The effect of workload on biological monitoring of occupational exposure to toluene and n-Hexane: contribution of physiologically based toxicokinetic modeling.
A physiologically based toxicokinetic model was used to examine the impact of work load on the relationship between the airborne concentrations and exposure indicator levels of two industrial solvents, toluene and n-Hexane. The authors simulated occupational exposure (8 hr/day, 5 days/week) at different concentrations, notably 20 ppm and 50 ppm, which are the current threshold limit values recommended by ACGIH for toluene and n-hexane, respectively. Different levels of physical activity, namely, rest, 25 W, and 50 W (for 12 hr followed by 12 hr at rest) were simulated to assess the impact of work load on the recommended biological exposure indices: toluene in blood prior to the last shift of the workweek, urinary o-cresol (a metabolite of toluene) at the end of the shift, and free (nonhydrolyzed) 2,5-hexanedione (a metabolite of n-hexane) at the end of the shift at the end of the workweek. In addition, urinary excretion of unchanged toluene was simulated. The predicted biological concentrations were compared with the results of both experimental studies among human volunteers and field studies among workers. The highest predicted increase with physical exercise was noted for toluene in blood (39 microg/L at 50 W vs. 14 microg/L at rest for 20 ppm, i.e., a 2.8-fold increase). The end-of-shift urinary concentrations of o-cresol and toluene were two times higher at 50 W than at rest (for 20 ppm, 0.65 vs. 0.33 mg/L for o-cresol and 43 vs. 21 microg/L for toluene). Urinary 2,5-hexanedione predicted for 50 ppm was 1.07 mg/L at 50 W and 0.92 mg/L at rest (+16%). The simulations that best describe the concentrations among workers exposed to toluene are those corresponding to 25 W or less. In conclusion, toxicokinetic modeling confirms the significant impact of work load on toluene exposure indicators, whereas only a very slight effect is noted on n-hexane kinetics. These results highlight the necessity of taking work load into account in risk assessment relative to toluene exposure.


[Prevalence and severity of dental caries and treatment needs in small Brazilian counties].
The aim of this study was to assess the prevalence and severity of dental caries and the need for dental treatment among schoolchildren in two small Brazilian counties. WHO criteria (1986) for the diagnosis of dental caries and treatment needs were adopted. All 6 to 12-year-old schoolchildren in both São João do Sul (n = 803) and Treviso (n = 382), both in the State of Santa Catarina, were invited to participate in the study. The response rate was 96% and 91% respectively. All kappa values for inter- and intra-examiner agreement were greater than 0.62. Prevalence of caries among 6 to 12-year-old children was 62.1% in São João do Sul and 63.6% in Treviso. Mean DMF-T for the same age group was 1.91 and 1.84 respectively. Need for treatment was high in both counties, however it was mainly related to simple clinical procedures. In conclusion, prevalence of dental caries among 6 to 12-year-old schoolchildren was lower in the two small counties studied than in other small communities in Brazil. The need for treatment was great, but it was related to simple clinical procedures. In addition, there is a need to collect further data from small towns to develop an oral health strategy appropriate to such areas.


Properties of epitopes of Pfs 48/45, a target of transmission blocking monoclonal antibodies, on gametes of different isolates of Plasmodium falciparum.
We have studied the properties of epitopes on Plasmodium falciparum gamete surface protein Pfs 48/45, a target antigen of malaria transmission blocking antibodies. Using a two site immunoradiometric assay we have defined three spacially separate, non-repeated, epitope regions on the peptides representing this antigen. Epitope region I is a target of monoclonal antibodies (MoAbs) which strongly suppress infectivity of gametocytes of P. falciparum to mosquitoes; the effect is complement independent and is mediated as effectively by the monovalent Fab fragments as by intact MoAb. Epitope region II consists of two spacially close subregions, IIa and IIb; variant forms of epitopes IIa and IIb occurred in different isolates of P. falciparum. Epitope region III also showed slight structural modification between isolates. MoAbs against regions II or III were relatively ineffective in suppressing gametocyte infectivity compared to MoAbs against region I. However, certain combinations of MoAbs against regions II and III together acted synergistically to suppress infectivity to mosquitoes. All these epitopes failed to react with MoAb when the antigen was presented in reduced form. A fourth epitope, however, was identified which reacted strongly with MoAb when the antigen was presented in reduced form. The MoAb against this epitope had no effect on the infectivity of gametocytes of P. falciparum to mosquitoes.


