Physical therapist student interest in full-time faculty positions.
A strong demand exists for allied health faculty in institutions of higher education. This study focused on physical therapists for the purposes of: 1) determining student physical therapist interest in full-time faculty positions at some point in their professional careers, 2) identifying factors that might influence student interest in full-time faculty positions at some point in their careers, and 3) being able to suggest ways in which students might be encouraged to consider academic careers in the future. Twenty-nine accredited professional physical therapist programs gave permission for their graduating students to be surveyed; 1,160 surveys were sent out, and 1,037 usable surveys were returned (89% return rate). Of the 1,037 respondents, 569 students (59%) expressed an interest in pursuing a full-time faculty position at some point in their career. Demographic data were reported, and chi 2 was used to analyze survey results statistically. The items that were statistically significant with regard to interest in a full-time faculty position were: 1) a physical therapist instructor had encouraged a student to pursue a full-time faculty position, 2) the student had a learning experience in which a faculty position was discussed as a career option, and 3) the student had a parent who was employed in education. Physical therapist faculty members were identified by students as the group with the greatest influence on a student's decision to choose an academic career. Students identified the following factors as negatives for pursuing full-time faculty positions: 1) having to be engaged in research projects, 2) being restricted to treating patients only occasionally, and 3) being required to speak before groups. The results of this study suggested methods that physical therapist faculty might employ to recruit students to academia, such as providing individual encouragement, discussing faculty positions as a career option, providing opportunity for students to become more comfortable with aspects of research and with public speaking, and informing students that in many academic settings one still can treat patients. Further research is needed to determine if these results can be generalized to other allied health professions.


Percutaneous transarticular atlantoaxial screw fixation using a cannulated screw system and image guidance.
In 2000 a cannulated screw stabilization system for posterior cervical instrumentation was introduced in our department for use in complex cervical fixation procedures. A special feature of the system is the use of thin Kirschner wires for drilling the screw paths and then placing the self-drilling, cannulated screws securely over the wires. Percutaneous application of C1-C2 transarticular screws is possible through tubes. An optional "atlas-claw" provides additional stability in cases of C1-C2 stabilization. 17 patients (10 female, 7 male, mean age 60 years) with complex cervical disorders and instability of different origin were stabilized using the Neon System (Ulrich Co., Ulm, Germany). Pathology included atlantoaxial instability based on rheumatoid arthritis (n = 12), odontoid fracture (n = 4) and os odontoideum mobile (n = 1). Computed navigation (STN 4.0, Zeiss or vector vision spine, brain lab) was used in 14 cases. Transarticular C1-C2 screw fixation was performed in 14 cases (4 patients with direct C1 massa lateralis screw fixation), craniocervical fixation (C0-C2/C3) was done in 3 patients. Percutaneous application of the C1-C2 screws was used in 7 patients. Atlas claws were applied in 8 patients. There was one medial perforation of a C2 pedicle wall and one malposition of the screw in C2 without reaching the lateral mass of C1. After a mean follow-up of 9 months there were no hardware failures and stable fusion in those cases followed after 12 months or more. Clinical results were excellent or good in 14/16 patients. Cannulated screws are an effective alternative in complex stabilization procedures of the cervical spine. The presented system is technically comfortable and allows safe percutaneous screw application as well as inclusion of computed navigation with high accuracy.


Biosynthesis of vitamin B12 by Propionibacterium freudenreichii subsp. shermanii ATCC 13673 using liquid acid protein residue of soybean as culture medium.
Vitamin B12 deficiency still persists, mainly caused by low intake of animal food products affecting vegetarians, vegans, and populations of underdeveloped countries. In this study, we investigate the biosynthesis of vitamin B12 by potential probiotic bacterium using an agroindustry residue, the liquid acid protein residue of soybean (LAPRS), as a low-cost, animal derivate-free alternative culture medium. Cultures of Propionibacterium freudenreichii subsp. shermanii ATCC 13673 growing in LAPRS for vitamin B12 biosynthesis were studied using the Plackett-Burman experimental approach, followed by a central composite design 22 to optimize the concentration of significant variables. We also performed a proteolytic treatment of LAPRS and evaluated the optimized-hydrolyzed medium influence on the microbial growth and metabolism in shaker flask and bioreactor experiments. In this all-plant source medium, P. freudenreichii subsp. shermanii produced high concentrations of cells and high amounts of vitamin B12 (0.6 mg/g cells) after process optimization. These results suggest the possibility of producing vitamin B12 by a potential probiotic bacterium in a very cheap, animal derivate-free medium to address the needs of specific population groups, at the same time reducing the production costs of this essential vitamin.


Factors associated with length of stay and hospital charges for patients hospitalized with mouth cellulitis.
Dental conditions that are neglected could progress to infectious lesions that are severe enough to require hospital admission for treatment. The objective of this study was to examine outcomes in patients hospitalized for cellulitis and abscesses of mouth in the USA in year 2008. The nationwide inpatient sample for the year 2008, a component database of the Healthcare Cost and Utilization Project, was used for the current study. All hospital discharges with a primary diagnosis for cellulitis or abscess of mouth (ICD-9-CM code 528.3) were selected for analysis. Outcomes, including length of stay in hospital (LOS) and hospitalization charges, were computed from the database and projected to national levels by using the discharge weight variable. The predictor variables were composed of sets of heterogeneous variables grouped into the following categories: demographic, health-related (comorbid conditions), hospital-specific, and insurance-related. The primary outcome variables were LOS and hospital charges. Multivariable linear regression analysis models were used to examine the association between predictor and outcome variables. A total of 4,044 hospital discharges were attributed primarily to cellulitis or abscess of mouth. About 45% of these discharges occurred in those aged between 18 and 45 years. The mean length of stay in hospital was 3.9 days, and the mean hospital charge was $24,290. The total USA hospitalization charge was close to $98 million. Private insurance plans were the major payers, accounting for $31 million of hospitalization charges. About 88% of all hospitalization were discharged routinely after treatment, and 2% were transfered to another short-term hospital. This study examines outcomes in patients hospitalized for cellulitis or abscess of mouth. Future studies must focus on identifying cohorts that are more prone to developing odontogenic infections that are severe enough to warrant hospitalization.


TSP1 and MMP9 genetic variants in sporadic prostate cancer.
Angiogenesis plays an important role in the initiation and progression of many malignancies including prostate cancer (PCa). Therefore, genes implicated in angiogenic pathways could be susceptibility candidate genes for this malignancy. In this respect, we investigated the impact of functional genetic variants of TSP1 (N700S) and MMP9 (-1562 C/T) genes on the development and progression of PCa. This case-control study included 101 PCa patients and 106 healthy controls analyzed by polymerase chain reaction -restriction fragment length polymorphism assay. No association was observed between any of the TSP1 genotypes and PCa risk or severity; however, subjects carrying one copy of the MMP9 T allele exhibited threefold higher risk of developing PCa (OR = 2.86; P = 0.004). Regarding prognostic value, a significant association was found between the occurrence of the MMP9 T allele and the high-grade tumor (OR = 3.21; P = 0.004) and the advanced disease (OR = 2.47; P = 0.026). We also analyzed the effect of the combined genotypes on PCa risk. The patients with two high-risk genotypes exhibited 2.8-fold higher risk of developing PCa than those with only low-risk genotypes, but the association was not statistically significant. These findings suggest that MMP9 polymorphism is an independent risk factor of PCa development and aggressiveness.


Parental exposure to natural mixtures of persistent organic pollutants (POP) induced changes in transcription of apoptosis-related genes in offspring zebrafish embryos.
Apoptosis is an integral element of development that may also be initiated by environmental contaminants. The aim of the present study was to assess potential changes in the regulation of apoptotic genes in zebrafish embryos following parental exposure to two natural mixtures of persistent organic pollutants (POP). The mixture from Lake Mjøsa contained exceptionally high concentrations of polybrominated diphenyl ethers (PBDE), as well as relatively high levels of polychlorinated biphenyls (PCB) and dichlorodiphenyltrichloroethane (DDT). The mixture from Lake Losna contained background concentrations of POP. Genes involved in the apoptotic machinery were screened for their expression profile at four time points during embryonic development. Thirteen and 15 genes involved in apoptosis were found to be significantly upregulated in the high-exposure and background exposure groups, respectively, compared with controls. Modulation of apoptotic genes was restricted only to the first time point, which corresponds with the blastula stage. Although there were substantial differences in POP concentrations between mixtures, genes underlying the apoptosis process showed almost similar responses to the two mixtures. In both exposure groups the main executors of apoptosis p53, casp 2, casp 6, cassp 8, and BAX displayed upregulation compared to controls, suggesting that these POP induce apoptosis via a p53-dependent mechanism. Upregulation of genes that play a critical role in apoptosis suggests that disturbance of normal apoptotic signaling during gametogenesis and embryogenesis may be one of the central mechanisms involved in adverse reproductive effects produced by POP in zebrafish.


[Anxiety as a variable in the student-patient relationship].
The aim of this study was to analyse the anxiety as a variable in the nursing students communication with patients. Data was obtained through interviews, reports and observations of 10 students during 3 moments: 3rd, 4th, and 6th, periods of undergraduate nursing course. Both students and patients anxiety was identified as a variable that interfered in the use of the therapeutic communication by the students.


Functional Results in Arthroscopic Treatment in Patients with Chronic Lateral Elbow Pain.
Modern surgery as elbow arthroscopic surgery is an accepted operation due to benefit in precise intra-articular lesion detection and minimally invasive surgery. To report the functional results when using arthroscopic surgery to treat chronic lateral elbow pain. The data was collected from 25 patients with chronic lateral elbow pain that failed in non-operative treatment and treated with elbow arthroscopic surgery. Five patients were excluded from this study due to diagnosed as instability that needed the ligament reconstruction. The etiology of pain were grouped in to tennis elbow (4 pts), plica (9 pts), tennis elbow combined with plica (4 pts) and cartilage lesion (3 pts). Thai quick DASH questionnaire was used to evaluate the functional results by comparing pre and post operation score and calculated statistic results with paired t-test by level of significance p < 0.05. The mean follow-up after surgery was 22 months by mean disability module pre and post-operative score is 68 and 18 respectively. In the occupation module was 74 and 25 respectively and in sports module was 81 and 17 respectively. All modules, scores was significant improved with p-value = 0.000, 0.000 and 0.004 respectively. The disability mean score in pre and post-operative along the diagnosis, tennis elbow mean score was 74 and 33, in plica lesion mean score was 65 and 11, combined lesions mean score was 60 and 18 and cartilage lesion mean score was 60 and 20. Approaching chronic lateral elbow pain with arthroscopy can maintain the signficant improvement of functional result in midterm follow-up.


