Patient-reported symptoms of radiation dermatitis during breast cancer radiotherapy: a pilot study.
To find out which symptoms most frequently and severely affect breast cancer patients during radiotherapy and how patients manage the symptoms and unmet needs. A cross-sectional survey was conducted with 111 patients who receive radiotherapy for breast cancer from January to April 2015 at Samsung Medical Center in Seoul, South Korea. Participants were asked about symptoms and discomfort due to radiotherapy, management methods for radiation dermatitis, unmet needs for radiation dermatitis care, and clinical and socio-demographic information. Of total, 108 out of 111 patients (97.3%) reported symptoms related to radiation dermatitis. Hyperpigmentation was the most commonly reported uncomfortable symptom followed by erythema. On average, patients reported 8.6 radiotherapy-induced skin problems (range, 0-11). Of total, 59 (53.2%) patients stated that they wanted care for radiation dermatitis, and 80.0, 59.4, and 51% of patients searched for information, used products, and visited the hospital to manage radiotherapy-related skin problems. Patients who experienced dryness, burning feelings, irritation, roughness, and hyperpigmentation were 11.73, 7.02, 5.10, 4.27, and 2.80 times more likely to have management needs than patients without those symptoms, respectively, adjusting age, current cycle of radiation therapy, chemotherapy, and type of surgery. Most of the breast cancer patients experience multiple symptoms associated with radiation dermatitis. Hyperpigmentation was the most common and uncomfortable symptom followed by erythema. Majority of patients wanted management for radiation dermatitis and patients who experienced dryness, burning feelings, irritation, roughness, and hyperpigmentation had higher needs for radiation dermatitis management.


Role of insulin-like growth factor binding protein-3 in allergic airway remodeling.
The hallmarks of allergic asthma are airway inflammation, obstruction, and remodeling. Airway remodeling may lead to irreversible airflow obstruction with increased morbidity and mortality. Despite advances in the treatment of asthma, the mechanisms underlying airway remodeling are still poorly understood. We reported that insulin-like growth factor (IGF) binding proteins (IGFBPs) contribute to extracellular matrix deposition in idiopathic pulmonary fibrosis; however, their contribution to airway remodeling in asthma has not been established. We hypothesized that IGFBP-3 is overexpressed in asthma and contributes to airway remodeling. We evaluated levels of IGFBP-3 in tissues and bronchoalveolar lavage fluid from patients with asthma at baseline and 48 hours after allergen challenge, in reparative epithelium in an in vitro wounding assay, and in conditioned media from cytokine- and growth factor-stimulated primary epithelial cells. IGFBP-3 levels and distribution were evaluated by Western blot, ELISA, and immunofluorescence. IGFBP-3 is increased in vivo in the airway epithelium of patients with asthma compared with normal control subjects. The concentration of IGFBP-3 is increased in the bronchoalveolar lavage fluid of patients with asthma after allergen challenge, its levels are increased in reparative epithelium in an in vitro wounding assay and in the conditioned medium of primary airway epithelial cell cultures stimulated with IGF-I. Our results suggest that one mechanism of allergic airway remodeling is through the secretion of the profibrotic IGFBP-3 from IGF-I-stimulated airway epithelial cells during allergic inflammation.


Genetics of germination-arrest factor (GAF) production by Pseudomonas fluorescens WH6: identification of a gene cluster essential for GAF biosynthesis.
The genetic basis of the biosynthesis of the germination-arrest factor (GAF) produced by Pseudomonas fluorescens WH6, and previously identified as 4-formylaminooxyvinylglycine, has been investigated here. In addition to inhibiting the germination of a wide range of grassy weeds, GAF exhibits a selective antimicrobial activity against the bacterial plant pathogen Erwinia amylovora. We utilized the in vitro response of E. amylovora to GAF as a rapid screen for loss-of-function GAF phenotypes generated by transposon mutagenesis. A Tn5 mutant library consisting of 6364 WH6 transformants was screened in this Erwinia assay, resulting in the identification of 18 non-redundant transposon insertion sites that led to loss of GAF production in WH6, as confirmed by TLC analysis. These insertions mapped to five different genes and four intergenic regions. Three of these genes, including two putative regulatory genes (gntR and iopB homologues), were clustered in a 13 kb chromosomal region containing 13 putative ORFs. A GAF mutation identified previously as affecting an aminotransferase also maps to this region. We suggest that three of the genes in this region (a carbamoyltransferase, an aminotransferase and a formyltransferase) encode the enzymes necessary to synthesize dihydroGAF, the putative immediate precursor of GAF in a proposed GAF biosynthetic pathway. RT-qPCR analyses demonstrated that mutations in the gntR and iopB regulatory genes, as well as in a prtR homologue identified earlier as controlling GAF formation, suppressed transcription of at least two of the putative GAF biosynthetic genes (encoding the aminotransferase and formyltransferase) located in this 13 kb region.


Lessons from Launching the Diabetes Prevention Program in a Large Integrated Health Care Delivery System: A Case Study.
There is urgent need for health systems to prevent diabetes. To date, few health systems have implemented the evidence-based Diabetes Prevention Program (DPP), and the few that have mostly partnered with community-based organizations to implement the program. Given the recent decision by the Centers for Medicare & Medicaid Services to reimburse for diabetes prevention, there is likely much interest in how such programs can be implemented within large health systems or how community partnerships can be expanded to support DPP implementation. Beginning in 2010, Montefiore Health System (MHS), a large health care system in the Bronx, NY, partnered with the Young Men's Christian Association (YMCA) of Greater New York to deliver the YMCA's DPP. Over 4 years, 1390 referrals to YMCA's DPP were made; 287 participants attended ≥3 classes, and average weight loss was 3.4%. Because of increased patient demand and internal capacity, MHS assumed responsibility for DPP implementation in May 2015. Fully integrating the program within the health system took 5-6 months, including configuring electronic health record templates/reports, hiring a coordinator, and creating clinical referral workflows/training guides. Billing workflows were designed for risk-based contracts. In the first 11 months of implementation, 1277 referrals were made, and referrals increased over time. Twenty-four class cycles were initiated, and 282 patients began attending classes. Average weight loss among 61 graduates from the Summer/Fall 2015 wave of MDPP classes was 3.8%. Additional opportunities for expansion include training allied health staff, providing patient incentives, increasing master trainer capacity, offering DPP to employees, and securing reimbursement.


The inferior frontal gyrus and phonological processing: an investigation using rTMS.
Repetitive transcranial magnetic stimulation (rTMS) offers a powerful new technique for investigating the distinct contributions of the cortical language areas. We have used this method to examine the role of the left inferior frontal gyrus (IFG) in phonological processing and verbal working memory. Functional neuroimaging studies have implicated the posterior part of the left IFG in both phonological decision making and subvocal rehearsal mechanisms, but imaging is a correlational method and it is therefore necessary to determine whether this region is essential for such processes. In this paper we present the results of two experiments in which rTMS was applied over the frontal operculum while subjects performed a delayed phonological matching task. We compared the effects of disrupting this area either during the delay (memory) phase or at the response (decision) phase of the task. Delivered at a time when subjects were required to remember the sound of a visually presented word, rTMS impaired the accuracy with which they subsequently performed the task. However, when delivered later in the trial, as the subjects compared the remembered word with a given pseudoword, rTMS did not impair accuracy. Performance by the same subjects on a control task that required the processing of nonverbal visual stimuli was unaffected by the rTMS. Similarly, performance on both tasks was unaffected by rTMS delivered over a more anterior site (pars triangularis). We conclude that the opercular region of the IFG is necessary for the normal operation of phonologically based working memory mechanisms. Furthermore, this study shows that rTMS can shed further light on the precise role of cortical language areas in humans.


Cross-sensitivity to topoisomerase II inhibitors in cytotoxic drug-hypersensitive Chinese hamster ovary cell lines.
We have isolated a Chinese hamster ovary cell line, designated ADR-1, which exhibits hypersensitivity to a range of drugs which are thought to inhibit the action of the enzyme topoisomerase II. These include anthracyclines, other classes of intercalating agents, and the epipodophyllotoxin, etoposide. No significant sensitivity to radiation, or to mono- and bifunctional alkylating agents was seen, although mild cross-sensitivity to the radiomimetic agent bleomycin was observed. We have monitored the level of DNA strand breaks induced by topoisomerase II inhibitors in ADR-1 cells using alkaline elution. At equimolar Adriamycin (doxorubicin) doses, more protein-associated DNA strand breaks are induced in ADR-1 cells than in wild-type cells. This enhanced level of drug-induced strand breaks does not appear to be a function of increased drug uptake as both lines accumulate similar levels of radiolabeled daunomycin. Both the rate of repair of strand breaks and the final percentage of strand breaks rejoined was equivalent in the 2 cell lines. These results are consistent with an enhancement in the level of topoisomerase II-dependent DNA breakage in ADR-1 cells following exposure to topoisomerase II inhibitors. We have previously reported the isolation of 2 bleomycin-sensitive Chinese hamster ovary cell lines, BLM-1 and BLM-2 (C. N. Robson et al., Cancer Res. 45:5304-5309, 1985). While BLM-1 exhibited cross-sensitivity only to Adriamycin, BLM-2 was shown to be hypersensitive not only to Adriamycin out also to certain alkylating agents and to ionizing radiation. In this paper, we show that both BLM-1 and BLM-2 also exhibit mild cross-sensitivity to a range of topoisomerase II inhibitors. These results indicate that intercalating agents and epipodophyllotoxins exert their cytotoxicity via common mechanisms and suggest that the maintenance of normal levels of cellular resistance to these agents requires the products of several different genes.


Assessment of costs to donor hospitals for organ transplantation.
In 1987, die Department of Health in the UK set up a working party to identify reasons contributing to a shortfall in donor organs. One recommendation was reimbursement to the District Health Authorities for costs incurred in providing the donor organs. The figure chosen was not to be seen as an incentive to donate organs, merely as an appropriate compensation for the costs incurred. There would be no direct payment to doctors, trustees or relatives of the donor. With the development of the competitive health care environment in the United Kingdom, the reimbursement of donating hospital costs is being considered with these data.


