Quality-of-Life Discrepancies Among Autistic Adolescents and Adults: A Rapid Review.
Quality of life (QoL) is a core outcome of occupational therapy, but it is decreased among autistic adolescents and adults. This is the first review of QoL from an occupational therapy standpoint. To identify self-reported QoL differences between autistic and nonautistic samples; investigate sex differences in QoL among autistic people; examine consistency in QoL among autistic people across age, intellectual disability (ID), and self- versus proxy-report method; and appraise occupational therapy-related interventions addressing QoL among autistic people. Articles published in peer-reviewed journals between 2010 and 2020, located through Academic Search Ultimate, PubMed, and OTseeker, along with the American Journal of Occupational Therapy, British Journal of Occupational Therapy, Canadian Journal of Occupational Therapy, and Australian Occupational Therapy Journal. Study Selection and Data Collection: Article samples consisted of at least 20% autistic females and used self-reported QoL measures. Qualitative research was excluded, as well as studies with participants younger than age 13 yr. Twenty-seven articles qualified (3 Level 1B, 13 Level 3B, and 11 Level 4). Autistic adolescents and adults demonstrated decreased self-reported QoL compared with nonautistic peers across age and ID presence. One article compared sex differences in QoL among autistic people. Interventions improved QoL among autistic people. Autistic adolescents and adults demonstrate decreased QoL in comparison with nonautistic peers. Questions remain related to sex differences in QoL among autistic people, an area for future research. Multiple evidence-based approaches to improve QoL in the autistic population are relevant to occupational therapy practice. What This Article Adds: Self-reported QoL among autistic adolescents and adults is clearly lower than among their nonautistic counterparts. This article provides information on multiple interventions related to occupational therapy to improve QoL among autistic people.


Beta-oxidation of polyunsaturated fatty acids with conjugated double bonds. Mitochondrial metabolism of octa-2,4,6-trienoic acid.
The mitochondrial beta-oxidation of octa-2,4,6-trienoic acid was studied with the aim of elucidating the degradation of unsaturated fatty acids with conjugated double bonds. Octa-2,4,6-trienoic acid was found to be a respiratory substrate of coupled rat liver mitochondria, but not of rat heart mitochondria. Octa-2,4,6-trienoyl-CoA, the product of the inner-mitochondrial activation of the acid, was chemically synthesized and its degradation by purified enzymes of beta-oxidation was studied spectrophotometrically and by use of h.p.l.c. This compound is a substrate of NADPH-dependent 2,4-dienoyl-CoA reductase or 4-enoyl-CoA reductase (EC 22.214.171.124), which facilitates its further beta-oxidation. The product obtained after the NADPH-dependent reduction of octa-2,4,6-trienoyl-CoA and one round of beta-oxidation was hex-4-enoyl-CoA, which can be completely degraded via beta-oxidation. It is concluded that polyunsaturated fatty acids with two conjugated double bonds extending from even-numbered carbon atoms can be completely degraded via beta-oxidation because their presumed 2,4,6-trienoyl-CoA intermediates are substrates of 2,4-dienoyl-CoA reductase.


2D fast rotational matching for image processing of biophysical data.
In 3D single particle reconstruction, which involves the translational and rotational matching of a large number of electron microscopy (EM) images, the algorithmic performance is largely dependent on the efficiency and accuracy of the underlying 2D image alignment kernel. We present a novel fast rotational matching kernel for 2D images (FRM2D) that significantly reduces the cost of this alignment. The alignment problem is formulated using one translational and two rotational degrees of freedom. This allows us to take advantage of fast Fourier transforms (FFTs) in rotational space to accelerate the search of the two angular parameters, while the remaining translational parameter is explored, within a limited range, by exhaustive search. Since there are no boundary effects in FFTs of cyclic angular variables, we avoid the expensive zero padding associated with Fourier transforms in linear space. To verify the robustness of our method, efficiency and accuracy tests were carried out over a range of noise levels in realistic simulations of EM images. Performance tests against two standard alignment methods, resampling to polar coordinates and self-correlation, demonstrate that FRM2D compares very favorably to the traditional methods. FRM2D exhibits a comparable or higher robustness against noise and a significant gain in efficiency that depends on the fineness of the angular sampling and linear search range.


Cortical mechanisms of human eating.
The hedonic component of eating is an underexplored topic within neuroscience, which is surprising given its importance for our survival and general well-being, as well as the obvious links to obesity and eating disorders. Based on findings from neuroimaging, this review gives an overview of the established principles, neural mechanisms and functional neuroanatomy of the primate and human brain processing systems involved in controlling eating. Four main processing principles underlying these processes are discussed: (1) motivation-independent discriminative processing of identity and intensity, (2) formation of learning-dependent multimodal sensory representations, (3) reward representations using mechanisms including selective satiation, and (4) representations of hedonic experience, monitoring/learning or direct behavioural change.


Functional Rarity: The Ecology of Outliers.
Rarity has been a central topic for conservation and evolutionary biologists aiming to determine the species characteristics that cause extinction risk. More recently, beyond the rarity of species, the rarity of functions or functional traits, called functional rarity, has gained momentum in helping to understand the impact of biodiversity decline on ecosystem functioning. However, a conceptual framework for defining and quantifying functional rarity is still lacking. We introduce 12 different forms of functional rarity along gradients of species scarcity and trait distinctiveness. We then highlight the potential key role of functional rarity in the long-term and large-scale maintenance of ecosystem processes, as well as the necessary linkage between functional and evolutionary rarity.


New deoxyribonuclease activity after bacteriophage P22 infection.
Extracts from P22-infected and uninfected cultures of Salmonella typhimurium were subjected to deoxyribonucleic acid (DNA)-cellulose and diethylaminoethyl-cellulose chromatography. Comparison of the elution patterns revealed that in infected cells there is a decrease in the amount of nuclease activity specific for denatured DNA and an increase in the amount of nuclease activity specific for native DNA. The latter activity was shown to differ from a similar host enzyme in Mg(2+), Mn(2+), and pH optima. This new activity is not found after infection of a lysogen with a nonvirulent phage or after infection under nonpermissive conditions with P22ts25.1 (a mutant in gene 25 that carries out no known functions other than adsorption and injection) and thus appears to be specified by the phage genome.


Recovery oriented phosphorus adsorption process in decentralized advanced Johkasou.
Decentralized advanced wastewater treatment using adsorption and desorption process for recovery and recycling oriented phosphorus removal was developed. Adsorbent particles made of zirconium were set in a column, and it was installed as subsequent stage of BOD and nitrogen removal type Johkasou, a household domestic wastewater treatment facility. The water quality of the effluent of adsorption column in a number of experimental sites was monitored. The effluent phosphorus concentration was kept below 1 mg l(-1) during 90 days at all the sites. Furthermore, over 80% of the sites achieved 1 mg l(-1) of T-P during 200 days. This adsorbent was durable, and deterioration of the particles was not observed over a long duration. The adsorbent collected from each site was immersed in alkali solution to desorb phosphorus. Then the adsorbent was reactivated by soaking in acid solution. The reactivated adsorbent was reused and showed almost the same phosphorus adsorption capacity as a new one. Meanwhile, the desorbed phosphorus was recovered with high purity as trisodium phosphate by crystallization. It is proposed as a new decentralized system for recycling phosphorus that paves the way to high-purity recovery of finite phosphorus.


Fanconi anemia with concurrent thumb polydactyly and dorsal dimelia: a case report with discussion of embryology.
Fanconi anemia is known to be associated with radial ray deficiency (thumb and radius hypoplasia), and its embryological basis remains to be poorly understood. We describe a rare case of Fanconi anemia with concurrent thumb polydactyly and dorsal dimelia. The embryological basis of limb abnormalities in Fanconi anemia patients is thought to be based on the complex interactions between the apical ectodermal ridge (where Fanconi anemia genes are expressed) and both the mesoderm (where Spalt-like 4 (SALL4) and Sonic hedgehog (SHH) are located and which are responsible for radial ray deficiency, thumb polydactyly, and triphalangism) and the dorsoventral axis (an error in that axis leads to dorsal dimelia).


Electronic tongue-based discrimination of Korean rice wines (makgeolli) including prediction of sensory evaluation and instrumental measurements.
A commercial electronic tongue was used to discriminate Korean rice wines (makgeolli) brewed from nine cultivars of rice with different amino acid and fatty acid compositions. The E-tongue was applied to establish prediction models with sensory evaluation or LC-MS/MS by partial least squares regression (PLSR). All makgeollis were classified into three groups by principal components analysis, and the separation pattern was affected by rice qualities and yeast fermentation. Makgeolli taste changed from the complicated comprising sweetness, saltiness, and umami to the uncomplicated, such as bitterness and then, sourness, with a decrease of amino acids and fatty acids in the rice. The quantitative correlation between E-tongue and sensory scores or LC-MS/MS by PLSR demonstrated that E-tongue could well predict most of the sensory attributes with relatively acceptable r(2), except for bitterness, but could not predict most of the chemical compounds responsible for taste attributes, except for ribose, lactate, succinate, and tryptophan.


[Alpha-ketoglutaric acid transamination of synthetic omega-amino acids in bacteria].
Bacteria utilizing synthetic lactams and omega-amino acids contain enzymes involved in transamination of epsilon-aminocaproic, zeta-aminoenanthic, eta-aminocaprilic acids with alpha-ketoglutaric acid. Natural and synthetic omega-amino acids are not inductors of the synthesis of corresponding transaminases. A strain of Pseudomonas dacunchae has been selected; it possesses an elevated activity of transamination of synthetic omega-amino acids, including zeta-aminoenanthic and eta-aminocaprilic acids.