Parents' Active Role and ENgagement in The review of their Stillbirth/perinatal death 2 (PARENTS 2) study: a mixed-methods study of implementation.
When a formal review of care takes places after the death of a baby, parents are largely unaware it takes place and are often not meaningfully involved in the review process. Parent engagement in the process is likely to be essential for a successful review and to improve patient safety. This study aimed to evaluate an intervention process of parental engagement in perinatal mortality review (PNMR) and to identify barriers and facilitators to its implementation. Mixed-methods study of parents' engagement in PNMR. Single tertiary maternity unit in the UK. Bereaved parents and healthcare professionals (HCPs). Parent engagement in the PNMR (intervention) was based on principles derived through national consensus and qualitative research with parents, HCPs and stakeholders in the UK. Recruitment rates, bereaved parents and HCPs' perceptions. Eighty-one per cent of bereaved parents approached (13/16) agreed to participate in the study. Two focus groups with bereaved parents (n=11) and HCP (n=7) were carried out postimplementation to investigate their perceptions of the process.Overarching findings were improved dialogue and continuity of care with parents, and improvements in the PNMR process and patient safety. Bereaved parents agreed that engagement in the PNMR process was invaluable and helped them in their grieving. HCP perceived that parent involvement improved the review process and lessons learnt from the deaths; information to understand the impact of aspects of care on the baby's death were often only found in the parents' recollections. Parental engagement in the PNMR process is achievable and useful for parents and HCP alike, and critically can improve patient safety and future care for mothers and babies. To learn and prevent perinatal deaths effectively, all hospitals should give parents the option to engage with the review of their baby's death.


X-ray repair cross-complementing group 1(XRCC1) genetic polymorphisms and thyroid carcinoma risk: a meta-analysis.
A number of studies have been conducted to explore the association of XRCC1 polymorphisms with thyroid cancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify this issue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed and statistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 cases and 3,557 controls). There were 6 studies (932 cases and 2,270 controls) of the Arg194Trp polymorphism, 7 studies (1432 cases and 3356 controls) of the Arg280His polymorphism and 9 studies (1,620 cases and 3,557 controls) for the Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism with thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for XRCC1 Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism. Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials.


A Report of Accelerated Coronary Artery Disease Associated with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common heritable form of vascular dementia and it is caused by mutations in the NOTCH3 gene. The neurologic manifestations of CADASIL syndrome have been well characterized; however, here we report one of the first de novo cases of CADASIL-associated coronary artery disease. A 45-year-old woman with a history of CADASIL and remote tobacco use presented with unstable angina. She was found to have diffuse and irregular narrowing of the left anterior descending artery and a drug eluting stent was deployed. Months later, she developed two subsequent episodes of unstable angina, requiring stent placement in the distal left anterior descending artery and the right coronary artery. Though the neurologic manifestations of CADASIL have been well described, these patients may also be predisposed to developing premature coronary artery disease. Patients with CADASIL and their physicians should be aware of this possible association because these patients may not be identified as high risk by traditional cardiovascular risk estimators. These patients may benefit from more aggressive interventions to reduce cardiac risk.


Cystatin C as a marker of early changes of renal function in Fabry nephropathy.
A sensitive, feasible and reproducible marker for renal function is necessary to evaluate the clinical efficacy of enzyme replacement therapy (ERT) in Fabry nephropathy. Serum creatinine has some limitations and cystatin C has been proposed, in other nephropathies, as a useful marker of renal function. The use of cystatin C as a marker of glomerular filtration rate (GFR) was investigated in Fabry patients receiving ERT. Renal function was evaluated with serum creatinine, serum cystatin C and estimated GFR (through Modification of Diet in Renal Disease [MDRD], Cockcroft-Gault [C&G] and Hoek formulae) in 21 Fabry patients receiving ERT with agalsidase alfa for 3 years and in 13 Fabry patients receiving agalsidase alfa for 4 years. During years of ERT while serum creatinine remained stable, cystatin C values showed a significant, increasing trend right from the first year of ERT. In Fabry disease, cystatin C is a sensitive and reliable marker of renal function, and it should be taken into account when evaluating GFR trends during ERT.


Application of antibodies against Borna disease virus phosphoprotein and nucleoprotein on paraffin sections.
In order to study the application of antibodies against recombinant proteins for detecting Borna disease virus (BDV) phosphoprotein (p24) and nucleoprotein (p40) (BDV‑p24/p40) on paraffin sections by immunohistochemistry. The purified fusion p24 and p40 proteins were used for the preparation of polyclonal and monoclonal anti‑p24 and anti‑40 antibodies, which were confirmed by ELISA and western blotting. Paraffin sections were made from BDV‑infected Sprague‑Dawley (SD) rats (n=20), PBS‑injected SD rats (n=20), normal SD rats (n=20) and normal C57 mice (n=20). Immunohistochemical staining was performed according to the EnVision™ two‑step protocol. Heat‑mediated antigen retrieval was performed using the retrieval buffer sodium citrate (1 mM; pH 6.0). All the antibodies against recombinant proteins exhibited good sensitivity and specificity. There were significant differences between the BDV‑infected group and the BDV‑uninfected group for poly‑ and monoclonal anti‑p24 and ‑p40 antibodies. These antibodies against recombinant proteins may be used effectively to detect BDV p24 and p40 in paraffin sections.


Specimen mammography-guided fine-needle aspirates of clinically occult benign and malignant lesions. Analysis of cell number and type.
The authors determine the cell counts and percentages of epithelial cells in fine-needle aspirates (FNA) of mammographically detected breast lesions. Specimen mammography-guided 20-gauge fine-needle aspirations were performed on 151 consecutive lesions. Cell counts were determined by flow cytometry of 106 consecutive aspirates. Semiquantitative determination of the percentage of epithelial cells was done by cytologic analysis of 151 aspirates. Single FNA cell counts were greater than 1000 for all lesions and greater than 7000 in 57% (31 of 54) of malignant and 35% (18 of 52) of benign lesions, P = 0.02. Fine-needle aspirates of soft tissue abnormalities had more than 7000 cells in 59% (27 of 46) of specimens, compared with 36% (22 of 61) in calcifications, P < 0.05. With the exception of fibroadenomas, the mammographic appearance of benign lesions, lesion size, and patient age had no association with cell counts. Ninety-three percent (76 of 82) of malignant lesion FNA and 80% (55 of 69) of benign lesion FNA had 50% or greater epithelial cells, P < 0.05. Fine-needle aspiration yields abundant cell counts of predominantly epithelial cells from most types of mammographically detected lesions and should be considered as a source of fresh cell samples for the study of benign and early malignant breast disease.


Effects of whole body vibration training on balance in adolescents with and without Down syndrome.
The present study aimed to determine whether a whole body vibration training program (WBV) is able to improve static standing balance in adolescents with and without Down syndrome (DS). Thirty adolescents with DS aged 11-20 years (DSG) and 27 adolescent, age/sex matched, without DS (CG) joined the study. Participants of each group were divided into two comparable groups, those who performed WVB (in DSG: VDSG; in CG: VCG) and those who did not perform WVB (in DSG: nVDSG; in CG: nVCG). Static-standing-balance under four conditions (C1: open-eyes/fixed-foot-support; C2: closed-eyes/fixed-foot-support; C3: open-eyes/compliant-foot-support; C4: closed-eyes/compliant-foot-support) was examine, before and after a 20-week WBV training program. For balance study, Postural-Parameters (PPs), based on center of pressure (COP) oscillations (anterior/posterior and medial/lateral COP excursion and COP mean velocity), and PPs ratios among the four conditions were calculated. After WBV training, no significant differences were found in any parameter in the VCG and nVCG and neither in the nVDSG, but there was a decrease of mean values in the analyzed PPs under C4, with significant differences in medial/lateral COP excursion and COP mean velocity, and a significant decrease in the ratio C4/C1 of the mean velocity in VDSG. Therefore, WBV training had positive effects in the balance of DS adolescents although only under specific conditions, with vision and somatosensory input altered. The positive results of this study are encouraging and open a wide field of research, looking for the most efficient program for this population.


Acceleration of hemopoietic recovery after autologous bone marrow transplantation by low doses of peripheral blood stem cells.
Twenty patients with advanced malignant disease submitted to autologous bone marrow transplantation with marrow either unpurged (10 patients) or purged in vitro with mafosfamide (10 patients) after ablative chemotherapy, received simultaneously autologous peripheral blood stem cells (PBSC) collected during one to three 3 h cytapheresis procedures. The kinetics of the hematological recovery of these patients were compared to those of a group of patients suffering from similar diseases and grafted in the same institution with either unpurged marrow only (14 patients) or purged in vitro with mafosfamide (six patients). The median times to reach 10(9)/l leukocytes, 0.5 x 10(9)/l polymorphs, and 50 x 10(9)/l platelets were reduced by 10, 10, and 13 days, respectively, in patients transfused with both autologous bone marrow and peripheral blood stem cells as compared to those receiving bone marrow only. A reduction in the numbers of days spent in hospital post-transplantation (p less than 0.01), of days of fever greater than 38 degrees C (p = NS), and of platelet (p = 0.07) and of red blood cell transfusions (p less than 0.01) were also observed in the group of patients grafted with bone marrow and PBSC.


