Protein coding gene trees in ciliates: comparison with rRNA-based phylogenies.
We have reexamined the phylogeny of the ciliates using alpha-tubulin and phosphoglycerate kinase gene sequences. For alpha-tubulin, we have compared the amino acid and nucleotide sequences of 20 species representing seven of the nine classes of the phylum (Karyorelictea, Heterotrichea, Hypotrichea, Oligohymenophorea, Colpodea, Nassophorea, and Litostomatea). The phylogenetic tree resembles a bush from which three monophyletic lineages can be distinguished which correspond to the three classes Hypotrichea, Oligohymenophorea, and Litostomatea. For phosphoglycerate kinase, we have compared the amino acid sequences from 7 species representing three classes (Heterotrichea, Hypotrichea, and Oligohymenophorea). The branching pattern is resolved in three deeply separated branches with an early emergence of the heterotrich. Our comparative analysis shows that if alpha-tubulin phylogeny is not informative at the interclass level, the preliminary data from the phosphoglycerate kinase molecule appear more promising. Nevertheless, at low taxonomic level and at the class level, the resolved phylogenetic relationships inferred from both protein and rRNA sequence data are congruent.


Posterior elongation in the annelid Platynereis dumerilii involves stem cells molecularly related to primordial germ cells.
Like most bilaterian animals, the annelid Platynereis dumerilii generates the majority of its body axis in an anterior to posterior temporal progression with new segments added sequentially. This process relies on a posterior subterminal proliferative body region, known as the "segment addition zone" (SAZ). We explored some of the molecular and cellular aspects of posterior elongation in Platynereis, in particular to test the hypothesis that the SAZ contains a specific set of stem cells dedicated to posterior elongation. We cloned and characterized the developmental expression patterns of orthologs of 17 genes known to be involved in the formation, behavior, or maintenance of stem cells in other metazoan models. These genes encode RNA-binding proteins (e.g., tudor, musashi, pumilio) or transcription factors (e.g., myc, id, runx) widely conserved in eumetazoans. Most of these genes are expressed both in the migrating primordial germ cells and in overlapping ring-like patterns in the SAZ, similar to some previously analyzed genes (piwi, vasa). The SAZ patterns are coincident with the expression of proliferation markers cyclin B and PCNA. EdU pulse and chase experiments suggest that new segments are produced through many rounds of divisions from small populations of teloblast-like posterior stem cells. The shared molecular signature between primordial germ cells and posterior stem cells in Platynereis thus corresponds to an ancestral "stemness" program.


A new magnetic bearing using Halbach magnet arrays for a magnetic levitation stage.
Next-generation lithography requires a high precision stage, which is compatible with a high vacuum condition. A magnetic levitation stage with six degrees-of-freedom is considered state-of-the-art technology for a high vacuum condition. The noncontact characteristic of magnetic levitation enables high precision positioning as well as no particle generation. To position the stage against gravity, z-directional electromagnetic levitation mechanisms are widely used. However, if electromagnetic actuators for levitation are used, heat is inevitably generated, which deforms the structures and degrades accuracy of the stage. Thus, a gravity compensator is required. In this paper, we propose a new magnetic bearing using Halbach magnet arrays for a magnetic levitation stage. The novel Halbach magnetic bearing exerts a force four times larger than a conventional magnetic bearing with the same volume. We also discuss the complementary characteristics of the two magnetic bearings. By modifying the height of the center magnet in a Halbach magnetic bearing, a performance compromise between levitating force density and force uniformity is obtained. The Halbach linear active magnetic bearing can be a good solution for magnetic levitation stages because of its large and uniform levitation force.


Role of elevated cytosolic calcium in the pathogenesis of complications in diabetes mellitus.
Both type I and type II diabetes mellitus are associated with derangements in the regulation of intracellular calcium. Hyperglycemia causes an acute rise in cytosolic calcium ([Ca2+]i) due to increased calcium influx and in certain cells to mobilization of intracellular calcium stores as well. The increase in calcium entry is secondary to the activation of calcium channels inhibitable by verapamil, nifedipine, or amlodipine. The stimulation of these calcium channels is mediated by the activation of G protein(s), leading to stimulation of various cellular pathways. Chronic hyperglycemia is also associated with decreased calcium exit from cells. The combination of increased calcium influx and decreased calcium efflux leads to sustained elevation in basal levels of [Ca2+]i. The latter abnormality may adversely affect cell function. Treatment of diabetic animals with calcium channel blockers normalizes cell [Ca2+]i and prevents and/or reverses the derangements in cellular function.


Pattern of polycyclic aromatic hydrocarbons (PAHs) pollution in communication air of Hangzhou, China.
Nine PAHs were surveyed in communication air of Hangzhou. The results indicated that the PAHs pollution is very serious and the total sum of 9 PAHs, on the average are 3.39-13.82 micrograms/m3. The PAHs signatures for all streets are similar to each other. Multivariate statistical techniques were used to investigate source apportionment for PAHs. A factor analysis/multiple regression model was successfully applied to the study. The most important three PAHs sources in communication air are diesel emission, gasoline engine emission, coal-burning accounting for 61.1 +/- 6.4%, 19.9 +/- 8.3%, 10.8 +/- 10.8% of total PAHs, respectively. The relationship for three source tracers and total PAHs is: [PAHs] = 1.471 (+/- 0.155) [Phen] + 2.538 (+/- 2.522) [1 - Mepy] + 2.254 (+/- 0.943) [Chry] + 1.022 (+/- 1.767).


[Blood Count Specimen].
The circulating blood volume accounts for 8% of the body weight, of which 45% comprises cellular components (blood cells) and 55% liquid components. We can measure the number and morphological features of blood cells (leukocytes, red blood cells, platelets), or count the amount of hemoglobin in a complete blood count: (CBC). Blood counts are often used to detect inflammatory diseases such as infection, anemia, a bleeding tendency, and abnormal cell screening of blood disease. This count is widely used as a basic data item of health examination. In recent years, clinical tests before consultation have become common among outpatient clinics, and the influence of laboratory values on consultation has grown. CBC, which is intended to count the number of raw cells and to check morphological features, is easily influenced by the environment, techniques, etc., during specimen collection procedures and transportation. Therefore, special attention is necessary to read laboratory data. Providing correct test values that accurately reflect a patient's condition from the laboratory to clinical side is crucial. Inappropriate medical treatment caused by erroneous values resulting from altered specimens should be avoided. In order to provide correct test values, the daily management of devices is a matter of course, and comprehending data variables and positively providing information to the clinical side are important. In this chapter, concerning sampling collection, blood collection tubes, dealing with specimens, transportation, and storage, I will discuss their effects on CBC, along with management or handling methods.


Assistive Technology for the Upper Extremities After Stroke: Systematic Review of Users' Needs.
Technical innovations have the potential to compensate for loss of upper-limb motor functions after stroke. However, majority of the designs do not completely meet the needs and preferences of the end users. User-centered design methods have shown that the attention to user perspectives during development of assistive technology leads to devices that better suit the needs of the users. To get more insight into the factors that can bring the design of assistive technology to higher levels of satisfaction and acceptance, studies about user perspectives on assistive technology for the upper limb after stroke are systematically reviewed. A database search was conducted in PubMed, EMBASE, CINAHL, PsycINFO, and Scopus from inception to August 2017, supplemented with a search of reference lists. Methodological quality of the included studies was appraised. User perspectives of stroke survivors, carers, and health care professionals were extracted. A total of 35 descriptive themes were identified, from which 5 overarching themes were derived. In total, 9 studies with information gathered from focus groups, questionnaires, and interviews were included. Barriers and enablers influencing the adoption of assistive technology for the upper limb after stroke emerged within 5 overarching but highly interdependent themes: (1) promoting hand and arm performance; (2) attitude toward technology; (3) decision process; (4) usability; and (5) practical applicability. Expected use of an assistive technology is facilitated when it has a clear therapeutic base (expected benefit in enhancing function), its users (patients and health care professionals) have a positive attitude toward technology, sufficient information about the assistive technology is available, and usability and practical applicability have been addressed successfully in its design. The interdependency of the identified themes implies that all aspects influencing user perspectives of assistive technology need to be considered when developing assistive technology to enhance its chance of acceptance. The importance of each factor may vary depending on personal factors and the use context, either at home as an assistive aid or for rehabilitation at a clinic.


[Analysis on therapeutic effect of acupoint-injection on chronic hepatitis B].
To search for an effective method for treatment of chronic hepatitis B. One hundred and twenty-three cases were randomly divided into a treatment group (n = 63) and a control group (n = 60). The treatment group were treated with injection of Huangqi injectio and Danshen Injectio into Ganshu (BL 18) and Zusanli (ST 36), once every other day; and the control group were treated with oral administration of Gankangning tablet and fufang yiganling tablet. The clinical symptoms, hepatic function, hepatitis B e antigen (HBeAg), hepatitis B virus-desoxyribose nucleic acid (HBV-DNA) were compared between the two groups. The total effective rate was 93.7% in the treatment group and 76.7% in the control group with significant difference between the two groups (P < 0.01); and the treatment group in hepatic function and the effects of turning negative for HBeAg and HBV-DNA was better than the control group (P < 0.01). Acupoint-injection has a better therapeutic effect on chronic hepatitis B.


Local thermodynamic stability scores are well represented by a non-central student's t distribution.
Local folding in mRNAs is closely associated w ith biological functions. In this study, we reveal the whole distribution of local thermodynamic stability in the complete genome of the poliovirus P3/Leon/37 and the single-stranded RNA sequences that corresponds to the nucleotide sequence of the complete genome sequence (1 667 867 bp) of Helicobacter pylori (H. pylori) strain 26695. Local thermodynamic stability in the RNA sequences is measured by two standard z -scores, significance score and stability score. To estimate the distribution of thermodynamic stability, a model based on the non-central Student's t distribution has been developed. Significant patterns of extremes that are either much more stable or unstable than expected by chance are detected. Our results indicate that the highly stable and statistically more significant folding regions are predominantly in non-coding sequences in the two genome sequences. Moreover, the highly unstable folding regions, on the contrary, are predominantly in the protein coding sequences of H. pylori. The observed differences across the complete genomic sequences are statistically very significant by a chi2-test. These extreme patterns may be useful in searching for target sequences for long-chain antisense RNA and for locating potential RNA functional elements involved in the regulation of gene expression including translation, mRNA localization and metabolism.