Preparation and evaluation of fluorine-18-labeled insulin as a molecular imaging probe for studying insulin receptor expression in tumors.
A convenient emulsion-based labeling method was used to synthesize fluorine-18-labeled insulin specifically B(1)-(4-[(18)F]fluorobenzoyl)insulin ((18)F-4b) in 6% overall radiochemical yield in 240 min. In vitro screening in MCF7 breast cancer cells demonstrated that the nonradioactive analogue (19)F-4a effectively competed with (125)I-insulin for the insulin receptor (IC50 = 10.6 nM) comparable to that for insulin (IC50 = 7.4 nM). (18)F-4b was also more stable than (125)I-insulin in mouse plasma with 50% remaining intact after 30 min. A biodistribution study in normal mice showed initial uptake of the tracer in the kidneys, liver, and gall bladder but rapid clearance via the urine/bladder which was also observed in murine models bearing insulin receptor positive tumors.


Collagen metabolism of human osteoarthritic articular cartilage as modulated by bovine collagen hydrolysates.
Destruction of articular cartilage is a characteristic feature of osteoarthritis (OA). Collagen hydrolysates are mixtures of collagen peptides and have gained huge public attention as nutriceuticals used for prophylaxis of OA. Here, we evaluated for the first time whether different bovine collagen hydrolysate preparations indeed modulate the metabolism of collagen and proteoglycans from human OA cartilage explants and determined the chemical composition of oligopeptides representing collagen fragments. Using biophysical techniques, like MALDI-TOF-MS, AFM, and NMR, the molecular weight distribution and aggregation behavior of collagen hydrolysates from bovine origin (CH-Alpha®, Peptan™ B 5000, Peptan™ B 2000) were determined. To investigate the metabolism of human femoral OA cartilage, explants were obtained during knee replacement surgery. Collagen synthesis of explants as modulated by 0-10 mg/ml collagen hydrolysates was determined using a novel dual radiolabeling procedure. Proteoglycans, NO, PGE(2), MMP-1, -3, -13, TIMP-1, collagen type II, and cell viability were determined in explant cultures. Groups of data were analyzed using ANOVA and the Friedman test (n = 5-12). The significance was set to p≤0.05. We found that collagen hydrolysates obtained from different sources varied with respect to the width of molecular weight distribution, average molecular weight, and aggregation behavior. None of the collagen hydrolysates tested stimulated the biosynthesis of collagen. Peptan™ B 5000 elevated NO and PGE(2) levels significantly but had no effect on collagen or proteoglycan loss. All collagen hydrolysates tested proved not to be cytotoxic. Together, our data demonstrate for the first time that various collagen hydrolysates differ with respect to their chemical composition of collagen fragments as well as by their pharmacological efficacy on human chondrocytes. Our study underscores the importance that each collagen hydrolysate preparation should first demonstrate its pharmacological potential both in vitro and in vivo before being used for both regenerative medicine and prophylaxis of OA.


Global gene regulatory network underlying miR165a in Arabidopsis shoot apical meristem.
Arabidopsis microRNA165a (miR165a) targets Class III Homeodomain Leucine-Zipper (HD-ZIPIII) transcription factors to regulate various aspects of plant development and stress response. Over-expression of miR165a mimics the loss-of-function phenotype of HD-ZIPIII genes and leading to ectopic organ formation, shoot apical meristem (SAM) termination, loss of leaf polarity, and defective vasculature development. However, the molecular mechanisms underlying these phenotypes remain unresolved. Here, we over-expressed miR165a in a dexamethasone inducible manner and identified differentially expressed genes in the SAM through RNA-Seq. Simultaneously, using multi-channel FACS combined with RNA-Seq approach, we characterized global transcriptome patterns in miR165a expressing cell-types compared to HD-ZIPIII expressing cell-types and other cell-types in SAM. By integrating our results we identified sets of genes which are up-regulated by miR165a as well have enriched expression in miR165a cell-types, and vice-versa. Known plant development related genes such as HD-ZIPIII and their targets LITTLE ZIPPERs, Like AUXIN RESISTANT 2, BEL1-like homeodomain 6, ROTUNDIFOLIA like 16 were found to be down-regulated. Among the up-regulated genes, GIBBERELLIN 2-OXIDASEs, various elemental transporters (YSL3, ZIFL1, SULTR), and other transporter genes were prominent. Thus, the genes identified in this study help to unravel the molecular mechanism of miR165a and HD-ZIPIII regulated plant development and stress response.


Knowledge of HBV and HCV and individuals' attitudes toward HBV- and HCV-infected colleagues: a national cross-sectional study among a working population in Japan.
Prejudice and discrimination in the workplace regarding the risk of transmission of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are increased by excess concerns due to a lack of relevant knowledge. Education to increase knowledge about HBV and HCV and their prevention could be the first step to reduce prejudice and discrimination. This study aimed to determine the association between the level of knowledge and negative attitudes toward HBV- and HCV-infected colleagues among the Japanese working population. An online anonymous nationwide survey involving about 3,000 individuals was conducted in Japan. The questionnaire consisted of knowledge of HBV and HCV, and attitudes toward HBV- and HCV-infected colleagues in the workplace. Knowledge was divided into three categories: "ensuring daily activities not to be infected"; "risk of infection"; and "characteristics of HBV/HCV hepatitis", based on the result of factor analysis. Multiple logistic regression analysis was applied. A total of 3,129 persons responded to the survey: 36.0% reported they worried about the possibility of transmission of HBV and HCV from infected colleagues; 32.1% avoided contact with infected colleagues; and 23.7% had prejudiced opinions about HBV and HCV infection. The participants were classified into tertiles. A higher level of knowledge of HBV and HCV was significantly associated with these three negative attitudes (P for trend < 0.005). This study suggests that increasing knowledge may decrease individuals' negative attitudes towards HBV- and HCV-infected colleagues. Thus, we should promote increased knowledge of HBV and HCV in stages to reduce negative attitudes toward HBV- and HCV-infected colleagues.


Comparison of Perioperative Outcomes of Total Laparoscopic and Robotically Assisted Hysterectomy for Benign Pathology during Introduction of a Robotic Program.
Study Objective. Prospectively compare outcomes of robotically assisted and laparoscopic hysterectomy in the process of implementing a new robotic program. Design. Prospectively comparative observational nonrandomized study. Design Classification. II-1. Setting. Tertiary caregiver university hospital. Patients. Data collected consecutively 24 months, 34 patients underwent laparoscopic hysterectomy, 25 patients underwent robotic hysterectomy, and 11 patients underwent vaginal hysterectomy at our institution. Interventions. Outcomes of robotically assisted, laparoscopic, and vaginal complex hysterectomies performed by a single surgeon for noncancerous indications. Measurements and Main Results. Operative times were 208.3 ± 59.01 minutes for laparoscopic, 286.2 ± 82.87 minutes for robotic, and 163.5 ± 61.89 minutes for vaginal (P < .0001). Estimated blood loss for patients undergoing laparoscopic surgery was 242.7 ± 211.37 cc, 137.4 ± 107.50 cc for robotic surgery, and 243.2 ± 127.52 cc for vaginal surgery (P = 0.05). The mean length of stay ranged from 1.8 to 2.3 days for the 3 methods. Association was significant for uterine weight (P = 0.0043) among surgery methods. Conclusion. Robotically assisted hysterectomy is feasible with low morbidity, a shorter hospital stay, and less blood loss. This suggests that robotic assistance facilitates a minimally invasive approach for patients with larger uterine size even during implementing a new robotic program.


Using an autologous fibrin sealant in the preventing of cerebrospinal fluid leak with large skull base defect following endoscopic endonasal transsphenoidal surgery.
Postoperative cerebrospinal fluid (CSF) leak following endoscopic endonasal transsphenoidal surgery (EETS) is associated with increased morbidity and mortality. This prospective study is the first evaluation of using autologous fibrin sealant for preventing postoperative CSF leak and related complications. 200 endoscopic endonasal transsphenoidal approaches were included in the study and reviewed retrospectively from September 2010 to June 2012. A total of 55 patients who have large skull base and diafragma sella defects, connected with basal cisterns or ventricles, were chosen for the study. The patients were operated via extended or classical endoscopic endonasal transsphenoidal approach. The skull base has been repaired using AFS combined with multilayer reconstruction in all cases. The incidence of CSF leak as a complication of EETS was analyzed. The ages of the patients ranged from 20 to 83 years (mean 49.3 years). There were 25 (46%) male patients and 30 (54%) females. All patients had tumors with suprasellar or parasellar extension. Postoperative CSF leak was determined in 2 patients (3.6%). There were no complications and allergic reactions associated with the use of AFS. Using of AFS combined with multilayer reconstruction technique is a safe and effective method to prevent CSF leak in large defects following EETS.


Amenable mortality revisited: the AMIEHS study.
There is a renewed interest in health system indicators. In 1976 a measure of quality of healthcare, amenable mortality, was introduced by Rutstein. This indicator is based on the concept that deaths from certain causes should not occur in the presence of timely and effective healthcare. In the project "Amenable mortality in the European Union: toward better indicators for the effectiveness of health systems" (AMIEHS), we introduce a new approach to the selection of indicators of amenable mortality. Based on predefined selection criteria and a broad review of the literature on the effectiveness of medical interventions, a first set of potential indicators of amenable mortality (causes of death) was selected. The timing of the introduction of medical innovations was established through reviews and questionnaires sent to national experts from seven participating European countries. The preselected indicators were then validated by a trend analysis that identified associations between the timing of innovations and cause-specific mortality trends and by a Delphi-procedure. After a short review of previous lists of amenable mortality indicators and a detailed description of the innovative procedure in the AMIEHS project we present a list of 14 causes of death that passed our selection criteria. We illustrate our empirical validation of these indicators using the examples of peptic ulcer and renal failure. The innovation developed in the AMIEHS study is a rigorous new approach to the concept of amenable mortality that includes empirical validation. Only validated indicators can be successfully used to assess the quality of healthcare systems in international comparisons.


