Tonsillectomy and adenotonsillectomy for recurrent throat infection in moderately affected children.
In previous clinical trials involving children severely affected with recurrent throat infection (7 or more well-documented, clinically important, adequately treated episodes of throat infection in the preceding year, or 5 or more such episodes in each of the 2 preceding years, or 3 or more such episodes in each of the 3 preceding years), we found tonsillectomy efficacious in reducing the number and severity of subsequent episodes of throat infection for at least 2 years. The results seemed to warrant the election of tonsillectomy in children meeting the trials' stringent eligibility criteria but also provided support for nonsurgical management. We undertook the present trials to determine 1) whether tonsillectomy would afford equivalent benefit in children who were less severely affected than those in our earlier trials but who nonetheless had indications for tonsillectomy comparable to those in general use, and 2) whether, in such children, the addition of adenoidectomy would confer additional benefit. We conducted 2 parallel randomized, controlled trials in the Ambulatory Care Center of Children's Hospital of Pittsburgh. To be eligible, children were required to have had a history of recurrent episodes of throat infection that met standards slightly less stringent than the standards used in our earlier trials regarding either the frequency of previous episodes or their clinical features or their degree of documentation, but not regarding >1 of those parameters. These reduced standards were nonetheless more stringent than those in current official guidelines, which list "3 or more infections of tonsils and/or adenoids per year despite adequate medical therapy" as an indication for tonsillectomy or adenotonsillectomy. Of 2174 children referred by physicians or parents, 373 met the current trials' eligibility criteria and 328 were enrolled. Of these, 177 children without obstructing adenoids or recurrent or persistent otitis media were randomized to either a tonsillectomy group, an adenotonsillectomy group, or a control group (the 3-way trial), and 151 children who had 1 or more such conditions were randomized to either an adenotonsillectomy group or a control group (the 2-way trial). Outcome measures were the occurrence of episodes of throat infection during the 3 years of follow-up; other, indirect measures of morbidity; and complications of surgery. By various measures, the incidence of throat infection was significantly lower in surgical groups than in corresponding control groups during each of the 3 follow-up years. However, even among control children, mean rates of moderate or severe episodes were low, ranging from 0.16 to 0.43 per year. Adenotonsillectomy was no more efficacious than tonsillectomy alone. Of 203 children treated with surgery, 16 (7.9%) had surgery-related complications of varying types and severity. The modest benefit conferred by tonsillectomy or adenotonsillectomy in children moderately affected with recurrent throat infection seems not to justify the inherent risks, morbidity, and cost of the operations. We conclude that, under ordinary circumstances, neither eligibility criteria such as those used for the present trials nor the criterion for surgery in current official guidelines are sufficiently stringent for use in clinical practice.


Day and night heat stress trigger different transcriptomic responses in green and ripening grapevine (vitis vinifera) fruit.
Global climate change will noticeably affect plant vegetative and reproductive development. The recent increase in temperatures has already impacted yields and composition of berries in many grapevine-growing regions. Physiological processes underlying temperature response and tolerance of the grapevine fruit have not been extensively investigated. To date, all studies investigating the molecular regulation of fleshly fruit response to abiotic stress were only conducted during the day, overlooking possible critical night-specific variations. The present study explores the night and day transcriptomic response of grapevine fruit to heat stress at several developmental stages. Short heat stresses (2 h) were applied at day and night to vines bearing clusters sequentially ordered according to the developmental stages along their vertical axes. The recently proposed microvine model (DRCF-Dwarf Rapid Cycling and Continuous Flowering) was grown in climatic chambers in order to circumvent common constraints and biases inevitable in field experiments with perennial macrovines. Post-véraison berry heterogeneity within clusters was avoided by constituting homogenous batches following organic acids and sugars measurements of individual berries. A whole genome transcriptomic approach was subsequently conducted using NimbleGen 090818 Vitis 12X (30 K) microarrays. Present work reveals significant differences in heat stress responsive pathways according to day or night treatment, in particular regarding genes associated with acidity and phenylpropanoid metabolism. Precise distinction of ripening stages led to stage-specific detection of malic acid and anthocyanin-related transcripts modulated by heat stress. Important changes in cell wall modification related processes as well as indications for heat-induced delay of ripening and sugar accumulation were observed at véraison, an effect that was reversed at later stages. This first day - night study on heat stress adaption of the grapevine berry shows that the transcriptome of fleshy fruits is differentially affected by abiotic stress at night. The present results emphasize the necessity of including different developmental stages and especially several daytime points in transcriptomic studies.


The catabolism of plasma glycoproteins in normal and injured rats.
The catabolism of (14)C-labelled plasma glycoprotein in rats was studied after injecting homologous plasma protein labelled in the N-acetylglucosamine and sialic acid moieties. In normal animals the catabolism was approximately described by a four-compartment model. The fractional rate of catabolism of the plasma-protein amino sugar was found to be 0.0305hr.(-1), corresponding to the degradation of 2.75mumoles/hr. The (14)C label was eliminated from the animals largely as carbon dioxide with a small proportion appearing in the urine. Freely circulating amino sugars or glycopeptides did not appear in the plasma as a result of the catabolic processes, and there was no evidence that the protein-bound amino sugars were reutilized in biosynthetic processes. A study of the distribution of (14)C label in the carcasses of animals 24hr. after injection provided evidence that the gastrointestinal tract accounted for 25-38% of the total catabolic pool; the lungs, kidneys, spleen and liver also appeared to contribute to catabolism. Studies were conducted with rats that had been treated with turpentine to induce an inflammatory reaction; the results could not be analysed kinetically, since the metabolism of plasma proteins in these animals did not appear to be in a steady state. The injected plasma protein disappeared from the intravascular pool more quickly than in normal animals, but there were no significant differences in the rates of excretion of the (14)C label.


Effects of measures on phase transitions in two cooperative susceptible-infectious-recovered dynamics.
In recent studies, it has been shown that a cooperative interaction in a co-infection spread can lead to a discontinuous transition at a decreased threshold. Here, we investigate the effects of immunization with a rate proportional to the extent of the infection on phase transitions of a cooperative co-infection. We use the mean-field approximation to illustrate how measures that remove a portion of the susceptible compartment, like vaccination, with high enough rates can change discontinuous transitions in two coupled susceptible-infectious-recovered dynamics into continuous ones while increasing the threshold of transitions. First, we introduce vaccination with a fixed rate into a symmetric spread of two diseases and investigate the numerical results. Second, we set the rate of measures proportional to the size of the infectious compartment and scrutinize the dynamics. We solve the equations numerically and analytically and probe the transitions for a wide range of parameters. We also determine transition points from the analytical solutions. Third, we adopt a heterogeneous mean-field approach to include heterogeneity and asymmetry in the dynamics and see if the results corresponding to homogeneous symmetric case stand.


Citrate anticoagulation for continuous renal replacement therapy in the critically ill.
Heparins are used for circuit anticoagulation during continuous renal replacement therapy (CRRT). Because heparins cause systemic anticoagulation, they increase the risk of bleeding. Citrate provides regional anticoagulation. Since citrate is a buffer as well, its use has metabolic consequences. The preferential use of citrate therefore remains controversial. A synthesis was performed of published studies comparing citrate to heparin for anticoagulation in CRRT with specific regard to feasibility, efficacy and safety. Search of the literature was made to explain the reported superiority of citrate. Citrate provides good metabolic control if and when a well-designed protocol is strictly followed. Randomized studies report similar or longer circuit survival with citrate compared to heparin and less bleeding. The largest randomized trial up to now found that citrate was better tolerated than heparin and improved patient and kidney survival, especially in patients after surgery, with sepsis, a high degree of organ failure or younger age. Both citrate and heparin interfere with inflammation. During critical illness, regional anticoagulation with citrate for CRRT seems superior to heparin anticoagulation concerning tolerance and safety, mainly due to less bleeding. Whether circuit survival is better depends on the modality. In addition, citrate seems to improve patient and kidney survival. This finding needs to be confirmed. Citrate seems to confer a specific benefit in severe organ failure and sepsis. To what extent citrate protects or heparin does harm in the setting of multiple organ failure needs to be unraveled.


Effect of nociceptin on insulin release in normal and diabetic rat pancreas.
Nociceptin (NC), also known as Orphanin FQ, is a brain peptide involved in the regulation of pain, but its role in the endocrine pancreas is poorly understood. The present study examines the pattern of distribution of NC and its effect on insulin and glucagon secretion after the onset of diabetes mellitus (DM). Male Wistar rats weighing 150-200 g were made diabetic with streptozotocin (60 mg/kg body weight, intraperitoneally). Four weeks after the induction of DM, pancreatic tissues were retrieved and processed for immunofluorescence, immunoelectron microscopy, and insulin and glucagon secretion. Isolated islets from non-diabetic and diabetic rats were used to determine the effect of NC on insulin release. NC was discerned in islet cells of non-diabetic control and diabetic rat pancreata. NC co-localized only with insulin in pancreatic beta cells. NC did not co-localize with either glucagon or somatostatin or pancreatic polypeptide. The number of NC-positive cells was markedly (p < 0.001) reduced after the onset of DM. Electron microscopy study showed that NC is located with insulin in the same secretory granules of the beta cells of both non-diabetic and diabetic rat pancreas. NC inhibits insulin release markedly (p < 0.05) from pancreatic tissue fragments of non-diabetic and diabetic rats. In contrast, NC at 10-12 M stimulates insulin release in isolated islets of DM rats. In conclusion, NC co-localizes with insulin only in the islet of Langerhans. The co-localization of NC with insulin suggests a role for NC in the regulation of pancreatic beta cell function.


