Highly selective room temperature acetylene sorption by an unusual triacetylenic phosphine MOF.
The new ligand tris(p-carboxyphenylethynyl)phosphine (P{C[triple bond, length as m-dash]CC6H4-4-CO2H}3) was used to synthesize a permanently porous Mn(ii)-based acetylenic phosphine coordination material, PCM-48. This triply-interpenetrated MOF contains 1-D microchannels that are decorated with electron-rich and adsorbate-accessible acetylenic moieties and phosphine lone pairs. PCM-48 has a moderate room-temperature C2H2 adsorption capacity (25.54 cm3 g-1) and displays high separation selectivities for C2H2 over CH4 (C2H2/CH4 = 23.3), CO2 (C2H2/CO2 = 4.3), and N2 (C2H2/N2 = 76.9) at 296 K.


Transcriptional changes in response to arbuscular mycorrhiza development in the model plant Medicago truncatula.
Significant changes in root morphology and physiology during arbuscular mycorrhiza (AM) development are likely to be controlled by specific gene expression pattern in the host plant. Until now, little was known about transcriptional changes which occur AM-exclusively; that is, they do not occur during other root-microbe associations, nor are they induced by improved phosphate nutrition. In order to identify such AM-exclusive gene inductions of Medicago truncatula, we used a pool of different RNA samples as subtractor population in a suppressive subtractive hybridization (SSH) experiment. This approach resulted in the identification of a number of new AM-regulated genes. None of these genes were expressed in nonmycorrhiza roots or leaves. Electronic data obtained by comparison of the cDNA sequences to expressed sequence tag (EST) sequences from a wide range of cDNA libraries in the M. truncatula EST database (Gene Index, MtGI) support the mycorrhiza specificity of the corresponding genes, because sequences in the MtGI that were found to match the identified SSH-cDNA sequences originated exclusively from AM cDNA libraries. The promoter of one of those genes, MtGst1, showing similarities to plant glutathione-S-transferase (GST) encoding genes, was cloned and used in reporter gene studies. In contrast to studies with the potato GST gene PRP, MtGst 1 promoter activity was detected in all zones of the root cortex colonized by Glomus intraradices, but nowhere else.


Socioeconomic determinants and metabolic syndrome: Results from the Isfahan Healthy Heart Program.
Introduction: The prevalence of metabolic syndrome (MetS) is increasing in Iran. We assessed the relationship between socioeconomic status (SES) and Mets components in the Iranian population. The sample for this study comprised a random cross-section of men and women from two province districts who participated in the Isfahan Healthy Heart Program (IHHP) in 2007. Each participant completed a questionnaire, underwent anthropometric testing and blood pressure measurements, and provided a blood sample. Mets was defined based on ATPIII criteria. Several SES dimensions, such as education, occupation, and number of children, as well as home, car, and personal computer ownership, were assessed to determine the participant's SES. A higher-than-average income, car ownership, owning or renting a private home, and having a computer are increasing towards increment in SES. All MetS components were more prevalent in participants defined as having a lower SES, while low HDL levels were more common in participants having an SES II (P>0.001). A multivariate analysis showed that having the lowest SES (I) increased the risk of MetS by 1.72 [1.44-2.07], whereas subjects having an SES III had a 1.23 [1.04-1.47] lower risk for MetS. The relationship between SES and Mets is due largely to behavioural factors, such as practicing unhealthy eating habits. Given the high prevalence of Mets in Iran, we propose that regular health check-ups may be useful in the early detection of the syndrome and, consequently, in the prevention of its effects. In addition, the early detection of MetS may result in the early diagnosis and prevention of cardiovascular diseases.


The effect of organic anion-transporting polypeptides 1B1, 1B3 and 2B1 on the antitumor activity of flavopiridol in breast cancer cells.
The contribution of organic anion transporting polypeptides (OATPs) to the cellular uptake of flavopiridol was investigated in OATP1B1-, OATP1B3- and OATP2B1-expressing Chinese hamster ovary (CHO) cells. Uptake of flavopiridol into these cells showed typical Michaelis-Menten kinetics with much higher transport capacity for OATP1B3 compared to OATP1B1 and OATP2B1 (Vmax/Km, 33.9 vs. 8.84 and 2.41 µl/mg/min, respectively). The predominant role of OATPs was further supported by a dramatic inhibition of flavopiridol uptake in the presence of the OATP substrate rifampicin. Uptake of flavopiridol by OATPs also seems to be an important determinant in breast cancer cells. The much higher mRNA level for OATP1B1 found in wild-type compared to ZR-75-1 OATP1B1 knockdown cells correlated with higher flavopiridol initial uptake leading to 4.6-fold decreased IC50 values in the cytotoxicity assay (IC50, 1.45 vs. 6.64 µM). Cell cycle profile also showed a clear incidence for a stronger cell cycle arrest in the G2/M phase for ZR-75-1 wild-type cells compared to OATP1B1 knockdown cells, further indicating an active uptake via OATP1B1. In conclusion, our results revealed OATP1B1, OATP1B3 and OATP2B1 as uptake transporters for flavopiridol in cancer cells, which may also apply in patients during cancer therapy.


Indonesian children fecal microbiome from birth until weaning was different from microbiomes of their mothers.
Gastrointestinal (GI) microbiota play an important role in human health and wellbeing and the first wave of gut microbes arrives mostly through vertical transmission from mother to child. This study has undertaken to understand the microbiota profile of healthy Southeast Asian mother-infant pairs. Here, we examined the fecal, vaginal and breast milk microbiota of Indonesian mothers and the fecal microbiota of their children from less than 1 month to 48 months old. To determine the immune status of children and the effect of diet at different ages, we examined the level of cytokines, bile acids in the fecal water and weaning food frequency. The fecal microbiota of the children before weaning contained mainly Bacteroides and Bifidobacterium, which presented at low abundance in the samples of mothers. After weaning, the fecal microbiome of children was mainly of the Prevotella type, with decreasing levels of Bifidobacterium, thus becoming more like the fecal microbiome of the mother. The abundance of infant fecal commensals generally correlated inversely with potential pathogens before weaning. The fecal Bifidobacterium in children correlated inversely with the consumption of complex carbohydrates and fruits after weaning. The specific cytokines related to the proliferation and maturation of immunity were found to increase after weaning. A decreasing level of primary bile acids and an increase of secondary bile acids were observed after weaning. This study highlights the change in the GI microbiota of infants to adult-type microbiota after weaning and identifies diet as a major contributing factor.


Preliminary estimates of nanoparticle number emissions from road vehicles in megacity Delhi and associated health impacts.
Rapid urbanisation in developing megacities like Delhi has resulted in an increased number of road vehicles and hence total particle number (ToN) emissions. For the first time, this study presents preliminary estimates of ToN emissions from road vehicles, roadside and ambient ToN concentrations, and exposure related excess deaths in Delhi in current and two future scenarios; business as usual (BAU) and best estimate scenario (BES). Annual ToN emissions are estimated as 1.37 × 10(25) for 2010 which are expected to increase by ∼4 times in 2030-BAU, but to decrease by ∼18 times in 2030-BES. Such reduction is anticipated due to a larger number of compressed natural gas driven vehicles and assumed retrofitting of diesel particulate filters to all diesel vehicles by 2020. Heavy duty vehicles emit the majority (∼65%) of ToN for only ∼4% of total vehicle kilometres traveled in 2010. Their contribution remains dominant under both scenarios in 2030, clearly requiring major mitigation efforts. Roadside and ambient ToN concentrations were up to a factor of 30 and 3 higher to those found in respective European environments. Exposure to ambient ToN concentrations resulted in ∼508, 1888, and 31 deaths per million people in 2010, 2030-BAU and 2030-BES, respectively.


Spontaneous de-differentiation correlates with extended lifespan in transformed thyroid epithelial cells: an epigenetic mechanism of tumour progression?
Normal thyroid follicular cells, like many highly differentiated epithelia, have limited proliferative capacity. We previously showed that this could be extended by expression of the SV40 large T oncogene, but that immortal lines always lost thyroid-specific differentiation. Detailed analysis now show that clones expressing T undergo 2 mutually exclusive fates. They either (i) remain well-differentiated, in which case they undergo irreversible growth arrest after 5 to 15 p.d., or (ii) spontaneously develop poorly differentiated sub-clones that exhibit greatly extended proliferative life spans (up to 75 p.d.). The frequency of this event (> 3 per 10(4) cell divisions) greatly exceeds that expected from somatic mutation, suggesting an epigenetic basis. This is supported by our finding of rare de-differentiated epithelial cells in normal thyroid that all generate clones with extended life spans, indistinguishable from the above, following introduction of SV40 T. Escape from early mortality in differentiated thyroid epithelium therefore requires not only loss of tumour suppressor gene function (induced here by SV40 T), but also a switch in differentiation programme, with the latter effectively converting the follicular cell into a cell type with increased intrinsic proliferative potential. The analogy between this in vitro model and the progression of thyroid cancer from the well-differentiated to the highly aggressive, anaplastic form suggests that de-differentiation may play a causal rather than a passive role in this critical switch in tumour behaviour.


[Perioperative management of lung cancer patients with cardiovascular complications].
Lung cancer patients with cardiovascular complications often require antithrombotic therapy. In this study, we discuss the present conditions and future problems associated with the perioperative management of such patients. We examined 36 lung cancer patients undergoing surgery who received antithrombotic therapy for cardiovascular complications. Twenty-one patients were administered unfractionated heparin in the perioperative period (heparin group). Fifteen patients were not administered unfractionated heparin in the perioperative period (no-heparin group). No significant intergroup differences were observed in operating time, intraoperative blood loss, duration of chest tube placement, and the number of hospitalization days. However, 2 serious cases of thromboembolism developed after surgery. One was a case of pulmonary thromboembolism and the other was one of superior mesenteric artery thromboembolism. These results suggest that the appropriate perioperative usage of heparin enables the standard surgical treatment of lung cancer patients with cardiovascular complications. We recommend the use of low-molecular-weight heparin or low-dose unfractionated heparin as the antithrombotic agent after lung cancer surgery.


