and from 1.32 ± 0.77 episodes/patient/year to 0.0048 ± 0.0008 episodes/patient/year (p < 0.001) for severe nocturnal hypoglycemia. A statistically significant improvement in the metabolic control was demonstrated when using insulin glargine. The glycated hemoglobin (HbA1c) decreased from 7.74 ± 1.71 % to 6.43 ± 1.39 % ( -1.31 ± 0.32 %, p < 0.001) in patients with T1DM, and from 8.13 ± 1.56 % to 6.72 ± 1.40 % ( -1.41 ± 0.28 %, p < 0.001) in patients with T2DM. A statistically significant (p < 0.001) increase in the number of patients with HbA1c < 5.4 % was further demonstrated. The decrease in fasting blood glucose (FBG) and 6-point blood sugar profile was also statistically significant in both types of diabetes (p < 0.001). Changes in therapy and subsequent treatment with insulin glargine were perceived positively by both physicians and patients. In the common clinical practice setting, the initiation of treatment with insulin glargine using the basal-bolus regime in patients with previous insulin therapy resulted in a reduction in the incidence of hypoglycemic events, including severe hypoglycemia and severe nocturnal hypoglycemia, and improved metabolic control in patients with diabetes (reduced glycated hemoglobin, fasting glucose values and 6-point blood glucose profile). Greater satisfaction with the current treatment was reported by both patients and physicians.Key words: basal-bolus regimen - diabetes mellitus - insulin glargine - observational project.


25-Hydroxyvitamin D deficiency and inflammation and their association with hemoglobin levels in chronic kidney disease.
There is limited information about the association of anemia with 25-hydroxyvitamin D [25(OH)D] deficiency and inflammation in the setting of decreased kidney function in the general population. We examined the association that anemia has with 25(OH)D deficiency and inflammation among 16,301 participants in the Third National Health and Nutrition Examination Survey (NHANES III). Measures of kidney function were estimated glomerular filtration rate (GFR) by using the Modification of Diet in Renal Disease equation. The age-adjusted prevalence of anemia (hemoglobin <12 g/dl) at an estimated GFR of 59-30 ml/min/1.73 m(2) was 17% increasing to 56% for those participants with an estimated GFR <30 ml/min/1.73 m(2), while the age-adjusted prevalence of elevated C-reactive protein (CRP >0.21 mg/dl) and reduced 25(OH)D (<20 ng/ml) was 50 and 30%, respectively. After adjusting for demographics, comorbidities and laboratory results, 25(OH)D <20 ng/ml (OR: 1.17; 95% CI: 1.03-1.32; p = 0.014) and log CRP (OR: 3.63; 95% CI: 2.4-5.48 per unit increase of log CRP; p < 0.0001) were associated with hemoglobin levels <12 g/dl. This study provides evidence that lower 25(OH)D and higher CRP levels are independently associated with lower hemoglobin concentrations in kidney disease subjects not requiring dialysis.


Acute regional enteritis.
Severe melena is a rare complication of acute regional enteritis. The hemorrhage is more severe when the large intestine is also involved. The difference betwee "real" acute regional enteritis and exacerbations of regional enteritis lies in their pathological appearance, development and complications.


Evolution of pleiotropy: epistatic interaction pattern supports a mechanistic model underlying variation in genotype-phenotype map.
The genotype-phenotype (GP) map consists of developmental and physiological mechanisms mapping genetic onto phenotypic variation. It determines the distribution of heritable phenotypic variance on which selection can act. Comparative studies of morphology as well as of gene regulatory networks show that the GP map itself evolves, yet little is known about the actual evolutionary mechanisms involved. The study of such mechanisms requires exploring the variation in GP maps at the population level, which presently is easier to quantify by statistical genetic methods rather than by regulatory network structures. We focus on the evolution of pleiotropy, a major structural aspect of the GP map. Pleiotropic genes affect multiple traits and underlie genetic covariance between traits, often causing evolutionary constraints. Previous quantitative genetic studies have demonstrated population-level variation in pleiotropy in the form of loci, at which genotypes differ in the genetic covariation between traits. This variation can potentially fuel evolution of the GP map under selection and/or drift. Here, we propose a developmental mechanism underlying population genetic variation in covariance and test its predictions. Specifically, the mechanism predicts that the loci identified as responsible for genetic variation in pleiotropy are involved in trait-specific epistatic interactions. We test this prediction for loci affecting allometric relationships between traits in an advanced intercross between inbred mouse strains. The results consistently support the prediction. We further find a high degree of sign epistasis in these interactions, which we interpret as an indication of adaptive gene complexes within the diverged parental lines.


Female tubal sterilization: the time has come to routinely consider removal.
Female sterilization, one of the most effective forms of pregnancy prevention, can be performed remote from pregnancy (interval sterilization) or around the time of delivery. Modern methods for sterilization include tubal interruption, salpingectomy, and transcervical sterilization. Tubal interruption has been the primary method for interval sterilization for decades, developing as a means of rapid intra-abdominal laparoscopic surgery at a time when instrumentation and operating systems were less sophisticated than today. New evidence that the most common ovarian cancer, serous adenocarcinoma, frequently may start in the Fallopian tube, has increased research and clinical use of salpingectomy as a preferred method for sterilization. With studies showing that the surgical risks with tubal interruption and salpingectomy are likely equivalent, even when performed at cesarean delivery, the rationale seems to be in place to change our clinical practice. However, we should ask why this revelation has not occurred sooner, even though surgical techniques have advanced and salpingectomy, unlike tubal occlusion or hysteroscopic sterilization, does not leave patients at risk for future intrauterine or ectopic pregnancy. We should not have started thinking about salpingectomy for female sterilization only once a decrease in ovarian cancer risk became part of the equation. Providers' failure to offer this option means that women and their true desires were not part of the conversation. If we had included the patient in the discussion, perhaps the higher efficacy of salpingectomy would have been what women desired all along.


ADIPONECTIN AS A POTENTIAL BIOMARKER OF LOW BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN WITH METABOLIC SYNDROME.
Adiponectin is an abundant adipokine, which has antiinflammatory, anti-atherosclerotic and vasoprotective actions, and potential antiresorptive effects on bone metabolism. It seems to be directly involved in the improvement and control of energy homeostasis, protecting bone health and predicting osteoporotic fracture risk. To examine the relationship between adiponectin level and bone mineral density (BMD) in post-menopausal women with metabolic syndrome (MetS) and low BMD, and to estimate the prognostic significance of adiponectin in osteoporosis. Clinical-laboratory cross-sectional study including 120 middle-aged and elder women (average 69.18±7.56 years). The anthropometric parameters were measured for all examinees. Lumbar spine and hip BMD, as well as body fat percentage, were measured using a Hologic DEXA scanner. In all subjects serum adiponectin concentration was measured by ELISA method. The level of adiponectin was significantly positively correlated with BMD-total, BMD of the lumbar spine and BMD of the femoral neck (r=0.618, r=0.521, r=0.567; p<0.01). Levels of adiponectin and BMD are significantly lower in post-menopausal women with MetS and osteoporosis compared to patients with osteopenia (856.87±453.43 vs. 1287.32±405.21 pg/mL, p<0.01; BMD, p<0.05), and the highest values in healthy examinees. A cut-off value of adiponectin level for osteoporosis/osteopenia was 1076.22/1392.74 pg/mL. Post-menopausal women with MetS have significantly lower adiponectin level and low BMD compared to healthy examinees. Adiponectin may be an early, significant and independent predictor of developing osteoporosis in women with MetS, especially in post-menopausal period.


Enzyme specificity in the metabolic activation of N-nitrosodimethylamine to a mutagen for Chinese hamster V79 cells.
In order to elucidate the mechanism of the metabolic activation of N-nitrosodimethylamine (NDMA), the relationship between NDMA demethylase (NDMAd) and NDMA mutagenicity in Chinese hamster V79 cells was investigated. The microsome-mediated activation system produced NDMA mutagenicity similar to the S9-mediated activation system, suggesting that microsomes are solely responsible for the activation process. Pretreatment of rats with ethanol- or acetone-induced microsomal NDMAd activity, and such treatment also enhanced microsome-mediated NDMA mutagenicity 6-7-fold. The patterns of NDMA activation by ethanol- and acetone-induced microsomes differed distinctly from that by phenobarbital-induced microsomes for both NDMAd and the mutagenicity. The former type of microsomes had a low Km for NDMA, but the latter appeared to have very high Km values, and NDMAd was highly positively related to NDMA mutagenicity. Purified cytochrome P-450 isozymes from acetone- and phenobarbital-induced microsomes, P-450ac and P-450b, respectively, were effective for the activation of NDMA to a mutagen in a reconstituted monooxygenase system. In parallel fashion to NDMAd activity, P-450ac was effective at low substrate concentrations, whereas P-450b exhibited appreciable activity only at high NDMA concentrations. The results demonstrate clearly that NDMAd, which is effectively catalyzed by a specific P-450 isozyme inducible by compounds such as ethanol, acetone, and isopropanol, is primarily responsible for the activation of NDMA to a mutagen.