Sugars, insulin sensitivity, and the postprandial state.
Since insulin resistance was first associated with type 2 diabetes and later with cardiovascular disease and hypertension, there has been considerable interest in the role of dietary and environmental factors. Sucrose and fructose have been a particular research focus. Research on animals, particularly rodents, has shown a clear and consistent effect of high-sucrose and high-fructose diets in decreasing insulin sensitivity. Experiments in humans have produced very conflicting results, with limited evidence for a negative effect on insulin sensitivity at higher intakes of fructose or sucrose (generally > 30% of daily energy from sucrose and > 15% of daily energy from fructose). Observation studies in humans have not shown a link between sucrose consumption and insulin sensitivity independent of other dietary factors. This is in contrast with several small studies that showed an improvement in insulin sensitivity after subjects followed dietary advice to lower the glycemic index of their food choices (where sugars were not a target for change). However, the pattern of postprandial glucose and insulin responses elicited by sucrose and fructose differs substantially from that elicited by starches, with lower troughs elicited by sucrose and fructose 2-3 h after eating. These differences in the pattern of postprandial responses offer a potential explanation for the conflicting results on insulin sensitivity, with the possibility that increases in insulin exposure may affect insulin sensitivity through down-regulation of insulin action.


Complete mitochondrial genome of Bombus terrestris (Hymenoptera: Apidae).
In this study, complete mitochondrial genome of the large earth bumblebee, Bombus terrestris, was first determined. The mitochondrial genome is 174 000 bp in length, and encodes 1 D-loop region, 2 ribosomal RNA genes, 13 protein-coding genes and 20 transfer RNA genes. Average GC content of this genome is 15%. nad6 and cob are overlapped with 12 bp, while atp8 and atp6 are overlapped with 18 bp. Phylogeny analysis indicates Bombus species exhibit closer genetic distance with Melipona species than with Apis species.


[Pharmacokinetics for the solutable type injections of propofol glycoside in rats].
To estimate the pharmacokinetics for two solution types of propofol glycoside injections in rats. A high performance liquid chromatography-high resolution mass spectrometry (HPLC-MS) was established for measuring propofol in rat plasma. Two kinds of propofol glycoside injections were developed and intravenously administered to rats via tail vein, respectively, and a commercially available propofol emulsion injection was intravenously administered as a control. Propofol plasma concentration-time curves were determined, and the pharmacokinetic parameters were estimated. HPLC-MS measurement was performed by using a quadrupole-orbit trap high-resolution mass spectrometer on a C18 chromatographic column. The mobile phase consisted of water and methanol (20:80, V/V). The ion source was an atmospheric pressure chemical ion source, and the negative ion was used for detection with a scanning mode of selective ion monitoring in which m/z 177.127 4 was used for propofol and m/z 149.096 1 used for thymol as an internal standard. A linear correlation between concentration and peak area ratio was constructed in the range of 50 μg/L-10.0 mg/L propofol. The limit of quantification was 50 μg/L propofol. The average recoveries of propofol from plasma were in the range of 93.6%-101.1%, and intra-day or inter-day relative standard deviation for measurement was <14%. The pharmacokinetic results showed that the two kinds of propofol glycoside injections exhibited the same pharmacokinetic behavior. However, the clearance and area under curve values of propofol for the two propofol glycoside injections were evidently increased as compared with those for propofol emulsion injection, respectively. Furthermore, their apparent distribution volumes were increased as well. Nevertheless, the propofol elimination half-life (t1/2) value of the newly developed propofol glycoside injections was the same as that of commercial propofol emulsion injection (approximately 1.5 h). The established HPLC-MS method can be used for measuring propofol concentration accurately in rat plasma. The clearance and distribution volumes of propofol glycoside injection are bigger than those of the propofol emulsion injection.


Physical training for asthma.
Physical training programmes have been designed for asthmatic subjects with the aim of improving physical fitness, neuromuscular coordination and self-confidence. Habitual physical activity increases physical fitness and lowers ventilation during mild and moderate exercise thereby reducing the likelihood of provoking exercise induced asthma. Exercise training may also reduce the perception of breathlessness through a number of mechanisms including strengthening respiratory muscles. Subjectively, many asthmatics report that they are symptomatically better when fit, but results from trials have varied and have been difficult to compare because of different designs and training protocols. The purpose of this review was to assess evidence for the efficacy and effectiveness of physical training in asthma. We searched the Cochrane Airways Group Specialised Register, SportDiscus and the Science Citation Index up to May 2005. Randomised trials in asthmatic subjects undertaking physical training. Subjects had to be eight years and older. Physical training had to be undertaken for at least 20 to 30 minutes, two to three times a week, over a minimum of four weeks. Eligibility for inclusion and quality of trials were assessed independently by two reviewers. Thirteen studies (455 participants) were included in this review. Physical training had no effect on resting lung function or the number of days of wheeze. The results of this review have shown that lung function and wheeze is not worsened by physical training in patients with asthma. Physical training improved cardiopulmonary fitness as measured by an increase in maximum oxygen uptake of 5.4 ml/kg/min (95% confidence interval 4.2 to 6.6) and maximum expiratory ventilation 6.0 L/min (95% confidence interval 1.5 to 10.4). There were no data concerning quality of life measurements. In people with asthma, physical training can improve cardiopulmonary fitness without changing lung function. It is not known whether improved fitness is translated into improved quality of life. It is comforting to know that physical training does not have an adverse effect on lung function and wheeze in patients with asthma. Therefore, there is no reason why patients with asthma should not participate in regular physical activity.


Alteration of the Disposition of Quinine in Healthy Volunteers After Concurrent Ciprofloxacin Administration.
This study evaluated the effects of concurrent ciprofloxacin administration on the disposition of quinine in healthy volunteers. Quinine (600-mg single dose) was administered either alone or with the 11th dose of ciprofloxacin (500 mg every 12 hours for 7 days) to 15 healthy volunteers in a crossover fashion. Blood samples collected at predetermined time intervals were analyzed for quinine and its major metabolite, 3-hydroxquinine, using a validated high-performance liquid chromatographic method. Administration of quinine plus ciprofloxacin resulted in significant increases (P < 0.05) in the total area under the concentration-time curve, maximum plasma concentration (Cmax), and terminal elimination half-life (T1/2b) of quinine compared with values with quinine dosing alone (AUC: 27.93 ± 8.04 vs. 41.62 ± 13.98 h·mg/L; Cmax: 1.37 ± 0.24 vs. 1.64 ± 0.38 mg/L; T1/2b: 16.28 ± 2.66 vs. 21.43 ± 3.22 hours), whereas the oral plasma clearance markedly decreased (23.17 ± 6.49 vs. 16.00 ± 5.27 L/h). In the presence of ciprofloxacin, there was a pronounced decrease in the ratio of AUC (metabolite)/AUC (unchanged drug) and highly significant decreases in Cmax and AUC of the metabolite (P < 0.05). Ciprofloxacin may increase the adverse effects of concomitantly administered quinine, which can have serious consequences on the patient. Thus, a downward dosage adjustment of quinine seems to be necessary when concurrently administered with ciprofloxacin.


Incorporating dynamics in E. coli dihydrofolate reductase enhances structure-based drug discovery.
Escherichia coli dihydrofolate reductase (DHFR) is a long-standing target for enzyme studies. The influence of protein motion on its catalytic cycle is significant, and the conformation of the M20 loop is of particular interest. We present receptor-based pharmacophore models-an equivalent of solvent-mapping of binding hotspots-based on ensembles of protein conformations from molecular dynamics simulations of DHFR.NADPH in both the closed and open conformation of the M20 loop. The optimal models identify DHFR inhibitors over druglike non-inhibitors; furthermore, high-affinity inhibitors of E. coli DHFR are preferentially identified over general DHFR inhibitors. As expected, models resulting from simulations with DHFR in the productive conformation with a closed M20 loop have better performance than those from the open-loop simulations. Model performance improves with increased dynamic sampling, indicating that including a greater degree of protein flexibility can enhance the quest for potent inhibitors. This was compared to the limited conformational sampling seen in crystal structures, which were suboptimal for this application.


Are Electrocardiographic Criteria Reliable for Left Ventricular Hypertrophy Detection in Indian Adults?
Left ventricular hypertrophy (LVH) detection is vital to the risk stratification of adults at risk of adverse cardiovascular events such as coronary heart disease, cerebrovascular disease, and aortic aneurysms. Electrocardiogram (ECG), a non-invasive, cost-effective instrument has been widely used as a screening tool for LVH. The objective of this study was to determine the diagnostic accuracy of seven frequently used ECG criteria in high-risk Indian adults in comparison with echocardiography. ECG and transthoracic echocardiography were performed in adults older than 18 years with at least one cardiac risk factor (chronic hypertension, obesity, ischemic heart disease, and type 2 diabetes mellitus). Precision and accuracy were calculated for the various ECG criteria against LVH based on left ventricular mass index (LVMI) and cardiac remodeling by echocardiography. A total of 220 participants were enrolled. Of these, 96 had LVH by echocardiography. There was marked variability in LVH detection by the different ECG criteria: 28 by Sokolow-Lyon criteria, 26 by Cornell criteria, 24 by Lewis criteria, 46 by Scott criteria, eight by Romhilt-Estes criteria, six by Modified Cornell criteria, and only two by Roberts criteria. Agreement statistics between ECG criteria and LVMI showed that none of them had a good agreement for LVH detection. None of the ECG criteria were sensitive enough to rule out ventricular hypertrophy. In the context of cardiac remodeling, the ECG criteria had high sensitivity but low specificity and, hence, limited clinical relevance.


Photoinduced Ru-Yb energy transfer and sensitised near-IR luminescence in a coordination polymer containing co-crystallised [Ru(bipy)(CN)4]2- and Yb(III) units.
Co-crystallisation of the anionic cyanometallate chromophore [Ru(bipy)(CN)4]2- with Yb(III) provides coordination polymers or oligomers containing Ru-CN-Yb bridges; in [K(H2O)4][Yb(H2O)6][Ru(bipy)(CN)4]2.5H2O Ru-->Yb energy-transfer (k > 5 x 10(6) s(-1)) results in partial quenching of the Ru-based luminescence and sensitised near-IR luminescence from the Yb(III) unit.


Markers of acute airway inflammation.
In asthma, acute inflammation induced by allergen challenge in allergic patients leads to an early and a late phase reaction. Immunoglobulin E (IgE)-mediated cell activation plays a crucial role in acute inflammation and leads to the release of proinflammatory mediators, such as histamine, eicosanoids, platelet-activating factor, oxygen-free radicals, neuropeptides and cytokines. These mediators are capable of inducing constriction of airways smooth muscle, increased secretion of mucus, and vasodilatation, as well as several important biological events, including modulation of the expression of adhesion molecules in endothelial and epithelial cells, and of inflammatory cell recruitment. Clinically, acute airway inflammation is characterized by a bronchoconstrictive response with acute symptoms, including wheezing and dyspnoea which can be reversed by short-acting bronchodilators, among which beta 2-agonists play a major role.