NOD2/CARD15 mutations and the risk of reoperation in patients with Crohns disease.
Three NOD2/CARD15 gene variants (3020insC, R702W, G908R) have been identified as genetic risk factors for Crohns disease patients. However the diagnostic and therapeutic relevance for clinical practice remains limited. The aim of this study was to evaluate the association between these variants, the risk of reoperation and disease phenotype. In 76 Crohns disease patients (41 female, 35 male) with a minimum 5 year follow-up, three polymorphisms of the NOD2/CARD15 gene (R702W, G908R, 3020insC) were tested. Detailed clinical and medical history including surgical procedures and reoperations were obtained by reviewing the medical charts and completed prospectively. Association between the need for reoperation, disease phenotypes and gene variants were analyzed. 24 patients (32%) showed at least one NOD2/CARD15 mutation. 25 patients (33%) required reoperation, 51 (67%) represented the control group. The expected trend that patients with NOD2/CARD15 variants have a higher frequency of reoperations was not confirmed to a level of statistical significance (p=0.2688). Two of the four patients (50%) with the 3020insC variant required further surgery. We did not confirm any association between NOD2/CARD15 mutations and age at diagnosis (p=0.4356), behavior (p=0.6610), or localization (p=0.4747) according to the Montreal classification. NOD2/CARD15 polymorphisms did not significantly affect the reoperation rate. Homozygosity for the 3020insC variant in the NOD2/CARD15 gene is associated with a high risk of reoperation. NOD2/CARD15 gene variants are not significantly associated with specific disease phenotypes.


Pleiotropic Functions of High Fat Diet in the Etiology of Osteoarthritis.
Obesity is a risk factor for osteoarthritis (OA). To investigate the roles of increased mechanical loading in the onset of obesity-induced OA, knee joints were histologically analyzed after applying a tail suspension (TS) model to a high-fat diet (HFD)-induced OA model. Mice were divided into four groups: normal diet (ND) with normal loading (NL) group; HFD with NL group; ND with TS group; and HFD with TS group. Whole knee joints were evaluated by immunohistological analysis. The infrapatellar fat pad (IPFP) was excised and mRNA expression profiles were compared by qPCR analysis. After twelve weeks of the diet, body weight was increased by HFD in both the NL group and TS group. Upon histological analysis, the irregularity of the surface layer of articular cartilage was observed only in the NL+HFD group. Osteophyte area increased as a result of HFD in both the NL and TS groups, although osteophyte area in the TS+HFD group was smaller than that of the NL+HFD group. In the evaluation of the IPFP by qPCR, adipokines and inflammatory cytokines also increased as a result of HFD. While TGF-β increased as a result of HFD, the trend was slightly lower in the TS group, in parallel with osteophyte area. To detect apoptosis of articular chondrocytes, TUNEL staining was employed. TUNEL-positive cells were abundantly observed in the articular cartilage in the HFD mice regardless of mechanical loading. IPFP inflammation, enhanced chondrocyte apoptosis, and osteophyte formation were seen even in the TS group as a result of a HFD. In all, these data demonstrate that HFD contributed to osteophyte formation through mechanical loading dependent and independent mechanisms.


Protected bronchoalveolar lavage. A new bronchoscopic technique to retrieve uncontaminated distal airway secretions.
We tested the effectiveness of protected bronchoalveolar lavage (PBAL), performed through a protected transbronchoscopic balloon-tipped (PBT) catheter, in collecting distal airway secretions with a minimal degree of contamination. The PBAL had less than or equal to 1% squamous epithelial cells in 91% of specimens and an absence of bacterial growth in 59% of patients without pneumonia. Using a threshold of 10(4) cfu/ml we had one false positive result in 33 patient without pneumonia and one false negative in 13 patients with pneumonia. Quantitative bacterial cultures of the PBAL specimens had a diagnostic sensitivity of 97% and a specificity of 92%, with a positive predictive value of 97% and a negative predictive value of 92%. The diagnostic efficiency was 96%. The presence of intracellular organisms in much greater than or equal to 2% of the recovered alveolar cells (Giemsa stain) was seen in all but two patients with pneumonia (on corticosteroids) and in none of the patients without pneumonia. Gram stains of the PBAL specimens were positive in all but one patient with pneumonia and negative in all but one patient without infection (patient with endobronchial narrowing secondary to neoplasm with false positive cultures). Either the Giemsa or the Gram stain was positive in all patients with pneumonia, allowing early and accurate diagnosis of lower respiratory tract infection before the results of cultures were available. The time off antibiotic therapy before bronchoscopy did not affect the result of PBAL cultures, contrary to what we observed for the protected brush specimen.


Limitations of the ARDS criteria during high-flow oxygen or non-invasive ventilation: evidence from critically ill COVID-19 patients.
The ratio of partial pressure of arterial oxygen to inspired oxygen fraction (PaO2/FIO2) during invasive mechanical ventilation (MV) is used as criteria to grade the severity of respiratory failure in acute respiratory distress syndrome (ARDS). During the SARS-CoV2 pandemic, the use of PaO2/FIO2 ratio has been increasingly used in non-invasive respiratory support such as high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The grading of hypoxemia in non-invasively ventilated patients is uncertain. The main hypothesis, investigated in this study, was that the PaO2/FIO2 ratio does not change when switching between MV, NIV and HFNC. We investigated respiratory function in critically ill patients with COVID-19 included in a single-center prospective observational study of patients admitted to the intensive care unit (ICU) at Uppsala University Hospital in Sweden. In a steady state condition, the PaO2/FIO2 ratio was recorded before and after any change between two of the studied respiratory support techniques (i.e., HFNC, NIV and MV). A total of 148 patients were included in the present analysis. We find that any change in respiratory support from or to HFNC caused a significant change in PaO2/FIO2 ratio. Changes in respiratory support between NIV and MV did not show consistent change in PaO2/FIO2 ratio. In patients classified as mild to moderate ARDS during MV, the change from HFNC to MV showed a variable increase in PaO2/FIO2 ratio ranging between 52 and 140 mmHg (median of 127 mmHg). This made prediction of ARDS severity during MV from the apparent ARDS grade during HFNC impossible. HFNC is associated with lower PaO2/FIO2 ratio than either NIV or MV in the same patient, while NIV and MV provided similar PaO2/FIO2 and thus ARDS grade by Berlin definition. The large variation of PaO2/FIO2 ratio indicates that great caution should be used when estimating ARDS grade as a measure of pulmonary damage during HFNC.


Phototropism in Hypocotyls of Radish: IV. Flank Growth and Lateral Distribution of cis- and trans-Raphanusanins in the First Positive Phototropic Curvature.
The first positive phototropic curvature induced by a pulse of unilateral white irradiation (0.1 watt per square meter, 30 seconds) of etiolated and de-etiolated Sakurajima radish (Raphanus sativus var hortensis f. gigantissimus Makino) hypocotyls was analyzed in terms of differential growth and growth inhibitor contents of the hypocotyls. In both etiolated and de-etiolated hypocotyls, the growth rates at the lighted sides were suppressed whereas those at the shaded ones showed no change. De-etiolation treatment induced a larger difference between the growth rates at the lighted and shaded sides of the hypocotyls, resulting in a larger curvature of de-etiolated seedlings than of etiolated ones. The contents of growth inhibitors, cis- and trans-raphanusanins, increased in the lighted but not in the shaded halves of the hypocotyls of etiolated seedlings. In de-etiolated seedlings, the two inhibitors increased due to the de-etiolation treatment. When de-etiolated seedlings were exposed to a pulse of unilateral irradiation the level of the two inhibitors remained high along the lighted side for 1 h following the light pulse, whereas at the shaded side the contents of the inhibitors abruptly decreased upon transfer to the dark, the difference between their amounts in the lighted and shaded sides being larger than in etiolated seedlings. Another growth inhibitor, raphanusamide, did not respond to the phototropic stimulus, although its amounts increased by the de-etiolation treatment. These data suggest that cis- and trans-raphanusanins are involved in the first positive phototropic response of radish hypocotyls, and that de-etiolation magnifies the phototropic response through induction of a larger lateral gradient of the raphanusanins in the hypocotyls by the phototropic stimulus.


Physiological and Histological Changes in Pancreatic Gland Associated with Ageing in Local Rabbits in Iraq.
The pancreas is a pear-shaped flat organ resembling the letter L, and yellowish to pink in color. This organ is of medical significance since it is associated with two life-threatening diseases including diabetes mellitus and pancreatic cancer. This study was conducted on male rabbits which were assigned into 3 age groups (6-month-old, 1-year-old, and 3-year-old rabbits). Physiological and histological changes of the pancreas were studied in the adopted age groups. The physiological aspect and the histological structure of the pancreas were also studied by the analysis of the level of pancreatic gland hormones and hormonal changes. Based on the results, there were significant differences in the concentration of pancreatic gland hormones. Insulin level in the second study group was more than that in the first and third groups, while the highest concentration of blood sugar (glucose) was observed in the third group, compared to the first and second. Although the basic structure of the pancreas was similar in all samples, changes were observed in the tissue structure of the pancreas throughout the process of aging. By the increase of age (from 1 to 3 years old), Langerhans islets increased in size, contained alpha and beta cells that were surrounded by a loose connective tissue in the third stage. Moreover, no significant difference was observed in the diameters of cells that produced enzymes at all stages of life. Physiological and histological changes indicated that age plays a role in the function and structure of the pancreas gland during different stages of life. In addition, this study indicated that the hormonal variability of the pancreas is closely related to the histological composition of gland components. Therefore, further studies on the role of factors, such as gender, different breeds, or environmental conditions seem to be necessary and may provide more information on factors that may affect the effectiveness and activity of the pancreas gland.


Envisioning Eye Care From a Rural Perspective: A Photovoice Project From India.
Background To understand barriers and promoters for accessing eye care by rural communities, we used a modified approach to Photovoice, a community-based participatory action research approach Methods Community members took photographs and wrote or spoke stories based upon a series of questions intended to facilitate deeper thinking. Fifteen rural paramedical team members who were affiliated with the rural network of L V Prasad Eye Institute, and 60 people from four villages reported barriers and promoters for eye care access for 20 villages Results Important barriers for accessing eye care included the following: no caretaker at home for grandchildren except for the grandparent(s), alcoholism, uncontrolled blood pressure, inadequate diabetes management, lack of escort for blind people and elders, affordability, and inadequate clinic staffing during summer season when farming villagers were available. Important promoters for seeking eye care included having a neighbor who had a good surgical outcome in one eye which resulted in the ability to resume work. The Photovoice project offered specific suggestions to hospital management for improving eye care access, including providing evening transportation, providing additional surgical staffing during busy summer season, and the creation of tool spectacle repair kits to be kept at the primary vision centers Conclusions This Photovoice project facilitated a deeper understanding of the important barriers and promoters for accessing eye care by villagers, and by the rural eye care team, offering specific suggestions to hospital management for improving eye care access and to communicate without any inhibiting factors like fear of hierarchy within the hospital administration.


