Give ears some respite from regular microsuctioning in bisphosphonate-induced osteonecrosis of the external ear canal.
This paper reports a case series of three elderly patients who were regularly attending ENT clinic every four to six weeks for ear canal care to address chronic otitis externa. All three patients had been taking bisphosphonate alendronic acid for years, and it is suspected that this drug was partly to blame for the progression of their chronic ear conditions. Some improvements were noted when the bisphosphonate was discontinued. The regular microsuctioning, and application of topical antibiotics with steroids, provided temporary relief of symptoms. The present pandemic shut down the routine clinic and the patients were not seen for four to five months. On latest review, it was a surprise to see that their ears seemed to have significantly improved, with healthy re-epithelialisation. It is thus believed that excessive and repeated microsuctioning in bisphosphonate-induced osteonecrosis of that external ear canal can delay re-epithelialisation, and gradually prolonging the intervals between microsuctioning could help in overall resolution of the disease.


Comparing Race/Ethnicity and Zip Code Socioeconomic Status for Surgical versus Nonsurgical Management of Proximal Humerus Fractures in a Medicare Population.
This study evaluated the effect of race/ethnicity and socioeconomic status (SES) on surgical utilization after proximal humerus fractures in a large Medicare cohort. The PearlDiver Medicare claims database was used to identify patients aged 65years and older with isolated, closed proximal humerus fractures, for whom race/ethnicity data were available (65.5% of identified fractures). Patients with polytrauma or neoplasm were excluded. Patient demographic, race/ethnicity, comorbidity, and median household income were compared for surgical versus nonsurgical management. Univariate and multivariable logistic regressions were used to determine disparities of surgical utilization based on the abovementioned factors. Of 133,218 patients with proximal humerus fracture identified, surgery was conducted for 4446 (3.3%). Those less likely to receive surgery were older (incrementally by increasing age bracket up to 85 years and older odds ratio [OR], 0.16, P < 0.001), male (OR, 0.79, P < 0.001), Black (OR, 0.51, P < 0.001) or Hispanic (0.61, P = 0.005), higher Elixhauser Comorbidity Index (per 2 increase OR, 0.86, P < 0.001), and low median household income (OR, 0.79, P < 0.001). The independent significance of race/ethnicity and SES point to disparities in surgical decision making/access to care. These findings highlight the need for increased attention on initiatives and policies that seek to eliminate racial disparities and improve health equity independent of SES.


Dentin bridge formation after mineral trioxide aggregate (MTA) pulpotomies in primary teeth.
To evaluate the results of using mineral trioxide aggregate (MTA) in pulpotomy procedures in primary teeth. Seven patients were selected and a total of 20 molars and two canines were treated with pulpotomy procedures using MTA instead of formocresol. After 6 months, 55% of the molars and 100% of the canines treated showed radiographic signs of dentin bridge formation. Also, 6 months after treatment, 60% of the molars showed root canal calcification (obliteration). Color change of the crown of the canines treated was noticeable. No clinical or radiographic signs of pathology was observed.


Vertebral compression and eosinophilia in a child with acute lymphatic leukemia.
A 10-year-old girl, presenting with fever, eosinophilia, and back pain, was diagnosed with pre-B CD10-positive acute lymphoblastic leukemia. Eosinophilia resolved rapidly during remission induction treatment, but diffuse spinal osteopenia with multiple compression fractures became manifest after 4 weeks. During subsequent treatment the spine remineralized slowly, and after 26 months vertebral bone regeneration was apparent. Eosinophilia and osteopenia are separately known as early manifestations of acute lymphoblastic leukemia, but their simultaneous occurrence is particularly interesting. A late bone marrow relapse was not accompanied by bone changes or eosinophilia.


Nonrecessively transmitted nonspherocytic hereditary haemolytic anaemia associated with increased red cell glutathione.
Hereditary haemolytic anaemia not associated with spherocytosis, ovalocytosis, stomatocytosis or haemoglobinopathy was observed in three members of a kindred. There were no demonstrable abnormalities of enzymes of the Embden-Myerhof pathway, the hexosemonophosphate shunt, or of a variety of non-glycolytic enzymatic activities assayed in patient erythrocytes. In each case, red cell glutathione was increased in concentration three to six standard deviations above our normal mean. Erythrocyte glutathione was normally stable and all sulfhydryl reacting material was shown by specific enzyme assays to represent either reduced (97%) or oxidized (3%) glutathione. No abnormality in active transport of oxidized glutathione was demonstrable in the red cells. This syndrome of unknown actiology was transmitted in autosomally dominant fashion or, alternatively, as a possibly x-chromosome linked disorder. Existing data did not permit the differentiation of these two possibilities.


Regulation of clinical microbiology and infection control--is the gain worth the pain?
In the USA, decreasing money for health has led medical professionals and the public to wonder whether cost containment is hurting patient care. In response to this, several regulatory bodies have instituted extensive review procedures under the label of 'quality assurance'. Anxiety in healthcare workers about the risk of HIV infection and chemical exposures has led to a profusion of rational and less-rational proposals, guidelines, and standards for employee protection. Concern about the validity of laboratory diagnostic tests has triggered laws, codes and rubrics about procedures and proficiency testing. A major premise of government now seems to be that 'an unregulated industry is an unsafe industry'. As a result, US hospitals find themselves reviewed, surveyed, examined, regulated and codified to a degree never before experienced. This quantity of review has been accompanied by problems of review quality, in the form of conflicting, vague and wasteful standards and regulations. What is at issue is finding the most efficient ways to address these problems. We must campaign for close cooperation between regulatory groups, clear distinction between sociopolitical and scientific justification for regulation, and cost-benefit analysis of the regulations and their impact. Laboratory and hospital infection control personnel are important to this effort because the epidemiological skills required for these tasks are the same abilities used to make clinical microbiology and hospital infection control effective and efficient. Similar problems and solutions may exist in other countries as well. The issue is particularly pertinent to the discussion of standards for hospital infection control in the European countries now preparing for economic unification.


Unusual late presentation of metastatic extrathoracic thymoma to gastrohepatic lymph node treated by surgical resection.
In advanced stages, thymic tumors tend to spread locally. Distant metastatic disease is rare. We present the first report of single metastatic abdominal lymph node in a 37-year-old female patient and 5 years after an extrapleural pneumonectomy for stage IV thymoma followed by radiotherapy with no other evidence of abdominal disease successfully treated by robotic surgical resection.


Structural determinants of Smad function in TGF-β signaling.
Smad transcription factors are central to the signal transduction pathway that mediates the numerous effects of the transforming growth factor β (TGF-β) superfamily of cytokines in metazoan embryo development as well as in adult tissue regeneration and homeostasis. Although Smad proteins are conserved, recent genome-sequencing projects have revealed their sequence variation in metazoan evolution, human polymorphisms, and cancer. Structural studies of Smads bound to partner proteins and target DNA provide a framework for understanding the significance of these evolutionary and pathologic sequence variations. We synthesize the extant mutational and structural data to suggest how genetic variation in Smads may affect the structure, regulation, and function of these proteins. We also present a web application that compares Smad sequences and displays Smad protein structures and their disease-associated variants.


Asymmetric structure of the native Rhodobacter sphaeroides dimeric LH1-RC complex.
Rhodobacter sphaeroides is a model organism in bacterial photosynthesis, and its light-harvesting-reaction center (LH1-RC) complex contains both dimeric and monomeric forms. Here we present cryo-EM structures of the native LH1-RC dimer and an LH1-RC monomer lacking protein-U (ΔU). The native dimer reveals several asymmetric features including the arrangement of its two monomeric components, the structural integrity of protein-U, the overall organization of LH1, and rigidities of the proteins and pigments. PufX plays a critical role in connecting the two monomers in a dimer, with one PufX interacting at its N-terminus with another PufX and an LH1 β-polypeptide in the other monomer. One protein-U was only partially resolved in the dimeric structure, signaling different degrees of disorder in the two monomers. The ΔU LH1-RC monomer was half-moon-shaped and contained 11 α- and 10 β-polypeptides, indicating a critical role for protein-U in controlling the number of αβ-subunits required for dimer assembly and stabilization. These features are discussed in relation to membrane topology and an assembly model proposed for the native dimeric complex.


Friend turned foe: TREM2 agonist in battles against tau.
In this important study, Jain et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220654) find that chronic TREM2 activation by AL002a antibody exacerbates the seeding and spread of pathological tau, enhances the disease-associated microglial signature, and increases neurite dystrophy in 5xFAD mice seeded with Alzheimer's disease tau.


Perceptions of research risk and undue influence: Implications for ethics of research conducted with cocaine users.
Despite the prominence of human laboratory and clinical trial research in the development of interventions for substance use disorders, this research presents numerous ethical challenges. Ethical principles outlined in the Belmont Report, including respect for persons, beneficence, and justice, have traditionally guided research conduct. Few empirical studies exist examining substance abuse research ethics. The present study examined perceptions of beneficence and respect for persons in substance use research, including relative risk and desired monetary compensation, using an online sample of cocaine users. The study was conducted on Amazon.com's Mechanical Turk (mTurk), a crowdsourcing website used for survey-based research. Of 1764 individuals screened, 138 reported past year cocaine use. These respondents completed a battery of standardized and experimenter-designed questionnaires used to characterize each respondent's self-reported attitudes, beliefs, and behaviors about drug use and the relative risks and desired monetary compensation associated with research participation. Ratings of relative risk revealed that most respondents found common research practices as less than or equal to the relative risk of everyday life. Receiving experimental medication outside the hospital was rated as the most risky research activity, but on average was not rated as presenting more risk than everyday life. Desired compensation for research participation was associated with the perceived risk of research activities. Increases in desired compensation for participation were only observed for research perceived as much more risky than everyday activities. These findings indicate that cocaine users assess risk in a way that is consistent with standard research practice.


Genomic and phenotypic characterization of Acinetobacter colistiniresistens isolated from the feces of a healthy member of the community.
Acinetobacter species are widely known opportunistic pathogens causing severe community and healthcare-associated infections. One such emerging pathogen, Acinetobacter colistiniresistens, is known to exhibit intrinsic resistance to colistin. We investigated the molecular characteristics of A. colistiniresistens strain C-214, isolated from the fecal sample of a healthy community member, as part of a cohort study being conducted in Segamat, Malaysia. Comparison of the whole genome sequence of C-214 with other A. colistiniresistens sequences retrieved from the NCBI database showed 95% sequence identity or more with many of the genome sequences representing that species. Use of the Galleria mellonella killing assay showed that C-214 was pathogenic in this model infection system. The strain C-214 had a colistin and polymyxin B MIC of 32 and 16 mg/L, respectively. Besides, it was resistant to cefotaxime, amikacin, and tetracycline and showed moderate biofilm-producing ability. Different genes associated with virulence or resistance to major classes of antibiotics were detected. We observed mutations in lpxA/C/D in C-214 and other A. colistiniresistens strains as probable causes of colistin resistance, but the biological effects of these mutations require further investigation. This study provides genomic insights into A. colistiniresistens, a potentially pathogenic bacterium isolated from a community member and notes the public health threat it may pose.