Spatial distribution of neurons innervated by chandelier cells.
Chandelier (or axo-axonic) cells are a distinct group of GABAergic interneurons that innervate the axon initial segments of pyramidal cells and are thus thought to have an important role in controlling the activity of cortical circuits. To examine the circuit connectivity of chandelier cells (ChCs), we made use of a genetic targeting strategy to label neocortical ChCs in upper layers of juvenile mouse neocortex. We filled individual ChCs with biocytin in living brain slices and reconstructed their axonal arbors from serial semi-thin sections. We also reconstructed the cell somata of pyramidal neurons that were located inside the ChC axonal trees and determined the percentage of pyramidal neurons whose axon initial segments were innervated by ChC terminals. We found that the total percentage of pyramidal neurons that were innervated by a single labeled ChC was 18-22 %. Sholl analysis showed that this percentage peaked at 22-35 % for distances between 30 and 60 µm from the ChC soma, decreasing to lower percentages with increasing distances. We also studied the three-dimensional spatial distribution of the innervated neurons inside the ChC axonal arbor using spatial statistical analysis tools. We found that innervated pyramidal neurons are not distributed at random, but show a clustered distribution, with pockets where almost all cells are innervated and other regions within the ChC axonal tree that receive little or no innervation. Thus, individual ChCs may exert a strong, widespread influence on their local pyramidal neighbors in a spatially heterogeneous fashion.


Gastric ulcer healing with ranitidine and cimetidine. A multicentre study.
A single-blind study of 339 patients in 19 centres compared the efficacy and tolerance of ranitidine in treating endoscopically confirmed gastric ulcers. Ranitidine (150 mg twice daily) was compared with cimetidine (1 g daily in divided doses) over 4 weeks, followed by a second 4-week treatment for any patient whose ulcer was not healed. In 292 patients who completed the study, endoscopy showed healing in 69% of patients receiving ranitidine and 59% receiving cimetidine after 4 weeks, and 90% and 88%, respectively, by 8 weeks. These results were not significantly different, and, similarly, healing rates for different ulcer sites did not differ. There were no serious adverse drug reactions during the study. Ranitidine is an effective and safe treatment for healing gastric ulcers, with a tendency to produce a faster healing rate than cimetidine during the first 4 weeks of treatment.


[The inclusion of new techniques of chromosome analysis has improved the cytogenetic profile of Turner syndrome].
To evaluate the effect of the improvement of chromosome analysis on the cytogenetic findings of Turner syndrome (TS) patients. Retrospective study of the results of the karyotypes of 260 patients with TS, regarding banding techniques, number of cells analyzed and results of investigation of Y-chromosome sequences. According to karyotype, divided in 45,X; sex chromosome mosaicism without Y; structural aberrations of sex chromosomes with or without mosaicism; sex chromosome mosaicism with Y. 45,X was the most frequent karyotype (108), followed by structural aberrations (88) and mosaics (58 without Y and 6 with Y). Introduction of banding techniques and increase in the number of cells analyzed resulted in progressive decrease of 45,X karyotype and increase of structural aberrations. The study of Y-chromosome sequences was performed in 96 cases of which 10 resulted positive. Improvement of chromosome analysis over the years has modified the cytogenetic profile of TS.


Complete surgical resection and short-term survival in acute invasive fungal rhinosinusitis.
Acute invasive fungal rhinosinusitis (AIFR) is a fulminant fungal infection seen in patients who are immunocompromised. Due to its rarity, there is little evidence regarding the appropriate antifungal treatment regimen, especially the degree of surgical intervention. To assess factors that impact short-term survival in AIFR as defined by survival to hospital discharge and to develop a staging system to predict survival and complete surgical resection. Fifty-four patients with histopathologically diagnosed AIFR who met inclusion criteria were identified between 1984 and 2014. Patient characteristics, disease extent, treatment modality, and short-term survival data were collected. Univariate analysis was performed to assess for factors associated with survival and increased likelihood of surgical resection. Of 52 patients with adequate documentation, 36 (69.2%) survived their hospital stay. Complete surgical resection was the only factor associated with improved survival (survival, 95.5%; p < 0.01). A surgical staging system was proposed to guide probability of complete resection and overall prognosis, with stage I disease limited to the nasal cavity, stage II involving the paranasal sinuses, stage III involving the orbit, and stage IV with skull base or intracranial extension. The χ2 analyses showed a decreased likelihood of complete surgical resection with stage III or IV disease compared with stage I (resection, 90.9%) (stage III resection, 37.5% [p = 0.01]; stage IV resection, 16.7% [p = 0.002]). There was a decreased likelihood of survival associated with increasing disease stage compared with stage I (survival, 100%) (stage II survival, 60% [p = 0.009]; stage III survival, 62.5% [p = 0.02]; stage IV survival, 54.6%, [p = 0.006]). Although further studies are needed to define specific treatment protocols, analysis of these data indicated that endoscopic sinus surgery with the goal of complete surgical resection may provide the best survival outcomes in select patients when complete surgical resection can be performed. Our staging system represents the first attempt to predict surgical success and prognosis in patients with AIFR.


Complete Metabolic Response on Interim 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict Long-Term Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy.
This study aims to investigate the prognostic role of complete metabolic response (CMR) on interim 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in patients with breast cancer (BC) receiving neoadjuvant chemotherapy (NAC) according to tumor subtypes and PET timing. Eighty-six consecutive patients with stage II/III BC who received PET/CT during or following NAC were included. Time-dependent receiver operating characteristic analysis and Kaplan-Meier analysis were used to determine correlation between metabolic parameters and survival outcomes. The median follow-up duration was 71 months. Maximum standardized uptake value (SUVmax) on an interim PET/CT independently correlated with survival by multivariate analysis (overall survival [OS]: hazard ratio: 1.139, 95% confidence interval: 1.058-1.226, p = .001). By taking PET timing into account, best association of SUVmax with survival was obtained on PET after two to three cycles of NAC (area under the curve [AUC]: 0.941 at 1 year after initiation of NAC) and PET after four to five (AUC: 0.871 at 4 years), while PET after six to eight cycles of NAC had less prognostic value. CMR was obtained in 62% of patients (23/37) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) BC, in 48% (12/25) triple-negative BC (TNBC), and in 75% (18/24) HER2-positive (HER2+) tumors. Patients with CMR on an early-mid PET had 5-year OS rates of 92% for ER+/HER2- tumors and 80% for TNBC, respectively. Among HER2+ subtype, 89% patients (16/18) with CMR had no relapse. CMR indicated a significantly better outcome in BC and may serve as a favorable imaging prognosticator. The Oncologist 2017;22:526-534 IMPLICATIONS FOR PRACTICE: This study shows a significantly better outcome for breast cancer (BC) patients who achieved complete metabolic response (CMR) on 18F-fluorodeoxyglucose emission tomography/computed tomography (PET/CT) during neoadjuvant chemotherapy, especially for hormone receptor-positive tumors and triple negative BC. Moreover, PET/CT performed during an early- or mid-course neoadjuvant therapy is more predictive for long-term survival outcome than a late PET/CT. These findings support that CMR may serve as a favorable imaging prognosticator for BC and has potential for application to daily clinical practice.


Presence and partitioning properties of the flame retardants pentabromotoluene, pentabromoethylbenzene and hexabromobenzene near suspected source zones in Norway.
The brominated flame retardants (BFRs), pentabromotoluene (PBT), pentabromoethylbenzene (PBEB) and hexabromobenzene (HBB), exhibit physical-chemical properties similar to other persistent organic pollutants, and have been in use as flame retardants for several decades. Data on these BFRs in diverse environmental samples can be found in studies from the 1970s and 1980s, as well as in recent years, though very little in the years in between. Due to a lack of data, the cause for the apparent re-emergence of these BFRs in recent studies is unclear, and could reflect changes in production volumes, accumulation of transformation products from BFR precursors, improved analytical techniques or simply a re-emergence in concern. Very little data are available on their environmentally relevant partitioning properties, which could help to explain the occurrence and fate of these BFRs. In this study we analysed for the presence of HBB, PBT, and PBEB in diverse environmental samples from potential Norwegian BFR source zones. Additionally, environmental partitioning properties of these BFRs as well as brominated benzenes were estimated and validated using experimental data for brominated benzenes. Of the three BFRs, HBB was identified in detectable quantities at most source zones, PBEB only near a metal recycling factory, and PBT only in a few additional locations from where PBEB was detected. Data from this study show that HBB is likely widely distributed, as verified both by chemical analysis and estimated properties. Measured HBB levels in wastewater treatment plants indicate that the treatment practices used in the study locations are not effective at lowering HBB levels, perhaps due to association with low density suspended solids (e.g. microplastics).