Factor XI binding to activated platelets is mediated by residues R(250), K(255), F(260), and Q(263) within the apple 3 domain.
To localize the platelet binding site on factor XI, rationally designed, conformationally constrained synthetic peptides were used to compete with [(125)I]factor XI binding to activated platelets. The major platelet binding energy resided within the sequence of amino acids T(249)-F(260). Homology scanning, using prekallikrein amino acid substitutions within the synthetic peptide T(249)-F(260), identified a major role for R(250) in platelet binding. Inhibition of [(125)I]factor XI binding to activated platelets by the recombinant Apple 3 domain of factor XI and inhibition by unlabeled factor XI were identical, whereas the recombinant Apple 3 domain of prekallikrein had little effect. A "gain-of-function" chimera in which the C-terminal amino acid sequence of the Apple 3 domain of prekallikrein was replaced with that of factor XI was as effective as the recombinant Apple 3 domain of factor XI and unlabeled factor XI in inhibiting [(125)I]factor XI binding to activated platelets. Alanine scanning mutagenic analysis of the recombinant Apple 3 domain of factor XI indicated that amino acids R(250), K(255), F(260), and Q(263) (but not K(252) or K(253)) are important for platelet binding. Thus, the binding energy mediating the interaction of factor XI with platelets is contained within the C-terminal amino acid sequence of the Apple 3 domain (T(249)-V(271)) and is mediated in part by amino acid residues R(250), K(255), F(260), and Q(263).


A Case of Immunoglobulin G4-Related Ophthalmic Disease With Unilateral Visual Field Impairment.
A 76-year-old man receiving maintenance therapy with oral steroids for immunoglobulin G4 (IgG4)-related disease presented to our hospital with the chief complaint of visual disturbance. His best corrected visual acuities of the right and left eye were 1.2 and 0.7, respectively. Humphrey visual field test revealed inferior auriculotemporal one-quarter blindness in the left eye. After detailed history-taking for IgG4-related disease, clinical diagnosis based on imaging revealed the marked pituitary/pituitary stalk enlargement with associated optic chiasm compression. Based on the history and initial evaluation findings, a diagnosis of IgG4-related ophthalmic disease was made. Intensified steroid therapy was performed, which led to symptom resolution. IgG4-related diseases are considered in the differential diagnosis when bilateral hemianopsia is observed. When unilateral visual acuity and visual field defects are present, IgG4-related diseases and other organ disorders should be considered.


Relationship between the Intake of n-3 Polyunsaturated Fatty Acids and Depressive Symptoms in Elderly Japanese People: Differences According to Sex and Weight Status.
n-3 polyunsaturated fatty acids (PUFAs) have been shown to have preventive effects against depression. In this study, we aimed to investigate the associations between the intake of n-3 PUFAs and depression among people according to sex and weight status. We utilized cross-sectional data from the Shika study in Japan. The study was conducted between 2013 and 2016. Data were collected from adults older than 65 years. Invitation letters were distributed to 2677 individuals, 2470 of whom participated in the study (92.3%). We assessed depressive states using the Japanese short version of the Geriatric Depression Scale (GDS-15). We assessed the intake of n-3 PUFAs using the validated food frequency questionnaire. One thousand six hundred thirty-three participants provided data, among which 327 (20.0%) exhibited depressive symptoms. When we performed the stratified analysis by sex and weight status, there were significant inverse relationships between total n-3 PUFAs, individual n-3 PUFAs, and n-3/n-6 PUFAs ratio and depressive symptoms in overweight/obese females. No correlations were observed between n-3 PUFAs intake and depressive states in males. The results demonstrated a relationship between n-3 PUFAs deficiencies and depressive states, particularly in overweight/obese females. Dietary modifications may help to prevent depressive symptoms in overweight/obese females.


A novel UDP-glucose transferase is part of the callose synthase complex and interacts with phragmoplastin at the forming cell plate.
Using phragmoplastin as a bait, we isolated an Arabidopsis cDNA encoding a novel UDP-glucose transferase (UGT1). This interaction was confirmed by an in vitro protein--protein interaction assay using purified UGT1 and radiolabeled phragmoplastin. Protein gel blot results revealed that UGT1 is associated with the membrane fraction and copurified with the product-entrapped callose synthase complex. These data suggest that UGT1 may act as a subunit of callose synthase that uses UDP-glucose to synthesize callose, a 1,3-beta-glucan. UGT1 also interacted with Rop1, a Rho-like protein, and this interaction occurred only in its GTP-bound configuration, suggesting that the plant callose synthase may be regulated by Rop1 through the interaction with UGT1. The green fluorescent protein--UGT1 fusion protein was located on the forming cell plate during cytokinesis. We propose that UGT1 may transfer UDP-glucose from sucrose synthase to the callose synthase and thus help form a substrate channel for the synthesis of callose at the forming cell plate.


[Efficacy and safety of maintenance intravesical instillation therapy with bacillus Calmette-Guerin and epirubicin for non-muscle invasive bladder cancer].
The objectives of this study were to evaluate the efficacy and toxicity of maintenance intravesical instillation therapy with bacillus Calmette-Guerin (BCG) and epirubicin for non-muscle invasive bladder cancer. From April 1999 to March 2010, 27 eligible patients were enrolled in this study. After receiving one cycle of epirubicin (100 mg/100 ml) by intravesical instillation, all patients received 6 weekly alternate intravesical instillation of BCG (80 mg/50 ml) and epirubicin (50 mg/50 ml), followed by 10 monthly instillations. Among the 27 patients, 19 were men and 8 were women, with a median age of 62.4 years (range, 37-78 years). Tumor pathologic stage was pTa in 25 patients, pT1 in 2 and there were no concomitant carcinoma in situ cases. Median follow-up was 37.1 months (range, 11-82 months). The 3- year recurrence-free and progression-free survival rates were 75.3% and 96.1%, respectively. Furthermore, a high completion rate of 81.5% was achieved in this study. Adverse events of grade 3 or higher occurred in 3 patients (11.1%), 1 patient had anaphylaxis. There were no treatment-related deaths. Maintenance intravesical instillation therapy with BCG and epirubicin is a favorable therapeutic option for non-muscle invasive bladder cancer. Given the safety and benefit profile found in this study, appropriate patient selection is warranted in the future.


Presence of double-stranded RNA and virus-like particles in Rhizopus isolates.
Fungal isolates belonging to four Rhizopus species were screened for the presence of double-stranded RNA (dsRNA) molecules. Five (two R. stolonifer, two R. microsporus, and one R. oryzae) of the 27 isolates examined harboured such genetic elements. Electrophoresis of the nucleic acids revealed five RNA patterns, with 1-5 discrete dsRNA bands. The molecular sizes corresponding to these bands were 2.2-14.8 kb. Gel electrophoresis of purified virus-like particles (VLPs) indicated only one capsid of similar size in all virus-harbouring strains; when investigated by electron microscopy, they were found to be polyhedral VLPs 40 nm in diameter. In one of the R. microsporus isolates an uncapsidated large dsRNA segment (14.8 kb) was observed. No phenotypic differences were observed between uninfected and virus-harbouring Rhizopus isolates.


Adult NREM Parasomnias: An Update.
Our understanding of non-rapid eye movement (NREM) parasomnias has improved considerably over the last two decades, with research that characterises and explores the causes of these disorders. However, our understanding is far from complete. The aim of this paper is to provide an updated review focusing on adult NREM parasomnias and highlighting new areas in NREM parasomnia research from the recent literature. We outline the prevalence, clinical characteristics, role of onset, pathophysiology, role of predisposing, priming and precipitating factors, diagnostic criteria, treatment options and medico-legal implications of adult NREM parasomnias.


Comparison of fresh and glutaraldehyde-treated autologous stented pericardium as pulmonary valve replacement.
The use of fresh autologous pericardium in valve surgery has shown poor results in the past mainly due to thickening and retraction. Recently, it has been suggested that a short treatment with glutaraldehyde might radically change its behavior. In an attempt to determine whether this disparity in results is due to the glutaraldehyde treatment or to a better present-day surgical technique, fresh and glutaraldehyde-treated autologous pericardium was mounted in a frame and implanted in the pulmonary position of adult sheep. Six survivors obtained in each group were sacrificed between 2 and 8 months in the "fresh" group and between 2 and 6 months in the "glutaraldehyde-treated" group. Macroscopically, the fresh pericardium became thickened and retracted in all specimens, eventually resulting in severe regurgitation, while the glutaraldehyde-treated, although slightly thickened, retained its pliability without significant retraction. Microscopically, viability of the central core of the collagen was more often preserved in the fresh pericardium. Endothelialization was irregular. In conclusion, short glutaraldehyde treatment seems to improve the results of autologous pericardium mounted on a valve stent. Its effect on calcification remains to be ascertained.


[Prudent optimism and the evolution of the main indicators of endemic tuberculosis in Romania in 2012].
The implementation of programmes for Tuberculosis Control (NPTC) in the medium term, starting in 1997, who under the auspices and the coordination of the Ministry of Health, was the guarantor of the achievements in these years in TB control, therapeutic success rate of cases being a constant source of 80%. The global incidence of TB (IG) (new cases and relapses) has decreased in the past 10 years with 42%, from a maximum of 142.2per 100 thousand in 2002, to 79.2 per 100 thousand in 2012. The incidence of TB in children between 0 and 14 years of age has dropped significantly, from 48.2 per 100 thousand in 2002 (1843) a t28.3per 100 thousand in 2011 (770). Mortality declined from 10.8% in 2002 to 6% in 2011. To increase the control of TB, and in accordance with the envisaged country strategy for the period 2013-2017, the anti-TB Programme will give priority to the following measures: gradual introduction of rapid molecular techniques able to identify in the shortest time TB and chemoresistancies; centralized procurement anti-TB drugs; better integration ofpractices of diagnosis and treatment of TB in children with standard practices for tuberculosis control; for a proper diagnosis and treatment to all people suffering from MDR-TB (until 2015).