Thalassaemia intermedia.
Most patients homozygous for beta thalassaemia have beta thalassaemia major, a severe illness requiring regular blood transfusions. However, some homozygotes remain well without regular transfusions and are described by the term thalassaemia intermedia. Three factors have now been identified which may result in beta thalassaemia intermedia: the inheritance of mild beta+ thalassaemia mutations, the co-inheritance of alpha thalassaemia and the inheritance of factors enhancing gamma-globin gene expression. In addition other less common genetic interactions also result in thalassaemia intermedia such as the compound heterozygous state for beta and delta beta thalassaemia. These patients need careful clinical follow up, especially since the complications of hypersplenism and iron overload (even in the absence of blood transfusion) can occur.


Problems of diagnoses in family studies.
This paper discusses applications of advances in psychiatric diagnostic practice to genetic research. Diagnostic misclassification and unreliability can lead to spurious conclusions about patterns of familial aggregation and co-aggregation of psychiatric disorders. Subject, occasion, information, observation and criterion variance are the major components of unreliability in diagnosis. Structured diagnostic criteria are useful for reducing errors; they may, however, lead to unjustified confidence due to their algorithmic and semi-quantitative format. Six misconceptions regarding such criteria are discussed. The choice of instruments and method of implementation must take into account the qualifications of interviewers and the need for blindness in the experimental design. A fundamental design decision in psychiatric genetic research is the choice between the family history or family study method. The costs and benefits of each method are examined. Finally, the psychiatric geneticist must face the problem of defining the ill phenotype. This is made difficult by the presence of phenocopies and the possibility that milder spectrum disorders and some symptom-free individuals may carry the genotype that underlies the phenotype of the more severe clinical form of the disorder.


A low angle quasi-elastic light scattering investigation of Chlamydomonas reinhardtii.
This paper outlines the results of the first homodyning low angle scattering experiment known to have been reported for motile particles. Low angle scattering QELS studies were carried out on a wild strain of Chlamydomonas reinhardtii at scattering angles of 3.3 degrees, 2.6 degrees and 1.7 degrees. The resultant experimental autocorrelation functions and scaling curves were compared with a theoretical model that had been successful previously at scattering angles greater than 15 degrees.


The Sleep Side of Aging and Alzheimer's Disease.
As we age, sleep patterns undergo significant modifications in micro and macrostructure, worsening cognition and quality of life. These are associated with remarkable brain changes, like deterioration in synaptic plasticity, gray and white matter, and significant modifications in hormone levels. Sleep alterations are also a core component of mild cognitive impairment (MCI) and Alzheimer's Disease (AD). AD night time is characterized by a gradual decrease in slow-wave activity and a substantial reduction of REM sleep. Sleep abnormalities can accelerate AD pathophysiology, promoting the accumulation of amyloid-β (Aβ) and phosphorylated tau. Thus, interventions that target sleep disturbances in elderly people and MCI patients have been suggested as a possible strategy to prevent or decelerate conversion to dementia. Although cognitive-behavioral therapy and pharmacological medications are still first-line treatments, despite being scarcely effective, new interventions have been proposed, such as sensory stimulation and Noninvasive Brain Stimulation (NiBS). The present review outlines the current state of the art of the relationship between sleep modifications in healthy aging and the neurobiological mechanisms underlying age-related changes. Furthermore, we provide a critical analysis showing how sleep abnormalities influence the prognosis of AD pathology by intensifying Aβ and tau protein accumulation. We discuss potential therapeutic strategies to target sleep disruptions and conclude that there is an urgent need for testing new therapeutic sleep interventions.


Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition.
The absorption of ciprofloxacin was higher when administered through a nasoduodenal tube than through a nasogastric tube, indicating that even though acidic gastric pH is needed for rapid disintegration, dissolved ciprofloxacin might not be stable in the gastric environment. If the length of exposure or the different gastric environment in each individual affects the overall absorption of ciprofloxacin, this could explain the reported variability in ciprofloxacin absorption and suggests the need for the development of an enteric-coated tablet. Further studies are needed to fully characterize the absorption of ciprofloxacin in patients with different illnesses, gastric transit times, gastrointestinal environments and of different ages.


Genome re-arrangements associated with loss of pathogenicity of the gamma-herpesvirus alcelaphine herpesvirus-1.
The alcelaphine herpesvirus 1 (AlHV-1) causes malignant catarrhal fever in ruminants. Previous work had shown that serial passage of AlHV-1 in culture resulted in genome alterations that are associated with a loss in pathogenicity. Here we have analysed the re-arrangements that occur in more detail. None of the observed re-arrangements was entirely consistent. However, they did all involve translocation of a similar region of DNA from around the centre of the genome to areas either next to or in between terminal repeat elements at either end of the genome. There was also a concomitant loss of the wild-type locus. These re-arrangements appeared to be associated with the loss of virulence and the appearance of cell-free virus.


Defective recognition of a nonclassical nuclear localization signal in neurodevelopmental disorders.
In this issue of Structure, Gonzalez et al. present the cryo-EM structure of Karyopherin-β2 bound to the proline-tyrosine nuclear localization signal (PY-NLS) of heterogeneous nuclear ribonucleoprotein H2 (HNRNPH2). The structure advances our understanding of not only the diversity of PY-NLSs but also the pathogenic mechanisms arising from HNRNPH2 variants.


A C-terminal truncated hepatitis C virus core protein variant assembles in vitro into virus-like particles in the absence of structured nucleic acids.
Little is known about the assembly pathway or structure of the hepatitis C virus (HCV). In this work a truncated HCcAg variant covering the first 120 aa (HCcAg.120) with a 32 aa N-terminal fusion peptide (6x Histag-Xpress epitope) was purified as a monomer under strong denaturing conditions. In addition, minor HCcAg.120 peaks exhibiting little different molecular mass by SDS-PAGE which possibly represents alternative forms harboring the N-termini of HCcAg.120 were detected. Analysis using gel filtration chromatography showed that HCcAg.120 assembled into high molecular weight structures in vitro in the absence of structured nucleic acids. The negative-stain electron microscopy analysis revealed that these structures correspond with spherical VLPs of uniform morphology and size distribution. The diameters of these particles ranged from 20 to 43nm with an average diameter of approximately 30 nm and were specifically immunolabelled with a mouse monoclonal antibody against the residues 5-35 of HCcAg. Results presented in this work showed that HCcAg.120 assembled in vitro into VLPs in the absence of structured nucleic acids with similar morphology and size distribution to those found in sera and hepatocytes from HCV-infected patients. Therefore, these VLPs would be important to elucidate the mechanisms behind the ability of HCcAg to assemble into a nucleocapsid structure.


[Cytoreductive, radical prostatectomy in metastatic prostate cancer].
The resection of the primary tumor in patients with metastatic prostate cancer is controversially debated. Retrospective clinical studies indicate survival benefits and prevention of secondary, locoregional complications; however, results of ongoing multicenter prospective studies are still lacking. This review highlights the rationale behind the cytoreductive prostatectomy and summarizes current clinical study results.


A four year experience treating incomplete thoracolumbar spine injuries in an East African country.
Traumatic spine injuries are one of the most common causes of disability and mortality. To assess post op neurologic status in patients with incomplete thoracic and lumbar spine injuries at two teaching hospitals in Addis Ababa, Ethiopia. Institution based retrospective cross-sectional study was conducted among 60 hospitalized patients in these hospitals from February 1, 2017-January 31, 2021. Forty five (75.0%) of the study participants were males. The mean age was 30.77 years (range: 12-65 year). Only 8(13.3%) patients were operated within 3 days of trauma. The most common injury site was the thoracolumbar junction (T11-L2) in 80.0%. Significant number of patients (56.7%) had sphincters dysfunction. Pedicle screw fixation with or without laminectomy was performed in 98.3%. After minimum six month follow up, 37(61.7%) patients had access to the physiotherapy. Thirty seven (61.7%) patients were non ambulatory (AIS B and C) at presentation, of which 29 (78.4%) were ambulatory on the follow-up. Overall, 54(90%) patients had neurologic improvement on the follow up and 37(61.7%) returned to work. Preoperative neurologic status and sphincter function were found to be significantly associated with treatment outcome with P value 0 .000 and 0.002 respectively. This study shows despite limited availability of post op physiotherapy, significant number of patientsreturned to work post-surgery. Preoperative neurologic function was an independent predictor of post-operative outcome.


Dietary adherence in well-controlled feeding studies.
In well-controlled feeding studies, participants are expected to adhere to a strict diet by consuming only and all foods provided by the research kitchen. They may find adherence more of a challenge with certain study design features. To assess this we mailed a post-study anonymous questionnaire to participants who had completed one of eight controlled feeding studies at the Pennington Biomedical Research Center, Baton Rouge, LA. Of the 154 respondents, more than 90% always or usually adhered to the diet. Of those who did not adhere, many deviated fewer than four times. Eating all of the foods provided was a greater challenge than refraining from eating foods not allowed. Diet assignment, the allowance of alcohol, and a self-selected Saturday meal affected adherence. The results of this research may be useful in designing controlled feeding studies. Our data indicate that diet adherence is good, and because deviations are few, they are unlikely to jeopardize study results.