Effects of propofol and etomidate on hydrogen peroxide-induced oxidative damage in hepatocyte.
The present investigation was undertaken to evaluate the protective effect of propofol and etomidate against hydrogen peroxide (H2O2) induced oxidative damage in human hepatic SNU761 cells by measuring lactate dehydrogenase (LDH). The cell line of human hepatocellular carcinoma was grown for 24 hours in dissociated cell culture. They were divided into eight groups: negative control (NC) group with no drug administration, positive control (PC) group with H2O2 250 micrometer and other groups pretreated with propofol (P; 1, 10, 50 micrometer) or etomidate (ET; 1, 10, 50 micrometer) followed H2O2 administration. After 7 hours, cell death was assessed by morphology under the light microscope and quantified by measuring the LDH in the culture media. In the light microscopic findings, the intact cells were increased in all three propofol groups compared to group PC. H2O2-induced LDH production was also significantly suppressed in all three propofol groups compared to group PC (P < 0.001). There were no significant differences in the microscopic findings and LDH production between the etomidate groups and group PC. These results suggest that the propofol has protective effect on the hepatocyte against H2O2-induced oxidative stress.


Similarities in the formation and removal of covalent DNA adducts in benzo(a)pyrene-treated BALB/3T3 variant cells with different induced transformation frequencies.
Classes of cell variants isolated from BALB/3T3-A31 clone 1 showing high, intermediate, and low susceptibility to ultraviolet light-induced transformation also demonstrated a differential response to benzo(a)pyrene (BP)-induced transformation. On the other hand, these variants showed an identical susceptibility to the killing effect of these carcinogens. The extent of BP binding to DNA was found to be very similar in all three classes of variants under transforming conditions. BP:DNA adducts from the variant cells were analyzed by high-pressure liquid chromatography. The same adducts (N2-(10S-[7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl)deoxyguanosine and a minute amount of the 7S enantiomer) were detected in the highly susceptible, the intermediately susceptible, and the resistant variant clones. Removal of the BP:DNA adduct occurred at an equally slow rate in all three classes of variant cells. These results indicate that the formation of stable covalent DNA adducts is not a sufficient condition for induction of transformation. Processes other than formation and removal of the stably bound BP:DNA covalent adducts are thus major factors controlling the susceptibility of BALB/3T3-A31 clone 1 variant cells to BP-induced transformation.


Development of novel drug delivery prototypes devices for targeted delivery drug therapy at the molecular level in aqueous media.
A novel approach in target specific molecular prototype drug delivery system concerns the attempt to employ radical affording substances (RAS) or radical quenching substances (RQS) as prodrugs able to produce irreversible damage on the desired target and therefore to stimulate cellular apoptosis. However, radical species generated can react quickly within the chemical environment prior to reaching its proper site of action. In this short communication, we report our investigations towards developing two alternative novel, simple, flexible and effective drug delivery systems that provide optimal dosage of drugs precisely where and when needed and therefore achieve and sustain a complex delivery profile. We have demonstrated the application of two effective molecular prototype delivery systems able to harness free radical reactivity within the laboratory where biological processes can be studied and controlled, leading to the prevention of disease and the development of new treatments for disease states mediated by free radicals.


Columellar Reconstruction following Nasal Continuous Positive Airway Pressure Injury.
Nasal continuous positive airway pressure is used increasingly to treat pulmonary immaturity in premature neonates. Nasal injury is common with nasal continuous positive airway pressure use, with full-thickness tissue loss at the columella among the most devastating complications. Columellar necrosis often imparts a full-thickness injury to the overlying columellar skin, the medial crura of the lower lateral nasal cartilages, the anteromedial inner nasal mucosal lining, and potentially the anterior septal cartilage. Consequently, the columella can become scarred and shortened. Although multiple techniques have been described to reconstruct the columella, no known technique has been specifically developed to treat the unique columellar defect common to severe nasal continuous positive airway pressure injury. Donor-site morbidity related to these techniques, and how growth of the reconstructed nose will proceed, are obvious concerns, especially in young children. The authors present a novel reconstruction technique that uses recreation of the defect with posteriorly based book flaps and auricular chondrocutaneous composite graft interposition. This technique has several advantages, including avoiding central facial scars, supplying well-matched skin color and texture, and facilitating robust tip support. The authors retrospectively review the use and outcomes of this technique from 1995 and 2016 on all patients with a history of nasal continuous positive airway pressure columellar necrosis at their center.


Relationship of colony-stimulating activity to apparent kill of human colony-forming cells by irradiation and hydroxyurea.
Suspensions of human bone marrow cells were subjected to 137Cs irradiation in vitro and then cultured in semisolid agar medium. Cultures of irradiated cells were stimulated with colony-stimulating activity (CSA) of different potencies, and it was found that the amount of stimulation applied to cultures influenced the apparent kill of colony-forming cells (CFC). It was also found that the effects of irradiation on colony formation were not confined to CFC kill since medium conditioned by cells during irradiation exhibited stimulatory and inhibitory properties after treatment by 600 and 1000 rads, respectively. Studies in which irradiated cells were pretreated with hydroxyurea indicated that CFC in the DNA synthetic phase of the cell cycle were particularly sensitive to low doses of irradiation. The proliferative capacity of CFC surviving 1000 rads was undiminished as judged by their ability to form large colonies. Estimates of CFC kill by hydroxyurea were also affected by the level of CSA.


Anxiety and depression influence the relation between disability status and quality of life in multiple sclerosis.
Disability status, depression and anxiety are important determinants of quality of life (QoL) in patients with multiple sclerosis (MS). We investigated whether anxiety and depression influence the relation between disability status and QoL in our cohort of recently diagnosed patients. Disability status [Expanded Disability Status Scale (EDSS)], anxiety and depression [Hospital Anxiety and Depression Scale (HADS)], and QoL (SF-36) were prospectively obtained in 101 MS patients. The relation between EDSS and SF-36 scales was examined using regression analyses, without and with adjustment for anxiety and depression. Interaction effects were investigated by comparing the relation between EDSS and QoL in patients with high and low anxiety and depression. In the unadjusted analyses, EDSS was significantly related to all SF-36 physical and mental health scales. After adjustment for anxiety and depression, EDSS was significantly related only to the SF-36 physical functioning, role-physical functioning and bodily pain scales. The relation between EDSS and these SF-36 scales was consistently higher in patients with more symptoms of anxiety or depression, suggesting that anxiety and depression strengthened the association of EDSS in these SF-36 physical health scales. After adjustment for anxiety and depression, EDSS was not significantly related to the SF-36 mental health scales and the general health scale. This finding is compatible with the hypothesis that anxiety and depression are intermediate factors in the association of EDSS with these SF-36 scales. Screening for symptoms of anxiety and depression is recommended in studies that use QoL as an outcome measure of treatment or intervention efficacy.


[Practice guidelines of the use of bisphosphonates in solid tumours with bone metastases and in multiple myeloma].
Bisphosphonates are indicated for the treatment of bone lesions in patients with solid tumours or multiple myeloma. Bisphosphonates have proven their effectiveness in reducing the number of bone complications (hypercalcemia, pain, disease-related fractures, spinal cord compression) and delaying their occurrence in patients with bone tumours; they have also been shown to reduce the need for bone surgery and palliative or pain-relieving radiotherapy in these patients. International recommendations for the treatment of bone lesions related to malignant solid tumours and multiple myeloma have been established. We have elaborated clinical practice guidelines on the use of bisphosphonates to assist treatment decision-making in bone oncology. The guide contains decision trees and tables with information to guide pre-treatment evaluation and patient follow-up, as well as indications and conditions of use of bisphosphonates. In 2007, the regional cancer network of Rhône-Alpes, ONCORA, formed a working group (GIP ONCORA) to elaborate the guideline. The final version was then discussed and adopted at a plenary session in July 2009, during a collaborative workshop on supportive care recommendations organized by ONCORA and the regional cancer network of Lorraine.


[Characteristics of multimedia counseling: a study of an interactive TV system].
The purpose of this study was to investigate communication characteristics of multimedia counseling. Eye-contact through an interactive TV system was made possible, within three degrees of angle, with a camera attached on the TV screens. Counseling sessions with 18 clients were conducted to study differences among three conditions: audio only, interactive TV, and conventional face-to-face. The variables examined were information transmission, feeling communication, rapport building, overall evaluation, etc. Eighty-three per cent of the clients positively evaluated the interactive TV system, with all of its indices significantly higher than the audio only condition. However, rapport building with the system was significantly lower than the face-to-face condition. Two common factors found for the conditions were defenseless communication and counselor warmth. A larger TV screen might facilitate rapport building. More work is needed to study applicability of multimedia counseling, as well as to develop new effective counselor styles for the kind of counseling.


Multifaceted activities of transcription factor EB in cancer onset and progression.
Transcription factor EB (TFEB) represents an emerging player in cancer biology. Together with microphthalmia-associated transcription factor, transcription factor E3 and transcription factor EC, TFEB belongs to the microphthalmia family of bHLH-leucine zipper transcription factors that may be implicated in human melanomas, renal and pancreatic cancers. TFEB was originally described as being translocated in a juvenile subset of pediatric renal cell carcinoma; however, whole-genome sequencing reported that somatic mutations were sporadically found in many different cancers. Besides its oncogenic activity, TFEB controls the autophagy-lysosomal pathway by recognizing a recurrent motif present in the promoter regions of a set of genes that participate in lysosome biogenesis; furthermore, its dysregulation was found to have a crucial pathogenic role in different tumors by modulating the autophagy process. Other than regulating cancer cell-autonomous responses, recent findings indicate that TFEB participates in the regulation of cellular functions of the tumor microenvironment. Here, we review the emerging role of TFEB in regulating cancer cell behavior and choreographing tumor-microenvironment interaction. Recognizing TFEB as a hub of network of signals exchanged within the tumor between cancer and stroma cells provides a fresh perspective on the molecular principles of tumor self-organization, promising to reveal numerous new and potentially druggable vulnerabilities.


Effect of atorvastatin on renal NO availability and tubular function in patients with stage II-III chronic kidney disease and type 2 diabetes.
Statins have beneficial effects on cardiovascular morbidity and mortality independently of reduction of plasma cholesterol. In patients with type 2 diabetes and nephropathy, chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-NMMA as an inhibitor of NO production. We performed a randomized, placebo-controlled, crossover study, using atorvastatin/placebo treatment for five days with a standardized diet and fluid intake. We measured brachial BP (bBP), central BP (cBP), GFR, urinary output (OU), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of albumin (UAER and UACR), AQP2 (u-AQP2) and ENaC (u-ENaCγ) and plasma concentrations of vasoactive hormones: renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide. During atorvastatin and placebo treatment, L-NMMA infusion, changed the effect variables significantly, but to the same extent, i.e. an increase in bBP and cBP, and a decrease in GFR, OU, CH2O, FENa, u-AQP2 and u-ENaCγ. In addition, renin and angiotensin II was reduced, aldosterone increased, and vasopressin, endothelin-1 and brain natriuretic hormone unchanged. During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, atorvastatin did not change nitric oxide availability in type 2 diabetics with nephropathy.