Higher asthma occurrence in an urban than a suburban area: role of house dust mite skin allergy.
Understanding of geographical differences in asthma prevalence may be helpful in explaining recent increases in the occurrence of asthma. We wondered whether differences in allergic sensitization or other factors could explain differences in reported occurrence of asthma between an urban centre and a neighbouring suburban area. From the European Community Respiratory Health Survey (ECRHS) questionnaire, responses on asthma symptoms and risk factors and results of 11 skin allergy tests were available from 656 young adults living in urban or south suburban Antwerp, Belgium. Answers to five asthma questions were selected as dependent variables, and eight personal or environmental risk factors, as well as house dust mite (HDM) allergy, as independent variables. The effect of each independent variable on the association of asthma variables with area was assessed. Prior asthma diagnosis, present asthma symptoms, the selected risk factors and HDM allergy were all more frequently recorded in urban Antwerp. Difference in HDM allergy accounted for most of the difference in prior (mostly childhood) asthma diagnosis, since correction for it decreased the odds ratio from 2.10 to 1.65. On the contrary, the regional differences in recent asthma symptoms were not explained by HDM allergy differences nor by any other factor under study. This urban-suburban comparison indicated that house dust mite allergy is a major determinant of prior (childhood) asthma, whereas factors contributing to higher urban prevalence of present asthma symptoms could not be identified. Furthermore, our results indicate that it may be inappropriate to combine data from neighbouring areas, when their similarity has not been verified.


Less stable tautomers form stronger hydrogen bonds: the case of water complexes.
Hydrogen bonding in cyclic complexes of water with tautomeric pairs of molecules M0 and M1 is calculated to be stronger by more than 25% for the less stable tautomer M1 in all cases where the energy gap between the two tautomers is large (ΔE(M0 - M1) > 10 kcal mol-1). This is accompanied by a large red-shift (>200 cm-1) of the N-H/O-H stretch frequency in the complexes involving M1. Large barriers for double proton transfer in both directions should permit an experimental verification. Exceptions to this rule were found in heterocycles with an N-C[double bond, length as m-dash]O fragment incorporated into a conjugated cycle resulting in two nearly degenerate tautomers - keto and enol forms. The wavefunction of the keto form has a large contribution from a zwitterionic VB structure which is also aromatic. This increases the polarity of the keto group, making the oxygen atom a strong H-bond acceptor. It can also stabilize the keto form below the aromatic enol form. In this case the extra-HB stabilization is observed for the most stable tautomer (i.e. for the keto form). H-bonding enhances the aromatic character of less aromatic molecules, but the more aromatic tautomers partially loose aromaticity.


Reframing the concept of alternative livelihoods.
Alternative livelihood project (ALP) is a widely used term for interventions that aim to reduce the prevalence of activities deemed to be environmentally damaging by substituting them with lower impact livelihood activities that provide at least equivalent benefits. ALPs are widely implemented in conservation, but in 2012, an International Union for Conservation of Nature resolution called for a critical review of such projects based on concern that their effectiveness was unproven. We focused on the conceptual design of ALPs by considering their underlying assumptions. We placed ALPs within a broad category of livelihood-focused interventions to better understand their role in conservation and their intended impacts. We dissected 3 flawed assumptions about ALPs based on the notions of substitution, the homogenous community, and impact scalability. Interventions based on flawed assumptions about people's needs, aspirations, and the factors that influence livelihood choice are unlikely to achieve conservation objectives. We therefore recommend use of a sustainable livelihoods approach to understand the role and function of environmentally damaging behaviors within livelihood strategies; differentiate between households in a community that have the greatest environmental impact and those most vulnerable to resource access restrictions to improve intervention targeting; and learn more about the social-ecological system within which household livelihood strategies are embedded. Rather than using livelihood-focused interventions as a direct behavior-change tool, it may be more appropriate to focus on either enhancing the existing livelihood strategies of those most vulnerable to conservation-imposed resource access restrictions or on use of livelihood-focused interventions that establish a clear link to conservation as a means of building good community relations. However, we recommend that the term ALP be replaced by the broader term livelihood-focused intervention. This avoids the implicit assumption that alternatives can fully substitute for natural resource-based livelihood activities.


A Cross-linking Mass Spectrometry Approach Defines Protein Interactions in Yeast Mitochondria.
Protein cross-linking and the analysis of cross-linked peptides by mass spectrometry is currently receiving much attention. Not only is this approach applied to isolated complexes to provide information about spatial arrangements of proteins, but it is also increasingly applied to entire cells and their organelles. As in quantitative proteomics, the application of isotopic labeling further makes it possible to monitor quantitative changes in the protein-protein interactions between different states of a system. Here, we cross-linked mitochondria from Saccharomyces cerevisiae grown on either glycerol- or glucose-containing medium to monitor protein-protein interactions under non-fermentative and fermentative conditions. We investigated qualitatively the protein-protein interactions of the 400 most abundant proteins applying stringent data-filtering criteria, i.e. a minimum of two cross-linked peptide spectrum matches and a cut-off in the spectrum scoring of the used search engine. The cross-linker BS3 proved to be equally suited for connecting proteins in all compartments of mitochondria when compared with its water-insoluble but membrane-permeable derivative DSS. We also applied quantitative cross-linking to mitochondria of both the growth conditions using stable-isotope labeled BS3. Significant differences of cross-linked proteins under glycerol and glucose conditions were detected, however, mainly because of the different copy numbers of these proteins in mitochondria under both the conditions. Results obtained from the glycerol condition indicate that the internal NADH:ubiquinone oxidoreductase Ndi1 is part of an electron transport chain supercomplex. We have also detected several hitherto uncharacterized proteins and identified their interaction partners. Among those, Min8 was found to be associated with cytochrome c oxidase. BN-PAGE analyses of min8Δ mitochondria suggest that Min8 promotes the incorporation of Cox12 into cytochrome c oxidase.


Evaluation of safety and efficacy of the TriPollar technology for treatment of wrinkles.
Patient demand for non-surgical, non-invasive, and no-downtime wrinkle reduction treatment procedures has grown dramatically over the past decade as new treatments and technologies have been introduced. This study was performed in order to evaluate the safety and efficacy of the TriPollar radiofrequency (RF) technology and intended for wrinkle reduction treatment. Thirty-seven Subjects were recruited in two sites and were treated for the reduction of facial wrinkles and rhytides and followed for 3 months after the last treatment. The safety of using the TriPollar system was established by the physicians' assessments and observations of adverse events after each treatment. To evaluate treatment efficacy, pre- and post-treatment photos were assessed using a blinded evaluation by two uninvolved physicians. No unexpected adverse side effects were detected or reported. All subjects participating in the study reported no pain or mild pain during the treatments. The photographic analysis of pre- and post-treatment by the two blinded physicians revealed improvement (downgrade of at least 1 score according to the Fitzpatrick scale) in 94% (according to first reviewer) and 97% (according to second reviewer) of study subjects. All patients (100%) were satisfied from treatment results to a different extent. The results of this study clearly indicate that the TriPollar system offers a non-invasive, effective, safe and virtually painless wrinkle and rhytides reduction treatment.


Coexistence of Ballistic and Fourier Regimes in the β Fermi-Pasta-Ulam-Tsingou Lattice.
Commonly, thermal transport properties of one-dimensional systems are found to be anomalous. Here, we perform a numerical and theoretical study of the β-Fermi-Pasta-Ulam-Tsingou chain, considered a prototypical model for one-dimensional anharmonic crystals, in contact with thermostats at different temperatures. We give evidence that, in steady state conditions, the local wave energy spectrum can be naturally split into modes that are essentially ballistic (noninteracting or scarcely interacting) and kinetic modes (interacting enough to relax to local thermodynamic equilibrium). We show numerically that the well-known divergence of the energy conductivity is related to how the transition region between these two sets of modes shifts in k space with the system size L, due to properties of the collision integral of the system. Moreover, we show that the kinetic modes are responsible for a macroscopic behavior compatible with Fourier's law. Our work sheds light on the long-standing problem of the applicability of standard thermodynamics in one-dimensional nonlinear chains, testbed for understanding the thermal properties of nanotubes and nanowires.


Varying the item format improved the range of measurement in patient-reported outcome measures assessing physical function.
Physical function (PF) is a core patient-reported outcome domain in clinical trials in rheumatic diseases. Frequently used PF measures have ceiling effects, leading to large sample size requirements and low sensitivity to change. In most of these instruments, the response category that indicates the highest PF level is the statement that one is able to perform a given physical activity without any limitations or difficulty. This study investigates whether using an item format with an extended response scale, allowing respondents to state that the performance of an activity is easy or very easy, increases the range of precise measurement of self-reported PF. Three five-item PF short forms were constructed from the Patient-Reported Outcomes Measurement Information System (PROMIS®) wave 1 data. All forms included the same physical activities but varied in item stem and response scale: format A ("Are you able to …"; "without any difficulty"/"unable to do"); format B ("Does your health now limit you …"; "not at all"/"cannot do"); format C ("How difficult is it for you to …"; "very easy"/"impossible"). Each short-form item was answered by 2217-2835 subjects. We evaluated unidimensionality and estimated a graded response model for the 15 short-form items and remaining 119 items of the PROMIS PF bank to compare item and test information for the short forms along the PF continuum. We then used simulated data for five groups with different PF levels to illustrate differences in scoring precision between the short forms using different item formats. Sufficient unidimensionality of all short-form items and the original PF item bank was supported. Compared to formats A and B, format C increased the range of reliable measurement by about 0.5 standard deviations on the positive side of the PF continuum of the sample, provided more item information, and was more useful in distinguishing known groups with above-average functioning. Using an item format with an extended response scale is an efficient option to increase the measurement range of self-reported physical function without changing the content of the measure or affecting the latent construct of the instrument.