Gaps in science and evidence-based interventions to respond to Intimate Partner Violence among Black gay and bisexual men in the U.S.: A Call for An Intersectional Social Justice Approach.
Intimate Partner Violence (IPV) is a prevalent, but underrecognized issue among sexual minorities (SM) broadly, but especially among Black Gay and Bisexual Men (BGBM). Over the last several years, acts of IPV among BGBM made national news, drawing attention to the unique ways that IPV plays out within this particular population. Yet, little research has examined the intersections between race and sexuality among BGBM, the lack of culturally responsive IPV services, their support needs, or the barriers that BGBM face when seeking IPV related services. When examined closely, the field of IPV has traditionally focused on cisgender heterosexual white woman as victims and cisgender white men as perpetrators, which has historically impacted the availability and quality of IPV services for other populations. This narrative critique of the IPV movement calls for an intersectional social justice and health equity approach to address the unique and intersectional needs of BGBM who experience IPV. By centering the intersectional needs of BGBM and the role that racism, homophobia, and heteronormative has played in shaping IPV-related services, this article challenges the IPV field to advance a social justice orientation in order to address the unmet needs of BGBM who experience IPV.


Use and validation of a survey tool to measure the perceived effectiveness of insulin prescribing safety interventions in UK hospitals.
To describe the use and validation of a survey tool to elicit the opinion of hospital pharmacists and medicines safety officers in the UK regarding the perceived effectiveness of strategies to improve insulin prescribing safety in hospitals. One respondent from each participating organization completed the survey on behalf of the main acute hospital in their trust (n = 92). A five-point Likert scale was used to determine opinion on how effective 22 different interventions were at promoting insulin safety at the respondent's trust. The tool, the Perception of Effectiveness of Prescribing Safety Interventions for Insulin (PEPSII) questionnaire, underwent content validity testing. The reliability was estimated using Cronbach's alpha (α). The PEPSII questionnaire demonstrated good reliability (α = 0.867). Outreach team review and mandatory insulin education were the highest-scoring interventions; the insulin passport was amongst the lowest scoring interventions. Most interventions were considered more effective by trusts using them compared to those who didn't, except for self-administration policies, electronic prescribing and the insulin passport. The perceived effectiveness of a variety of insulin prescribing safety strategies in UK hospitals was described by leveraging a purposely developed survey tool. The results describe current levels of support for recommended interventions, and may facilitate the direction of both local and national insulin prescribing safety improvement efforts.


The pleiotropic CymR regulator of Staphylococcus aureus plays an important role in virulence and stress response.
We have characterized a novel pleiotropic role for CymR, the master regulator of cysteine metabolism. We show here that CymR plays an important role both in stress response and virulence of Staphylococcus aureus. Genes involved in detoxification processes, including oxidative stress response and metal ion homeostasis, were differentially expressed in a DeltacymR mutant. Deletion of cymR resulted in increased sensitivity to hydrogen peroxide-, disulfide-, tellurite- and copper-induced stresses. Estimation of metabolite pools suggests that this heightened sensitivity could be the result of profound metabolic changes in the DeltacymR mutant, with an increase in the intracellular cysteine pool and hydrogen sulfide formation. Since resistance to oxidative stress within the host organism is important for pathogen survival, we investigated the role of CymR during the infectious process. Our results indicate that the deletion of cymR promotes survival of S. aureus inside macrophages, whereas virulence of the DeltacymR mutant is highly impaired in mice. These data indicate that CymR plays a major role in virulence and adaptation of S. aureus for survival within the host.


Longitudinal changes in magnetic resonance imaging biomarkers of the gluteal muscle groups and functional ability in Duchenne muscular dystrophy: a 12-month cohort study.
Quantitative magnetic resonance imaging (MRI) is considered an objective biomarker of Duchenne muscular dystrophy (DMD), but the longitudinal progression of MRI biomarkers in gluteal muscle groups and their predictive value for future motor function have not been described. To explore MRI biomarkers of the gluteal muscle groups as predictors of motor function decline in DMD by characterizing the progression over 12 months. A total of 112 participants with DMD were enrolled and underwent MRI examination of the gluteal muscles to determine fat fraction and longitudinal relaxation time (T1). Investigations were based on gluteal muscle groups including flexors, extensors, adductors, and abductors. The North Star Ambulatory Assessment and timed functional tests were performed. All participants returned for follow-up at an average of 12 months and were divided into two subgroups (functional stability/decline groups) based on changes in timed functional tests. Univariable and multivariable logistic regression methods were used to explore the risk factors associated with future motor function decline. For the functional decline group, all T1 values decreased, while fat fraction values increased significantly over 12 months (P<0.05). For the functional stability group, only the fat fraction of the flexors and abductors increased significantly over 12 months (P<0.05). The baseline T1 value was positively correlated with North Star Ambulatory Assessment and negatively correlated with timed functional tests at the 12-month follow-up (P<0.001), while the baseline fat fraction value was negatively correlated with North Star Ambulatory Assessment and positively correlated with timed functional tests at the 12-month follow-up (P<0.001). Multivariate regression showed that increased fat fraction of the abductors was associated with future motor function decline (model 1: odds ratio [OR]=1.104, 95% confidence interval [CI]: 1.026~1.187, P=0.008; model 2: OR=1.085, 95% CI: 1.013~1.161, P=0.019), with an area under the curve of 0.874. Fat fraction of the abductors is a powerful predictor of future motor functional decline in DMD patients at 12 months, underscoring the importance of focusing early on this parameter in patients with DMD.


Impact of positive legionella urinary antigen test on patient management and improvement of antibiotic use.
To assess the incidence of legionella infection over a 27 month period at a large university hospital. The present retrospective cohort study enrolled patients with legionellosis, defined as those presenting a positive urinary antigen for legionella together with a medical history, clinical findings, and radiological findings consistent with pneumonia. These patients were evaluated to determine the relation between their test results and changes in treatment modalities. A control group of patients with pneumonia but a negative urinary antigen test for legionella were also analysed. Twenty seven of 792 assessed patients tested positive for legionella. In 22 of these patients, legionella active antibiotics were administered empirically. In seven patients, the test results prompted a legionella specific treatment, whereas in 12 cases, non-specific antibiotics were stopped within 24 hours. Overall, treatment was altered in more than half of the patients as a result of the test results. The urinary antigen may have a direct impact on clinical management of pulmonary legionellosis. However, patient comorbidities and individual clinical judgment are still important for determining the best treatment to be given in each individual case.


Burden of diarrhea and antibiotic use among children in low-resource settings preventable by Shigella vaccination: A simulation study.
Shigella is a leading cause of diarrhea and dysentery in children in low-resource settings, which is frequently treated with antibiotics. The primary goal of a Shigella vaccine would be to reduce mortality and morbidity associated with Shigella diarrhea. However, ancillary benefits could include reducing antibiotic use and antibiotic exposures for bystander pathogens carried at the time of treatment, specifically for fluoroquinolones and macrolides (F/M), which are the recommended drug classes to treat dysentery. The aim of the study was to quantify the reduction in Shigella attributable diarrhea, all diarrhea, and antibiotic use in the first 2 years of life that could be prevented by a Shigella vaccine. We used data from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, a birth cohort study that followed 1,715 children with twice weekly surveillance for enteric infections, illnesses, and antibiotic use for the first 2 years of life from November 2009 to February 2014 at 8 sites. We estimated the impact of 2 one-dose (6 or 9 months) and 3 two-dose (6 and 9 months, 9 and 12 months, and 12 and 15 months) Shigella vaccines on diarrheal episodes, overall antibiotic use, and F/M use. Further, we considered additional protection through indirect and boosting effects. We used Monte Carlo simulations to estimate the absolute and relative reductions in the incidence of diarrhea and antibiotic use comparing each vaccination scenario to no vaccination. We analyzed 9,392 diarrhea episodes and 15,697 antibiotic courses among 1,715 children in the MAL-ED birth cohort study. There were 273.8 diarrhea episodes, 30.6 shigellosis episodes, and 457.6 antibiotic courses per 100 child-years. A Shigella vaccine with a mean vaccine efficacy of 60% against severe disease given at 9 and 12 months prevented 10.6 (95% CI [9.5, 11.5]) Shigella diarrhea episodes of any severity per 100 child-years (relative 34.5% reduction), 3.0 (95% CI [2.5, 3.5]) F/M courses for Shigella treatment per 100 child-years (relative 35.8% reduction), and 5.6 (95% CI [5.0, 6.3]) antibiotic courses of any drug class for Shigella treatment per 100 child-years (relative 34.5% reduction). This translated to a relative 3.8% reduction in all diarrhea, a relative 2.8% reduction in all F/M courses, a relative 3.1% reduction in F/M exposures to bystander pathogens, and a relative 0.9% reduction in all antibiotic courses. These results reflect Shigella incidence and antibiotic use patterns at the 8 MAL-ED sites and may not be generalizable to all low-resource settings. Our simulation results suggest that a Shigella vaccine meeting WHO targets for efficacy could prevent about a third of Shigella diarrhea episodes, antibiotic use to treat shigellosis, and bystander exposures due to shigellosis treatment. However, the reductions in overall diarrhea episodes and antibiotic use are expected to be modest (<5%).