Dynamic Contrast-Enhanced Magnetic Resonance Imaging as Imaging Biomarker for Vascular Normalization Effect of Infigratinib in High-FGFR-Expressing Hepatocellular Carcinoma Xenografts.
Overexpression of fibroblast growth factor receptor (FGFR) contributes to tumorigenesis, metastasis, and poor prognosis of hepatocellular carcinoma (HCC). Infigratinib-a pan-FGFR inhibitor-potently suppresses the growth of high-FGFR-expressing HCCs in part via alteration of the tumor microenvironment and vessel normalization. In this study, we aim to assess the utility of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as a non-invasive imaging technique to detect microenvironment changes associated with infigratinib and sorafenib treatment in high-FGFR-expressing HCC xenografts. Serial DCE-MRIs were performed on 12 nude mice bearing high-FGFR-expressing patient-derived HCC xenografts to quantify tumor microenvironment pre- (day 0) and post-treatment (days 3, 6, 9, and 15) of vehicle, sorafenib, and infigratinib. DCE-MRI data were analyzed using extended generalized kinetic model and two-compartment distributed parameter model. After treatment, immunohistochemistry stains were performed on the harvested tumors to confirm DCE-MRI findings. By treatment day 15, infigratinib induced tumor regression (70 % volume reduction from baseline) while sorafenib induced relative growth arrest (185 % volume increase from baseline versus 694 % volume increase from baseline of control). DCE-MRI analysis revealed different changes in microcirculatory parameters upon exposure to sorafenib versus infigratinib. While sorafenib induced microenvironment changes similar to those of rapidly growing tumors, such as a decrease in blood flow (F), fractional intravascular volume (vp), and permeability surface area product (PS), infigratinib induced the exact opposite changes as early as day 3 after treatment: increase in F, vp, and PS. Our study demonstrated that DCE-MRI is a reliable non-invasive imaging technique to monitor tumor microcirculatory response to FGFR inhibition and VEGF inhibition in high-FGFR-expressing HCC xenografts. Furthermore, the microcirculatory changes from FGFR inhibition manifested early upon treatment initiation and were reliably detected by DCE-MRI, creating possibilities of combinatorial therapy for synergistic effect.


A CRISPR-Based Method for Constructing Conditional Mutations of Essential Genes in Cyanobacteria.
Cyanobacteria, a group of diverse bacteria capable of oxygenic photosynthesis, are excellent models for investigating many important cellular processes, such as photosynthesis, nitrogen fixation, and prokaryotic cell differentiation. They also have great potential to become the next-generation cell factories for sustainable biosynthesis of valuable products. However, genetic manipulation in cyanobacteria is not as convenient as in other model bacteria. Particularly, handling essential genes in cyanobacteria has been difficult due to the lack of appropriate tools, limiting our understanding of many important cellular functions encoded by them. We recently develop a CRISPR-based method for constructing the conditional mutants of cyanobacterial essential genes by engineering the ribosome binding site to a theophylline-responsive riboswitch. Here, we provide the details of this method. The principle of this method could be used to construct conditional mutants in a wide range of bacterial species.


Purification and biochemical properties of Pitton's type 2 beta-lactamase (SHV-1).
A five-step procedure has been developed for purifying Pitton's type 2 plasmid-mediated beta-lactamase (PIT-2, also called SHV-1) from cultures of a hyperproducing variant of an Escherichia coli K12 strain carrying the plasmid p453. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed a single protein band with a molecular weight of about 27,500. The amino acid composition of the protein and the amino acid sequence of the NH2-terminal region have been determined. PIT-2 enzyme contains 272 amino acid residues with 2 cysteines. Studies of the S-carboxymethylated protein (previously reduced or unreduced) suggest that these two residues are presumably in the form of free sulphydryl groups in the native protein. Conversely, TEM-2 beta-lactamase contains 2 cysteine residues which are in the form of a disulphide bond. Comparison of PIT-2 with other beta-lactamases was made using the difference index (DI) of Metzger et al. The PIT-2 enzyme appeared more closely related to the TEM-type penicillinases (DI of 6.5).


Thoracic Spine Pain and Factors Associated in High School Students.
Thoracic spine pain (TSP) is relatively common in children and adolescents. To determine the prevalence of TSP in adolescents and analyze its association with sociodemographic characteristics, use of electronic devices, physical activity, and mental health. Cross-sectional epidemiological study. A high school in Bauru City, São Paulo, Brazil. In total, 1,628 students aged 14-18 years. Participants were selected by cluster sampling in two stages, and data were collected via face-to-face interviews. Data regarding the following were collected: (1) sociodemographic aspects; (2) use of electronic devices; (3) regular physical activity level; (4) mental health; and (5) TSP. The prevalence of TSP was 51.5% (95% confidence interval, 49.1-53.9) and the variables associated with TSP were female participant sex (prevalence ratio [PR] = 1.96; 1.61-2.38), use of computers for >3 hours per day (PR = 1.29; 1.01-1.66), use of computers >3 times per week (PR = 1.35; 1.03-1.75), use of cell phones in a semi-lying position (PR = 1.37; 1.11-1.69), use of cell phones for >3 hours per day (PR = 1.44; 1.12-1.85), use of tablets in the sitting position (PR = 1.47; 1.07-2.01), and presence of mental health problems (PR = 2.10; 1.63-2.70). Physical activity was a protective factor (PR = 0.84; 0.73-0.96). There is a high prevalence of TSP in adolescents, with a marked association with female participant sex, use of electronic devices, and presence of mental health problems Physical activity is a protective factor. Understanding the relationship between risk factors and adolescent spinal pain may be important in both the prevention and treatment of spinal pain in this age group.


Nitrogen fertilization rate affects communities of ammonia-oxidizing archaea and bacteria in paddy soils across different climatic zones of China.
Nitrogen fertilization has important effects on nitrification. However, how the rate of nitrogen fertilization affects nitrification potential, as well as the communities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB), remains unclear. We performed a large-scale investigation of nitrification potential and ammonia-oxidizer communities in Chinese paddy fields at different nitrogen fertilization rates across different climatic zones. It was found that the nitrification potential at the high nitrogen fertilization rate (≥150 kg-1 N ha-1) was 23.35 % higher than that at the intermediate rate (100-150 kg-1 N ha-1) and 20.77 % higher than that at the low rate (< 100 kg-1 N ha-1). The nitrification potential showed no significant variation among different nitrogen fertilization rates across climatic zones. Furthermore, the AOA and AOB amoA gene abundance at the high nitrogen fertilization rate was 481.67 % and 292.74 % higher (p < 0.05) than that at the intermediate rate, respectively. Correlation analysis demonstrated a significant positive correlation between AOB abundance and nitrification potential. AOA and AOB community composition differed significantly among nitrogen fertilization rates. Moreover, soil NH4+ content, pH, water content, bulk density, and annual average temperature were regarded as key environmental factors influencing the community structure of ammonia-oxidizers. Taken together, the nitrogen fertilization rate had a significant impact on the communities of AOA and AOB but did not significantly alter the nitrification potential. Our findings provide new insights into the impact of nitrogen fertilization management on nitrification in rice paddy fields.


BCL6 represses CHEK1 and suppresses DNA damage pathways in normal and malignant B-cells.
BCL6 is a transcriptional repressor protein that is expressed in a developmentally regulated fashion during B-cell maturation. Specifically, BCL6 is required for formation of germinal centers in response to T-cell dependent antigen activation. Germinal center B-cells feature the ability to tolerate rapid proliferation and simultaneous genetic recombination. Genetic lesions that cause constitutive expression of BCL6 are commonly associated with diffuse large B-cell lymphomas (DLBCL). Recent studies show that BCL6 contributes to the germinal center phenotype by directly repressing genes involved in sensing or responding to DNA damage including ATR, TP53 and CDKN1A. The CHEK1 protein is activated through phosphorylation by the ATR kinase domain in response to DNA damage. Activated CHEK1 can phosphorylate and modulate the activity a number of proteins including p53, providing a link between ATR sensing of DNA damage and p53 checkpoint activity. Herein we show that BCL6 can directly bind to a DNA consensus element in the CHEK1 promoter and repress its expression in normal and malignant B-cells. DLBCL cells can be killed by a specific BCL6 peptide inhibitor (BPI) that interferes with corepressor binding to the BCL6 BTB domain. BPI could reactivate CHEK1 in DLBCL cells, suggesting that its induction might contribute to BPI anti-lymphoma effects. Therefore, BCL6 can suppress multiple genes involved in a common pathway sensing, transducing and responding to genotoxic stress.


Quantifying fractionation and rate in human atrial fibrillation using monophasic action potentials: implications for substrate mapping.
To use monophasic action potentials (MAPs) to better assess the rate and the presence of fractionated electrograms during the mapping of atrial fibrillation (AF). Substrate mapping is increasingly central to AF ablation. However, traditional bipolar signals poorly represent waveform shape, making it unclear whether fractionation reflects local waveform variations, true electrogram fragmentation, or noise, and raising issues on whether their spectral dominant frequencies (DFs) accurately estimate AF rate. In 28 patients with paroxysmal or persistent AF (left atrial diameters 44 +/- 8 mm), we studied 49 epochs of right atrial MAPs during AF. We compared fractionation, spectral and time-domain AF rate estimates using MAPs and bipolar electrograms obtained by filtering the MAPs. Fractionation was overestimated in bipolar rather than MAP electrograms (P = 0.005) and often reflected artefacts on the MAPs. Conversely, local waveform variability in the MAPs, including alternans or fractionation, was often uniform in the bipolar electrograms. The measured AF cycle length (CL) was accurately represented by the DF of the MAPs (r = 0.73, P < 0.001) but, due to double counting, not by the DF of bipolar signals (r = 0.29, P = 0.07). Spectral CL estimates were therefore accurate (< or = 20 ms from measured CL) for 77% of MAPs but for 45% of bipolar signals only. A novel autocorrelation method better estimated CL in MAPs (r = 0.92; P < 0.001) and bipoles (r = 0.82; P < 0.001), with 89 and 77% accuracy, respectively (P < 0.01). Atrial fibrillation organization and rate are better represented by MAPs, which portray fibrillatory waveform shape, than by bipolar recordings. This approach may more reliably portray electrogram variability, fragmentation, and rate for the mapping of AF substrates.


Set-up and validation of an adsorptive stripping voltammetric method for kynurenic acid determination in human urine.
Validation of an adsorptive stripping voltammetric method for kynurenic acid determination in urine, was presented. The selection of appropriate validation parameters, the design consideration for evaluation and the problem of endogenous metabolites were discussed. The considered fundamental criteria for assessing the reliability and overall performance of the method in the urine matrix were selectivity, linearity and range, limit of quantitation, accuracy, precision and analyte stability. The intermediate precision was also evaluated by means of a full factorial design. An HPLC method with fluorimetric detection was used as a reference method to assess the accuracy. The analysis in urine required a pH control as pointed out by robustness testing and the found kynurenic acid concentration in daily urine ranged from 5 to 40 microM.