Positive effect of the hepatitis C virus nonstructural 5A protein on viral multiplication.
Hepatitis C virus infection (HCV), is a major cause of liver disease worldwide, and are frequently resistant to the interferon alpha treatment. The nonstructural (NS) 5A protein of HCV has been proposed to be involved in this resistance. Additional studies have pointed out a role for NS5A in several other cellular interactions as well as an important role of its adaptative mutations in HCV genome replication. However, no infectious system is available to assess the role of NS5A in the HCV life cycle. Thus, we have constructed a recombinant system directly demonstrating for the first time that the expression of NS5A confers a multiplicative advantage to Sindbis virus, a virus close to HCV. This advantage seemed to be related to an anti-apoptotic effect of the NS5A protein. At a later stage, a possible nuclear localization of NS5A was observed, likely due to apoptotic cleavages of this protein. The NS5A protein was also shown to induce the interleukin-8 (IL-8) mRNA and to activate the NF-kappaB pathway independently of the Sindbis virus. Together, our data suggest that the activation of NF-kappaB could lead to the anti-apoptotic activity of NS5A and explain the viral multiplicative advantage conferred by the expression of the NS5A protein.


Monitoring considerations in recombinant human erythropoietin therapy.
Effective monitoring of chronic hemodialysis patients treated with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) includes an initial evaluation of the patient, the patient's anemia, and the patient's iron stores. Assessment of iron stores includes obtaining hematocrit and hemoglobin levels, reticulocyte count, red cell indices, serum ferritin level, transferrin percent saturation, and the patient's transfusion history. If iron stores are inadequate to support the increased erythropoiesis induced by the therapy, appropriate iron replacement therapy should be provided. Monitoring also involves assessment of BP (and its control), because development or exacerbation of hypertension is the most significant side effect associated with this treatment. Because the dose-response relationship for r-HuEPO therapy has been clearly documented, a target hematocrit and target rate of increase in hematocrit can be established. As anemia improves, continued monitoring of hematocrit, hemoglobin, red cell indices, serum ferritin level, and transferrin percent saturation will ensure that depleted iron stores are noted and treated as necessary. Heparin requirements during dialysis, blood chemistries, and blood access problems should also be monitored. No data currently exist suggesting that dialyzer reuse is compromised by r-HuEPO therapy. Quality-of-life surveys show improvement with r-HuEPO treatment and effective reduction of anemia. There is also some indication that morbidity is lessened and survival improved when anemia is treated with r-HuEPO therapy.


First-time application of droplet digital PCR for methylation testing of the 11p15.5 imprinting regions.
Beckwith-Wiedemann syndrome and Silver-Russel syndrome are two imprinting disorders caused by opposite molecular alterations in 11p15.5. With the current diagnostic tests, their molecular diagnosis is challenging due to molecular heterogeneity and mosaic occurrence of the most frequent alterations. As the determination of precise (epi)genotype of patients is relevant as the basis for a personalized treatment, different approaches are needed to increase the sensitivity of diagnostic testing of imprinting disorders. We established methylation-specific droplet digital PCR approaches (MS-ddPCR) for the two imprinting centers in 11p15.5, and analyzed patients with paternal uniparental disomy of chromosome 11p15.5 (upd(11)pat) and other imprinting defects in the region. The results were compared to those from MS-MLPA (multiplex ligation-dependent probe amplification) and MS-pyrosequencing. MS-ddPCR confirmed the molecular alterations in all patients and the results matched well with MS-MLPA. The results of MS-pyrosequencing varied between different runs, whereas MS-ddPCR results were reproducible. We show for the first time that MS-ddPCR is a reliable and easy applicable method for determination of MS-associated changes in imprinting disorders. It is therefore an additional tool for multimethod diagnostics of imprinting disorders suitable to improve the diagnostic yield.


Dynamics of specific antibody responses induced in mallards after infection by or immunization with low pathogenicity avian influenza viruses.
Natural infections with different subtypes of low pathogenicity avian influenza viruses (LPAIVs) are very common in wild duck populations. Recent outbreaks of high pathogenicity avian influenza virus (HPAIV) H5N1 in Eurasian and African countries stimulated monitoring activities in aquatic wild bird populations. Surveillance mainly focused on virus detection. Only a few serologic investigations have been conducted so far, although such data may retrospectively elucidate epidemiologic patterns of different AIV subtypes in the populations under study. To better understand the immunologic and serologic reactions of mallards after infection with LPAIV, we investigated the AIV type- and subtype-specific antibody dynamics in mallards after different LPAIV infections by hemagglutination inhibition, competitive enzyme-linked immunosorbent assay, and western blot analysis, as appropriate. Four groups of mallard ducks were used: 1) naturally infected birds, 2) birds that were experimentally infected with LPAIV, 3) birds that were immunized with inactivated virus preparations, and 4) negative control birds. Ducks were monitored for up to 15 mo, and serum samples were investigated every 1-4 wk. It could be shown that infection with LPAIV in mallards can be traced serologically over prolonged periods of time.


Mutational landscape and underlying mutational processes in chronic lymphocytic leukemia.
Sequencing studies have been instrumental in understanding the genetic basis of chronic lymphocytic leukemia (CLL). Our recent whole-genome sequencing study focusing on lower cytogenetic risk CLL demonstrated that CLL mutations can be attributed to 3 key mutational processes-2 types of activation induced-cytidine deaminase (AID) signatures and an aging signature-that operate at different times throughout CLL evolution.


Psychometric evaluation of the Swedish Quality of Dyadic Relationships scale - homogeneity and construct validity.
The Quality of Dyadic Relationships is a self-assessment scale used to evaluate various aspects of relationship quality. Psychometric evaluation by the developers of the instrument has led to a nontested amended version. Further psychometric testing is thus warranted, and the aim of this study was to evaluate homogeneity, construct validity (in terms of concurrent, discriminant and known-groups validity) and any floor and ceiling effects of the Quality of Dyadic Relationships. Forty-seven cohabitant couples (47 women with a mean age of 30.0 years and 47 men with a mean age of 31.5 years) answered the Quality of Dyadic Relationships, the Relationship Assessment Scale (to test concurrent validity) and the Perceived Stress Scale (to test discriminant validity). Homogeneity (internal consistency) was calculated by Cronbach's alpha. Concurrent and discriminant validity were estimated as correlations between Quality of Dyadic Relationships and the other instruments. Assessment of known-groups validity was based on the variables of parental status and gender. Floor and ceiling effects were evaluated according to frequency distribution. The overall homogeneity was good with acceptable Cronbach's alpha values (α > 0.70) for all subscales but dyadic sexuality. Concurrent validity and discriminant validity were found. Known-groups validity was indicated by significant differences between individuals with different parental status on the total QDR index, where the ones without children scored higher. No difference between the genders was found. No significant floor effects were found, but a significant ceiling effect was found in the subscale dyadic sensuality, with 27.7% of respondents scoring maximum. In all, the QDR showed promising psychometric properties and may be used for screening and follow-up purposes. However, it can benefit from further development, as suggested by the ceiling effect in the subscale dyadic sensuality and the low internal consistency in the subscale dyadic sexuality.


CuI incorporated cobalt ferrite nanoparticles as a magnetically separable catalyst for oxidative amidation reaction.
A Cu-incorporated magnetic nanocatalyst (CoFe2O4@SiO2-SH-CuI) has been developed by immobilizing CuI on the modified surface of CoFe2O4 magnetic nanoparticles. The surface of the silica coated cobalt ferrite magnetic core was first treated with 3-mercaptopropyl triethoxysilane to produce the thiol functionalized nanoparticle CoFe2O4@SiO2-SH. Further treatment of the nanoparticle with CuI produced the desired magnetic nanocatalyst. The versatility of the catalyst has been demonstrated for the synthesis of N-(pyridin-2-yl) benzamide via oxidative amidation of aryl aldehydes with 2-amino pyridine in the presence of an oxidant. The reaction was carried out in DMSO at 80 °C using TBHP (70% aqueous) in the presence of 20 wt% of the catalyst. Notably, the catalyst could be separated from the reaction mixture in the presence of an external magnetic field. During the study, a new compound N-(pyridin-2-yl)anthracene-2-carboxamide has been synthesized and its turn on fluorescence sensing properties towards various metal ions have been studied. Fluorescence experiments and theoretical studies indicated that the newly synthesized carboxamide molecule can be used for fluorescence sensing of the Hg2+ ion in aqueous solution.


Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway.
Breast and prostate cancer preferentially metastasize in the skeleton, inducing locally increased bone resorption by osteoclasts. Bisphosphonates (BPs), potent inhibitors of osteoclasts and bone resorption, are able to reduce metastatic bone lesions, but the metastasis-related cellular target molecules for BPs have not yet been identified. In osteoclasts, nitrogen-containing BPs inhibit the function of the mevalonate pathway, impairing the prenylation and activation of small GTPases. In addition, direct effects of BPs on cancer cells have been suggested. In the present study, the effects of two clinically used BPs, the amino-BP alendronate and clodronate, on adhesion, invasion, and migration of human PC-3 prostate cancer cells were examined in vitro. We also studied the possible role of the mevalonate pathway in invasion and migration of PC-3 cells using the beta-hydroxy-beta-methylglutaryl-CoA reductase inhibitor mevastatin and the mevalonate pathway intermediates mevalonate (mevalonic acid lactone), geranylgeraniol, and trans-trans-farnesol. The results demonstrate that alendronate pretreatment very effectively inhibited in vitro invasion of prostate cancer cells in a dose-dependent manner, with an IC50 as low as approximately 1 pM. The inhibition was similar to that of mevastatin. Clodronate also inhibited invasion, but the IC50 was 0.1 microM. Importantly, geranylgeraniol and trans-trans-farnesol reversed the inhibitory effect of alendronate and mevastatin but not the clodronate-induced inhibition of invasion. Alendronate pretreatment also inhibited migration, which was partially reversed by geranylgeraniol and trans-trans-farnesol. Adhesion of PC-3 cells to various matrices was reduced, and their F-actin organization was changed. Alendronate pretreatment also inhibited invasion of human Du-145 prostate and MDA-MB-231 breast cancer cells. As a conclusion, the results demonstrate that the mevalonate pathway leading to protein prenylation is important for cancer cell invasion and migration in vitro. They further suggest that interference with this pathway is involved in inhibition of invasion and migration of prostate cancer cells by the amino-BP alendronate but that the mechanism of clodronate inhibition is different. It is possible that BPs have therapeutic potential in preventing the spread of prostate cancer.