Cognitive functions and psychopathological symptoms in early-onset schizophrenia.
Type and extent of objectively tested cognitive impairments (attention, verbal fluency, nonverbal reasoning) and their association with self-ratings (Paranoia Depression Scale; Frankfurt Complaint Questionnaire) and clinical assessments (Brief Psychiatric Rating Scale, Scales for the Assessment of Positive Symptoms and Negative Symptoms) of psychopathological symptoms were studied in a sample of 74 adolescents primarily suffering from chronic schizophrenia (DSM-III-R; mean duration of illness = 3.4 years), including 15 patients with a very early onset (< 14 years). Special consideration was given to the differentiation between positive and negative symptoms. In cross-sectional analyses, the schizophrenic adolescents were remarkably impaired in both cognitive functions (attention, reasoning) and psychopathological measures (BPRS, SANS, SAPS). However, factor analysis yielded orthogonal factors for cognitive and psychopathological parameters, and canonical correlation analyses did not find a significant correlation between these two areas. As the degree of objectively measured cognitive impairment in chronic schizophrenic adolescents cannot be predicted by the severity of individual psychopathological symptoms, a multidimensional evaluation of the symptomatology seems to be appropriate. Moreover, premorbid disturbances (motor and/or language developmental disorders) and onset characteristics (age, pattern, subdiagnosis), and their relationship to cognitive impairments were investigated. Premorbid disturbances were confirmed as risk factors for the subsequent occurrence of cognitive impairments.


The clinical course of acute otitis media in high-risk Australian Aboriginal children: a longitudinal study.
It is unclear why some children with acute otitis media (AOM) have poor outcomes. Our aim was to describe the clinical course of AOM and the associated bacterial nasopharyngeal colonisation in a high-risk population of Australian Aboriginal children. We examined Aboriginal children younger than eight years who had a clinical diagnosis of AOM. Pneumatic otoscopy and video-otoscopy of the tympanic membrane (TM) and tympanometry was done every weekday if possible. We followed children for either two weeks (AOM without perforation), or three weeks (AOM with perforation), or for longer periods if the infection persisted. Nasopharyngeal swabs were taken at study entry and then weekly. We enrolled 31 children and conducted a total of 219 assessments. Most children had bulging of the TM or recent middle ear discharge at diagnosis. Persistent signs of suppurative OM (without ear pain) were present in most children 7 days (23/30, 77%), and 14 days (20/26, 77%) later. Episodes of AOM did not usually have a sudden onset or short duration. Six of the 14 children with fresh discharge in their ear canal had an intact or functionally intact TM. Perforation size generally remained very small (<2% of the TM). Healing followed by re-perforation was common. Ninety-three nasophyngeal swabs were taken. Most swabs cultured Streptococcus pneumoniae (82%), Haemophilus influenzae (71%), and Moraxella catarrhalis (95%); 63% of swabs cultured all three pathogens. In this high-risk population, AOM was generally painless and persistent. These infections were associated with persistent bacterial colonisation of the nasopharynx and any benefits of antibiotics were modest at best. Systematic follow up with careful examination and review of treatment are required and clinical resolution cannot be assumed.


Utilization of Corn Steep Liquor for the Production of Fairy Chemicals by Lepista sordida Mycelia.
There are various potential practical uses of fairy chemicals (FCs) in the fields of agriculture, cosmetics, and medicine; however, the production costs of FCs are very high. To enable the practical use of FCs, more efficient and inexpensive methods of culturing the mycelia of FCs-producing fungi and producing FCs need to be developed. The purpose of the present study was to determine methods of reducing the production costs of FCs and mycelia of the FCs-producing fungus Lepista sordida. We investigated the effects of four food industrial by-products, i.e., corn steep liquor (CSL), rice bran, wheat bran, and Japanese liquor lees, as nutritional additives in the liquid culture medium of the fungus. We found that CSL was more effective than the other tested additives in increasing the production of FCs and mycelia. Medium containing 1% CSL was optimal for increasing the mycelial yield while medium containing 6% CSL was optimal for increasing the production of FCs. The reason for this difference in the optimal CSL concentration was considered to be related to the stress on the mycelia caused by the amount of nutrients in the liquid medium. These results are expected to facilitate the practical use of FCs and the mycelia of FCs-producing fungi.


Rehospitalization after pediatric living-donor liver transplantation.
Although rehospitalization is one of the factors affecting quality of life after successful liver transplantation, the effects of rehospitalization have not been assessed to date. Of 40 consecutive cases of pediatric living-donor liver transplantation (LDLT) performed between April 1994 and October 2000, 28 patients with a graft survival of more than 1 year were enrolled in this study to examine rehospitalization after successful LDLT. The rate and cause of rehospitalization were analyzed retrospectively on the basis of medical records. A total of 23 of the 28 patients were rehospitalized. There were 84 episodes of rehospitalization. The mean number of rehospitalization days per episode per patient was 21.06 +/- 21.02 days. The rate of total rehospitalization days to the days after the hospitalization for LDLT was 6.56% +/- 8.73%. Rehospitalization episodes were attributable to the following: cholangitis (21.4%), viral infection (16.7%), and portal stenosis (PS) (13.1%). Rehospitalization as the result of rejection accounted for 9.5% of the episodes. The period of rehospitalization was long in the case of cholangitis (49.7 +/- 62.4 days), PS (13.8 +/- 13.4 days), and rejection (52.9 +/- 45.4 days). Although there were a lot of rehospitalization episodes as the result of viral infection subsequent to cholangitis, each rehospitalization period lasted 4.4 +/- 6.6 days. It is suggested that prevention of cholangitis and PS, which were the causes of frequent and long rehospitalization periods, would result in a reduction of rehospitalization and therefore a better quality of life after pediatric LDLT.


Spontaneous physical activity protects against fat mass gain.
It is unclear whether elevated spontaneous physical activity (SPA, very low-intensity physical activity) positively influences body composition long term. We determined whether SPA and caloric intake were differentially related to the growth curve trajectories of body weight, fat mass (FM) and fat-free mass (FFM) between obesity resistant and Sprague-Dawley rats at specific age intervals. Body composition, SPA and caloric intake were measured in selectively-bred obesity-resistant and out-bred Sprague-Dawley rats from 1 to 18 months. Data from development throughout maturation were analyzed by longitudinal growth curve modeling to determine the rate and acceleration of body weight, FM- and FFM-gain. Obesity-resistant rats had a lower rate of FM gain overall, a lower acceleration in body weight early in life, significantly greater SPA and lower cumulative caloric intake. Greater SPA in obesity-resistant rats was significantly associated with a lower rate of FM gain overall and lower acceleration in body weight early in life. Obesity resistant rats lost less FFM compared with Sprague-Dawley rats despite that obesity-resistant rats had a lower acceleration in FFM gain early in life. Obesity-resistant rats gained less FM and more FFM per gram body weight and were less energy efficient than Sprague-Dawley rats. Caloric intake was significantly and positively related to body weight, FM and FFM gain in both groups. Circadian patterns of caloric intake were group and age-dependent. Our data demonstrate that elevated and sustained SPA during development and over the lifespan are related to the reduced the rate of FM gain and may preserve FFM. These data support the idea that SPA level is a reproducible marker that reliably predicts propensity for obesity in rats, and that elevated levels of SPA maintained during the lifespan promote a lean phenotype.