BioSAXS Measurements Reveal That Two Antimicrobial Peptides Induce Similar Molecular Changes in Gram-Negative and Gram-Positive Bacteria.
Two highly active short broad-spectrum AMPs (14D and 69D) with unknown mode of action have been investigated in regards to their effect against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria methicillin-resistant Staphylococcus aureus (MRSA). Minimal inhibitory concentration (MIC) measurements using a cell density of 108 cfu/ml resulted in values between 16 and 32 µg/ml. Time-kill experiments using 108 cfu/ml revealed complete killing, except for 69D in combination with MRSA, where bacterial load was reduced a million times. Small-angle X-ray scattering of biological samples (BioSAXS) at 108 cfu/ml was applied to investigate the ultrastructural changes in E. coli and MRSA in response to these two broad-spectrum AMPs. In addition, electron microscopy (EM) was performed to visualize the treated and non-treated bacteria. As expected, the scattering curves generated using BioSAXS show the ultrastructure of the Gram-positive and Gram-negative bacteria to be very different (BioSAXS is not susceptible to the outer shape). After treatment with either peptide, the scattering curves of E. coli and MRSA cells are much more alike. Whereas in EM, it is notoriously difficult to observe changes for spherical Gram-positives; the BioSAXS results are superior and reveal strongly similar effects for both peptides induced in Gram-positive as well as Gram-negative bacteria. Given the high-throughput possibility and robust statistics, BioSAXS can support and speed up mode of action research in AMPs and other antimicrobial compounds, making a contribution toward the development of urgently needed drugs against resistant bacteria.


A focused ultrasoft x-ray microbeam for targeting cells individually with submicrometer accuracy.
The application of microbeams is providing new insights into the actions of radiation at the cell and tissue levels. So far, this has been achieved exclusively through the use of collimated charged particles. One alternative is to use ultrasoft X rays, focused by X-ray diffractive optics. We have developed a unique facility that uses 0.2-0.8-mm-diameter zone plates to focus ultrasoft X rays to a beam of less than 1 microm diameter. The zone plate images characteristic K-shell X rays of carbon or aluminum, generated by focusing a beam of 5-10 keV electrons onto the appropriate target. By reflecting the X rays off a grazing-incidence mirror, the contaminating bremsstrahlung radiation is reduced to 2%. The focused X rays are then aimed at selected subcellular targets using rapid automated cell-finding and alignment procedures; up to 3000 cells per hour can be irradiated individually using this arrangement.


Propionate assimilation in the flagellate Polytomella caeca. An inducible mitochondrial enzyme system.
1. The assimilation of propionate by Polytomella caeca involves the beta-oxidation of this fatty acid. 2. Propionate-grown cells immediately oxidize propionate, beta-hydroxypropionate, malonic semialdehyde and acetate; acetate-grown cells oxidize propionate rapidly only after a lag of 2hr., and this adaptation of resting cells to propionate involves the formation of the enzymes of beta-oxidation. 3. The beta-hydroxypropionate dehydrogenase and malonic semialdehyde dehydrogenase activities of both propionate-grown and propionate-adapted cells are partly located in mitochondrial fractions. 4. Mitochondria isolated from propionate-grown cells, and also those from acetate-grown cells fully adapted to propionate, oxidize succinate, alpha-oxoglutarate, beta-hydroxypropionate and malonic semialdehyde; oxidation of these substrates is tightly coupled to the phosphorylation of ADP. 5. Mitochondria from acetate-grown cells exhibit ADP-dependent oxidation of succinate and alpha-oxoglutarate, but do not oxidize beta-hydroxypropionate or malonic semialdehyde. Mitochondria isolated from acetate-grown cells adapted to propionate for 5hr. slowly oxidize beta-hydroxypropionate and malonic semialdehyde, but no tightly coupled phosphorylation is detectable. 6. Two of the inducible enzymes of propionate oxidation are located within the NAD-impermeable barrier and appear to be membrane-bound. 7. The formation of the inducible enzymes is inhibited by cycloheximide and actinomycin D, but not by chloramphenicol.


Children with atopic dermatitis show clinical improvement after Lactobacillus exposure.
The role of probiotics in the treatment of atopic dermatitis (AD) is not clearly established. Further clinical trials with new probiotic formulations are warranted. To assess the effects of Lactobacillus paracasei (LP) and Lactobacillus fermentum (LF), and their mixture on the disease severity, quality of life, and immune biomarkers of children with AD. A double-blind, prospective, randomized placebo-controlled study was conducted on 220 children aged 1-18 years with moderate-to-severe AD (Trial number: NCT01635738). The children were randomized to receive LP, LF, LP + LF mixture, and placebo for 3 months. Changes in severity scoring of atopic dermatitis (SCORAD), Family Dermatology Life Quality Index (FDLQI), and Children's Dermatology Life Quality Index (CDLQI) scores in the different groups and at different visits were evaluated. Skin prick tests, levels of IgE, IFN-γ, IL-4, TGF-β, and TNF-α, and urine biomarkers were also evaluated. Children who received LP, LF, and LP + LF mixture showed lower SCORAD scores than the placebo group (P < 0.001), and this difference remained even at 4 months after discontinuing the probiotics. The FDLQI and CDLQI scores were lower in the LP, LF, and LP + LF mixture group than in the placebo group (P = 0.02 and 0.03). IgE, TNF-α, urine eosinophilic protein X, and 8-OHdG levels decreased, whereas IFN-γ and TGF-β increased in the probiotic groups, but these did not reach statistical significance except for IL-4 (P = 0.04). In subgroup analyses, SCORAD scores significantly decreased after probiotic treatment especially in children younger than age 12, with breastfeeding > 6 months, and with mite sensitization (P < 0.001). Supplementation of a probiotic mixture of LP and LF is associated with clinical improvement in children with AD.


Deficiencies in the Fanconi anemia DNA damage response pathway increase sensitivity to HPV-associated head and neck cancer.
Patients with the rare genetic disease, Fanconi anemia (FA), are highly susceptible to squamous cell carcinomas arising at multiple anatomic sites including the head and neck region. Human papillomaviruses (HPVs), particularly HPV16, are associated with ∼20% of head and neck squamous cell carcinomas (HNSCCs) in the general population. Some but not other investigators have reported that HNSCCs in FA patients are much more frequently positive for HPV. In addition, studies have demonstrated an interaction between the HPV16 E7 oncoprotein and the FA pathway, a DNA damage response pathway deficient in FA patients. On the basis of these studies, it was hypothesized that the FA pathway contributes to repair of DNA damage induced by HPV16 E7, providing one explanation for why FA patients are predisposed to HPV-associated HNSCCs. To determine the importance of the FA pathway in modulating the oncogenic abilities of E7, we crossed K14E7 transgenic (K14E7) and fancD2 knockout mice (FancD2(-/-)) to establish K14E7/FancD2(-/-) and K14E7/FancD2(+/+) mice and monitored their susceptibility to HNSCC when treated with a chemical carcinogen. K14E7/FancD2(-/-) mice had a significantly higher incidence of HNSCC compared with K14E7/FancD2(+/+) mice. This difference correlated with an increased proliferative index and the increase in expression of biomarkers that are used to assess levels of DNA damage. These animal studies support the hypotheses that FA patients have increased susceptibility to HPV-associated cancer and that the FA DNA damage response pathway normally attenuates the oncogenic potential of HPV16 E7.


Nutritional factors may modify the toxic action of methyl mercury in fish-eating populations.
The historical record of clinical cases of methyl mercury poisoning dates back to the 19th century when the first chemical synthesis occurred. The potent fungicidal properties of both methyl and the closely related ethyl mercury compound were subsequently discovered, which led to widespread agricultural application for prevention of fungal infection in seed grain. Several catastrophic outbreaks of poisoning occurred in the mid-20th century when the treated seed grain was mistakenly used to prepare homemade bread. The largest outbreak took place in rural Iraq in the early 1970s. Human poisonings also occurred in Japan due to the release of methyl mercury into bodies of fresh and ocean water. The most infamous outbreak occurred in the area of Minamata Bay: methyl mercury, which was unwittingly discharged into the ocean water, avidly accumulated in the aquatic food chain to such an extent that people who consumed fish were severely poisoned. Today, human exposure to methyl mercury occurs from consumption of fish and sea mammals. Inorganic mercury that is present in aquatic sediments is methylated by microorganisms and accumulates in the aquatic food chain. Although no cases of clinical poisoning have been reported, a number of epidemiological studies have been carried out that raise the possibility of prenatal damage. Previous studies (especially the Iraq outbreak) indicate that the prenatal stage of the life cycle is the most vulnerable. However, ongoing epidemiological studies of heavy fish consumers of the Seychelles Islands in the Indian Ocean do not reveal adverse effects. To the contrary, the results of some developmental tests that were conducted on prenatally exposed children indicate beneficial outcomes that correlate with mercury levels during pregnancy. This article discusses the potential role of micronutrients in fish as a plausible explanation for these findings.


DOG1 expression is predicted by the seed-maturation environment and contributes to geographical variation in germination in Arabidopsis thaliana.
Seasonal germination timing of Arabidopsis thaliana strongly influences overall life history expression and is the target of intense natural selection. This seasonal germination timing depends strongly on the interaction between genetics and seasonal environments both before and after seed dispersal. DELAY OF GERMINATION 1 (DOG1) is the first gene that has been identified to be associated with natural variation in primary dormancy in A. thaliana. Here, we report interaccession variation in DOG1 expression and document that DOG1 expression is associated with seed-maturation temperature effects on germination; DOG1 expression increased when seeds were matured at low temperature, and this increased expression was associated with increased dormancy of those seeds. Variation in DOG1 expression suggests a geographical structure such that southern accessions, which are more dormant, tend to initiate DOG1 expression earlier during seed maturation and achieved higher expression levels at the end of silique development than did northern accessions. Although elimination of the synthesis of phytohormone abscisic acid (ABA) results in the elimination of maternal temperature effects on dormancy, DOG1 expression predicted dormancy better than expression of genes involved in ABA metabolism.


Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1-transformed acute lymphoblastic leukemia cells.
The Philadelphia chromosome (Ph) encoding the oncogenic BCR-ABL1 kinase defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. ALL cells are derived from B cell precursors in most cases and typically carry rearranged immunoglobulin heavy chain (IGH) variable (V) region genes devoid of somatic mutations. Somatic hypermutation is restricted to mature germinal center B cells and depends on activation-induced cytidine deaminase (AID). Studying AID expression in 108 cases of ALL, we detected AID mRNA in 24 of 28 Ph(+) ALLs as compared with 6 of 80 Ph(-) ALLs. Forced expression of BCR-ABL1 in Ph(-) ALL cells and inhibition of the BCR-ABL1 kinase showed that aberrant expression of AID depends on BCR-ABL1 kinase activity. Consistent with aberrant AID expression in Ph(+) ALL, IGH V region genes and BCL6 were mutated in many Ph(+) but unmutated in most Ph(-) cases. In addition, AID introduced DNA single-strand breaks within the tumor suppressor gene CDKN2B in Ph(+) ALL cells, which was sensitive to BCR-ABL1 kinase inhibition and silencing of AID expression by RNA interference. These findings identify AID as a BCR-ABL1-induced mutator in Ph(+) ALL cells, which may be relevant with respect to the particularly unfavorable prognosis of this leukemia subset.


Time Trends in Ovarian Cancer Survival in Estonia by Age and Stage.
The objective of the study was to examine temporal trends in ovarian cancer (OC) survival in Estonia during 1995 to 2009 in relation to age and stage. Estonian Cancer Registry data on all adult cases of primary OC diagnosed during 1995 to 2009 and followed up for vital status until 2014 were used to estimate relative survival ratios (RSRs). Cohort analysis was used to estimate 1-, 2-, and 5-year RSRs for patients diagnosed in 1995 to 1999, 2000 to 2004, and 2005 to 2009. Analysis was performed by age at diagnosis (<50; 50-59; 60-69; 70+ years) and stage (International Federation of Gynecology and Obstetrics 1988). Among 2296 women included in the study, the age-adjusted 5-year RSR improved from 27% in 1995 to 1999 to 38% in 2005 to 2009. Survival increase of 10% units from 1995 to 1999 to 2005 to 2009 was seen for women aged 50 to 59 and 60 to 69 years. Among younger and older women, the respective changes were smaller. In 1995 to 1999, the difference in survival between the youngest and oldest age groups was 41% units. This decreased over the study period to 37% units. From 1995 to 1999 to 2005 to 2009, the 5-year RSR increased from 82% to 91% for stage I patients; from 48% to 67% for stage II patients; from 25% to 35% for stage III patients; and from 11% to 16% for stage IV patients. The study showed an improvement of OC survival in Estonia in all age and stage groups, but particularly among younger women and those with early stage disease. Slower progress among older women is of great concern.


Patients' experiences of isolation in psychiatric inpatient care: Insights from a meta-ethnographic study.
Historically, people with mental ill-health have been isolated from society. Although mental health care has moved from closed to more open forms of care, in many societies care is still provided in locked wards, and people with mental ill-health are sometimes secluded from their fellow patients, families, friends, and visitors. The aim of this study was to illuminate patients' experiences of isolation in psychiatric inpatient care. A systematic review of qualitative research was conducted, and the key findings were subjected to meta-ethnographic synthesis. The findings were twofold: 'being admitted to prison' and 'having access to shelter'. The experience of isolated care as prison-like symbolizes patients' longing for freedom and feeling restricted and limited by rules, stripped of rights, abandoned, controlled, powerless, and unsupported. In contrast, the experience of isolation as shelter symbolizes safety and the opportunity to regain control over one's own situation. A stigmatizing public view holds that people with mental ill-health are dangerous and unpredictable and, therefore, unsafe to themselves and others. Being placed in isolation because these fears contribute to self-stigma among patients. Promoting a sheltered experience in which isolation is used with respect for patients and the reasons are made explicit may encourage recovery. A shift in emphasis in ward culture from observation to engagement is needed to reduce blame, shift patient experiences from prison to shelter, and to support autonomy as a therapeutic intervention.


Adaptation of a smoking cessation and prevention website for urban American Indian/Alaska Native youth.
Tobacco use among American Indian youth is a disproportionately significant problem. We adapted and modified an existing web-based and youth-focused tobacco control program to make it appropriate for young urban American Indian/Alaska Natives (AI/ANs). The results of the focus group indicate that AI/AN youth were very receptive to the use of a web-based Zine-style intervention tool. They wanted the look and feel of the website to be more oriented toward their cultural images. Future research should examine if successful programs for reducing non-ceremonial tobacco use among urban AI/AN youth can keep young irregular smokers from becoming adult smokers.


Erm(41)-dependent inducible resistance to azithromycin and clarithromycin in clinical isolates of Mycobacterium abscessus.
The ribosomal methylase Erm(41) confers inducible resistance to macrolides in Mycobacterium abscessus. The aim of this work was to systematically study and compare drug susceptibility to clarithromycin and azithromycin in M. abscessus and Mycobacterium chelonae clinical isolates with a particular focus on inducible drug resistance. Clinical isolates of M. abscessus subsp. abscessus (n = 21), M. abscessus subsp. bolletii (n = 16), M. abscessus subsp. massiliense (n = 10) and M. chelonae (n = 22) were characterized regarding their erm(41) and rrl genotypes and subjected to drug susceptibility testing (DST) for clarithromycin and azithromycin. Microdilution DST was performed in cation-adjusted Mueller-Hinton broth (pH 7.4) with readings at days 3, 7 and 12 and with pre-incubation at subinhibitory macrolide concentrations for erm(41) induction. In addition, the influence of variations in pH and growth medium on DST results was examined. MICs of azithromycin were consistently higher than those of clarithromycin. In strains with an inducible erm(41) gene, high median MICs of ≥256 mg/L on day 12 were observed for both clarithromycin and azithromycin. Inducible resistance was at least as pronounced for azithromycin as for clarithromycin. Our findings do not support the suggestion of a preferential use of azithromycin over clarithromycin in order to limit inducible macrolide resistance. Both compounds provoked a comparable resistance phenotype in M. abscessus. Caution is needed when using either azithromycin or clarithromycin for treatment of M. abscessus infections.


The first experiences of robotic single-site cholecystectomy in Asia: a potential way to expand minimally-invasive single-site surgery?
Herein, we firstly present the robotic single-site cholecystectomy (RSSC) as performed in Asia and evaluate whether it could overcome the limitations of conventional laparoscopic single-site cholecystectomy. From October 2013 to November 2013, RSSC for benign gallbladder (GB) disease was firstly performed consecutively in five patients. We evaluated these early experiences of RSSC and compared factors including clinicopathologic factors and operative outcomes with our initial cases of single-fulcrum laparoscopic cholecystectomy (SFLC). Four female patients and one male patient underwent RSSC. Neither open conversion nor bile duct injury or bile spillage was noted during surgery. In comparisons with SFLC, patient-related factors in terms of age, sex, Body Mass Index, diagnosis, and American Society of Anesthesiologist score showed no significant differences between two groups. There were no significant differences in the operative outcomes regarding intraoperative blood loss, bile spillage during operation, postoperative pain scale values, postoperative complications, and hospital stay between the two groups (p<0.05). Actual dissection time (p=0.003) and total operation time (p=0.001) were significantly longer in RSSC than in SFLC. There were no drain insertion or open conversion cases in either group. RSSC provides a comfortable environment and improved ergonomics to laparoscopic single-site cholecystectomy; however, this technique needs to be modified to allow for more effective intracorporeal movement. As experience and technical innovations continue, RSSC will soon be alternative procedure for well-selected benign GB disease.


Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity.
Mammalian lifespan differs by >100 fold, but the mechanisms associated with such longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts isolated from 16 species of mammals and maintained under identical cell culture conditions. We developed a pipeline for obtaining species-specific ortholog sequences, profiled gene expression by RNA-seq and small molecules by metabolite profiling, and identified genes and metabolites correlating with species longevity. Cells from longer lived species up-regulated genes involved in DNA repair and glucose metabolism, down-regulated proteolysis and protein transport, and showed high levels of amino acids but low levels of lysophosphatidylcholine and lysophosphatidylethanolamine. The amino acid patterns were recapitulated by further analyses of primate and bird fibroblasts. The study suggests that fibroblast profiling captures differences in longevity across mammals at the level of global gene expression and metabolite levels and reveals pathways that define these differences.


Leukocyte coping capacity: a novel technique for measuring the stress response in vertebrates.
Methods used to quantify the stress response in animals are vital tools in many areas of biology. Here we describe a new method of measuring the stress response, which provides rapid results and can be used in the field or laboratory. After a stressful event, we measure the capacity of circulating leukocytes to produce a respiratory burst in vitro in response to challenge by phorbol myristate acetate (PMA). During the respiratory burst leukocytes produce oxygen free radicals, and the level of production can be measured directly as chemiluminescence. When in vitro PMA-stimulated whole blood chemiluminescence is measured directly after a stressful event, we define the response as the leukocyte coping capacity (LCC). In an experiment badgers (Meles meles), which were caught as part of an on-going population study, were either transported to a central site prior to blood sampling or blood was collected at their site of capture. Transported animals had a significantly lower LCC and showed changes in leukocyte composition that were indicative of stress. We conclude that the stress of transport reduced LCC in badgers and that LCC serves as a quantitative measure of stress. Potential applications of this method are discussed.


