CyberKnife: a robotic radiosurgery system.
The CyberKnife is a radiosurgical system consisting of a linear accelerator and robotic arm. Using guidance imaging, the system precisely locates tumors and delivers multiple beams of radiation therapy directly to the tumor site while minimizing radiation exposure of surrounding tissue. The CyberKnife has the capacity to treat tumors up to 6 cm in size and holds promise as a new radiosurgery treatment modality.


Phasevarion-Regulated Virulence in the Emerging Pediatric Pathogen Kingella kingae.
Kingella kingae is a common etiological agent of pediatric osteoarticular infections. While current research has expanded our understanding of K. kingae pathogenesis, there is a paucity of knowledge about host-pathogen interactions and virulence gene regulation. Many host-adapted bacterial pathogens contain phase variable DNA methyltransferases (mod genes), which can control expression of a regulon of genes (phasevarion) through differential methylation of the genome. Here, we identify a phase variable type III mod gene in K. kingae, suggesting that phasevarions operate in this pathogen. Phylogenetic studies revealed that there are two active modK alleles in K. kingae Proteomic analysis of secreted and surface-associated proteins, quantitative PCR, and a heat shock assay comparing the wild-type modK1 ON (i.e., in frame for expression) strain to a modK1 OFF (i.e., out of frame) strain revealed three virulence-associated genes under ModK1 control. These include the K. kingae toxin rtxA and the heat shock genes groEL and dnaK Cytokine expression analysis showed that the interleukin-8 (IL-8), IL-1β, and tumor necrosis factor responses of THP-1 macrophages were lower in the modK1 ON strain than in the modK1::kan mutant. This suggests that the ModK1 phasevarion influences the host inflammatory response and provides the first evidence of this phase variable epigenetic mechanism of gene regulation in K. kingae.


Myocardial infarction caused by rheumatoid vasculitis: histological evidence of the involvement of T lymphocytes.
Rheumatoid arthritis (RA) is a chronic joint disease that can be complicated with extra-articular manifestations due to vasculitis. We describe a patient with RA who developed systemic vasculitis and died of myocardial infarction. Autopsy demonstrated vasculitis of the left anterior descendent and circumflex coronary arteries, which were narrowed or occluded with organizing thrombosis. Formation of granuloma with multinucleated giant cells was also observed in media of the circumflex artery. There was no microscopic evidence of atheroma formation in the coronary arteries. Of note, there was a follicle-like infiltration of CD45RO-positive T lymphocytes in interna of the left coronary arteries and the right renal artery. Although not frequently reported, coronary vasculitis as a cause of myocardial infarction should be considered in patients with RA. Moreover, our results suggest that infiltration of T lymphocytes might be involved in the development of rheumatoid vasculitis.


[Neotropical plant morphology].
An analysis on plant morphology and the sources that are important to the morphologic interpretations is done. An additional analysis is presented on all published papers in this subject by the Revista de Biología Tropical since its foundation, as well as its contribution to the plant morphology development in the neotropics.


[The incidence of Dirofilaria immitis in dogs of Havana City].
The significance of the knowledge of the incidence of Dirofilaria immitis in the dog is emphasized since dirofilariasis is a zoonosis which produce subcutaneous tumors which clinical-etiological diagnosis is very difficult. Adult forms are often located in the skin. The percentage of parasitized dogs found in the Havana city is reported. One-hundred-and-two necropsies of gadder dogs depicted that 6,86% of them had Dirofilaria immitis. Results were negative in the remaining 93,13%.


Efficient light storage in a Lambda system due to coupling between lower levels.
We show analytically and numerically that the application, during the storage time, of an additional weak field connecting the lower levels (LLs) of a Lambda system can modify the spin coherence and the amplitude of the retrieved probe without causing distortion. The LL coupling field adds an additional phase-dependent term to the probe propagation equation. The retrieved probe is amplified when the total relative phase Phi=0 or pi and decreased when Phi=pi/2.


Physical aggression and expressive vocabulary in 19-month-old twins.
In the prevention of physical aggression, possible etiological links with language development are rarely taken into account. Indeed, little is known about when language and aggressive behavior become linked during development and which mechanisms are responsible for this association. This study investigated the association between physical aggression and language in late infancy with a genetic design that involved 562 19-month-old twins. A modest but significant correlation (r = -.20) was found between physical aggression and expressive vocabulary. Substantial heritability was found for physical aggression. Quantitative genetic modeling suggests that the correlation between expressive vocabulary and physical aggression cannot be explained by shared etiologies. However, phenotype-to-phenotype models indicate that the covariation can be entirely accounted for by a significant phenotypic path from expressive vocabulary to physical aggression. The implications of these results for early prevention of chronic physical aggression are discussed.


An alternative way to cover ventral penile skin defect in Mathieu technique.
Mathieu technique is used satisfactorily in distal penile hypospadias without chordee or with minimal chordee. After using this technique, a large defect may sometimes appear on the ventral surface of the penis. To cover the defect, a few techniques, including preputial island flap, Byar's flap and Ombrédanne-Nesbit's flap, are used. We describe a new flap to cover the defect more cosmetically. Twenty-four patients ranging in age from one year to 14 years (median age 6.5 years) were operated on. In the patients for whom the defect could not be covered primarily, a longitudinal incision was made along the midline through the penile shaft skin from penile radix up to the border of preputial skin. The relaxed penile skin, which was incised on the dorsal surface, could be approached and sutured easily on the ventral surface without stretching. The new defect that developed on the dorsal surface was closed with the prepuce matching the defect. Nine patients, two with chordee and seven without chordee, underwent this technique. The cosmetic and functional results were excellent in all patients and none of the patient's parents complained about the cosmetic aspect. Only one fistula complication, which healed spontaneously, developed on the 20th postoperative day. Considering these results, we may conclude that excellent cosmetic results can be accomplished by the use of this flap technique.


Endocrine surgery: where are we today? A national survey of young endocrine surgeons.
In recent years, there has been a growing interest in endocrine surgery. Educational objectives have been published by the American Association of Endocrine Surgeons (AAES), but data have not been collected describing the recruitment pool, fellowship, or postfellowship experiences. A survey was distributed to endocrine surgeons in practice <7 years and endocrine surgery fellows. Demographic, training, and practice data were collected. The survey response rate was 69% (46/67); 85% were practicing endocrine surgeons and 15% were fellows. In all, 72% of respondents completed an endocrine surgery fellowship, 17% completed surgical oncology, and the remaining individuals completed no fellowship. The mean age was 38 (32-49) years; 39% were women, 67% were white, 26% were Asian, 11% were Hispanic, and 2% were black. A total of 89% completed residency at academic centers. Endocrine surgery fellows performed significantly more endocrine surgery cases in residency than the average graduating chief resident. Mentorship was a critical factor in fellows' decisions to pursue endocrine surgery. Fellows graduated with a median (range) of 150 (50-300) thyroid, 80 (35-200) parathyroid, 10 (2-50) neck dissection, 13 (0-60) laparoscopic adrenal, and 3 (0-35) endocrine-pancreas. Fellows felt the least prepared in neck dissection and pancreas. Of the respondents, 76% of endocrine surgeons in practice are at academic centers, and 75% have practices where most cases are endocrine based. Exposure to endocrine surgery and mentorship are powerful factors that influence residents to pursue careers in endocrine surgery. Significant variation is found in the case distribution of fellowships with a relative paucity in neck dissection, pancreas procedures, and research. Recruitment to endocrine surgery should begin in residency, and the standardization of training should be a goal.


Systematic quantum chemical study of DNA-base tautomers.
The relative energies of the energetically low-lying tautomers of pyridone, cytosine, uracil, thymine, guanine, and iso-cytosine are studied by a variety of different quantum chemical methods. In particular, we employ density functional theory (DFT) using the six functionals HCTH407, PBE, BP86, B-LYP, B3-LYP, and BH-LYP, and the ab initio methods Hartree-Fock (HF), standard second-order Møller-Plesset perturbation theory (MP2), an improved version of it (SCS-MP2), and quadratic configuration interaction including single and double excitations (QCISD) and perturbative triple corrections [QCISD(T)]. A detailed basis set study is performed for the formamide/formamidic acid tautomeric pair. In general, large AO basis sets of at least valence triple-zeta quality including f-functions (TZV) are employed, which are found to be necessary for an accurate energetic description of the various structures. The performance of the more approximate methods is evaluated with QCISD(T)/TZV(2df,2dp) data taken as reference. In general it is found that DFT is not an appropriate method for the problem. For the tautomers of pyridone and cytosine, most density functionals, including the popular B3-LYP hybrid, predict a wrong energetic order, and only for guanine, the correct sequence of tautomers is obtained with all functionals. Out of the density functionals tested, BH-LYP, which includes a rather large fraction of HF exchange, performs best. A consistent description of the nonaromatic versus aromatic tautomers seems to be a general problem especially for pure, nonhybrid functionals. Tentatively, this could be assigned to the exchange potentials used while the functional itself, including the correlation part, seems to be appropriate. Out of the ab initio methods tested, the new SCS-MP2 approach seems to perform best because it effectively reduces some outliers obtained with standard MP2. It outperforms the much more costly QCISD method and seems to be a very good compromise between computational effort and accuracy.


Quantification of nanoparticle dose and vesicular inheritance in proliferating cells.
Assessing dose in nanoparticle-cell interactions is inherently difficult due to a complex multiplicity of possible mechanisms and metrics controlling particle uptake. The fundamental unit of nanoparticle dose is the number of particles internalized per cell; we show that this can be obtained for large cell populations that internalize fluorescent nanoparticles by endocytosis, through calibration of cytometry measurements to transmission electron microscopy data. Low-throughput, high-resolution electron imaging of quantum dots in U-2 OS cells is quantified and correlated with high-throughput, low-resolution optical imaging of the nanoparticle-loaded cells. From the correlated data, we obtain probability distribution functions of vesicles per cell and nanoparticles per vesicle. Sampling of these distributions and comparison to fluorescence intensity histograms from flow cytometry provide the calibration factor required to transform the cytometry metric to total particle dose per cell, the mean value of which is 2.4 million. Use of the probability distribution functions to analyze particle partitioning during cell division indicates that, while vesicle inheritance is near symmetric, highly variable vesicle loading leads to a highly asymmetric particle dose within the daughter cells.