Lower levels of soluble β-amyloid precursor protein, but not β-amyloid, in the frontal cortex in schizophrenia.
We identified a sub-group (25%) of people with schizophrenia (muscarinic receptor deficit schizophrenia (MRDS)) that are characterised because of markedly lower levels of cortical muscarinic M1 receptors (CHRM1) compared to most people with the disorder (non-MRDS). Notably, bioinformatic analyses of our cortical gene expression data shows a disturbance in the homeostasis of a biochemical pathway that regulates levels of CHRM1. A step in this pathway is the processing of β-amyloid precursor protein (APP) and therefore we postulated there would be altered levels of APP in the frontal cortex from people with MRDS. Here we measure levels of CHRM1 using [3H]pirenzepine binding, soluble APP (sAPP) using Western blotting and amyloid beta peptides (Aβ1-40 and Aβ1-42) using ELISA in the frontal cortex (Brodmann's area 6: BA 6; MRDS = 14, non-MRDS = 14, controls = 14). We confirmed the MRDS cohort in this study had the expected low levels of [3H]pirenzepine binding. In addition, we showed that people with schizophrenia, independent of their sub-group status, had lower levels of sAPP compared to controls but did not have altered levels of Aβ1-40 or Aβ1-42. In conclusion, whilst changes in sAPP are not restricted to MRDS our data could indicate a role of APP, which is important in axonal and synaptic pruning, in the molecular pathology of the syndrome of schizophrenia.


Incidence and risk factors of thromboembolism in systemic lupus erythematosus: a comparison of three ethnic groups.
To compare the incidence and risk factors for thromboembolic events in systemic lupus erythematosus (SLE) patients of different ethnic backgrounds. SLE patients who were newly diagnosed or were referred within 6 months of diagnosis between 1996 and 2002 were prospectively followed up for the occurrence of thromboembolic events. Cumulative hazard and risk factors for thromboembolism were evaluated and compared among patients of different ethnic origins. We studied 625 patients who fulfilled the American College of Rheumatology criteria for SLE (89% women): 258 Chinese, 140 African Americans, and 227 Caucasians. The mean +/- SD age at SLE diagnosis was 35.7 +/- 14 years. After a followup of 3,094 patient-years, 48 arterial events and 40 venous events occurred in 83 patients. The overall incidence of arterial and venous thromboembolism was 16/1,000 patient-years and 13/1,000 patient-years, respectively. The cumulative hazard of arterial events at 60 months after the diagnosis of SLE was 8.5%, 8.1%, and 5.1% for the Chinese, African Americans, and Caucasians, respectively. The corresponding cumulative risk of venous events was 3.7%, 6.6%, and 10.3%, respectively (P = 0.008 for Chinese versus Caucasians, by log rank test). Smoking, obesity, antiphospholipid antibodies, and use of antimalarial agents and exogenous estrogens were less frequent in the Chinese patients. In Cox regression models, low levels of high-density lipoprotein (HDL) cholesterol, Chinese ethnicity, oral ulcers, and serositis predicted arterial events, whereas male sex, low levels of HDL cholesterol, antiphospholipid antibodies, non-Chinese ethnicity, obesity, renal disease, and hemolytic anemia predicted venous events. There are ethnic differences in the incidence of arterial and venous thromboembolism in patients with SLE that cannot be fully explained by the clinical factors studied. Further evaluation of other genetic and immunologic factors is warranted.


[Novel CHST6 compound heterozygous mutations cause macular corneal dystrophy in a Chinese family].
The aim of this study was to identify mutations of CHST6 gene in a Chinese family with macular corneal dystrophy (MCD) and to investigate the histopathological changes of MCD. Corneal button of the proband was obtained from penetrating keratoplasty for the treatment of severe corneal dystrophy. The sections and ultrathin sections of this specimen were examined under light microscope and transmission electron microscope (TEM). Genomic DNA was extracted from leukocytes in peripheral blood from the family members. The coding region of CHST6 was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by direct sequencing and restriction enzyme digestion. Histochemical study revealed positive results of colloidal iron stain. TEM revealed enlargement of smooth endoplasmic reticulum and the presence of intracytoplasmic vacuoles. Two mutations, Q298X Y358H, were identified in exon 3 of CHST6. Three patients were compound heterozygotes of these two mutations. The C892T transversion occurred at codon 298 turned the codon of glutamine to a stop codon; the T1072C transversion occurred at codon 358 caused a missense mutation, tyrosine to histidine. All six unaffected family members were heterozygotes. These two mutations were not detected in any of the 100 control subjects. The novel compound heterozygous mutation results in loss of CHST6 function and causes the occurrence of MCD. This is the first report of this gene mutation.


Percutaneous extensor tenotomy for chronic tennis elbow using an 18G needle.
Tennis elbow is a common orthopaedic problem presenting in office orthopaedics, but its exact patho-aetiology has not been identified to date. It is treated operatively when conservative measures including multiple local steroid injections are not helpful to the patients. This was a retrospective study to assess the outcome of tennis elbow patients on whom percutaneous release of the common extensor origin was performed using an 18 gauge hypodermic needle. 17 patients with 21 elbows were included in the study. Data was collected by going through the patients' medical records, and follow -up by questionnaire mailed to the patient's home, to assess the outcome and patient satisfaction with the procedure. 14 of the 21 (66.7%) elbows became completely pain free. The time taken to achieve a completely pain free elbow ranged from 1 day to 3 months (average 60.3 days). Those that did not achieve a pain free elbow had a residual pain of 1.5 to 8.5 on the VAS (average 2.64). 9 elbows (42.9%) had an excellent outcome, 7(33.3%) had good, 4(19%) had satisfactory and 1(4.8%) had poor outcomes. Tennis elbow probably results from degenerative tear of common extensor origin and a percutaneous tenotomy using an 18 gauge hypodermic needle is a simple, safe, patient friendly, effective and easily reproducible method of treating it in those who require surgery and can be done as an office procedure.


Short, double elastic nailing of severely displaced distal pediatric radial fractures: A new method for stable fixation.
Short double elastic nailing is a minimal invasive, modified ESIN (elastic stable intramedullary nailing) technique for severely displaced distal radial fracture in children. The aim of this technical report is to introduce our new method and evaluate the final results of the procedure. We reviewed retrospectively 24 patients who underwent short double elastic nailing due to distal radial fractures between November 2012 and December 2015. Indications for surgery included closed, severely displaced, unstable metaphyseal or diametaphyseal fractures of the radius. The fractures were stabilized by 2 prebent short elastic titanium nails inserted from the distal side of the fracture. In cases of associated ulnar fracture, a classic anterograd ESIN nailing was also performed. Patients were mobilized immediately in a removable short splint which was removed after 1 to 2 weeks. There has been no additional splinting or casting. There were 17 males and 7 females with an average age of 9.8 years (range, 4-16 years). The right hand was involved in 16 cases and the left hand in 8 cases. The average follow-up was 17.8 months (range, 7-28 months). Of the 24 patients, 3 presented irritation of the skin, which resolved after removal of the radial nail. All the patients regained full range of motion without any complications. Our technique is an effective, safe, and easily learnable procedure for unstable fractures of the distal third of the radius. It achieves good functional and radiological results, and allows early mobilization without the need of casting. Avoiding the physeal plates, we reduce the risk of iatrogenic postoperative deformity. Further prospective and biomechanical investigations are necessary to verify our experience.


[Effect of antibiotics on the indices on nonspecific immunity].
Multiple (for 14 and 20 days) administrations of antibiotics, such as tetraolean, tetracycline and penicillin from the beginning of the animal immunization (rabbits and albino rats) with typhoid fever and candidosis vaccines inhibited activity of both the non-specific and the specific immunity.


Intentional replantation for iatrogenic perforation of the furcation: a case report.
Intentional replantation is an accepted endodontic procedure for treatment of teeth in which conventional surgical endodontic treatment is contraindicated. This article presents a rare case of intentional replantation of a mandibular molar that had severe periodontal destruction resulting from iatrogenic perforation of the furcation. A 17-month follow-up evaluation revealed an asymptomatic and functional tooth with no radiographic signs of pathosis. The favorable results obtained might be attributed to the preservation of the vitality of the periodontal ligament; the absence of damaging pressure during extraction; the minimal extraoral treatment time; the use of nonrigid splinting; and the immediate repair of the perforation during a one-visit endodontic procedure. The results obtained with this tooth may indicate the possibility of a successful surgical technique for this otherwise hopeless complication of endodontic therapy.