Programmable cells of monocytic origin (PCMO): a source of peripheral blood stem cells that generate collagen type II-producing chondrocytes.
The focus of this study was a new adult pluripotent cell derived from human peripheral blood monocytes identified as a "programmable cell of monocytic origin" (PCMO). In contrast to bone marrow-derived stem cells, these cells can be harvested from peripheral venous blood without aspiration of the bone marrow and have multilineage potential comparable to that of mesenchymal stem cells (MSC). The aim of this study was to evaluate the potential of PCMOs to differentiate into collagen type II-producing chondrocytes using various extrinsic cues (TGFbeta-1, IGF-1, BMP-2, and BMP-7). Collagen type I and II proteins were localized using immunohistochemistry and quantified by enzyme-linked immunosorbent assays (ELISA). The shape of the differentiating PCMOs was monitored with electron microscopy. Collagen type I and II messenger RNA expression was analyzed using real-time reverse transcriptase-polymerase chain reaction (RT PCR) and regular RT PCR. Immunohistochemistry revealed a strong accumulation of collagen type II after a 6-week incubation period with BMP-2, BMP-7, TGF-beta, IGF-I, and TGF-beta, and IGF-1. Collagen type I was only mildly induced by the applied stimulants. Electron microscopy findings showed a shift from a monocyte-like structure to a chondrocyte-like structure after 2 weeks of stimulation. Stimulation of PCMOs with BMP-2, BMP-7, TGF-beta, IGF-I, and TGF-beta, and IGF-1 induced a chondrogenic differentiation with continuous expression of collagen type II mRNA and protein over several weeks time. Collagen type I and II expression in undifferentiated PCMOs or in control cells incubated without any stimulant was not detected. PCMOs have the potential to differentiate into collagen type II synthesizing chondrocytes. The ability to reprogram and differentiate PCMOs from peripheral blood into sizable quantities might enable their clinical application in cartilage repair after mechanical injury or in cases of osteoarthritis.


Immune proteins, enzymes and electrolytes in human peripheral lymph.
Values of various biochemical constituents of leg lymph in 27 normal men have been presented. Concentration of immunoglobulins, complement proteins, acute phase reactants, enzymes, electrolytes and other small molecular weight substances were measured.


Catehol-o-methyltransferase gene Val158met polymorphism as a potential predictor of response to computer-assisted delivery of cognitive-behavioral therapy among cocaine-dependent individuals: Preliminary findings from a randomized controlled trial.
Findings from uncontrolled studies suggest that the COMT Val108/158Met polymorphism may affect response to cognitive behavioral therapy (CBT) in some populations. Using data from a randomized controlled trial evaluating computerized CBT (CBT4CBT), we evaluated treatment response by COMT genotype, with the a priori hypothesis that Val carriers would have improved response to computerized delivery of CBT. 101 cocaine-dependent individuals, of whom 81 contributed analyzable genetic samples, were randomized to standard methadone maintenance treatment plus CBT4CBT or standard treatment alone in an 8 week trial. There was a significant genotype by time effect on frequency of cocaine use from baseline to the end of the 6 month follow-up, suggesting greater reductions over time for Val carriers relative to individuals with the Met/Met genotype. There was a significant treatment condition by genotype interactions for rates of participants attaining 21 or more days of continuous abstinence as well as self-reported percent days of abstinence, suggesting less cocaine use among Val carriers when assigned to CBT compared to standard treatment. Exploration of possible mechanisms using measures of attentional biased also pointed to greater change over time in these measures among the Val carriers assigned to CBT. These are the first data from a randomized controlled trial indicating significant interactions of COMT polymorphism and behavioral therapy condition on treatment outcome, where Val carriers appeared to respond particularly well to computerized CBT. These preliminary data point to a potential biomarker of response to CBT linked to its putative mechanism of action, enhanced cognitive control.


Male size, mating success, and breeding habitat partitioning in the whitespotted sawyer Monochamus scutellatus (Say) (Coleoptera: Cerambycidae).
The whitespotted swayer Monochamus scutellatus (Say) (Coleoptera: Cerambycidae) breeds in recently killed conifers in northeastern North America, especially white pine Pinus strobus L. We cut down 4 white pines in Pocahontas County, West Virginia, in June 1981, in order to study the behavior of sawyers attracted to the trees. Far greater numbers of both male and female sawyers were attracted to the largest of the trees cut. At all trees, females preferred the parts of the tree of greater circumference. These preferences may be related to greater larval survival in large-circumference regions. Male and female numbers at breeding site peaked at about 1200-1500 h EST; at this time, males generally outnumbered females by about 2:1. We placed males in 3 size classes: L (>2.0 cm), M (≦2.0 cm, ≧1.8 cm), and S (<1.8 cm). At the largest of our 4 trees, L males disproportionately frequented the portion of the trunk preferred by females. L males were far more successful than M and S males in mating and in agonistic encounters with other males. L males were thus apparently able to exclude smaller males from the preferred region to some extent.


The added value of (1,3)-β-D-glucan for the diagnosis of Invasive Candidiasis in ICU patients: a prospective cohort study.
Beta-D-Glucan (BDG) testing has been suggested to support the diagnosis of candidemia and invasive candidiasis. The actual benefit in critically ill high-risk patients in intensive care units (ICU) has not been verified so far. In ICU patients receiving empirical echinocandin treatment for suspected invasive candidiasis (IC), serial BDG testing using the Fujifilm Wako Beta-Glucan Test was performed, starting on the first day of echinocandin administration and every 24-48 h afterwards. Diagnostic accuracy was determined for single testing and serial testing strategies using a range of cut-off values. In addition, we compared the added value of these testing strategies when their results were introduced as additional predictors into a multivariable logistic regression model controlling for established risk factors of IC. A total of 174 ICU patients, forty-six of which (25.7%) classified as cases of IC, were included in our study. Initial BDG testing showed moderate sensitivity (74%, 95%CI 59-86%) and poor specificity (45%, 95% CI 36-54%) for IC which could hardly be improved by follow-up testing. While raw BDG values or test results obtained with very high thresholds improved the predictive performance of our multivariable logistic regression model for IC, neither single nor serial testing with the manufacturer-proposed low-level cut-off showed substantial benefit. In our study of critically ill intensive care patients at high risk for candidemia or invasive candidiasis, diagnostic accuracy of BDG testing was insufficient to inform treatment decisions. Improved classification was only achieved for cases with very high BDG values.


Estimation of temperature dependent parameters of a batch alcoholic fermentation process.
In this work, a procedure was established to develop a mathematical model considering the effect of temperature on reaction kinetics. Experiments were performed in batch mode in temperatures from 30 to 38 degrees C. The microorganism used was Saccharomyces cerevisiae and the culture media, sugarcane molasses. The objective is to assess the difficulty in updating the kinetic parameters when there are changes in fermentation conditions. We conclude that, although the re-estimation is a time-consuming task, it is possible to accurately describe the process when there are changes in raw material composition if a re-estimation of parameters is performed.


Identifying Gene Interaction Networks.
In this chapter, we introduce interaction networks by describing how they are generated, where they are stored, and how they are shared. We focus on publicly available interaction networks and describe a simple way of utilizing these resources. This chapter features two case studies, both of which utilize Cytoscape, an open source and user-friendly network visualization and analysis tool. In the first example, we demonstrate the basic functionalities of Cytoscape by building an interaction network from a publicly available database, analyzing its topological features, and performing gene ontology enrichment. For the second section, we constructed a network from scratch starting with an experimental gene expression dataset. From there, we implement more advanced visual annotations of the network and perform subnetwork enrichment. The methods described are applicable to larger networks that can be collected from various resources.


Rietveld refinement of AgCa10(PO4)7 from X-ray powder data.
Polycrystalline silver(I) deca-calcium heptakis(orthophos-phate), AgCa10(PO4)7, was obtained by solid-state reaction. It is isotopic with members of the series MCa10(PO4)7 (M = Li, Na, K and Cs), and is closely related to the structure of β-Ca3(PO4)2. The crystal structure of the title compound is built up from a framework of [CaO9] and two [CaO8] polyhedra, one [CaO6] octa-hedron (site symmetry 3.) and three PO4 tetra-hedra (one with site symmetry 3.). The Ag(+) cation is likewise located on a threefold rotation axis and resides in the cavities of the rigid [Ca10(PO4)7](-) framework. It is surrounded by three O atoms in an almost regular triangular environment.


Prognostic indicators of persistent carotid intima-media thickness increase in postpartum period in a population of normotensive women with gestational diabetes mellitus.
The association between gestational diabetes mellitus (GDM) and common carotid artery (CCA)-intima media thickness (IMT) is still controversial. In the present study, we aimed to compare the CCA-IMT measured in GDM women to that obtained in healthy pregnant women in the third trimester of pregnancy. Secondly, we investigated the main independent predictors of persistent CCA-IMT increase (defined as CCA-IMT ≥ 0.6 mm) in postpartum period in GDM women. 30 consecutive GDM women and 30 healthy pregnant women matched for anagraphic age (34.1 ± 4.5 vs 32.8 ± 4.2 yrs, p = 0.25), ethnicity (caucasian 56.7 vs 63.3%, p = 0.59), gestational age (36.2 ± 1.7 vs 36.5 ± 1.6 weeks, p = 0.48) and cardiovascular risk factors were examined in this prospective case-control study. All women underwent obstetric visit, blood tests, conventional transthoracic echocardiography implemented with two-dimensional speckle tracking echocardiography analysis of left ventricular and left atrial myocardial strain parameters and carotid ultrasound examination at two time points: 36-38 weeks' gestation and 6-10 weeks after delivery. At 36.2 ± 1.7 weeks of gestation, CCA-IMT was significantly increased in GDM women than controls (0.81 ± 0.11 vs 0.55 ± 0.12, p < 0.001). Twelve GDM women (40% of the total) were found with persistent CCA-IMT increase (0.76 ± 0.14 mm) in postpartum period (8.2 ± 2.2 weeks), whereas the remaining 18 (60% of the total) showed a normalization in CCA-IMT (0.56 ± 0.1 mm). At multivariate logistic regression analysis, third trimester body mass index (BMI) (OR 1.78, 95%CI 1.24-2.54, p = 0.01), glycosylated hemoglobin (HbA1C) (OR 1.51, 95%CI 1.13-1.89, p = 0.03) and neutrophil-to-lymphocyte ratio (NLR) (OR 1.68, 95%CI 1.25-4.65, p = 0.02) resulted to be independently associated with persistent CCA-IMT increase in postpartum period in GDM women. A BMI ≥ 29.2 Kg/m2, an HbA1C ≥ 37.5 mmol/mol and a NLR ≥ 5.5 were the best cut-off values for identifying GDM women with persistent CCA-IMT increase in postpartum period. GDM is associated with increased CCA-IMT during pregnancy. This increase may be persistent in postpartum period in GDM women with obesity, uncontrolled diabetes and increased inflammatory markers.