Sulfadiazines reduce gingivitis and plaque formation in beagle dogs.
The effect of zinc sulfadiazine (ZnSD) and silver sulfadiazine (AgSD) on reducing plaque formation and gingivitis was studied in 12 beagle dogs over a 14-week period. 12 beagle dogs were scaled, root planed and pumiced to bring them to a similar level of gingival health, prior to placing them on a diet of Purina Dog Chow softened with canned gravy and molasses to promote the build-up of plaque and the initiation of gingivitis. At the end of 8 weeks, the dogs were determined to have substantial bacterial plaque accumulation and apparent gingivitis. Thereafter, 4 dogs were treated 2 x daily with topical applications of 3% zinc sulfadiazine; 4 dogs were treated with 2% silver sulfadiazine while 4 dogs were treated with placebo gel serving as control over a 14-week treatment period. By week 2, the zinc and silver sulfadiazine dogs showed a significant decrease in gingival index which was maintained throughout the study. Additionally, by week 2, the % of sites with bleeding was also seen to decrease significantly in the experimental groups. The plaque index remained consistent in all 3 groups until week 6 when the 2 experimental groups indicated significant decrease in plaque accumulation as compared to controls. Probing depths were also seen to decrease significantly in the experimental groups after 10 weeks of therapy. The mean stain index was similar in all 3 groups of dogs throughout the study. Data indicate that both zinc and silver sulfadiazine inhibit plaque formation and reduce existing gingivitis in beagle dogs.


Shear stress experienced by echinoderm eggs in the oviduct during spawning: potential role in the evolution of egg properties
Shear stresses experienced by eggs in the oviduct of the echinoid Arbacia punctulata during spawning were calculated using engineering equations that describe laminar flow through pipes. Shear stresses in the oviduct ranged from 0 to 58.7 Pa. Two properties of eggs were identified that have the potential either to minimize the shear stress in the oviduct or to reduce the damage experienced by eggs exposed to high shear stress. These properties are the viscosity of the eggs and the presence of extracellular layers on eggs of A. punctulata. The viscosity of eggs decreases with increasing shear rates, which reduces the magnitude of shear stress experienced in the oviduct, while the extracellular layers mitigate the effect of shear stress on the eggs. Eggs with intact extracellular layers were damaged less frequently than were those with the extracellular layers removed. The results of this research indicate that physical stresses may be important selective factors in the evolution of gamete properties.


Distribution of glycinergic neuronal somata in the rat spinal cord.
Glycine transporter 2 (GlyT2) mRNA is exclusively expressed in glycinergic neurons, and is presently considered a reliable marker for glycinergic neuronal somata. In this study, we have performed non-radioactive in situ hybridization to localize GlyT2 mRNA in fixed free-floating sections of cervical (C2 and C6), thoracic (T5), lumbar (L2 and L5) and sacral (S1) segments of the rat spinal cord. The results showed that in all segments the majority of the GlyT2 mRNA labeled (glycinergic) neuronal somata was present in the deep dorsal horn and the intermediate zone (laminae III-VIII), with around 50% (range 43.7-70.9%) in laminae VII&VIII. In contrast, the superficial dorsal horn, the motoneuronal cell groups and the area around the central canal contained only few glycinergic neuronal somata. The density (number of glycinergic neuronal somata per mm(2)) was also low in these areas, while the highest densities were found in laminae V to VIII. The lateral spinal nucleus and the lateral cervical nucleus also contained a limited number of glycinergic neurons. Our findings showed that the distribution pattern of the glycinergic neuronal somata is similar in all the examined segments. The few differences that were found in the relative laminar distribution between some of the segments, are most likely due to technical reasons. We therefore conclude that the observed distribution pattern of glycinergic neuronal somata is present throughout the spinal cord. Our findings further showed that the non-radioactive in situ hybridization technique for identifying GlyT2 mRNA in fixed free-floating sections is a highly efficient tool for identifying glycinergic neurons in the spinal cord.


Markers of oxidative stress and systemic vasoconstriction in pregnant women drinking > or =48 g of alcohol per day.
The precise pathway by which alcohol causes the characteristic features of fetal alcohol spectrum disorders is unknown. Proposed mechanisms for fetal injury from maternal alcohol use include cellular damage from oxidative stress and impaired fetal oxygenation related to maternal systemic vasoconstriction. Our objective was to compare the levels of urinary markers of oxidative stress and systemic vasoconstriction between women consuming large amounts of alcohol during pregnancy and women who did not drink alcohol during pregnancy. Pregnant women consuming > or =48 g alcohol per day (n = 29) on average and pregnant women who abstained from alcohol use (n = 39) were identified using detailed interviews and home visits. Random maternal urine specimens were collected. Urinary levels of the oxidative stress marker, 8-isoprostane F2alpha, and of the vasoactive prostaglandin metabolites, 2,3-dinor-6-keto-prostaglandin F1alpha (a vasodilator) and 11-dehydro-thromboxane B2 (a vasoconstrictor), were measured using mass spectrometric methods. All analyte levels were corrected for urinary creatinine. In crude analyses, there was no significant difference in 8-isoprostane F2alpha between pregnant drinkers and nondrinkers (2.16 vs. 2.08 ng/mg creatinine, respectively, p = 0.87). There were no significant differences between the drinking and nondrinking groups in levels of 2,3-dinor-6-keto-prostaglandin F1alpha (1.03 vs. 1.17 ng/mg creatinine, respectively, p = 0.50), 11-dehydro-thromboxane B2 (0.72 vs. 0.59 ng/mg creatinine, respectively, p = 0.21), or the ratio of vasodilatory metabolite to vasoconstrictive metabolite (1.73 vs. 2.72, respectively, p = 0.14). Adjusting for maternal age, marital status, smoking, and gestational age at sampling did not substantially alter the results. Our results show no difference in levels of urinary eicosanoid markers of oxidative stress and systemic vasoconstriction between pregnant women who drink heavily and pregnant women who abstain. These findings speak against a role for maternal oxidative stress or systemic vasoconstriction in the pathogenesis of alcohol damage to the fetus.


Bionomics of Anopheline species and malaria transmission dynamics along an altitudinal transect in Western Cameroon.
Highland areas of Africa are mostly malaria hypoendemic, due to climate which is not appropriate for anophelines development and their reproductive fitness. In view of designing a malaria control strategy in Western Cameroon highlands, baseline data on anopheline species bionomics were collected. Longitudinal entomological surveys were conducted in three localities at different altitudinal levels. Mosquitoes were captured when landing on human volunteers and by pyrethrum spray catches. Sampled Anopheles were tested for the presence of Plasmodium circumsporozoite proteins and their blood meal origin with ELISA. Entomological parameters of malaria epidemiology were assessed using Mac Donald's formula. Anopheline species diversity and density decreased globally from lowland to highland. The most aggressive species along the altitudinal transect was Anopheles gambiae s.s. of S molecular form, followed in the lowland and on the plateau by An. funestus, but uphill by An. hancocki. An. gambiae and An. ziemanni exhibited similar seasonal biting patterns at the different levels, whereas different features were observed for An. funestus. Only indoor resting species could be captured uphill; it is therefore likely that endophilic behaviour is necessary for anophelines to climb above a certain threshold. Of the ten species collected along the transect, only An. gambiae and An. funestus were responsible for malaria transmission, with entomological inoculation rates (EIR) of 90.5, 62.8 and zero infective bites/human/year in the lowland, on the plateau and uphill respectively. The duration of gonotrophic cycle was consistently one day shorter for An. gambiae as compared to An. funestus at equal altitude. Altitudinal climate variations had no effect on the survivorship and the subsequent life expectancy of the adult stage of these malaria vectors, but most probably on aquatic stages. On the contrary increasing altitude significantly extended the duration of gonotrophic cycle and reduced: the EIR, their preference to human blood and consequently the malaria stability index. Malaria epidemiological rooting in the outskirts of Western Cameroon highlands evolves with increasing altitude, gradually from stable to unstable settings. This suggests a potential risk of malaria epidemic in highlands, and the need for a continuous epidemiological surveillance.


Recent decline in the incidence of human immunodeficiency virus infection among California men who have sex with men.
Monitoring the incidence of human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) is imperative for developing targeted prevention programs and evaluating their effectiveness. The authors used California counseling and testing data to estimate the temporal trend in HIV incidence among MSM in California. HIV incidence rates were retrospectively calculated among MSM who had received at least 1 HIV test at a public California counseling and testing site between 1997 and 2007 and had a prior HIV-negative test from any HIV testing source. All study subjects were weighted on the basis of the interval between the last HIV-negative test and the current HIV test to account for the right-truncation bias introduced by more frequent testers. The authors observed that the HIV incidence rate among MSM in California increased from 2.0/100 person-years (95% confidence interval (CI): 1.8, 2.2) in 1997 to 2.4/100 person-years (95% CI: 2.2, 2.6) in 2003 and then decreased to 1.9/100 person-years (95% CI: 1.7, 2.0) in 2006. Trend analyses showed that both the increase (P < 0.001) and the decrease (P < 0.01) were statistically significant. The study showed that HIV incidence among MSM in California had decreased since 2003.


Are patient information leaflets contributing to informed consent for cataract surgery?
To assess, against a checklist of specific areas of required information and using standard published criteria, to what extent leaflets given before cataract surgery provided patients with enough information to give adequately informed consent. Twelve ophthalmology departments in the West Midlands region were asked to submit the cataract information leaflets given to their patients at the preoperative assessment for analysis. Using criteria published by the General Medical Council, British Medical Association, and Medical Defence Union the leaflets were assessed for their contribution to informed consent for patients considering cataract surgery. Leaflets were scored according to the information they provided on: diagnosis, prognosis, treatment options, costs to the patient, details about the procedure, its purpose, likely benefits, how to prepare for it, what to expect during and after the operation, and the common as well as serious complications that may occur. The readability of the information was also assessed. All the units' leaflets provided information on diagnosis, the lifestyle changes required postoperatively, and cost involved to the patient. Only five units had leaflets that mentioned the risks involved in cataract surgery. The other areas of information were covered by 50-75% of the leaflets. Fifty per cent of the leaflets included a diagram. The average SMOG readability score was high. Although present cataract information leaflets make some contribution to the process of informed consent, most do not address important areas outlined by the General Medical Council. Many of the areas of information that are required for informed consent could easily be covered, and should be borne in mind when designing patient information leaflets. Resources are available on the internet including toolkits, guides, and means of assessment for the production of patient information leaflets.