Within you, without you: HIV-1 Rev and RNA export.
Nucleo-cytoplasmic transport of RNA is one of many cellular pathways whose illumination has progressed hand in hand with understanding of retroviral mechanisms. A recent paper in Cell reports the involvement of an RNA helicase in the pathway by which HIV exports partially spliced and unspliced RNA out of the nucleus. This suggests the ubiquity of RNA helicases in RNA export from the nucleus, and has novel mechanistic implications.


Characterization of solvent-extractable organics in urban aerosols based on mass spectrum analysis and hygroscopic growth measurement.
To characterize atmospheric particulate organics with respect to polarity, aerosol samples collected on filters in the urban area of Nagoya, Japan, in 2009 were extracted using water, methanol, and ethyl acetate. The extracts were atomized and analyzed using a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) and a hygroscopicity tandem differential mobility analyzer. The atmospheric concentrations of the extracted organics were determined using phthalic acid as a reference material. Comparison of the organic carbon concentrations measured using a carbon analyzer and the HR-ToF-AMS suggests that organics extracted with water (WSOM) and ethyl acetate (EASOM) or those extracted with methanol (MSOM) comprise the greater part of total organics. The oxygen-carbon ratios (O/C) of the extracted organics varied: 0.51-0.75 (WSOM), 0.37-0.48 (MSOM), and 0.27-0.33 (EASOM). In the ion-group analysis, WSOM, MSOM, and EASOM were clearly characterized by the different fractions of the CH and CO(2) groups. On the basis of the hygroscopic growth measurements of the extracts, κ of organics at 90% relative humidity (κ(org)) were estimated. Positive correlation of κ(org) with O/C (r 0.70) was found for MSOM and EASOM, but no clear correlation was found for WSOM.


COVID-19 Vaccination Acceptance among Healthcare Staff in Sudan, 2021.
Elderly and patients with comorbid conditions have higher risk of infection and complications. Vaccination hesitancy is defined as the refusal of vaccine or the delay in accepting it despite the availability of vaccines and vaccination services. This study was aimed at assessing knowledge, perception, and acceptability of healthcare staff towards different types of COVID-19 vaccination. A multicenter hospital-based descriptive cross-sectional study was implemented to study the knowledge, perception, and acceptability of healthcare staff towards COVID-19 vaccination. Multistage sampling technique was applied. Data were collected through a self-administered questionnaire filled by the participants. 400 participants were studied. 61% of the participants were females, and the most frequent age reported was between 18 and 35 years (67%). A statistically significant association (p = 0.048) was found between knowledge about vaccination and professions. The most common vaccine type known and accepted was AstraZeneca vaccine. On assessing acceptability of COVID-19 vaccination, acceptance rate was high (63.8%) and 22.7% of the participants had already got vaccinated. The rejection rate among our staff was 27.4%. This study was conducted in April, 2021. Majority of our healthcare staff believed that vaccination is the key to combat the pandemic. One of the issues and concerns about vaccination was the safety and the risk of developing acute adverse events (p = 0.001). Encouraging factor for vaccination was the fear of getting infection themselves and their families. The present study revealed the presence of good knowledge and acceptability among medical staff towards COVID-19 vaccinations in Sudan.