Changes in return to work among patients in vocational rehabilitation: a self-determination theory perspective.
The aim of the current study was to examine whether patient perceptions of autonomy support from the treatment team in a vocational rehabilitation program will be associated with change (increase) in need satisfaction, autonomous motivation, perceived competence, well-being, physical activity, and return to work (RTW), and whether the self-determination theory (SDT) Model of Health Behavior will provide adequate fit to the data. A total of 90 participants were enrolled in a longitudinal study and completed measures at four time points over 15 months. Participants reported increases in all variables, and in general these changes were maintained at six weeks post-rehabilitation and at 15 months post-baseline. As well, the SDT Model of Health Behavior provided adequate fit to the data. These results underscore the importance of health care practitioners' providing support for their patients' autonomy, competence, and relatedness to improve well-being, physical activity, and RTW in the context of vocational rehabilitation. Implications for Rehabilitation Vocational rehabilitation that emphasizes physical activity is associated with increases in patients' well-being, physical activity, and return to work (RTW). It is important for health care practitioners to provide support for their patients' autonomy, competence, and relatedness in the context of vocational rehabilitation, as doing so is associated with increases in patients' autonomous motivation, perceived competence, and psychosocial outcomes.


Methylation of histone H3 and H4 by PRMT5 regulates ribosomal RNA gene transcription.
In an effort to understand the epigenetic regulation of ribosomal RNA gene (rDNA) expression we have previously demonstrated the role of DNA methyltransferases and methyl CpG binding proteins in rRNA synthesis. Here, we studied the role of protein arginine methyltransferase PRMT5 and the two methylated histones H3R8Me2 and H4R3Me2, in rDNA expression in Epstein Barr virus- transformed primary B-cells (LCLs) and in HeLa cells responding to serum-regulated growth. Chromatin immunoprecipitation assay showed that histones H3 and H4 associated with rRNA promoters were differentially methylated at arginine residues 8 and 3, respectively, depending on its transcriptional activity. Association of PRMT5 and methylated H3 with the unmethylated promoters in resting B-cells was significantly reduced in rapidly growing LCLs. Unlike PRMT5 and H3R8Me2, histone H4 associated with both methylated and unmethylated rRNA promoters in resting B-cells was methylated at the R3 residue. However, a dramatic decrease in R3 methylation of H4 recruited to the unmethylated rRNA promoters was observed in LCLs while it remained unaltered in the fraction bound to the methylated promoters. Differential interaction of PRMT5 and methylation of H3 and H4 associated with the rRNA promoters was also observed when serum starved HeLa cells were allowed to grow in serum replenished media. Ectopic expression of PRMT5 suppressed activity of both unmethylated and methylated rRNA promoter in transient transfection assay whereas siRNA mediated knockdown of PRMT5 increased rRNA synthesis in HeLa cells. These data suggest a key role of PRMT5 and the two methylated histones in regulating rRNA promoter activity.


Measurement of B --> K*gamma branching fractions and charge asymmetries.
The branching fractions of the exclusive decays B0-->K(*0)gamma and B+-->K(*+)gamma are measured from a sample of (22.74+/-0.36)x10(6) BB decays collected with the BABAR detector at the PEP-II asymmetric e(+)e(-) collider. We find B (B0-->K(*0)gamma) = [4.23+/-0.40(stat)+/-0.22(syst)]x10(-5), B(B+-->K(*+)gamma) = [3.83+/-0.62(stat)+/-0.22(syst)]x10(-5) and constrain the CP-violating charge asymmetry to be -0.170<A(CP)(B-->K(*)gamma)<0.082 at 90% C.L.


Predicting subsequent task performance from goal motivation and goal failure.
Recent research has demonstrated that the cognitive processes associated with goal pursuit can continue to interfere with unrelated tasks when a goal is unfulfilled. Drawing from the self-regulation and goal-striving literatures, the present study explored the impact of goal failure on subsequent cognitive and physical task performance. Furthermore, we examined if the autonomous or controlled motivation underpinning goal striving moderates the responses to goal failure. Athletes (75 male, 59 female, Mage = 19.90 years, SDage = 3.50) completed a cycling trial with the goal of covering a given distance in 8 min. Prior to the trial, their motivation was primed using a video. During the trial they were provided with manipulated performance feedback, thus creating conditions of goal success or failure. No differences emerged in the responses to goal failure between the primed motivation or performance feedback conditions. We make recommendations for future research into how individuals can deal with failure in goal striving.


Aberrant stress-induced Hsp70 expression in immune cells in multiple sclerosis.
Heat shock protein 70 (Hsp70), a prominent member of the heat shock protein family, is a stress-induced chaperone, contributing to the "protein triage" mechanism. However, we and others have previously shown that chaperonin activity of Hsp70 also promotes immune recognition of protein/peptide antigens, including myelin autoantigens. Hsp70 has been strikingly elevated in multiple sclerosis (MS) lesions. In a search for the mechanism of Hsp70 up-regulation in MS, we analyzed Hsp70 expression in peripheral blood mononuclear cells (PBMCs) from MS patients (n = 49), healthy controls (n = 40), and patients with rheumatoid arthritis, (RA; n = 13). Hsp70 was detected by Western blot, and Hsp70 levels were quantified by ELISA. We found that Hsp70 was expressed at low levels in ex vivo PBMCs. However, after heat shock, Hsp70 was up-regulated significantly more (up to sixfold) in MS patients compared with healthy controls. This significant overproduction of Hsp70 was also seen following another stress condition, LPS stimulation. Hsp70 is a product of several independent genes, and we found the HSPA1B gene product to be the major form responsible for Hsp70 protein overexpression in PBMCs. Hsp70 overexpression was preceded by increased nuclear presence of heat shock factor 1 (HSF1). HSF1 activation depends on phosphorylation, and we found that inhibition of the A group of protein kinase C isoenzymes significantly reduced inducible Hsp70 production. These results indicate that immune cells from MS patients are more prone to Hsp70 induction under stress conditions, suggesting a possible link between Hsp70 overexpression and development of autoimmunity.


Density functional theory studies on the microphase separation of amphiphilic comb copolymers in a selective solvent.
The density functional theory was used to study systematically the microphase separation of amphiphilic comb block copolymers with hydrophilic backbone and hydrophobic side chains in a selective solvent. The effects of the length of backbone and side chains, the grafted density, as well as solvent quality were investigated, and a phase diagram was mapped out. In addition, several novel morphologies, such as toroidal micelles, cage-like micelles, and "sphere-in-vesicle" nanostructure, were identified. The knowledge obtained may provide useful information for future experimental investigations.


[Peduncular hallucinosis due to a small hemorrhage around the substantia nigra: a case report].
An 81-year-old female developed peduncular hallucination due to a small hemorrhage around the right substantia nigra is reported. Her hallucination was visual, not accompanying any other type of hallucination. It was vivid, colorful, well described, and recognized as unreal by herself. Different from most of the previous reports, she had no sleep abnormality and the hallucination occurred in daytime and at night, not relating to eye opening or closing. As the lesion of this case was quite restricted to around the right substantia nigra and not affecting the brainstem reticular formation, we speculate that the hallucination itself was induced by the stimulation of mesocorticolimbic system. The other characteristics of the hallucination such as appearing in evening, occurring with eye closing, and accompanying sleep disturbance might be induced when the brainstem involved more widely.


Pharmacogenomic Discovery to Function and Mechanism: Breast Cancer as a Case Study.
Biomedical research is undergoing rapid change, with the development of a series of analytical omics techniques that are capable of generating Biomedical Big Data. These developments provide an unprecedented opportunity to gain novel insight into disease pathophysiology and mechanisms of drug action and response-but they also present significant challenges. Pharmacogenomics is a discipline within Clinical Pharmacology that has been at the forefront in defining, taking advantage of, and dealing with the opportunities and challenges of this aspect of the Post-Genome Project world. This overview will describe the evolution of germline pharmacogenomic research strategies as we have moved from an era of candidate genes to agnostic genome-wide association studies (GWAS) coupled with the functional and mechanistic pursuit of GWAS signals. Germline pharmacogenomic studies of breast cancer endocrine therapy will be used to illustrate research strategies that are being applied broadly to omics studies of drug response phenotypes.


[Writing and publication of a medical article].
To advance in their strategies to manage patients, clinicians need new research results. To be accessible, medical research must be published. Writing and publishing medical articles should respect principles that are described in this article. Good writing is based on a logical organization and the application of scientific style. Organization according to the IMRD structure (Introduction, Methods, Results, Discussion) allows one to present the reasons for and objectives of the study (Introduction), details on whatever has been done to answer the question (Methods), data on the actual study population and answers to the main question (Results), and a critical appraisal of these results, given the limits of the study and current knowledge (Discussion). The main elements of scientific style are precision, clarity, fluidity and concision. Finally, submitting a paper to a scientific journal implies presenting the work in a covering letter and respecting rules for formatting a manuscript (order of presentation, typography, etc.).


Vaccine-induced canine distemper in European mink, Mustela lutreola.
This report describes vaccine-induced canine distemper virus (CDV) infection in four European mink (Mustela lutreola) induced by the administration of a multivalent, avian-origin vaccine. Clinical signs consisting of seizures, ataxia, facial twitching, oculonasal discharge, hyperkeratosis of footpads, and anorexia developed 16-20 days postvaccination. Conjunctival smears from one animal were positive for CDV antigen by direct fluorescent antibody testing, confirming the clinical diagnosis. The four mink died 16-26 days postvaccination. Gross and microscopic lesions that were diagnostic for CDV infection included interstitial pneumonia, lymphoid depletion, nonsuppurative encephalitis, and dermatitis. Vaccine-strain virus was isolated from tissues of three animals. Cases of vaccine-induced distemper in mustelids using avian-origin vaccine have seldom been reported.


Review of IL-17 inhibitors for psoriasis.
Background: The development of biologic agents directed against distinct cytokines and receptors has advanced the therapeutic options available for psoriasis patients. Evidence from preclinical studies suggests that IL-17 may contribute to the pathogenesis of psoriasis. Objective: The objective was to review the safety and efficacy profile for each IL-17 inhibitor by evaluating phase III clinical trial data. Methods: We reviewed the results of phase III clinical trials for the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab. Results: At week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was above 60% for the most efficacious dose of each agent with favorable and comparable safety profiles. The most commonly reported adverse events were nasopharyngitis, headache, and upper respiratory tract infection. Conclusions: The clinical improvement among psoriasis patients on IL-17 inhibitors is similar or superior to the improvement seen with commercially produced biologic agents available accompanied by a favorable short-term safety profile. The results of the phase III trials indicate that IL-17 inhibitors are effective therapeutic options for psoriasis patients.