Effect of high-dose cranberry juice on the pharmacodynamics of warfarin in patients.
Case reports suggest an association between cranberry juice and potentiation of warfarin. Studies using 240 ml of cranberry juice daily demonstrated no interaction. It is unknown if higher amounts of cranberry juice will interact with warfarin. Cranberry juice at 240 ml twice daily does not alter the pharmacodynamics of warfarin. To determine if high-dose cranberry juice (240 ml twice daily) alters the pharmacodynamic action of warfarin. Ten male patients taking stable doses of warfarin were given cranberry juice at 240 ml twice daily for 7 days. Prothrombin times were drawn at baseline and days 2, 6 and 8 after administration of the juice. Prothrombin times were averaged for each day and mean times were compared from each study day to baseline using repeated measures ANOVA. There was no statistical difference between mean prothrombin time at baseline and any day tested during juice administration. Cranberry juice (240 ml twice daily for 1 week) did not alter the pharmacodynamics of warfarin in patients.


Wrong egg in the usual nest: thyroid papillary carcinoma within a branchial cleft cyst.
Branchial cleft cysts are the most common lesions to arise laterally in the neck. Ectopic thyroid tissue within a branchial cleft cyst is rare, and a papillary carcinoma arising from this tissue is extremely rare. We present a case of a lateral neck cyst representing a primary papillary carcinoma that arose in ectopic thyroid tissue within a branchial cleft cyst in a 41-year-old woman. After the mass was surgically excised, thyroid ultrasonography, thyroid scintigraphy, and whole-body F18-fluorodeoxyglucose-positron emission tomography/computed tomography detected no abnormality. The negative findings notwithstanding, surgery on the thyroid gland was planned, but the patient refused it. Therefore, she was followed up with ultrasonography and scintigraphy for 5 years, during which time she exhibited no evidence of recurrence. Total thyroidectomy is still the primary option in such cases, but when it cannot be performed for any reason, vigilant follow-up is essential.


Molecular Origin of the Glass Transition in Polyelectrolyte Assemblies.
Water plays a central role in the assembly and the dynamics of charged systems such as proteins, enzymes, DNA, and surfactants. Yet it remains a challenge to resolve how water affects relaxation at a molecular level, particularly for assemblies of oppositely charged macromolecules. Here, the molecular origin of water's influence on the glass transition is quantified for several charged macromolecular systems. It is revealed that the glass transition temperature (Tg) is controlled by the number of water molecules surrounding an oppositely charged polyelectrolyte-polyelectrolyte intrinsic ion pair as 1/Tg ∼ ln(nH2O/nintrinsic ion pair). This relationship is found to be "general", as it holds for two completely different types of charged systems (pH- and salt-sensitive) and for both polyelectrolyte complexes and polyelectrolyte multilayers, which are made by different paths. This suggests that water facilitates the relaxation of charged assemblies by reducing attractions between oppositely charged intrinsic ion pairs. This finding impacts current interpretations of relaxation dynamics in charged assemblies and points to water's important contribution at the molecular level.


Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation as a result of its membrane interactions.
The biological activity of the Alzheimer's disease amyloid beta protein may be related to modulation of membrane lipid peroxidation. The effect of amyloid beta protein fragment 25-35 [A beta(25-35)] on lipid peroxidation was examined in liposomes enriched with polyunsaturated fatty acids. The activity of A beta(25-35) was compared to that of A beta(25-35) with either a scrambled sequence [A beta(25-35)scram] or a peptide sequence in which methionine was replaced with leucine [A beta(25-35) met]. A beta(25-35) inhibited lipid peroxidation in a dose- and time-dependent manner. The antioxidant activity of A beta(25-35) was observed at concentrations as low as 10 nM. The relative antioxidant activities of the amyloid beta protein fragments were as follows: A beta(25-35) > A beta(25-35) met > A beta(25-35)scram. The two more potent peptides intercalated into the membrane hydrocarbon core, as determined by small-angle x-ray diffraction approaches. These findings indicate that the amphiphilic A beta(25-35) peptide inhibits lipid peroxidation at low concentrations as a result of physicochemical interactions with the membrane lipid bilayer.


The immune response to nematode parasites: modulation of mast cell numbers and function during Strongyloides stercoralis infections in nonhuman primates.
Mucosal mast cell numbers are modulated in the intestines of rodents during parasitic infections. These mast cells can degranulate in response to worm antigens, and this event has been suggested to play a protective role for the host. To examine whether mast cells in higher animals play a role in protecting from disseminated parasitic disease, mast cell numbers and responsiveness to parasite antigens were evaluated in 5 Erythrocebus patas infected with the human intestinal nematode Strongyloides stercoralis. Initial infection and subsequent challenge infections were associated with increase in jejunal histamine and mast cell numbers, and these mast cells could release histamine in response to parasite antigens. Jejunal mast cell numbers returned to normal during a chronic phase of infection. The cells lost their ability to respond to antigenic stimulation following limited steroid treatment. Subsequent activation of chronic infections to fatal disseminated disease by more prolonged steroid treatment was associated with a marked decrease in jejunal mast cell numbers and histamine. In one animal which succumbed to severe disease without steroid treatment, jejunal mast cells were refractory to worm antigens.


A perspective on nonresonant and resonant electronic response theory for time-dependent molecular properties.
The development of electronic response theory in quantum chemistry has been reviewed, starting from the early 1970's and reaching the current state-of-the-art. The general theory has been applied to the calculation of a large number of spectroscopic parameters over the years, and it has been implemented for the majority of standard electronic structure methods. Two formulations of response theory, the Ehrenfest expectation value and the quasi-energy derivative formulation, have turned into leading alternatives for the derivation of computationally tractable expressions of response functions, and they are here reviewed with an attempt to, as far as possible, leave out technical details. A set of four steps are identified as common in derivations of response functions, and the two formulations are compared along this series of steps. Particular emphasis is given to the situation when the oscillation of the weak external electromagnetic field is in resonance with a transition frequency of the system. The formation of physically sound response functions in resonance regions of the spectrum is discussed in light of the causality condition and the Kramers-Kronig relations, and it is achieved in wave function theory by means of the introduction of relaxation parameters in a manner that mimics what one sees in density matrix theory. As a working example, equations are illustrated by their application to a two-state model for para-nitroaniline including the ground and the lowest charge-transfer state in the electric dipole approximation.


Feline panleukopaenia virus in captive non-domestic felids in South Africa.
An outbreak of feline panleukopaenia virus (FPLV) infection was diagnosed by pathology, electron microscopy and polymerase chain reaction (PCR) in vaccinated captive-bred subadult cheetahs in South Africa. Subsequent to this disease outbreak, 12 cases of FPLV diagnosed on histology were confirmed by PCR in captive African black-footed cat, caracal, cheetah, lion, ocelot and serval. Phylogenetic analyses of the viral capsid protein gene on PCR-positive samples, vaccine and National Center for Biotechnology Information (NCBI) reference strains identified a previously unknown strain of FPLV, present since at least 2006, that differs from both the inactivated and the modified live vaccine strains. A previously described South African strain from domestic cats and cheetahs was identified in a serval. Surveys of FPLV strains in South African felids are needed to determine the geographical and host species distribution of this virus. Since non-domestic species may be reservoirs of parvoviruses, and since these viruses readily change host specificity, the risks of FPLV transmission between captive-bred and free-ranging carnivores and domestic cats and dogs warrant further research.


Increased survival among lower-birthweight children in Southern Brazil.
To analyze factors associated with survival in the first year of life. A historical cohort study was carried out using data from live birth and mortality information systems, including 90,153 live birth records and 1,053 records of death before age one year in hospitals in the cities of Florianópolis and São José, Southern Brazil, between 1999 and 2006. Survival curves were estimated (Kaplan-Meier) for birthweight categories, date of birth (four-year periods), and type of maternity. Proportional hazard ratios for mortality were calculated using Cox regression. Survival (98.8%) did not change among all birthweight categories, but increased among babies born weighing under 2,000 g (77.7% to 81.2%, p=0.029), between 1999-2002 and 2003-2006. There was an increase in the proportion of babies under 2,000 g in the second period. Type of hospital was significantly associated with probability of survival. Probability of survival is higher among babies born in private hospitals and in the teaching hospital in all birthweight categories combined and for babies born weighing under 2,000 g. Survival among the latter increased in the most recent period. However, the infant mortality rate did not change between the two periods given the increase in the prevalence of children with ligther birth weight.


A Self-Activation Loop Maintains Meristematic Cell Fate for Branching.
In plants and animals, self-renewing stem cell populations play fundamental roles in many developmental contexts. Plants differ from most animals in their retained ability to initiate new cycles of growth and development, which relies on the establishment and activity of branch meristems. In seed plants, branching is achieved by stem-cell-containing axillary meristems, which are initiated from a leaf axil meristematic cell population originally detached from the shoot apical meristem. It remains unclear how the meristematic cell fate is maintained. Here, we show that ARABIDOPSISTHALIANAHOMEOBOXGENE1 (ATH1) maintains the meristem marker gene SHOOT MERISTEMLESS (STM) expression in the leaf axil to enable meristematic cell fate maintenance. Furthermore, ATH1 protein interacts with STM protein to form a STM self-activation loop. Genetic and biochemical data suggest that ATH1 anchors STM to activate STM as well as other axillary meristem regulatory genes. This auto-regulation allows the STM locus to remain epigenetically active. Taken together, our findings provide a striking example of a self-activation loop that maintains the flexibility required for stem cell niche re-establishment during organogenesis.


Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing.
Colossoma macropomum, or tambaqui, is the largest native Characiform species found in the Amazon and Orinoco river basins, yet few resources for genetic studies and the genetic improvement of tambaqui exist. In this study, we identified a large number of single-nucleotide polymorphisms (SNPs) for tambaqui and constructed a high-resolution genetic linkage map from a full-sib family of 124 individuals and their parents using the genotyping by sequencing method. In all, 68,584 SNPs were initially identified using minimum minor allele frequency (MAF) of 5%. Filtering parameters were used to select high-quality markers for linkage analysis. We selected 7,734 SNPs for linkage mapping, resulting in 27 linkage groups with a minimum logarithm of odds (LOD) of 8 and maximum recombination fraction of 0.35. The final genetic map contains 7,192 successfully mapped markers that span a total of 2,811 cM, with an average marker interval of 0.39 cM. Comparative genomic analysis between tambaqui and zebrafish revealed variable levels of genomic conservation across the 27 linkage groups which allowed for functional SNP annotations. The large-scale SNP discovery obtained here, allowed us to build a high-density linkage map in tambaqui, which will be useful to enhance genetic studies that can be applied in breeding programs.