BY55/CD160 cannot be considered a cytotoxic marker in cytomegalovirus-specific human CD8(+) T cells.
CD160/BY55 is a glucosyl-phosphatidylinositol (GPI)-anchored cell membrane receptor that is expressed primarily in natural killer (NK) cells. Its presence in CD8(+) T lymphocytes is considered to be a marker of cytotoxic activity, although there are few data in this regard. In the present work, we analysed the expression of CD160 in subpopulations of cytomegalovirus (CMV)-specific CD8(+) T cells. Subpopulations were defined by CD28 and CD57 expression and exhibited varying degrees of differentiation and cytotoxic potential, as evaluated by the expression of perforin, interferon (IFN)-gamma and interleukin (IL)-7Ralpha/CD127. We included subjects with different intensities of anti-viral immune response. Results showed that the terminally differentiated CD28(-) CD57(+) subset displaying the highest level of perforin expressed CD160 at a level similar to that of memory CD28(+) CD57(-)perforin(-) cells. A comparison of the expression of perforin in CD160(+) cells versus CD160(-) cells showed that expression was significantly higher in the absence of CD160. Interestingly, the CMV-specific CD8(+) T cell subset from a patient with ongoing CMV reactivation did not begin to express CD160 until day +92 of the follow-up period. Taken together, our data show that CD160 cannot be considered a cytotoxic marker in CMV-specific CD8(+) T cells.


Effect of Time-of-Flight Information on PET/MR Reconstruction Artifacts: Comparison of Free-breathing versus Breath-hold MR-based Attenuation Correction.
Purpose To evaluate the magnitude and anatomic extent of the artifacts introduced on positron emission tomographic (PET)/magnetic resonance (MR) images by respiratory state mismatch in the attenuation map. Materials and Methods The method was tested on 14 patients referred for an oncologic examination who underwent PET/MR imaging. The acquisition included standard PET and MR series for each patient, and an additional attenuation correction series was acquired by using breath hold. PET data were reconstructed with and without time-of-flight (TOF) information, first by using the standard free-breathing attenuation map and then again by using the additional breath-hold map. Two-tailed paired t testing and linear regression with 0 intercept was performed on TOF versus non-TOF and free-breathing versus breath-hold data for all detected lesions. Results Fluorodeoxyglucose-avid lesions were found in eight of the 14 patients included in the study. The uptake differences (maximum standardized uptake values) between PET reconstructions with free-breathing versus breath-hold attenuation ranged, for non-TOF reconstructions, from -18% to 26%. The corresponding TOF reconstructions yielded differences from -15% to 18%. Conclusion TOF information was shown to reduce the artifacts caused at PET/MR by respiratory mismatch between emission and attenuation data. © RSNA, 2016 Online supplemental material is available for this article.


Work-Life Balance among Married Women Employees.
Family-work conflict (FWC) and work-family conflict (WFC) are more likely to exert negative influences in the family domain, resulting in lower life satisfaction and greater internal conflict within the family. Studies have identified several variables that influence the level of WFC and FWC. Variables such as the size of family, the age of children, the work hours and the level of social support impact the experience of WFC and FWC. However, these variables have been conceptualized as antecedents of WFC and FWC; it is also important to consider the consequences these variables have on psychological distress and wellbeing of the working women. to study various factors which could lead to WFC and FWC among married women employees. The sample consisted of a total of 90 married working women of age between 20 and 50 years. WFC and FWC Scale was administered to measure WFC and FWC of working women. The obtained data were analyzed using descriptive and inferential statistics. Carl Pearson's Correlation was used to find the relationship between the different variables. The findings of the study emphasized the need to formulate guidelines for the management of WFCs at organizational level as it is related to job satisfaction and performance of the employees.


Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU: a randomized trial.
Antibiotic-resistant bacteria are associated with increased patient morbidity and mortality. It is unknown whether wearing gloves and gowns for all patient contact in the intensive care unit (ICU) decreases acquisition of antibiotic-resistant bacteria. To assess whether wearing gloves and gowns for all patient contact in the ICU decreases acquisition of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) compared with usual care. Cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from January 4, 2012, to October 4, 2012. In the intervention ICUs, all health care workers were required to wear gloves and gowns for all patient contact and when entering any patient room. The primary outcome was acquisition of MRSA or VRE based on surveillance cultures collected on admission and discharge from the ICU. Secondary outcomes included individual VRE acquisition, MRSA acquisition, frequency of health care worker visits, hand hygiene compliance, health care–associated infections, and adverse events. From the 26,180 patients included, 92,241 swabs were collected for the primary outcome. Intervention ICUs had a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1000 patient-days (95% CI, 17.57 to 25.94) in the baseline period to 16.91 acquisitions per 1000 patient-days (95% CI, 14.09 to 20.28) in the study period, whereas control ICUs had a decrease in MRSA or VRE from 19.02 acquisitions per 1000 patient-days (95% CI, 14.20 to 25.49) in the baseline period to 16.29 acquisitions per 1000 patient-days (95% CI, 13.48 to 19.68) in the study period, a difference in changes that was not statistically significant (difference, −1.71 acquisitions per 1000 person-days, 95% CI, −6.15 to 2.73; P = .57). For key secondary outcomes, there was no difference in VRE acquisition with the intervention (difference, 0.89 acquisitions per 1000 person-days; 95% CI, −4.27 to 6.04, P = .70), whereas for MRSA, there were fewer acquisitions with the intervention (difference, −2.98 acquisitions per 1000 person-days; 95% CI, −5.58 to −0.38; P = .046). Universal glove and gown use also decreased health care worker room entry (4.28 vs 5.24 entries per hour, difference, −0.96; 95% CI, −1.71 to −0.21, P = .02), increased room-exit hand hygiene compliance (78.3% vs 62.9%, difference, 15.4%; 95% CI, 8.99% to 21.8%; P = .02) and had no statistically significant effect on rates of adverse events (58.7 events per 1000 patient days vs 74.4 events per 1000 patient days; difference, −15.7; 95% CI, −40.7 to 9.2, P = .24). The use of gloves and gowns for all patient contact compared with usual care among patients in medical and surgical ICUs did not result in a difference in the primary outcome of acquisition of MRSA or VRE. Although there was a lower risk of MRSA acquisition alone and no difference in adverse events, these secondary outcomes require replication before reaching definitive conclusions. clinicaltrials.gov Identifier: NCT0131821.


Obesity and COPD: associated symptoms, health-related quality of life, and medication use.
There is little data about the combined effects of COPD and obesity. We compared dyspnea, health-related quality of life (HRQoL), exacerbations, and inhaled medication use among patients who are overweight and obese to those of normal weight with COPD. We performed secondary data analysis on 364 Veterans with COPD. We categorized subjects by body mass index (BMI). We assessed dyspnea using the Medical Research Council (MRC) dyspnea scale and HRQoL using the St. George's Respiratory Questionnaire. We identified treatment for an exacerbation and inhaled medication use in the past year. We used multiple logistic and linear regression models as appropriate, with adjustment for age, COPD severity, smoking status, and co-morbidities. The majority of our population was male (n = 355, 98%) and either overweight (n = 115, 32%) or obese (n = 138, 38%). Obese and overweight subjects had better lung function (obese: mean FEV(1) 55.4% ±19.9% predicted, overweight: mean FEV(1) 50.0% ±20.4% predicted) than normal weight subjects (mean FEV(1) 44.2% ±19.4% predicted), yet obese subjects reported increased dyspnea [adjusted OR of MRC score ≥2 = 4.91 (95% CI 1.80, 13.39], poorer HRQoL, and were prescribed more inhaled medications than normal weight subjects. There was no difference in any outcome between overweight and normal weight patients. Despite having less severe lung disease, obese patients reported increased dyspnea and poorer HRQoL than normal weight patients. The greater number of inhaled medications prescribed for obese patients may represent overuse. Obese patients with COPD likely need alternative strategies for symptom control in addition to those currently recommended.


Effective antibacterial and antioxidant properties of methanolic extract of Laurus nobilis seed oil.
This study was carried out to determine the in vitro antimicrobial and antioxidant activities of the essential oil, seed oil, and methanolic extract of seed oil obtained from Laurus nobilis L. (Lauraceae). The methanolic extract of seed oil exhibited more effective antibacterial activity comparing to essential oil and seed oil, GC-MS analyses of the essential oil resulted in the identification of 25 compounds. 1.8-Cineol (44.72%), a-Terpinyl acetate (12.95%), Sabinene (12.82%) were the main components. The fatty acid composition was characterized with the high content of linoleic acid (40.79%) and lauric acid (38.08%). The 50% (IC50) inhibition activity of the essential oil on the free radical DPPH was determined as 94.655 mg ml(-1), whereas IC50 value of methanolic extract of seed oil was found unstable. In the case of the linoleic acid system, oxidation of linoleic acid was inhibited by essential oil and methanolic extract of seed oil, which showed 64.28 and 88.76% inhibition, respectively. The inhibition value of the methanolic extract of seed oil was quite close to the synthetic antioxidant BHT, 92.46% inhibition.