Schlafen 1 inhibits the proliferation and tube formation of endothelial progenitor cells.
Endothelial progenitor cells (EPCs) are the major source of cells that restore the endothelium during reendothelialization. This study was designed to investigate whether Schlafen 1 (Slfn1) has an effect on the proliferation and tube formation of EPCs in vivo. Slfn1 was expressed in rat EPCs. The overexpression of Slfn1 suppressed the proliferation and tube formation of EPCs; conversely, the knockdown of Slfn1 by shRNA promoted the proliferation and tube formation of EPCs. Furthermore, when Slfn1 was overexpressed, the EPCs were arrested in the G1 phase of the cell cycle. In contrast, when Slfn1 was knocked down, the EPCs progressed into the S phase of the cell cycle. Additionally, the overexpression of Slfn1 decreased the expression of Cyclin D1, whereas the knockdown of Slfn1 increased the expression of Cyclin D1; these findings suggest that Cyclin D1 is downstream of Slfn1 in Slfn1-mediated EPC proliferation. Taken together, these results indicate a key role for Slfn1 in the regulation of EPC biological behavior, which may provide a new target for the use of EPCs during reendothelialization.


Analysis of surgical treatments for earlobe keloids: analysis of 174 lesions in 145 patients.
Treatments for earlobe keloids include surgical excision, postoperative radiotherapy, steroid injection, taping stabilization, and pressure therapy. However, to date, there is no universally accepted treatment strategy for earlobe keloid therapy. A total of 174 lesions in 145 patients who attended the keloid/scar specialist clinic at the Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, between 2006 and 2011 were included and were classified as having primary keloids or recurring keloids. Mild scars, such as hypertrophic scars, were excluded from this study. Appropriate surgical approaches, postoperative adjuvant therapies, such as radiotherapy, and postsurgical self-management were applied. The postsurgical radiotherapy modalities were 15 Gy administered in three fractions over 3 days and 10 Gy administered in two fractions over 2 days. Recurrence during the following 18-month follow-up period was recorded. Of the 174 lesions, 85.6 percent were primary keloids and 14.4 percent were recurrent keloids. Their recurrence rates were 4.7 percent and 0 percent, respectively. The overall recurrence rate was 4.0 percent. Complications during the 18-month follow-up period were not observed. The groups treated with 15-Gy and 10-Gy postsurgical radiotherapy did not differ significantly in terms of recurrence rate (p>0.05). Earlobe keloids can be treated by customized plans that involve appropriate surgical modalities, postoperative radiotherapy, and self-management. Postsurgical radiotherapy with 10 Gy of radiotherapy administered in two fractions over 2 days can be used successfully to treat earlobe keloids. Therapeutic, IV.


Finding cancer's weakest link.
The biological programs of vertebrates exhibit a remarkable degree of functional degeneracy, adaptive compensation and robustness, to preserve homeostasis and generate reproducible phenotypic outputs irrespective of variations in signal strength, noise and quality. Cancers are difficult to treat not only because they are so mechanistically diverse but also because they adapt or evolve in response to any pharmacological elective pressure we impose upon them. Hence, an ideal cancer drug target would exert a function both necessary for cancer cell survival and functionally non-redundant, rendering it impossible for tumor cells to compensate for, or evolve independence from, the inhibitory effect of any drug aimed at that target. In this review, we discuss the unique, non-degenerate and highly pleiotropic role played by Myc in coordinating, engaging and maintaining the diverse intracellular and extracellular programs required for cell proliferation in vivo. These properties make Myc a compelling candidate cancer drug target, at least in principle: an assertion recently reinforced by new in vivo genetic data.


Communicative interactions between subpopulations of human T lymphocytes required for generation of suppressor effector function in a primary antibody response.
The cellular interactions necessary for generation of human T suppressor effector function were examined in a primary in vitro antigen-specific anti-DNP antibody-forming system. During the induction of the anti-DNP response, it was found that T cells of both T4+ and T8+ subsets were necessary to suppress antibody formation, whereas after activation, only the T8+ subset was required. Thus, a population of T4+ T cells appears to be necessary to activate or induce a subset of T8+ cells to suppress. The T4+ suppressor inducer population, like the resting or activated T8+ suppressor effector subset, was sensitive to low dose irradiation. Moreover, the radiosensitive T4+ subset and the previously defined T4+JRA+ subset were shown to be functionally similar or complementary in that both were required for generation of suppressor effector function. These findings suggest that T-T interactions between radiosensitive T4+JRA+ T cells and radiosensitive T8+ T cells are necessary for suppression of primary antigen-specific antibody production in man.


Specificity and sensitivity of gp210 autoantibodies detected using an enzyme-linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis.
Between 10% and 42% of patients with primary biliary cirrhosis (PBC) have been reported to have autoantibodies directed against a restricted epitope of gp210, a glycoprotein of the nuclear pore membrane. The prevalence and specificity of these antibodies was studied in a French series of 285 patients with PBC and 497 control individuals affected with other liver or autoimmune diseases. Sera were analyzed by an enzyme-linked immunosorbent assay (ELISA) that used a synthetic polypeptide containing the predominant autoepitope of gp210, in parallel to immunoblotting of gp210 protein and immunofluorescence microscopy. Autoantibodies to the gp210 epitope detected by ELISA were 25.5% sensitive and 99.5% specific for the diagnosis of PBC. These results were in agreement with a 99.4% specificity with immunoblotting analysis and a 96.6% specificity with immunofluorescence. In a subset of PBC patients without detectable antimitochondrial autoantibodies (AMA), gp210 autoantibodies were found in 7 of 15 patients (47%). Therefore, gp210 autoantibodies are highly specific for PBC and may be of particular utility in assessing patients without AMA or with other atypical presentations.


Characterization of an outbreak of hand, foot, and mouth disease in Nanchang, China in 2010.
Recent outbreaks of human enterovirus 71 (EV71) infection and EV71-associated hand, foot, and mouth disease (HFMD) in China have affected millions and potentially lead to life-threatening complications in newborns. Furthermore, these outbreaks represent a significant global public health issue in the world. Understanding the epidemiology of HFMD and EV71 infection and their transmission patterns in China is essential for controlling outbreaks. However, no studies on the outbreaks of HFMD and EV71 infection in China during 2010 have been reported. In this report, we carried out an epidemiological analysis to study an outbreak of HFMD and EV71 infection in 2010 in the city of Nanchang in the Jiangxi province of People's Republic of China. From April 7 to May 11, 2010, a total of 109 HFMD cases were reported, and in this report the HFMD cases were studied by both epidemiological and laboratory analyses. The epidemiological study indicates that children aged younger than 8 years old represented more than 90% of the reported cases, with the age group of 1-3 years containing the highest number of cases. Laboratory studies detected a high prevalence of EV71 amongst the cases in our study, suggesting EV71 as a common enterovirus found in HFMD cases in Nanchang. Phylogenetic analysis of the sequence of the VP1 region of four EV71 isolates indicated that the Nanchang strains belong to the C4 subgenotype commonly found in China during outbreaks in 2008 but contain distinct variations from these strains. Our study for the first time characterizes the epidemiology of HFMD and EV71 infection in China in 2010 and furthermore, provides the first direct evidence of the genotype of EV71 circulating in Nanchang, China. Our study should facilitate the development of public health measures for the control and prevention of HFMD and EV71 infection in at-risk individuals in China.


Detection of pulmonary hypertension with multidetector CT and echocardiography alone and in combination.
To test the reliability of potentially new computed tomographic (CT) indicators of pulmonary hypertension (PH) and to establish whether a combination of CT and echocardiographic measurements was more predictive of PH than either test alone. The institutional review board approved this retrospective study; patient consent was not required. Seventy-seven patients undergoing right-sided heart catheterization were examined. CT diameters of the main pulmonary artery, ascending aorta, and thoracic vertebra and cross-sectional area of the main pulmonary artery were measured. Segmental and subsegmental arterial diameters were recorded, and segmental artery size was compared with adjacent bronchus size by using a semiquantitative scoring system. The relationship between CT measurements and mean pulmonary arterial pressure (mPAP) was tested with linear regression. Multivariate regression was used to establish a composite index of mPAP by using CT markers of PH with echocardiography-derived right ventricular systolic pressure (RVSP). Post hoc logistic regression and receiver operating characteristic curve analysis were performed to test the diagnostic ability of the CT-echocardiography composite. The ratios of the diameter of the main pulmonary artery to the diameter of the ascending aorta (R(2) = 0.45; P < .001) and of the cross-sectional area of the pulmonary artery to the diameter of the ascending aorta (R(2) = 0.45; P < .001) correlated equally with mPAP. The ratio of the diameter of the main pulmonary artery to the diameter of the thoracic vertebra, the segmental arterial diameter, and the segmental artery-to-bronchus ratio were related to mPAP but did not strengthen correlations compared with the ratio of the diameter of the main pulmonary artery to the diameter of the ascending aorta alone. A composite index of the ratio of the diameter of the main pulmonary artery to the diameter of the ascending aorta and echocardiography-derived RVSP was more strongly related (R(2) = 0.55) to mPAP and was more significantly predictive of PH than either measure alone. A combination of CT and echocardiographic markers of PH is more closely related to mPAP than either test in isolation.


A unified strategy targeting the thiodiketopiperazine mycotoxins exserohilone, gliotoxin, the epicoccins, the epicorazines, rostratin A and aranotin.
A unified synthetic strategy directed towards mycotoxins belonging to the thiodiketopiperazine family is reported. The building blocks for a number of natural products--including exserohilone, gliotoxin, the epicoccins, the epicorazines, rostratin A and aranotin--have been synthesised stereoselectively from a common precursor. This key intermediate was constructed through an efficient and highly diastereoselective [2+2] cycloaddition between a ketene and an enecarbamate derived from L-pyroglutamic acid. The annelation of the second ring was accomplished through ring-closing metathesis and enol ether-olefin ring-closing metathesis to provide both cis- and trans-annelated azabicyclic cyclohexenones, as well as an annelated seven-membered cyclic enol ether. A Pd-catalysed elimination of allyl acetate gave rise to the cyclohexadienol structure of gliotoxin. Dimerisation of one building block to afford the diketopiperazine core was demonstrated.