The substituent effect on nonlinear current voltage characteristics in a two-terminal molecular electronic device.
We present a quantum mechanical tunneling model for electron transport through a molecular junction and address the model with the results of quantum chemical electronic structure calculations. The model gives insight into the origin of the substituent effect on the current versus applied voltage characteristics of molecular junctions.


Identifying the independent effect of HbA1c variability on adverse health outcomes in patients with Type 2 diabetes.
To characterize the relationship between HbA1c variability and adverse health outcomes among US military veterans with Type 2 diabetes. This retrospective cohort study used Veterans Affairs and Medicare claims for veterans with Type 2 diabetes taking metformin who initiated a second diabetes medication (n = 50 861). The main exposure of interest was HbA1c variability during a 3-year baseline period. HbA1c variability, categorized into quartiles, was defined as standard deviation, coefficient of variation and adjusted standard deviation, which accounted for the number and mean number of days between HbA1c tests. Cox proportional hazard models predicted mortality, hospitalization for ambulatory care-sensitive conditions, and myocardial infarction or stroke and were controlled for mean HbA1c levels and the direction of change in HbA1c levels during the baseline period. Over a mean 3.3 years of follow-up, all HbA1c variability measures significantly predicted each outcome. Using the adjusted standard deviation measure for HbA1c variability, the hazard ratios for the third and fourth quartile predicting mortality were 1.14 (95% CI 1.04, 1.25) and 1.42 (95% CI 1.28, 1.58), for myocardial infarction and stroke they were 1.25 (95% CI 1.10, 1.41) and 1.23 (95% CI 1.07, 1.42) and for ambulatory-care sensitive condition hospitalization they were 1.10 (95% CI 1.03, 1.18) and 1.11 (95% CI 1.03, 1.20). Higher baseline HbA1c levels independently predicted the likelihood of each outcome. In veterans with Type 2 diabetes, greater HbA1c variability was associated with an increased risk of adverse long-term outcomes, independently of HbA1c levels and direction of change. Limiting HbA1c fluctuations over time may reduce complications.


Mapping the matrix: the ways of neocortex.
While we know that the neocortex occupies 85% of our brains and that its circuits allow an enormous flexibility and repertoire of behavior (not to mention unexplained phenomena like consciousness), a century after Cajal we have very little knowledge of the details of the cortical circuits or their mode of function. One simplifying hypothesis that has existed since Cajal is that the neocortex consists of repeated copies of the same fundamental circuit. However, finding that fundamental circuit has proved elusive, although partial drafts of a "canonical circuit" appear in many different guises of structure and function. Here, we review some critical stages in the history of this quest. In doing so, we consider the style of cortical computation in relation to the neuronal machinery that supports it. We conclude that the structure and function of cortex honors two major computational principles: "just-enough" and "just-in-time."


Submandibular space infection: a potentially lethal infection.
The aims of this study were to review the clinical characteristics and management of submandibular space infections and to identify the predisposing factors of life-threatening complications. This was a retrospective study at a tertiary academic center. We retrieved and evaluated the records of all patients admitted to the University of Padua Otolaryngology Clinic at Treviso Regional Hospital with the diagnosis of submandibular space infection for the period 1998-2006. The following variables were reviewed: demographic data, pathogenesis, clinical presentation, associated systemic diseases, bacteriology, imaging studies, medical and surgical treatment, and complications. A multivariate logistic regression analysis was undertaken using a forward stepwise technique. Multivariate analysis identified four risk factors for complications. Anterior visceral space involvement (odds ratio (OR) 54.44; 95% confidence interval (CI) 5.80-511.22) and diabetes mellitus (OR 17.46; 95% CI 2.10-145.29) were the most important predictive factors in the model. Logistic regression analysis also confirmed other comorbidities (OR 11.66; 95% CI 1.35-100.10) and bilateral submandibular swelling (OR 10.67; 95% CI 2.73-41.75) as independent predictors for life-threatening complications. Airway obstruction and spread of the infection to the mediastinum are the most troublesome complications of submandibular space infections. Therefore, the maintenance of a secure airway is paramount. Patients with cellulitis and small abscesses can respond to antibiotics alone. Surgical drainage should be performed in patients with larger abscesses, Ludwig's angina, anterior visceral space involvement, and in those who do not respond to antibiotic treatment. Moreover, the clinical assessment in patients with comorbidities, especially diabetes mellitus, requires a high level of suspicion for potential life-threatening complications. Early surgical drainage should always be considered in these patients, even in seemingly less critical cases.


Development of large-scale functional networks over the lifespan.
The development of large-scale functional organization of the human brain across the lifespan is not well understood. Here we used magnetoencephalographic recordings of 53 adults (ages 18-89) to characterize functional brain networks in the resting state. Slow frequencies engage larger networks than higher frequencies and show different development over the lifespan. Networks in the delta (2-4 Hz) frequency range decrease, while networks in the beta/gamma frequency range (> 16 Hz) increase in size with advancing age. Results show that the right frontal lobe and the temporal areas in both hemispheres are important relay stations in the expanding high-frequency networks. Neuropsychological tests confirmed the tendency of cognitive decline with older age. The decrease in visual memory and visuoconstructive functions was strongly associated with the age-dependent enhancement of functional connectivity in both temporal lobes. Using functional network analysis this study elucidates important neuronal principles underlying age-related cognitive decline paving mental deterioration in senescence.


Ocular manifestations of endemic syphilis (bejel).
Bejel or nonvenereal syphilis is a treponemal infection that is still endemic in many parts of the world including Saudi Arabia. The authors have examined 17 patients with clinical findings consistent with bejel. All patients had positive serologic tests for bejel. There were 11 male and six female patients, with a mean age of 54 years (range, 37-73 years). Results of clinical examination showed uveitis in nine patients, optic atrophy in six, and chorioretinitis scars in six. In four patients who needed intraocular surgery, two aqueous specimens showed positive antibodies for Treponema pallidum.


Bone disease in β thalassemia patients: past, present and future perspectives.
Bone disorders in patients with thalassemia major (TM) and intermedia (TI) constitute complex conditions that result from various factors affecting the growing skeleton. Although much progress has been made in our understanding of the natural history, pathogenesis and clinical manifestations of β- and δβ-thalassemia, bone manifestations remain a puzzle for the clinician. In this review, we outline the key points in the current literature on the pathogenesis and management of bone disease in patients with TM and TI who were conventionally treated in recent decades with frequent blood transfusions and iron chelation. Prevention, early recognition and treatment are the most effective strategies for the management of bone disease in these patients. However, further studies are required to maintain optimal bone health for both TM and TI patients. Studying bone disease in patients with non-transfusion dependent TI, which seems to worsen considerably with age, is important to delineate the effect of the disease itself on bone health without the intervening factors of transfusions, iron intoxication and chelation.


Methylenetetrahydrofolate reductase and reduced folate carrier-1 genotypes and methotrexate serum concentrations in patients with rheumatoid arthritis.
We investigated the genotypes of methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier-1 (RFC-1), and the serum concentrations of methotrexate (MTX) in 100 outpatients with rheumatoid arthritis (RA). Frequencies of MTHFR C677T and A1298C were similar to those reported in Japanese RA patients, while frequencies of RFC-1 G80A genotypes differed from those reported in RA patients in the United States. No correlations were found between these genotypes and serum MTX levels.


Functional Independence and Difficulty Scale: Instrument development and validity evaluation.
To validate the Functional Independence and Difficulty Scale, a new instrument that assesses both independence and difficulty in carrying out basic activities of daily living. First, we developed an item list for our construct through a literature review. Second, an expert panel evaluated the item list using the modified Delphi method. Third, to evaluate psychometric properties, a random sample of 593 community-dwelling older adults aged ≥ 65 years from Shiki City, Japan, was surveyed by mail. We developed an instrument comprising 14 items: getting up from bed, standing up from a chair, standing up from the floor, dressing, putting on pants, eating, cleaning after toileting, washing, brushing teeth, opening a PET bottle, cutting toenails, walking inside, walking outside and going up or down four to six steps. Function scores for basic activities of daily living ranged from 14-42, with higher scores representing better function. Internal consistency was acceptable (Cronbach's alpha = 0.92). Spearman's partial correlation coefficients controlled for sex and age between the new assessment tool, and the Katz Index and Tokyo Metropolitan Institute of Gerontology Index of Competence were 0.81 (P < 0.01) and 0.63 (P < 0.01), respectively. This new tool for assessment of the basic activities of daily living showed good internal consistency and validity. This assessment tool might be applicable in research and clinical practice to evaluate the basic activities of daily living of community-dwelling elderly Japanese people. Geriatr Gerontol Int 2016; 16: 1127-1137.


Effects of prostaglandin F2α (PGF2α) on cell-death pathways in the bovine corpus luteum (CL).
Prostaglandin F2α (PGF2α) may differentially affect viability of luteal cells by inducing either proliferation or cell death (via apoptosis or necroptosis). The diverse effects of PGF2α may depend on its local vs. systemic actions. In our study, we determined changes in expression of genes related to: (i) apoptosis: caspase (CASP) 3, CASP8, BCL2 associated X (BAX), B-cell lymphoma 2 (BCL2) and (ii) necroptosis: receptor-interacting protein kinase (RIPK) 1, RIPK3, cylindromatosis (CYLD), and mixed lineage kinase domain-like (MLKL) in the early and mid-stage corpus luteum (CL) that accompany local (intra-CL) vs. systemic (i.m.) analogue of PGF2α (aPGF2α) actions. Cows at day 4 (n = 24) or day 10 (n = 24) of the estrous cycle were treated by injections as follows: (1) systemic saline, (2) systemic aPGF2α (25 mg; Dinoprost), (3) local saline, (4) local aPGF2α (2.5 mg; Dinoprost). After 4 h, CLs were collected by ovariectomy. Expression levels of mRNA and protein were investigated by RT-q PCR, Western blotting and immunohistochemistry, respectively. We found that local and systemic administration of aPGF2α in the early-stage CL resulted in decreased expression of CASP3 (P < 0.01), but CASP8 mRNA expression was up-regulated (P < 0.05). However, the expression of CASP3 was up-regulated after local aPGF2α treatment in the middle-stage CL, whereas systemic aPGF2α administration increased both CASP3 and CASP8 expression (P < 0.01). Moreover, we observed that both local and systemic aPGF2α injections increased RIPK1, RIPK3 and MLKL expression in the middle-stage CL (P < 0.05) while CYLD expression was markedly higher after i.m. aPGF2α injections (P < 0.001). Moreover, we investigated the localization of necroptotic factors (RIPK1, RIPK3, CYLD and MLKL) in bovine CL tissue after local and systemic aPGF2α injections in the bovine CL. Our results demonstrated for the first time that genes related to cell death pathways exhibit stage-specific responses to PGF2α administration depending on its local or systemic actions. Locally-acting PGF2α plays a luteoprotective role by inhibiting apoptosis and necroptosis in the early CL. Necroptosis is a potent mechanism responsible for structural CL regression during PGF2α-induced luteolysis in cattle.