Effect of aqueous extract of Vernonia amygdalina on atherosclerosis in rabbits.
Extracts of Vernonia amygdalina (V. amygdalina) have been shown to affect the serum lipid profile of some laboratory animals in previous studies. Its impact on serum lipid profile and the histological changes in atherosclerosis has not been studied. Our aim was to determine the effects of V. amygdalina on atherosclerotic lesions induced in rabbits on high-cholesterol diet. 18 male rabbits were randomly divided into three groups of control, atherogenic diet, and atherogenic diet + 200 mg/kg of V. amygdalina. The rabbits were fed a normal diet (control group) or a diet supplemented by 0.5% cholesterol and 1% methionine (second and third groups, respectively) for 12 weeks. The fasting sera of all animals were collected at baseline and at the end of the 12 weeks, to determine the levels of lipid profile and the aortas underwent pathomorphological examination. The two groups on the atherogenic diet had significantly increased serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the control group. The serum triglyceride (TG) was not statistically different in all three groups. High-density lipoprotein cholesterol (HDL-C) was significantly increased in the V. amygdalina group, compared to the control group but there was no statistically significant difference between the two groups on atherogenic diet. The two groups of rabbits that were on high-cholesterol diet (atherogenic diet group, as well as the atherogenic diet + 200 mg/kg of V. amygdalina) developed histological evidence of atherosclerosis. However, there was no histological difference between the lesions observed in these two groups. The use of 200 mg/kg of aqueous extract of V. amygdalina in rabbits did not appear to exert a significant effect on the serum lipid profile. It also did not appear to have any beneficial effect on the development of atherosclerotic lesions.


[North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance].
Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.


[Hospitalization for primary care sensitive conditions in municipalities with full local health management control in Rio Grande do Sul State, Brazil].
We assess the quality of care provided in the cities with full health system management, in the state of Rio Grande do Sul, Brazil, by means of the rate of hospitalizations for primary care sensitive conditions, between 1995 and 2005. The following were considered as hospitalizations for sensitive conditions: diabetes mellitus, heart failure, hypertension, chronic obstructive pulmonary disease and immunopreventive diseases in individuals aged between 20 and 59 years. Findings reveal that, beginning in 2001, there has been a reduction in rates in almost all cities. Through the Poisson regression we didn't observe a lower rates after the full health system management. Among cities with full health system management, rates of hospitalizations for ambulatory care sensitive conditions increased as the population size decreased. Hospitalizations for ambulatory care sensitive conditions were found to be low-cost, easily-operated indicators and can produce knowledge about health systems, enabling their quality improvement.


Prevalence of Elevated Serum IgG4 Level among Patients Diagnosed or Suspected with Cardiovascular Disorders.
Immunoglobulin G4 (IgG4)-related disease, that is characterized by the elevation of circulating IgG4 level and the tissue-infiltration of IgG4-positive plasma cells, can target the cardiovascular tissue, although the diagnosis of IgG4-related cardiovascular lesion is not easy owing to the substantial risk for the tissue sampling. We herein examined the serum IgG4 levels among cardiac patients. In patients who were admitted to the cardiology department (n=477) and those who underwent computed tomography coronary artery angiography (n=401), elevated serum IgG4 level (≥135 mg/dL) was found 23 (4.8%) and 17 (4.2%), respectively. However, among those with elevated serum IgG4, only two patients could be clinicopathologically diagnosed with IgG4-related disease. Cardiovascular organ involvement may aggravate the prognosis of IgG4-related disease which in general not life-threatening. Considering that the non-negligible prevalence of high IgG4 level among cardiac patients who were not diagnosed with IgG4-related disease, however, physicians should not count too much on the serum IgG4 levels for the diagnosis of IgG4-related cardiovascular lesions, especially when histopathologic findings are not available, or when other-tissue involvement of IgG4-related disease is not apparent. (This is a translation of J Jpn Coll Angiol 2017; 57: 91-98.).


[Modern imaging and stereotaxy].
The authors present their technique of utilization in stereotaxic neurosurgery of CT and IRM documents realized in standard condition. Besides, they present an original apparatus that allows to combine the advantages of Leksell and Talairach's stereotaxic system.


Rapid screening of different chelating agents in the lead extraction from cathode ray tube (CRT) funnel glass.
The cathode ray tube (CRT) glass is one of the most important problem that afflicts the electronic waste disposal whose solution lies in the identification of efficient and ecofriendly processes to detoxify and reutilize lead-contained funnel glass. This study is focused on a rapid screening of different chemical and mechanochemical processes to reduce lead content in waste CRT glass downgrading the risk correlated to it. In particular, as a possibility to clean waste CRT glass, treatments of lead-containing glass with different chelating agents (EDTA, NTA, ATMP, EDTMP and HEDP) were performed to evaluate their extractive capabilities. Furthermore, the influence of the grinding, the chelating agent functional groups (polyamino-carboxylic acid, carboxylic acid, and polyamino phosphonic acid), and the time and the temperature on lead content reduction were analyzed. ESEM and EDS analysis were performed on all the samples to evaluate the lead amount before and after the treatments.


Molecular Mechanisms of Microbial Survivability in Outer Space: A Systems Biology Approach.
Since the dawn of space exploration, the survivability of terrestrial life in outer space conditions has attracted enormous attention. Space technology has enabled the development of advanced space exposure facilities to investigate in situ responses of microbial life to the stress conditions of space during interplanetary transfer. Significant progress has been made toward the understanding of the effects of space environmental factors, e.g., microgravity, vacuum and radiation, on microorganisms exposed to real and simulated space conditions. Of extreme importance is not only knowledge of survival potential of space-exposed microorganisms, but also the determination of mechanisms of survival and adaptation of predominant species to the extreme space environment, i.e., revealing the molecular machinery, which elicit microbial survivability and adaptation. Advanced technologies in -omics research have permitted genome-scale studies of molecular alterations of space-exposed microorganisms. A variety of reports show that microorganisms grown in the space environment exhibited global alterations in metabolic functions and gene expression at the transcriptional and translational levels. Proteomic, metabolomic and especially metabolic modeling approaches as essential instruments of space microbiology, synthetic biology and metabolic engineering are rather underrepresented. Here we summarized the molecular space-induced alterations of exposed microorganisms in terms of understanding the molecular mechanisms of microbial survival and adaptation to drastic outer space environment.


DMMG: Dual Min-Max Games for Self-Supervised Skeleton-Based Action Recognition.
In this work, we propose a new Dual Min-Max Games (DMMG) based self-supervised skeleton action recognition method by augmenting unlabeled data in a contrastive learning framework. Our DMMG consists of a viewpoint variation min-max game and an edge perturbation min-max game. These two min-max games adopt an adversarial paradigm to perform data augmentation on the skeleton sequences and graph-structured body joints, respectively. Our viewpoint variation min-max game focuses on constructing various hard contrastive pairs by generating skeleton sequences from various viewpoints. These hard contrastive pairs help our model learn representative action features, thus facilitating model transfer to downstream tasks. Moreover, our edge perturbation min-max game specializes in building diverse hard contrastive samples through perturbing connectivity strength among graph-based body joints. The connectivity-strength varying contrastive pairs enable the model to capture minimal sufficient information of different actions, such as representative gestures for an action while preventing the model from overfitting. By fully exploiting the proposed DMMG, we can generate sufficient challenging contrastive pairs and thus achieve discriminative action feature representations from unlabeled skeleton data in a self-supervised manner. Extensive experiments demonstrate that our method achieves superior results under various evaluation protocols on widely-used NTU-RGB+ D, NTU120-RGB+D and PKU-MMD datasets.


Desensitization of beta-adrenergic receptor-coupled adenylate cyclase in cerebral cortex after in vivo treatment of rats with desipramine.
Continuous treatment (1-10 days) of rats with desipramine (10 mg/kg, twice per day) caused desensitization of the beta-adrenergic receptor-coupled adenylate cyclase system of cerebral cortical membranes. The decrease in the isoproterenol-stimulated adenylate cyclase activity was more rapid and greater than the decrease in the number of beta-adrenergic receptors in membranes during treatment of the membrane donor rats with desipramine, indicating that the desensitization occurring at an early stage of the treatment was not accounted for solely by the decrease in the receptor number. Neither the guanine nucleotide regulatory protein (N) nor the adenylate cyclase catalyst was impaired by the drug treatment, since there was no decrease in the cyclase activity measured in the presence or absence of GTP, guanyl-5'-yl-beta-gamma-imidodiphosphate [Gpp(NH)p], NaF, or forskolin. Gpp(NH)p-induced activation of membrane adenylate cyclase developed with a lag time of a few minutes in membranes from control or drug-treated rats. The lag was shortened by the addition of isoproterenol, indicating that beta-receptors were coupled to N in such a manner as to facilitate the exchange of added Gpp(NH)p with endogenous GDP on N. This effect of isoproterenol rapidly decreased during the drug treatment of rats. Thus, functional uncoupling of the N protein from receptors was responsible for early development of desensitization of beta-adrenergic receptor-mediated adenylate cyclase in the cerebral cortex during desipramine therapy.


A nested cohort study of 6,248 early breast cancer patients treated in neoadjuvant and adjuvant chemotherapy trials investigating the prognostic value of chemotherapy-related toxicities.
The relationship between chemotherapy-related toxicities and prognosis is unclear. Previous studies have examined the association of myelosuppression parameters or neuropathy with survival and reported conflicting results. This study aims to investigate 13 common chemotherapy toxicities and their association with relapse-free survival and breast cancer-specific survival. Chemotherapy-related toxicities were collected prospectively for 6,248 women with early-stage breast cancer from four randomised controlled trials (NEAT; BR9601; tAnGo; Neo-tAnGo). Cox proportional-hazards modelling was used to analyse the association between chemotherapy-related toxicities and both breast cancer-specific survival and relapse-free survival. Models included important prognostic factors and stratified by variables violating the proportional hazards assumption. Multivariable analysis identified severe neutropenia (grades ≥3) as an independent predictor of relapse-free survival (hazard ratio (HR) = 0.86; 95% confidence interval (CI), 0.76-0.97; P = 0.02). A similar trend was seen for breast cancer-specific survival (HR = 0.87; 95% CI, 0.75-1.01; P = 0.06). Normal/low BMI patients experienced more severe neutropenia (P = 0.008) than patients with higher BMI. Patients with fatigue (grades ≥3) showed a trend towards reduced survival (breast cancer-specific survival: HR = 1.17; 95% CI, 0.99-1.37; P = 0.06). In the NEAT/BR9601 sub-group analysis by treatment component, this effect was statistically significant (HR = 1.61; 95% CI, 1.13-2.30; P = 0.009). This large study shows a significant association between chemotherapy-induced neutropenia and increased survival. It also identifies a strong relationship between low/normal BMI and increased incidence of severe neutropenia. It provides evidence to support the development of neutropenia-adapted clinical trials to investigate optimal dose calculation and its impact on clinical outcome. This is important in populations where obesity may lead to sub-optimal chemotherapy doses.