Comparison of Aphakic Refraction and Biometry-Based Formulae for Secondary In-The-Bag and Sulcus-Implanted Intraocular Lens Power Estimation in Children.
The aim of the study was to compare the accuracy of refractive outcomes in children undergoing secondary in-the-bag or cilliary sulcus intraocular lens (IOL) implantation, using aphakic refraction (AR)-based formulae (Hug and Khan) and biometry-based formulae (Holladay 1, Hoffer Q, SRK/T, and SRK II). In this retrospective study, a total of 65 eyes of 44 patients who underwent secondary in-the-bag or cilliary sulcus IOL implantation were included and divided into 2 groups: 39 eyes of the in-the-bag IOL group and the other 26 eyes of the sulcus-implanted IOL group. Holladay 1, Hoffer Q, SRK/T, and SRK II formulae were employed depending on the biometric data, while Hug and Khan formulae were used based on preoperative AR. The prediction error (PE) and the absolute value of predicted error (APE) were compared between the 2 groups and formulae. In the in-the-bag IOL group, nonsignificant differences of APE were found among the 6 formulae, while the Holladay 1, Hoffer Q, SRK/T, and SRK II all demonstrated a significant hyperopic shift of median PE value compared to the Hug formula (p < 0.05, all), and Holladay 1 and SRK II also showed a significant hyperopic shift of PE compared to the Khan formula (p < 0.05, both). Higher percentages of eyes with PE <1 D were found using Hoffer Q and SRK/T. In the sulcus-implanted group, the Holladay 1, Hoffer Q, and SRK/T had a significantly smaller median value of APE than the Hug and Khan formulae (p < 0.05, all), and the SRK II had a significantly smaller median value of APE than the Hug formula (p < 0.05), while Holladay 1 had the lowest value of APE. Higher percentages of eyes within PE <1 D were found using Holladay 1, Hoffer Q, and SRK/T, while the highest one was SRK/T. Significantly larger hyperopic shifts of median PE value using all the 6 formulae were found in eyes with sulcus-implanted IOL than eyes with in-the-bag implanted IOL (p < 0.05, all). In the eyes of with in-the-bag implanted IOL, the Hug and Khan formulae had significantly smaller APE values when compared with the eyes with sulcus-implanted IOL (p < 0.05, both). Whether IOL was in the bag or implanted in the sulcus, almost all the formulae showed hyperopic shift, SRK/T showed the best accuracy. Biometry-based formulae were superior to AR-based formulae in accuracy of IOL power calculation, especially when IOL was implanted in the sulcus. In-the-bag IOL implantation should always be with higher priorities, especially when using AR-based formulae in IOL power calculation.


Mathematical and experimental analyses of oppositional algorithms.
Evolutionary algorithms (EAs) are widely employed for solving optimization problems with rugged fitness landscapes. Opposition-based learning (OBL) is a recent tool developed to improve the convergence rate of EAs. In this paper, we derive the probabilities that distances between OBL points and the optimization problem solution are less than the distance between a given EA individual and the optimal solution. We find that the quasi-reflected opposition point yields the highest probability and is the most likely candidate to be closer to the optimal solution. We then employ CEC 2013 competition benchmark problems and select a set of trajectory optimization problems from the European Space Agency to study the performance of three OBL algorithms in conjunction with three different EAs. The CEC 2013 test suit simulations indicate that quasi-reflection accelerates the performance of the EA, especially for more difficult composition functions. The space trajectory experiments reveal that differential evolution with opposition generally returns the best objective function value for the chosen minimization problems.


Cytochrome P4502E in vivo and in vitro in the dwarf goat: effects of enzyme induction and the applicability of chlorzoxazone as marker substrate.
Cytochrome P4502E activities, inducibility and the applicability of chlorzoxazone as a marker substrate for this enzyme were investigated in female dwarf goats. Goats were treated with either isoniazid or beta-naphthoflavone. Treatment with isoniazid resulted in a 1.4 fold increase of the chlorzoxazone hydroxylation rate in hepatic microsomes. Aniline- and p-nitrophenol hydroxylation rates were increased by roughly the same extent (1.6 and 1.25 fold resp.) and increased levels of cytochrome P4502E apoproteins were found by Western blotting. Treatment with the cytochrome P4501A inducer beta-naphthoflavone resulted in a 2.5 fold induction of the in vitro chlorzoxazone hydroxylation rate, whereas the hydroxylation rates of aniline and p-nitrophenol were not induced. After treatment with isoniazid, chlorzoxazone plasma clearance was increased from 5.0 mL/min/kg to 11.0 mL/min/kg. Chlorzoxazone was almost completely excreted in the urine as conjugated hydroxy metabolites. These results do not support the hypothesis that cytochrome P4502E is of particular importance in goats, as has been suggested earlier. Furthermore, chlorzoxazone has limited value as a marker substrate for this enzyme, since cytochrome P4501A enzymes appear to play an important role in its biotransformation.


Transduction of antisense cyclin D1 using two-step gene transfer inhibits the growth of rat hepatoma cells.
Cyclin D1, one of the G(1) cyclins, is frequently overexpressed in several types of carcinomas and is thought to play an important role in tumorigenesis and tumor progression including hepatocellular carcinoma. We constructed a retrovirus vector-carrying rat cyclin D1 cDNA in the reverse orientation, resulting in expression of antisense (AS) cyclin D1 mRNA. For efficient transduction of this recombinant retrovirus, two-step gene transfer was performed. The rat hepatoma cell line (dRLh84) was infected with this recombinant retrovirus after preinfection with adenovirus expressing the retrovirus receptor. In the rat hepatoma cells, AS cyclin D1 mRNA was expressed, inducing a decrease in the expression of endogenous cyclin D1 mRNA and an inhibition of cell growth. Moreover, two-step gene transfer of AS cyclin D1 into s.c. hepatoma xenografts resulted in inhibition of tumor growth and prolonged animal survival. In the virus-infected tumor xenografts, expression of cyclin D1 was immunohistochemically inhibited, and apoptosis of hepatoma cells was detected. These findings suggest that transduction of AS cyclin D1 is useful as an adjunct to standard treatments for hepatocellular carcinoma.


Treatment of locally aggressive well-differentiated thyroid cancer.
The object of this study, conducted at Unicamp between 1988 and 1998, was to evaluate retrospectively the outcome of patients treated for locally aggressive well-differentiated thyroid carcinomas (LATC). Nineteen (42%) of 45 patients with thyroid carcinomas were considered to have LATC. The preoperative diagnosis of carcinoma was made either by fine needle aspiration biopsy (15 patients) or during surgery (4 patients). The usual prognostic factors were analyzed and classified according to risk groups. Survival was evaluated using the Kaplan-Meier method. Most of the patients were female (73%), with a mean age of 48 years. Eighteen (95%) had papillary carcinomas. Four patients were classified as high risk (21%) and the remaining 15 (79%) as intermediate risk. All patients underwent total thyroidectomy and different types of neck dissections. The structures invaded by tumors were strap muscles and trachea (four cases); recurrent nerve and larynx (three cases); manubrium, esophagus, and jugular vein (two cases); and hyoid bone and pharynx (one case). Complete tumor resection was carried out according to the extent of local invasion; no postoperative deaths resulted. Details of the procedures are provided in Table 4 and in the Discussion. Postoperative radioactive iodine treatment was used in 15 patients (79%). A mean follow-up (+/-7 years) revealed 13 (68%) patients without disease, 4 patients (21%) alive with controlled systemic disease, and 2 (11%) deaths from distant metastasis. The Kaplan-Meir survival curve was comparable with other studies in the literature. This study found that the frequency of LATC (42%) was higher than in most studies. Aggressive surgical therapy to treat these tumors is compatible with a low recurrence rate and long-term survival in a significant proportion of patients.


How slowing senescence translates into longer life expectancy.
Mortality decline has historically been largely a result of reductions in the level of mortality at all ages. A number of leading researchers on ageing, however, suggest that the next revolution of longevity increase will be the result of slowing down the rate of ageing. In this paper, we show mathematically how varying the pace of senescence influences life expectancy. We provide a formula that holds for any baseline hazard function. Our result is analogous to Keyfitz's 'entropy' relationship for changing the level of mortality. Interestingly, the influence of the shape of the baseline schedule on the effect of senescence changes is the complement of that found for level changes. We also provide a generalized formulation that mixes level and slope effects. We illustrate the applicability of these models using recent mortality decline in Japan and the problem of period to cohort translation.


Stem infusions enhanced methionine content of soybean storage protein.
The quality of soybean (Glycine max [L.] Merrill) seed storage protein is limited by its low methionine (Met) content. Met supplementation of an in vitro soybean cotyledon culture has been shown to increase Met content by 21.9% due to an inhibition of the synthesis of the Met-devoid beta subunit of 7S storage protein (JF Thompson et al. 1981, Phytochemistry 20: 941-945). The objective of this research was to determine if Met supplementation of intact plants would result in a similar improvement in soybean protein quality. A solution including 10 millimolar d,l malic acid plus 10 millimolar K(2)HPO(4) with or without 20 millimolar d,l Met or 20 millimolar Na(2)SO(4) was infused throughout seed development into lower stem internodes of soybeans (cv ;Williams 79' or ;Williams 82') grown under both greenhouse and field conditions. Pediatric intravenous kits were used to infuse an average of 51.2 milliliters per plant. Met content of whole soybean seeds from intact plants receiving Met infusions increased by as much as 22.7%. Even greater (up to 31.0%) increases in cysteine (Cys) content were noted, indicating that soybean plants are able to metabolize Met to Cys, or that supplemental Met allows Cys accumulation by some other mechanism. Electrophoretic patterns showed a dramatic decrease in the synthesis of the beta subunit of 7S storage protein when Met was supplemented, and this effect was not confined to seeds at the lower nodes. In addition, seeds from upper compared to lower plant nodes (regardless of infusion treatment) had greater protein content (45.0 versus 41.6 w/w%), and different protein composition, as indicated by significantly different amino acid profiles. Methionine supplementation of intact soybean plants improved protein quality through an alteration in storage protein composition.


Art as a tool for pastoral care.
Argues for the use of art in the delivery of pastoral care, especially with small children, the handicapped, and persons with emotional problems. Offers an example of such usage with a hospitalized spastic quadraplegic boy. Explores ways in which one's faith also might be expressed using visual modes rather than verbal ones.