Agricultural Leaders' Influence on the Safety Culture of Workers.
Most US farmers are small, independent owner-operators, many of whom are exempt from safety regulation and enforcement, as well as age restrictions relative to family members performing hazardous tasks. These smaller farms account for a disproportionate share of the total fatality and injury statistics from farming incidents, contributing to an agriculture-industry death rate that is seven times greater than all occupations combined. In contrast, large agricultural enterprises that employ larger numbers of non-family workers are more regulated and more highly incentivized by economic, supply chain, and societal factors to implement cultures of safety, and are more readily influenced by agricultural opinion leaders, agribusinesses, farm organizations, and agricultural media. These agricultural influencer institutions must find ways to play more significant roles in changing the culture on operations that use only family labor. They will find willing partners in safety organizations such as the Agricultural Safety and Health Council of America (ASHCA), Agricultural Extension, and other health and safety advocates, including the National Institute for Occupational Safety and Health (NIOSH)-funded agricultural research centers. The overall workplace injury statistics for agriculture remain alarming; however, with leadership from the larger farm operations, and help from ASHCA, academia, the healthcare community, and others, the current culture of workplace safety and health in agriculture can be impacted in positive ways.


On Improving CRISPR for Editing Plant Genes: Ribozyme-Mediated Guide RNA Production and Fluorescence-Based Technology for Isolating Transgene-Free Mutants Generated by CRISPR.
CRISPR/Cas9-mediated genome editing technology has been used to successfully edit numerous genes in various organisms including plants. There are still two major challenges in using CRISPR/Cas9 technology for gene editing in plants. First, there are very limited choices of promoters that are suitable for in vivo production of single-guide RNAs (sgRNAs), which is complementary to the target sequence and which guides Cas9 to generate double-strand breaks at the target site. It is especially difficult to produce sgRNA molecules with temporal and spatial precision. Second, there is a lack of efficient methods for identifying plants that (1) contain heritable and stable mutations generated by CRISPR/Cas9, and (2) no longer harbor the CRISPR/Cas9 construct and other transgenes. In this chapter, we describe the development of a ribozyme-based strategy that enables the production of sgRNA molecules from any chosen promoter. More importantly, the ribozyme-based technology makes it feasible to produce sgRNAs with temporal and spatial precision, greatly expanding the scope and applications of CRISPR/Cas9 technology. We also developed a fluorescence-based technology that allows us to efficiently and reliably isolate Cas9-free stable Arabidopsis mutants. Thus, we provide effective protocols to overcome two important obstacles in using CRISPR/Cas9 for editing genes in plants.


Stress, breakfast cereal consumption and cortisol.
Recent research has shown that regular consumption of breakfast cereal is associated with lower stress levels and reports of better physical and mental health. The present study examined this issue using an objective indicator of stress, salivary cortisol. The results showed that stress was associated with higher cortisol levels and daily consumption of breakfast cereal was associated with lower cortisol levels. Although it was not possible to rule out all the alternative explanations of the association between breakfast cereal consumption and cortisol, analyses did show that the effect could not be accounted for by general health or nutritional status. The effects of breakfast cereal consumption and stress were also independent, which shows that the effects of breakfast found here cannot be due to stress buffering. Further research manipulating the nutrient content of the breakfast cereal is now required to provide further information about the mechanisms underlying this effect.


Development of a fully automated peripheral anterior chamber depth analyzer and evaluation of its accuracy.
The aim of this study was to improve the scanning peripheral anterior chamber depth analyzer (SPAC) for measuring anterior chamber depth (ACD), differentiating eyes with shallow anterior chamber, and automatically categorizing eyes into subgroups based on the ACD values. We also investigated its accuracy for measuring anterior ocular biometry. The improved SPAC system was equipped with an auto-focusing system for measuring ACD from the optical axis to the limbus without contacting the ocular surface, in addition to an auto-measuring system for determining central corneal thickness (CCT) and corneal radius of curvature (CRC). This system was also equipped with an auto-diagnosing program for differentiating eyes with narrow angle and an auto-classifying program for categorizing eyes into 12 subgroups according to the ACD values. A dummy eye was used for investigating the measurement accuracy and reproducibility of CCT, CRC, and ACD. Measurement duration and clinical availability were investigated using healthy subjects and glaucoma patients. The SPAC-measured CCT, CRC, and ACD values were very similar to the theoretical values obtained from the dummy eye and their coefficients of variation were less than 1%. This system completed ACD measurement in 15.6+/-1.0 seconds and the mean coefficient of variation of ACD was 8.8+/-2.3%. The improved SPAC system successfully differentiated eyes with narrow angle from those with wide open angle. The improved SPAC system can measure ACD easily with good accuracy and reproducibility, and is considered to be suitable for evaluating ACD in routine examinations and screening eyes with narrow angle.


Conformation of peptide fragments of proteins in aqueous solution: implications for initiation of protein folding.
Applications of sensitive new technologies, in particular, two-dimensional NMR spectroscopy, have allowed detection of folded structures in short peptide fragments of proteins in aqueous solution under conditions where native proteins fold. These structures are in rapid dynamic exchange with unfolded states. These observations provide evidence in support of models for protein folding which postulate localized regions of folded structure as initiation sites for the folding process. Since these initiation processes are expected to be rapid, such models are consistent with kinetic evidence that the rate-determining steps of protein folding occur late in the process and probably involve rearrangement of incorrectly folded intermediates.


Gastrointestinal manifestations of progressive systemic sclerosis.
Management of patients with progressive systemic sclerosis requires a thorough gastroenterological examination and a profound knowledge of possible gastrointestinal manifestations of the disease. The esophagus is the gastrointestinal segment most often involved. Smooth muscle atrophy leads to a loss of esophageal peristalsis, a defect of the lower esophageal sphincter, and gastric hypomotility, thus predisposing to severe reflux esophagitis. A rational diagnostic approach includes standard manometry and endoscopy. The prevention of strictures is the main aim of therapeutic efforts that may consist of lifestyle changes, prokinetic drugs, long-term application of proton pump inhibitors, and, if inevitable, surgical intervention. Involvement of the small intestine and colon is less common but may lead to life-threatening complications like chronic pseudoobstruction or pneumatosis cystoides intestinalis. The main therapeutic options consist of antibiotics for bacterial overgrowth and nutritional supplementation. Recently, a preliminary study with octreotide yielded promising results. Anorectal dysfunction can lead to fecal incontinence or rectal prolapse.


Determinants for Substrate Specificity of Protein Phosphatase 2A.
Protein phosphatase 2A- (PP2A-) catalyzed dephosphorylation of target substrate proteins is widespread and critical for cellular function. PP2A is predominantly found as a heterotrimeric complex of a catalytic subunit (C), a scaffolding subunit (A), and one member of 4 families of regulatory subunits (B). Substrate specificity of the holoenzyme complex is determined by the subcellular locale the complex is confined to, selective incorporation of the B subunit, interactions with endogenous inhibitory proteins, and specific intermolecular interactions between PP2A and target substrates. Here, we discuss recent studies that have advanced our understanding of the molecular determinants for PP2A substrate specificity.


EMI and microwave absorbing efficiency of polyaniline-functionalized reduced graphene oxide/γ-Fe2O3/epoxy nanocomposite.
Polyaniline-decorated reduced graphene oxide/ferrite nanofiller (RGPF) prepared by the solution mixing method in three different ratios (1 : 3, 1 : 1 and 3 : 1) of polyaniline-decorated reduced graphene oxide and ferrite have been studied for microwave absorption properties in defence application. The polyaniline-decorated reduced graphene oxide/ferrite and neat ferrite nano-fillers have been used for the preparation of an epoxy nanocomposite (RGPFE) of 60 wt%. The distribution of the RGPF nanofiller in the epoxy matrix was analyzed by field emission scanning electron microscopy. Further, thermal gravimetric analyses revealed the excellent thermal stability of the nanocomposites. A vibrating sample magnetometer was employed to find out the magnetic behavior of the prepared nanocomposites. The complex permittivity and permeability were investigated to evaluate the principal properties in the frequency range from 2 to 18 GHz. These results show that an epoxy nanocomposite with 60 wt% RGPF filler in the ratio of 3 : 1 has maximum dielectric loss. Finally, these electromagnetic data were used to calculate the reflection loss of the epoxy nanocomposites, and showed good agreement between the calculated and measured data of these nanocomposites. The minimum reflection loss was observed as -10.26 dB in the X band with a thickness of 3.0 mm, and the bandwidth was 8.47 GHz for RL ≤-10 dB. On the basis of the above observations, these nanocomposites could be a good candidate for electromagnetic interference shielding (EMI) and microwave absorption applications.


Vascular healing and integration of a fully bioresorbable everolimus-eluting scaffold in a rabbit iliac arterial model.
We aimed to investigate a fully bioresorbable poly-l-lactide (PLLA) scaffold to assess vascular remodelling in comparison to a permanent polymeric metal DES. Twenty-five New Zealand white rabbits received an Absorb bioresorbable vascular scaffold (BVS, 1.0 and 1.1) or a CYPHER sirolimus-eluting stent (SES) in the iliac arteries. Twelve arteries were harvested at one month for scanning electron microscopy (SEM) analysis (BVS 1.1). The other implanted (BVS 1.0) arteries (n=32) were explanted at three, six and 36 months for light microscopic analysis. Re-endothelialisation assessed at one month was incomplete in both BVS and SES by SEM, with a trend towards greater coverage in SES (endothelialisation above strut: 32.2% vs. 60.6%, p=0.10). However, light microscopic analysis at later time points revealed greater endothelial coverage in BVS than in SES at 36 months (100.0% vs. 93.3%, p=0.05). Inflammation scores were comparable between arteries implanted with BVS and SES at three months (1.1 vs. 1.1, p=0.99), which decreased over time in the BVS implanted arteries (36 months: 0.0 vs. 0.2, p=0.05). At 36 months, BVS were completely resorbed, and resorption sites were replaced by connective tissue. BVS in the rabbit iliac artery model demonstrated ongoing vascular healing at three and six months, and complete vessel restoration, re-endothelialisation and no to minimal vascular inflammation at 36 months.