Mechanism of folate transport across the human colonic basolateral membrane.
Previous studies from our laboratory have demonstrated the existence of a folate transporter in the human colonic apical membranes. The current studies were undertaken to examine the possible presence and function of a folate carrier in the human colonic basolateral membrane vesicles (BLMV). BLMV were purified from mucosal scrapings of colons of organ donors by a Percoll-density gradient centrifugation technique, and uptake studies were performed using a rapid filtration technique. Our results on [(3)H]Pte-Glu uptake are summarized as follows: 1) uptake was sensitive to osmolarity of the incubation medium; 2) Na(+) removal from the incubation medium did not affect folate uptake into BLMV; 3) uptake was significantly increased with decreasing incubation buffer pH from 8 to 4; 4) uptake demonstrated saturation kinetics with an apparent Michaelis constant of 9.6 +/- 0.48 microM and a maximal velocity of 8.10 +/- 0.36 pmol x mg protein(-1) x 10 s(-1); 5) uptake was markedly inhibited by the structural analog methotrexate (inhibitory constant = 8.28 +/- 1.0 microM); 6) uptake into BLMV demonstrated a trans-stimulation phenomenon; 7) anion exchange inhibitors DIDS and SITS significantly inhibited folate uptake; and 8) uptake was potential-insensitive, as voltage clamping of vesicles or making them inside positive with K(+)/valinomycin failed to influence folate uptake. Western blot analysis using purified human colonic basolateral membrane preparations and specific polyclonal antibodies against the human reduced folate carrier (hRFC) has shown expression of the hRFC protein at this membrane domain. These data demonstrate the existence of a pH-dependent, DIDS-sensitive, electroneutral, carrier-mediated mechanism for folate transport across the human colonic basolateral membranes.


Circular RNA expression profile in the spinal cord of morphine tolerated rats and screen of putative key circRNAs.
Morphine tolerance developed after repeated or continuous morphine treatment is a global health concern hindering the control of chronic pain. In our previous research, we have reported that the expression of lncRNAs and microRNAs have been greatly modified in the spinal cord of morphine tolerated rats, and the modulating role of miR-873a-5p, miR-219-5p and miR-365 have already been confirmed. However, whether circular RNAs, another essential kind of non-coding RNA, are involved in the pathogenesis of morphine tolerance is still beyond our knowledge. In this study, we conducted microarray analysis for circRNA profile and found a large number of circRNAs changed greatly in the spinal cord by morphine treatment. Among them, we selected nine circRNAs for validation, and seven circRNAs are confirmed. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) analysis were used for functional annotation. Besides, we confirmed the modified expression of seven circRNAs after validation by real-time PCR, selected 3 most prominently modulated ones among them and predicted their downstream miRNA-mRNA network and analyzed their putative function via circRNA-miRNA-mRNA pathway. Finally, we enrolled the differentially expressed mRNAs derived from the identical spinal cord, these validated circRNAs and their putative miRNA targets for ceRNA analysis and screened a promising circRNA-miRNA-mRNA pathway in the development of morphine tolerance. This study, for the first time, provided valuable information on circRNA profile and gave clues for further study on the circRNA mechanism of morphine tolerance.


Application of hyperosmotic agent to determine gastric cancer with optical coherence tomography ex vivo in mice.
Noninvasive tumor imaging could lead to the early detection and timely treatment of cancer. Optical coherence tomography (OCT) has been reported as an ideal diagnostic tool for distinguishing tumor tissues from normal tissues based on structural imaging. In this study, the capability of OCT for functional imaging of normal and tumor tissues based on time- and depth-resolved quantification of the permeability of biomolecules through these tissues is investigated. The orthotopic graft model of gastric cancer in nude mice is used, normal and tumor tissues from the gastric wall are imaged, and a diffusion of 20% aqueous solution of glucose in normal stomach tissues and gastric tumor tissues is monitored and quantified as a function of time and tissue depth by an OCT system. Our results show that the permeability coefficient is (0.94+/-0.04)x10(-5) cms in stomach tissues and (5.32+/-0.17)x10(-5) cms in tumor tissues, respectively, and that tumor tissues have a higher permeability coefficient compared to normal tissues in optical coherence tomographic images. From the results, it is found that the accurate and sensitive assessment of the permeability coefficients of normal and tumor tissues offers an effective OCT image method for detection of tumor tissues and clinical diagnosis.