Endothelin-1 receptor binding assay for high throughput chemical screening.
An endothelin-1 (ET-1) receptor-binding assay, in microtiter format, has been developed for use in high throughput chemical or natural product screening. A rat smooth muscle, clonal cell line derived from embryonic thoracic aorta and designated A10 has been shown to consistently express high-affinity ET-1 receptors. A 96-well microtiter filtration plate, with individual PVDF membranes attached to the bottom of each well, was used for separation. In saturation binding assays, using [125I]Tyr13-ET-1, Scatchard analysis was monophasic, indicating a single high-affinity population of receptors with Kd = 0.12 nM with approximately 40,000 receptors per cell. The Ki values for peptides, known to bind at the ET receptor, were as follows: ET-1, 0.14 nM; ET-2, 0.16 nM; sarafotoxin S6b, 0.6 nM; VIC, 0.2 nM; ET-3, 16 nM; and big human ET, greater than 1 microM. ET receptors on A10 cells were stable for at least 2 months when stored at -20 degrees C. The assay is suitable for automation, because it is stable and reproducible. This method gave a 90% reduction in radioactive waste compared to tissue homogenate assays that use glass fiber filtration and cell harvesters.


[The effects of different herbal compound and extracts from different extraction methods on hypoxia tolerance in mice].
Objective: To investigate the effects of different prescription compositions of traditional Chinese medicine and its different extraction methods of compound formula extracts on hypoxia tolerance in mice, in order to preferably select their prescription compositions and preparation extraction methods. Methods: Male BALB/c mice were randomly divided into 6 groups: blank control group, compound danshen group, compound Rhodiola Rosea alcohol-water extract group (Rhodiola rosea, Astragali Radix, Polygonati Rhizoma, Lycii Fructus), compound Rhodiola Rosea water extract group, compound Astragalus alcohol-water extract group (Astragali Radix, Polygonati Rhizoma, Lycii Fructus) and compound Astragalus water extract group, 30 mice in each group. Each group was administered continuously by gavage for 10 d. The blank group was gavaged with sterilized injection water. The mice in the other groups were treated with 0.15 g/kg of compound danshen, 3 g/kg of compound Rhodiola Rosea alcohol-water extract or water extract, and 1.7 g/kg of compound Astragalus alcohol-water extract or water extract, respectively. Each group was subjected to normobaric hypoxia tolerance test, sodium nitrite toxicity survival test and acute cerebral ischemia-hypoxia test 1 h after the last gavage, and the mice brain tissues were used to determine the activity of antioxidant enzymes and metabolites related to oxidative stress. Results: Compared with the blank control group, in normobaric hypoxia tolerance test, the survival time of mice in the compound danshen group and the compound Astragalus alcohol-water extract group and water extraction group was prolonged significantly (P<0.01), and the number of open-mouth gasping after cerebral ischemia and hypoxia was increased significantly (P<0.05). There was no statistical difference in survival time after sodium nitrite injection in each group. Compared with the blank control group, the activities of T-AOC, SOD, GSH and CAT were increased significantly (P<0.05, P<0.01) and the content of MDA was decreased significantly (P<0.01) in the compound Astragalus water extract group. Compared with the compound danshen group, the activities of SOD, CAT and GSH were increased significantly (P<0.01, P<0.05) and the content of MDA was decreased significantly (P<0.05). Conclusion: Compound Astragalus water extraction has the best effect of hypoxia tolerance, compound Rhodiola Rosea can eliminate Rhodiola rosea and consists of Astragali Radix, Polygonati Rhizoma, Lycii Fructus and its extraction method is water extraction.


Prevalence of hepatitis B and C markers in volunteer blood donors in Crete. A 5-year study.
Greece is a country with an intermediate prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Crete, the third-largest island of the Mediterranean sea, has a different prevalence of viral hepatitis. One-eighth of the total island population, of 550,000, was included in a 5-year study of blood donors from three out of four blood banks, serving three out of four prefectures of the island. Markers for HBV and HCV were studied and evaluated according to geographical area, gender and age of donor. A total of 65219 blood donors were studied. A greater number of males than females were hepatitis B surface antigen (HBsAg) positive (0. 41% vs 0.28%, respectively) with a peak at a younger age for males and older age for females. Males are more frequently exposed to HBV and become carriers more often than females. For HCV, an opposite gender trend was found, females being infected more frequently (0. 49%) than males (0.37%). Statistical differences were found among geographical areas of the island. Hence, Crete is an area of low endemicity for HBsAg in blood donors. The HCV infectivity is more similar to Northern Europe than to other neighbouring countries. Differences in geographical distribution within the island and during different years indicate the need for extended epidemiological surveys for valid results.


Agreement between the Cochrane risk of bias tool and Physiotherapy Evidence Database (PEDro) scale: A meta-epidemiological study of randomized controlled trials of physical therapy interventions.
The Cochrane risk of bias (CROB) tool and Physiotherapy Evidence Database (PEDro) scale are used to evaluate risk of bias of randomized controlled trials. We assessed the level of agreement between the instruments. We searched the Cochrane Library to identify trials included in systematic reviews evaluating physical therapy interventions. For trials that met our inclusion criteria (primary reference in Cochrane review, review used CROB (2008 version), indexed in PEDro), CROB items were extracted from the reviews and PEDro items and total score were downloaded from PEDro. Kappa statistics were used to determine the agreement between CROB and PEDro scale items that evaluate similar constructs (e.g., randomization). The total PEDro score was compared to the CROB summary score (% of items met) using an Intraclass Correlation Coefficient. Sensitivity analyses explored the impact of the CROB "unclear" category and variants of CROB blinding items. Kappa statistics were used to determine agreement between different thresholds for "acceptable" risk of bias between CROB and PEDro scale summary scores. We included 1442 trials from 108 Cochrane reviews. Agreement was "moderate" for three of the six CROB and PEDro scale items that evaluate similar constructs (allocation concealment, participant blinding, assessor blinding; Kappa = 0.479-0.582). Agreement between the summary scores was "poor" (Intraclass Correlation Coefficient = 0.285). Agreement was highest when the CROB "unclear" category was collapsed with "high" and when participant, personnel and assessor blinding were evaluated separately in CROB. Agreement for different thresholds for "acceptable" risk of bias between CROB and PEDro summary scores was, at best, "fair". There was moderate agreement for half of the PEDro and CROB items that evaluate similar constructs. Interpretation of the CROB "unclear" category and variants of the CROB blinding items substantially influenced agreement. Either instrument can be used to quantify risk of bias, but they can't be used interchangeably.


Superdiffusion from Emergent Classical Solitons in Quantum Spin Chains.
Finite-temperature spin transport in the quantum Heisenberg spin chain is known to be superdiffusive, and has been conjectured to lie in the Kardar-Parisi-Zhang (KPZ) universality class. Using a kinetic theory of transport, we compute the KPZ coupling strength for the Heisenberg chain as a function of temperature, directly from microscopics; the results agree well with density-matrix renormalization group simulations. We establish a rigorous quantum-classical correspondence between the "giant quasiparticles" that govern superdiffusion and solitons in the classical continuous Landau-Lifshitz ferromagnet. We conclude that KPZ universality has the same origin in classical and quantum integrable isotropic magnets: a finite-temperature gas of low-energy classical solitons.


Modulating Optical Characteristics of Nanoimprinted Plasmonic Device by Re-Shaping Process of Polymer Mold.
Metal nanostructures exhibit specific optical characteristics owing to their localized surface plasmon resonance (LSPR) and have been studied for applications in various optical devices. The LSPR property strongly depends on the size and shape of metal nanostructures; thus, plasmonic devices must be designed and fabricated according to their uses. Nanoimprint lithography (NIL) is an effective process for repeatedly fabricating metal nanostructures with controlled sizes and shapes and require optical properties. NIL is a powerful method for mass-producible, low-cost, and large-area fabrication. However, the process lacks flexibility in adjusting the size and shape according to the desirable optical characteristics because the size and shape of metal nanostructures are determined by a single corresponding mold. Here, we conducted a re-shaping process through the air-plasma etching of a polymer's secondary mold (two-dimensional nanopillar array made of cyclo-olefin polymer (COP)) to modulate the sizes and shapes of nanopillars; then, we controlled the spectral characteristics of the imprinted plasmonic devices. The relationship between the structural change of the mold, which was based on etching time, and the optical characteristics of the corresponding plasmonic device was evaluated through experiments and simulations. According to evaluation results, the diameter of the nanopillar was controlled from 248 to 139 nm due to the etching time and formation of a pit structure. Consequently, the spectral properties changed, and responsivity to the surrounding dielectric environment was improved. Therefore, plasmonic devices based on the re-shaped COP mold exhibited a high responsivity to a refractive index of 906 nm/RIU at a wavelength of 625 nm.


Human umbilical vein endothelial cells accelerate oxalate-induced apoptosis of human renal proximal tubule epithelial cells in co-culture system which is prevented by pyrrolidine dithiocarbamate.
Oxalate is the most common component of kidney stones and elevated urinary levels induce renal tubular cell toxicity and death which is essential for crystal attachment. Endothelial cells, in some studies have been shown to regulate certain functions of renal proximal tubule cells. The aim of this study was to evaluate the effect of endothelial cells on tubular cell apoptosis in a co-culture system mimicking the in vivo renal physiological settings. The human umbilical vein endothelial cells (HUVEC) and human renal proximal tubule epithelial cells (RPTEC) were exposed to increasing concentrations (0-1.0 mM) of oxalate with or without 10 μM PDTC pretreatment for 24 h. In HUVEC, RPTEC and HUVEC-RPTEC co-cultures, the cell viability was measured using the WST-1 assay and cell death with the TUNEL analysis using the flow cytometry. The treatment of RPTECs with oxalate lead to 8.9-26.2% cell death which was reduced to 0-1.6% with the PDTC pretreatment. The death rate of RPTECs was significantly increased by 15-19% at different oxalate concentrations when co-cultured with HUVECs. In contrast, cell viability was not substantially altered in PDTC pretreated RPTECs that were co-cultured with HUVECs. Apoptosis was the way of cell death as similar rate of apoptosis was observed in cell culture systems. Although cell viability of RPTECs was further reduced when co-cultured with HUVECs, it was restored with the pretreatment of PDTC. This is the first study focusing on the role of endothelial cells on RPTEC apoptosis following hyperoxaluria.