Violence against animals and people: is aggression against living creatures generalized?
An association between childhood cruelty to animals and dangerous aggression against people at a later age could have important implications regarding early detection and treatment, preventive psychiatry, and a social ethic that encourages positive attitudes toward living creatures in general. Research reports in the literature are inconsistent and inconclusive regarding a possible relationship between animal cruelty and aggression against people. Although a single act is not predictive of another act, a pattern of substantial animal abuse may conceivably be associated with a pattern of recurrent violence directed against people. In the present study, extensive interview schedules were administered to aggressive criminals, nonaggressive criminals, and noncriminals. The nature of abuse was described for each subject who gave a history of substantial abuse. A clear relationship was found between early substantial abuse and recurrent violence against people. Possible explanations for conflicting results in the literature are discussed.


[Palliative care of patients with severe dementia].
Dementia is an important public health problem due to the complex challenges it poses during the progression of the disease and especially during its end-of-life stage. The aim of this article is to consider the issues that arise from the use of commonly administered therapies in patients with severe dementia. Scenarios where excessive or futile therapeutic interventions might occur are discussed. The article concludes that it is advisable to analyze the clinical criteria and ethical considerations related to the administration of those treatments in order to develop and disseminate better practice guidelines for health professionals.


Processing nanoporous organic polymers in liquid amines.
Rigid network structures of nanoporous organic polymers provide high porosity, which is beneficial for applications such as gas sorption, gas separation, heterogeneous (photo)catalysis, sensing, and (opto)electronics. However, the network structures are practically insoluble. Thus, the processing of nanoporous polymers into nanoparticles or films remains challenging. Herein, we report that nanoporous polymers made via a Knoevenagel-like condensation can be easily processed into nanoparticles (115.7 ± 40.8 nm) or a flawless film by using liquid amines as a solvent at elevated temperatures. FTIR spectra revealed that the carboxyl groups in the nanoporous polymers act as reactive sites for amines, forming new functionalities and spacing the polymeric chains to be dissolved in the liquid amines. The processed film was found to be CO2-philic despite the low surface area, and further able to be transformed into a fine carbon film by thermal treatment.


[A study of ITS sequence as a molecular marker in the phylogeny of Drosophila nasuta subgroup].
A total of 1.1 kb including whole ITS (intertranscribed spacer), part of 5.8S rDNA and 2S rDNA were sequenced. The results reveal that D. pallidifrons, Taxon I and Taxon J share the same sequence, and D. albomicans and D. s. neonasuta have the other same one. Among the sequences, there were a handful of insertions, deletions and substitutions. Insertions and deletions occur mainly between outgroup and ingroups; yet only 1 insertion and 12 deletions were detected in D. niveifrons, and 1 deletion was found in D. s. sulfurigaster. Among all the substitutions in outgroup and ingroups, totally 55 transitions and 65 transvertions were detected. The value of transition transvertion is quite different to that of mitochondrial genome. We applied parsimony and NJ methods to reconstruct the phylogenetic relationships of the 7 taxa. They show that D. niveifrons is on the basis of the trees, which suggests that it be less related to the rest; D. albomicans, D. s. neonasuta, D. pallidifrons, Taxon I and Taxon J are more related. We suggested that more related topology of D. s. sulfurigaster and D. s. neonasuta due to the specific evolution of ITS, yet not meaning their real relationships. Sequence variations and phylogeny analysis reveal that the ITS may be not an informative marker to nasuta subgroup. However, secondary structure analysis by using PCFOLD 4.0 reveals that the structure of the ITS is quite conservative; the stem-loop of ITS 3'-end may be an important structure of rDNA splicing.


Kinetics of monocytoid B lymphocytes in localized inflammatory lesions induced by lipopolysaccharide in mice.
Immunohistochemistry was used to study the kinetics of B lymphocytes (B-lys) in the early stages of the localized inflammatory response induced in SMA mice by the subcutaneous injection of lipopolysaccharide (LPS). At the injection sites, medium-sized B-lys formed early inflammatory lesions with neutrophils and activated macrophages on days 1 and 2. The B-lys were morphologically similar to monocytes, but were not stained with Mac1 antibody. Remarkably the B-lys showed the phenotypes of B220+, IgM+, IgD (slight to negative), Ly-1- and CD23- by double immunohistochemical staining. The B-lys were also positive for alkaline phosphatase. Consequently the B-lys could be identified as monocytoid B-lys or marginal zone B-lys. Plasmacytic B-lys and plasma cells were first observed on days 3 and 4, but no lymphoid follicles were found at the injection sites. In the inguinal lymph nodes, the same B-lys responses were mainly induced in the paracortical lesions (T cell areas) preceding the formation of activated germinal centers (GC). These findings suggested that the B-lys, induced by injections of LPS, matured into plasma cells in the localized inflammatory lesions independent of GC, and that they were different from follicular B-lys.


Discovery of the Elusive UDP-Diacylglucosamine Hydrolase in the Lipid A Biosynthetic Pathway in Chlamydia trachomatis.
Constitutive biosynthesis of lipid A via the Raetz pathway is essential for the viability and fitness of Gram-negative bacteria, includingChlamydia trachomatis Although nearly all of the enzymes in the lipid A biosynthetic pathway are highly conserved across Gram-negative bacteria, the cleavage of the pyrophosphate group of UDP-2,3-diacyl-GlcN (UDP-DAGn) to form lipid X is carried out by two unrelated enzymes: LpxH in beta- and gammaproteobacteria and LpxI in alphaproteobacteria. The intracellular pathogenC. trachomatislacks an ortholog for either of these two enzymes, and yet, it synthesizes lipid A and exhibits conservation of genes encoding other lipid A enzymes. Employing a complementation screen against aC. trachomatisgenomic library using a conditional-lethallpxHmutantEscherichia colistrain, we have identified an open reading frame (Ct461, renamedlpxG) encoding a previously uncharacterized enzyme that complements the UDP-DAGn hydrolase function inE. coliand catalyzes the conversion of UDP-DAGn to lipid Xin vitro LpxG shows little sequence similarity to either LpxH or LpxI, highlighting LpxG as the founding member of a third class of UDP-DAGn hydrolases. Overexpression of LpxG results in toxic accumulation of lipid X and profoundly reduces the infectivity ofC. trachomatis, validating LpxG as the long-sought-after UDP-DAGn pyrophosphatase in this prominent human pathogen. The complementation approach presented here overcomes the lack of suitable genetic tools forC. trachomatisand should be broadly applicable for the functional characterization of other essentialC. trachomatisgenes.IMPORTANCEChlamydia trachomatisis a leading cause of infectious blindness and sexually transmitted disease. Due to the lack of robust genetic tools, the functions of manyChlamydiagenes remain uncharacterized, including the essential gene encoding the UDP-DAGn pyrophosphatase activity for the biosynthesis of lipid A, the membrane anchor of lipooligosaccharide and the predominant lipid species of the outer leaflet of the bacterial outer membrane. We designed a complementation screen against theC. trachomatisgenomic library using a conditional-lethal mutant ofE. coliand identified the missing essential gene in the lipid A biosynthetic pathway, which we designatedlpxG We show that LpxG is a member of the calcineurin-like phosphatases and displays robust UDP-DAGn pyrophosphatase activityin vitro Overexpression of LpxG inC. trachomatisleads to the accumulation of the predicted lipid intermediate and reduces bacterial infectivity, validating thein vivofunction of LpxG and highlighting the importance of regulated lipid A biosynthesis inC. trachomatis.


The separation pin distinguishes the pro- and anti-recombinogenic functions of Saccharomyces cerevisiae Srs2.
Srs2 is an Sf1a helicase that helps maintain genome stability in Saccharomyces cerevisiae through its ability to regulate homologous recombination. Srs2 downregulates HR by stripping Rad51 from single-stranded DNA, and Srs2 is also thought to promote synthesis-dependent strand annealing by unwinding D-loops. However, it has not been possible to evaluate the relative contributions of these two distinct activities to any aspect of recombination. Here, we used a structure-based approach to design an Srs2 separation-of-function mutant that can dismantle Rad51-ssDNA filaments but is incapable of disrupting D-loops, allowing us to assess the relative contributions of these pro- and anti-recombinogenic functions. We show that this separation-of-function mutant phenocopies wild-type SRS2 in vivo, suggesting that the ability of Srs2 to remove Rad51 from ssDNA is its primary role during HR.


[Adverse drug reactions or adverse events of Chaihu Injection: a systematic review].
Chaihu Injection (CI), which is widely used in treatment of febrile diseases, is an aqueous solution of Chaihu (Radix Bupleuri Chinensis) or Nanchaihu (Radix Bupleuri Scorzonerifolii) prepared by steam distillation. This study aims at finding out the possible causes for adverse drug reaction or adverse event (ADR/AE) caused by CI and assessing its safety based on existing evidence. Manual search was not conducted. Electronic search was conducted by two authors in China National Knowledge Internet (CNKI) database and Chongqing VIP database (VIP). The search ended in June 30th, 2009. Studies of ADR/AE induced by CI were collected comprehensively without considering language of literature and outcome indicators. Search results were not limited by patient's age, gender, race, primary disease, etc. Interventions were using CI alone or CI combined with other drugs (Chinese herbal medicine decoction or other drugs containing Chaihu were excluded). Two authors conducted data extraction independently. Microsoft Excel software was used to develop data extraction forms. Because of heterogeneity of the studies, only a descriptive analysis was conducted. Totally 83 studies with 203 cases were included in this review. Without the yield data and total amount of using, we cannot tell the incidence of ADR/AE induced by CI as well as assess the risk and safety of CI. The constituent ratio of severe cases was higher in children and old people than in other age groups. For most intramuscular cases, ADR/AE happened in 30 min after injection (constituent ratio of cumulative incidence in 30 min was 93.8%); for intravenously guttae patients, 4 cases of ADR/AE happened in the process of infusion; for first users, constituent ratio of cumulative incidence in 30 min and constituent ratio of cumulative incidence of severe cases in 30 min were higher than cases who had used CI before. Most ADRs/AEs were caused by incorrect use of CI, such as excessive doses (5 cases), intravenously guttae administration (6 cases), and violating incompatibility rules (7 cases). The incidence ratios of ADR and AE for severe and mild cases were 1.7:1 and 1.1:1, respectively; the ratios of the three relevant levels described as definitely related, most probably related and possibly related in the two types (severe and mild) of cases were 25:14:5 and 44:9:16, respectively. Present evidence with low level shows that incorrect use is the main cause of ADR/AE of CI. Whether CI is proper for children and old people still needs further research. Training for correct use of CI is necessary for medical workers. Much improvement in reporting ADR/AE based on "Recommendations for Reporting Adverse Drug Reactions and Adverse Events of Traditional Chinese Medicine" is in need.