The Caenorhabditis elegans gene sdc-2 controls sex determination and dosage compensation in XX animals.
We have identified a new X-linked gene, sdc-2, that controls the hermaphrodite (XX) modes of both sex determination and X chromosome dosage compensation in Caenorhabditis elegans. Mutations in sdc-2 cause phenotypes that appear to result from a shift of both the sex determination and dosage compensation processes in XX animals to the XO modes of expression. Twenty-eight independent sdc-2 mutations have no apparent effect in XO animals, but cause two distinct phenotypes in XX animals: masculinization, reflecting a defect in sex determination, and lethality or dumpiness, reflecting a disruption in dosage compensation. The dosage compensation defect can be demonstrated directly by showing that sdc-2 mutations cause elevated levels of several X-linked transcripts in XX but not XO animals. While the masculinization is blocked by mutations in sex determining genes required for male development (her-1 and fem-3), the lethality, dumpiness and overexpression of X-linked genes are not, indicating that the effect of sdc-2 mutations on sex determination and dosage compensation are ultimately implemented by two independent pathways. We propose a model in which sdc-2 is involved in the coordinate control of both sex determination and dosage compensation in XX animals and acts in the regulatory hierarchy at a step prior to the divergence of the two pathways.


Long-term infection of goats with bluetongue virus serotype 25.
Toggenburg Orbivirus (TOV) is the prototype of bluetongue virus serotype 25 (BTV-25). It was first detected in goats in Switzerland in 2008. The virus does not induce clinical signs in infected goats. In field samples viral RNA could be detected only in goats and never in other ruminants. BTV-25 RNA was repeatedly detected for more than one year in the blood of goats from a single flock in Principality of Liechtenstein. Since viral persistence over such a long period has never been reported for bluetongue, blood samples from 110 goats and 2 sheep of that flock were collected during a period of up to two years and analyzed for the presence of BTV-25 RNA and antibodies. Most of the animals which tested positive for BTV-25 RNA, remained positive during the whole investigation period. Moreover, five of these goats were BTV-25 RNA positive over a period of 19-25 months. A weak antibody response against BTV VP7 was commonly observed. As BTV-25 cannot be propagated in any culture system, the presence of virus could only be demonstrated in samples by viral RNA detection using RT-qPCR. To address the question of infectivity of the virus in blood from long-term positive animals, goats were experimentally infected with this blood. Viral replication was demonstrated by increasing RNA amounts. Thus, our findings provide evidence that BTV-25 can persist much longer in an infected host than known so far for other BTV serotypes. Hence, persistence of infectious BTV represents an additional important factor in BTV epidemiology.


The active identification and management of chronic refractory breathlessness is a human right.
Chronic refractory breathlessness is defined as breathlessness at rest or on minimal exertion that will persist chronically despite optimal treatment of the underlying cause(s). At any time, 1% of the population report a modified Medical Research Council dyspnoea score of ≥ 3 chronically. Despite the prevalence, severity and chronicity of this symptom and an evidence base of affordable and safe interventions, chronic refractory breathlessness remains grossly undertreated. Many patients and clinicians accept the presence of the chronic refractory breathlessness as an inevitable part of an illness, with no thought of treating the symptom despite an evidence base for its safe treatment. Consensus statements from major respiratory clinician organisations now endorse such a clinical course. Failure to inquire about, assess and properly treat chronic refractory breathlessness with opioids as outlined in specialist clinical guidelines is now an unacceptable level of care ethically and is, arguably, a breach of people's human rights. Adequate pain control through access to pain relief is now accepted as a human right and, given its burden across the world, the symptomatic treatment of chronic refractory breathlessness should be seen in exactly the same way.


Genome sequence and comparative genome analysis of Lactobacillus casei: insights into their niche-associated evolution.
Lactobacillus casei is remarkably adaptable to diverse habitats and widely used in the food industry. To reveal the genomic features that contribute to its broad ecological adaptability and examine the evolution of the species, the genome sequence of L. casei ATCC 334 is analyzed and compared with other sequenced lactobacilli. This analysis reveals that ATCC 334 contains a high number of coding sequences involved in carbohydrate utilization and transcriptional regulation, reflecting its requirement for dealing with diverse environmental conditions. A comparison of the genome sequences of ATCC 334 to L. casei BL23 reveals 12 and 19 genomic islands, respectively. For a broader assessment of the genetic variability within L. casei, gene content of 21 L. casei strains isolated from various habitats (cheeses, n = 7; plant materials, n = 8; and human sources, n = 6) was examined by comparative genome hybridization with an ATCC 334-based microarray. This analysis resulted in identification of 25 hypervariable regions. One of these regions contains an overrepresentation of genes involved in carbohydrate utilization and transcriptional regulation and was thus proposed as a lifestyle adaptation island. Differences in L. casei genome inventory reveal both gene gain and gene decay. Gene gain, via acquisition of genomic islands, likely confers a fitness benefit in specific habitats. Gene decay, that is, loss of unnecessary ancestral traits, is observed in the cheese isolates and likely results in enhanced fitness in the dairy niche. This study gives the first picture of the stable versus variable regions in L. casei and provides valuable insights into evolution, lifestyle adaptation, and metabolic diversity of L. casei.


Experiences of Using a Consumer-Based Mobile Meditation App to Improve Fatigue in Myeloproliferative Patients: Qualitative Study.
Myeloproliferative neoplasm (MPN) patients suffer from long-term symptoms and reduced quality of life. Mindfulness meditation is a complementary therapy shown to be beneficial for alleviating a range of cancer-related symptoms; however, in-person meditation interventions are difficult for cancer patients to attend. Meditation via a mobile phone app represents a novel approach in MPN patients for delivering meditation. The study aimed to report MPN patients' (ie, naïve or nearly naïve meditators) perceptions of meditation and explore their experiences in the context of using a mobile phone for meditation after participation in an 8-week consumer-based meditation app feasibility study. MPN patients (n=128) were recruited nationally through organizational partners and social media. Eligible and consented patients were enrolled into 1 of 4 groups, 2 that received varying orders of 2 consumer-based apps (10% Happier and Calm) and 2 that received one of the apps alone for the second 4 weeks of the 8-week intervention after an educational control condition. Participants were asked to perform 10 min per day of mobile phone-based meditation, irrespective of the app and order in which they received the apps. At the conclusion of the study, participants were asked whether they would like to participate in a 20-min phone interview comprising 9 to 10 questions to discuss their perceptions and experiences while using the mobile phone meditation apps. The interviews were transcribed verbatim and imported into NVivo 12 (QSR International) for coding and analysis, using a combination of deductive and inductive methods to organize the data, generate categories, and develop themes and subthemes. A total of 48 MPN patients completed postintervention interviews, of which 29% (14/48) of the patients only used the 10% Happier app, 21% (10/48) of the patients only used the Calm app, and 46% (22/48) of the patients used both apps during the 8-week intervention. Themes identified in the analysis of interview data related to (1) perceptions of meditation before, during, and after the study, (2) perceptions of the Calm app, (3) perceptions of the 10% Happier app, (4) perceived impacts of using the meditation apps, (5) overall experiences of participating in the study, (6) recommendations surrounding meditation for other MPN patients, and (7) plans to continue meditation. The qualitative findings of this study suggest that MPN patients who are naïve or nearly naïve meditators perceived mobile phone meditation as enjoyable, preferred the Calm app over the 10% Happier app, perceived the Calm app as more appealing (eg, narrator's voice and different meditations or background sounds offered), and perceived beneficial effects of meditation on mental health, sleep, fatigue, and pain. Future research is needed to better understand the efficacy of mobile phone meditation on MPN patient outcomes and meditation app design features that enhance uptake among its users.


Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time.
We explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI) funded trials has increased over time. We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease. Trials were included if direct costs >$500,000/year, participants were adult humans, and the primary outcome was cardiovascular risk, disease or death. The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000, whether they registered in clinicaltrials.gov prior to publication, used active or placebo comparator, and whether or not the trial had industry co-sponsorship. We tabulated whether the study reported a positive, negative, or null result on the primary outcome variable and for total mortality. 17 of 30 studies (57%) published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 (8%) trials published after 2000 (χ2=12.2,df= 1, p=0.0005). There has been no change in the proportion of trials that compared treatment to placebo versus active comparator. Industry co-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward null findings. The number NHLBI trials reporting positive results declined after the year 2000. Prospective declaration of outcomes in RCTs, and the adoption of transparent reporting standards, as required by clinicaltrials.gov, may have contributed to the trend toward null findings.