Evaluating a dementia learning community: exploratory study and research implications.
Access times for, the costs and overload of hospital services are an increasingly salient issue for healthcare managers in many countries. Rising demand for hospital care has been attributed partly to unplanned admissions for older people, and among these partly to the increasing prevalence of dementia. The paper makes a preliminary evaluation of the logic model of a Dementia Learning Community (DLC) intended to reduce unplanned hospital admissions from care homes of people with dementia. A dementia champion in each DLC care home trained other staff in dementia awareness and change management with the aims of changing work routines, improving quality of life, and reducing demands on external services. Controlled mixed methods realistic evaluation comparing 13 intervention homes with 10 controls in England during 2013-15. Each link in the assumed logic model was tested to find whether that link appeared to exist in the DLC sites, and if so whether its effects appeared greater there than in control sites, in terms of selected indicators of quality of life (DCM Well/Ill-Being, QUALID, end-of-life planning); and impacts on ambulance call-outs and hospital admissions. The training was implemented as planned, and triggered cycles of Plan-Do-Study-Act activity in all the intervention care homes. Residents' well-being scores, measured by dementia care mapping, improved markedly in half of the intervention homes but not in the other half, where indeed some scores deteriorated markedly. Most other care quality indicators studied did not significantly improve during the study period. Neither did ambulance call-out or emergency hospital admission rates. PDSA cycles appeared to be the more 'active ingredient' in this intervention. The reasons why they impacted on well-being in half of the intervention sites, and not the others, require further research. A larger, longer study would be necessary to measure definitively any impacts on unplanned hospital admissions. Our evidence suggested revising the DLC logic model to include care planning and staff familiarisation with residents' personal histories and needs as steps towards improving residents' quality of life.


Cooperative binding of annexin A2 to cholesterol- and phosphatidylinositol-4,5-bisphosphate-containing bilayers.
Biological membranes are organized into dynamic microdomains that serve as sites for signal transduction and membrane trafficking. The formation and expansion of these microdomains are driven by intrinsic properties of membrane lipids and integral as well as membrane-associated proteins. Annexin A2 (AnxA2) is a peripherally associated membrane protein that can support microdomain formation in a Ca(2+)-dependent manner and has been implicated in membrane transport processes. Here, we performed a quantitative analysis of the binding of AnxA2 to solid supported membranes containing the annexin binding lipids phosphatidylinositol-4,5-bisphosphate and phosphatidylserine in different compositions. We show that the binding is of high specificity and affinity with dissociation constants ranging between 22.1 and 32.2 nM. We also analyzed binding parameters of a heterotetrameric complex of AnxA2 with its S100A10 protein ligand and show that this complex has a higher affinity for the same membranes with Kd values of 12 to 16.4 nM. Interestingly, binding of the monomeric AnxA2 and the AnxA2-S100A10 complex are characterized by positive cooperativity. This cooperative binding is mediated by the conserved C-terminal annexin core domain of the protein and requires the presence of cholesterol. Together our results reveal for the first time, to our knowledge, that AnxA2 and its derivatives bind cooperatively to membranes containing cholesterol, phosphatidylserine, and/or phosphatidylinositol-4,5-bisphosphate, thus providing a mechanistic model for the lipid clustering activity of AnxA2.


Female Anopheles gambiae antennae: increased transcript accumulation of the mosquito-specific odorant-binding-protein OBP2.
New interventions are required to optimally and sustainably control the Anopheles sp. mosquitoes that transmit malaria and filariasis. The mosquito olfactory system is important in host seeking (transmission) and mate finding (reproduction). Understanding olfactory function could lead to development of control strategies based on repelling parasite-carrying mosquitoes or attracting them into a fatal trap. Our initial focus is on odorant binding proteins with differential transcript accumulation between female and male mosquitoes. We report that the odorant binding protein, OBP2 (AGAP003306), had increased expression in the antennae of female vs. male Anopheles gambiae sensu stricto (G3 strain). The increased expression in antennae of females of this gene by quantitative RT-PCR was 4.2 to 32.3 fold in three independent biological replicates and two technical replicate experiments using A. gambiae from two different laboratories. OBP2 is a member of the vast OBP superfamily of insect odorant binding proteins and belongs to the predominantly dipteran clade that includes the Culex oviposition kairomone-binding OBP1. Phylogenetic analysis indicates that its orthologs are present across culicid mosquitoes and are likely to play a conserved role in recognizing a molecule that might be critical for female behavior. OBP2 has increased mRNA transcript accumulation in the antennae of female as compared to male A. gambiae. This molecule and related molecules may play an important role in female mosquito feeding and breeding behavior. This finding may be a step toward providing a foundation for understanding mosquito olfactory requirements and developing control strategies based on reducing mosquito feeding and breeding success.


Variation Among Phytophthora cinnamomi Isolates from Oak Forest Soils in the Eastern United States.
Phytophthora cinnamomi isolates from geographically diverse oak forest soils in the Mid-Atlantic regions were studied to determine the extent of genotypic, phenotypic, and pathogenic variation. Four microsatellite loci were targeted for genetic analysis. Phenotypic characteristics measured included sexual and asexual spore dimensions and colony growth rate and morphology. Red oak (Quercus rubra) logs were inoculated with selected isolates to determine relative pathogenicity. Microsatellite analysis showed that the genetic variability of P. cinnamomi isolates was low, with two predominant microsatellite fingerprint groups (MFG). Isolates in MFG1 (48% of the total isolates examined) were characterized by DNA fragment lengths of 120 and 122 bp at locus d39, 169 and 170 bp at locus e16, and 254 and 255 bp at locus g13. MFG2 isolates were characterized by marker sizes of 122 and 124 bp at locus d39, 161 and 163 bp at locus e16, and 247 and 248 bp at locus g13. Asexual and sexual spore dimensions varied greatly among isolates but were similar to previously published descriptions. Phenotypic differences were most pronounced when data were grouped by MFG; the most significant were colony morphology and growth rate. Neither characteristic was a reliable predictor of isolate genotype. Differences in growth rates of MFGs were observed, with MFG1 being less tolerant at higher incubation temperatures. No variation in pathogenicity was observed on red oak logs. The low level of phenotypic and genotypic variation of P. cinnamomi suggest that other factors such as climate might play a more important role in its northern distribution and the diseases it causes.


Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study.
PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.


Artificial light at night causes reproductive failure in clownfish.
The Earth is getting brighter at night, as artificial light at night (ALAN) continues to increase and extend its reach. Despite recent recognition of the damaging impacts of ALAN on terrestrial ecosystems, research on ALAN in marine systems is comparatively lacking. To further our understanding of the impacts of ALAN on marine organisms, this study examines how the reproductive fitness of the common clownfish Amphiprion ocellaris is influenced by the presence of ALAN. We assessed how exposure to low levels of ALAN affects (i) frequency of spawning, (ii) egg fertilization success, and (iii) hatching success of A. ocellaris under control (12 : 12 day-night) and treatment (12 : 12 day-ALAN) light regimes. While we found exposure to ALAN had no impact on the frequency of spawning or fertilization success, ALAN had dramatic effects on hatching. Amphiprion ocellaris eggs incubated in the presence of ALAN simply did not hatch, resulting in zero survivorship of offspring. These findings suggest ALAN can significantly reduce reproductive fitness in a benthic-spawning reef fish. Further research in this field is necessary to fully understand the extent of this impact on population and community dynamics in the wild.


Proposal to modify Rule 6, Rule 10a, and Rule 12c of the International Code of Nomenclature of Prokaryotes.
According to the current versions of Rule 10a and Rule 12c of the International Code of Nomenclature of Prokaryotes, names of a genus or subgenus and specific epithets may be taken from any source and may even be composed in an arbitrary manner. Based on these rules, names may be composed of any word or any combination of elements derived from any language with a Latin ending. We propose modifying these rules by adding the text, currently part of Recommendation 6, according to which words from languages other than Latin or Greek should be avoided as long as equivalents exist in Latin or Greek or can be constructed by combining word elements from these two languages. We also propose modification of Rule 6 by adopting some of the current paragraphs of Recommendation 6 to become part of the Rule.


Two-phase anaerobic digestion of source sorted OFMSW (organic fraction of municipal solid waste): performance and kinetic study.
The results of a two-phase system operated in different conditions, treating the source-sorted organic fraction of municipal solid waste (SS-OFMSW), coming mainly from fruit and vegetable markets, are presented. Hydraulic retention time (HRT) in the hydrolytic reactor and in the methanogenic reactor and also the temperature in the hydrolytic reactor (mesophilic and thermophilic conditions) are varied in order to evaluate the effect of these factors. The methanogenic reactor is always operated within the thermophilic range. Optimum operating conditions are found to be around 12 days (total system) using the mesophilic range of temperature in the first reactor. Specific gas production (SGP) in these conditions is around 0.6 m3/kg TVS. A kinetic study is also carried out, using the first and the step diffusional models. The latter gives much better results, with fitted constants comparable to other studies. Finally, a comparison with a one-phase system is carried out, showing that a two-phase system is much more appropriate for the digestion of this kind of highly biodegradable substrate in thermophilic conditions.