Landscape genomics and a common garden trial reveal adaptive differentiation to temperature across Europe in the tree species Alnus glutinosa.
The adaptive potential of tree species to cope with climate change has important ecological and economic implications. Many temperate tree species experience a wide range of environmental conditions, suggesting high adaptability to new environmental conditions. We investigated adaptation to regional climate in the drought-sensitive tree species Alnus glutinosa (Black alder), using a complementary approach that integrates genomic, phenotypic and landscape data. A total of 24 European populations were studied in a common garden and through landscape genomic approaches. Genotyping-by-sequencing was used to identify SNPs across the genome, resulting in 1990 SNPs. Although a relatively low percentage of putative adaptive SNPs was detected (2.86% outlier SNPs), we observed clear associations among outlier allele frequencies, temperature and plant traits. In line with the typical drought avoiding nature of A. glutinosa, leaf size varied according to a temperature gradient and significant associations with multiple outlier loci were observed, corroborating the ecological relevance of the observed outlier SNPs. Moreover, the lack of isolation by distance, the very low genetic differentiation among populations and the high intrapopulation genetic variation all support the notion that high gene exchange combined with strong environmental selection promotes adaptation to environmental cues.


The effects of implicit modeling of nonpolar solvation on protein folding simulations.
Implicit solvent models, in which the polar and nonpolar solvation free-energies of solute molecules are treated separately, have been widely adopted for molecular dynamics simulation of protein folding. While the development of the implicit models is mainly focused on the methodological improvement and key parameter optimization for polar solvation, nonpolar solvation has been either ignored or described by a simplistic surface area (SA) model. In this work, we performed the folding simulations of multiple β-hairpin and α-helical proteins with varied surface tension coefficients embedded in the SA model to clearly demonstrate the effects of nonpolar solvation treated by a popular SA model on protein folding. The results indicate that the change in the surface tension coefficient does not alter the ability of implicit solvent simulations to reproduce a protein native structure but indeed controls the components of the equilibrium conformational ensemble and modifies the energetic characterization of the folding transition pathway. The suitably set surface tension coefficient can yield explicit solvent simulations and/or experimentally suggested folding mechanism of protein. In addition, the implicit treatment of both polar and nonpolar components of solvation free-energy contributes to the overestimation of the secondary structure in implicit solvent simulations.


Black soldier fly as dietary protein source for broiler quails: meat proximate composition, fatty acid and amino acid profile, oxidative status and sensory traits.
In the perspective of improving the sustainability of meat production, insects have been rapidly emerging as innovative feed ingredient for some livestock species, including poultry. However, at present, there is still limited knowledge regarding the quality and sensory traits of the derived meat. Therefore, the present study tested the effect of a partial substitution of soya bean meal and oil with defatted black soldier fly (Hermetia illucens) larvae meal (H) in the diet for growing broiler quails (Coturnix coturnix japonica) on meat proximate composition, cholesterol, amino acid and mineral contents, fatty acid profile, oxidative status and sensory characteristics. To this purpose, three dietary treatments were designed: a control diet (C) and two diets (H1 and H2) corresponding to 10% and 15% H inclusion levels, respectively, were fed to growing quails from 10 to 28 days of age. At 28 days of age, quails were slaughtered and breast meat was used for meat quality evaluations. Meat proximate composition, cholesterol content and oxidative status remained unaffected by H supplementation as well as its sensory characteristics and off-flavours perception. Differently, with increasing the dietary H inclusion, the total saturated fatty acid and total monounsaturated fatty acid proportions raised to the detriment of the polyunsaturated fatty acid fraction thus lowering the healthiness of the breast meat. The H2 diet increased the contents of aspartic acid, glutamic acid, alanine, serine, tyrosine and threonine thus further enhancing the biological value of the meat protein. As a direct result of the dietary content of Ca and P, the meat of quails fed with the highest H level, displayed the highest Ca and the lowest P values. Therefore, meat quality evaluations confirmed H to be a promising insect protein source for quails. The only potential drawback from feeding H to broiler quails regarded the fatty acid profile of the meat, therefore requiring further research efforts to understand to what extent the fatty acid profile of H can be improved.


Glycosylated metal chelators as anti-parasitic agents with tunable selectivity.
Trypanosoma cruzi and Leishmania amazonensis are the causative agents of Chagas' disease and leishmaniasis, respectively. These conditions affect millions of people worldwide, especially in developing countries. As such, there is an urgent need for novel, efficient and cost-effective treatments for these diseases, given the growing resistance and side-effects of current therapies. This work details the synthesis and evaluation of the anti-parasitic activity of novel amino- and iminopyridyl metal chelators, their glycosylated derivatives and some of their metal complexes. Our results revealed the potent and metal-dependent activity for the aminopyridyl compounds: Cu(ii) complexes were most effective against T. cruzi trypomastigotes, while Zn(ii) complexes presented excellent activity against L. amazonensis promastigotes. In addition, the compounds showed excellent selectivity indexes and very low relative toxicity as judged by in vitro and in vivo studies, respectively, using RAW macrophages and Galleria mellonella larvae model.


Multiview-video-plus-depth coding based on the advanced video coding standard.
This paper presents a multiview-video-plus-depth coding scheme, which is compatible with the advanced video coding (H.264/AVC) standard and its multiview video coding (MVC) extension. This scheme introduces several encoding and in-loop coding tools for depth and texture video coding, such as depth-based texture motion vector prediction, depth-range-based weighted prediction, joint inter-view depth filtering, and gradual view refresh. The presented coding scheme is submitted to the 3D video coding (3DV) call for proposals (CfP) of the Moving Picture Experts Group standardization committee. When measured with commonly used objective metrics against the MVC anchor, the proposed scheme provides an average bitrate reduction of 26% and 35% for the 3DV CfP test scenarios with two and three views, respectively. The observed bitrate reduction is similar according to an analysis of the results obtained for the subjective tests on the 3DV CfP submissions.


Systemic reaction rates with omalizumab, subcutaneous immunotherapy, and combination therapy in children with allergic asthma.
Background: For children with moderate-to-severe persistent allergic asthma, omalizumab is effective. However, it is expensive, and there are no current guidelines for discontinuation. Subcutaneous immunotherapy (SCIT) is the only approach that can provide persistent beneficial effects after treatment is discontinued. However, SCIT is contraindicated in poorly controlled asthma. Therefore, we performed, to our knowledge, the first U.S. study that exclusively compared the safety of omalizumab, SCIT, and combination (omalizumab and SCIT) therapy in children with allergic asthma. Objective: We hypothesize that the systemic reaction (SR) rates in children who receive combination therapy are comparable with omalizumab alone. Methods: We performed a retrospective study of children ages 6-18 years old with allergic asthma who, from July 2010 to June 2017, received SCIT, omalizumab, or combination therapy in our children's allergy clinic. Our primary end point was to determine the SR rate among each of these groups. Results: We reviewed the records of 89 patients: 30 patients with SCIT (1550 injections), 30 patients with omalizumab (729 injections), and 29 patients with combination therapy (954 injections). In the SCIT group, 19 SRs (1.2% of injections) occurred in 10 patients (33%). In the omalizumab group, three SRs (0.4% of injections) occurred in three patients (10%). Similarly, in the combination group, three SRs (0.3% of injections) occurred in three patients (10%). Compared with the SR rate in the SCIT group, both omalizumab and combination groups had significantly lower SR rates (p = 0.045 and p = 0.011, respectively). The SR rates in children who received omalizumab and children who received combination therapy were not statistically different (p = 0.73). Conclusion: Children with moderate-severe persistent allergic asthma who received omalizumab or combination therapy had significantly lower SR rates compared with children with allergic asthma who received SCIT alone. SCIT in children treated with omalizumab was safe and may serve both as an omalizumab-sparing treatment and as a bridge to safely administer SCIT.


[The impact of sepsis bundles on mortality in patients with sepsis shock: a prospective clinical study].
To survey the impact of sepsis bundle on prognosis of septic shock. From January 2007 to June 2008, a prospective clinical study was conducted on consecutive adult patients with sepsis shock in intensive care unit (ICU). The study of sepsis bundle on septic shock was divided into before training (from January to September 2007) and trained phases (from October 2007 to June 2008), and the patients were divided into control group and death group. The relationship between sepsis bundle index and prognosis at 6 hours and 24 hours was analyzed with logistic regression analysis. The independent factors of death due to septic shock were looked for. The compliance of sepsis bundles, duration of mechanical ventilation (MV), ICU stay, and 28-day mortality were noted. One hundred patients, including 51 patients before training and 49 patients after training were enrolled for study. Thirty-six patients survived and 64 patients died. All the patients met the criteria for the diagnosis of sepsis shock. Through analysis of the parameters with logistic regression, it could be found that 6-hour early goal-directed therapy (EGDT) and 24-hour EGDT were the two independent protective factors of death, and standardized regression coefficient was 0.046 and 0.120 respectively (both P < 0.01). Compliance with sepsis bundles was low in training phase, the compliance increased apparently after training. Among them, 6-hour EGDT and 24-hour EGDT compliance increased to 55.1%, 65.3% from 19.6%, 35.3% (both P < 0.01). Compared with the group before training, the duration of MV [(166.6+/-156.4) hours vs. (113.6+/-73.6) hours], that of ICU stay [(9.4+/-7.6) days vs. (6.0+/-3.9) days] and 28-day mortality (72.5% vs. 55.1%, P < 0.05 or P < 0.01) was significantly lower after training. Sepsis bundle is able to improve survival rate in patients in septic shock. Compliance with sepsis bundles is low before training, and training can improve the compliance and decrease mortality rate of septic shock.