Control of protein synthesis and mRNA degradation by microRNAs.
MicroRNAs represent a large family of non-coding small RNAs that function as the major endogenous triggers for RNA interference. Hundreds of microRNAs have been identified through small RNA cloning, bioinformatic predictions, and high-throughput pyrosequencing. They are believed to suppress gene expression through post-transcriptional regulation via either translational repression or mRNA turnover. Over one third of human genes are predicted targets for microRNAs. However, even after extensive studies, the function of microRNAs and the precise mechanism by which they suppress gene expression remain elusive. Although controversy remains, recent advances have shined new light on how microRNAs regulate their targets. A better understanding of the mechanism should facilitate studies of their function.


Minimizing shrinkage of acute brain slices using metal spacers during histological embedding.
The morphological structure of neurons provides the basis for their functions and is a major focus of contemporary neuroscience studies. Intracellular staining of single cells in acute slices is a well-established approach, offering high-resolution information on neuronal morphology, complementing their physiology. Despite major technical advances, however, a common histological artifact often precludes precise morphological analysis: shrinkage of the sampled tissue after embedding for microscopy. Here, we describe a new approach using a metal spacer, sandwiched between two coverslips to reduce shrinkage of whole-mount slice preparations during embedding with aqueous mounting medium under a coverslip. This approach additionally allows imaging the slices from both sides to obtain better quality images of deeper structures. We demonstrate that the use of this spacer system can efficiently and stably reduce the shrinkage of slices, whereas conventional embedding methods without spacer or with agar spacer cause severe, progressive shrinkage after embedding. We further show that the shrinkage of slices is not uniform and artifacts in morphology and anatomical parameters produced cannot be compensated using linear correction algorithms. Our study, thus, emphasizes the importance of preventing the deformation of slice preparations and offers an effective means for reducing shrinkage and associated artifacts during embedding.


First-admission rates of schizophrenia in Denmark, 1980-1997: have they been increasing?
Studies have revealed a decrease in the treated incidence of schizophrenia up to 1990. The reasons remain open to question. The authors examined first-admission rates of schizophrenia during the 1990s in Denmark. The results showed a significant increase in first-admission rates of both sexes. Apparently, the shift of diagnostic classification system in 1994 from ICD-8 to ICD-10 did not explain the increase as a whole, nor did the changing number of psychiatric beds during the decades.


Dual-modal computer-assisted evaluation of axillary lymph node metastasis in breast cancer patients on both real-time elastography and B-mode ultrasound.
To propose a computer-assisted method for quantifying the hardness of an axillary lymph node on real-time elastography (RTE) and its morphology on B-mode ultrasound; and to combine the dual-modal features for differentiation of metastatic and benign axillary lymph nodes in breast cancer patients. A total of 161 axillary lymph nodes (benign, n=69; metastatic, n=92) from 158 patients with breast cancer were examined with both B-mode ultrasound and RTE. With computer assistance, five morphological features describing the hilum, size, shape, and echogenic uniformity of a lymph node were extracted from B-mode, and three hardness features were extracted from RTE. Single-modal and dual-modal features were used to classify benign and metastatic nodes with two computerized classification approaches, i.e., a scoring approach and a support vector machine (SVM) approach. The computerized approaches were also compared with a visual evaluation approach. All features exhibited significant differences between benign and metastatic nodes (p<0.001), with the highest area under the receiver operating characteristic curve (AUC) of 0.803 and the highest accuracy (ACC) of 75.2% for a single feature. The SVM on dual-modal features achieved the largest AUC (0.895) and ACC (85.7%) among all methods, exceeding the scoring (AUC=0.881; ACC=83.6%) and the visual evaluation methods (AUC=0.830; ACC=84.5%). With the leave-one-out cross validation, the SVM on dual-modal features still obtained an ACC as high as 84.5%. Dual-modal features can be extracted from RTE and B-mode ultrasound with computer assistance, which are valuable for discrimination between benign and metastatic lymph nodes. The SVM on dual-modal features outperforms the scoring and visual evaluation methods, as well as all methods using single-modal features. The computer-assisted dual-modal evaluation of lymph nodes could be potentially used in daily clinical practice for assessing axillary metastasis in breast cancer patients.


Distribution of ocular biometric parameters and refraction in a population-based study of Australian children.
To study the distribution of spherical equivalent refraction and ocular biometric parameters in a young Australian population. Noncontact methods were used to examine ocular dimensions and cycloplegic autorefraction in a stratified random cluster sample of year 1 Sydney school students (n = 1765), mean age 6.7 years (range, 5.5-8.4 years). Repeated measures of axial length, anterior chamber depth, and greatest and least corneal radius of curvature (CR1, CR2, respectively) were taken in each eye. Refraction was measured as the spherical equivalent. Mean spherical equivalent refraction in right eyes was +1.26 +/- 0.03 D (SEM; range, -4.88 to +8.58). The distribution was peaked (kurtosis 14.4) and slightly skewed to the right (skewness, 1.7). Prevalence of myopia, defined as spherical equivalent refraction < or = -0.5 D, was 1.43% (95% CI, 0.94-2.18) in the overall population. Axial length, anterior chamber depth, and corneal radii of curvature were normally distributed. The mean axial length in right eyes was 22.61 +/- 0.02 mm (SEM; range, 19.64-25.35). The mean anterior chamber depth was 3.34 +/- 0.01 mm (SEM; range, 2.14-4.06). Mean CR1 was 7.85 +/- 0.01 mm (SEM) and mean CR2 was 7.71 +/- 0.01 mm (SEM). The distribution of axial length/mean corneal radius ratio was peaked (leptokurtic) with a mean of 2.906. Mean axial length was longer, anterior chambers were deeper, and corneas were flatter in the boys. A peaked (leptokurtic) distribution of spherical equivalent refraction was present in this predominantly hyperopic 6-year-old population. The results also showed that ocular biometric measures were normally distributed, with statistically significant gender differences found in measurements.


Detection of human parvovirus B19 infection in first-trimester fetal loss.
To investigate the frequency of parvovirus B19 infection in first-trimester fetal loss, as measured by B19 DNA polymerase chain reaction in placental tissue in a prospective descriptive study from a nonendemic area. Placental tissues from first-trimester fetal losses were examined for presence of B19 DNA by polymerase chain reaction in a prospective study during 30 months. For comparison, placental tissues from second-trimester fetal losses, as well as from full-term normal pregnancies, were also studied. B19 DNA was detected by polymerase chain reaction in one of 36 (3%) placental tissues from first-trimester fetal losses. In second-trimester fetal losses, eight of 64 (12%) samples were B19 DNA positive. None of the 53 placental tissues from full-term normal pregnancies were B19 DNA positive. In first-trimester fetal losses, maternal serum from the B19 DNA-positive sample was B19 immunoglobulin (Ig)G positive but B19 IgM negative. In second-trimester fetal losses, six of six tested B19 DNA-positive samples were both B19 IgG and IgM positive. The frequency of first-trimester fetal loss associated with parvovirus B19 infection was low, 3%, during a nonepidemic period in Sweden, as measured by B19 DNA-specific polymerase chain reaction in placental tissue.


Effect of carbohydrate intake on kidney function and structure in SHR/N-cp rats. A new model of NIDDM.
The SHR/N corpulent (cp) rat is a genetically obese rat that develops hyperglycemia, hyperinsulinemia, and proteinuria. This study was designed to evaluate the effects of high carbohydrate (CHO) intake on renal function and structure in this animal model and to determine whether the renal effects are related to the type of CHO ingested. Two groups of 5-wk-old obese male SHR/N-cp rats and lean male littermates were fed diets containing 54% CHO in the form of sucrose or starch. After 12 wk, renal function parameters, including creatinine clearance, urinary glucose excretion, and urinary protein excretion, were measured. Renal morphology was evaluated by semiquantitative light and electron microscopy. On either diet, obese rats had significantly higher urinary glucose and protein excretions than their lean littermates. Mean creatinine clearance (ml/min) in obese rats did not differ significantly from values observed in lean rats. When corrected for body weight, creatinine clearance (ml.min-1.kg-1) tended to be lower in obese than in lean rats, but the difference was significant (P less than .02) only for obese and lean sucrose-fed animals. Obese rats fed sucrose compared with their obese counterparts fed starch had higher body weight (+8%, P less than .05), glucose excretion (+63%, P less than .02), and protein excretion (+242%, P less than .005). In obese rats, protein excretion correlated with glucose excretion (r = .71, P less than .01). Glomerular lesions consisting of mesangial expansion and intercapillary nodules were found in obese but not in lean rats. Moreover, obese rats fed sucrose had a significantly greater number of involved glomeruli than obese rats fed starch.(ABSTRACT TRUNCATED AT 250 WORDS)


Histiocytosis and bone: experience from one major Sydney teaching hospital.
Langerhans cell histiocytosis (LCH) has diverse presentations which can bring it before all physicians regardless of specialty. A retrospective audit was undertaken at Westmead Hospital, Sydney, Australia, to ascertain the incidence, epidemiology and clinical features of patients with LCH over a 10-year period (1994-2004). A total of 12 patients was identified (six male, six female). Eleven patients had involvement of the skeletal system, three of the patients had pulmonary LCH and only one patient presented with soft tissue involvement (nose and antrum). Three patients had diabetes insipidus. Our results are consistent with that noted in the published literature and confirm the low incidence, diverse nature of presentation and the differing treatment strategies available for this rare and yet interesting condition.


[Importance of the study of cephalometric values in a patient with Melnick-Needles syndrome (clinical case)].
The Authors exposed cephalometric analysis in a patient with Melnick and Needles syndrome. Craniomaxillary, maxillofacial, dentomaxillary, skeleton and soft tissue spatial ratio have been evalued.