Preschoolers' psychosocial problems: in the eyes of the beholder? Adding teacher characteristics as determinants of discrepant parent-teacher reports.
In this study, we explored informant characteristics as determinants of parent-teacher disagreement on preschoolers' psychosocial problems. Teacher characteristics were included in the analyses, in addition to child and parent factors. Psychosocial problems of 732 4-year olds from a Norwegian community sample were assessed by parents and teachers (CBCL-TRF). Furthermore, teachers reported on their education, experience and relationship to the child. Parental stress and psychopathology were also measured. Teachers rated children considerably lower than their parents did, especially on internalizing problems. When teachers rated more child problems, this was strongly associated with conflict in the teacher-child relationship, which predicted disagreement more than other factors. The highest agreement was on boys' externalizing problems. Girls' behavior was rated much lower by teachers than boys' behavior compared to parents' ratings. Possible teacher perception biases are discussed, such as teacher-child conflict, non-identification of internalizing problems, and same-gender child preference.


The effect of oxytocin on the contractile force of human atrial trabeculae.
We performed an in vitro examination of the inotropic effect of oxytocin, chlorobutanol, and their combination to assess the effect of these drugs on the contractile force of human atrial trabeculae. Right atrial tissue samples were obtained during cardiac surgery with cardiopulmonary bypass. Trabeculae of the atrial appendage were dissected and mounted on muscle stands in a modified Krebs-Henseleit buffer bath. This isometric atrial trabecula preparation was subjected to a cumulative pharmacological protocol of either pure oxytocin, pure chlorobutanol, or a combination of the two drugs until no further change occurred in either developed force or resting force of the atrial trabeculae. A "no drug" buffer solution was used to assess the effect of time on the natural decay of the atrial preparation. The relative developed force of oxytocin plus chlorobutanol solution and pure chlorobutanol were similar in magnitude and lower than that in control experiments (P < 0.001) Pure oxytocin did not change the contractile force of atrial tissue. We conclude that pure oxytocin does not have a cardiodepressive effect in this human atrial preparation. Chlorobutanol has a negative inotropic effect, which is of a magnitude similar to a combined solution of chlorobutanol and oxytocin. Therefore, chlorobutanol added as a preservative to the commercial synthetic oxytocin solution may contribute to hypotension observed in patients after an intravenous bolus injection. We obtained specimens of heart tissue from patients undergoing cardiac surgery and conducted a laboratory study of the effects of oxytocin and its preservative (chlorobutanol) on these tissue samples. Chlorobutanol decreased the ability of the heart to contract, while as pure oxytocin had no effect. This explains why maternal blood pressure may decrease and provides impetus to produce oxytocin with another, safer preservative.


Long-Term Outcomes of Childhood Left Ventricular Noncompaction Cardiomyopathy: Results From a National Population-Based Study.
Long-term outcomes for childhood left ventricular noncompaction (LVNC) are uncertain. We examined late outcomes for children with LVNC enrolled in a national population-based study. The National Australian Childhood Cardiomyopathy Study includes all children in Australia with primary cardiomyopathy diagnosed before 10 years of age between 1987 and 1996. Outcomes for subjects with LVNC with a dilated phenotype (LVNC-D) were compared with outcomes for those with dilated cardiomyopathy. Propensity-score analysis was used for risk factor adjustment. There were 29 subjects with LVNC (9.2% of all cardiomyopathy subjects), with a mean annual incidence of newly diagnosed cases of 0.11 per 100 000 at-risk individuals. Congestive heart failure was the initial symptom in 24 of 29 subjects (83%), and 27 (93%) had LVNC-D. The median age at diagnosis was 0.3 (interquartile interval, 0.08-1.3) years. The median duration of follow-up was 6.8 (interquartile interval, 0.7-24.0) years for all subjects and 24.7 (interquartile interval, 23.3 - 27.7) years for surviving subjects. Freedom from death or transplantation was 48% (95% confidence interval [CI], 30-65) at 10 years after diagnosis and 45% (95% CI, 27-63) at 15 years. In competing-risk analysis, 21% of subjects with LVNC were alive with normal left ventricular systolic function, and 31% were alive with abnormal function at 15 years. Propensity-score matching between subjects with LVNC-D and those with dilated cardiomyopathy suggested a lower freedom from death/transplantation at 15 years after diagnosis in the subjects with LVNC-D (LVNC-D, 46% [95% CI, 26-66] versus dilated cardiomyopathy, 70% [95% CI, 42-97]; P=0.08). Using propensity-score inverse probability of treatment-weighted Cox regression, we found evidence that LVNC-D was associated with a greater risk of death or transplantation (hazard ratio, 2.3; 95% CI, 1.4-3.8; P=0.0012). Symptomatic children with LVNC usually present in early infancy with a predominant dilated phenotype. Long-term outcomes are worse than for matched children with dilated cardiomyopathy.


Construction of a highly efficient DNA nanotube sensor with peroxide-like activity.
The G-quadruplex/heme complexes are special DNA-based artificial metalloenzymes with peroxidase-like activity and are widely used in biosensing and biocatalysis. However, their peroxidase-like activity is not satisfactory. Due to the high programmability and good stability of DNA, DNA as a scaffold material is promising for enhancing the activity of artificial metalloenzymes. In this work, an effective DNA nanotube-based peroxidase was constructed using a self-assembly strategy. To improve the activity of G-quadruplex/heme complexes, a new method for the construction of G-quadruplex/heme complex arrays was proposed in a simple and inexpensive way. By designing the toes of DNA nanotubes as G-quadruplexes, G-quadruplex arrays could be formed on pure DNA nanotubes, and then the G-quadruplex arrays bind to heme to form a nanotube-supported DNAzyme termed as DNTzyme. Agarose gel electrophoresis, circular dichroism, and fluorescence microscopy were used to characterize DNTzyme. What is more, because the loading of DNAzyme on DNA nanotubes can increase their biological stability, a hydrogen peroxide detection sensor was constructed using the enhanced enzymatic activity and excellent stability of DNTzyme. The sensor could accurately and efficiently detect peroxide and show enhanced fluorescence with a detection limit of 49 nM for H2O2 and 1.4 μM for TBHP, and a color development time of about 5 min. This sensor is expected to have applications in bio-detection, biocatalysis, and drug delivery.


Cytologic comparison of the percentage of mast cells in lymph node aspirate samples from clinically normal dogs versus dogs with allergic dermatologic disease and dogs with cutaneous mast cell tumors.
OBJECTIVE To compare percentages of mast cells in lymph node (LN) aspirate samples from clinically normal dogs, dogs with allergic dermatologic disease (ADD), and dogs with cutaneous mast cell tumors (MCTs). DESIGN Prospective cross-sectional study. ANIMALS 20 healthy dogs (group 1), 20 dogs with ADD (group 2), and 20 dogs with an MCT on the head or limbs (group 3). PROCEDURES LN aspirate samples were obtained from easily accessible LNs in group 1, affected skin regions in group 2, and the likely draining LN or LNs of the MCT in group 3; the percentage of mast cells was manually determined for each LN. For group 3, LNs were cytologically categorized with a modified version of a published metastasis categorization scheme. RESULTS Median (range) percentage of mast cells in aspirate samples was 0% (0% to 0.1%) for group 1, 0.05% (0% to 0.55%) for group 2, and 0.4% (0% to 77.4%) for group 3. In group 3, 16 LNs (13 dogs) were palpably normal in size; 6 of these had evidence of possible or certain metastasis. Seven LNs (7 dogs) in group 3 were palpably enlarged, and 5 of these had evidence of certain metastasis. CONCLUSIONS AND CLINICAL RELEVANCE This study provided evidence to support the use of a uniform cytologic grading system to further define nodal metastasis in dogs with MCTs as well as estimates of the percentage of mast cells in LN aspirate samples for healthy dogs and dogs with ADD. Palpably normal LNs in dogs with cutaneous MCT may contain metastasis.


[Pedicle agenesis in the cervical spine].
Congenital absence of a cervical pedicle is rare, and because of the associated enlargement of the intervertebral foramen, may be confused with a "dumbbell" tumour. A recent observation of this anomaly has prompted this report. Based on the findings of 29 reported cases in the literature, the characteristic radiological features of the abnormality are described and the differential diagnosis as well as the clinical implications of this disorder are discussed.