Selective nonoperative management in 1,856 patients with abdominal gunshot wounds: should routine laparotomy still be the standard of care?
To evaluate the safety of a policy of selective nonoperative management (SNOM) in patients with abdominal gunshot wounds. Selective nonoperative management is practiced extensively in stab wounds and blunt abdominal trauma, but routine laparotomy is still the standard of care in abdominal gunshot wounds. The authors reviewed the medical records of 1,856 patients with abdominal gunshot wounds (1,405 anterior, 451 posterior) admitted during an 8-year period in a busy academic level 1 trauma center and managed by SNOM. According to this policy, patients who did not have peritonitis, were hemodynamically stable, and had a reliable clinical examination were observed. Initially, 792 (42%) patients (34% of patients with anterior and 68% with posterior abdominal gunshot wounds) were selected for nonoperative management. During observation 80 (4%) patients developed symptoms and required a delayed laparotomy, which revealed organ injuries requiring repair in 57. Five (0.3%) patients suffered complications potentially related to the delay in laparotomy, which were managed successfully. Seven hundred twelve (38%) patients were successfully managed without an operation. The rate of unnecessary laparotomy was 14% among operated patients (or 9% among all patients). If patients were managed by routine laparotomy, the unnecessary laparotomy rate would have been 47% (39% for anterior and 74% for posterior abdominal gunshot wounds). Compared with patients with unnecessary laparotomy, patients managed without surgery had significantly shorter hospital stays and lower hospital charges. By maintaining a policy of SNOM instead of routine laparotomy, a total of 3,560 hospital days and $9,555,752 in hospital charges were saved over the period of the study. Selective nonoperative management is a safe method for managing patients with abdominal gunshot wounds in a level 1 trauma center with an in-house trauma team. It reduces significantly the rate of unnecessary laparotomy and hospital charges.


Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney.
Good glycemic control is crucial to prevent the onset and progression of late diabetic complications, but insulin treatment often fails to achieve normalization of glycemic control to the level seen in healthy controls. In fact, recent experimental studies indicate that insufficient treatment with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which did not restore glycemic control, to streptozotocin (STZ)-diabetic rats using noninvasive hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) and blood oxygenation level-dependent (BOLD) (1)H-MRI to determine renal metabolic flux and oxygen availability, respectively. Suboptimal insulin administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates. The results demonstrate the importance of tight glycemic control in insulinopenic diabetes, and that insulin, when administered insufficiently, adds an additional burden on top of poor glycemic control.


3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology.
To study the distribution and predominant orientations of fibrillar collagen at different depths throughout the entire thickness of the human cornea. This information will form the basis of a full three-dimensional reconstruction of the preferred orientations of corneal lamellae. Femtosecond laser technology was used to delaminate the central zones of five human corneas into three separate layers (anterior, mid, and posterior stroma), each with predetermined thicknesses. Wide-angle x-ray diffraction was used to study the gross collagen fibril orientation and distribution within each layer. The middle and posterior parts of the human cornea demonstrated a preferential orthogonal arrangement of collagen fibrils, directed along the superior-inferior and nasal-temporal meridians, with an increase in the number of lamellae toward the periphery. However, the anterior cornea (33% of total corneal thickness) showed no systematic preferred lamellar orientation. In the posterior two thirds of the human cornea, collagen lies predominantly in the vertical and horizontal meridians (directed toward the four major rectus muscles), whereas collagen in the anterior third of the cornea is more isotropic. The predominantly orthogonal arrangement of collagen in the mid and posterior stroma may help to distribute strain in the cornea by allowing it to withstand the pull of the extraocular muscles, whereas the more isotropic arrangement in the anterior cornea may play an important role in the biomechanics of the cornea by resisting intraocular pressure while at the same time maintaining corneal curvature.


Theory of the spontaneous optical emission of nanosize photonic and plasmon resonators.
We provide a self-consistent electromagnetic theory of the coupling between dipole emitters and dissipative nanoresonators. The theory that relies on the concept of quasinormal modes with complex frequencies provides an accurate closed-form expression for the electromagnetic local density of states of any photonic or plasmonic resonator with strong radiation leakage, absorption, and material dispersion. It represents a powerful tool to calculate and conceptualize the electromagnetic response of systems that are governed by a small number of resonance modes. We use the formalism to revisit Purcell's factor. The new formula substantially differs from the usual one; in particular, it predicts that a spectral detuning between the emitter and the resonance does not necessarily result in a Lorentzian response in the presence of dissipation. Comparisons with fully vectorial numerical calculations for plasmonic nanoresonators made of gold nanorods evidence the high accuracy of the predictions achieved by our semianalytical treatment.


Total disc replacement for chronic discogenic low back pain: a Cochrane review.
Systematic literature review. To assess the effect of total disc replacement for chronic low back pain due to lumbar degenerative disc disease compared with fusion or other treatment options. There is an increasing use in disc replacement devices for degenerative disc disease, but their effectiveness compared with other interventions such as fusion of the motion segment or conservative treatment remains unclear. A comprehensive search in PubMedCentral, MEDLINE, EMBASE, BIOSIS, ClinicalTrials.gov, and FDA trials register was conducted. Randomized controlled trials comparing total disc replacement with any other intervention for degenerative disc disease were included. Risk of bias was assessed using the criteria of the Cochrane Back Review Group. Quality of evidence was graded according to the GRADE approach. Two review authors independently selected studies, assessed risk of bias, and extracted data. Results and upper bounds of confidence intervals were compared with predefined clinically relevant differences. We included 7 randomized controlled trials with a follow-up of 24 months. There is risk of bias in the included studies due to sponsoring and absence of any kind of blinding. One study compared disc replacement with rehabilitation and found a significant advantage in favor of surgery, which, however, did not reach the predefined threshold. Six studies compared disc replacement with fusion and found that the mean improvement in visual analogue scale score of back pain was 5.2 mm higher (2 studies; 95% confidence interval 0.2-10.3) with a low quality of evidence. The improvement of Oswestry disability index score at 24 months in the disc replacement group was 4.3 points more than in the fusion group (5 studies; 95% confidence interval 1.85-6.68) with a low quality of evidence. Both upper bounds of the confidence intervals were below the predefined clinically relevant difference. Although statistically significant, the differences in clinical improvement were not beyond generally accepted boundaries for clinical relevance. Prevention of adjacent level disease and/or facet joint degeneration was not properly assessed. Therefore, because we think that harm and complications may occur after some years, the spine surgery community should be prudent to adopt this technology on a large scale, despite the fact that total disc replacement seems to be effective in treating low back pain in selected patients, and in the short term is at least equivalent to fusion surgery.


Protein Ingestion before Sleep Increases Muscle Mass and Strength Gains during Prolonged Resistance-Type Exercise Training in Healthy Young Men.
It has been demonstrated that protein ingestion before sleep increases muscle protein synthesis rates during overnight recovery from an exercise bout. However, it remains to be established whether dietary protein ingestion before sleep can effectively augment the muscle adaptive response to resistance-type exercise training. Here we assessed the impact of dietary protein supplementation before sleep on muscle mass and strength gains during resistance-type exercise training. Forty-four young men (22 ± 1 y) were randomly assigned to a progressive, 12-wk resistance exercise training program. One group consumed a protein supplement containing 27.5 g of protein, 15 g of carbohydrate, and 0.1 g of fat every night before sleep. The other group received a noncaloric placebo. Muscle hypertrophy was assessed on a whole-body (dual-energy X-ray absorptiometry), limb (computed tomography scan), and muscle fiber (muscle biopsy specimen) level before and after exercise training. Strength was assessed regularly by 1-repetition maximum strength testing. Muscle strength increased after resistance exercise training to a significantly greater extent in the protein-supplemented (PRO) group than in the placebo-supplemented (PLA) group (+164 ± 11 kg and +130 ± 9 kg, respectively; P < 0.001). In addition, quadriceps muscle cross-sectional area increased in both groups over time (P < 0.001), with a greater increase in the PRO group than in the PLA group (+8.4 ± 1.1 cm(2) vs. +4.8 ± 0.8 cm(2), respectively; P < 0.05). Both type I and type II muscle fiber size increased after exercise training (P < 0.001), with a greater increase in type II muscle fiber size in the PRO group (+2319 ± 368 μm(2)) than in the PLA group (+1017 ± 353 μm(2); P < 0.05). Protein ingestion before sleep represents an effective dietary strategy to augment muscle mass and strength gains during resistance exercise training in young men. This trial was registered at clinicaltrials.gov as NCT02222415.


Parental social status and intrasexual competitiveness among adolescents.
A study among 1,881 adolescents (52.3% girls) with a mean age of 19.1 years examined the effects of parental social status upon intrasexual competitiveness. Whereas females were consistently more intrasexually competitive the higher the socio-economic status of their parents, males with parents of the lowest socio-economic status tended to be more intrasexually competitive than those with parents of medium socio-economic status, and nearly as intrasexually competitive as those with parents of high socio-economic status. Only among adolescents with parents of low socio-economic status were males more intrasexually competitive than females. Among males and females, higher levels of intrasexual competitiveness were related to a higher family income, to a higher occupational status of the father as well as of the mother, and to a higher educational level of the mother. Only among females were higher levels of intrasexual competitiveness associated with a higher educational level of the father. Males whose fathers had only elementary education had a relatively high level of intrasexual competitiveness. The results are discussed in the context of the multifaceted nature of human status, and the potential relevance of intrasexual competitiveness for individuals of high versus low social status.


Reactive uptake kinetics of NO3 on multicomponent and multiphase organic mixtures containing unsaturated and saturated organics.
We investigated the reactive uptake of NO(3) (an important night-time oxidant in the atmosphere) on binary mixtures containing an unsaturated organic (methyl oleate) and saturated molecules (diethyl sebacate, dioctyl sebacate, and squalane) which we call matrix molecules. These studies were carried out to better understand the reactivity of unsaturated organics in multicomponent and multiphase atmospheric particles. For liquid binary mixtures the reactivity of methyl oleate depended on the matrix molecule. Assuming a bulk reaction, H(matrix)√(D(matrix)k(oleate)) varied by a factor of 2.7, and assuming a surface reaction H(matrix)(S)K(matrix)(S)k(oleate)(S) varied by a factor of 3.6, where H(matrix)√(D(matrix)k(oleate) and H(matrix)(S)K(matrix)(S)k(oleate)(S) are constants extracted from the data using the resistor model. For solid-liquid mixtures, the reactive uptake coefficient depended on exposure time: the uptake decreased by a factor of 10 after exposure to NO(3) for approximately 90 min. By assuming either a bulk or surface reaction, the atmospheric lifetime of methyl oleate in different matrices was estimated for moderately polluted atmospheric conditions. For all liquid mixtures, the lifetime was in the order of a few minutes (with an upper limit of 35 min). These lifetimes can be used as lower limits to the lifetimes in semi-solid mixtures. Our studies emphasize that the lifetime of unsaturated organics (similar to methyl oleate) is likely short if the particle matrix is in a liquid state.