Aspirin increases NMDA receptor subunit 2A concentrations in rat hippocampus.
The N-methyl-d-aspartate receptor (NMDAR), a heteromeric protein, is a glutamate receptor that has three classes of subunits: NR1, NR2, and NR3. It has been reported that these receptors are involved in synaptogenesis, synaptic plasticity, and many other processes in the central nervous system. The aim of this study is to investigate the efficacy of aspirin on hippocampal NMDARs. Sixteen rats were studied in two groups, with eight animals in each group. The first group was the control group, and the second one was the aspirin-given group. Aspirin (acetylsalicylic acid) was administered orally to the rats (200 mg/kg). Tissue samples were obtained after 3 h. The brain was removed, and both hippocampi were dissected out for evaluation. It was found that acute doses of aspirin caused increases on the levels of NMDAR 2A (NR2A) receptors and malondialdehyde (MDA), the end product of lipid peroxidation. Production was significantly increased in the aspirin-given group. We know that MDA is a marker for free radical-mediated tissue damage. In conclusion, lipid peroxidation, caused by acute doses of aspirin may lead to excitotoxicity effects by a hippocampal NR2A-mediated mechanism.


Mechanoreceptors sensitive to flow at the gastroduodenal junction of the cat.
Vagal afferent activity was recorded from the cervical vagus simultaneously with intraluminal pressure and flow rate at the proximal duodenum, in cats anesthetized with pentobarbital sodium. Thirty-seven mechanoreceptors that adapted slowly to maintained pressure changes were found to be sensitive to the flow of saline through the pylorus. The passage of liquid was associated with an increase of pressure equal to one-tenth of that necessary to trigger a response of the receptors during the distension of a small balloon. The frequency of discharge was increased by the passage of liquid for positive back pressures < or = 1.5 kPa but not when back pressure was negative. The relationship between the discharge of the receptor and the flow rate was complex and showed an hysteresis. We conclude that there exist slowly adapting mechanoreceptors sensitive to distension of the duodenum that can also sense the passage of liquid.


High field electron paramagnetic resonance characterization of electronic and structural environments for paramagnetic metal ions and organic free radicals in Deepwater Horizon oil spill tar balls.
In the first use of high-field electron paramagnetic resonance (EPR) spectroscopy to characterize paramagnetic metal-organic and free radical species from tar balls and weathered crude oil samples from the Gulf of Mexico (collected after the Deepwater Horizon oil spill) and an asphalt volcano sample collected off the coast of Santa Barbara, CA, we are able to identify for the first time the various paramagnetic species present in the native state of these samples and understand their molecular structures and bonding. The two tar ball and one asphalt volcano samples contain three distinct paramagnetic species: (i) an organic free radical, (ii) a [VO](2+) containing porphyrin, and (iii) a Mn(2+) containing complex. The organic free radical was found to have a disc-shaped or flat structure, based on its axially symmetric spectrum. The characteristic spectral features of the vanadyl species closely resemble those of pure vanadyl porphyrin; hence, its nuclear framework around the vanadyl ion must be similar to that of vanadyl octaethyl porphyrin (VOOEP). The Mn(2+) ion, essentially undetected by low-field EPR, yields a high-field EPR spectrum with well-resolved hyperfine features devoid of zero-field splitting, characteristic of tetrahedral or octahedral Mn-O bonding. Although the lower-field EPR signals from the organic free radicals in fossil fuel samples have been investigated over the last 5 decades, the observed signal was featureless. In contrast, high-field EPR (up to 240 GHz) reveals that the species is a disc-shaped hydrocarbon molecule in which the unpaired electron is extensively delocalized. We envisage that the measured g-value components will serve as a sensitive basis for electronic structure calculations. High-field electron nuclear double resonance experiments should provide an accurate picture of the spin density distribution for both the vanadyl-porphyrin and Mn(2+) complexes, as well as the organic free radical, and will be the focus of follow-up studies.


In support of the telomere concept.
The frequency of recovered X-ray-induced (4000R) rearrangements that, in all probability mimic terminal deletions of the X chromosome was only one of, roughly, 10-5 X chromosomes screened for tip deficiencies. Although the single exception looks terminally deleted, it is probably capped by a very short or nonpolytene telomeric segment. It is apparent from these data that the probability of "healing" or stabilization of a terminally deleted X in the zygotic nucleus or developing embryo of Drosophila melanogaster is vanishingly small. The telomeric caps in two obviously interstitial deficiencies that were recovered represent, roughly, 1/500 of the length of a mitotic chromosome. These findings give some indication of the extreme difficulty of detecting short telomeric segments capping either deleted polytene chromosomes or deleted metaphase chromosomes of, for example, humans.


High virus-to-cell ratios indicate ongoing production of viruses in deep subsurface sediments.
Marine sediments cover two-thirds of our planet and harbor huge numbers of living prokaryotes. Long-term survival of indigenous microorganisms within the deep subsurface is still enigmatic, as sources of organic carbon are vanishingly small. To better understand controlling factors of microbial life, we have analyzed viral abundance within a comprehensive set of globally distributed subsurface sediments. Phages were detected by electron microscopy in deep (320 m below seafloor), ancient (∼14 Ma old) and the most oligotrophic subsurface sediments of the world's oceans (South Pacific Gyre (SPG)). The numbers of viruses (10(4)-10(9) cm(-3), counted by epifluorescence microscopy) generally decreased with sediment depth, but always exceeded the total cell counts. The enormous numbers of viruses indicate their impact as a controlling factor for prokaryotic mortality in the marine deep biosphere. The virus-to-cell ratios increased in deeper and more oligotrophic layers, exhibiting values of up to 225 in the deep subsurface of the SPG. High numbers of phages might be due to absorption onto the sediment matrix and a diminished degradation by exoenzymes. However, even in the oldest sediments, microbial communities are capable of maintaining viral populations, indicating an ongoing viral production and thus, viruses provide an independent indicator for microbial life in the marine deep biosphere.


The impact on adolescents of a Transtheoretical Model-based programme on fruit and vegetable consumption.
The present study aimed to evaluate the impact of a Transtheoretical Model-based programme titled 'Fruit & Vegetable-Friendly' on the fruit and vegetable (F&V) consumption of adolescents. A quasi-experimental study. The 'Fruit & Vegetable-Friendly', a multicomponent intervention based on the Transtheoretical Model, was completed in eight weeks. The data were collected one week before the intervention, one week after the completion of the intervention and six months after the post-test with an F&V intake questionnaire and the stages of change, processes of change (α = 0·91), situational self-efficacy (α = 0·91) and decisional balance (α = 0·90 for pros, α = 0·87 for cons) scales. Data were analysed with the Friedman, Wilcoxon and marginal homogeneity tests. A public secondary school in Istanbul, Turkey. Seven hundred and two adolescents. The mean (sd) F&V intake of adolescents in the passive stages rose from the daily average at the time of the pre-test of 3·40 (1·79) portions to 5·45 (2·54) portions on the post-test and to 5·75 (2·70) portions on the follow-up test (P < 0·01). While the students in the passive stages represented 41·6 % of the participants prior to the programme, this rate fell to 23·7 % at the post-test and to 22·7 % at the follow-up. Students in the active stages first represented 58·5 % of the participants; this rate rose to 76·4 % at the post-test and to 77·2 % at the follow-up test. The programme was effective in increasing the amount of F&V the adolescents consumed on a daily basis.


Overlooked retained intraocular foreign body.
The most common cause for litigation against ophthalmologists in a trauma case is a missed intraocular foreign body (IOFB). IOFBs cause internal eye damage, but some will come to rest in the posterior segment of the eye. We presented a 57-year-old male who was referred to the ophthalmologist due to decreased visual acuity in his left eye. Slit lamp examination of his left eye showed no pathological findings. Goldmann contact lens examination showed IOFB which was lying in the vitreous body in the inferior-temporal region. Retinal rupture was noticed at 7 o'clock. The optical coherence tomography (OCT) examination was performed and it showed atrophic macular area as well as decreased peripapillar retinal fiber layers thickness. Ultrasound showed the IOFB in vitreous body cavity. History revealed that the patient had an accidental trauma, 48 years ago, when an old bomb from World War II (WWII) exploded. Due to the decrease in visual acuity and fibrosis of the vitreous body surgical intervention was performed on his left eye (phacoemulsification with intraocular lens implantation, pars plana vitrectomy and instrumental extraction of foreign body). The intraocular foreign body (IOFB) was asymptomatic for 48 years. Symptoms depend on material and localization of the foreign body and the type of injury.


Differentiation between cerebral alveolar echinococcosis and brain metastases with radiomics combined machine learning approach.
Cerebral alveolar echinococcosis (CAE) and brain metastases (BM) share similar in locations and imaging appearance. However, they require distinct treatment approaches, with CAE typically treated with chemotherapy and surgery, while BM is managed with radiotherapy and targeted therapy for the primary malignancy. Accurate diagnosis is crucial due to the divergent treatment strategies. This study aims to evaluate the effectiveness of radiomics and machine learning techniques based on magnetic resonance imaging (MRI) to differentiate between CAE and BM. We retrospectively analyzed MRI images of 130 patients (30 CAE and 100 BM) from Xinjiang Medical University First Affiliated Hospital and The First People's Hospital of Kashi Prefecture, between January 2014 and December 2022. The dataset was divided into training (91 cases) and testing (39 cases) sets. Three dimensional tumors were segmented by radiologists from contrast-enhanced T1WI images on open resources software 3D Slicer. Features were extracted on Pyradiomics, further feature reduction was carried out using univariate analysis, correlation analysis, and least absolute shrinkage and selection operator (LASSO). Finally, we built five machine learning models, support vector machine, logistic regression, linear discrimination analysis, k-nearest neighbors classifier, and Gaussian naïve bias and evaluated their performance via several metrics including sensitivity (recall), specificity, positive predictive value (precision), negative predictive value, accuracy and the area under the curve (AUC). The area under curve (AUC) of support vector classifier (SVC), linear discrimination analysis (LDA), k-nearest neighbors (KNN), and gaussian naïve bias (NB) algorithms in training (testing) sets are 0.99 (0.94), 1.00 (0.87), 0.98 (0.92), 0.97 (0.97), and 0.98 (0.93), respectively. Nested cross-validation demonstrated the robustness and generalizability of the models. Additionally, the calibration plot and decision curve analysis demonstrated the practical usefulness of these models in clinical practice, with lower bias toward different subgroups during decision-making. The combination of radiomics and machine learning approach based on contrast enhanced T1WI images could well distinguish CAE and BM. This approach holds promise in assisting doctors with accurate diagnosis and clinical decision-making.