Osteosarcoma in a Marfan patient with a novel premature termination codon in the FBN1 gene.
Osteosarcoma is a malignant neoplasm of mesenchymal origin that is presumed to arise from osteoblasts. Considered a rare tumor, approximately 1000 cases of osteosarcoma are diagnosed in the United States each year, and osteosarcoma of the foot is rarer still. Marfan syndrome (MFS) is a rare genetic disorder that affects 1 in 5000 individuals and is caused by mutations in the fibrillin 1 (FBN1) gene. MFS phenotype affects several body systems, including soft connective tissue and bone. Here we report, for the first time, an individual with MFS that was treated for osteosarcoma. Surgically resected tissue was used to initiate an osteosarcoma cell line (PSU-OS-M) that exhibits attachment-independent growth and loss of contact inhibition in vitro. Genomic DNA was isolated from the tumor cells, and primers that anneal to intronic regions were used to amplify and sequence all 65 coding exons of the FBN1 gene. A two base pair insertion that results in a novel premature termination codon (PTC) was found in exon 52. Protein from the normal allele is detectable in PSU-OS-M cell-conditioned medium, but protein from the mutant allele was not detectable. Immunofluorescent microscopy demonstrates that PSU-OS-M cells can assemble fibrillin 1 microfibrils in culture, and fibronectin assembly is normal. As such, the PSU-OS-M cell line is to our knowledge the first oncogenically transformed cell line with a mutant fibrillin gene and may serve as a useful tool for studying molecular mechanisms of MFS and nonsense-mediated decay.


Developmental identity versus typology: Lucy has only four sacral segments.
Both interspecific and intraspecific variation in vertebral counts reflect the action of patterning control mechanisms such as Hox. The preserved A.L. 288-1 ("Lucy") sacrum contains five fused elements. However, the transverse processes of the most caudal element do not contact those of the segment immediately craniad to it, leaving incomplete sacral foramina on both sides. This conforms to the traditional definition of four-segmented sacra, which are very rare in humans and African apes. It was recently suggested that fossilization damage precludes interpretation of this specimen and that additional sacral-like features of its last segment (e.g., the extent of the sacral hiatus) suggest a general Australopithecus pattern of five sacral vertebrae. We provide updated descriptions of the original Lucy sacrum. We evaluate sacral/coccygeal variation in a large sample of extant hominoids and place it within the context of developmental variation in the mammalian vertebral column. We report that fossilization damage did not shorten the transverse processes of the fifth segment of Lucy's sacrum. In addition, we find that the extent of the sacral hiatus is too variable in apes and hominids to provide meaningful information on segment identity. Most importantly, a combination of sacral and coccygeal features is to be expected in vertebrae at regional boundaries. The sacral/caudal boundary appears to be displaced cranially in early hominids relative to extant African apes and humans, a condition consistent with the likely ancestral condition for Miocene hominoids. While not definitive in itself, a four-segmented sacrum accords well with the "long-back" model for the Pan/Homo last common ancestor. Am J Phys Anthropol 160:729-739, 2016. © 2016 Wiley Periodicals, Inc.


When fever is more than infection: two cases of vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS).
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, but serious systemic hypersensitivity reaction associated with a range of medications. We present two cases of vancomycin-induced DRESS, which occurred simultaneously in the orthopaedic ward in an outer metropolitan hospital. These cases demonstrate the complexity in the diagnosis and management of this inflammatory syndrome on the background of known infection as well as evidence for linezolid as an alternative to vancomycin. The first case was managed conservatively, but developed progressive renal and liver injury along with demonstrated cytomegalovirus reactivation and recurrent colitis, and was eventually palliated. The second was commenced on intravenous glucocorticoids and achieved remission, although had ongoing renal dysfunction at the time of discharge from outpatient follow-up.


Activin stimulates spermatogonial proliferation in germ-Sertoli cell cocultures from immature rat testis.
Activin and inhibin are peptide hormones produced in the gonads which may act as autocrine and/or paracrine regulators of testicular function. Sertoli cells produce inhibin, and it has recently been shown that Leydig cells can produce activin in vitro. To further explore the local actions of activin and inhibin in the testis, Sertoli and germ cells were isolated from immature rats and cocultured in vitro. In these cultures we demonstrate that activin A and activin B, but not inhibin A, stimulated spermatogonial proliferation in vitro. Activin increased [3H]thymidine incorporation 2- to 4-fold in cocultures after 48-72 h of treatment. Using autoradiography, the label was localized in the clusters of spermatogonia adhering to the Sertoli cell monolayer. Additionally, activin stimulated a reaggregation of the cultures into tubule-like structures. Fluorescence-activated cytometry was used to analyze the cell population based on size, DNA content, and lipid content. Sertoli cells were identified using Nile Red staining of intracellular lipid droplets; spermatogonia are Nile Red-negative. Activin treatment caused a marked increase in the fraction of Nile Red-negative cells in the cocultures. Activin also caused an increase in the percentage of these cells having 4C DNA. Lastly, specific binding of activin A to 2C, but not 4C, germ cells was demonstrated. These data demonstrate that activin acts as a regulator of spermatogonial proliferation in the male.


Palladium-Catalyzed Synthesis of Indanone via C-H Annulation Reaction of Aldehydes with Norbornenes.
A novel methodology for the synthesis of indanone derivates has been developed. The palladium-catalyzed annulation reaction of o-bromobenzaldehydes with norbornene derivatives is achieved through extremely concise reaction processes. The indanone skeleton was established directly via C-H activation of the aldehyde group under a mild reaction condition. This method is simple and practical, which simplified the traditional synthesis method for the rapid construction of indanone.


[Effect of vasopressin on energy metabolism of the brain in adult and aged rats].
Content of adenosine phosphate, creatine phosphate, Pi, lactate and ATPase activity were studied in brain of 8-10- and 25-27-months old rats. Content of ATP and ADP and the Na+, K+-ATPase activity were decreased while the level of Pi was increased in rat brain cortex during ageing. Administration of vasopressin caused an increase in lactate, Pi and Na+, K+-ATPase activity, whereas creatine phosphate decreased in the adult rat hypothalamus. Changes in energy metabolism were more pronounced in old rats: simultaneously with the decrease in creatine phosphate and more marked, as compared with adults, increase in Pi and lactate, the content of ATP decreased, ADP and AMP - increased and the Na+, K+-ATPase was distinctly activated in stem and brain cortex.


Rastonia solanacearum type Ⅲ effectors target host 14-3-3 proteins to suppress plant immunity.
14-3-3 proteins play important roles in plant metabolism and stress response. Tomato 14-3-3 proteins, SlTFT4 and SlTFT7, serve as hubs of plant immunity and are targeted by some pathogen effectors. Ralstonia solanacearum with more than 70 type Ⅲ effectors (T3Es) is one of the most destructive plant pathogens. However, little is known on whether R. solanacearum T3Es target SlTFT4 and SlTFT7 and hence interfere with plant immunity. We first detected the associations of SlTFT4/SlTFT7 with R. solanacearum T3Es by luciferase complementation assay, and then confirmed the interactions by yeast two-hybrid approach. We demonstrated that 22 Ralstonia T3Es were associated with both SlTFT4 and SlTFT7, and five among them suppressed the hypersensitive response induced by MAPKKKα, a protein kinase which associated with SlTFT4/SlTFT7. We further demonstrated that suppression of MAPKKKα-induced HR and plant basal defense by the T3E RipAC depend on its association with 14-3-3 proteins. Our findings firstly demonstrate that R. solanacearum T3Es can manipulate plant immunity by targeting 14-3-3 proteins, SlTFT4 and SlTFT7, providing new insights into plant-R. solanacearum interactions.


Ethnic disparities in prevalence and impact of risk factors of chronic kidney disease.
There is substantial heterogeneity in literature regarding the epidemiology for chronic kidney disease (CKD) in different Asian populations. We aimed to assess the prevalence and risk factors of CKD in a multi-ethnic Asian population in Singapore. We examined 4499 participants of Chinese, Malay and Indian ethnicity, aged 24-95 years, who participated in the Singapore Prospective Study Program. CKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m(2) or the presence of micro/macroalbuminuria. The age, sex-standardized prevalence of CKD was 12.8% (11.4%, 18.6% and 17.6% in Chinese, Malays and Indians). Older age and the presence of diabetes, hypertension and dyslipidaemia were significantly associated with CKD in all ethnic groups. Clinical, metabolic, socioeconomic and behavioral factors accounted for 68% and 78% of excess risk of CKD in Malays and in Indians, respectively. Diabetes (45%) and dyslipidaemia (16%) among Malays and hypertension among Indians (23%) had greater population-attributable risk of CKD. The prevalence of CKD is high in all three major Asian ethnic groups, in particular Malays and Indians, but risk factors are similar to those reported from previous studies in Western populations. The association of modifiable risk factors with CKD emphasizes the need to screen and treat high-risk populations for early detection and prevention of CKD.