Metabolism of anthocyanins by human gut microflora and their influence on gut bacterial growth.
Consumption of anthocyanins has been related with beneficial health effects. However, bioavailability studies have shown low concentration of anthocyanins in plasma and urine. In this study, we have investigated the bacterial-dependent metabolism of malvidin-3-glucoside, gallic acid and a mixture of anthocyanins using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal human large intestine conditions. Most anthocyanins have disappeared after 5 h incubation while gallic acid remained constant through the first 5 h and was almost completely degraded following 24 h of fermentation. Incubation of malvidin-3-glucoside with fecal bacteria mainly resulted in the formation of syringic acid, while the mixture of anthocyanins resulted in formation of gallic, syringic and p-coumaric acids. All the anthocyanins tested enhanced significantly the growth of Bifidobacterium spp. and Lactobacillus-Enterococcus spp. These results suggest that anthocyanins and their metabolites may exert a positive modulation of the intestinal bacterial population.


Brain abnormalities in Duchenne muscular dystrophy: phosphorus-31 magnetic resonance spectroscopy and neuropsychological study.
Duchenne muscular dystrophy (DMD) is one of a range of muscular dystrophies caused by abnormalities of the short arm of the X chromosome (Xp21), which often cause mental retardation in addition to progressive muscular weakness. Normal dystrophin expression is lacking in both skeletal muscle and brain of affected subjects. Phosphorus-31 magnetic resonance spectroscopy has shown several abnormalities in skeletal muscle in DMD. We looked for similar abnormalities in brain in patients with DMD and related the findings to neuropsychological test results. We studied by magnetic resonance spectroscopy 19 boys (aged 76-167 months) diagnosed as having DMD and 19 control boys of similar age (87-135 months). Intelligence quotient (IQ) was assessed with the Wechsler Intelligence Scale for children. The DMD patients had significantly higher values than the controls in the brain ratios of inorganic phosphate to adenosine triphosphate (mean 0.53 [SD 0.21] vs 0.36 [0.09], p = 0.003), to phosphomonoesters (0.40 [0.07] vs 0.29 [0.07], p = 0.0001), and to phosphocreatine (0.44 [0.10] vs 0.37 [0.08], p = 0.02). There were significant differences between the DMD patients and the controls in full-scale IQ (76 [16] vs 101 [16], p = 0.0001), performance IQ (78 [17] vs 94 [14], p = 0.003), and verbal IQ (78 [17] vs 106 [17], p = 0.0001). These altered metabolite ratios parallel the findings in dystrophic muscle and suggest bioenergetic similarities in tissues that lack dystrophin.


[Social representations of the relationships between plant vases and the dengue vector].
To investigate how houseplant 'caretakers' represent the relationship between plant vases and breeding sites for the dengue vector, in order to reformulate educational policies. The present study was carried out among caretakers from three São Paulo State municipalities in which dengue is known to exist and in which extensive educational activities had been previously conducted. Twenty households from each of the municipalities studied were selected based on larval density evaluation bulletins elaborated by SUCEN (Endemic Disease Control Coordination) and classified as positive or negative for the presence of Aedes aegypti larvae in plant vases. The 60 participants were aged 20-65 years and were directly involved in plant care. Interviews were carried out using a semi-structured questionnaire, and recorded in cassette tapes. Data were tabulated using the collective subject discourse technique. Negative representations found included: erroneous information in the population's imaginary universe; disbelief that a 'tiny little mosquito' could cause such extensive problems; belief in the disease only after its concrete manifestation; and mistrust in educational activities in general. Positive representations included: understanding of the basic mechanism of dengue transmission; appreciation of the role and constant presence of sanitary authorities; understanding of their own share of responsibility in fighting the disease. With respect to vector control activities, the exceedingly synthetic messages emitted by the sanitary authorities prevent the information from being assimilated by the population to the desirable extent. Educational activities must be understood by the population to which they are destined if any behavioral changes are to take place.


Analysis of platinum content in biodegradable carboplatin-impregnated beads and retrospective assessment of tolerability for intralesional use of the beads in dogs following excision of subcutaneous sarcomas: 29 cases (2011-2014).
OBJECTIVE To evaluate platinum content in biodegradable carboplatin-impregnated beads and retrospectively assess tolerability and outcome data for dogs treated by intralesional placement of such beads following surgical excision of subcutaneous sarcomas. DESIGN Evaluation study and retrospective case series. SAMPLE 9 carboplatin-impregnated beads and 29 client-owned dogs. PROCEDURES Platinum content in 9 carboplatin-impregnated beads from 3 lots was measured by spectrophotometry, and calculated carboplatin content was compared with the labeled content. Medical records were searched to identify dogs with subcutaneous sarcomas for which treatment included placement of carboplatin-impregnated beads between 2011 and 2014. Signalment, tumor characteristics, surgical and histologic data, adverse events, and local recurrences were recorded. Associations between variables of interest and adverse events or local disease-free interval were analyzed. RESULTS In vitro analysis identified a mean ± SD platinum content of 5.38 ± 0.97 mg/bead. Calculated carboplatin content (10.24 ± 1.84 mg/bead) was significantly greater than the labeled amount (4.6 mg/bead). Bead weight and total platinum content differed significantly among lots, but platinum content per bead weight did not. Mild-to-moderate local adverse events were reported for 11 of 29 tumors; all resolved without additional surgery. No dogs had signs of systemic toxicosis. Overall local disease-free rates 1, 2, and 3 years after surgery were 70%, 70%, and 58%, respectively, as determined by Kaplan-Meier analysis. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated beads were well tolerated; however, results of in vitro tests indicated that caution is needed because of manufacturing inconsistencies.


Role of interleukin 1 beta in esophageal squamous cell carcinoma.
Interleukin (IL)-1 beta has been reported to be a marker of shorter survival in gastric and colorectal adenocarcinoma. In the present study, we examined the potential role and prognostic value of IL-1 beta in esophageal squamous cell carcinoma (SCC). Human esophageal SCC cell line, CE81T, was selected for cellular and animal experiments, in which biological changes after experimental manipulation of IL-1 beta signaling were explored, including tumor growth, invasion capacity, and the sensitivity to treatment. Moreover, 147 esophageal SCC samples were analyzed using immunohistochemical staining to correlate the expression of IL-1 beta with clinical outcome. Our data revealed that IL-1 beta was significantly overexpressed both at mRNA and protein levels in cancer specimens compared to nonmalignant tissues. When IL-1 beta signaling was blocked, tumor growth, invasion ability, and treatment resistance were attenuated. Activation of NF-kappa B, increase of E2-EPF ubiquitin carrier protein and subsequent epithelial-mesenchymal transition might be the underlying mechanisms of the more aggressive tumor growth in IL-1 beta-positive esophageal cancer. The immunochemistry findings indicate that positivity staining of IL-1 beta correlated significantly with higher clinical stage, lower response rate to concurrent chemoradiotherapy (CCRT), and higher recurrence rate after curative treatment. Moreover, IL-1 beta was a significant predictor of survival in patients undergoing surgical intervention or definite CCRT. In conclusion, IL-1 beta is significantly linked to poor prognosis for patients with esophageal cancer and may be a promising molecular target for therapeutic intervention for esophageal SCC.


In vivo conversion of 3H-L-tryptophan into 3H-serotonin in brain areas of adrenalectomized rats.
Rats were adrenalectomized 10 days before we estimated in vivo the conversion index of (3)H-tryptophan into radioactive serotonin in brainstem and telediencephalon. We found that the conversion index in the brainstem of adrenalectomized rats is smaller than in the same area of sham-operated rats. Conversely, the conversion index in the telediencephalon was similar in the two groups of rats. The serotonin concentrations were unchanged by adrenalectomy, which suggests that in brainstem the decrease of tryptophan hydroxylase is reflected by the conversion index estimation and not by measurement of serotonin steady-state concentrations.


Atypical femoral fracture in an osteogenesis imperfecta patient successfully treated with teriparatide.
We report a case of a successfully healed atypical femoral fracture (AFF) following treatment with teriparatide in a patient with osteogenesis imperfecta (OI). To our knowledge, no successful treatment of AFFs with teriparatide in this subpopulation has ever been described. This is a case report of an AFF treated with teriparatide. The patient was treated with hormone replacement therapy for 18 years and bisphosphonates for 9 years before suffering a spontaneous AFF in the form of a dislocated noncomminute transverse fracture of the right femoral shaft, and an open reduction and internal fixation (ORIF) with a T2 Femoral Nail was done. Due to nonunion and another fracture distal to the nail, the patient was reoperated on with exchange ORIF and off-label treatment with teriparatide 20 μg/day was started. An X-ray 1 month later showed early signs of fracture healing. A subsequent X-ray 6 months after the last operation showed a solid healing of both right femoral fractures. This is a rare case that highly suggests a potential fracture healing effect of teriparatide treatment and highlights a potential significant practical therapeutic consideration in relation to the management of AFF with delayed healing.


Communication among preschoolers with and without disabilities in same-age and mixed-age classes.
Communicative interactions of preschool children with and without disabilities in classrooms of same or mixed ages were compared. Sixteen children with developmental disabilities (most with mild or moderate mental retardation) and 32 children without disabilities between 1.5 and 4.5 years of age were randomly assigned at the beginning of the school year to either a same- or mixed-age grouping of 6 children. They were observed 6 months later interacting with classmates in a standard free-play environment. Results showed that children in mixed-age classes took more turns in conversations with partners with disabilities than did children in same-age classrooms. They also received more turns from their partners with disabilities, which were more often responses than initiations in the mixed-age as compared to same-age classes. In contrast, during communicative interactions with partners without disabilities, children in both types of classes did not significantly differ in number or types of turns. Children of a similar developmental level also had similar communicative interaction styles.