Alterations in cysteine proteinase content of rat lung associated with development of Pneumocystis carinii infection.
The rate of hydrolysis of three cysteine-type proteinase substrates, N-benzyloxycarbonyl-Arg-Arg-4-methyl-7-coumarylamide (AMC) (cathepsin B), Arg-AMC (cathepsin H), and N-benzyloxycarbonyl-Phe-Arg-AMC (cathepsin L), were determined in rat lung throughout the time course of the induction of Pneumocystis carinii infection by immunosuppression. Cathepsin B-like and cathepsin L-like activities fell below control values initially, but from week 8 of the immunosuppressive treatment significant increases above the control were noted. Cathepsin H-like activity was greater than control levels from week 3, and by week 12 it was 7,600% of the mean control value. When compared with the relative degree of infection, as assessed from the number of cysts present in lung impression smears, cathepsin B-like and cathepsin L-like activities were significantly increased only at heavy parasite burdens while cathepsin H-like activity displayed a close correlation with parasite number (r = 0.884; P less than 0.001). Activity was detected in lysates of purified P. carinii with all three substrates. Treatment of heavily infected animals with co-trimoxazole cleared the lungs of P. carinii, and this was accompanied by a marked reduction in proteinase activity, in particular, cathepsin H-like activity, which fell from 108- to 3-fold the mean control value following drug treatment. Analysis of cathepsin H isozyme patterns by fluorography following isoelectric focusing revealed differences between treated and control lung samples. In the immunosuppressed group, there was a time-dependent increase in the intensity of some of the bands observed in the controls and an appearance of several novel bands which corresponded to bands observed in lysates of P. carinii. It is likely, therefore, that the increased proteinase activity observed in the treated group is due, at least in part, to isozymes from P. carinii; consequently, cathepsin H-like activity might be of use diagnostically in the identification of P. carinii infection and in the estimation of parasite burden.


A narrative review of sociodemographic risk and disparities in screening, diagnosis, treatment, and outcomes of the most common extrathoracic malignancies in the United States.
There is a well-established association between multiple sociodemographic risk factors and disparities in cancer care. These risk factors include minority race and ethnicity, low socioeconomic status (SES) including low income and education level, non-English primary language, immigrant status, and residential segregation, and distance to facilities that deliver cancer care. As cancer care advances, existing disparities in screening, treatment, and outcomes have become more evident. Lung cancer remains the most common and fatal malignancy in the United States, with breast, colorectal, and prostate cancer being the three most common and deadly extrathoracic malignancies. Achieving the best outcomes for patients with these malignancies relies on strong physician-patient relationships leading to robust screening, early diagnosis, and early referral to facilities that can deliver multidisciplinary care and multimodal therapy. It is likely that challenges experienced in developing patient trust and understanding, providing access to screening, and building referral pipelines for definitive therapy in lung cancer care to vulnerable populations are paralleled by those in extrathoracic malignancies. Likewise, progress made in delivering optimal care to all patients across sociodemographic and geographic barriers can serve as a roadmap. Therefore, we provide a narrative review of current disparities in screening, treatment, and outcomes for patients with breast, prostate, and colorectal malignancies.


The main pigment of the dormant Mycobacterium smegmatis is porphyrin.
Upon transition of Mycobacterium smegmatis into the dormant state, accumulation of a dark brown fluorescent pigment was observed. This pigment gave bright red fluorescence in both cells and the culture medium. Based on 1H-NMR, MALDI and UV spectra, the fluorescent compounds, extracted from the culture medium as well as from the dormant cells, were concluded to be a mixture of free coproporphyrin III and uroporphyrin III and their corresponding methyl esters. A possible significance of porphyrin pigment accumulation in the dormant cells is discussed.


Generation of in vitro natural cytotoxicity of horse lymphocytes against sarcoid-derived tumor cells not expressing major histocompatibility complex antigens.
To analyze in vitro lymphocyte-mediated immune responses of horses with sarcoids against allogeneic sarcoid cells containing endogenous retrovirus but not expressing major histocompatibility complex antigens. Lymphocyte-mediated immune reactions were assessed by means of proliferative responses in mixed lymphocyte tumor cell culture (MLTC) assay and lymphocyte-mediated cytotoxicity against various equine target cells. 12 horses with sarcoid tumors and 15 control horses. Blood lymphocytes were cocultured in MLTC with allogeneic sarcoid cells (Mc-1, BayMc-1), equine testis cells, or normal equine dermal fibroblasts. Lymphocytes were assayed for proliferative responses by [3H]thymidine uptake and for cytotoxicity against the same targets by 51Cr release assay. The lymphocyte populations were analyzed for some common surface markers. Lymphocytes from horses with sarcoids exerted an anamnestic proliferative response in MLTC against Mc-1 cells, but this procedure never generated cytotoxic lymphocytes. However, lymphocytes from all horses cultured in medium with 10% allogeneic serum only had selective. natural cytotoxicity against Mc-1 that was generated without DNA synthesis. Approximately 80% of the lymphocytes disappeared during culture; however the remaining population of small, viable lymphocytes indicated a decrease of CD4+ T lymphocytes, but numbers of T cells with receptors for Helix pomatia A hemagglutinin were unaffected. Few lymphocytes had Fc-receptors for IgG, were complement-reactive positive cells or were B cells expressing surface immunoglobulin. Results may indicate a natural defense system, which preferentially recognizes and lyses tumor cells that are deficient in surface expression of major histocompatibility complex antigens, without intervention of conventional T-cell receptors or antibodies.


Cardioprotection by endoplasmic reticulum stress-induced autophagy.
This study tested the hypothesis that the induction of autophagy by producing therapeutic amounts of endoplasmic reticulum (ER) stress in the heart before an ischemic insult would ameliorate/reduce subsequent lethal myocardial ischemic/reperfusion (I/R) injury (similar to ischemic preconditioning). A dose-response study with both tunicamycin and thapsigargin was performed to determine the optimal dose (0.3 mg/kg) for inducing autophagy for cardioprotection. The Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned into five groups: normal control (injected with saline only), high (3 mg/kg), and low (0.3 mg/kg) doses of tunicamycin or thapsigargin, respectively. After 48 h, the rats were subjected to an isolated working heart preparation: 30 min ischemia followed by 2 h of reperfusion with continuous left ventricular function monitoring. At the end, the hearts were subjected to either measurement of infarct size or cardiomyocyte apoptosis. Some hearts (from different sets of experiments) were used for transmission electron microscopy (TEM), confocal microscopy, or Western blot analysis. Tunicamycin and thapsigargin, irrespective of the dose, induced sufficient ER stress, as evidenced by the increased phosphorylation or activation of eIF2α and PERK. Such ER stress potentiated autophagy in the heart, as evidenced by an increase in LC3-II, beclin-1, and Atg5. This was also supported by TEM, clearly showing the production of autophagosomes, and by confocal microscopy, showing upregulation of eIF2α and beclin-1. The autophagy produced with lower doses of tunicamycin and thapsigargin in the face of myocardial I/R resulted in reduction of the I/R injury, as evidenced by improved left ventricular function and reduced myocardial infarct size and cardiomyocyte apoptosis. In concert, an induction of GRP78 and activation of Akt and Bcl-2 occurred. The higher doses conversely were detrimental for the heart and were associated with induction of CHOP and downregulation of Akt. The results thus display the proof of concept that induction of autophagy by ER stress (therapeutic amount) before ischemia (similar to ischemic preconditioning) could reduce subsequent lethal ischemic reperfusion injury.


Selection and Validation of Reference Genes for Quantitative Real-Time PCR Normalization in Athetis dissimilis (Lepidoptera: Noctuidae) Under Different Conditions.
Reference genes are the key to study gene expression patterns using quantitative real-time PCR (qRT-PCR). No studies on the reference genes of Athetis dissimilis, an important agricultural pest, have been reported. In order to determine the reference genes for qRT-PCR normalization in A. dissimilis under different conditions, 10 candidate genes [18S ribosomal protein (18S), 28S ribosomal protein (28S), arginine kinase (AK), elongation factor 1 alpha (EF1-α), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal protein L32 (RPL32), ribosomal protein L40 (RPL40), alpha-tubulin (α-TUB), beta-actin (β-ACT), and beta-tubulin (β-TUB)] of A. dissimilis were selected to evaluate their stability as reference genes under different biotic and abiotic conditions by using five tools, geNorm, NormFinder, BestKeeper, ΔCt, and RefFinder. Furthermore, CSP1 and superoxide dismutase (SOD) were used as target genes to validate the candidate reference genes. The results showed that different reference genes were needed under different experimental conditions, among which, EF-1α, RPL40, and 18S are most suitable reference genes for studying genes related development stages of A. dissimilis, RPL40 and α-TUB for larval tissues, α-TUB and 28S for adult tissues, EF-1α and β-ACT for insecticidal treatments, β-ACT and 28S for temperature treatments, EF-1α and β-ACT for starvation treatments, RPL40 and 18S for dietary treatments, and 18S, 28S, and α-TUB for all the samples. These results provide suitable reference genes for studying gene expression in A. dissimilis under different experimental conditions, and also lay the foundation for further research into the function of related genes in A. dissimilis.


Development of a novel fungicide, tolprocarb.
Tolprocarb developed by Mitsui Chemicals Agro, Inc. (Tokyo, Japan) was discovered as a new oomycete fungicide. However, its antifungal spectrum and action mechanisms against fungi are completely different from those of the original compound, iprovalicarb. Tolprocarb has a potent and highly controlled effect on a rice blast fungus Magnaporthe grisea, and its mode of action was revealed to be the inhibition of polyketide synthase in the melanin biosynthesis pathway. In addition, tolprocarb induced systemic acquired resistance in Arabidopsis thaliana and rice (Oryza sativa L.). Owing to these double modes of action, tolprocarb can effectively control not only rice blast but also bacterial diseases, and has a low risk of developing fungicide-resistant isolates. Tolprocarb also provides long-term residual activity. A meta-analysis was performed in order to demonstrate tolprocarb's superior control against panicle blast in paddy fields. In addition, tolprocarb did not show cross-resistance against the fungi that are resistant to dehydratase inhibitor in melanin biosynthesis (Melanin Biosynthesis Inhibitor-Dehydratase; MBI-D) or respiratory complex III: cytochrome bc 1 at Quinone outside site inhibitor (Quinone outside Inhibitor; QoI). Owing to its stable effects, tolprocarb appears to be a suitable choice for practical use against fungi in the rice production field.