Abnormal glucose tolerance during pregnancy in Pima Indian women. Long-term effects on offspring.
The long-term effects on offspring of abnormal glucose tolerance detected during pregnancy were examined in 552 Pima Indian offspring 5-24 yr of age. Fasting hyperinsulinemia, presumably reflecting increased insulin resistance, occurred at an earlier age in the offspring of women who had abnormal glucose tolerance during pregnancy, and these offspring were more obese and had higher rates of abnormal glucose tolerance. When confounding factors were controlled, a 1 mM higher 2-h postload glucose concentration during pregnancy resulted in a significantly higher prevalence of diabetes in the offspring (odds ratio = 162). Maternal 2-h glucose concentration during pregnancy was also a significant predictor of glucose concentration during pregnancy in the offspring (P = 0.011). Thus, the metabolic abnormalities associated with the diabetic pregnancy result in long-term effects on the offspring, including insulin resistance, obesity, and diabetes, which in turn may contribute to transmission of risk for developing the same problems in the next generation.


Clinical characteristics and outcomes of pregnant women with COVID-19 and comparison with control patients: A systematic review and meta-analysis.
In a large-scale study, 128176 non-pregnant patients (228 studies) and 10000 pregnant patients (121 studies) confirmed COVID-19 cases included in this Meta-Analysis. The mean (confidence interval [CI]) of age and gestational age of admission (GA) in pregnant women was 33 (28-37) years old and 36 (34-37) weeks, respectively. Pregnant women show the same manifestations of COVID-19 as non-pregnant adult patients. Fever (pregnant: 75.5%; non-pregnant: 74%) and cough (pregnant: 48.5%; non-pregnant: 53.5%) are the most common symptoms in both groups followed by myalgia (26.5%) and chill (25%) in pregnant and dysgeusia (27%) and fatigue (26.5%) in non-pregnant patients. Pregnant women are less probable to show cough (odds ratio [OR] 0.7; 95% CI 0.67-0.75), fatigue (OR: 0.58; CI: 0.54-0.61), sore throat (OR: 0.66; CI: 0.61-0.7), headache (OR: 0.55; CI: 0.55-0.58) and diarrhea (OR: 0.46; CI: 0.4-0.51) than non-pregnant adult patients. The most common imaging found in pregnant women is ground-glass opacity (57%) and in non-pregnant patients is consolidation (76%). Pregnant women have higher proportion of leukocytosis (27% vs. 14%), thrombocytopenia (18% vs. 12.5%) and have lower proportion of raised C-reactive protein (52% vs. 81%) compared with non-pregnant patients. Leucopenia and lymphopenia are almost the same in both groups. The most common comorbidity in pregnant patients is diabetes (18%) and in non-pregnant patients is hypertension (21%). Case fatality rate (CFR) of non-pregnant hospitalized patients is 6.4% (4.4-8.5), and mortality due to all-cause for pregnant patients is 11.3% (9.6-13.3). Regarding the complications of pregnancy, postpartum hemorrhage (54.5% [7-94]), caesarean delivery (48% [42-54]), preterm labor (25% [4-74]) and preterm birth (21% [12-34]) are in turn the most prevalent complications. Comparing the pregnancy outcomes show that caesarean delivery (OR: 3; CI: 2-5), low birth weight (LBW) (OR: 9; CI: 2.4-30) and preterm birth (OR: 2.5; CI: 1.5-3.5) are more probable in pregnant woman with COVID-19 than pregnant women without COVID-19. The most prevalent neonatal complications are neonatal intensive care unit admission (43% [2-96]), fetal distress (30% [12-58]) and LBW (25% [16-37]). The rate of vertical transmission is 5.3% (1.3-16), and the rate of positive SARS-CoV-2 test for neonates born to mothers with COVID-19 is 8% (4-16). Overall, pregnant patients present with the similar clinical characteristics of COVID-19 when compared with the general population, but they may be more asymptomatic. Higher odds of caesarean delivery, LBW and preterm birth among pregnant patients with COVID-19 suggest a possible association between COVID-19 infection and pregnancy complications. Low risk of vertical transmission is present, and SARS-CoV-2 can be detected in all conception products, particularly placenta and breast milk. Interpretations of these results should be done cautiously due to the heterogeneity between studies; however, we believe our findings can guide the prenatal and postnatal considerations for COVID-19 pregnant patients.


Catalytic formation of monosaccharides: from the formose reaction towards selective synthesis.
The formose reaction (FR) has been long the focus of intensive investigations as a simple method for synthesis of complex biologically important monosaccharides and other sugar-like molecules from the simplest organic substrate-formaldehyde. The fundamental importance of the FR is predominantly connected with the ascertainment of plausible scenarios of chemical evolution which could have occurred on the prebiotic Earth to produce the very first molecules of carbohydrates, amino- and nucleic acids, as well as other vitally important substances. The practical importance of studies on the FR is the elaboration of catalytic methods for the synthesis of rare and non-natural monosaccharides and polyols. This Minireview considers the FR from the point of view of chemists working in the field of catalysis with emphasis on the mechanisms of numerous parallel and consequent catalytic transformations that take place during the FR. Based on its kinetics, the FR may be considered as a non-radical chain process with degenerate branching. The Minireview also considers different approaches to the control of selectivity of carbohydrate synthesis from formaldehyde and lower monosaccharides.


SOIL and SOIL-NO at catchment scale--a case study for an agriculture-dominated catchment.
A one-dimensional model, SOIL/SOIL-NO, is used to simulate the water and nitrogen balance at catchment scale. The objective is to use the model in simulating the effects of best management practices on nitrogen runoff. The model was applied to individual farm fields in an agriculture dominated catchment and simulations were carried out for the period from 94-98. The results were promising. The simulated nitrogen runoff agreed quite well with the measured nitrogen loss at the main station. The effects of best management practices like optimal fertiliser application, catch crops and irrigation were simulated. For this particular catchment, the introduction of catch crops resulted in the best effect on reducing nitrogen runoff from agricultural dominated catchments.


Molar extinction coefficients and the photon absorption efficiency of dental photoinitiators and light curing units.
The light absorption of dental photoinitiators should correlate with the spectral emission profiles of dental light curing units compared on an equivalent basis. Spectral data of dental photoinitiators and light curing units can be used to define the photon absorption efficiency (PAE) obtained by integrating the product of the absorption and emission spectra in terms of photons. This parameter can be used to identify the best performance for photochemical process with specific photoinitiators. The efficiency of two LED and one QTH lamps were tested comparing their performances with the photoinitiators camphorquinone (CQ); phenylpropanedione (PPD); monoacylphosphine oxide (Lucirin TPO); and bisacylphosphine oxide (Irgacure 819). Absorption and emission spectra of the photoinitiators and the LED (Ultrablue I and Ultrablue IS) and QTH (Optilux 401) LCUs were determined in the 360-550nm range. CQ exhibited an absorption centered in the blue region and, although the maxima of PPD, MAPO, and BAPO were in the UV-A region, their absorption extended to the visible region. Power output maxima of the LCUs were at 467 (Ultrablue I), 454 (Ultrablue IS) and 493nm (Optilux 401), and the total power densities were 170+/-1, 470+/-4 and 444+/-4mW/cm(2), respectively. The use of the PAE allows a prediction of the most efficient photoinitiator/LCU systems. For similar photoinitiator concentrations, Lucirin and CQ are most efficiently photoinitiated by the QTH unit, whereas the high-power LED device is more efficient for Irgacure. PPD is photoactivated similarly by both LCUs.


A Case of Esophageal Cancer Treated by Thoracoscopic Esophagectomy after Bilateral Cadaveric Lung Transplantation.
With de novo cancer, esophagectomy after lung transplantation (LTx) can be challenging because of intrathoracic adhesions, delayed wound healing, and postoperative pulmonary complications, which might be lethal. A 52-year-old woman with esophageal cancer had undergone bilateral LTx for end-stage diffuse panbronchiolitis at 50 years of age. Thoracoscopic esophagectomy was performed. Bilateral bronchial arteries and subcarinal and bilateral bronchial lymph nodes were preserved to maintain blood supply to the transplanted bronchi. No ischemic changes were observed in either bronchi. The patient's postoperative course was uneventful. Although she underwent chemoradiation therapy for recurrence at the left cervical paraesophageal lymph node, she remains alive with good disease control and well-maintained respiratory function. Minimally invasive surgery with careful attention to blood supply to the transplanted bronchi was useful for treating esophageal cancer after LTx.


Is early invasive management as ST elevation myocardial infarction warranted in de Winter's sign?-a "peak" into the widow-maker.
de Winter's sign was first described by de Winter et al. in 2008 as a new electrocardiographic (EKG) pattern of acute proximal left anterior descending coronary artery (LAD) occlusion. Instead of the normal presentation of ST elevation, it is described as depression of ST segment at the J point in the precordial leads V1-V6, which are upsloping leading to hyper-acute T waves, with ST elevation in aVR. The initial retrospective systematic analysis proved this sign to be present in about 2% of anterior myocardial infarction. This review aims to address the important question of mode and urgency of intervention, on detection of de Winter's sign. In this review, we take a look at the de Winter's sign EKG characteristics, accuracy in diagnosis, typical patient presentation, and the outcomes of early intervention. We conducted a Medline search using various combinations of "de Winter's sign," "STEMI equivalent," "cardiac catheterization," and "thrombolysis" to identify pivotal research articles published before June 1, 2019, for inclusion in this review. Concurrently, major practice guidelines, trial bibliographies, and pertinent reviews were examined to ensure inclusion of relevant trials. A consensus among the authors was used to choose items for narrative inclusion. The following section reviews data from pivotal trials to determine the need for early invasive management in de Winter's sign. Research articles reviewed evaluating cardiac catheterization in de Winter's sign. de Winter's sign, although rare (~2%), should be promptly recognized, as it reveals underlying severe coronary artery pathology, frequently involving the LAD which is associated with a high rate of mortality. This systematic review emphasizes awareness and strong consideration of early activation of the cardiac catheterization lab with PPCI; which may yield better treatment outcomes. The evidence suggests that de Winter's sign, presenting with ST depression and T wave elevation, should indeed be treated as ST-elevation myocardial infarction (STEMI) equivalent, with prompt recognition and early intervention.


Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans.
7-Ethyl-10[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin (CPT-11), a DNA topoisomerase I inhibitor, undergoes several metabolic pathways to generate conjugated and unconjugated derivatives that could be excreted from the body. The objective of this study was to determine the oxidative metabolites of CPT-11 recovered in human urine samples and to identify cytochrome P450 (CYP) involved in their formation. In addition to the already known metabolites of CPT-11 [SN-38, SN-38-G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC), and 7-ethyl-10-(4-amino-1-piperidino) carbonyloxycamptothecin (NPC)], we isolated three oxidized metabolites from the urine of two children and two adults given CPT-11. M1 and M2 (molecular weight, 602) were hydroxylated, respectively, on the CPT moiety and on the terminal piperidine ring of CPT-11. M3 had a molecular mass of 602, but its urine concentration in patients was too low to establish its chemical structure by liquid chromatography/mass spectrometry. In vitro incubations with cells expressing CYP2C8, CYP2C9, CYP1A1, CYP1A2, or CYP3A7 did not produce any detectable metabolites. Only CYP3A4 produced both APC and NPC, resulting from the oxidation of the piperidinylpiperidine side chain of CPT-11 along with metabolite M2. The metabolism of CPT-11 by CYP3A5 was markedly different because neither APC or NPC nor M2 was produced, whereas only one new metabolite, M4 (molecular weight, 558), was generated by de-ethylation of the CPT moiety. No previous study has reported the presence of the M4 metabolite. Production of APC, NPC, M2, and M4 was prevented by ketoconazole, a specific CYP3A inhibitor. The parameters of CPT-11 biotransformation into M2 and M4 were examined using cell lines expressing, respectively, with CYP3A4 and CYP3A5, indicating that CPT-11 is preferentially metabolized by CYP3A4. In conclusion, CYP3A plays a major role in the metabolism of CPT-11, with some differences of the metabolic profile exhibited by 3A4 and 3A5.


Testing visual capabilities for medical surveillance or to ensure job fitness.
A rationale is presented for designing screening-type eye examinations to document visual capabilities for specific jobs or changes in visual function following exposure to specific ocular hazards. Possible applications to clinical situations are also discussed. A battery of tests that includes contrast (glare) sensitivity, distortions in macular imaging, and color vision is detailed for use with three populations: automobile driver's license applicants, visual display operators, and laser users, including military as well as nonmilitary installers and repairers of optical fibers for communications.


Phase 1 study of topical perillyl alcohol cream for chemoprevention of skin cancer.
Perillyl alcohol (POH) is a natural product derived from plants such as cherry and lavendin. Previous studies have indicated that topical POH inhibits ultraviolet (UV) B-induced skin carcinogenesis in vivo, and it may be an effective chemopreventive agent for skin cancer. We performed a 1-mo, first-in-man, Phase 1 trial of topically administered POH cream in human subjects. Endpoints included safety and evaluation of any histopathological changes in skin after 1 mo use of POH cream. We randomized 25 subjects with normal, healthy skin with little or no sun damage and no history of skin cancer in a double-blind fashion to receive topical POH (0.76% wt/wt) on 1 forearm with placebo cream applied to the other forearm twice daily for 30 days. Subjects were monitored for toxicity, and a 4 mm punch biopsy in the treated area was performed at the end of study for histopathological evaluation. The topical cream was well tolerated. No serious cutaneous toxicities, systemic toxicities, or histopathological abnormalities were observed. A total of 8 subjects (32%) reported mild adverse events possibly or probably related to use of cream including reversible appearance of 1 to 2 small papules. However, there was no significant difference between lesions appearing on the POH treated forearm vs. the placebo-treated forearm.


[Diabetes mellitus in the elderly population in an urban area of Southern Brazil: a mortality and hospital morbidity study].
This study aimed to investigate the mortality trend and hospital morbidity from diabetes mellitus (DM) in an elderly population from Maringá, PR. The death information was obtained from the Brazilian Official Mortality Information System and hospitalization data from the official Hospital Information of the National Health System. Mortality data were analyzed from 1979 to 1998 and morbidity data from 1996 to 1998, both for people 60 years old and over. Population data were estimated from the national demographic census. From 1979 to 1998, the proportional mortality and mortality rate for DM in the elderly have increased 16% and 91.1%, respectively, for both sexes. The mortality rate increased from 72 to 137.6 per 100,000 inhabitants, an increase of 147.8% for men and 61.9% for women, more importantly after 80 years old. From the hospital admissions for endocrine, nutritional and metabolic diseases, nearly 60% were for Dm and among those, 30% for men and 70% for women. During the study period, hospitalization rates have decreased in all age groups. It is important for the municipality to recognize and improve the health promotion services specifically those addressed to the risk factors for DM in the community.


Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary.
A few years before reproductive senescence, primordial follicles are depleted from the ovary at a dramatically accelerated rate. It has been proposed that this depletion is due to transient increases in gonadotropin levels. To test this hypothesis, we used mice that produce chronically elevated levels of serum LH via expression of an LHbeta subunit transgene. Ovaries were collected from transgenic and control mice, and complete serial sections were prepared for histological examination. Each section was scanned for morphological abnormalities, and every fifth section was sampled to estimate the total number of primordial, primary, and large preantral follicles per ovary. Until 3 wk postpartum, ovaries from transgenic and control mice were morphologically similar. By 5 wk, control ovaries contained many healthy primordial, primary, and large preantral follicles as well as atretic follicles. Transgenic ovaries contained blood-filled cysts, misshapen granulosa cells, luteinized cells, and approximately 45% fewer primordial follicles than controls. By 3 mo, transgenic ovaries had about 68% fewer primordial follicles and 53% fewer primary follicles than controls. These results suggest that, in addition to having profound effects on growing follicles, chronically elevated LH levels deplete the primordial follicle pool and thus may hasten the onset of reproductive senescence.


Isolation and reconstitution of iron- and manganese-containing superoxide dismutases from Bacteroides thetaiotaomicron.
Superoxide dismutase (SOD) from extracts of anaerobically maintained Bacteroides thetaiotaomicron was a dimer of equally sized 23,000-molecular-weight monomers joined noncovalently. A preparation with a specific activity of 1,200 U/mg contained 1.1 g-atom of Fe, 0.6 g-atom of Zn, and less than 0.05 g-atom of Mn per mol of dimer. The apoprotein, prepared by dialysis of iron-SOD in 5 M guanidinium chloride-20 mM 8-hydroxyquinoline, had no superoxide-scavenging activity when renatured without exogenous metal. Enzymatic activity was restored to the denatured apoprotein by dialysis against either 1 mM Fe(NH4)2 or 1 mM MnCl2 in 20 mM Tris (pH 7.0). The Fe-reconstituted enzyme and the native enzyme were inhibited approximately 50% by 0.2 mM NaN3, whereas the Mn-reconstituted enzyme was inhibited 60% by 10 mM NaN3. Aeration of the anaerobic cells resulted in a fourfold induction of an azide-resistant SOD. The enzyme (43,000 molecular weight) isolated from aerated cells was a dimer of equally sized subunits. The metal content was 1.0 g-atom of Mn, 0.55 g-atom of Fe, and 0.3 g-atom of Zn per mol of dimer. Enzymatic activity of the denatured apoprotein from this enzyme was also restored on addition of either iron or manganese. The constitutive Fe-SOD and the O2-induced Mn-SOD, tested alone and in combination, migrated identically on acrylamide gels, had similar amino acid compositions, and had alanine as the sole N-terminal amino acid. These data are consistent with the synthesis of a single apoprotein in either anaerobically maintained or oxygenated cells. We have observed a similar phenomenon with SOD from Bacteroides fragilis (E. M. Gregory, Arch. Biochem. Biophys. 238:83-89, 1985).


Venous Collateral Pathways in Superior Thoracic Inlet Obstruction: A Systematic Analysis of Anatomy, Embryology, and Resulting Patterns.
OBJECTIVE. For this study, we reviewed 56 standard-of-care CT examinations over a timespan of 2 years from patients with superior thoracic inlet venous obstruction and identified eight thoracic collateral pathways for venous blood return to the right heart. We evaluated each pathway individually from an anatomic and a pathophysiologic perspective for a better understanding of how such pathways form and what patterns can be expected. MATERIALS AND METHODS. All 56 patients were scanned according to our standard CT protocol. Images of the thoracic region were acquired in the craniocaudal direction during breath-holding using a second-generation dual-source CT scanner. Contrast medium was administered via a cubital or antecubital vein; the amount of contrast material ranged from 49 to 81 mL depending on patient body weight. RESULTS. Of the 56 patients, CT showed superior vena cava syndrome exclusively in 22 (39%) patients and showed superior vena cava syndrome and involvement of the left or right brachiocephalic vein or even the subclavian vein in the remaining 34 (61%) patients. We could not find any remarkable feature leading to the formation of only one collateral pathway or to a specific pattern depending on underlying cause or the level or the extent of obstruction. Thus, we believe that there are no specific patterns for how these venous detours form and that they are most probably driven by pressure gradients. CONCLUSION. Recognizing imaging findings associated with venous collateral pathways may prevent misdiagnosis or unnecessary follow-up examinations. Furthermore, knowledge of these collateral pathways and an understanding of the underlying cause can support interventional radiologists and vascular surgeons in planning interventional procedures and revascularization procedures.


Identification and characterization of Toxoplasma gondii aspartic protease 1 as a novel vaccine candidate against toxoplasmosis.
Toxoplasma gondii is an obligate intracellular parasite that can pose a serious threat to human health by causing toxoplasmosis. There are no drugs that target the chronic cyst stage of this infection; therefore, development of an effective vaccine would be an important advance. Aspartic proteases play essential roles in the T. gondii lifecycle. The parasite has four aspartic protease encoding genes, which are called toxomepsin 1, 2, 3 and 5 (TgASP1, 2, 3 and 5, respectively). Bioinformatics approaches have enabled us to identify several promising linear-B cell epitopes and potential Th-cell epitopes on TgASP1, thus supporting its potential as a DNA vaccine against toxoplasmosis. We expressed TgASP1 in Escherichia coli and used the purified protein to immunize BALB/c mice. The antibodies obtained were used to determine where TgASP1 was localized in the parasite. We also made a TgASP1 DNA vaccine construct and evaluated it for the level of protection conferred to mice against infection with the virulent RH strain of T. gondii. TgASP1 appears to be a membrane protein located primarily at the tip of the T. gondii tachyzoite. Investigation of its potential as a DNA vaccine showed that it elicited strong humoral and cellular immune responses in mice, and that these responses were mediated by Th-1 cells. Mice immunized with the vaccine had greater levels of protection against mortality following challenge with T. gondii RH tachyzoites than did those immunized with PBS or the empty vector control. TgASP1 is a novel candidate DNA vaccine that merits further investigation.


Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma.
Previous studies have demonstrated the in vitro and in vivo activity of CC-5013 (Revlimid), an immunomodulatory analog (IMiD) of thalidomide, in multiple myeloma (MM). In the present study, we have examined the anti-MM activity of rapamycin (Rapamune), a specific mTOR inhibitor, combined with CC-5013. Based on the Chou-Talalay method, combination indices of less than 1 were obtained for all dose ranges of CC-5013 when combined with rapamycin, suggesting strong synergism. Importantly, this combination was able to overcome drug resistance when tested against MM cell lines resistant to conventional chemotherapy. Moreover, the combination, but not rapamycin alone, was able to overcome the growth advantage conferred on MM cells by interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), or adherence to bone marrow stromal cells (BMSCs). Combining rapamycin and CC-5013 induced apoptosis of MM cells. Differential signaling cascades, including the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3'-kinase/Akt kinase (PI3K/Akt) pathways, were targeted by these drugs individually and in combination, suggesting the molecular mechanism by which they interfere with MM growth and survival. These studies, therefore, provide the framework for clinical evaluation of mTOR inhibitors combined with IMiDs to improve patient outcome in MM.


Expressions of MiR-132 in patients with chronic hepatitis B, posthepatitic cirrhosis and hepatitis B virus-related hepatocellular carcinoma.
To explore the expressions of miR-132 in patients with chronic hepatitis B, posthepatitic cirrhosis and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and to investigate its possible mechanism affecting the function of the body. Among 125 patients with HBV, there were 44 cases of chronic hepatitis, 42 cases of liver cirrhosis and 39 cases of liver cancer. Their liver function and HBV-deoxyribonucleic acid (HBV-DNA) viral load as well as the expressions of micro ribonucleic acid-132 (miR-132), phosphoinositide 3-kinase (PI3K), phosphorylated-protein kinase B (p-Akt) and hepatitis B X protein (HBx), were detected. There were significant differences in some liver function indexes and the HBV-DNA level among the three groups of patients (p < 0.05). The HBV-DNA level was 6.91 Lg copies/mL in the liver cancer group and 5.34 Lg copies/mL in the chronic hepatitis B group. Differences in the expression level of miR-132 among the three groups were notable (p < 0.05), but this expression level had a negative correlation with the HBV-DNA level. The expressions of PI3K and p-Akt proteins and messenger ribonucleic acids (mRNAs) were markedly different among the three groups (p < 0.05). HBx was expressed in the three groups of patients, and liver cancer patients with the highest expression degree of HBx accounted for 46%. Differences in the expression of miR-132 among the three groups are evident, which may be associated with differences in liver function, the HBV-DNA level, HBx and the expressions of PI3K and p-Akt proteins to a certain degree.


Bikinin-like inhibitors targeting GSK3/Shaggy-like kinases: characterisation of novel compounds and elucidation of their catabolism in planta.
Plant GSK-3/Shaggy-like kinases are key players in brassinosteroid (BR) signalling which impact on plant development and participate in response to wounding, pathogens and salt stress. Bikinin was previously identified in a chemical genetics screen as an inhibitor targeting these kinases. To dissect the structural elements crucial for inhibition of GSK-3/Shaggy-like kinases by bikinin and to isolate more potent compounds we synthesised a number of related substances and tested their inhibitory activity in vitro and in vivo using Arabidopsis thaliana. A pyridine ring with an amido succinic acid residue in position 2 and a halogen in position 5 were crucial for inhibitory activity. The compound with an iodine substituent in position 5, denoted iodobikinin, was most active in inhibiting BIN2 activity in vitro and efficiently induced brassinosteroid-like responses in vivo. Its methyl ester, methyliodobikinin, showed improved cell permeability, making it highly potent in vivo although it had lower activity in vitro. HPLC analysis revealed that the methyl residue was rapidly cleaved off in planta liberating active iodobikinin. In addition, we provide evidence that iodobikinin and bikinin are inactivated in planta by conjugation with glutamic acid or malic acid and that the latter process is catalysed by the malate transferase SNG1. Brassinosteroids participate in regulation of many aspects of plant development and in responses to environmental cues. Thus compounds modulating their action are valuable tools to study such processes and may be an interesting opportunity to modify plant growth and performance in horticulture and agronomy. Here we report the development of bikinin derivatives with increased potency that can activate BR signalling and mimic BR action. Methyliodobikinin was 3.4 times more active in vivo than bikinin. The main reason for the superior activity of methyliodobikinin, the most potent compound, is its enhanced plant tissue permeability. Inactivation of bikinin and its derivatives in planta involves SNG1, which constitutes a novel pathway for modification of xenobiotic compounds.


Timing of tourniquet release in total knee arthroplasty: A meta-analysis.
For total knee arthroplasty (TKA), the tourniquet is routinely employed for better visualization, less blood loss, and easier cementation. However, the time to release tourniquet remains controversial. Therefore, we performed current meta-analysis to assess whether releasing tourniquet before wound closure is more effective in reducing blood loss than releasing tourniquet after wound closure in TKA without an increased risk of complications. To conduct this meta-analysis, we searched Medline, Embase, Web of science, and the Cochrane library up to November 2016, for randomized controlled trials comparing tourniquet releasing before and after wound closure in TKA. A meta-analysis was performed following the guidelines of the Cochrane Reviewer's Handbook and the PRISMA statement. Methodological quality of the trials was assessed using the Cochrane risk assessment scale. The data of the included studies were analyzed using Stata 12.0. Sixteen trials involving 1010 patients were identified in current meta-analysis. Our meta-analysis demonstrated that there were no significant differences in the 2 groups in terms of calculated blood loss (weighted mean difference [WMD] = 160.65, 95% confidence interval [CI]: -0.2 to 321.49, P = .05), postoperative blood loss (WMD = -45.41, 95% CI: -120.11 to 29.29, P = .233),postoperative hemoglobin decline (WMD = 0.16, 95% CI: -2.5 to 2.82, P = .905), transfusion volume (WMD = 79.19, 95% CI: -5.05 to 163.44, P = .065),transfusion rates (relative risk [RR] = 1.19, 95% CI: 0.95-1.50, P = .134), major complications (RR = 0.51, 95% CI: 0.15-1.73, P = .278), and deep vein thrombosis (RR = 0.44, 95% CI: 0.14-1.37, P = .157).Compared with the group of releasing tourniquet after wound closure, the group of releasing tourniquet before wound closure had a higher volume of total blood loss (WMD = 130.96, 95% CI: 58.83-203.09, P = .000) and a longer operation time (WMD = 6.56, 95% CI: 3.12-10.01, P = .000). However, releasing tourniquet before wound closure could reduce minor complications (RR = 0.53, 95% CI: 0.34-0.82, P = .004). On the basis of current meta-analysis, the method of releasing tourniquet before wound closure could increase total blood loss and operation time; nevertheless, the risk of complications decreased. Thus, if patients are in severe anemia condition, the tourniquet perhaps should be released after wound closure to decrease blood loss. In contrary, releasing tourniquet before wound closure to decrease the risk of complications would be a better choice.


Hyperhomocysteinemia, thrombosis and vascular biology.
Epidemiological evidence suggests that hyperhomocysteinemia (HH) is an independent risk factor for arterial thrombotic diseases such as acute myocardial infarction, stroke, peripheral ischemic occlusive disorders as well as venous thromboembolism. This article presents a hypothesis to explain the pathogenesis of increases in plasma homocysteine level and associated increased risk of thrombotic disease. It is based on the data in the literature and results from our laboratory on the impact of folate induced HH in rats. These results include: a) Effects on whole blood coagulation, which is characterized by increased velocity of coagulation, increased firmness of the formed coagulum and prolonged initiation phase of the coagulation; b) Genetic regulation of blood cells, which is characterized by increased platelet activation, impaired fibrinolysis and impaired function of the contact activation pathway of coagulation, and c) Reduced functional activities of single coagulation factors FXII:C, FX:C and FII:C.


Toward Characterizing the Genetic Basis of Trace Organic Contaminant Biotransformation in Activated Sludge: The Role of Multicopper Oxidases as a Case Study.
Activated sludge treatment leverages the ability of microbes to uptake and (co)-metabolize chemicals and has shown promise in eliminating trace organic contaminants (TrOCs) during wastewater treatment. However, targeted interventions to optimize the process are limited as the fundamental drivers of the observed reactions remain elusive. In this work, we present a comprehensive workflow for the identification and characterization of key enzymes involved in TrOCs biotransformation pathways in complex microbial communities. To demonstrate the applicability of the workflow, we investigated the role of the enzymatic group of multicopper oxidases (MCOs) as one putatively relevant driver of TrOCs biotransformation. To this end, we analyzed activated sludge metatranscriptomic data and selected, synthesized, and heterologously expressed three phylogenetically distinct MCO-encoding genes expressed in communities with different TrOCs oxidation potentials. Following the purification of the encoded enzymes, we screened their activities against different substrates. We saw that MCOs exhibit significant activities against selected TrOCs in the presence of the mediator compound 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid and, in some cases, also in the presence of the wastewater contaminant 4'-hydroxy-benzotriazole. In the first case, we identified oxidation products previously reported from activated sludge communities and concluded that in the presence of appropriate mediators, bacterial MCOs could contribute to the biological removal of TrOCs. Similar investigations of other key enzyme systems may significantly advance our understanding of TrOCs biodegradation and assist the rational design of biology-based water treatment strategies in the future.