S100B is not a reliable prognostic index in paediatric TBI.
As far as paediatric traumatic brain injury is concerned, it is difficult to quantify the extent of the primary insult, to monitor secondary changes and to predict neurological outcomes by means of the currently used diagnostic tools: physical examination, Glasgow Coma Scale (GCS) score and computed tomography. For this reason, several papers focused on the use of biochemical markers (S100B, neuron-specific enolase) to detect and define the severity of brain damage and predict outcome after traumatic head injury or cardiac arrest. The aim of this paper is measuring the range of S100B serum concentrations in children affected by traumatic brain injury and describing the possible roles of this protein in the reaction to trauma. Fifteen children aged 1-15 years were included in the study. Traumatic brain injury severity was defined by paediatric GCS score as mild (9 patients), moderate (2 patients) or severe (4 patients). Blood samples for S100B serum measurement were taken at emergency department admission and after 48 h. The serum S100B concentration was higher in the group of severe trauma patients, who scored the lowest on the GCS at admission, and among them, the highest values were reported by the children with concomitant peripheral lesions. The role of S100B in paediatric traumatic brain injury has not been clarified yet, and the interpretation of its increase when the head trauma is associated with other injuries needs the understanding of the physiopathological mechanisms that rule its release in the systemic circulation. The levels of S100B in serum after a brain injury could be related to the mechanical discharge from a destroyed blood-brain barrier, or they could be due to the active expression by the brain, as a part of its involvement in the systemic inflammatory reaction. Early increase of this protein is not a reliable prognostic index of neurological outcome after pediatric traumatic brain injury, since even very elevated values are compatible with a complete neurological recovery.


Characterization of tumor microvascular structure and permeability: comparison between magnetic resonance imaging and intravital confocal imaging.
Solid tumors are characterized by abnormal blood vessel organization, structure, and function. These abnormalities give rise to enhanced vascular permeability and may predict therapeutic responses. The permeability and architecture of the microvasculature in human osteosarcoma tumors growing in dorsal window chambers in athymic mice were measured by confocal laser scanning microscopy (CLSM) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Dextran (40 kDa) and Gadomer were used as molecular tracers for CLSM and DCE-MRI, respectively. A significant correlation was found between permeability indicators. The extravasation rate K(i) as measured by CLSM correlated positively with DCE-MRI parameters, such as the volume transfer constant K(trans) and the initial slope of the contrast agent concentration-time curve. This demonstrates that these two techniques give complementary information. Extravasation was further related to microvascular structure and was found to correlate with the fractal dimension and vascular density. The structural parameter values that were obtained from CLSM images were higher for abnormal tumor vasculature than for normal vessels.


Carotid plaque neovascularization and hemorrhage detected by MR imaging are associated with recent cerebrovascular ischemic events.
Pathologic studies suggest that neovascularization and hemorrhage are important features of plaque vulnerability for disruption. Our aim was to determine the associations of these features in carotid plaques with previous cerebrovascular ischemic events by using high-resolution CE-MRI. Forty-seven patients (36 men; mean age 72.5 ± 10 years) underwent CE-MRI and MRA examinations for carotid plaque at 3T. IPH presence was recorded. Neovascularity was categorized by the degree of adventitial enhancement (0, absent; 1, <50%; 2, ≥50%). Reader variability was assessed by using weighted κ. Associations with events were determined by using multivariable logistic regression. Intra- and inter-reader agreement for grading adventitial enhancement were good to excellent. IPH was present in 49% of patients and was associated with events (P = .03). Patients grouped by categories 0, 1, and 2 adventitial enhancement had increasing frequencies of events (14% category 0, 48% category 1, 65% category 2; P = .02). Events were associated with IPH (OR, 10.18; 95% CI, 1.42-72.21) and adventitial enhancement (compared with category 0: OR, 14.90, 95% CI, 0.98-225.93 for category 1; OR, 51.17, 95% CI, 3.4-469.8 for category 2) after controlling for age, sex, cardiovascular risk factors, wall thickness, and stenosis. Stenosis was not associated with events. Adventitial enhancement and IPH are independently associated with previous events and may provide important insight into stroke risk not achievable by stenosis.


A genotype-phenotype correlation with gender-effect for hearing impairment caused by TECTA mutations.
Alpha-tectorin is a noncollagenous component of the tectorial membrane which plays an essential role in auditory transduction. In several DFNA12 families mutations in TECTA, the gene encoding alpha-tectorin, were shown to cause hearing impairment (HI) with different phenotypes depending on the location of the mutation. Here we report a Turkish family displaying autosomal dominant inherited HI. Linkage analysis revealed significant cosegregation (LOD score: 4.6) of the disease to markers on chromosome 11q23.3- q24. This region contains the TECTA gene which was subsequently sequenced. A nucleotide change in exon 13, 4526T>G, was detected leading to a substitution from cysteine to glycine at codon 1509 of the TECTA protein. This cysteine is located in vWFD4 domain, a protein domain which is supposed to be involved in disulfide bonds and protein-protein interactions. It is conspicuous that the phenotype in this family correlates with other families, also displaying mutations involving conserved cysteines. In all three families these mutations result in progressive HI involving high frequencies. In contrast, mutations which are not affecting the vWFD domains seem to provoke mid-frequency sensorineural HI. Furthermore, evaluation of clinical data in our family revealed a gender effect for the severity of hearing impairment. Males were significantly more affected than females. The identification of the third family displaying a missense mutation in the vWFD domain of alpha-tectorin underlines the phenotype-genotype correlation based on different mutations in TECTA.


Cognitive analysis of specific threat beliefs and safety-seeking behaviours in generalised anxiety disorder: revisiting the cognitive theory of anxiety disorders.
Generalised anxiety disorder (GAD) has been an uneasy member of the anxiety disorders group since its inclusion in the third edition of the DSM. Multiple theories and treatment protocols for GAD and its defining symptom, excessive worry, have comparable efficacy in treating GAD symptoms. Crucially, these theories of GAD and excessive worry fail to explain when and why worry is excessive and when it is adaptive. In this paper we propose a cognitive behavioural account of the difference between excessive and adaptive states of worry and explore the theme of threat and the function of safety-seeking behaviours as seen in GAD. Specifically, we incorporate the concept of inflated responsibility in a cognitive behavioural analysis of threat appraisal and safety-seeking behaviours in excessive worry and GAD. It is proposed that when worry is used as a strategy intended to increase safety from perceived social or physical threat then it should be conceptualised as a safety-seeking behaviour. However, when worry is used as a strategy to solve a problem which the person realistically can resolve or to deal explicitly with the feeling of anxiety then it functions as an adaptive coping behaviour. We also propose that the theme of threat in GAD centres on an inflated sense of responsibility for external everyday situations, and the function of safety-seeking behaviours is to attain certainty that responsibility has been fulfilled. The clinical implications of this cognitive behavioural analysis of excessive worry are discussed, as well as future research directions.


Potassium and chloride currents in rat gastric enterochromaffin-like cells.
The gastric enterochromaffin-like (ECL) cell secretes histamine in response to secretagogues (gastrin, acetylcholine) by calcium signaling-dependent exocytosis of intracellular vacuoles containing the hormone. ECL cells were isolated from rat fundic gastric mucosa by elutriation and density-gradient centrifugation. Currents across the plasma membrane were measured using whole cell patchclamp methods. These cells had a low conductance of 0.5 nS and resting potential of -50 mV. Depolarization activated a K+ current that was blocked by Ba2+. Steady-state current in absence of K+ was due to Cl- because of the magnitude of the reversal potential and the effects of Cl- removal. Stimulation of secretion by gastrin, cholecystokinin octapeptide (CCK-8), and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate activated the Cl- conductance with a time course similar to that of histamine release. Therefore the ECL cell maintains a high resting potential, largely due to K+ currents, and stimulation of secretion activates a Cl- current, perhaps deriving from the membrane of the secretory granule that fuses with the plasma membrane. The depolarization that ensues may activate the K+ current to maintain the membrane potential during exocytosis.


Comparison of Salmonella Prevalence Rates in Bovine Lymph Nodes across Feeding Stages.
Peripheral lymph nodes (LNs) located in the fatty tissues of beef carcasses have been shown to harbor Salmonella and, thus, potentially contaminate ground beef. Salmonella prevalence within LNs is known to differ among feedlots. Two South Texas feeding operations (identified as locations A and B) known to harbor salmonellae in the feedlot environment, while historically producing cattle with opposing rates (one "high" and one "low") of Salmonella prevalence in LNs, were used in this study. To determine whether this difference was due to cattle source or factors associated with different stages of feeding, weanling steers of common and known origin were followed through normal feeding stages at both operations. Eighty Angus-sired beef steers were harvested at each of four feeding stages: 1, postweaning; 2, background or stocker; 3, 60 days on feed; and 4, 120 days on feed. Left and right subiliac and superficial cervical LNs ( n = 304) were collected from each carcass, and similar node types were pooled by animal ( n = 152). Results showed a difference ( P < 0.05) in prevalence of Salmonella in bovine lymph nodes between location A and location B and among feeding stages in location B. Salmonella was not isolated from any feeding stage 1 (postweaning) or location A LN samples. Within location B, there was an increase in Salmonella prevalence as cattle moved into later stages of feeding: at 22.2% (4 of 18), 77.8% (14 of 18), and 94.4% (17 of 18) for feeding stages 2, 3, and 4, respectively. Although the reasons for the differences seen between feeding operations and for increased Salmonella prevalence in LNs at later feeding stages remain unexplained, these results indicate that factors other than cattle source are likely influencing Salmonella prevalence in LNs.