Occupational cancer in Denmark. Cancer incidence in the 1970 census population.
Data sources and creation of data files. The cohort of persons who were 20-64 years of age at the time of the 1970 census has been followed for cancer incidence for a ten-year period. The study was made by linkage of individual records from the 1970 census, the Central Population Register, death certificates, and cancer registrations. Data were included on individual characteristics recorded in the census on prevalent cancer cases at the time of the census and on deaths, emigrations, and incident cancer cases during the ten-year follow-up period. The study includes a total of 2.8 million persons, of whom 2.0 million were economically active at the time of the 1970 census. A total of 115,000 incident cancer cases were registered during the follow-up period, and 77,000 of these occurred in persons who were economically active in 1970. The classifications used in the census included 218 codes for occupation and 245 codes for industry. The Cancer Registry data included 639 codes for diagnosis. Cancer incidence by social groups in Denmark. The cancer incidence was tabulated across 32 socioeconomic groups for 43 cancer sites among the men and 45 cancer sites among the women. The study showed an almost twofold difference in the overall cancer incidence between the socioeconomic groups of the men. Self-employed farmers were at low risk (RR 0.68), and unskilled workers in shipping/fishing were at high risk (RR 1.28) when the cancer incidence among all economically active men was used for the comparison. The social pattern in cancer incidence correlated well with the pattern for cancer mortality among men. As a rough estimate, the cumulative incidence for all cancer among persons under 75 years of age could be reduced by 32% if all Danish men had the cancer incidence of farmers. There was a fivefold or larger difference between the socioeconomic groups in the incidence for nine cancer sites. These nine cancer sites together represented 7% of the cumulative incidence for all cancer. Estimated in a similar way, the cumulative incidence could be reduced by 44% if all Danish men had the site-specific cancer incidence of the respective low-risk groups. The overall cancer incidence among the women varied from a relative risk of 0.71 for unskilled workers in agriculture to a relative risk of 1.18 for self-employed women in other industries I (dentists, lawyers, etc) when the cancer incidence among all economically active women was used for the comparison.(ABSTRACT TRUNCATED AT 400 WORDS)


Dose Estimation Curves Following In Vitro X-ray Irradiation Using Blood From Four Healthy Korean Individuals.
Cytogenetic dosimetry is useful for evaluating the absorbed dose of ionizing radiation based on analysis of radiation-induced chromosomal aberrations. We created two types of in vitro dose-response calibration curves for dicentric chromosomes (DC) and translocations (TR) induced by X-ray irradiation, using an electron linear accelerator, which is the most frequently used medical device in radiotherapy. We irradiated samples from four healthy Korean individuals and compared the resultant curves between individuals. Aberration yields were studied in a total of 31,800 and 31,725 metaphases for DC and TR, respectively, obtained from 11 X-ray irradiation dose-points (0, 0.05, 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4, and 5 Gy). The dose-response relationship followed a linear-quadratic equation, Y=C+αD+βD², with the coefficients C=0.0011 for DC and 0.0015 for TR, α=0.0119 for DC and 0.0048 for TR, and β=0.0617 for DC and 0.0237 for TR. Correlation coefficients between irradiation doses and chromosomal aberrations were 0.971 for DC and 0.6 for TR, indicating a very strong and a moderate correlation, respectively. This is the first study implementing cytogenetic dosimetry following exposure to ionizing X-radiation.


The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo.
Formation of neuromuscular synapses requires a series of inductive interactions between growing motor axons and differentiating muscle cells, culminating in the precise juxtaposition of a highly specialized nerve terminal with a complex molecular structure on the postsynaptic muscle surface. The receptors and signaling pathways mediating these inductive interactions are not known. We have generated mice with a targeted disruption of the gene encoding MuSK, a receptor tyrosine kinase selectively localized to the postsynaptic muscle surface. Neuromuscular synapses do not form in these mice, suggesting a failure in the induction of synapse formation. Together with the results of an accompanying manuscript, our findings indicate that MuSK responds to a critical nerve-derived signal (agrin), and in turn activates signaling cascades responsible for all aspects of synapse formation, including organization of the postsynaptic membrane, synapse-specific transcription, and presynaptic differentiation.


Rational Design of a Red Fluorescent Sensor for ALDH1A1 Displaying Enhanced Cellular Uptake and Reactivity.
High aldehyde dehydrogenase 1A1 (ALDH1A1) activity has emerged as a reliable marker for the identification of both normal and cancer stem cells. To facilitate the detection, molecular imaging, and sorting of stem cells, a green fluorescent probe based on the xanthene dye scaffold was recently developed. However, green dyes are less amenable to multicolor imaging because most commercial reagents are also green. Overcoming this limitation will enable the simultaneous tracking of multiple stem cell markers. Herein, we report the development of a red congener, red-AlDeSense. Through chemical tuning we were able to achieve excellent isoform selectivity and chemostability, a good turn on response, and enhanced cellular uptake and reactivity. Importantly, red-AlDeSense represents one of only a few turn-on sensors in the red region that use the d-PeT quenching mechanism. By employing red-AlDeSense and a green anti-CD44 antibody, we were able to demonstrate staining of these two stem cell markers is independent of one another in A549 lung adenocarcinoma cells.


Revisiting a non-significant findings study: a parent mentor intervention trial as exemplar.
The purpose of this paper is to describe an interactive process for revising a parent social support intervention study with non-significant quantitative findings but strong clinical significance. We will present the methodological challenges that were problematic in the original intervention that potentially contributed to the non-significant findings, and a revised plan of action for conducting a future parent social support intervention. Of note, we have reconsidered the theory used to frame the original study, the randomization process, the intervention clarity and fidelity plan, what measures would better capture the effect, and the development of a more robust analysis plan that considers intra-family correlation, mediation and moderation (mixed model analysis). We will present the revision for each of these methods supported by recent empirical literature. Although this process may not be appropriate for all non-significant interventions, it should be considered with any study that has clinical significance.


The Bone-Forming Properties of Periosteum-Derived Cells Differ Between Harvest Sites.
The development of alternatives for autologous bone grafts is a major focus of bone tissue engineering. To produce living bone-forming implants, skeletal stem and progenitor cells (SSPCs) are envisioned as key ingredients. SSPCs can be obtained from different tissues including bone marrow, adipose tissue, dental pulp, and periosteum. Human periosteum-derived cells (hPDCs) exhibit progenitor cell characteristics and have well-documented in vivo bone formation potency. Here, we have characterized and compared hPDCs derived from tibia with craniofacial hPDCs, from maxilla and mandible, respectively, each representing a potential source for cell-based tissue engineered implants for craniofacial applications. Maxilla and mandible-derived hPDCs display similar growth curves as tibial hPDCs, with equal trilineage differentiation potential toward chondrogenic, osteogenic, and adipogenic cells. These craniofacial hPDCs are positive for SSPC-markers CD73, CD164, and Podoplanin (PDPN), and negative for CD146, hematopoietic and endothelial lineage markers. Bulk RNA-sequencing identified genes that are differentially expressed between the three sources of hPDC. In particular, differential expression was found for genes of the HOX and DLX family, for SOX9 and genes involved in skeletal system development. The in vivo bone formation, 8 weeks after ectopic implantation in nude mice, was observed in constructs seeded with tibial and mandibular hPDCs. Taken together, we provide evidence that hPDCs show different profiles and properties according to their anatomical origin, and that craniofacial hPDCs are potential sources for cell-based bone tissue engineering strategies. The mandible-derived hPDCs display - both in vitro and in vivo - chondrogenic and osteogenic differentiation potential, which supports their future testing for use in craniofacial bone regeneration applications.


A Response to Commentaries.
Our article "NFL Player Health Care: Addressing Club Doctors' Conflicts of Interests and Promoting Player Trust" focused on an inherent structural conflict that faces club doctors in the National Football League. The conflict stems from club doctors' dual role of providing medical care to players and providing strategic advice to clubs. We recommended assigning these roles to different individuals, with the medical staff members who are responsible for providing player care being chosen and subject to review and termination by a committee of medical experts selected equally by the NFL and the NFL Players Association. Recognizing that the problem of structural conflict of interest is deeply entrenched and that our recommendation is a significant departure from the status quo, we invited comment from a diverse and highly qualified group of experts. There is considerable common ground among the commentators. All but one agreed with us that, despite the best intentions of upstanding professionals, there is a structural conflict of interest in the club doctors' relationship with players, and the commentaries were generally supportive of our recommendation for change. There are also meaningful disagreements, however. Some commentators think that the proposal is on the right track but does not go far enough to reduce the structural conflict of interest, and one commentary wholly disagrees with our analysis and recommendations.


Assessment of body mass index and blood pressure among university students in, Enugu, South East, Nigeria.
Body Mass Index (BMI) has been described as a significant predictor of Blood Pressure (B.P) but few studies have demonstrated this association in our environment. The study aims to determine the pattern of relationship between BMI and blood pressure in our environment. Two thousand and ninety six (2096) students in two Universities located in Enugu, South East Nigeria completed the study. The blood pressure, weight and height were measured. Body mass index was calculated as weight in Kilograms divided by height in meters square (kg/m2). More females than males were underweight (9.4% versus 4.7%). More males than females were overweight (8% versus 4%).Obesity occurred more in males than females (7% versus 0.9%). Blood pressure parameters increased significantly with BMI (p < 0.0001) with higher values in males than in females; (the mean systolic blood pressure 124.88 +/- 10.97 mmHg versus 114.93 +/- 6.82 mmHg, P < 0.0001; the mean diastolic blood pressure was 80.1 +/- 7.2 mmHg versus 73.36 +/- 6.82 mmHg, p = 0.035 and the mean arterial Pressure (MAP) 95.02 +/- 7.78 mmHg versus 87.2 +/- 9.58 mmHg, p < 0.0001). A significant relationship between BMI and Blood pressure was demonstrated among university students in South East Nigeria.