Lessons learned after 20 years of real-world experience with natalizumab.
While natalizumab (NTZ) is an effective therapy for multiple sclerosis (MS), it is associated with an increased risk of progressive multifocal leukoencephalopathy (PML). After 20 years (2002-2022) of experience with NTZ at our center, we observed no cases of PML. We evaluated the likelihood of experiencing PML in a subset of our treatment cohort, as well as reviewed treatment practices at our center that may mitigate PML risk. For this retrospective study, we reviewed patient characteristics, treatment practices, and clinical and MRI findings in patients receiving NTZ from 2006 to 2020. Observation of no PML cases was compared to the global and US PML incidences, and to the expected incidence based on published risk estimates. 766 patients were evaluated. The number of NTZ infusions received ranged from 1 to 126, with a mean of 28. Patients received neurological examination prior to each infusion, which sometimes resulted in a pause in therapy to rule out PML if clinical worsening occurred. Extended interval dosing (EID) was the overall dosing schedule for 31% of patients. EID did not result in higher rates of radiological disease worsening than standard interval dosing (SID) patients. Depending on the analysis conducted, the finding of 0 PML cases in our cohort ranged from slightly unexpected to slightly expected. The utilization of EID as well as regular clinical monitoring of patients may have lowered PML risk while still maintaining NTZ efficacy.


Prospects for adoptive T-cell therapy for invasive fungal disease.
Invasive fungal disease (IFD) is a cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. As more potent broad-spectrum antifungal agents are used in prophylaxis, drug resistance and less common fungal species have increased in frequency. Here we review current treatments available for IFD and examine the potential for adoptive T-cell treatment to enhance current therapeutic choices in IFD. There is growing evidence supporting the role of T cells as well as phagocytes in antifungal immunity. T cells recognizing specific antigens expressed on fungal morphotypes have been identified and the role of T-cell transfer has been explored in animal models. The clinical efficacy of adoptive transfer of antigen-specific T cells for prophylaxis and treatment of viral infections post-HSCT has raised interest in developing good manufacturing practice (GMP)-compliant methods for manufacturing and testing fungus-specific T cells after HSCT. As the outcomes of IFD post-HSCT are poor, reconstitution of antifungal immunity offers a way to correct the underlying deficiency that has caused the infection rather than simply pharmacologically suppress fungal growth. The clinical development of fungus specific T cells is in its early stages and clinical trials are needed in order to evaluate safety and efficacy.


Prolonged small-intestinal transit time in cystic fibrosis.
A lactulose hydrogen breath test was performed on 10 patients with cystic fibrosis and 15 control subjects matched for age and sex. All normal subjects had a fasting breath hydrogen concentration of less than 20 ppm. In contrast, seven of the patients with cystic fibrosis had high concentrations (25-170 ppm), which fell to 20 ppm or below on prolonged fasting (14-23 hours). Two patients showed no rise in breath hydrogen concentrations after lactulose, and in one patient the breath hydrogen concentration rose at 15 minutes, suggesting bacterial colonisation of the small bowel. Seven of the patients had prolonged small-bowel transit times (160-390 minutes) compared with those in the control group (50-150 minutes).


A phase II clinical study of combining FOLFIRI and bevacizumab plus erlotinib in 2nd-line chemotherapy for patients with metastatic colorectal cancer.
We conducted an open-label single-arm phase II study by combining irinotecan (FOLFIRI) and bevacizumab (BV) plus erlotinib (ER) in 2nd-line chemotherapy for patients with metastatic colorectal cancer (mCRC).Eligible mCRC patients received 1st-line standard chemotherapy but still had progressive disease. They were given FOLFIRI plus BV at 2.5 mg/kg on day 1 per 2-week cycle, and daily 150 mg ER. The primary endpoint is progression-free survival (PFS).A total of 122 patients enrolled in the study. Among them, 55.7% were male patients and median age was 58.4 years (29-72 years). Median PFS was 7.1 months (95% CI 4.3-10.2). Median overall survival (OS) was 13.5 months (95% CI 9.7-16.4). No patients had complete responses, 24 patients had partial response (19.6%) and 59 had stable disease (48.4%). The most frequent adverse event (AE) was rash, with 66 patients (54.1%) had grade 3/4 rash. Other frequent grade 3/4 AEs were fatigue (n = 36, 29.5%), bleeding (n = 31, 25.4%), neutropenia (n = 23, 18.9%), and platelets (n = 14, 11.5%).Combining FOLFIRI and BV plus ER in 2nd-line chemotherapy is efficient to treat mCRC patients with acceptable safety.


The significance of lobular carcinoma in situ and atypical lobular hyperplasia of the breast.
The significance of lobular neoplasia (LN), lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH)) found at core needle biopsy (CNB) of the breast remains uncertain. There is a consistent risk of underestimating malignancy after the diagnosis of LN on CNB. The aim of this study was to determine if patients with a CNB result of LN need surgical excision. Patients were identified by searching the institutions pathology database for the terms "lobular carcinoma in situ" and "atypical lobular hyperplasia" over 20 years. Excluded from this study were those with core needle biopsy (CNB) results of ductal carcinoma in situ, atypical ductal hyperplasia, radial scar, or papilloma. Upgrade was defined as final surgical pathology of invasive carcinoma and/or ductal carcinoma in situ that was directly correlated to the site of the initial biopsy containing LN. LN was found at CNB in 285 patients, and 71 % (n = 201) had subsequent surgical excisions. All patients with pleomorphic LCIS (pLCIS) underwent surgical excision. Following patients with pLCIS, patients with the diagnosis of LCIS were most likely to undergo surgical excision (80 %). Final pathology of the surgically excised specimens confirmed LN in 72 % (n = 144). Also, 13 % (n = 26) of the operated patients were upgraded to malignancy, including 8 % of ALH and 19 % of LCIS cases. This is the largest series of surgical excisional pathology following LN on CNB ever reported. The likelihood of finding malignancy at surgical excision after CNB showing LN was 13 %. Patients with the diagnosis of LN on CNB should be considered for surgical excision.


Subnanosecond charge photogeneration and recombination in polyfluorene copolymer-fullerene solar cell: effects of electric field.
Influence of electric field on the subnanosecond charge photogeneration dynamics in the polymer solar cell based on polyfluorene copolymer BisDMO-PFDTBT blended with PC(61)BM was examined with transient absorption spectroscopy. The charge dynamics showed no difference under short- or open-circuit conditions and under a forward bias of 0.79 V (1.6 × 10(5) V/cm), implying negligible field effects on the subnanosecond dynamics of charge photogeneration/recombination. However, under the reverse biases of -2 V (4.0 × 10(5) V/cm) and -5 V (1.0 × 10(6) V/cm), significant enhancement of charge photogeneration and apparent suppression of polaron pair recombination were observed, which agrees with the field-assisted enhancement of external quantum efficiency of the solar cell devices.


Priming of human myeloid leukemic cell lines HL-60 and U-937 with retinoic acid for differentiation effects of cyclic adenosine 3':5'-monophosphate-inducing agents and a T-lymphocyte-derived differentiation factor.
The human cell lines HL-60 (acute promyelocytic leukemia) and U-937 (histiocytic monoblast-like lymphoma) differentiate to functionally mature cells by incubation with retinoic acid (RA). This differentiation is potentiated by agents known to increase intracellular cyclic adenosine 3':5'-monophosphate (cAMP) levels. The present study shows that these cells can be primed for differentiation by treatment for approximately one day with RA followed by exposure to a cAMP-inducing agent. The reverse sequence was ineffective. Thus, HL-60 could be primed by incubation for less than 20 hr with 10 nM RA to respond by differentiation to the addition of 10 nM prostaglandin E2 or 1 nM cholera toxin, whereas 10 nM RA alone was almost inactive. RA-primed HL-60 also responded with differentiation to a concentration of T-lymphocyte-derived differentiation-inducing factor which alone was inactive. U-937 primed by incubation for 24 hr with 100 nM RA responded to cAMP-inducing agents and differentiation-inducing factor, which alone were inactive on this cell line. Priming of these cell lines does not depend on the normal rate of protein synthesis, as it occurs even better in the presence of a concentration of cycloheximide that inhibits growth completely, suggesting that a decrease in synthesis of some protein(s) favors RA-induced differentiation. Cycloheximide alone produced some priming of HL-60 but not of U-937. HL-60, but not U-937, primed with RA responded to adenosine triphosphate and other nucleoside triphosphates, consistent with the notion that modulation of the RA effect may be mediated through protein kinase activity at the plasma membrane. The finding that myeloid cell lines, like HL-60 and U-937, blocked at a late stage of maturation can be primed by RA to respond to cAMP-inducing agents and differentiation-inducing factor may improve our understanding of the arrest in maturation typical of some forms of leukemia.


Care of the burn patient.
A burn injury creates a significant alteration in the functioning and structural integrity of the skin. Major burns also affect all systems of the body. Understanding the systemic response is essential for treatment and a multidisciplinary team approach is necessary. This article reviews causes of burn injury and evaluation of burn injury, including zones of tissue damage, amount and severity of injury and the Rule of Nines method of determining Total Body Surface Area. Systemic responses to burn injury include vascular, pulmonary, renal and gastrointestinal. The article continues by reviewing pulmonary and respiratory problems, mechanical ventilation, fluid resuscitation, and nutrition. Non-operative and operative wound care is covered, including the nursing diagnoses of infection and pain. Issues involved in patient rehabilitation include scarring and contractures, body image and family support, and the seven adaptive stages for burn victims (adaptive, problem of pain, search for meaning, investment in recuperation, acceptance of losses, investment in rehabilitation, and reintegration of identity). In the treatment of a burn patient, each member of the healthcare team brings a different but equally important therapeutic intervention to the care of the patient's many needs.


High sensitivity of rat foetal germ cells to low dose-rate irradiation.
To investigate the response of germ and Sertoli cells to gamma-irradiation at two distinct periods of testicular development in rat foetuses. Pregnant rats were exposed to 60Co gamma-rays at days 15, 19 or 21 post-coitum (p.c.), at doses ranging from 0.1 to 1.5Gy, and at different dose-rates. Testicular weight, seminiferous tubule condition and the number of germ and Sertoli cells were measured at early and late times after irradiation. Apoptosis was studied by the ISEL method and p53 expression was studied by immunohistochemistry. At high dose-rates (> or = 3.3 Gy min(-1)), 1.5 Gy radiation at day 15 p.c. had a short-term effect on germ cell survival. A large proportion of these cells rapidly underwent p53-independent apoptosis. Apoptotic cells were strongly clustered. The remaining germ cells divided and differentiated normally leading to a majority of normal tubules in the adult testis. However, at low dose-rate (0.6mGy min(-1)), much greater depopulation of the seminiferous tubules occurred. When irradiation was given at day 19 p.c., the same dose had a delayed effect on germ cells, leading to sterility. Sertoli cells had a normal survival for irradiation at day 15 p.c. Their proliferation became higher in prepubescent testis compared with controls, when irradiation occurred at day 19 p.c. The position of gonocytes in the cell cycle at the time of irradiation seems to be a determining parameter for inducing gonocyte apoptosis. The strong effect of irradiation on germ cells at very low dose-rate and the appearance of clusters of apoptotic gonocytes may be a consequence of the syncitial organization of germ cells, favouring their cell synchronisation or the transmission of death signalling when they are in a radiosensitive period.