Xianfanghuomingyin, a Chinese Compound Medicine, Modulates the Proliferation and Differentiation of T Lymphocyte in a Collagen-Induced Arthritis Mouse Model.
In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferon γ [IFNγ], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA.


The binding of L-tryptophan to serum albumins in the presence of non-esterified fatty acids.
Bovine, human and rat serum albumins were defatted and palmitic acid, oleic acid and lauric acid added in various molar ratios. The binding of L-tryptophan to these albumins was measured at 20 degrees C in a 0.138 M salt solution at pH 7.4, by using an ultrafiltration technique, and analysed in terms of n, the number of available tryptophan-binding sites per albumin molecule, with apparent association constant, k. 2. n and k were 0.90 and 2.3x10(-4)M(minus-1) respectively for defatted bovine serum albumin and 0.87 and 9.7x10(-3)M(-minus-1) for human albumin. Addition of palmitic acid did not decrease n until the molar ratio, fatty acid/bovine albumin, approached and exceeded 2. The decrease in k was small and progressive. In contrast, lauric caused a marked decrease in n and k at ratios as low as 0.5. A similar distinction between the effects on n of palmitic acid and oleic acid and those of lauric acid was seen for human albumin. k for human albumin was not significantly affected by fatty acids under the conditions studied. 3. It is concluded that primary long-chain fatty acid sites interact only weakly with the tryptophan site on albumin and that inhibition of tryptophan binding occurs when secondary long-chain sites are occupied. Primary medium-chain fatty acid sites are distinct from primary long-chain sites but may be grouped with secondary long-chain sites. 4. The relationship between free and bound tryptophan in samples of rat plasma (Stoner et al., 1975) is discussed in terms of a similar but limited study of rat albumin.


Arabidopsis BLADE-ON-PETIOLE1 and 2 promote floral meristem fate and determinacy in a previously undefined pathway targeting APETALA1 and AGAMOUS-LIKE24.
The transition to flowering is a tightly controlled developmental decision in plants. In Arabidopsis, LEAFY (LFY) and APETALA1 (AP1) are key regulators of this transition and expression of these genes in primordia produced by the inflorescence meristem confers floral fate. Here, we examine the role of architectural regulators BLADE-ON-PETIOLE1 (BOP1) and BOP2 in promotion of floral meristem identity. Loss-of-function bop1 bop2 mutants show subtle defects in inflorescence and floral architecture but in combination with lfy or ap1, synergistic defects in floral meristem fate and determinacy are revealed. The most dramatic changes occur in bop1 bop2 ap1-1 triple mutants where flowers are converted into highly branched inflorescence-like shoots. Our data show that BOP1/2 function distinctly from LFY to upregulate AP1 in floral primordia and that all three activities converge to down-regulate flowering-time regulators including AGAMOUS-LIKE24 in stage 2 floral meristems. Subsequently, BOP1/2 promote A-class floral-organ patterning in parallel with LFY and AP1. Genetic and biochemical evidence support the model that BOP1/2 are recruited to the promoter of AP1 through direct interactions with TGA bZIP transcription factors, including PERIANTHIA. These data reveal an important supporting role for BOP1/2 in remodeling shoot architecture during the floral transition.


Fluorous-Directed Assembly of DNA Origami Nanostructures.
An orthogonal, noncovalent approach to direct the assembly of higher-order DNA origami nanostructures is described. By incorporating perfluorinated tags into the edges of DNA origami tiles we control their hierarchical assembly via fluorous-directed recognition. When we combine this approach with Watson-Crick base-pairing we form discrete dimeric constructs in significantly higher yield (8x) than when either molecular recognition method is used in isolation. This integrated "catch-and-latch" approach, which combines the strength and mobility of the fluorous effect with the specificity of base-pairing, provides an additional toolset for DNA nanotechnology, one that enables increased assembly efficiency while requiring significantly fewer DNA sequences. As a result, our integration of fluorous-directed assembly into origami systems represents a cheap, atom-efficient means to produce discrete superstructures.


Adsorption of herbicidally active degradate 2-(2,4-dichloro-3-methylphenoxy)propanoic acid on an andosol.
The adsorption of 2-(2,4-dichloro-3-methylphenoxy)propanoic acid (DMPA) on the surface horizon of a humus-rich Andosol was examined. To investigate the mechanisms of adsorption, chemically treated Andosols, such as organic matter removed Andosol, organic matter and active metals removed Andosol, and clay minerals of the Andosol, were prepared. Furthermore, humic acid was extracted from the Andosol. The mechanisms of the DMPA adsorption were identified by using those untreated and chemically treated Andosols and the humic acid. The amount of DMPA adsorbed increased with decreasing equilibrium pH value. Active surface hydroxyl groups were identified as the most important soil functional group in DMPA adsorption. The predominant mechanism of DMPA adsorption on the Andosol is a ligand-exchange reaction, in which an active surface hydroxyl on Al and/or Fe is replaced by a carboxylic group of DMPA. A comparative study revealed that the amount of DMPA adsorbed was slightly greater than that of (2,4-dichlorophenoxy)acetic acid (2,4-D), especially at equilibrium pH values below 5. This is because the octanol-water partition coefficient (log Kow) of DMPA in the equilibrium pH range is higher than that of 2,4-D, and SOM participates in the adsorption process through a hydrophobic interaction.


Bilateral same-session ureteroscopy: its efficacy and safety for diagnosis and treatment.
To report the results of bilateral same-session ureteroscopy in patients with bilateral pathologies in urinary system. From among nearly 3000 patients who had undergone diagnostic or therapeutic ureteroscopy in our center, 23 (13 females and 10 males) were treated with bilateral same-session ureteroscopy. Pathologies included bilateral ureteral stone in 19, hematuria of unknown etiology in 3, and bilateral obstructive uropathy in 1. Hospital and follow-up records of the patients were reviewed in this study. Of 19 patients with bilateral ureteral stone, 11 had anuria and increased serum creatinine. Ureteroscopy was successful in 9, and the stones were fragmented. Ureteroscopy insertion was not successful in 1, and in 1 another, upper ureteral stone was pushed into the Kidney. Six patients had normal urine output and normal serum creatinine. In 5 of them, ureteroscopy was done and the stones were fragmented, but due to ureteral stricture, ureteroscopy was impossible in 1. In 2 patients with oliguria and increased serum creatinine, bilateral ureteral stones were extracted successfully. Of 3 patients with hematuria of unknown origin, 2 had normal ureteroscopy, and 1 had a small non-opaque stone that was extracted successfully. In 1 patient with obstructive uropathy and the diagnosis of obstructive megaureter, bilateral ureteroscopy was done and bilateral ureteral stents were placed. Finally, from 23 patients, 21 had successful bilateral same-session ureteroscopy. Postoperative complications included pyrogenic infection in 2 and gross hematuria in 4, all of which were resolved with medical treatment. Bilateral same-session ureteroscopy is an appropriate therapeutic and diagnostic option, with its own specific indications. It can reduce hospital stay, prevent multiple anesthesias, and alleviate the costs. We recommend this approach in patients with bilateral ureteral pathologies, provided that they are amenable to ureteroscopy.


Predominant expression of murine Bmx tyrosine kinase in the granulo-monocytic lineage.
In the course of systematic cloning of protein tyrosine kinases (PTKs) expressed in hematopoietic stem and progenitor cells, we have identified the murine homologue of human Bmx. It encodes a protein containing the five domains characteristic of the Tec family of cytoplasmic src-related PTKs: pleckstrin homology (PH), Tec homology (TH), src homology 3 and 2 (SH3 and SH2), and tyrosine kinase (TK). In adults, Bmx expression was found primarily in bone marrow and at a lower level in lung and heart. During fetal development it was also found in the spleen at late stage of gestation and in neonates. Analysis of bone marrow subpopulations showed that Bmx was expressed in the progenitor cell population and maturing hematopoietic cells of the granulo/monocytic lineage where expression increased with maturation and differentiation. At the periphery, a high level of Bmx expression was also found in neutrophils and monocytes/macrophages. Bmx expression was not detected in the primitive hematopoietic stem cell population, and cells of the B-, T-, and erythroid-lineages. It was also not detected in most of the cell lines examined. Our results indicate that Bmx is another member of the Btk/Itk/Tec PTK family, which is predominantly expressed in the granulo-monocytic lineage within the hematopoietic system.


Epigallocatechin gallate and coenzyme Q10 attenuate cisplatin-induced hepatotoxicity in rats via targeting mitochondrial stress and apoptosis.
Despite the extensive use of cisplatin (CP) as a chemotherapeutic agent, its clinical use is often restricted by undesirable side effects, such as toxicity to normal tissues. The aim of this study was to probe the effect of a combinatorial treatment of low multiple doses of antioxidants on CP-induced toxicity and the mitochondrial apoptotic pathway in hepatocytes. Animals received a single toxic dose of CP (7.5 mg/kg body weight) with or without combined multiple doses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight, respectively). CP-treated animals showed altered biochemical parameters, denoting hepatotoxicity, which was markedly improved by the multidose treatment with EGCG + CoQ10. The increased levels of oxidants found in the cytosolic and mitochondrial fractions isolated from the liver of CP-administered rats were significantly attenuated by the combinatorial doses of antioxidants. EGCG + CoQ10 ameliorated the CP-induced compromised antioxidant defenses, oxidative modification of macromolecules, decreased activities of respiratory chain enzymes, altered membrane depolarization, and swelling of liver mitochondria. Furthermore, EGCG + CoQ10 treatment inhibited CP-induced apoptosis by suppressing the activation and mitochondrial accumulation of proapoptotic proteins and preventing the inhibition of antiapoptotic protein expression, cytochrome c efflux, caspase-3 activation, and DNA fragmentation. Histological findings further confirmed the protective effects of EGCG + CoQ10 against CP-induced cellular injury. Our findings revealed that the combination of EGCG and CoQ10, owing to their individual antioxidant properties, can be an effective remedy, which by maintaining redox hemostasis attenuate the mitochondrial stress-mediated molecular and cellular processes involved in CP-induced liver toxicity and cell death.