Adoptive Cell Transfer: Is it a Promising Immunotherapy for Colorectal Cancer?
The last decade has witnessed significant advances in the adoptive cell transfer (ACT) technique, which has been appreciated as one of the most promising treatments for patients with cancer. Utilization of ACT can enhance the function of the immune system or improve the specificity and persistence of transferred cells. Various immune cells including T lymphocytes, natural killer cells, dendritic cells, and even stem cells can be used in the ACT despite their different functional mechanisms. Colorectal cancer (CRC) is among the most common malignancies and causes millions of deaths worldwide every year. In this review, we discuss the status and perspective of the ACT in the treatment of CRC.


Patellar Tendon Strain Associates to Tendon Structural Abnormalities in Adolescent Athletes.
High mechanical strain is thought to be one of the main factors for the risk of tendon injury, as it determines the mechanical demand placed upon the tendon by the working muscle. The present study investigates the association of tendon mechanical properties including force, stress and strain, and measures of tendon micromorphology and neovascularization, which are thought to be indicative of tendinopathy in an adolescent high-risk group for overuse injury. In 16 adolescent elite basketball athletes (14-15 years of age) we determined the mechanical properties of the patellar tendon by combining inverse dynamics with magnetic resonance and ultrasound imaging. Tendon micromorphology was determined based on a spatial frequency analysis of sagittal plane ultrasound images and neovascularization was quantified as color Doppler area. There was a significant inverse relationship between tendon strain and peak spatial frequency (PSF) in the proximal tendon region (r = -0.652, p = 0.006), indicating locally disorganized collagen fascicles in tendons that are subjected to high strain. No such associations were present at the distal tendon site and no significant correlations were observed between tendon force or stress and tendon PSF as well as between tendon loading and vascularity. Our results suggest that high levels of tendon strain might associate to a micromorphological deterioration of the collagenous network in the proximal patellar tendon, which is also the most frequent site affected by tendinopathy. Neovascularization of the tendon on the other hand seems not to be directly related to the magnitude of tendon loading and might be a physiological response to a high frequency of training in this group. Those findings have important implications for our understanding of the etiology of tendinopathy and for the development of diagnostical tools for the assessment of injury risk.


TMBP200, a microtubule bundling polypeptide isolated from telophase tobacco BY-2 cells is a MOR1 homologue.
Bundles of microtubules and cross-bridges between microtubules in the bundles have been observed in phragmoplasts, but proteins responsible for forming the cross-bridges have not been identified. We isolated TMBP200, a novel microtubule bundling polypeptide with an estimated relative molecular mass of about 200,000 from telophase tobacco BY-2 cells. Ultrastructural observation of microtubules bundled by purified TMBP200 in vitro revealed that TMBP200 forms cross-bridges between microtubules. The structure of the bundles and lengths of the cross-bridges were quite similar to those observed in phragmoplasts, suggesting that TMBP200 participates in the formation of microtubule bundles in phragmoplasts. The cDNA encoding TMBP200 was cloned and the deduced amino acid sequence showed homology to a class of microtubule-associated proteins including Xenopus XMAP215, human TOGp and Arabidopsis MOR1.


Urban American Indian Community Health Beliefs Associated with Addressing Cancer in the Northern Plains Region.
American Indians residing in the Northern Plains region of the Indian Health Service experience some of the most severe cancer-related health disparities. We investigated ways in which the community climate among an American Indian population in an urban community in the Northern Plains region influences community readiness to address cancer. A Community Readiness Assessment, following the Community Readiness Model, conducted semi-structured interviews with eight educators, eight students, and eight community leaders from the American Indian community in Omaha's urban American Indian population and established the Northern Plains region community at a low level of readiness to address cancer. This study reports on a subsequent qualitative study that analyzed all 24 interview transcriptions for emergent themes to help understand the prevailing attitude of the community toward cancer. A synthesis of six emergent themes revealed that the community's perceptions of high levels of severity and barriers, paired with perceptions of low levels of susceptibility and benefits, lead to low levels of self-efficacy, all of which are reflected in minimal cues to action and little effort to address cancer. These findings, interpreted through the lens of the Health Belief Model, can inform the development of more community-based, comprehensive, and culturally appropriate approaches to address the multilevel determinants of health behaviors in relation to cancer among American Indians in the Northern Plains region.


Improved alternatives for estimating in-use material stocks.
Determinations of in-use material stocks are useful for exploring past patterns and future scenarios of materials use, for estimating end-of-life flows of materials, and thereby for guiding policies on recycling and sustainable management of materials. This is especially true when those determinations are conducted for individual products or product groups such as "automobiles" rather than general (and sometimes nebulous) sectors such as "transportation". We propose four alternatives to the existing top-down and bottom-up methods for estimating in-use material stocks, with the choice depending on the focus of the study and on the available data. We illustrate with aluminum use in automobiles the robustness of and consistencies and differences among these four alternatives and demonstrate that a suitable combination of the four methods permits estimation of the in-use stock of a material contained in all products employing that material, or in-use stocks of different materials contained in a particular product. Therefore, we anticipate the estimation in the future of in-use stocks for many materials in many products or product groups, for many regions, and for longer time periods, by taking advantage of methodologies that fully employ the detailed data sets now becoming available.


Site-specific and bulk-phase generation of hydroxyl radicals in the presence of cupric ions and thiol compounds.
Addition of a thiol compound to a solution containing Cu2+ and H2O2 resulted in the generation of hydroxyl radicals (OH.). These radicals were able to oxidize salicylic acid and tryptamine in a reaction that was strongly inhibited by the OH.-scavenger mannitol. Covalent coupling of the thiol compound to tryptamine did not significantly influence the degradation of the indole moiety subsequent to addition of H2O2 and Cu2+. The inhibiting effect of mannitol, however, was strongly reduced, indicating that the scavenger could not interfere with site-specific reactions of OH..


Noninvasive evaluation of the extracranial carotid arteries in patients with cerebrovascular events and atrial fibrillations.
Noninvasive carotid artery testing was performed in 73 patients with nonvalvular atrial fibrillation who were referred because of symptoms or signs of cerebrovascular disease. Thromboembolism related to atrial fibrillation without valvular heart disease was the probable source of cerebral ischemia in 25 (80%) of 31 patients with stroke and coexisting atherosclerotic disease at the carotid artery bifurcation in six (20%). Nonvalvular atrial fibrillation was the probable source of symptoms in nine (70%) of 13 of patients with transient cerebral ischemia, while coexisting carotid artery disease was present in four (30%). Nonvalvular atrial fibrillation accounted for the symptoms in four of five patients with amaurosis fugax, with atherosclerotic carotid artery disease present in one. The remaining 24 patients had nonhemispheric symptoms of cerebrovascular disease, including vertebrobasilar insufficiency, dizziness, and syncope, and only one had a carotid lesion. A significantly higher proportion of patients with focal hemispheric symptoms had coexisting carotid disease than patients with nonfocal symptoms had, suggesting that atherosclerotic cerebrovascular disease contributes to stroke in patients with nonvalvular atrial fibrillation. Noninvasive carotid artery testing may be helpful in identifying atherosclerotic lesions at the carotid artery bifurcation in patients with atrial fibrillation and cerebrovascular disease, because different therapeutic modalities may be appropriate when two potential sources of cerebral ischemia are present.


The value of private patient information in the physician-patient relationship: a game-theoretic account.
This paper presents a game-theoretical model of the physician-patient relationship. There is a conflict of interests between physician and patient, in that the physician prefers the patient to always obtain a particular treatment, even if the patient would not consider this treatment in his interest. The patient obtains imperfect cues of whether or not he needs the treatment. The effect of an increase in the quality of the patient's private information is studied, in the form of an improvement in the quality of his cues. It is shown that when the patient's information improves in this sense, he may either become better off or worse off. The precise circumstances under which either result is obtained are derived.


[Development of ovaries in bovine fetuses].
The growth of ovaries, development of germ cells, formation of sex cords, folliculogenesis and dependence of these processes on the gonad morphogenesis stages were studied on 68 embryos and foetuses at the age of 1.5 to 9 months. Sex differentiation of ovaries was shown to take place in 1.5 month old embryo. The cords of connective tissue's cortical stroma appear also in 1.5 month old embryo, they develop in the dorsoventral direction and reach the gonad's covering epithelium in 6 month old foetuses. The formation of the medulla rudiment starts in 1.5 month old embryo when the gonad is separated from mesonephros and connected with it via the ovary gate. In 4 month old foetuses the ovary net transforms into a stellate structure. Important morphogenetic processes, such as the development of the ovary somatic elements, entry of the oocytes into meiotic prophase, formation of the sex cords and folliculogenesis, develop in the dorsoventral direction Germ cells in 9 month old foetuses are enclosed into primordial or, growing follicles.