A prognostic model for predicting 10-year survival in patients with primary melanoma. The Pigmented Lesion Group.
To develop a prognostic model, based on clinical and pathologic data that are routinely available to the clinician, that would estimate the chance for survival of a patient with primary cutaneous melanoma after definitive surgical therapy. Cohort analytical study. University medical center. 488 patients with primary cutaneous melanoma who had no apparent metastatic disease. Patients were followed prospectively for at least 10 years. An independent validation sample of 142 patients was used to assess the stability of the model. Six clinical and pathologic variables that predict survival and are readily available to the clinician were used to develop a prediction model. The variables were tested for their association with death by using a univariate logistic regression model. Point estimates were generated for the probability of surviving melanoma at 10 years. Variables that were statistically significantly associated with survival were retained for testing in a logistic regression model. 488 patients were followed prospectively for a median of 13.5 years (minimum, 10.0 years; maximum, 20.5 years). The overall 10-year survival of the study group was 78%. Four variables were found to be independent predictors of survival. Presented as adjusted odds ratios, from strongest to weakest relative predictive strength, these variables were tumor thickness (odds ratio, 50.8), site of primary melanoma (odds ratio, 4.4), age of the patient (odds ratio, 3.0), and sex of the patient (odds ratio, 2.0). The four-variable model was significantly more accurate than tumor thickness alone, particularly for predicting death. Overall, use of the model reduced the error rate of the prediction of death by 50%. A prognostic model that uses four readily accessible variables more accurately predicts outcome in patients with primary melanoma than does tumor thickness alone. This four-variable model can identify patients at high risk for the recurrence of disease, an identification that becomes increasingly important as adjuvant therapies are developed for treatment of melanoma.


Chaotic component obscured by strong periodicity in voice production system.
The effect of glottal aerodynamics in producing the nonlinear characteristics of voice is investigated by comparing the outputs of the asymmetric composite model and the two-mass model. The two-mass model assumes the glottal airflow to be laminar, nonviscous, and incompressible. In this model, when the asymmetric factor is decreased from 0.65 to 0.35, only 1:1 and 1:2 modes are detectable. However, with the same parameters, four vibratory modes (1:1, 1:2, 2:4, 2:6) are found in the asymmetric composite model using the Navier-Stokes equations to describe the complex aerodynamics in the glottis. Moreover, the amplitude of the waveform is modulated by a small-amplitude noiselike series. The nonlinear detection method reveals that this noiselike modulation is not random, but rather it is deterministic chaos. This result agrees with the phenomenon often seen in voice, in which the voice signal is strongly periodic but modulated by a small-amplitude chaotic component. The only difference between the two-mass model and the composite model is in their descriptions of glottal airflow. Therefore, the complex aerodynamic characteristics of glottal airflow could be important in generating the nonlinear dynamic behavior of voice production, including bifurcation and a small-amplitude chaotic component obscured by strong periodicity.


Buddhism and medical futility.
Religious faith and medicine combine harmoniously in Buddhist views, each in its own way helping Buddhists enjoy a more fruitful existence. Health care providers need to understand the spiritual needs of patients in order to provide better care, especially for the terminally ill. Using a recently reported case to guide the reader, this paper examines the issue of medical futility from a Buddhist perspective. Important concepts discussed include compassion, suffering, and the significance of the mind. Compassion from a health professional is essential, and if medical treatment can decrease suffering without altering the clarity of the mind, then a treatment should not be considered futile. Suffering from illness and death, moreover, is considered by Buddhists a normal part of life and is ever-changing. Sickness, old age, birth, and death are integral parts of human life. Suffering is experienced due to the lack of a harmonious state of body, speech, and mind. Buddhists do not believe that the mind is located in the brain, and, for Buddhists, there are ways suffering can be overcome through the control of one's mind.


Improving transparency to build trust in real-world secondary data studies for hypothesis testing-Why, what, and how: recommendations and a road map from the real-world evidence transparency initiative.
Real-world data (RWD) and the derivations of these data into real-world evidence (RWE) are rapidly expanding from informing healthcare decisions at the patient and health system level to influencing major health policy decisions, including regulatory approvals and coverage. Recent examples include the approval of palbociclib in combination with endocrine therapy for male breast cancer and the inclusion of RWE in the label of paliperidone palmitate for schizophrenia. This interest has created an urgency to develop processes that promote trust in the evidence-generation process. Key stakeholders and decision-makers include patients and their healthcare providers; learning health systems; health technology assessment bodies and payers; pharmacoepidemiologists and other clinical reseachers, and policy makers interested in bioethical and regulatory issues. A key to optimal uptake of RWE is transparency of the research process to enable decision-makers to evaluate the quality of the methods used and the applicability of the evidence that results from the RWE studies. Registration of RWE studies-particularly for hypothesis evaluating treatment effectiveness (HETE) studies-has been proposed to improve transparency, trust, and research replicability. Although registration would not guarantee better RWE studies would be conducted, it would encourage the prospective disclosure of study plans, timing, and rationale for modifications. A joint task force of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) recommended that investigators preregister their RWE studies and post their study protocols in a publicly available forum before starting studies to reduce publication bias and improve the transparency of research methods. Recognizing that published recommendations alone are insufficient, especially without accessible registration options and with no incentives, a group of experts gathered on February 25 and 26, 2019, in National Harbor, Maryland, to explore the structural and practical challenges to the successful implementation of the recommendations of the ISPOR/ISPE task force for preregistration. This positioning article describes a plan for making registration of HETE RWE studies routine. The plan includes specifying the rationale for registering HETE RWE studies, the studies that should be registered, where and when these studies should be registered, how and when analytic deviations from protocols should be reported, how and when to publish results, and incentives to encourage registration. Table 1 summarizes the rationale, goals, and potential solutions that increase transparency, in addition to unique concerns about secondary data studies. Definitions of terms used throughout this report are provided in Table 2.


Rapid molecular detection of invasive species in ballast and harbor water by integrating environmental DNA and light transmission spectroscopy.
Invasive species introduced via the ballast water of commercial ships cause enormous environmental and economic damage worldwide. Accurate monitoring for these often microscopic and morphologically indistinguishable species is challenging but critical for mitigating damages. We apply eDNA sampling, which involves the filtering and subsequent DNA extraction of microscopic bits of tissue suspended in water, to ballast and harbor water sampled during a commercial ship's 1400 km voyage through the North American Great Lakes. Using a lab-based gel electrophoresis assay and a rapid, field-ready light transmission spectroscopy (LTS) assay, we test for the presence of two invasive species: quagga (Dreissena bugensis) and zebra (D. polymorpha) mussels. Furthermore, we spiked a set of uninfested ballast and harbor samples with zebra mussel tissue to further test each assay's detection capabilities. In unmanipulated samples, zebra mussel was not detected, while quagga mussel was detected in all samples at a rate of 85% for the gel assay and 100% for the LTS assay. In the spiked experimental samples, both assays detected zebra mussel in 94% of spiked samples and 0% of negative controls. Overall, these results demonstrate that eDNA sampling is effective for monitoring ballast-mediated invasions and that LTS has the potential for rapid, field-based detection.


Breakfast Clubs: Starting the Day in a Positive Way.
Breakfast clubs are widely promoted as having a beneficial impact on children's behavior at the start of the school day, which can be conducive to their learning within the classroom. However, the few available studies that have considered the impact of breakfast club attendance on children's behavior have yielded mixed results and no studies to date have directly observed children's behavior within the breakfast club setting. Using a combination of real-time observation and filmed breakfast club footage, the aims of the current study were to: (1) devise a set of observational criteria appropriate for use in the breakfast club setting; (2) investigate the occurrence of both positive and negative behaviors. A sample of 30 children aged between 3 and 11 years were recruited from 3, opportunistically sampled primary school breakfast clubs in the North East of England, UK. The behaviors they displayed within the breakfast club setting on two separate days were observed and coded for subsequent analysis. Results of the investigation showed that children's behavior could be classified into three positive and three negative behavioral categories. Using these categories to code children's behavior as they engaged in breakfast club showed that children displayed more positive than negative behaviors within the breakfast club setting and this was the case regardless of the type of activity (i.e., quiet or boisterous) children were involved in. Findings are discussed in relation to breakfast club policy, implementation, and evaluation.


Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors.
Here, we report the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. Initially, we investigate the virus binding dynamics to validate the better binding performance of the heteromultivalent moieties as compared to homomultivalent ones. The heteromultivalent binding moieties are transferred to nanostructures with a bowl-like shape matching the viral spherical surface. Unlike the conventional homomultivalent inhibitors, the heteromultivalent ones exhibit a half maximal inhibitory concentration of 32.4 ± 13.7 μg/ml due to the synergistic multivalent effects and the topology-matched shape. At a dose without causing cellular toxicity, >99.99% reduction of virus propagation has been achieved. Since multiple binding sites have also been identified on the S protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), we envision that the use of heteromultivalent nanostructures may also be applied to develop a potent inhibitor to prevent coronavirus infection.


The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants.
Plants have always been used as medicines since ancient times to treat diseases. The knowledge around the active components of herbal preparations has remained nevertheless fragmentary: the biosynthetic pathways of many secondary metabolites of pharmacological importance have been clarified only in a few species, while the chemodiversity present in many medicinal plants has remained largely unexplored. Despite the advancements of synthetic biology for production of medicinal compounds in heterologous hosts, the native plant species are often the most reliable and economic source for their production. It thus becomes fundamental to investigate the metabolic composition of medicinal plants to characterize their natural metabolic diversity and to define the biosynthetic routes in planta of important compounds to develop strategies to further increase their content. We present here a number of case studies for selected classes of secondary metabolites and we review their health benefits and the historical developments in their structural elucidation and characterization of biosynthetic genes. We cover the cases of benzoisoquinoline and monoterpenoid indole alkaloids, cannabinoids, caffeine, ginsenosides, withanolides, artemisinin, and taxol; we show how the "early" biochemical or the more recent integrative approaches-based on omics-analyses-have helped to elucidate their metabolic pathways and cellular compartmentation. We also summarize how the knowledge generated about their biosynthesis has been used to develop metabolic engineering strategies in heterologous and native hosts. We conclude that following the advent of novel, high-throughput and cost-effective analytical technologies, the secondary metabolism of medicinal plants can now be examined under the lens of systems biology.


Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.
Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. ClinicalTrials.gov Identifier: NCT01990768.