Rational design of yolk-shell silicon dioxide@hollow carbon spheres as advanced Li-S cathode hosts.
Short cycle life and low Coulombic efficiency, in conjunction with fast self-discharge, render lithium-sulfur batteries impractical for commercial applications. In this work, we demonstrated that a "yolk-shell" structure with a polar silicon dioxide (SiO2) core in a hollow carbon sphere (SiO2@HC) acts as a highly efficient sulfur host. Such nanoarchitecture benefits from both a physical barrier and chemical adsorption via a carbon shell and a polar SiO2 core. Furthermore, the internal void space could buffer the huge volume expansion of active sulfur during lithiation. The resulting SiO2@HC/S composite exhibits a high mass S loading (∼76 wt%), high initial specific capacity of 1200 mA h g-1 at 0.2C, superior rate performance (728 mA h g-1 at 3C), ultraslow capacity decay of 0.056% per cycle at a high rate of 2C and an extraordinary anti-self-discharge feature.


Reduction in thrombus formation by placement of endovascular stents at endarterectomy sites in baboon carotid arteries.
Although antithrombotic therapies with aspirin, dipyridamole, and heparin have decreased thrombo-occlusive events, they have not abolished these complications. Endovascular mechanical support, first reported by Dotter in 1969, has been proposed as a means to reduce both acute and chronic vessel closure by providing a supporting framework for the disrupted and sometimes dissected arterial wall. To determine the effects of placing self-expanding stainless steel wire endoprostheses on the accumulation of thrombus at sites of carotid artery endarterectomy we measured platelet deposition continuously for 90 minutes and at 24 and 48 hours by gamma camera imaging of autologous 111In-labeled platelets in six stented and nonstented endarterectomized baboons that received heparin but no antiplatelet agents. At nonstented endarterectomy sites 5.36 +/- 1.25 x 10(8), 4.78 +/- 0.98 x 10(8), and 4.55 +/- 0.81 x 10(8) platelets per cm were deposited at 30, 60, and 90 minutes, respectively. In contrast, stented endarterectomy sites accumulated 0.99 +/- 0.31 x 10(8), 0.66 +/- 0.33 x 10(8), and 0.80 +/- 0.36 x 10(8) platelets per cm at 30 minutes (p = 0.02), 60 minutes (p = 0.004), and 90 minutes (p = 0.002), respectively. Platelet deposition remained reduced at 24 and 48 hours in stented endarterectomized carotid arteries (ECAs) when assessed as a ratio between net radioactivity in the endarterectomized region versus whole blood radioactivity (p = 0.006 and p = 0.009, respectively). Both stented and nonstented ECAs remained patent acutely, although two of six nonstented ECAs occluded by 30 days. By comparison 11 of 14 nonstented ECAs remained patent in another group of control animals. Scanning electron microscopy of control and stented arteries at 30 days demonstrated equivalently confluent endothelium. We postulate that endovascular stents reduce the thrombogenic effects of flap formation, tearing, dissection, and vasospasm in ECAs.


Dental microstructure and life history in subfossil Malagasy lemurs.
When compared with their recently extinct relatives, living lemurs represent a mere fraction of a broad radiation that occupied unique niches in the recent past. Among living lemurs, indrids exhibit the fastest rates of dental development. This dental precocity is tightly correlated with rapid pace of postnatal dental eruption, early replacement of the deciduous teeth, high dental endowment at weaning, and relatively slow somatic growth. This pattern is in stark contrast to that seen in extant lemurids, where somatic development is highly accelerated and dental development is relatively slow. We report on the pace of dental development in one species of palaeopropithecid, the sister group to extant indrids. Like much smaller modern indrids, the chimpanzee-sized Palaeopropithecus ingens was dentally precocious at birth as evidenced by the advanced state of molar crown formation. This finding implies a pattern characteristic of Propithecus and other indrids-rapid dental development despite relatively prolonged gestation. Gestation length in this one species of subfossil lemur was likely greater than 9 months. Our results demonstrate that large body size in primates does not preclude exceedingly rapid dental development.


The interaction of water molecules with purple membrane suspension using 2H double-quantum filter, 1H and 2H diffusion nuclear magnetic resonance.
Bacteriorhodopsin is a membrane protein of the purple membrane (PM) of Halobacterium salinarum, which is isolated as sheets of highly organized two-dimensional hexagonal microcrystals and for which water molecules play a crucial role that affects its function as a proton pump. In this paper we used single- and double-quantum (2)H NMR as well as (1)H and (2)H diffusion NMR to characterize the interaction of water molecules with the PM in D(2)O suspensions. We found that, under the influence of a strong magnetic field on a concentrated PM sample (0.61 mM), the PM sheets affect the entire water population and a residual quadrupolar splitting (upsilon(q) approximately 5.5 Hz, 298 K, at 11.7 T) is observed for the D(2)O molecules. We found that the residual quadrupolar coupling, the creation time in which a maximal DQF signal was obtained (tau(max)), and the relative intensity of the (2)H DQF spectrum of the water molecules in the PM samples (referred to herein as NMR order parameters) are very sensitive to temperature, dilution, and chemical modifications of the PM. In concentrated PM samples in D(2)O, these NMR parameters seem to reflect the relative organization of the PM. Interestingly, we have observed that some of these parameters are sensitive to the efficiency of the trimer packing, as concluded from the apo-membrane behavior. The data for dionized blue membrane, partially delipidated sample, and detergent-treated PM show that these D(2)O NMR order parameters, which are magnetic field dependent, are sensitive to the structural integrity of the PM. In addition, we revealed that heating the PM sample inside or outside the NMR magnet has, after cooling, a different effect on the NMR characteristics of the water molecules in the concentrated PM suspensions. The difference in the D(2)O NMR order parameters for the PM samples, which were heated and cooled in the presence and in the absence of a strong magnetic field, corroborates the conclusions that the above D(2)O order parameters are indirect reflections of both microscopic and macroscopic order of the PM samples. In addition, (1)H NMR diffusion measurements showed that at least three distinct water populations could be identified, based on their diffusion coefficients. These water populations seem to correlate with different water populations previously reported for the PM system.


Passive immunity in calf diarrhea: vaccination with K99 antigen of enterotoxigenic Escherichia coli and rotavirus.
Twenty-four pregnant cows were vaccinated intramuscularly with K99 extract from enterotoxigenic Escherichia coli and inactivated rotavirus as follows: six cows were injected with 2 ml of oil-adjuvanted vaccine; six cows were injected with 0.5 ml of oil-adjuvanted vaccine; six cows were injected with 4 ml of aluminum hydroxide-adjuvanted vaccine twice with a four-week interval; and six cows were unvaccinated as controls. Calves born to these cows were challenged with enterotoxigenic E. coli at 6 to 18 h after birth. Serum and milk antibodies to K99 and rotavirus in cows vaccinated with either dose of oil vaccine were significantly increased until at least 28 days after calving. In cows vaccinated with alhydrogel vaccine, there was a significant K99 antibody increase in serum and in colostrum but not in milk and a significant rotavirus antibody increase only in colostrum. Five of six calves born to unvaccinated cows developed enterotoxic colibacillosis after challenge, and all excreted the challenge strain of enterotoxigenic E. coli. None of the 18 calves in the three vaccinated groups developed clinical colibacillosis, and fecal excretion of the challenge organism was reduced. A combined enterotoxigenic E. coli-rotavirus vaccine may prove useful in preventing some outbreaks of calf diarrhea.


Action of surface-active agents on arylsulfatase-C of human cultured fibroblasts.
Arylsulfatase-C is a microsomal membrane-bound enzyme with unusual biochemical and genetic properties. Whether it is a single enzyme hydrolyzing different sterol sulfates or a complex of enzymes, with each enzyme hydrolyzing a specific substrate, has not been resolved. Its locus has been mapped to the human X chromosome but appears to escape inactivation. As a first step to clarify its biochemical properties, a systematic search was undertaken for a suitable detergent that can release this enzyme from human cultured fibroblast membranes in a form that is biologically active and electrophoretically mobile. Four non ionic (Triton X-100, Nonidet P-40, Digitonin, and saponin) and four amphoteric (lysolecithin, Zwittergent, Miranol, and Chaps) detergents were studied. At 1% concentration, they released more than 80% of the activity into a low-speed supernatant fraction, except for Saponin which had no effect. With Triton X-100 and Miranol representing the two groups of detergents, significant release occurred only when the detergent concentrations exceeded their respective critical micelle concentrations, thus indicating that arylsulfatase-C is an integral membrane protein. The apparent molecular weight of the detergent-enzyme complex, ascertained by gel filtration, was 85,000 in the presence of Triton X-100 and 335,000 in the presence of Miranol. However, only the preparation solubilized by Miranol (and Chaps, to a lesser degree) permitted migration of the enzyme in nitrocellulose acetate during electrophoresis at pH 7.0, while the enzyme extracted with all other detergents remained at the origin. Therefore, the amphoteric detergent, Miranol, appears to fulfill the requirements for further characterization of the membrane-bound arylsulfatase-C in human cultured fibroblasts.