Regulation of ADP-ribosylation factor 4 expression by small leucine zipper protein and involvement in breast cancer cell migration.
ADP-ribosylation factor 4 (ARF4) is a member of the Ras superfamily of small guanine nucleotide-binding proteins. ARF4 is known to interact with the epidermal growth factor receptor (EGFR) and mediates the EGF-dependent signal pathway, and has an anti-apoptotic function in human glioblastoma-derived U373MG cells. Although ARF4 plays a role in cancer cells, the molecular mechanism underlying regulation of its expression and its exact functions in breast cancer are unknown. In this study, we investigated the regulatory mechanism of ARF4 expression and its involvement in breast cancer cell migration. Our results show that phorbol 12-myristate 13-acetate (PMA) treatment increases ARF4 expression at both the transcriptional and translational levels. We found that the novel transcription factor small leucine zipper protein (sLZIP) binds directly to the CRE motif of the -43 to -35 region in the ARF4 promoter and regulates PMA-induced ARF4 expression. We also found that PMA-stimulated ARF4 expression increases AP-1 promoter activity, leading to induction of breast cancer cell migration. These results indicate that sLZIP-regulated ARF4 expression in response to PMA is involved in breast cancer cell migration, and sLZIP and ARF4 are potential therapeutic target molecules for treating breast cancer invasion and metastasis.


Absence of G(s)alpha gene mutations in childhood thyroid tumors after Chernobyl in contrast to sporadic adult thyroid neoplasia.
Heterotrimeric G proteins participate in the signal transduction cascade. Adult thyroid tumors have been shown to harbor specific point mutations in codons 201 and 227 of the G(s)alpha subunit of the adenylate cyclase stimulator. This protein affects the GDP/GTP turnover and finally results in an enhanced activation of G(s) and thus adenylate cyclase. We attempted to find out if G(s)alpha gene mutations were present in thyroid tumors of children from Belarus after the Chernobyl nuclear accident. Paraffin sections of 20 thyroid tumors were used for PCR amplification by oligonucleotide intron primers flanking exons 8 and 9, encompassing codon 201 and 227, respectively. By direct sequencing of the 274-bp amplification product, we did not detect any mutations of the G(s)alpha gene in codon 201 or 227. In contrast to thyroid neoplasia of adults, G(s)alpha gene mutations do not play a role in the development of childhood thyroid tumors after the Chernobyl reactor accident.


Start-up and stabilization of an Anammox process from a non-acclimatized sludge in CSTR.
Development of an Anammox (anaerobic ammonium oxidation) process using non-acclimatized sludge requires a long start-up period owing to the very slow growth rate of Anammox bacteria. This article addresses the issue of achieving a shorter start-up period for Anammox activity in a well-mixed continuously stirred tank reactor (CSTR) using non-acclimatized anaerobic sludge. Proper selection of enrichment conditions and low stirring speed of 30 +/- 5 rpm resulted in a shorter start-up period (82 days). Activity tests revealed the microbial community structure of Anammox micro-granules. Ammonia-oxidizing bacteria (AOB) were found on the surface and on the outer most layers of granules while nitrite-oxidizing bacteria (NOB) and Anammox bacteria were present inside. Fine-tuning of influent NO2(-)/NH4+ ratio allowed Anammox activity to be maintained when mixed microbial populations were present. The maximum nitrogen removal rate achieved in the system was 0.216 kg N/(m(3) day) with a maximum specific nitrogen removal rate of 0.434 g N/(g VSS day). During the study period, Anammox activity was not inhibited by pH changes and free ammonia toxicity.


Endogenous oils derived from human adipocytes are potent adjuvants that promote IL-1α-dependent inflammation.
Obesity is characterized by chronic inflammation associated with neutrophil and M1 macrophage infiltration into white adipose tissue. However, the mechanisms underlying this process remain largely unknown. Based on the ability of oil-based adjuvants to induce immune responses, we hypothesized that endogenous oils derived from necrotic adipocytes may function as an immunological "danger signal." Here we show that endogenous oils of human origin are potent adjuvants, enhancing antibody responses to a level comparable to Freund's incomplete adjuvant. The endogenous oils were capable of promoting interleukin (IL)-1α-dependent recruitment of neutrophils and M1-like macrophages, while simultaneously diminishing M2-like macrophages. We found that endogenous oils from subcutaneous and omental adipocytes, and from healthy and unhealthy obese individuals, promoted comparable inflammatory responses. Furthermore, we also confirmed that white adipocytes in visceral fat of metabolically unhealthy obese (MUO) individuals are significantly larger than those in metabolically healthy obese individuals. Since adipocyte size is positively correlated with adipocyte death, we propose that endogenous oils have a higher propensity to be released from hypertrophied visceral fat in MUO individuals and that this is the key factor in driving inflammation. In summary, this study shows that adipocytes contain a potent oil adjuvant which drives IL-1α-dependent proinflammatory responses in vivo.


The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.
Mitoxantrone is the first drug approved for the treatment of secondary progressive multiple sclerosis (SPMS) in the United States. This assessment considers use of mitoxantrone in the treatment of MS. Mitoxantrone probably reduces the clinical attack rate and reduces attack-related MRI outcomes in patients with relapsing MS (Type B recommendation). Also, mitoxantrone may have a beneficial effect on disease progression in patients with MS whose clinical condition is worsening (Type B recommendation). The potential for serious toxicity of mitoxantrone, however, must be taken into account when considering this therapy in individual patients. Moreover, because the potential clinical benefits on disease progression appear to be only modest, the results of the single phase III trial should be replicated in another (and hopefully much larger) clinical study before this agent is widely recommended for the treatment of patients with MS.


Risk factors for serious injury in Finnish agriculture.
Previous studies indicate 20% of injuries represent 80% of injury costs in agriculture. To help prevent the most costly injuries, we aimed to identify characteristics and risk factors associated with serious injuries. We analyzed insurance records of 93,550 self-employed Finnish farmers. We ranked injury causes by claim cost and used multiple logistic regressions to identify risk factors for (any) injury and serious injury (injuries exceeding claim costs of 2000 euros). A total of 5,507 compensated injuries occurred in 2002 (rate 5.9/100 person-years), and 1,167 or 21% of them (rate 1.25/100 person-years) were serious. The causes/sources resulting in highest average claim costs were motor vehicles; stairs, scaffoldings, and ladders; trailers and wagons; floors, walkways, and steps; other structures and obstacles; augers, mills, and grain handling equipment; horses; combines and harvesting equipment; tractor steps; and uneven and slippery terrain. Older age, male gender, higher income level, greater field size, residing on the farm, Finnish language (vs. Swedish), occupational health service (OHS) membership, and animal production were risk factors for injury. The risk factors for serious injury were similar; however, the effects of age, income level, and the raising of horses were more prominent. Language, residence, ownership status, and OHS membership were not risk factors for serious injury. Cost-effective prevention efforts should address the following risk factors: older age, male gender, larger income and operation size, livestock production (particularly dairy, swine, and horses), motor vehicle incidents, falls from elevation, and slips, trips and falls.


Safety and Durability of Effect with Long-Term, Open-Label Droxidopa Treatment in Patients with Symptomatic Neurogenic Orthostatic Hypotension (NOH303).
Neurogenic orthostatic hypotension (nOH) is associated with insufficient norepinephrine release in response to postural change. The objective of this study was to evaluate the long-term safety and durability of efficacy of the norepinephrine precursor droxidopa in patients with symptomatic nOH. This multinational study consisted of 3 sequential phases: a 3-month open-label droxidopa treatment phase followed by a 2-week double-blind, placebo-controlled withdrawal phase, and a 9-month open-label extension phase in which all patients received droxidopa. Patients were adults diagnosed with symptomatic nOH associated with Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. Efficacy was evaluated using patient- and investigator-reported questionnaire responses and the orthostatic standing test. Safety was assessed through adverse event (AE) reports and vital signs. A total of 102 patients received treatment with droxidopa. Initial improvements from baseline in patient-reported nOH symptom severity and impact on daily activities, evaluated using the Orthostatic Hypotension Questionnaire, exceeded 50% and were maintained throughout the 12-month study. Decreased nOH severity was also reflected in clinician and patient ratings on the Clinical Global Impression questionnaire. Standing systolic and diastolic blood pressures were increased from baseline throughout the study with droxidopa treatment. The most frequently reported AEs were falls, urinary tract infection, and headache. There was a low incidence (≤2%) of cardiac AEs (eg, first-degree atrioventricular block, supraventricular extrasystoles). Long-term, open-label treatment with droxidopa for up to 12 months was generally well tolerated and provided durable improvements in nOH signs and symptoms.


Reactivation of fungal spores in water following UV disinfection: Effect of temperature, dark delay, and real water matrices.
The occurrence of fungi in water supply systems causes many environmental problems (e.g., odor, taste, turbidity, formation of mycotoxins); it has been an area of increasing concern in recent years. Ultraviolet irradiation can inactivate fungi efficiently. However, its reactivation poses further challenges in water purification. The reactivation characteristics of waterborne fungi under different environmental conditions have rarely been reported. In this study, the effects of temperatures and dark delay on the reactivation of three genera of fungal spores (Trichoderma harzianum, Aspergillus niger, Penicillium polonicum) were evaluated. The reactivation levels among these fungal spores were compared in phosphate buffer solution (PBS) and in real groundwater. It was found that lower temperature can inhibit the photoreactivation of fungi, whereas higher temperatures would promote the process. A long-term dark delay can inhibit the photoreactivation of fungi effectively. The dark repair of fungal spores almost do not occur neither in PBS nor in real groundwater. Finally, the photoreactivation percentage in real groundwater was higher than that in PBS. This study will provide a basis for controlling the reactivation of fungi in water.


More is different: Reconstituting complexity in microtubule regulation.
Microtubules are dynamic cytoskeletal filaments that undergo stochastic switching between phases of polymerization and depolymerization-a behavior known as dynamic instability. Many important cellular processes, including cell motility, chromosome segregation, and intracellular transport, require complex spatiotemporal regulation of microtubule dynamics. This coordinated regulation is achieved through the interactions of numerous microtubule-associated proteins (MAPs) with microtubule ends and lattices. Here, we review the recent advances in our understanding of microtubule regulation, focusing on results arising from biochemical in vitro reconstitution approaches using purified multiprotein ensembles. We discuss how the combinatory effects of MAPs affect both the dynamics of individual microtubule ends, as well as the stability and turnover of the microtubule lattice. In addition, we highlight new results demonstrating the roles of protein condensates in microtubule regulation. Our overall intent is to showcase how lessons learned from reconstitution approaches help unravel the regulatory mechanisms at play in complex cellular environments.