Bone mineral density in women with type II diabetes mellitus.
Bone mineral density (BMD) was assessed in 28 women with type II diabetes mellitus and compared to 207 age-matched nondiabetic women. Mean BMD, as measured by dual-photon absorptiometry, 1.12 +/- 0.3 g/cm2 (+/- SEM), was similar to the mean BMD of control subjects, 1.06 +/- 0.1 g/cm2. Only 1 of the 28 diabetic patients had a BMD less than 0.95 g/cm2 ("fracture threshold"), whereas 25% of the control subjects had a BMD below that level. When diabetic and control subjects were matched for weight as well as age, the data continued to show similar BMD among both groups. Moreover, the disparity between the proportion of weight-matched controls (25%) and diabetic subjects (1 of 28) with a BMD below the fracture threshold persisted. Among the group of 17 diabetic subjects receiving insulin, there was a positive relationship between BMD and insulin dose. There was no significant relationship between BMD, duration of diabetes, or hemoglobin Alc. Thus, women with type II diabetes are not at increased risk for diminished BMD and may be protected against bone loss.


Coping and health service utilisation in a UK study of paediatric sickle cell pain.
To assess sickle cell pain and coping in children and to examine the relation between these factors and the utilisation of health services. Cross sectional study involving 67 children with sickle cell disease attending three London hospitals. Interviews and questionnaires involved measures of pain, health service utilisation, and coping responses (measured with the Coping Strategies Questionnaire (CSQ), revised for children with sickle cell disease). Medical data on complications, haemoglobin (Hb) levels, and foetal haemoglobin (HbF) percentage were also collected. Pain accounted for about 24% of hospital service use, independent of age, sex, number of with sickle cell disease complications, and Hb levels. However, 42% of patients had not utilised hospital services in the past 12 months. Three higher order factors emerged from analysis of the CSQ (active coping, affective coping, passive adherence coping). Pain severity was predicted by passive adherence coping, while utilisation of hospital services was predicted by active coping. Sickle cell disease in children involves severe recurrent pain leading to hospitalisation in some cases. Psychological coping patterns are relevant to both pain experience, and the use of acute hospital services. It is likely that children would benefit from community based interventions that incorporate both medical and psychological assessments.


Significance of bisphosphonates on angiogenesis in vivo and their effect under geranyl-geraniol addition - could it alter the treatment of bisphosphonate-associated necrosis of the jaw?
The aim of this study was to contribute to the understanding of the inhibitory effects of bisphosphonates on tissues, with a special focus on angiogenesis. Referring to bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ), it should be shown that the local addition of the isoprenoid geranyl-geraniol (GGOH) prevents vascularization processes. A mouse model with n = 24 animals which received an injection of a collagen matrix was used. In 4 subgroups (n = 6), we examined the effect of zoledronate on the sprouting of capillary-like structures into the matrix, with and without the presence of geranyl-geraniol, as well as testing against control groups with PBS injections or collagen matrix containing PBS instead of GGOH. This was followed by a histological evaluation of the capillary-like structures. Zoledronate inhibits the sprouting of blood vessels into a collagen matrix in vivo; in the presence of GGOH this effect is significantly weakened by a factor of 3.9 (p = 0.00068). This work commits to the investigation of the pathophysiology of BP-ONJ and shows a possible causal therapeutic path via the topical application of GGOH.


Complex Gill Disease: an Emerging Syndrome in Farmed Atlantic Salmon (Salmo salar L.).
Gill disorders have become a significant problem during the marine phase of farming Atlantic salmon (Salmo salar L.). The term complex gill disease (CGD) includes a wide range of clinical gill disease presentations generally occurring from the end of summer to early winter on marine Atlantic salmon farms. The gross and histological lesions observed are the resultant culmination of exposure to a mixture of environmental insults, pathogenic organisms and farm management practices. None of the three principal agents purportedly associated with CGD (Desmozoon lepeophtherii, salmon gill poxvirus or Candidatus Branchiomonas cysticola) have been cultured successfully in-vitro, so individual in-vivo challenge studies to identify their pathogenesis have not been possible. Studies of cohabitation of single pathogen-infected fish with naïve fish, and epidemiological investigations are required urgently to elucidate the roles of these pathogens and other factors in CGD.


Using patient admission characteristics alone to predict mortality of critically ill patients: A comparison of 3 prognostic scores.
This study compared the performance of 3 admission prognostic scores in predicting hospital mortality. Patient admission characteristics and hospital outcome of 9549 patients were recorded prospectively. The discrimination and calibration of the predicted risks of death derived from the Simplified Acute Physiology Score (SAPS III), Admission Mortality Prediction Model (MPM0 III), and admission Acute Physiology and Chronic Health Evaluation (APACHE) II were assessed by the area under the receiver operating characteristic curve and a calibration plot, respectively. Of the 9549 patients included in the study, 1276 patients (13.3%) died after intensive care unit admission. Patient admission characteristics were significantly different between the survivors and nonsurvivors. All 3 prognostic scores had a reasonable ability to discriminate between the survivors and nonsurvivors (area under the receiver operating characteristic curve for SAPS III, 0.836; MPM0 III, 0.807; admission APACHE, 0.845), with best discrimination in emergency admissions. The SAPS III model had a slightly better calibration and overall performance (slope of calibration curve, 1.03; Brier score, 0.09; Nagelkerke R(2), 0.297) compared to the MPM0 III and admission APACHE II model. All 3 intensive care unit admission prognostic scores had a good ability to predict hospital mortality of critically ill patients, with best discrimination in emergency admissions.


Dynamics of sewage outfall plumes based on Landsat-8-derived sea surface salinity and tidal characteristics.
In the face of growing marine pollution, assessment of the sewage outfall discharges is essential as it affects the seawater quality. The study demonstrates sea surface salinity (SSS) variations caused by sewage discharges and links it with tidal characteristics to hypothesize the dynamics of sewage outfall plumes. SSS is estimated using a multilinear regression model based on Landsat-8 (L8) OLI reflectance and in situ SSS data of 2013-2014. Using the validated model, the SSS of the 2018 image is predicted and evidenced by its relationship with colored dissolved organic matter (CDOM). The preliminary results of the hypothesis are encouraging and found that the dispersion patterns of outfall plumes exhibit distinct characteristics depending on the intra-tidal range and hour. The findings indicate a lower SSS in the outfall plume zone than in ambient seawater due to dilution caused by partially treated sewage discharges from diffusers. The plumes observed during the macro tidal range are long and narrowly spread alongshore. In contrast, during the meso and microtidal ranges, the plumes are shorter and are primarily dispersed offshore rather than alongshore. During slack times, low salinity levels are visibly concentrated around outfalls as there is no water movement to disperse the accumulated sewage discharges from diffusers. These observations suggest that slack periods and low-tidal conditions could be significant factors contributing to the accumulation of pollutants in coastal waters. The study further suggests more datasets such as wind speed, wind direction, and density variations are needed to understand the processes influencing the outfall plume dynamics and variation in SSS. The study recommends increasing the treatment capabilities of existing treatment facilities from primary to tertiary treatment levels. Furthermore, it is important to warn and educate the public about the health risks associated with exposure to partially treated sewage that is discharged from outfalls.


Identification and biological consequences of the O-GlcNAc modification of the human innate immune receptor, Nod2.
Nucleotide-binding oligomerization domain 2 (Nod2) is an intracellular receptor that can sense the bacterial peptidoglycan component, muramyl dipeptide. Upon activation, Nod2 induces the production of various inflammatory molecules such as cytokines and chemokines. Genetic linkage analysis identified and revealed three major mutations in Nod2 that are associated with the development of Crohn's disease. The objective of this study is to further characterize this protein by determining whether Nod2 is posttranslationally modified by O-N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation is one type of posttranslational modification in which the O-GlcNAc transferase transfers GlcNAc from UDP-GlcNAc to selected serine and threonine residues of intracellular proteins. We found that wild-type Nod2 and a Nod2 Crohn's-associated variant are O-GlcNAcylated and this modification affects Nod2's ability to signal via the nuclear factor kappa B pathway.


Role of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and cdc42 in hydrogen peroxide-induced senescence-like morphogenesis.
The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis has been described. The aim of this work was to investigate whether TGF-beta1-independent changes in protein synthesis are involved in this morphogenesis and to study possible mechanisms occurring earlier than TGF-beta1 overexpression. Among the multiple TGF-beta1-independent changes in protein neosynthesis, followed or not by posttranslational modifications, identified by proteomic analysis herein, those of ezrin, L-caldesmon, and HSP27 were particularly studied. Rho-GTPase cdc42 was shown to be responsible for p38(MAPK) activation, in turn triggering phosphorylation of L-caldesmon and HSP27. Cdc42 was also shown to be mainly responsible for the increase in TGF-beta1 mRNA level observed at 24 h after treatment with H(2)O(2) and onward. This study further clarified the mechanisms of senescence-like morphogenesis in addition to the previously demonstrated role of TGF-beta1 signaling pathways.


Increased oxidative stress in the placenta tissue and cell culture of tumour-bearing pregnant rats.
Placental dysfunction leads to foetal damage, which jeopardises the exchange between the maternal and foetal systems. We evaluated the effects of tumour growth on the activity of antioxidant enzymes and oxidative stress in placental tissue and cell culture from tumour-bearing pregnant rats compared to non-tumour-bearing pregnant rats that were ascitic fluid injected. Ascitic fluid is obtained from Walker tumour-bearing rats and contains a cytokine called Walker factor (WF), which is a molecule similar to proteolysis-inducing factor (PIF), and induces changes in protein metabolism and oxidative stress. Pregnant Wistar rats were distributed into control (C), tumour-bearing (W) and ascitic fluid injected (A) groups and were sacrificed on days 16, 19 and 21 of pregnancy to analyse the profile of enzyme activities (glutathione-S-transferase (GST), catalase (CAT), alkaline phosphatase (AP)) and malondialdehyde (MDA) content in placental tissue. Meanwhile, placenta samples from all groups were obtained on day 21, placed in primary culture and treated with WF for 72 h. The presence of tumour or ascitic fluid reduced the protein content of the placental tissue. On day 16 there was a significant reduction in AP activity in W rats, and on day 19, CAT activity and MDA content significantly increased. These results indicate that the presence of cancer decreased antioxidant enzyme capacity in the placenta, increasing the amount of oxidation in these cells, which may contribute to irreversible placental damage and compromisefoetal development. WF treatment induces similar changes in placental cells in primary culture, resulting in less cell viability and increased oxidative stress. These results indicate that WF, provided by the tumour or inoculation of ascitic fluid, has negative effects on placental homeostasis, which impairs foetal health.