Distinct Agonist Regulation of Muscarinic Acetylcholine M2-M3 Heteromers and Their Corresponding Homomers.
Each subtype of the muscarinic receptor family of G protein-coupled receptors is activated by similar concentrations of the neurotransmitter acetylcholine or closely related synthetic analogs such as carbachol. However, pharmacological selectivity can be generated by the introduction of a pair of mutations to produce Receptor Activated Solely by Synthetic Ligand (RASSL) forms of muscarinic receptors. These display loss of potency for acetylcholine/carbachol alongside a concurrent gain in potency for the ligand clozapine N-oxide. Co-expression of a form of wild type human M2 and a RASSL variant of the human M3 receptor resulted in concurrent detection of each of M2-M2 and M3-M3 homomers alongside M2-M3 heteromers at the surface of stably transfected Flp-In(TM) T-REx(TM) 293 cells. In this setting occupancy of the receptors with a muscarinic antagonist was without detectable effect on any of the muscarinic oligomers. However, selective agonist occupancy of the M2 receptor resulted in enhanced M2-M2 homomer interactions but decreased M2-M3 heteromer interactions. By contrast, selective activation of the M3 RASSL receptor did not significantly alter either M3-M3 homomer or M2-M3 heteromer interactions. Selectively targeting closely related receptor oligomers may provide novel therapeutic opportunities.


Cluster effects within the local effect model.
The local effect model predicts the relative biological effectiveness (RBE) for different ions and cell lines starting from the corresponding experimental photon data and an amorphous track structure model. Here we present an extension of the model that takes cluster effects of single-strand breaks (SSBs) at the nanometer scale into account. In line with the main idea of the local effect model, we take the yields of SSBs and double-strand breaks (DSBs) from experimental photon data and use a Monte Carlo method to distribute them onto the DNA. We score clusters of SSBs where individual SSBs are separated by less than 25 bp as additional DSBs. Assuming that the number of DSBs is a measure of cell lethality, we derive a modified cell survival curve for photons that takes these cluster effects into account. In combination with an improved radial dose distribution, we find that the extended local effect model including cluster effects reproduces most experimental data better than the original local effect model and thus enhances the accuracy of the local effect model.


Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.
Podosomes are dynamic cytoskeletal membrane structures with local adhesive and proteolytic activity. They are critically involved in angiogenesis and vascular adaptive growth. Here, we studied in HUVECs and murine small vessels whether shear stress controls podosome assembly and local proteolytic activity. Podosomes were characterized by immunohistochemistry, and their proteolytic activity was assessed as degradation imprints in fluorescent gelatin that was used as growth substrate. Compared with controls (10 dyn/cm(2)), the number of podosomes formed per time was doubled when cells were exposed to low shear stress (0.3 dyn/cm(2)) or even increased 5-fold under static conditions. This was a result of an enhanced expression of VEGF after reduction of shear stress. Consequently, enhanced podosome formation could be prevented by a VEGF receptor antagonist as well by interruption of VEGF signaling via inhibition of PI3K, Src, or p38. Increase of podosome assembly went along with significantly augmented cell motility. In vivo experiments in mouse arteries confirmed increased endothelial podosome numbers when shear stress was abolished by vessel occlusion. We conclude that shear stress, by reducing VEGF release, inhibits podosome assembly. Hence, endothelial cell-mediated matrix proteolysis and migratory activity are inhibited, thereby stabilizing the structure of the vessel wall.-Fey, T., Schubert, K. M., Schneider, H., Fein, E., Kleinert, E., Pohl, U., Dendorfer, A. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.


A Pilot Clinical Study of Liquid Ubiquinol Supplementation on Cardiac Function in Pediatric Dilated Cardiomyopathy.
Pediatric dilated cardiomyopathy (PDCM) is a life-threatening type of cardiac muscle dysfunction in children. Ubiquinone is a lipid-soluble nutrient that participates in energy synthesis. Recently, a novel hydrophilic ubiquinol supplement was developed. The purpose of this study was to assess the effect of liquid ubiquinol supplementation (10 mg/kg body weight/day) on cardiac function in children with PDCM. Ten children diagnosed with PDCM were recruited to this study and administered with liquid ubiquinol for 24 weeks. The cardiac function was measured by echocardiography. The New York Heart Association (NYHA) functional classification was used to assess symptoms of heart failure. Plasma coenzyme Q10 levels were measured during the study. Ejection fraction (EF) and fractional shortening (FS) were significantly higher than the baseline values until week 16 of supplementation. Subjects who had higher plasma coenzyme Q10 concentration had significantly better EF and FS values. In addition, 30% of the subjects showed improvement in the NYHA classification after 24 weeks of supplementation. Liquid ubiquinol supplementation is associated with an increase the level of coenzyme Q10 to complementary improve cardiac function (particularly EF and FS) and ameliorate the symptoms of heart failure in children with PDCM.


Cholesterol content and heat sensitivity of nine mammalian cell lines.
The cholesterol, phospholipid and protein contents of nine mammalian cell lines, three lymphoid and six attached cell lines, were measured, along with the sensitivity of the cells to hyperthermia at 42 degrees and 44 degrees C. The free cholesterol content and the protein content per cell correlated positively with the time required to kill 99 per cent of the cells at 44 degrees C. The phospholipid content showed a less significant positive correlation whilst the cholesterol ester content and the cholesterol:phospholipid molar ratio did not correlate with heat sensitivity. There were no correlations observed when the levels of these cell components were compared to heat survival at 42 degrees C. As the three lymphoid lines are small, very heat sensitive cells, the six monolayer lines were analysed separately. In this case, only the protein and the free cholesterol content maintained a significant correlation (at the 5 per cent level). It is concluded that the levels of cholesterol or phospholipid cannot be used as reliable indicators of the heat sensitivity of a cell.


Effects of Physical Activity on Quality of Life, Anxiety and Depression in Breast Cancer Survivors: A Systematic Review and Meta-Analysis.
Anxiety, depression, and poor quality of life were considered important concerns that hindered the rehabilitation of breast cancer survivors. A number of studies have investigated the effects of physical activity, but they have not reached the same conclusions. This review aimed to identify the effects of physical activity on quality of life, anxiety, and depression in breast cancer survivors. PubMed, Embase, Web of Science, CINAHL, PsycINFO, SinoMed, CNKI, Vip and WanFang database were searched for the time period between January 1, 2012, and April 30, 2022. Studies were included if they were randomized controlled trials of the effects of physical activity on quality of life, anxiety or depression in breast cancer survivors. The tool of the Joanna Briggs Institute was used to assess the quality of the included studies. R software version 4.3.1 was used for meta-analysis. A total of 26 studies involving 2,105 participants were included in the systematic review. Among these, 20 studies involving 1,228 participants were included in the meta-analysis. Compared with the control group, the results indicated that physical activity can significantly improve quality of life (Hedges' g = 0.67; 95% CI 0.41 to 0.92) and reduce anxiety (Hedges' g = - 0.28; 95% CI - 0.46 to - 0.10) in breast cancer survivors. However, the effect of physical activity on depression (Hedges' g = - 0.46; 95% CI - 0.99 to 0.06) was not statistically significant. Physical activity was an effective intervention to improve quality of life and reduce anxiety in breast cancer survivors, as well as showed positive trends in depression, although without statistical significance. More well-designed studies are required to clarify the effects of different types of physical activities on the quality of life, anxiety, and depression among breast cancer survivors. CRD42022363094. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=363094.


The effect of stress on core and peripheral body temperature in humans.
Even though there are indications that stress influences body temperature in humans, no study has systematically investigated the effects of stress on core and peripheral body temperature. The present study therefore aimed to investigate the effects of acute psychosocial stress on body temperature using different readout measurements. In two independent studies, male and female participants were exposed to a standardized laboratory stress task (the Trier Social Stress Test, TSST) or a non-stressful control task. Core temperature (intestinal and temporal artery) and peripheral temperature (facial and body skin temperature) were measured. Compared to the control condition, stress exposure decreased intestinal temperature but did not affect temporal artery temperature. Stress exposure resulted in changes in skin temperature that followed a gradient-like pattern, with decreases at distal skin locations such as the fingertip and finger base and unchanged skin temperature at proximal regions such as the infra-clavicular area. Stress-induced effects on facial temperature displayed a sex-specific pattern, with decreased nasal skin temperature in females and increased cheek temperature in males. In conclusion, the amplitude and direction of stress-induced temperature changes depend on the site of temperature measurement in humans. This precludes a direct translation of the preclinical stress-induced hyperthermia paradigm, in which core temperature uniformly rises in response to stress to the human situation. Nevertheless, the effects of stress result in consistent temperature changes. Therefore, the present study supports the inclusion of body temperature as a physiological readout parameter of stress in future studies.


[Histochemical study of the activity of several enzymes in the process of immunogenesis in monkeys orally infected with viruses of the tick-borne encephalitis complex].
The activity of succinate dehydrogenase, acid and alkaline phosphatase was studied histochemically in immunocompetent organs of Macacus rhesus monkeys orally infected with viruses of the tick-borne encephalitis complex with different biological properties. A gradual increase in the activity of acid phosphatase and succinate dehydrogenase was observed by the 10th--15th day of the experiment followed by its decline to normal by 90 days. The content of alkaline phosphatase in lympoid organs diminished markedly in the first day of the study and then increased by 15--30 days after antigenic stimulation.


Separation of a murine leukaemia virus protein kinase activity from its Pr65gag polyprotein substrate after DNA--cellulose chromatography.
We have recently found that, in vitro, the murine leukaemia virus (MuLV)-associated protein kinase activity predominantly phosphorylates Pr65gag, a virus protein present in relatively small amounts in partially purified virus preparations. Other virus proteins, such as p10, Pr27gag and Pr40gag, are also phosphorylated in vitro, but to a lesser degree. Furthermore, when immature core subparticles which are enriched in Pr65gag are prepared from virions by Sepharose 6B exclusion column chromatography, about 50% of the kinase activity (as assayed with the exogenous substrate phosvitin) remains associated with the cores. We report here that this core-associated activity is distinct from Pr65gag since it can be separated from Pr65gag by chromatography on denatured DNA--cellulose columns followed by centrifugation of the 0.2 M-NaCl-eluted fraction. Under these conditions, Pr65gag is pelleted while the kinase activity, which can phosphorylate both endogenous (MuLV Pr65gag and p10) as well as exogenous (phosvitin) substrates, remains in the supernatant. Interestingly, when the amount of Pr65gag is reduced, as in such preparations, p10 then becomes more heavily phosphorylated.