Projections to the subcortical forebrain from anatomically defined regions of the medial geniculate body in the rat.
Although the auditory cortex is believed to be the principal efferent target of the medial geniculate body (MG), our recent behavioral studies indicate that in rats the conditioned coupling of emotional responses to an acoustic stimulus is mediated by subcortical projections of the MG. In the present study we have therefore used WGA-HRP as an anterograde and retrograde axonal marker to (1) define the full range of subcortical efferent projections of the MG; (2) identify the cells of origin within the MG of each projection; and (3) determine whether the subregions of the MG that project to subcortical areas receive inputs from acoustic relay nuclei of the mid-brain, particularly the inferior colliculus. The rat MG was first parcelled into three major cytoarchitectural areas: the ventral, medial, and dorsal divisions. The suprageniculate nucleus, located within the body of the MG just dorsal to the medial division, was also identified. Efferent projections of the MG were determined by combined anterograde and retrograde tracing methods. Injections of WGA-HRP in the MG produced anterograde transport to cortex and several subcortical areas, including the posterior caudate-putamen and amygdala, the ventromedial nucleus of the hypothalamus, and the subparafascicular thalamic nucleus. The cells of origin of the subcortical projections were then mapped retrogradely after injections in the anterogradely labeled areas. Injections in the caudate-putamen or amygdala retrogradely labeled the medial division of the MG and the suprageniculate nucleus, as well as several adjacent areas of the posterior thalamus surrounding the MG. In contrast, injections in the ventromedial nucleus of the hypothalamus or the subparafascicular thalamic nucleus only produced labeling in the areas surrounding MG. Afferents to MG from the inferior colliculus were then identified. The central nucleus of the inferior colliculus, the main lemniscal acoustic relay nucleus in the midbrain, was found to project to the ventral and medial divisions of the MG. In contrast, the dorsal cortex and external nucleus of the inferior colliculus project to each division of the MG and to several additional nuclei in adjacent areas of the posterior thalamus. These data demonstrate that the medial division of MG, the suprageniculate nucleus, and immediately adjacent areas of the posterior thalamus provide a direct linkage between auditory neurons in the inferior colliculus and subcortical areas of the forebrain and thereby support the view that thalamic sensory nuclei relay afferent signals to subcortical as well as cortical areas.


Controversies in the Management of Pediatric Musculoskeletal Infections: An International Viewpoint.
Pediatric musculoskeletal infections (MSIs) are a major contributor to the global burden of musculoskeletal disease in children and young adults. If untreated, or treated inappropriately or inadequately, pediatric bone and joint infections can be fatal or result in morbidity that causes significant functional disabilities to the patient and economic burden to the family and the community at large. The past decade has witnessed many advances in this field with respect to early diagnosis, management, and prevention of complications. It is important to discuss the current controversies in the management of pediatric MSIs with an international perspective. This discussion should include the controversies associated with the early diagnosis and identification of pediatric MSI in diverse settings; the controversies involved in the nonsurgical and surgical management of acute pediatric MSIs; and the controversies associated with the management of sequelae of pediatric MSI.


Microbial Diversity Profiling of Gut Microbiota of Macropus giganteus Using Three Hypervariable Regions of the Bacterial 16S rRNA.
Animal faecal contamination of surface waters poses a human health risk, as they may contain pathogenic bacteria or viruses. Of the numerous animal species residing along surface waterways in Australia, macropod species are a top contributor to wild animals' faecal pollution load. We characterised the gut microbiota of 30 native Australian Eastern Grey Kangaroos from six geographical regions (five kangaroos from each region) within South East Queensland in order to establish their bacterial diversity and identify potential novel species-specific bacteria for the rapid detection of faecal contamination of surface waters by these animals. Using three hypervariable regions (HVRs) of the 16S rRNA gene (i.e., V1-V3, V3-V4, and V5-V6), for their effectiveness in delineating the gut microbial diversity, faecal samples from each region were pooled and microbial genomic DNA was extracted, sequenced, and analysed. Results indicated that V1-V3 yielded a higher taxa richness due to its larger target region (~480 bp); however, higher levels of unassigned taxa were observed using the V1-V3 region. In contrast, the V3-V4 HVR (~569 bp) attained a higher likelihood of a taxonomic hit identity to the bacterial species level, with a 5-fold decrease in unassigned taxa. There were distinct dissimilarities in beta diversity between the regions, with the V1-V3 region displaying the highest number of unique taxa (n = 42), followed by V3-V4 (n = 11) and V5-V6 (n = 8). Variations in the gut microbial diversity profiles of kangaroos from different regions were also observed, which indicates that environmental factors may impact the microbial development and, thus, the composition of the gut microbiome of these animals.


Biomimetic block copolymer particles with gated nanopores and ultrahigh protein sorption capacity.
The design of micro- or nanoparticles that can encapsulate sensitive molecules such as drugs, hormones, proteins or peptides is of increasing importance for applications in biotechnology and medicine. Examples are micelles, liposomes and vesicles. The tiny and, in most cases, hollow spheres are used as vehicles for transport and controlled administration of pharmaceutical drugs or nutrients. Here we report a simple strategy to fabricate microspheres by block copolymer self-assembly. The microsphere particles have monodispersed nanopores that can act as pH-responsive gates. They contain a highly porous internal structure, which is analogous to the Schwarz P structure. The internal porosity of the particles contributes to their high sorption capacity and sustained release behaviour. We successfully separated similarly sized proteins using these particles. The ease of particle fabrication by macrophase separation and self-assembly, and the robustness of the particles makes them ideal for sorption, separation, transport and sustained delivery of pharmaceutical substances.


Mutations in RNA Methyltransferase Gene NSUN5 Confer High Risk of Outflow Tract Malformation.
NSUN5, encoding a cytosine-5 RNA methyltransferase and located in the 7q11.23 locus, is a candidate gene for tetralogy of Fallot (TOF). Deletion of the 7q11.23 locus in humans is linked to cardiac outflow tract (OFT) disorders including TOF. We identified four potential pathogenic mutations in the coding region of NSUN5 and which were enriched in TOF patients by an association study of 132 TOF patients and 2,000 in-house controls (P = 1.44 × 10-5). We then generated a Nsun5 null (Nsun5 -/-) mouse model to validate the human findings by defining the functions of Nsun5 in OFT morphogenesis. The OFT did not develop properly in the Nsun5 deletion embryonic heart. We found a misalignment of the aorta and septum defects caused by the delayed fusion of the membraneous ventricular spetum as an OFT development delay. This caused OFT development delay in 27 of 64 (42.2%) Nsun5 -/- mice. Moreover, we also found OFT development delay in 8 of 51 (15.7%) Nsun5 +/- mice. Further functional experiments showed that the loss of Nsun5 function impaired the 5-methylcytosine (m5C) modification and translation efficiency of essential cardiac genes. Nsun5 is required for normal OFT morphogenesis and it regulates the m5C modification of essential cardiac genes. Our findings suggest the involvement of NSUN5 in the pathogenesis of TOF.


Plasma opioids in the newborn in relation to the mode of delivery.
Elevated plasma concentrations of beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) are present in vaginally delivered babies in the first 24 h of life. To establish if fetal distress or different types of delivery influence the secretion of these peptides in the neonatal period, we studied 16 vaginally delivered newborns (VD), 11 neonates extracted through elective cesarean section (CS) and 8 babies suffering from acute intralabor fetal distress (FD). In all groups of newborns the plasma levels of beta-LPH and beta-EP were measured in arterial and venous cord blood, at 1 and 24 h from delivery. beta-LPH and beta-EP were determined by specific radioimmunoassays after silicic acid extraction and Sephadex G-75 column chromatography. In cord plasma, there were no differences between arterial and venous concentrations of either beta-LPH or beta-EP in any of the groups. In the 1st h after delivery the plasma levels of VD newborns were similar to umbilical cord values (beta-LPH: 19.9 +/- 5.2; beta-EP: 18.1 +/- 2.4), while those of CS (beta-LPH: 30.6 +/- 4.5; beta-EP: 30.1 +/- 5.8) and FD (beta-LPH: 64.9 +/- 11.8; beta-EP: 65.7 +/- 24.4) showed a significant increase. At the 24th h of life the plasma concentrations of both peptides decreased significantly in the three groups, but CS and FD babies showed significantly higher plasma values than VD newborns (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Spectroscopic determination of proton position in the proton-coupled electron transfer pathways of donor-acceptor supramolecule assemblies.
A homologous set of porphyrin derivatives possessing an isocyclic five-membered ring appended with an amidinium functionality has been used to examine proton-coupled electron transfer (PCET) through well-characterized amidine-carboxylic acid interfaces. Conjugation between the porphyrin chromophore and the amidinium interface can be altered by selective reduction of the isocyclic ring of an amidinium-purpurin to produce an amidinium-chlorin. The highly conjugated amidinium-purpurin displays large spectral shifts in the visible region upon alteration of the amidinium/amidine protonation state; no such change is observed for the chlorin homologue. Analysis of the UV-vis absorption and emission profiles of the amidinium-purpurin upon deprotonation allows for the measurement of the porphyrinic-amidinium acidity constant for the ground state (pKa = 9.55 +/- 0.1 in CH3CN) and excited state (pKa)= 10.40 +/- 0.1 in CH3CN). The absorption spectrum of the purpurin also provides a convenient handle for determining the protonation state of assembled interfaces. In this way, the purpurin macrocycle provides a general tool for PCET studies because it can be used to determine the location of a proton within PCET interfaces formed from carboxylic acid electron acceptors including dinitrobenzenes (DNBs) and naphthalenediimide (NI), which have been used extensively in previous PCET studies. An amidine-carboxylic acid interface is observed for electron-rich acceptors, whereas the ionized amidinium-carboxylate interface is observed for electron-poor acceptors. The PCET kinetics for purpurin/chlorin associated to NI are consistent with an amidine-carboxylic acid interface, which is also verified spectrally.