An online survey to understand the needs of caregivers of family members with 22q11 deletion syndrome.
Most individuals with 22q11.2 deletion syndrome (22q11DS) have multi-system and lifelong needs requiring substantial support. Their primary caregivers are usually family members who dedicate lifelong time and effort to their role. The pressures of their roles can negatively impact caregivers' psychosocial well-being, suggesting a need for additional support for this community who currently have no specialised interventions available. This online study surveyed 103 caregivers of family members with 22q11DS to determine the barriers to accessing support that they faced, the kind of support they would value and whether an online intervention could meet their needs. The caregivers indicated that a brief online intervention focused on teaching practical skills and connecting them with a peer network of support would be most valuable. Future studies are planned that will build on these results by designing and testing online interventions tailored to this community.


Unravelling faradaic electrochemical efficiencies over Fe/Co spinel metal oxides using surface spectroscopy and microscopy techniques.
Cobalt and iron metal-based oxide catalysts play a significant role in energy devices. To unravel some interesting parameters, we have synthesized metal oxides of cobalt and iron (i.e. Fe2O3, Co3O4, Co2FeO4 and CoFe2O4), and measured the effect of the valence band structure, morphology, size and defects in the nanoparticles towards the electrocatalytic hydrogen evolution reaction (HER), the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR). The compositional variations in the cobalt and iron precursors significantly alter the particle size from 60 to <10 nm and simultaneously the shape of the particles (cubic and spherical). The Tauc plot obtained from the solution phase ultraviolet (UV) spectra of the nanoparticles showed band gaps of 2.2, 2.3, 2.5 and 2.8 eV for Fe2O3, Co3O4, Co2FeO4 and CoFe2O4, respectively. Further, the valence band structure and work function analysis using ultraviolet photoelectron spectroscopy (UPS) and core level X-ray photoelectron spectroscopy (XPS) analyses provided better structural insight into metal oxide catalysts. In the Co3O4 system, the valence band structure favors the HER and Fe2O3 favors the OER. The composites Co2FeO4 and CoFe2O4 show a significant change in their core level (O 1s, Co 2p and Fe 2p spectra) and valence band structure. Co3O4 shows an overpotential of 370 mV against 416 mV for Fe2O3 at a current density of 2 mA cm-2 for the HER. Similarly, Fe2O3 shows an overpotential of 410 mV against the 435 mV for Co3O4 at a current density of 10 mA cm-2 for the OER. However, for the ORR, Co3O4 shows 70 mV improvement in the half-wave potential against Fe2O3. The composites (Co2FeO4 and CoFe2O4) display better performance compared to their respective parent oxide systems (i.e., Co3O4 and Fe2O3, respectively) in terms of the ORR half-wave potential, which can be attributed to the presence of the oxygen vacancies over the surface in these systems. This was further corroborated in density functional theory (DFT) simulations, wherein the oxygen vacancy formation on the surface of CoFe2O4(001) was calculated to be significantly lower (∼50 kJ mol-1) compared to Co3O4 (001). The band diagram of the nanoparticles constructed from the various spectroscopic measurements with work function and band gap provides in-depth understanding of the electrocatalytic process.


[Effects of caveolin-1 on biologic behavior of laryngeal squamous cell carcinoma HEp2 cell line GU].
To investigate the effects of caveolin-1 on the biologic behavior of laryngeal squamous cell carcinoma HEp2 cell line in vitro. Eukaryotic expression vector of human caveolin-1 gene was constructed and transfected into HEp2 cells by Lipofectamine. The clones stably overexpressing caveolin-1 were identified by real-time PCR and Western blotting. Cell proliferation viability was tested by MTT assay. Anchorage-independent growth was determined by assaying colony formation in soft agar. Flow cytometry was used to assess the cell cycle and apoptosis. The relative phosphorylation level of EGFR and ERK1/2 were detected by Western blotting. Localization of caveolin-1 and EGFR were studied by laser confocal laser scanning microscopy. The expression vector of caveolin-1 was constructed and three clones stably overexpressing caveolin-1 were obtained. Comparing with the parental HEp2 cells, the transfected cells exhibited a slower growth rate and formed fewer colonies in soft agar. The results of FACS analysis revealed that overexpression of caveolin-1 resulted in the cell cycle arrest at G0/G1 phase and increased the apoptotic cell fraction. EGFR was found to colocalize with caveolin-1 in transfected cells by confocal laser scanning microscopy and Western blotting results showed that overexpression of caveolin-1 reduced the phosphorylation of EGFR and Erkl/2. Overexpression of caveolin-1 suppresses the growth of HEp2 cells and induces apoptosis and inhibition of EGFR-MAPK signaling pathway may be involved in its mechanism.


Porous Copolymer Resins: Tuning Pore Structure and Surface Area with Non Reactive Porogens.
In this review, the preparation of porous copolymer resin (PCR) materials via suspension polymerization with variable properties are described by tuning the polymerization reaction, using solvents which act as porogens, to yield microporous, mesoporous, and macroporous materials. The porogenic properties of solvents are related to traditional solubility parameters which yield significant changes in the surface area, porosity, pore volume, and morphology of the polymeric materials. The mutual solubility characteristics of the solvents, monomer units, and the polymeric resins contribute to the formation of porous materials with tunable pore structures and surface areas. The importance of the initiator solubility, surface effects, the temporal variation of solvent composition during polymerization, and temperature effects contribute to the variable physicochemical properties of the PCR materials. An improved understanding of the factors governing the mechanism of formation for PCR materials will contribute to the development and design of versatile materials with tunable properties for a wide range of technical applications.


Matsuoka's CPG With Desired Rhythmic Signals for Adaptive Walking of Humanoid Robots.
The desired rhythmic signals for adaptive walking of humanoid robots should have proper frequencies, phases, and shapes. Matsuoka's central pattern generator (CPG) is able to generate rhythmic signals with reasonable frequencies and phases, and thus has been widely applied to control the movements of legged robots, such as walking of humanoid robots. However, it is difficult for this kind of CPG to generate rhythmic signals with desired shapes, which limits the adaptability of walking of humanoid robots in various environments. To address this issue, a new framework that can generate desired rhythmic signals for Matsuoka's CPG is presented. The proposed framework includes three main parts. First, feature processing is conducted to transform the Matsuoka's CPG outputs into a normalized limit cycle. Second, by combining the normalized limit cycle with robot feedback as the feature inputs and setting the required learning objective, the neural network (NN) learns to generate desired rhythmic signals. Finally, in order to ensure the continuity of the desired rhythmic signals, signal filtering is applied to the outputs of NN, with the aim of smoothing the discontinuous parts. Numerical experiments on the proposed framework suggest that it can not only generate a variety of rhythmic signals with desired shapes but also preserve the frequency and phase properties of Matsuoka's CPG. In addition, the proposed framework is embedded into a control system for adaptive omnidirectional walking of humanoid robot NAO. Extensive simulation and real experiments on this control system demonstrate that the proposed framework is able to generate desired rhythmic signals for adaptive walking of NAO on fixed and changing inclined surfaces. Furthermore, the comparison studies verify that the proposed framework can significantly improve the adaptability of NAO's walking compared with the other methods.


Evaluating blood-brain barrier permeability in a rat model of type 2 diabetes.
This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood-brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes. The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood-brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood-brain barrier permeability in 173 different brain areas. In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood-brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected. Small vessel disease as assessed by permeability in the blood-brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood-brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.


Use of a cotton tape tie in laparoscopic colorectal surgery.
In this short article we describe the use of a cotton tape tie in laparoscopic colorectal surgery. This technique is useful in: (i) retraction and manipulation of the bowel; (ii) exteriorization of a bulky specimen; and (iii) occlusion of the rectal lumen to permit effective cytocidal rectal lavage.


Regulation of connective tissue growth factor (CTGF/CCN2) gene transcription and mRNA stability in smooth muscle cells. Involvement of RhoA GTPase and p38 MAP kinase and sensitivity to actin dynamics.
Connective tissue growth factor (CTGF/CCN2) is an immediate early gene-encoded polypeptide modulating cell growth and collagen synthesis. The importance of CTGF/CCN2 function is highlighted by its disregulation in fibrotic disorders. In this study, we investigated the regulation and signaling pathways that are required for various stimuli of intracellular signaling events to induce the expression of the endogenous CTGF/CCN2 gene in smooth muscle cells. Incubation with the bioactive lysolipid sphingosine 1-phosphate (S1P) produced a threefold increase, whereas stimulation with either fetal bovine serum or anisomycin induced an even stronger activation (eightfold) of CTGF/CCN2 expression. Using a combination of pathway-specific inhibitors and mutant forms of signaling molecules, we found that S1P- and fetal bovine serum-induced CTGF/CCN2 expression were dependent on both RhoA GTPase and p38 mitogen-activated protein kinase transduction pathways, whereas the effects of anisomycin largely involved p38 and phosphatidyl inositol 3-kinase signaling mechanisms. However, activation via these signaling events was absolutely dependent on actin cytoskeleton integrity. In particular, RhoA-dependent regulation of the CTGF/CCN2 gene was concomitant to increased polymerization of actin microfilaments resulting in decreased G- to F-actin ratio and appeared to be achieved at the transcriptional level. The p38 signaling pathway was RhoA-independent and led to CTGF/CCN2 mRNA stabilization. Use of actin-binding drugs showed that the actual physical state of monomeric G-actin is a critical determinant for CTGF/CCN2 gene induction. These data indicate that distinct cytoskeletally based signaling events within the intracellular signaling machinery affect either transcriptionally or post-transcriptionally the expression of the CTGF/CCN2 gene in smooth muscle cells.


Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside Elicits Life-span Extension and Stress Resistance in Caenorhabditis elegans.
The advancements in the field of gerontology have unraveled the signaling pathways that regulate life span, suggesting that it might be feasible to modulate aging. To this end, we isolated a novel phytomolecule Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside (ARX) from Premna integrifolia and evaluated its antiaging effects in Caenorhabditis elegans The spectral data analysis revealed the occurrence of a new compound ARX. Out of the three tested pharmacological doses of ARX, viz. 5, 25, and 50 µM, the 25-µM dose was able to extend life span in C. elegans by more than 39%. The present study suggests that ARX affects bacterial metabolism, which in turn leads to dietary restriction (DR)-like effects in the worms. The effect of ARX on worms with mutations (mev-1, eat-2, sir-2.1, skn-1, daf-16, and hsf-1) indicates that ARX-mediated life-span extension involves mechanisms associated with DR and maintenance of cellular redox homeostasis. This study is the first time report on longevity-promoting activity of ARX in C. elegans mediated by stress and DR-regulating genes. This novel phytomolecule can contribute in designing therapeutics for managing aging and age-related diseases.


The Tomato Kinase Pti1 Contributes to Production of Reactive Oxygen Species in Response to Two Flagellin-Derived Peptides and Promotes Resistance to Pseudomonas syringae Infection.
The Pti1 kinase was identified from a reverse genetic screen as contributing to pattern-triggered immunity (PTI) against Pseudomonas syringae pv. tomato (Pst). The tomato genome has two Pti1 genes, referred to as Pti1a and Pti1b. A hairpin-Pti1 (hpPti1) construct was developed and was used to generate two independent stable transgenic tomato lines that had reduced transcript abundance of both genes. In response to P. syringae pv. tomato inoculation, these hpPti1 plants developed more severe disease symptoms, supported higher bacterial populations, and had reduced transcript accumulation of PTI-associated genes, as compared with wild-type plants. In response to two flagellin-derived peptides, the hpPti1 plants produced lesser amounts of reactive oxygen species (ROS) but showed no difference in mitogen-activated protein kinase (MAPK). Synthetic Pti1a and Pti1b genes designed to avoid silencing were transiently expressed in the hpPti1 plants and restored the ability of the plants to produce wild-type levels of ROS. Our results identify a new component of PTI in tomato that, because it affects ROS production but not MAPK signaling, appears to act early in the immune response.


CPMCnet: an integrated information and internet resource.
The Network and Computer Systems department of the Health Sciences Library developed CPMCnet, an UNIX-based information and Internet server at Columbia-Presbyterian Medical Center. The project linked Gopher and World-Wide Web protocols as well as clients into an integrated application, providing the advantages of both. Development and use of CPMCnet has opened new channels of communication among information providers and end-users.


[Radiofrequency ablation using the HALO system in the treatment of Barrett's oesophagus].
In recent years radiofrequency ablation using the HALO system in the treatment of Barrett's oesophagus has become established. The HALO system consists of a circumferential ablation using a balloon-based electrode and a focal ablation using an endoscope-mounted bipolar electrode on an articulated platform. In combination with prior endoscopic resection radiofrequency ablation is a valuable therapeutic technique in selected patients with early Barrett's neoplasia. Clinical trials demonstrate that radiofrequency ablation is highly effective and durable, has low complication rates, preserves the functional integrity of the oesophagus, is easy to apply and the regenerating neosquamous epithelium is free of pre-existing oncogenetic alterations.


A putative LysR-type transcriptional regulator PrhO positively regulates the type III secretion system and contributes to the virulence of Ralstonia solanacearum.
LysR-type transcriptional regulators (LTTRs) are ubiquitous and abundant amongst bacteria and control a variety of cellular processes. Here, we investigated the effect of Rsc1880 (a putative LTTR, hereafter designated as PrhO) on the pathogenicity of Ralstonia solanacearum. Deletion of prhO substantially reduced the expression of the type III secretion system (T3SS) both in vitro and in planta, and resulted in significantly impaired virulence in tomato and tobacco plants. Complementary prhO completely restored the reduced virulence and T3SS expression to that of the wild-type. Moreover, PrhO-dependent T3SS and virulence were conserved amongst R. solanacearum species. However, deletion of prhO did not alter biofilm formation, swimming mobility and in planta growth. The expression of some type III effectors was significantly reduced in prhO mutants, but the hypersensitive response was not affected in tobacco leaves. Consistent with the key regulatory role of HrpB on T3SS, PrhO positively regulated the T3SS through HrpB. Furthermore, PrhO regulated hrpB expression via two close paralogues, HrpG and PrhG, which are two-component response regulators and positively regulate hrpB expression in a parallel manner. However, deletion of prhO did not alter the expression of phcA, prhJ and prhN, which are also involved in hrpB regulation. In addition, PrhO was expressed in a cell density-dependent manner, but negatively repressed by itself. No regulation was observed for HrpB, PhcA and PrhN on prhO expression. Taken together, we genetically demonstrated that PrhO is a novel virulence regulator of R. solanacearum, which positively regulates T3SS expression through HrpG, PrhG and HrpB and contributes to virulence.


Effects of actinomycin D on generation time and morphogenesis in Paramecium.
The sensitivity of Paramecium tetraurelia (=P. aurelia syngen 4) cells to pulse treatments with various doses of Actinomycin D (AMD) was estimated by comparing the generation times of treated and untreated sister cells. It was found that the delay of division in treated cells depended on the concentration of AMD, on their "age" at the time of the pulse treatment, and on their individual sensitivity. Sensitivity of Paramecium to AMD changes during the cell cycle in a predictable way. About 3 1/2 hr before the normally expected cell fission (total generation time approximately 5 1/2 hr) there is a decrease of sensitivity. Thereafter, the cell enters a new stage with a progressive increase of sensitivity. This 2nd phase ends at the "transition point" (approximately 2 hr before cell division), when sensitivity drops abruptly. The division process itself may be altered and slowed down by high concentrations of AMD, even if the drug is applied after the transition point, but this process can never be completely annulled. The impairment of the division mechanism may lead to morphologic anomalies in the offspring. Resorption of oral anlagen in P. tetraurelia probably never occurs during the cell cycle after AMD treatment. The reason for individual variability of the cells, mechanisms controlling development, and the question of an obligate sequence of gene action in each cell cycle are discussed.


Anti-clastogenic activity of two structurally related pterocarpans purified from Bituminaria bituminosa in cultured human lymphocytes.
Plant-derived isoflavones are currently receiving much attention because of their phyto-estrogenic, antioxidant, anti-mutagenic, and anti-tumor activities. In this study we have evaluated the clastogenic and anti-clastogenic activities in human lymphocytes of two structurally related pterocarpans, iso-flavonoid derivatives, termed erybraedin C and bitucarpin A, recently purified from Bituminaria bituminosa and chemically characterized. Mitomycin C (MMC) and the radio-mimetic bleomycin (BL) were used as reference clastogens. The end point studied was micronucleus formation. The results obtained in this study indicate that erybraedin C and bitucarpin A, when assayed alone, do not affect either the mitotic index or the cell-proliferation index of human lymphocytes. Interestingly, both compounds appear to be non-clastogenic in the range of concentrations used. In contrast, both substances seem to affect significantly the clastogenic effects induced by BL and MMC. A 1-h pre-exposition of the cell culture to erybraedin C was necessary to display its anti-clastogenic potential against BL, whereas bitucarpin A was inactive in this respect, with a structure-activity relationship. In contrast, the clastogenic activity of MMC was significantly reduced by both erybraedin C and bitucarpin A, using either a pre-incubation schedule or simultaneous treatment. These results suggest that the protective effects displayed by the two anti-clastogenic compounds against MMC could be due to the induction or inhibition of cellular reductive metabolic enzymes.


Reorganization energy associated with small polaron mobility in iron oxide.
The reorganization energy is an important quantity controlling electron transfer rates. The internal contribution arising from the energy to reorganize donor/acceptor bonds can be evaluated by the "direct" and "4-point" methods. We examine how spatial separation leading to the noninteracting character of the donor and acceptor affects the reorganization energy. We show that the direct method captures contributions from interaction of the donor and acceptor while the 4-point method does not, and the two methods converge at large separation. Comparing reorganization energies determined by the two methods yields a measure of the degree of interaction between the initial and final states. The analysis is illustrated in the characterization of small polarons in iron oxides.


Electron paramagnetic resonance studies on copper(II)-cyclodextrin systems.
Three copper(II) complexes containing beta-cyclodextrin (betaCD) derivatives as ligands [mono-6-methylamino-6-deoxy-betaCD dithiocarbamate (CDTC), mono-6-histamino-6-deoxy-betaCD (CDHM) and mono-6-Nalpha-arginyl-6-deoxy-betaCD (CDARG)] have been studied by electron paramagnetic resonance. The spectra have been recorded at X- and S-bands and different temperatures and simulated to obtain the best set of magnetic parameters. In particular, the 300 K spectra are typical of the slow motion regime, as expected considering the high molecular weight of the ligands. Some structural characteristics of the complexes are proposed on the basis of dynamic and covalency parameters obtained from simulation.


Anti-HIV effects of HIV vectors.
We have recently developed an HIV-1 packaging cell line, psi 422, as an improved tool for anti-HIV gene therapy. After stable transfection with an HIV-1 or HIV-2 vector, psi 422 has been shown to synthesize virions able to transduce CD4+ T cells and macrophages. We now report that HIV vectors per se, in the absence of antiviral genes, inhibit HIV infection of transduced cells. This antiviral effect was shown to be due, at least in part, to a TAR and RRE decoy effect. These data highlight further advantages of HIV-derived gene delivery systems for HIV therapy, in addition to CD4 cell targeting and the ability to transduce nondividing cells.


Influence of Nurse Staffing Levels on Resident Weight Loss Within German Nursing Homes.
In Germany, there is no empirical evidence regarding the relationship between nurse staffing levels and care outcomes in nursing homes. The current study explored differences in nurse staffing levels between facilities with and without resident weight loss. The analyses were conducted at the facility level (N = 166) and involved weight loss assessment of 8,665 residents. Separate models for residents with and without cognitive impairment were computed. The regression analyses showed that nursing facilities where no weight loss occurred among residents without cognitive impairment had a lower number of residents per RN and additional care staff. However, no differences were found between facilities with and without weight loss among residents with cognitive disabilities. Further research is needed to identify factors leading to weight loss among residents with cognitive disabilities, including teamwork and work climate in nursing homes. [Res Gerontol Nurs. 2018; 11(1):48-56.].