Photobiomodulation therapy improves both inflammatory and fibrotic parameters in experimental model of lung fibrosis in mice.
Lung fibrosis (LF) is a chronic and progressive lung disease characterized by pulmonary parenchyma progressive lesion, inflammatory infiltration, and interstitial fibrosis. It is developed by excessive collagen deposition and other cellular matrix components, resulting in severe changes in the alveolar architecture. Considering the absence of effective treatment, the aim of this study was to investigate the effect of photobiomodulation therapy (PBMT) on the development of PF. For this purpose, we used C57BL6 mice subjected to induction of LF by bleomycin administration (1.5 U/kg) by orotracheal route and, after 14 days of the induction, mice were treated with PBMT applied to the thorax 1×/day for 8 days (wavelength 660 ± 20 nm, power 100 mW, radiant exposure 5 J/cm2, irradiance 33.3 mW/cm2, spot size 2.8cm2, total energy 15 J, time of irradiation: 150 s) and inflammatory and fibrotic parameters were evaluated with or without PBMT. Our results showed that PBMT significantly reduced the number of inflammatory cells in the alveolar space, collagen production, interstitial thickening, and static and dynamic pulmonary elastance. In addition, we observed reduced levels of IL-6 e CXCL1/KC released by pneumocytes in culture as well as reduced level of CXCL1/KC released by fibroblasts in culture. We can conclude that the PBMT improves both inflammatory and fibrotic parameters showing a promising therapy which is economical and has no side effects.


Attributional style in psychosis--the role of affect and belief type.
People holding persecutory beliefs have been hypothesised to show a self-serving attributional style, which functions to protect self-esteem Bentall, Corcoran, Howard, Blackwood, and Kinderman (2001). Experimental support for this has been mixed. Freeman et al. (1998) suggested depressed and grandiose subgroups of those with persecutory beliefs might explain events differently. In this study, 71 participants completed measures of delusional beliefs, depression and attributional style. We hypothesised that those with persecutory beliefs would form grandiose and depressed subgroups, and that a self-serving attributional style would characterise only the grandiose subgroup. Hypotheses were partially confirmed. Clear subgroups were evident and only those with both persecutory and grandiose beliefs showed an externalising attributional style for negative events. Depression, irrespective of co-occurring persecutory beliefs, was related to a reduced self-serving bias and an externalising attributional style for positive events. On their own, persecutory beliefs were not related to any particular attributional style. Depressed and grandiose subgroups of those with persecutory beliefs might account for some of the inconsistencies in the attribution literature. Even within a single symptom group, care should be taken in both research and therapy to consider individual symptom patterns.


Masticatory motor programs in Australian herbivorous mammals: diprotodontia.
Movement of the jaw during molar occlusion is determined by the sequence of activity in the adductor muscles and this sequence is one way to define a masticatory motor program. Based on the similarity of molar structure, it is probable that the American opossum and the early Tertiary mammals that gave rise to all Australian marsupials probably shared a common "primitive" masticatory motor program. The distinct and various patterns of movement of the jaw in the major groups of Australian marsupial herbivores (diprotodontids) are achieved by both subtle and substantial shifts in the timing of the primitive sequence. All diprotodonts divide jaw movements during occlusion into a vertical Phase Im and horizontal Phase IIm, but the number of muscles involved and the level of activity associated with each phase varies considerably. In macropodids (potoroos and kangaroos) Phase Im dominates; in wombats Phase IIm dominates and in koalas the two phases are more evenly divided, with a more equal distribution of muscles between them. The motor program of koalas parallels that of some placental ungulates, while both macropodids and wombats have motor programs unique among mammals.


Cerebrospinal fluid microRNAs are potential biomarkers of temporal lobe epilepsy and status epilepticus.
There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls. Differential expression of 20 microRNAs was detected between patient groups and controls. A validation phase included an expanded cohort and samples from patients with other neurological diseases. This identified lower levels of miR-19b in temporal lobe epilepsy compared to controls, status epilepticus and other neurological diseases. Levels of miR-451a were higher in status epilepticus compared to other groups whereas miR-21-5p differed in status epilepticus compared to temporal lobe epilepsy but not to other neurological diseases. Targets of these microRNAs include proteins regulating neuronal death, tissue remodelling, gliosis and inflammation. The present study indicates cerebrospinal fluid contains microRNAs that can support differential diagnosis of temporal lobe epilepsy and status epilepticus from other neurological and non-neurological diseases.


Multiscale Community Blockmodel for Network Exploration.
Real world networks exhibit a complex set of phenomena such as underlying hierarchical organization, multiscale interaction, and varying topologies of communities. Most existing methods do not adequately capture the intrinsic interplay among such phenomena. We propose a nonparametric Multiscale Community Blockmodel (MSCB) to model the generation of hierarchies in social communities, selective membership of actors to subsets of these communities, and the resultant networks due to within- and cross-community interactions. By using the nested Chinese Restaurant Process, our model automatically infers the hierarchy structure from the data. We develop a collapsed Gibbs sampling algorithm for posterior inference, conduct extensive validation using synthetic networks, and demonstrate the utility of our model in real-world datasets such as predator-prey networks and citation networks.


Expression of NLRR3 orphan receptor gene is negatively regulated by MYCN and Miz-1, and its downregulation is associated with unfavorable outcome in neuroblastoma.
Our previous study showed that expression of NLRR3 is significantly high in favorable neuroblastomas (NBL), whereas that of NLRR1 is significantly high in unfavorable NBLs. However, the molecular mechanism of transcriptional regulation of NLRR3 remains elusive. This study was undertaken to clarify the transcriptional regulation of NLRR3 and its association with the prognosis of NBL. NLRR3 and MYCN expressions in NBL cell lines were analyzed after induction of cell differentiation, MYCN knockdown, and overexpression. The transcriptional regulation of NLRR3 was analyzed by luciferase reporter and chromatin immunoprecipitation assays. Quantitative PCR was used for examining the expression of NLRR3, Miz-1, or MYCN in 87 primary NBLs. The expression of NLRR3 mRNA was upregulated during differentiation of NBL cells induced by retinoic acid, accompanied with reduced expression of MYCN, suggesting that NLRR3 expression was inversely correlated with MYCN in differentiation. Indeed, knockdown of MYCN induced NLRR3 expression, whereas exogenously expressed MYCN reduced cellular NLRR3 expression. We found that Miz-1 was highly expressed in favorable NBLs and NLRR3 was induced by Miz-1 expression in NBL cells. MYCN and Miz-1 complexes bound to NLRR3 promoter and showed a negative regulation of NLRR3 expression. In addition, a combination of low expression of NLRR3 and high expression of MYCN was highly associated with poor prognosis. NLRR3 is a direct target of MYCN, which associates with Miz-1 and negatively regulates NLRR3 expression. NLRR3 may play a role in NBL differentiation and the survival of NBL patients by inversely correlating with MYCN amplification.


Quality of Root Canal Fillings Performed by Undergraduate Students and the Related Factors on the Treatment Outcome: A 2- to 5-Year Follow-Up.
To evaluate radiographically the quality of root canal fillings performed by undergraduate students between 2012 and 2015, and to investigate the impact of their quality in correlation with root type, preoperative periapical status, and type of restorative treatment on the treatment outcome. Six hundred seventy-seven non-surgical root canal treatments were performed by undergraduate students from the Aristotle University of Thessaloniki at the endodontic department clinics between 2012 and 2015. Two hundred forty-four teeth (349 roots) fulfilled the criteria and were clinically and radiographically re-examined between 2016 and 2017, and the outcome was classified as "success" or "failure." Root canal fillings were radiographically evaluated in terms of apical extension and density. The root filling was classified as acceptable when both parameters were rated as acceptable. Statistical analysis was performed using generalized estimating equations. Pairwise comparisons were performed by the sequential Bonferroni method. Intra-examiner and inter-examiner agreements were checked by the intraclass correlation coefficient and Cohen's kappa. The statistical significance level was set at P<0.05. The percentage of the roots with acceptable root canal fillings was 40.4%. The molar roots demonstrated the lowest rate (30.7%) compared with the anterior (53%, P<0.05) and premolar teeth (43%, P>0.05). The results of the correlation of the quality of the root canal fillings with the root type, preoperative periapical status, type of coronal restoration, and the treatment outcome showed that the unacceptable quality of root canal filling in relation to root or presence of periapical lesion or crown revealed the lowest success rates (47.2%, 40.3%, and 52.3%, respectively). In contrast, results showed that roots with canal fillings of acceptable quality demonstrated success rates close to 90%, regardless of the other variables. Within the limitations of the present study, the percentage of radiographically acceptable root canal fillings performed in the undergraduate clinic of the Department of Endodontology at Aristotle University of Thessaloniki was low (40.4%). Results showed that there was a strong association of higher success rates with root fillings of acceptable quality.


Novel Effects of Rosa damascena Extract on Patients with Neurocognitive Disorder and Depression: A Clinical Trial Study.
Dementia as a major cognitive neurological disorder is defined as impairment in one or more cognitive territories compared with the former level of performance. This disorder disrupts patient's independence, and the patient would need others aid in order of doing daily and complex activities. The aim of this study was to evaluate the efficacy of Rosa damascena extract in the improvement of cognitive function in patients with dementia. This study is a randomized double-blind, placebo-controlled clinical trial on 40 patients older than 55 years with dementia referred to Specialized Elderly Patients Clinic in 2015-2016. Patients were divided randomly into two groups (control and intervention). The intervention group used donepezil and R. damascena capsules, and in control group, placebo capsule instead of R. damascena added on donepezil. Four test was filled three times at the study initiation, after month one and also after month three: Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination Revised (ACE-R) were used for cognition evaluation, for depression assessment, Geriatric Depression Scale was administered, and checklist of memory and behavioral disorders were filled. The results showed add-on donepezil and R. damascena versus placebo improved cognitive impairment based on MMSE with P = 0.002, ACE-R with total P = 0.001, depression (P = 0.012), behavioral disorders (P < 0.001), and daily activity (P < 0.001). The R. damascena extract affected cognitive impairment of dementia patients significantly and also have significant effects on improving depression and behavioral problems.