A pseudoaneurysm of the right hepatic artery treated successfully with a stent graft - A case report.
Haemobilia caused by pseudoaneurysms of the right hepatic or cystic artery is rare. Haemobilia classically causes gastro-intestinal hemorrhage, jaundice and upper abdominal pain. A 76-year old female underwent laparoscopic cholecystectomy because of a severe acute on chronic cholecystitis. A massive arterial bleeding occurred during surgery, which was controlled with hemoclips. Approximately one week after surgery the patient developed severe colic pains and cholestatic liver enzyme alterations. Endo-ultrasound showed normal-width bile ducts, however during a subsequent ERCP haemobilia was observed. On computed tomography a pseudoaneurysm of the right hepatic artery was seen. Selective embolization was initially successful, however, a rebleed was observed two weeks later and a 6 × 50 mm Viabahn stent graft was placed in the right hepatic artery uneventfully. The patient remained free of complaints during 3-years of follow-up. Pseudoaneurysms of the cystic or hepatic arteries are described to be cholecystectomy or cholecystitis related. The etiology of the pseudoaneurysm in this case can be inflammatory or iatrogenic. Embolization is the golden standard in pseudoaneurysm treatment. Stent graft implantation has not been frequently described as an alternative option to surgery after a failed attempt of embolization. This case report presents a probable cholecystitis related pseudoaneurysm of the right hepatic artery, which caused haemobilia after cholecystectomy. The pseudoaneurysm was successfully eliminated with a stent graft after embolization had failed. Stent grafts should be considered a minimal invasive and effective alternative after failed embolization of a pseudoaneurysm.


The transcription factor TCFL5 responds to A-MYB to elaborate the male meiotic program in mice.
The testis-specific transcription factor, TCFL5, expressed in pachytene spermatocytes regulates the meiotic gene expression program in collaboration with the transcription factor A-MYB. In male mice, the transcription factors STRA8 and MEISON initiate meiosis I. We report that STRA8/MEISON activates the transcription factors A-MYB and TCFL5, which together reprogram gene expression after spermatogonia enter into meiosis. TCFL5 promotes the transcription of genes required for meiosis, mRNA turnover, miR-34/449 production, meiotic exit, and spermiogenesis. This transcriptional architecture is conserved in rhesus macaque, suggesting TCFL5 plays a central role in meiosis and spermiogenesis in placental mammals. Tcfl5em1/em1 mutants are sterile, and spermatogenesis arrests at the mid- or late-pachytene stage of meiosis. Moreover, Tcfl5+/em1 mutants produce fewer motile sperm.


The screening of Alzheimer's patients with CSF biomarkers, modulates the distribution of APOE genotype: impact on clinical trials.
Polymorphism of the apolipoprotein E gene (APOE) plays a role in the level of neuropathological lesions and in drug response in Alzheimer's disease (AD). The aim of this study was to investigate whether the selection of AD patients based on cerebrospinal fluid (CSF) biomarkers assessment may be biased by their APOE distribution. We studied the relationships between APOE genotype and CSF biomarkers levels in a total of 432 patients (AD, n = 244; non-AD, n = 188) explored for cognitive disorders. We studied the distribution of APOE genotypes among AD patient subgroups selected by various cut-offs of CSF biomarkers. Strategies of screening based on CSF Aβ1-42 lead to overselection of ε4/ε4 patients in the AD group. Screening based on tau levels did not change Apoe4 distribution in the AD group. CSF Aβ1-42 discriminated better AD patients with at least one ε4 than AD patients with no ε4. A strong allele-effect relationship was detected between APOE genotype and CSF amyloid-β (Aβ1-42) in AD patients. Selecting AD patients on CSF amyloid levels only may create an overselection of ε4/ε4 carriers, and might potentially bias the population of patients included in clinical trial studies.


Evaluating home environments of persons with dementia: interrater reliability and validity of the Home Environmental Assessment Protocol (HEAP).
This article reports on an interrater reliability and preliminary validity study of an investigator-developed tool, the Home Environmental Assessment Protocol (HEAP) for use in homes of persons with dementia. The HEAP consists of 192 items that are summed into separate indices representing the number of hazards, adaptations, and level of clutter and comfort in eight areas of the home. Interrater reliability was examined among four raters, two environmental experts and two non-experts, who observed 22 dementia households. The Kappa statistic was used to evaluate agreement level for each measured item and found that agreement ranged from slight to almost perfect. Intraclass correlations (ICCs), were used to evaluate agreement level for indices. The hazard index in each room ranged from fair (0.36) to moderate (0.66) for all raters. For the adaptation, clutter and comfort indices in each room, ICCs ranged from 0.51 to 0.90 for all raters. Agreement level between expert and non-expert raters differed minimally for all indices. Adaptations to dining rooms (r= -0.080, p = 0.001), kitchens (r = -0.52, p = 0.02) and bedrooms (r = -0.76, p = 0.001) were associated with patient deficits such that more adaptations were made in homes of dependent persons. Low Mini-Mental Status Examination scores were associated with fewer hazards, more adaptations, and less clutter. Findings show that both experts and non-expert raters use the HEAP consistently. Also, measured attributes are related to cognitive and functional status in the expected direction.


Six to success: improving primary care management of pediatric overweight and obesity.
Despite the existence of established guidelines addressing pediatric obesity, many primary care providers fail to successfully implement recommendations. This study measured the impact of Six to Success, a weight management program based on the Chronic Care Model, on primary care provider adherence to pediatric weight management guidelines. We used comprehensive pre- and postimplementation chart audits (N = 396) to conduct a quality improvement study at a hospital-based pediatric outpatient clinic. Charts of patients with a body mass index percentile at or above the 85th percentile (preimplementation, n = 90; postimplementation, n = 97) were audited for 23 identification, assessment, and prevention measures recommended in the care of the pediatric overweight/obese patient. Statistically significant improvements to clinical guideline adherence were found in the following areas: correct diagnosis, physical examination, lifestyle assessment, use of motivational interviewing, and prevention strategies. These findings suggest that Six to Success can be an effective method of improving primary care provider adherence to established pediatric weight management guidelines.


Non-pathogenic commensal Escherichia coli bacteria can inhibit degranulation of mast cells.
The mast cell's (MC) ability to rapidly release presynthesized mediators allows it to play a critical role in the immune system's first-line response to pathogens. Although recent research has illuminated the role of MCs in bacterial infection, little is known about how non-pathogenic bacteria influence MC responses. To characterize the influence of non-pathogenic Escherichia coli bacteria on MCs. High concentrations of live E. coli strongly down-modulated the degranulation of murine peritoneal MCs under all activator conditions. Bacteria did not induce MC degranulation by themselves, and staining of MCs showed they were still entirely viable. Dead bacteria and bacterial supernatant had no effect on MC degranulation. Ex vivo experiments confirmed that E. coli exposure down-modulates subsequently induced MC degranulation and that this effect lasts for up to a few days after exposure. Our results show that high doses of non-pathogenic E. coli bacteria can function as a strong, direct inhibitor of MC degranulation. This suggests a possible basis for future antiallergic treatment or prophylaxis with commensal bacteria, i.e. probiotics.


WEB 2086. A potent PAF antagonist exerts protective effect toward PAF-induced gastric damage.
Single intravenous administration of platelet activating factor (PAF; 4 micrograms/kg) induced reproducible gastric damage in the conscious rat which was prevented by WEB 2086, a potent and specific PAF-antagonist. Intravenous and oral ED50s in protecting rats from gastric damage were 61 and 633 micrograms/kg, respectively. Because of the reported association between septic shock and gastrointestinal ulceration, the therapeutic potential of PAF-antagonists might be broader than previously thought.


Evaluation of a high-throughput H295R homogenous time resolved fluorescence assay for androgen and estrogen steroidogenesis screening.
The H295R test guideline assay evaluates the effect of test substances on synthesis of 17β-estradiol (E2) and testosterone (T). The objective of this study was to leverage commercial immunoassay technology to develop a more efficient H295R assay to measure E2 and T levels in 384-well format. The resulting Homogenous Time Resolved Fluorescence assay platform (H295R-HTRF) was evaluated against a training set of 36 chemicals derived from the OECD inter-laboratory validation study, EPA guideline 890.1200 aromatase assay, and azole fungicides active in the HT-H295R assay. Quality control performance criteria were met for all conditions except E2 synthesis inhibition where low basal hormone synthesis was observed. Five proficiency chemicals were active for both the E2 and T endpoints, consistent with guideline classifications. Of the nine OECD core reference chemicals, 9/9 were concordant with outcomes for E2 and 7/9 for T. Likewise, 9/13 and 11/13 OECD supplemental chemicals were concordant with anticipated effects for E2 and T, respectively. Of the 10 azole fungicides screened, 7/10 for E2 and 8/10 for T exhibited concordant outcomes for inhibition. Generally, all active chemicals in the training set demonstrated equivalent or greater potency in the H295R-HTRF assay, supporting the sensitivity of the platform. The adaptation of HTRF technology to the H295R model provides an efficient way to evaluate E2 and T modulators in accordance with guideline specifications.


Simultaneous adsorption of Cd²⁺ and BPA on amphoteric surfactant activated montmorillonite.
The study mainly investigated the simultaneous adsorption of bisphenol A (BPA) and Cd(2+) from aqueous solution on octadecane-betaine modified montmorillonite (BS-Mt). The characteristics of the obtained materials were analyzed by X-ray diffraction (XRD), Fourier-transform infrared (FTIR), Specific surface area (BET) and Scanning electron microscopy/Energy disperse spectroscopy (SEM/EDS), confirming that BS-18 was successfully introduced into Mt. Also, factors including initial solution pH, initial Cd(2+)/BPA concentration, contact time and adsorbent dosage on the adsorption processes were shown to be crucial for Cd(2+) adsorption, whereas had negligible effects on BPA adsorption. In this study, we found that pseudo-second-order model fitted well with the adsorption kinetic studies for both Cd(2+) and BPA with an equilibrium time of 24 h. The Cd(2+) and BPA adsorption isotherm could be well described by Freundlich model and Langmuir model, respectively. On the basis of kinetic models, the maximum adsorption capacity of Cd(2+) in aqueous solution was slightly enhanced after modification, indicating that Cd(2+) adsorption on BS-Mt was mainly attributed to direct electrostatic attraction and the chelate reaction, while the dramatic enhancement of maximum adsorption capacity for BPA was due to the hydrophobic interaction.