Dynamics of hepatitis C virus monitored by real-time quantitative polymerase chain reaction during first 2 weeks of IFN-beta treatment are predictive of long-term therapeutic response.
The relation between the change in hepatitis C virus (HCV) RNA levels at the start of interferon-beta (IFN-beta) treatment and the long-term therapeutic response remains poorly defined. In 20 patients with chronic hepatitis C who received IFN-beta (total dose 126-756 MU), the changes in serum HCV RNA during the first 2 weeks of therapy were monitored by real-time quantitative polymerase chain reaction (PCR). The serum HCV RNA level decreased rapidly during the first 24 h of therapy (first phase) and more slowly thereafter (second phase), with a mean exponential decay rate of 1.17 log10/day and 0.37 log10/day, respectively. Three patients had a sustained virologic response, 10 patients had a transient response, and 7 patients had no response. The differences in the rate of first-phase viral decline among the three groups were not significant (p = 0.21), but the differences in the rate of second-phase viral decline were significant (p = 0.0021). The mean decay rate between the end of the first 24 h and day 14 was 0.96 +/- 0.43 log10/day in sustained responders, 0.39 +/- 0.30 log10/day in transient responders, and 0.13 +/- 0.09 log10/day in nonresponders. We conclude that during the first 2 weeks of therapy, changes in serum HCV RNA levels as monitored by real-time quantitative PCR can be used to predict the long-term response to treatment with IFN-beta.


Katoite under pressure: an ab initio investigation of its structural, elastic and vibrational properties sheds light on the phase transition.
The evolution under pressures up to 65 GPa of structural, elastic and vibrational properties of the katoite hydrogarnet, Ca3Al2(OH)12, is investigated with an ab initio simulation performed at the B3LYP level of theory, by using all-electron basis sets with the Crystal periodic program. The high-symmetry Ia3d phase of katoite, stable under ambient conditions, is shown to be destabilized, as pressure increases, by interactions involving hydrogen atoms and their neighbors which weaken the hydrogen bonding network of the structure. The corresponding thermodynamical instability is revealed by anomalous deviations from regularity of its elastic constants and by numerous imaginary phonon frequencies, up to 50 GPa. Interestingly, as pressure is further increased above 50 GPa, the Ia3d structure is shown to become stable again (all positive phonon frequencies and regular elastic constants). However, present calculations suggest that, above about 15 GPa and up to at least 65 GPa, a phase of I4[combining macron]3d symmetry (a non-centrosymmetric subgroup of Ia3d) becomes more stable than the Ia3d one, being characterized by strengthened hydrogen bonds. At low-pressures (between about 5 GPa and 15 GPa), both phases show some instabilities (more so for I4[combining macron]3d than for Ia3d), thus suggesting either the existence of a third phase or a possible phase transition of second order.


Induction of pyruvate carboxylase apoenzyme and holoenzyme in 3T3-L1 cells during differentiation.
The specific activity of pyruvate carboxylase [pyruvate:carbon-dioxide ligase (ADP-forming); EC 22.214.171.124] in 3T3-L1 cells increases approximately 20-fold when these cells differentiate to an adipocyte-like form [Mackall, J. C. & Lane, M. D. (1977) Biochem. Biophys. Res. Commun. 79, 720-725]. A specific antibody to the purified rat liver enzyme quantitatively precipitated pyruvate carboxylase from 3T3-L1 crude homogenates. Use of this immunological technique permitted us to demonstrate that the increase in pyruvate carboxylase activity is due to an increase in the intracellular concentration of the enzyme. The content of pyruvate carboxylase in differentiated 3T3-L1 cells is sufficiently high (1-2% of total protein) that the increase in this large protein (subunit M(r) = 130,000) can be visualized when 3T3-L1 crude extracts are subjected to electrophoresis on sodium dodecyl sulfate/polyacrylamide gels. When 3T3-L1 cells differentiated in the presence of avidin, they contained less than 5% of the pyruvate carboxylase activity of cells that differentiated in the absence of avidin. However, the immunoprecipitable pyruvate carboxylase content of the avidin-treated cells was essentially the same as that of cells that differentiated without avidin. Full activity of the enzyme was rapidly restored in the avidin-treated cells upon the addition of excess biotin. The recovery of activity was closely correlated with the incorporation of [(14)C]biotin into immunoprecipitable pyruvate carboxylase. The rapidity with which the activity was restored and the insensitivity of the process to inhibitors of protein synthesis strongly suggest that the apoenzyme of pyruvate carboxylase accumulates during differentiation in the presence of avidin.


Broccoli microgreens have hypoglycemic effect by improving blood lipid and inflammatory factors while modulating gut microbiota in mice with type 2 diabetes.
This study aims to explore the hypoglycemic effect of lyophilized broccoli microgreens on type 2 diabetes (T2D) in mice. The experiment lasted 18 weeks, including 1 week of adaptation (normal diet) and 17-week experimental period (high-fat diet). After ingestion of broccoli microgreens, the body weight and glucose homeostasis were improved. Meanwhile, the blood lipid status, antioxidant indexes, and inflammatory factors level were improved. Moreover, the insulin resistance and the pathological changes in mice organs were reversed. In addition, the composition of gut microbiota and the production of propionic acid in intestinal content were improved. Our experiment proved that broccoli microgreens have the ability to regulate T2D and improve symptoms of mice T2D induced by high-fat diet and streptozotocin (STZ). PRACTICAL APPLICATIONS: For years, the functionality of broccoli microgreens has attracted much attention. This article will prove the therapeutic effect of broccoli microgreens on T2D and explain its principle of action in the management of T2D.


CD34 expression by inflammatory fibroid polyps of the stomach.
The phenotype of the proliferated spindled cells and the histogenesis of inflammatory fibroid polyp (IFP) have been a matter of debate. To clarify the immunohistochemical profile of the main cellular component, we reviewed histologically and studied immunohistochemically 11 cases (12 lesions) of IFP of the stomach. The lesions ranged in size from 0.4 to 3.0 cm (mean, 1.0 cm). All of the IFPs occurred in the antrum. Seven cases (63.6%) were accompanied by carcinoma or adenoma, which in two cases was present in covering epithelium. Grossly, eight IFPs were sessile, and four were polypoid. Microscopically, seven (58.3%) occupied both the mucosa and submucosa. Four (33.3%) were confined to the mucosa, and one was localized only in the submucosa. They were characterized by proliferation of relatively uniform spindled cells, often in a whorl-like arrangement around the blood vessels and glands. Eosinophilic and lymphocytic infiltration of varying degree was always present. The spindled cells in all of the IFPs were diffusely immunoreactive for vimentin and CD34. Seven (58.3%) were focally positive for histiocytic markers, such as KP1 and HAM56. Three (25%) showed focal immunoreactivity for alpha smooth muscle actin. Cytokeratin, desmin, S100 protein, Factor VIII RAG, and Ki-67 were negative in these spindled cells. The principle proliferating cells in IFPs in this study showed variable degrees of histiocytic and myofibroblastic lines of differentiation. Under the influence of some etiologic factors, the primitive, uncommitted spindled mesenchymal cells exhibiting CD34 immunoreactivity around the blood vessels and glands in the lower portion of mucosa and submucosa might play a role in development of IFP.


A portrait of resilience in caregiving.
The current study investigated biopsychosocial resilience in an older adult caregiver. A case study was selected for in-depth exploration of resilience in caregiving identified through biopsychosocial (i.e., salivary cortisol) methods. An exemplar of a woman caring for an adult child dying from a genetic disease is presented in the context of multiple stressors. Significant stress was found to be buffered by cognitive reframing and acceptance of interpersonal limits. Early experiences in caregiving for others with terminal illnesses provided a frame of reference, and difficult family dynamics added a layer of complexity. During periods identified as stressful, cortisol levels rose outside of normal bounds. The study implications are that mixed-methods (i.e., biopsychosocial) studies yield important results on individual differences within similar contexts.


The Contribution of a Collagen Patch Coated With Fibrin Glue in Sealing Upper Gastrointestinal Defects: An Experimental Study.
We aimed to evaluate the safety and efficacy of sealing primary upper gastrointestinal (GI) perforations with a collagen patch coated with fibrin glue (Tachosil®). Thirty New Zealand rabbits were used in this study. An iatrogenic gastric perforation was created, and primary repair was performed on the control group. Tachosil®, without suturing the deficit, was used in the intervention group. Leakage was observed in 3 (20%) and 2 rabbits (13.3%) in the control and intervention group, respectively; however, the difference was not statistically significant (p=0.62). Moreover, adhesions formed in 10/15 and all rabbits in the intervention and control group, respectively (p=0.014); however, based on the Zuhlke adhesion's classification, there was no statistically significant difference between the two groups. A collagen patch coated with fibrin glue is not a replacement but can be considered a safe option for the reinforcement of suturing, preventing leakages in the upper GI tract.


Human bocavirus infection in children with acute gastroenteritis and healthy controls.
Human bocavirus (HBoV) is a novel virus which can cause respiratory tract disease in infants and children. Recently, the prevalence of this virus was studied worldwide not only in the respiratory tract, but also in the gastrointestinal tract. The results of this study focusing on the HBoV detection in stool samples showed that HBoV could only be found in the stool of children with acute gastroenteritis (0.9%), not in the healthy control samples. Moreover, the complete coding sequences of these HBoV also showed very conserved sequences.


Towards Organized Hybrid Nanomaterials at the Air/Water Interface Based on Liquid-Crystal/ZnO Nanocrystals.
The ability to self-assemble nanosized ligand-stabilized metal oxide or semiconductor materials offers an intriguing route to engineer nanomaterials with new tailored properties from the disparate components. We describe a novel one-pot two-step organometallic approach to prepare ZnO nanocrystals (NCs) coated with deprotonated 4-(dodecyloxy)benzoic acid (i.e., an X-type liquid-crystalline ligand) as a model LC system (termed ZnO-LC1 NCs). Langmuir and Langmuir-Blodgett films of the resulting hybrids are investigated. The observed behavior of the ZnO NCs at the air/water interface is rationalized by invoking a ZnO-interdigitation process mediated by the anchored liquid-crystalline shell. The ordered superstructures form according to mechanism based on a ZnO-interdigitation process mediated by liquid crystals (termed ZIP-LC). The external and directed force applied upon compression at the air/water interface and the packing of the ligands that stabilize the ZnO cores drives the formation of nanorods of ordered internal structure. To study the process in detail, we follow a nontraditional protocol of thin-film investigation. We collect the films from the air/water interface in powder form (ZnO-LC1 LB), resuspend the powder in organic solvents and utilize otherwise unavailable experimental techniques. The structural and physical properties of the resulting superlattices were studied by using electron microscopy, atomic force microscopy, X-ray studies, dynamic light scattering, thermogravimetric analysis, UV/Vis absorption, and photoluminescence spectroscopy.