Common psychocutaneous disorders in children.
The prevalence of psychosomatic disorders among dermatological patients is high but frequently unreported because of difficulties in diagnosing and treating this patient group. Psychiatric and psychological factors may play different roles in the pathogenic mechanism of some skin diseases. The mainstay of diagnosis and treatment is the differentiation between skin disorders associated with psychiatric illness and those of a purely psychiatric nature. Dermatologists and psychiatrists should be aware of this pathology and work together as a team to resolve difficult cases, especially in children. The present paper highlights the psychocutaneous diseases most frequently seen by dermatologists in pediatric population.


Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma.
To determine baseline characteristics predictive of response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Pooled analysis of two multicenter, double-blind, randomized, placebo-controlled phase III studies with omalizumab. One thousand seventy allergic asthma patients symptomatic despite moderate-to-high doses (mean, 725 micro g/d) of inhaled beclomethasone dipropionate (BDP). Omalizumab (n = 542) or placebo (n = 528) were administered at a 4-weekly subcutaneous dose of at least 0.016 mg/kg/IgE (IU/mL) for 16 weeks in addition to stable BDP therapy. Univariate logistic regression was performed to explore baseline variables predictive of best response. Various aspects of response (reduced symptom scores, reduced usage of rescue medication, improved lung function, improved quality of life [QoL]) were explored as well as a composite definition of response (response in at least one of these four aspects with no asthma exacerbation during 16 weeks of treatment). Time to onset of response as well as the ability to predict eventual response were also determined for the composite definition of response. A consistent pattern of predictive covariates was seen over all definitions of response (except for QoL). For the composite definition, a history of emergency asthma treatment in the past year was the factor most predictive (p = 0.015) of best response on active treatment (response rate for those with such history was 67% for omalizumab and 42% for placebo; for those without a history the response rates were 63% and 54%, respectively). Another factor predictive of best response on active treatment was high BDP dose (p = 0.037; response rate for those treated with >or= 800 micro g/d was 65% for omalizumab and 40% for placebo; for those treated with < 800 micro g/d, the response rates were 63% and 55%, respectively). A low FEV(1) was also predictive (p = 0.072; response rates for those with FEV(1) <or= 65% predicted were 60% for omalizumab and 40% for placebo; for those with FEV(1) >or= 65% predicted, the response rates were 67% and 53%, respectively). Seventy-six percent of patients had at least one of these factors. This subgroup showed odds of being a responder (composite definition) 2.25 times higher (95% confidence interval, 1.68 to 3.01) than placebo. Some 38% of patients treated with omalizumab showed a response (composite definition) at the first evaluation time point at 4 weeks, increasing to 64% at week 16 (vs 48% for placebo; p < 0.001). Among omalizumab responders at 16 weeks, only 61% had responded at 4 weeks whereas 87% had responded at 12 weeks. Patients who benefit most when omalizumab is administered as add-on therapy are those receiving high doses of BDP, those with a history of frequent emergency asthma treatment, and those with poor lung function. Patients should be treated with omalizumab for a minimum duration of 12 weeks.


Male pelvic anatomy/post-prostatectomy incontinence.
There is an intricate relationship between structure, position, and function within the lower urinary tract. To understand the individual problems that may occur with post-prostatectomy incontinence, it is necessary to be aware of these relationships.


Pattern stability and error correction during in-phase and antiphase four-ball juggling.
The authors studied pattern stability and error correction during in-phase and antiphase 4-ball fountain juggling. To obtain ball trajectories, they made and digitized high-speed film recordings of 4 highly skilled participants juggling at 3 different heights (and thus different frequencies). From those ball trajectories, the authors determined and analyzed critical events (i.e., toss, zenith, catch, and toss onset) in terms of variability of point estimates of relative phase and temporal correlations. Contrary to common findings on basic instances of rhythmic interlimb coordination, in-phase and antiphase patterns were equally variable (i.e., stable). Consistent with previous findings, however, pattern stability decreased with increasing frequency. In contrast to previous results for 3-ball cascade juggling, negative lag-one correlations for catch-catch intervals were absent, but the authors obtained evidence for error corrections between catches and toss onsets. That finding may have reflected participants' high skill level, which yielded smaller errors that allowed for corrections later in the hand cycle.


Maternal animal model with correlation between maternal environmental effects of related dams.
A procedure to take into account the nongenetic relationship between maternal effects in adjacent generations is presented. It considers a correlation between maternal environments provided by a dam and its daughters (lambda). The dispersion structure of the maternal animal model was modified to include a correlation matrix (E) that relates the maternal permanent environmental effects. The structures of the E matrix and its inverse (E(-1)) are described. Both matrices are completely defined by the correlation coefficient lambda. An algorithm to compute these matrices from pedigree information was also developed. Furthermore, a Bayesian analysis of this model including the lambda parameter was developed using Gibbs sampling, with Metropolis steps for the nonstandard conditional distributions. With simulated data, the proposed model reduced the bias in all estimates of dispersion parameters when an antagonism between the maternal effects received by a daughter and its future maternal environment existed. This model also provides an estimate of the environmental relationship between the maternal effects of dams and daughters by the lambda parameter. The same Bayesian analysis was also carried out with weaning weight data of the Bruna dels Pirineus breed. The posterior means (standard deviation) of (co)variance ratios were .214 (.081) for direct heritability (h2d), .107 (.033) for maternal heritability (h2m), .047 (.020) for the proportion of variance due to maternal environmental effects (c2m), and -.034 (.043) for the genetic correlation between direct and maternal effects (r(dm)). The posterior mean of lambda parameter was -.190, and 76% of its marginal posterior distribution took negative values. As occurred with simulated data, considering the maternal environmental correlation in the analysis implied higher h2m estimates, lower c2m and h2d estimates, and less negative values for the marginal posterior distribution of r(dm). These results were considered as evidence of the environmental antagonism between maternal effects provided by a dam and its daughters to weaning weight of their progeny in the Bruna dels Pirineus breed.


Novel missense mutation in the RSPO4 gene in congenital hyponychia and evidence for a polymorphic initiation codon (p.M1I).
Anonychia/hyponychia congenita is a rare autosomal recessive developmental disorder characterized by the absence (anonychia) or hypoplasia (hyponuchia) of finger- and/or toenails frequently caused by mutations in the R-spondin 4 (RSPO4) gene. Three hypo/anonychia consanguineous Pakistani families were ascertained and genotyped using microsatellite markers spanning the RSPO4 locus on chromosome 20p13. Mutation screening of the RSPO4 gene was carried out by direct sequencing of the entire coding region and all intron-exon boundaries. Mutations in the RSPO4 gene were identified in all families including a novel missense mutation c.178C>T (p.R60W) and two recurrent variants c.353G>A (p.C118Y) and c.3G>A (p.M1I). The c.3G>A variant was identified in unaffected family members and a control sample in a homozygous state. This study raises to 17 the number of known RSPO4 mutations and further expands the molecular repertoire causing hypo/anonychia. The c.353G>A emerges as a recurrent change with a possible founder effect in the Pakistani population. Our findings suggest that c.3G>A is not sufficient to cause the disorder and could be considered a polymorphism.


Prescription medication use during pregnancy and risk of infant leukemia (United States).
We explored whether maternal medication use during pregnancy may be an important etiologic area for investigation in studies of infant leukemia. In this case-control study, associations were explored between specific medications as recorded in the medical records of 243 mothers of infants who were diagnosed with leukemia at < 18 months of age and 393 mothers ol infants without leukemia identified through random digit dialing. Cases included 157 acute lymphoblastic (ALL), 77 acute myeloid (AML), and nine other leukemias. A total of 27 different drugs that were prescribed for at least six women were analyzed. Overall, non-statistically significant negative associations (Odds ratios, OR < 0.5) were observed with amoxicillin, nystatin, clomiphene, levothyroxine, cefaclor, and trimethobenzamide HCL. When cases were restricted to either myeloid or lymphoblastic leukemia, cotrimoxazole was prescribed for five ALL case mothers and no matched controls; no association with cotrimoxazole was observed with AML. Given the number of comparisons, chance cannot be ruled out for any of the associations found here. However, a strength of this study is the lack of recall bias. The disparate data observed between AML and ALL in some instances may indicate areas of interest; they will be explored further in a case-control study of infant leukemia that is currently underway.


Synthesis and biological activity of tripeptidyl polyoxins as antifungal agents.
Three tripeptidyl polyoxins were synthesized and found to inhibit Candida albicans. Compared with the naturally occurring polyoxin D, the three synthetic polyoxins had little effect on chitin synthetase when assayed with a C. albicans membrane preparation. However, all the compounds inhibited growth, affected cell morphology in a manner similar to that of polyoxin D, and were hydrolyzed by cell extracts of C. albicans. Hydrolysis did not occur extracellularly, and at least one of the synthetic polyoxins, leucyl-norleucyl-uracil polyoxin C, inhibited peptide uptake, suggesting entrance into the cell via the peptide transport system. Thus, the intact tripeptidyl polyoxins are inactive prodrugs that are converted to active moieties by cellular enzymes.


[Tourism and risk of infection (author's transl)].
Great streams of tourists flow every year from the Federal Republic to southern countries. The danger of infection with serious tropical diseases such as smallpox, cholera or leprosy is fairly small, statistically speaking. Even exotic parasitoses merit only individual medical interest in the majority of cases. Of greater importance are the cosmopolitan infectious diseases such as typhoid fever, paratyphoid, salmonella enteritis, poliomyelitis, viral hepatitides which are transmitted orally and altogether are imported in no small numbers. The alteration of the mode of living caused by the holiday and frequently a false confidence in the hygienic conditions favor the infection. Almost independent of the behavior of the tourists are the infections produced by insect bites, such as malaria or the leishmaniases, which often end fatally for lack of recognition. Here, a better enlightment of the travelers, the use of prophylactic agents and improvement of diagnosis must be instituted.