No change in hemoglobin mass after 40 days of physical activity in previously untrained adults.
A high hemoglobin mass (Hb(mass)) is associated with a high maximum aerobic power (VO(2max)), however, the extent to which Hb(mass) is influenced by training is currently unclear. Accordingly, this study monitored changes in Hb(mass) and VO(2max) in 12 previously untrained adults (aged 18-25 years) following 40 days of regular physical activity. Hb(mass) and VO(2max) were assessed at the start and end of a 40-day physical activity program, which comprised of approximately 40 min of daily, moderate-intensity physical activity. Relative VO(2max) increased by 11.3%, yet there was no significant change in relative Hb(mass) (1.7%) and body mass (0.2%) during the 40-day period. There was a significant correlation between Hb(mass) and VO(2max) at the start of the study (r=0.58, P=0.05), but not between the change in relative VO(2max) and the change in relative Hb(mass) (r=-0.07, P=0.83). Our results support the concept of relative stability in Hb(mass) with approximately 1 month of moderate-intensity physical activity suggesting that Hb(mass) may be used for talent identification and possibly for anti-doping purposes.


Gastroprotective activity of α-terpineol in two experimental models of gastric ulcer in rats.
Several plant essential oils, as well as terpenes present in essential oils, have shown gastroprotective activity. The aim of the present work was to evaluate the gastroprotective activity of α-terpineol, a monoterpene alcohol which is present in essential oils of various plants. The gastroprotective activity of α-terpineol was evaluated in rats by assessing the changes in ethanol and indomethacin-induced gastric ulcer scores and on gastric secretory volume and total acidity in pylorus-ligated rats. Alpha-terpineol was administrated orally at the doses of 10, 30, and 50 mg/kg one hour before administration of the ulcer inducing agents by the pylorus ligation procedure. The involvement of endogenous prostaglandins in the protective effect of α-terpineol in ethanol-induced gastric lesions test was assessed by administration of indomethacin (10 mg/kg, s.c.) 30 min before oral administration of α-terpineol at the dose of 50 mg/kg. α-terpineol presented gastroprotective activity against ethanol-induced ulcers at the doses of 10, 30, and 50 mg/kg. Epoxy-carvone at the dose of 10 mg/kg did not present gastroprotective activity against ulcer induced by indomethacin, but at the doses of 30 and 50 mg/kg it attenuated the gastric damages induced by this agent significantly. Pretreatment with indomethacin did not prevent the gastroprotective effect of α-terpineol on ethanol-induced ulcers. Alpha-terpineol also did not affect the gastric secretion in pylorus-ligated rats. The results suggest that α-terpineol presents gastroprotective action which does not involve either an increase in the synthesis of endogenous prostaglandin or a decrease in the gastric acid secretion.


Do topical repellents divert mosquitoes within a community? Health equity implications of topical repellents as a mosquito bite prevention tool.
Repellents do not kill mosquitoes--they simply reduce human-vector contact. Thus it is possible that individuals who do not use repellents but dwell close to repellent users experience more bites than otherwise. The objective of this study was to measure if diversion occurs from households that use repellents to those that do not use repellents. The study was performed in three Tanzanian villages using 15%-DEET and placebo lotions. All households were given LLINs. Three coverage scenarios were investigated: complete coverage (all households were given 15%-DEET), incomplete coverage (80% of households were given 15%-DEET and 20% placebo) and no coverage (all households were given placebo). A crossover study design was used and coverage scenarios were rotated weekly over a period of ten weeks. The placebo lotion was randomly allocated to households in the incomplete coverage scenario. The level of compliance was reported to be close to 100%. Mosquito densities were measured through aspiration of resting mosquitoes. Data were analysed using negative binomial regression models. Repellent-users had consistently fewer mosquitoes in their dwellings. In villages where everybody had been given 15%-DEET, resting mosquito densities were fewer than half that of households in the no coverage scenario (Incidence Rate Ratio [IRR]=0.39 (95% confidence interval [CI]: 0.25-0.60); p<0.001). Placebo-users living in a village where 80% of the households used 15%-DEET were likely to have over four-times more mosquitoes (IRR=4.17; 95% CI: 3.08-5.65; p<0.001) resting in their dwellings in comparison to households in a village where nobody uses repellent. There is evidence that high coverage of repellent use could significantly reduce man-vector contact but with incomplete coverage evidence suggests that mosquitoes are diverted from households that use repellent to those that do not. Therefore, if repellents are to be considered for vector control, strategies to maximise coverage are required.


Genetics, cytogenetics, and epigenetics of colorectal cancer.
Most of the colorectal cancer (CRC) cases are sporadic, only 25% of the patients have a family history of the disease, and major genes causing syndromes predisposing to CRC only account for 5-6% of the total cases. The following subtypes can be recognized: MIN (microsatellite instability), CIN (chromosomal instability), and CIMP (CpG island methylator phenotype). CIN occurs in 80-85% of CRC. Chromosomal instability proceeds through two major mechanisms, missegregation that results in aneuploidy through the gain or loss of whole chromosomes, and unbalanced structural rearrangements that lead to the loss and/or gain of chromosomal regions. The loss of heterozygosity that occur in the first phases of the CRC cancerogenesis (in particular for the genes on 18q) as well as the alteration of methylation pattern of multiple key genes can drive the development of colorectal cancer by facilitating the acquisition of multiple tumor-associated mutations and the instability phenotype.


Low vaccine efficacy of mumps component among MMR vaccine recipients in Chennai, India.
Introduction of MMR vaccine was believed to have resulted in a decline in the incidence of measles, mumps and rubella infections. However, recent reports suggest the re-emergence of mumps infection worldwide in the vaccinated populations. It was proposed that the reason for this re-emergence was poor efficacy of MMR vaccine. The present study was aimed to investigate mumps infection in MMR vaccinated and non-vaccinated populations in Chennai, India. Blood samples were collected from acute mumps cases (n=74, 42<12 yr age, 54% males) and investigated for IgM antibody against mumps, IgG antibody against measles, mumps and rubella viruses by ELISA. Sixty seven (91%) patients had received MMR vaccine. All the 67 vaccinated cases were positive for parotitis, and mumps IgM. However, only 10 (15%) were positive for IgG. All samples (100%) were positive for rubella and measles IgG. These findings showed the occurrence of mumps infection among MMR vaccinated individuals in Chennai, India. The MMR vaccine failed to generate anti-mumps IgG. The reason may be low vaccine efficacy of the mumps component of the MMR vaccine used.


Treatment of periocular hyperpigmentation due to lead of kohl (surma) by penicillamine: a single group non-randomized clinical trial.
Periocular hyperpigmentation is a condition in which skin of eyelids become darker in color than the normal surrounding skin. Lead and other heavy metals produce increased pigmentation because of deposition of metal particles in the dermis and increased epidermal melanin production. This study was conducted to evaluate the dual effect of chelation therapy in treating periocular hyperpigmentation and lead toxicity. The study population consisted of nine females complaining from dark coloration of their eyelids. The nine females were continuously using kohl as eyeliner. Lead levels in conjunctiva and serum before and after D-penicillamine (D-PCN) oral administration were estimated in relation to vertical, horizontal length, and degree of hyperpigmentation score. Highly significant P values (0.000) were obtained as regard to the conjunctival lead levels, serum lead levels, horizontal length, and degree of darkness score before and after D-PCN therapy. A less significant P value (0.040) was recorded as regard to the vertical length. Regardless other causes, this study spots the light on a new concept for periocular hyperpigmentation from lead toxicity in adult females using kohl and suggests D-PCN in a low divided dose (750 mg/day) for its treatment.


A computationally efficient hypothesis testing method for epistasis analysis using multifactor dimensionality reduction.
Multifactor dimensionality reduction (MDR) was developed as a nonparametric and model-free data mining method for detecting, characterizing, and interpreting epistasis in the absence of significant main effects in genetic and epidemiologic studies of complex traits such as disease susceptibility. The goal of MDR is to change the representation of the data using a constructive induction algorithm to make nonadditive interactions easier to detect using any classification method such as naïve Bayes or logistic regression. Traditionally, MDR constructed variables have been evaluated with a naïve Bayes classifier that is combined with 10-fold cross validation to obtain an estimate of predictive accuracy or generalizability of epistasis models. Traditionally, we have used permutation testing to statistically evaluate the significance of models obtained through MDR. The advantage of permutation testing is that it controls for false positives due to multiple testing. The disadvantage is that permutation testing is computationally expensive. This is an important issue that arises in the context of detecting epistasis on a genome-wide scale. The goal of the present study was to develop and evaluate several alternatives to large-scale permutation testing for assessing the statistical significance of MDR models. Using data simulated from 70 different epistasis models, we compared the power and type I error rate of MDR using a 1,000-fold permutation test with hypothesis testing using an extreme value distribution (EVD). We find that this new hypothesis testing method provides a reasonable alternative to the computationally expensive 1,000-fold permutation test and is 50 times faster. We then demonstrate this new method by applying it to a genetic epidemiology study of bladder cancer susceptibility that was previously analyzed using MDR and assessed using a 1,000-fold permutation test.