Targeted control of kinetics of beta-amyloid self-association by surface tension-modifying peptides.
Brain tissue from Alzheimer's patients contains extracellular senile plaques composed primarily of deposits of fibrillar aggregates of beta-amyloid peptide. beta-Amyloid aggregation is postulated to be a major factor in the onset of this neurodegenerative disease. Recently proposed is the hypothesis that oligomeric intermediates, rather than fully formed insoluble fibrils, are cytotoxic. Previously, we reported the discovery of peptides that accelerate beta-amyloid aggregation yet inhibit toxicity in vitro, in support of this hypothesis. These peptides contain two domains: a recognition element designed to bind to beta-amyloid and a disrupting element that alters beta-amyloid aggregation kinetics. Here we show that the aggregation rate-enhancing activity of the disrupting element correlates strongly with its ability to increase surface tension of aqueous solutions. Using the Hofmeister series as a guide, we designed a novel peptide with terminal side-chain trimethylammonium groups in the disrupting domain. The derivatized peptide greatly increased solvent surface tension and accelerated beta-amyloid aggregation kinetics by severalfold. Equivalent increases in surface tension in the absence of a recognition domain had no effect on beta-amyloid aggregation. These results suggest a novel strategy for targeting localized changes in interfacial energy to specific proteins, as a way to selectively alter protein folding, stability, and aggregation.


Impact of cancer on adherence to glucose-lowering drug treatment in individuals with diabetes.
Adherence to glucose-lowering drug (GLD) treatment regimens is crucial for metabolic control and improving prognosis. Because a diagnosis of cancer might have an impact on adherence to medication, this study explored changes in adherence to GLDs following a cancer diagnosis. All new users of GLDs between 1998 and 2011 who lived in the Eindhoven Cancer Registry-PHARMO Database Network catchment area were selected. Those with a primary cancer diagnosis during follow-up were considered cases and matched with eligible controls without cancer during follow-up. Medication possession ratio (MPR) was used as indicator for medication adherence. Segmented linear auto-regression analysis with interrupted time series was used to assess changes in MPR for cases compared with controls (i.e. overall trend) due to (any) cancer diagnosis and specific cancer types. From the 52,228 GLD users selected, 3,281 cases with cancer and 12,891 controls without cancer during follow-up were included in the study. In our analyses, before cancer diagnosis the MPR increased by 0.10% per month (95% CI 0.10, 0.10). Besides a significant drop in MPR at the time of cancer diagnosis of -6.3% (95% CI -6.5, -6.0), there was an ongoing, yet lower, monthly decline in MPR (-0.20%; 95% CI -0.21, -0.20) after cancer diagnosis. The largest drops in MPR at the time of cancer diagnosis, in the range of 11-15%, were seen among patients with stage IV disease and gastrointestinal or pulmonary cancers. Our findings indicate a clear decline in adherence to GLD treatment regimens following a cancer diagnosis. The reason for the decline in MPR needs to be further elucidated.


Analysis of synonymous codon usage in FAD7 genes from different plant species.
In this study, the codon bias of the FAD7 genes among 10 different plant species was analyzed to identify general patterns of codon usage in the FAD7 genes. Our results showed that U-ended or A-ended codons were preferentially used in FAD7 for dicots, whereas G-ended or C-ended codons were preferentially used in FAD7 for monocots. An ENC-plot showed that some other factors may influence the codon usage of FAD7, except mutation bias in plant species. A correlation analysis between the codon adaptation index and GC or GC3s contents demonstrated that the codon usage bias of the FAD7 gene in plant species could be influenced by the gene expression level. The cluster analysis of relative synonymous codon usage values and phylogenetic trees of protein sequences for FAD7 genes confirm that the codon preference of FAD7 is influenced by genetic relationships. Moreover, Arabidopsis thaliana and Nicotiana tabacum were predicted to be the most appropriate expression hosts for the FAD7 genes from dicots, and Zea mays may be suitable for the expression of the FAD7 genes from monocots. Our results provide useful insights into the evolutionary relationships of plant species.


Early amniocentesis versus transabdominal chorion villus sampling for prenatal diagnosis.
A major disadvantage of amniocentesis is that test results are usually available only after 18 weeks gestation. Early amniocentesis can now be done between 9 to 14 weeks gestation. The objective was to assess the safety and accuracy of early amniocentesis compared with chorion villus sampling. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched. Date of last search: October 1998. Randomised trials comparing early amniocentesis with transabdominal chorion villus sampling. One reviewer assessed eligibility and trial quality. Three studies were included. Sampling failure was 0.4% in the early amniocentesis group compared to 2% in the chorion villus group (relative risk 0.23, 95% confidence interval 0.08 to 0.65). Consequently, more women in the chorion villus sampling group needed a second prenatal diagnostic test (relative risk 0.43, 95% confidence interval 0.21 to 0.88). There were no statistically significant differences in the laboratory failures (relative risk 0.43, 95% confidence interval 0. 17 to 1.10) or number of women with various chromosomal abnormalities (relative risk 0.51, 95% confidence interval 0.26 to 1. 04). Combined total pregnancy loss in the early amniocentesis group was 6.2% (57/915) compared with 5% (46/917) in the chorion villus sampling group (relative risk 1.24, 95% confidence interval 0.85 to 1.81). There were more spontaneous miscarriages after early amniocentesis (4.4% versus 2.3%, relative risk 1.92, 95% confidence interval 1.14 to 3.23). There was no difference in the incidence of neonatal respiratory distress and anomalies in the newborn infants. The incidence of talipes was greater in the early amniocentesis group, although haemangiomas were more common in the chorion villus sampling group. Current data suggest that early amniocentesis is associated with a greater risk of spontaneous miscarriage and neonatal talipes compared to transabdominal chorion villus sampling. An increased risk of these complications needs to be weighed against fewer technical difficulties and the possibility of fewer neonatal haemangiomas.


The role of inhibition in oscillatory wave dynamics in the cortex.
Cortical oscillations arise during behavioral and mental tasks, and all temporal oscillations have particular spatial patterns. Studying the mechanisms that generate and modulate the spatiotemporal characteristics of oscillations is important for understanding neural information processing and the signs and symptoms of dynamical diseases of the brain. Nevertheless, it remains unclear how GABAergic inhibition modulates these oscillation dynamics. Using voltage-sensitive dye imaging, pharmacological methods, and tangentially cut occipital neocortical brain slices (including layers 3-5) of Sprague-Dawley rat, we found that GABAa disinhibition with bicuculline can progressively simplify oscillation dynamics in the presence of carbachol in a concentration-dependent manner. Additionally, GABAb disinhibition can further simplify oscillation dynamics after GABAa receptors are blocked. Both GABAa and GABAb disinhibition increase the synchronization of the neural network. Theta frequency (5-15-Hz) oscillations are reliably generated by using a combination of GABAa and GABAb antagonists alone. These theta oscillations have basic spatiotemporal patterns similar to those generated by carbachol/bicuculline. These results are illustrative of how GABAergic inhibition increases the complexity of patterns of activity and contributes to the regulation of the cortex.


Novel interventions to reduce oxidative-stress related brain injury in neonatal asphyxia.
Perinatal asphyxia-induced brain injury may present as hypoxic-ischemic encephalopathy in the neonatal period, and disability including cerebral palsy in the long term. The brain injury is secondary to both the hypoxic-ischemic event and the reoxygenation-reperfusion following resuscitation. Early events in the cascade of brain injury can be classified as either inflammation or oxidative stress through the generation of free radicals. The objective of this paper is to present efforts that have been made to limit the oxidative stress associated with hypoxic-ischemic encephalopathy. In the acute phase of ischemia/hypoxia and reperfusion/reoxygenation, the outcomes of asphyxiated infants can be improved by optimizing the initial delivery room stabilization. Interventions include limiting oxygen exposure, and shortening the time to return of spontaneous circulation through improved methods for supporting hemodynamics and ventilation. Allopurinol, melatonin, noble gases such as xenon and argon, and magnesium administration also target the acute injury phase. Therapeutic hypothermia, N-acetylcysteine2-iminobiotin, remote ischemic postconditioning, cannabinoids and doxycycline target the subacute phase. Erythropoietin, mesenchymal stem cells, topiramate and memantine could potentially limit injury in the repair phase after asphyxia. To limit the injurious biochemical processes during the different stages of brain injury, determination of the stage of injury in any particular infant remains essential. Currently, therapeutic hypothermia is the only established treatment in the subacute phase of asphyxia-induced brain injury. The effects and side effects of oxidative stress reducing/limiting medications may however be difficult to predict in infants during therapeutic hypothermia. Future neuroprotection in asphyxiated infants may indeed include a combination of therapies. Challenges include timing, dosing and administration route for each neuroprotectant.


Antimycin A fermentation. I. Production and selection of strains.
Increase in antimycin A production was achieved through a parallel strain and medium improvement program: a 125-fold augmentation (75 to 9,500 mug/ml) was obtained. The selective system included antimycin A productivity, conidiation, sensitivity to ultraviolet radiation, growth rate and yield, and absence of pigment and actinomycin D production. Among the original strains tested one natural isolate possessed high productivity and several of the above characteristics, and was selected for mutagenesis. Spontaneous and induced variability was then exploited in isolating high-producing strains. The first mutagen used was ultraviolet radiation; it was replaced by ethylenimine when it became no longer efficient in increasing variability. As new, high producers were isolated, the medium was modified to best suit their requirements for still higher productivity. The critical environmental factors were absence of phosphate and organic salts, concentration of the nitrogen source and ratio organic/inorganic nitrogen, ratio ammonium sulfate/calcium carbonate, and addition of slowly utilizable carbon sources, such as lactose and oil; optimum temperature and initial pH were 25 degrees C and 7.0. Aeration/agitation requirements of improved strains were high. Fermentation was characterized by abrupt pH changes which impaired rapid accumulation of the antibiotic. Antimycin A was produced during both the trophophase and idiophase.


Ultrasonic methods of predicting the estimated date of confinement.
The present study examines the relative accuracy of 2 ultrasonic methods of predicting the estimated date of confinement (EDC). The first technique, mean projected gestational age (MPGA), utilizes 2 fetal biparietal diameter (BPD) readings between 19 and 30 weeks' gestation with at least a 3-week interval between examinations. The 2 values are fitted to the mean of the standard curve as closely as possible and an EDC is predicted. The second method, growth adjusted sonographic age (GASA), is based on 1 BPD measurement in the second trimester and another in the third. The first is plotted on the mean and then readjusted depending on the percentile into which the second falls (below 25, 25 to 75, above 75). The EDC was blindly predicted in 120 patients, 60 by the MPGA method and 60 by the GASA technique. These were compared with 60 controls whose EDCs were predicted on the basis of excellent clinical dates. The interval between the predicted EDC and the actual delivery date was calculated for each patient and the results were compared. There was no statistical difference between the 2 techniques.