The auxin response factor gene family in banana: genome-wide identification and expression analyses during development, ripening, and abiotic stress.
Auxin signaling regulates various auxin-responsive genes via two types of transcriptional regulators, Auxin Response Factors (ARF) and Aux/IAA. ARF transcription factors act as critical components of auxin signaling that play important roles in modulating various biological processes. However, limited information about this gene family in fruit crops is currently available. Herein, 47 ARF genes were identified in banana based on its genome sequence. Phylogenetic analysis of the ARFs from banana, rice, and Arabidopsis suggested that the ARFs could be divided into four subgroups, among which most ARFs from the banana showed a closer relationship with those from rice than those from Arabidopsis. Conserved motif analysis showed that all identified MaARFs had typical DNA-binding and ARF domains, but 12 members lacked the dimerization domain. Gene structure analysis showed that the number of exons in MaARF genes ranged from 5 to 21, suggesting large variation amongst banana ARF genes. The comprehensive expression profiles of MaARF genes yielded useful information about their involvement in diverse tissues, different stages of fruit development and ripening, and responses to abiotic stresses in different varieties. Interaction networks and co-expression assays indicated the strong transcriptional response of banana ARFs and ARF-mediated networks in early fruit development for different varieties. Our systematic analysis of MaARFs revealed robust tissue-specific, development-dependent, and abiotic stress-responsive candidate MaARF genes for further functional assays in planta. These findings could lead to potential applications in the genetic improvement of banana cultivars, and yield new insights into the complexity of the control of MaARF gene expression at the transcriptional level. Finally, they support the hypothesis that ARFs are a crucial component of the auxin signaling pathway, which regulates a wide range of physiological processes.


Drosophila melanogaster-based screening for multihost virulence factors of Pseudomonas aeruginosa PA14 and identification of a virulence-attenuating factor, HudA.
Pseudomonas aeruginosa is an important opportunistic human pathogen that interacts with phylogenetically diverse nonmammalian hosts, including plants, nematodes, and insects. Here, we exploited the P. aeruginosa-induced killing of the fruit fly Drosophila melanogaster as an assay system to screen for virulence-attenuated mutants of P. aeruginosa PA14. Fifteen nonredundant mutants were isolated from 4,018 random transposon (TnphoA) insertion clones, and 13 out of them (86.7%) displayed significantly reduced virulence in a murine peritonitis model as well. The TnphoA insertion sites of the 15 mutants were determined; already known virulence genes (dsbA, pvdI, fhlB, pilF, and wspF) and new virulence genes such as PA0253 (hudR), PA0369, PA2077, PA0272, PA2113, PA2965 (fabF1), and PA2002 were identified; one insertion was located at the intergenic region between PA1928 and PA1929; and the other two insertions were located in the genes (PA14_35740 and PA14_36000) within a putative genomic island, indicating a potential pathogenicity island of PA14. Further characterization of hudR, a virulence gene which encodes a MarR/SlyA family transcription factor, revealed that elevated expression of PA0254 (hudA [homologous to UbiD]) was necessary and sufficient for the virulence attenuation of the hudR mutant. The HudR protein repressed the hudAR operon by directly binding to its upstream promoter region. Collectively, these results validate the relevance of the D. melanogaster model for the high-throughput identification of new virulence factors involved in the multihost pathogenesis of P. aeruginosa.


Impact of the degree of urbanization on composition and structure of helminth communities in the Mongolian racerunner (Eremias argus) Peters, 1869.
The effects of the degree of urbanization on the composition and mean abundance of helminth species and the structure of helminth communities in the Mongolian racerunner were investigated along a rural-urban gradient in the region of Ulan-Ude city (the Republic of Buryatia, Russia) and neighbouring rural districts. Racerunners were obtained from key areas and categorized into three grades based on the degree of urbanization. In this study, a total of 208 lizards were examined. The helminth communities in the Mongolian racerunner were studied at the infracommunity and component community levels. The nematode Spauligodon pseudoeremiasi was a sensitive bioindicator of the degree of urbanization in our study. All parameters of helminth infracommunities in the Mongolian racerunner were significantly reduced with increasing degree of urbanization of the key areas. Two parameters of helminth component communities (the proportion of hosts infected with parasites and the Shannon index) were significantly reduced with increasing degree of urbanization. The decline recorded in parameters of helminth infracommunities and component communities in the Mongolian racerunner were probably connected with the attenuation of the relationships between helminths, having a complex life cycle with intermediate hosts along the rural-urban gradient.


Systematic identification and characterization of long non-coding RNAs in mouse mature sperm.
Increasing studies have shown that mature spermatozoa contain many transcripts including mRNAs and miRNAs. However, the expression profile of long non-coding RNAs (lncRNAs) in mammalian sperm has not been systematically investigated. Here, we used highly purified RNA to investigate lncRNA expression profiles in mouse mature sperm by stranded-specific RNA-seq. We identified 20,907 known and 4,088 novel lncRNAs transcripts, and the existence of intact lncRNAs was confirmed by RT-PCR and fluorescence in situ hybridization on two representative lncRNAs. Compared to round spermatids, 1,794 upregulated and 165 downregulated lncRNAs and 4,435 upregulated and 3,920 downregulated mRNAs were identified in sperm. Based on the "Cis and Trans" RNA-RNA interaction principle, we found 14,259 targeted coding genes of differently expressed lncRNAs. In terms of Gene ontology (GO) analysis, differentially expressed lncRNAs targeted genes mainly related to nucleic acid metabolic, protein modification, chromatin and histone modification, heterocycle compound metabolic, sperm function, spermatogenesis and other processes. In contrast, differentially expressed transcripts of mRNAs were highly enriched for protein metabolic process and RNA metabolic, spermatogenesis, sperm motility, cell cycle, chromatin organization, heterocycle and aromatic compound metabolic processes. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the differentially expressed lncRNAs were involved in RNA transport, mRNA surveillance pathway, PI3K-Akt signaling pathway, AMPK signaling pathway, protein processing in endoplasmic reticulum. Metabolic pathways, mRNA surveillance pathway, AMPK signaling pathway, cell cycle, RNA transport splicesome and endocytosis incorporated with the differentially expressed mRNA. Furthermore, many lncRNAs were specifically expressed in testis/sperm, and 880 lncRNAs were conserved between human and mouse. In summary, this study provides a preliminary database valuable for identifying lncRNAs critical in the late stage of spermatogenesis or important for sperm function regulation, fertilization and early embryo development.


The global momentum for smokefree public places: best practice in current and forthcoming smokefree policies.
The Global Smokefree Partnership has recently prepared a map of smokefree campaigns and policies around the world. It focuses primarily on countries that are parties to the WHO Framework Convention on Tobacco Control, but other countries were included. The smokefree status of 172 countries was mapped. Of these countries, 31 (18.0%) have established comprehensive smokefree policies, either nationally or at state or city level - best practice; 25 (14.6%) are planning to implement smokefree policies in 2008 or 2009; and 51(29.6%) are making significant progress with smokefree policies. Only 65 countries (37.8%) have limited or no smokefree polices. A selection of countries representing best practices in smokefree policies or planning to implement smokefree policies in 2008 or 2009 is highlighted. They illustrate the significant global momentum for smokefree policies, the success of established policies, the importance of civil society and the sharing of experience between countries.


DNA methylation links prenatal smoking exposure to later life health outcomes in offspring.
Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring. We identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10-7) associated with exposure to maternal smoking in adolescents and adults. Mendelian randomization analyses provided evidence for a causal role of four maternal smoking-related CpG sites on an increased risk of inflammatory bowel disease or schizophrenia. Further mediation analyses showed some evidence of cg25189904 in GNG12 gene mediating the effect of exposure to maternal smoking on schizophrenia-related outcomes. DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.


Experimental cardiac allograft survival across major histocompatibility complex barriers in the rhesus monkey following T lymphocyte-depleted autologous marrow transplantation. I. In vitro T lymphocyte depletion studies.
We have developed a rhesus monkey model consisting of myeloablative total-body irradiation and T lymphocyte-depleted autologous bone marrow transplantation followed by MHC-mismatched heterotopic cardiac allograft implantation that has provided an opportunity to study the role of marrow T cells in cardiac allograft rejection. In order to assess quantitatively the effects of low numbers of residual marrow T cells following depletion, methods to deplete rhesus marrow extensively and to detect residual T cells following depletion at levels below the sensitivity of standard assays have been developed. A rhesus marrow limiting dilution assay has been developed that quantifies less than 1 T cell in 10(5) marrow cells and is superior to traditional detection methods by at least 3 logs. In a direct comparison of four T cell depletion methods, effective depletion has been achieved with complement-mediated cytotoxicity (C'MC), erythrocyte rosetting, and counterflow centrifugal elutriation (CCE), the latter with a simplified single-flow rate protocol. Median marrow T cell depletions of 2.1, 1.1, and 3.1 logs, and total nucleated cell losses of 40%, 61%, and 42% respectively, have been observed. A reported use of ricin A-chain-like toxins for the enhancement of C'MC was of low efficacy with rhesus peripheral blood T cell targets. CCE followed by C'MC has resulted in a median 4.8 logs depletion with residual marrow T cell contents less than 0.001%. Thus, C'MC, E-rosetting, and particularly CCE are effective methods of T cell depletion--and, when used in combination, extensively eliminate marrow T cells. A rhesus marrow limiting dilution assay detects residual T cells at these low levels. These techniques provide a basis for the quantitative study of the role of T cells in organ graft rejection following T lymphocyte-depleted autologous marrow transplantation.