Dientamoeba fragilis in children: a systematic review on diagnostic considerations and efficacy of treatment.
Introduction: The presence of D. fragilis in feces is characterized by an asymptomatic carrier ship to a spectrum of gastrointestinal symptoms. However, a causal relationship remains to be elucidated. In this systematic review, we aimed to evaluate the relationship between the eradication of D. fragilis and symptoms to establish the strength of evidence that D. fragilis in symptomatic children warrants antibiotic treatment.Areas covered: This systematic review covers a challenge in daily clinical practice. Is it necessary to test for D. fragilis in children with gastrointestinal symptoms and does a positive fecal PCR test warrant treatment?Expert opinion: Testing for D. fragilis seems justified in a selection of children with persistent unexplained chronic abdominal pain and diarrhea. Treatment of D. fragilis should be withhold until other causes like celiac disease have been excluded. Both microscopic and Real Time-PCR methods (or a combination of the two) can be used for diagnosis. Paromomycin or clioquinol are antibiotics of choice based on their small spectrum of activity, fewer side effects, and better eradication rates than metronidazole. Future randomized studies, with strict inclusion criteria, appropriate diagnostic testing, and doses of antibiotics based on bodyweight are warranted.


CD28 stimulation triggers NF-kappaB activation through the CARMA1-PKCtheta-Grb2/Gads axis.
CD28 stimulation contributes to activation of the IL-2 promoter by up-regulating the activity of several transcription factors, including nuclear factor kappaB (NF-kappaB)/Rel family members. However, the signal-transducing cascades linking the CD28 molecule and activation of NF-kappaB remain unclear. Protein kinase C (PKC) , CARMA1 and Bcl10 have recently been reported to integrate TCR-mediated NF-kappaB activation. However, since the data in these studies were drawn from experiments in which T cells were usually stimulated with both TCR and CD28, the relative contributions of TCR- and CD28-mediated signals to initiation of the NF-kappaB pathway remain elusive. To examine the role of these molecules in NF-kappaB activation through CD28-mediated stimulation, Bcl10 was over-expressed in Jurkat cells and their NF-kappaB activation by CD28- or TCR-cross-linking was evaluated. We found that CD28 stimulation alone can induce NF-kappaB activation in Bcl10-over-expressing Jurkat cells, whereas TCR stimulation alone has only little effect. In addition, we found that Bcl10-induced NF-kappaB activation through CD28-mediated stimulation could be blocked by the dominant-negative form of PKC or CARMA1. Furthermore, genetic studies revealed that Grb2/Gads binding, but not phosphatidylinositol 3-kinase binding, is important in CD28-mediated NF-kappaB activation. These findings indicate that the PKC-CARMA1-Bcl10 signaling pathway participates in the CD28 co-stimulatory signal independently of the TCR-signaling pathway, which leads us to propose that the activation of the NF-kappaB-signaling pathway via PKC-CARMA1-Bcl10 may be markedly dependent on CD28 stimulation rather than TCR stimulation.


[Social capital and health information in the context of small scale farmers' livelihoods].
The study explores the relationship between social capital and health information among small-scale farmers in the context of their livelihoods. Having such information could promote the use of agriculture practices with fewer health impacts by reducing farmers' exposure to highly toxic pesticides. We implemented a longitudinal study design with measurements in July 2007 (T1) and February 2010 (T2), within 12 agricultural communities in Ecuador (n=208 farmers). The dependent variables were based on information regarding agricultural production practices, among them: integrated pest management (IPM) and pesticide toxicity. Independent variables included participation in organizations and social cohesion, among other aspects of social capital. Results suggest that health information is disseminated through structures of social capital, depending on its value of use in the context of the mode of production in which small scale agriculture is developed.


Health and exercise-related medical issues among 1,212 ultramarathon runners: baseline findings from the Ultrarunners Longitudinal TRAcking (ULTRA) Study.
Regular exercise is associated with substantial health benefits; however, little is known about the health impact of extreme levels of exercise. This study examined the prevalence of chronic diseases, health-care utilization, and risk factors for exercise-related injuries among ultramarathon runners. Retrospective, self-reported enrollment data from an ongoing longitudinal observational study of 1,212 active ultramarathon runners were analyzed. The most prevalent chronic medical conditions were allergies/hay fever (25.1%) and exercise-induced asthma (13.0%), but there was a low prevalence of serious medical issues including cancers (4.5%), coronary artery disease (0.7%), seizure disorders (0.7%), diabetes (0.7%), and human immunodeficiency virus (HIV) infection (0.2%). In the year preceding enrollment, most (64.6%) reported an exercise-related injury that resulted in lost training days (median of 14 days), but little nonattendance of work or school due to illness, injury, or exercise-related medical conditions (medians of 0 days for each). The knee was the most common area of exercise-related injury. Prior year incidence of stress fractures was 5.5% with most (44.5%) involving the foot. Ultramarathon runners who sustained exercise-related injuries were younger (p<0.001) and less experienced (p<0.01) than those without injury. Stress fractures were more common (p<0.01) among women than men. We conclude that, compared with the general population, ultramarathon runners appear healthier and report fewer missed work or school days due to illness or injury. Ultramarathon runners have a higher prevalence of asthma and allergies than the general population, and the prevalence of serious medical issues was nontrivial and should be recognized by those providing medical care to these individuals. Ultramarathon runners, compared with shorter distance runners, have a similar annual incidence of exercise-related injuries but higher proportion of stress fractures involving the foot, and it is the younger and less experienced ultramarathoners who appear most at risk for injury.


Achilles tendon rupture. Diagnosis and management.
Achilles tendon rupture is one of the most common tendon failures that affects the lower extremity. Several podiatric and orthopedic publications discuss the various treatment options for this rupture. This review intends to increase the physician's awareness of risk factors that contribute to Achilles tendon rupture and of how these factors should be considered in the decision-making process. By performing a comprehensive history and physical examination, the treating physician can select the most appropriate procedure or technique and maximize the patient's functional outcome.


Efficient free fatty acid production in engineered Escherichia coli strains using soybean oligosaccharides as feedstock.
To be competitive with current petrochemicals, microbial synthesis of free fatty acids can be made to rely on a variety of renewable resources rather than on food carbon sources, which increase its attraction for governments and companies. Industrial waste soybean meal is an inexpensive feedstock, which contains soluble sugars such as stachyose, raffinose, sucrose, glucose, galactose, and fructose. Free fatty acids were produced in this report by introducing an acyl-ACP carrier protein thioesterase and (3R)-hydroxyacyl-ACP dehydratase into E. coli. Plasmid pRU600 bearing genes involved in raffinose and sucrose metabolism was also transformed into engineered E. coli strains, which allowed more efficient utilization of these two kinds of specific oligosaccharide present in the soybean meal extract. Strain ML103 (pRU600, pXZ18Z) produced ~1.60 and 2.66 g/L of free fatty acids on sucrose and raffinose, respectively. A higher level of 2.92 g/L fatty acids was obtained on sugar mixture. The fatty acid production using hydrolysate obtained from acid or enzyme based hydrolysis was evaluated. Engineered strains just produced ~0.21 g/L of free fatty acids with soybean meal acid hydrolysate. However, a fatty acid production of 2.61 g/L with a high yield of 0.19 g/g total sugar was observed on an enzymatic hydrolysate. The results suggest that complex mixtures of oligosaccharides derived from soybean meal can serve as viable feedstock to produce free fatty acids. Enzymatic hydrolysis acts as a much more efficient treatment than acid hydrolysis to facilitate the transformation of industrial waste from soybean processing to high value added chemicals.


Biological roles of translesion synthesis DNA polymerases in eubacteria.
Biological systems are strongly selected to maintain the integrity of their genomes by prevention and repair of external and internal DNA damages. However, some types of DNA lesions persist and might block the replication apparatus. The universal existence of specialized translesion synthesis DNA polymerases (TLS polymerases) that can bypass such lesions in DNA implies that replication blockage is a general biological problem. We suggest that the primary function for which translesion synthesis polymerases are selected is to rescue cells from replication arrest at lesions in DNA, a situation that, if not amended, is likely to cause an immediate and severe reduction in cell fitness and survival. We will argue that the mutagenesis observed during translesion synthesis is an unavoidable secondary consequence of this primary function and not, as has been suggested, an evolved mechanism to increase mutation rates in response to various stresses. Finally, we will discuss recent data on additional roles for translesion synthesis polymerases in the formation of spontaneous deletions and in transcription-coupled TLS, where the coupling of transcription to TLS is proposed to allow the rescue of the transcription machinery arrested at DNA lesions.


Expression of N-acetylglucosaminyltransferase V in endometrial cancer correlates with poor prognosis.
N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyses beta1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cell proteins. The present study aimed to investigate GnT-V expression and its prognostic significance in endometrial cancer. N-acetylglucosaminyltransferase V expression was studied by immunohistochemistry in 74 surgically resected endometrial cancers, and the staining intensity was evaluated. High GnT-V expression in tumour cells was found in 43 (58.1%) of the 74 cases, and was positively correlated with advanced patient age, histological grade, and lymph vascular space involvement. Patients with high GnT-V expression had significantly impaired overall survival and progression-free survival (PFS) (P=0.0041 and P=0.0023, respectively) compared to patients with low expression of GnT-V. On multivariate analysis, GnT-V expression was an independent prognostic factor for PFS (P=0.0364). beta1-6 branching of asparagine-linked oligosaccharides was also detected in GnT-V-positive endometrial cancer cells by leukoagglutinating phytohaemagglutinin (L(4)-PHA) staining, and the molecular size of the major glycoproteins recognised by L(4)-PHA was approximately 60-200 kDa by lectin blot analysis. These results suggested that high GnT-V expression was correlated with an unfavourable clinical outcome, and that GnT-V is involved in the malignant potential of endometrial cancer by increasing the synthesis of beta1-6 branching of asparagine-linked oligosaccharides.