Use of health care resources and cost of care for adults with constipation.
Constipation is a multisymptom disorder that frequently compromises quality of life and leads patients to seek medical advice. To evaluate the clinical and fiscal effects of constipation, we assessed health care resource use by patients with constipation enrolled in a large state Medicaid program. We identified 105,130 patients older than age 18 who saw a physician at least once for constipation and were enrolled in the California Medicaid program (Medi-Cal). We then studied health care resource use and costs (reimbursed by Medi-Cal) in 76,854 patients without supplementary insurance. The 15-month analysis period encompassed 3 months before and 12 months after the first visit. The prevalence of comorbid conditions was assessed in the sample of 105,130 patients. During the study period, 106,555 physician visits were for constipation; the total associated cost was $3,016,017 ($39/patient). The total cost for gastrointestinal procedures and laboratory testing was $14,052,503 ($183/patient). There were 41,723 over-the-counter and 1665 prescription drug purchases; the total cost was $388,780 ($5/patient). Approximately 0.6% of patients (n = 479) were admitted to the hospital for constipation; the total cost was $1,433,708 ($2993/admission). The total direct health care costs for patients with constipation in the Medi-Cal system for the 15-month period was $18,891,008 ($246/patient). Within 12 months of the first physician visit for constipation, 5657 of 105,130 patients had hemorrhoids and 2288 had intestinal impaction or obstruction. Adults seeking treatment for constipation account for significant health care resource use and often have comorbid conditions. The clinical and fiscal burden of constipation in US adults cannot be disregarded or trivialized.


Women with breast cancer: experience of chemotherapy-induced pain: triangulation of methods.
Chemotherapy treatment for cancer diseases can cause body pain during adjuvant therapy. The aim was to describe the perceived impact of adjuvant chemotherapy-induced pain (CHIP) on the daily lives of women with newly diagnosed breast cancer, using triangulation. Fifty-seven women scheduled for chemotherapy in doses of 75 mg/m or greater of epirubicin and/or docetaxel participated. Twenty-two of these women registered pain with values of 4 or more on the visual analog scale on day 10 following chemotherapy. Of these 22, 16 participated in an interview and colored a printed body image. A qualitative thematic stepwise analysis of the interviews was performed. Chemotherapy-induced pain had a profound impact on daily life. Ten women reported the worst possible pain, with visual analog scale scores of 8 to 10. Three different categories crystallized: perception (A) of manageable pain, which allowed the women to maintain their daily lives; perception (B) of pain beyond imagination, whereby the impact of pain had become more complex; and perception (C) of crippling pain, challenging the women's confidence in survival. The findings highlight the inability to capture CHIP with 1 method only; it is thus necessary to use complimentary methods to capture pain. We found that pain had a considerable impact on daily life, with surprisingly high scores of perceived pain, findings that to date have been poorly investigated qualitatively. Nurses need to (1) better identify, understand and treat CHIP, using instruments and protocols; and (2) provide improved communication about pain and pain management.


Dynamic interactions of gas exchange, body mass, and progressive exercise in children.
Cardiopulmonary exercise testing (CPET) is increasingly used as a biomarker of fitness in children. Maximal or peak values remain the most common variables obtained in CPET, but these physiologically challenging high-intensity work rates (WR) are often not achieved. We hypothesized that interactions of gas exchange, heart rate (HR), and WR CPET variables (slopes) could yield useful mechanistic and clinical insights that might enhance the clinical utility of CPET in children. We further hypothesized that the dependence of the slope on body mass could be predicted by the first-principle analysis of body size and physiological response. One hundred and sixty-nine healthy participants (8-18 yr old, body mass index <95th percentile, 82 females) underwent dual x-ray absorptiometry scan to estimate lean body mass (LBM) and performed a ramp-type progressive cycle ergometry exercise protocol with a breath-by-breath measurement of gas exchange. Linear regression was used to calculate the slopes among VO2, VCO2, VE, HR, and WR. ΔWR/ΔHR (r = 0.87) and ΔVO2/ΔHR (r = 0.96) were strongly correlated with VO2peak, whereas ΔVO2/ΔWR (r = 0.42) and ΔVE/ΔVCO2 (r = -0.51) were mildly correlated with peak values. LBM was more highly correlated with those slopes predicted to be body size dependent (P < 0.0001) compared with total body mass. The data largely supported our original hypotheses. Unlike peak or maximal values, which are derived from no more than a few data points at the end of a progressive exercise test, the CPET slopes were calculated from a much larger data set obtained throughout the test. An analysis of these slopes might ultimately prove useful clinically and in research studies when peak values are not achieved.


Endoscopic ultrasonography and idiopathic acute pancreatitis.
Idiopathic acute pancreatitis is a diagnostic challenge for gastroenterologists. The possibility of finding a cause for pancreatitis usually relies on how far the diagnostic study is taken. Endoscopic explorations such as endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography can help to determine the cause of pancreatitis. Furthermore, microscopic bile examination and magnetic resonance cholangiopancreatography can also be helpful in the work up of these patients. In this article an approximation to the diagnostic approach to patients with idiopathic acute pancreatitis is made, taking into account the reported evidence with which to choose between the different available explorations.


Reliability and validity of the Vietnamese version of the 9-item Utrecht Work Engagement Scale.
The present study investigated the reliability and validity of a newly developed Vietnamese version of the 9-item Utrecht Work Engagement Scale (UWES-9-V) in a sample of hospital nurses in Hanoi, Vietnam. The UWES-9 was translated into Vietnamese following a standard procedure. A survey was conducted of 949 registered nurses in a large tertiary general hospital in Hanoi, Vietnam, in 2018, using a self-administered questionnaire including the Vietnamese UWES-9, other scales measuring health status, work performance, job demand, job control, and workplace social support, and questions pertaining to demographic variables. Cronbach's alpha and interclass correlation coefficients (ICC) were calculated to assess reliability. Explanatory and confirmatory factor analyses were conducted to assess factorial validity. Convergent validity was tested based on associations between the UWES-9-V and subscales and other scales. The Cronbach's alpha coefficients of the UWES-9-V and the Vigor, Absorption, and Dedication subscales were 0.93, 0.86, 0.77, and 0.90, respectively. ICC of the UWES-9-V in a subsample after 3 months was 0.48. Confirmatory factor analyses indicated an acceptable fit of both one-factor and three-factor structures, with the three-factor model having the better fit. The UWES-9-V and its subscales correlated with depression, anxiety and stress, health-related quality of life and health condition, job performance, and psychosocial work environment. The study findings suggest that the UWES-9-V is a reliable and valid instrument to measure work engagement among hospital nurses in Vietnam, a low- and middle-income country. Future studies should confirm the validity and reliability of the UWES-9-V among various occupations.


Interstitial deletion 2(p11.2p13): a rare chromosomal abnormality.
We report on an infant with a karyotype of 46,XY,del(2) (p11.2p13), the fourth reported case in the literature. At birth, the child had eventration of the diaphragm. His phenotype was suggestive of a connective tissue disorder with scoliosis, pectus carinatum, long slender fingers, camptodactyly, cryptorchidism, hypertonia and myopia. His facial appearance was mildly dysmorphic and strongly resembled a previously reported patient with the same deletion. The child expired at 2 months of age. Some generalizations can be made about the phenotype for del(2)(p11.2p13), despite reporting of cases at different ages.


Assessment of Fractional-Order Arterial Windkessel as a Model of Aortic Input Impedance.
Goal: Fractional-order Windkessel model is proposed to describe the aortic input impedance. Compared with the conventional arterial Windkessel, the main advantage of the proposed model is the consideration of the viscoelastic nature of the arterial wall using the fractional-order capacitor (FOC). Methods: The proposed model, along with the standard two-element Windkessel, three-element Windkessel, and the viscoelastic Windkessel models, are assessed and compared using in-silico data. Results: The results show that the fractional-order model fits better the moduli of the aortic input impedance and fairly approximates the phase angle. In addition, by its very nature, the pseudo-capacitance of FOC makes the proposed model's dynamic compliance complex and frequency-dependent. Conclusions: The analysis of the proposed fractional-order model indicates that fractional-order impedance yields a powerful tool for a flexible characterization of the arterial hemodynamics.


A rare cause of short stature: Leri Weill dyschondrosteosis.
Short stature is a common pediatric problem. It may occur rarely as a result of genetic disorders. Leri-Weill dyschondrosteosis (LWD) is one of the rare genetic disorders of skeletal system resulting with short stature. It is characterized by shortness of stature and Madelung deformity of the wrist. Here we report a case of LWD with some skeletal stigmas of Turner syndrome. She has also depressed medial tibial condyles that to our knowledge, has not previously been reported in LWD.


Localised drug release using MRI-controlled focused ultrasound hyperthermia.
Thermosensitive liposomes provide a mechanism for triggering the local release of anticancer drugs, but this technology requires precise temperature control in targeted regions with minimal heating of surrounding tissue. The objective of this study was to evaluate the feasibility of using MRI-controlled focused ultrasound (FUS) and thermosensitive liposomes to achieve thermally mediated localised drug delivery in vivo. Results are reported from ten rabbits, where a FUS beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43°C for 20-30 min. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Unabsorbed liposomes were flushed from the vasculature by saline perfusion 2 h later, and tissue samples were harvested from heated and unheated thigh regions. The fluorescence intensity of the homogenised samples was used to calculate the concentration of doxorubicin in tissue. Closed-loop control of FUS heating using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9°C, 41.0°C and 44.8°C, respectively, over a period of 20 min. Doxorubicin concentrations were significantly higher in tissues sampled from heated than unheated regions of normal thigh muscle (8.3 versus 0.5 ng/mg, mean per-animal difference = 7.8 ng/mg, P < 0.05, Wilcoxon matched pairs signed rank test). The results show the potential of MRI-controlled focused ultrasound hyperthermia for enhanced local drug delivery with temperature-sensitive drug carriers.