Assessment of passive respiratory mechanics in infants: double versus single occlusion?
The single breath or occlusion technique (SOT) is widely used to assess passive respiratory mechanics in infants, but depends on various underlying assumptions. Recently, it has been proposed that such measurements could be internally validated by performing two brief airway occlusions during the same expiration. The aim of this study was to evaluate the use of the double occlusion technique (DOT) using a new commercially available program (Jaeger MasterScreen BabyBody Erich Jaeger GmbH, Würzburg, Germany). Paired measurements of respiratory system compliance (Crs) and resistance (Rrs) using both SOT and DOT were obtained in 18 healthy sedated infants (age range 4-41 weeks, weight 2.7-9.9 kg). There was close agreement between both methods of assessing Crs in all infants, the mean within-subject difference (95% confidence interval (CI)) for DOT-SOT being -0.06 (-0.55- +0.42) mL x kPa(-1) x kg(-1). By contrast, estimates of Rrs,DO were on average 20% lower than those for Rrs,SO, (mean within-subject difference (95% CI) being -0.67 (-1.04- -0.31) kPa x L(-1) x s; p<0.01). The relatively lower values obtained for Rrs,DO may reflect the higher mean lung volume at which it was calculated. Further work is required to investigate the clinical and epidemiological relevance of this new approach, and whether there are any advantages of using both techniques when assessing passive mechanics in infants.


Real-Time PCR: an Effective Tool for Measuring Transduction Efficiency in Human Hematopoietic Progenitor Cells.
Accurate measurement of gene transfer into hematopoietic progenitor cells is an essential prerequisite for assessing the utility of gene therapy approaches designed to correct hematologic defects. We developed a reliable method to measure transduction efficiency at the level of the progenitor cell with real-time polymerase chain reaction (PCR) analysis of individual progenitor-derived colonies. We hypothesized that this method would demonstrate better sensitivity and specificity than are currently achievable with conventional PCR. An oncoretroviral vector containing the enhanced green fluorescent protein was used to transduce human CD34+ cells derived from bone marrow or granulocyte-colony-stimulating factor-mobilized peripheral blood. Progenitor assays were set up and colonies plucked after visualization by fluorescence microscopy. By analyzing microscopically identified fluorescent samples and nontransduced samples, we calculated an overall sensitivity and specificity of 90.2 and 95.0%, respectively. Real-time PCR had higher specificity and sensitivity than conventional PCR as analyzed by generalized linear models (P = 0.002 and P = 0.019, respectively). In conclusion, we found real-time PCR to have superior sensitivity and specificity compared to conventional PCR in determining transduction efficiency of hematopoietic progenitor cells.


Frequency of celiac disease and distribution of HLA-DQ2/DQ8 haplotypes among siblings of children with celiac disease.
Celiac disease (CD) is a multifactorial disease, but genetic factors play a major role in its etiology. It has been known that human leucocyte antigen (HLA)-DQ2/DQ8 haplotypes are one of the most important predisposing genetic factors. The risk of developing CD in first-degree relatives and especially siblings of celiac patients is quite high because of having the same HLA haplotypes. To evaluate the frequency of CD and the distribution of the HLA-DQ2/DQ8 haplotypes in siblings of celiac patients. Patients with biopsy-proven CD and their siblings were included in the study; those who did not have HLA genotyping were excluded from the study. All siblings were on a gluten-containing diet. The HLA genotyping, tissue transglutaminase antibody IgA antibody test, and total IgA test were performed in all participants. A total of 57 celiac patients and their 112 siblings were included in the study. The mean age of celiac patients and siblings were 10.30 ± 3.87 years and 9.90 ± 6.11 years, respectively. HLA-DQ2/DQ8 alleles were detected in 98.2% of patients with CD and 90.2% of siblings of celiac patients. HLA-DQ genotypes were present in all siblings diagnosed with CD. Tissue transglutaminase antibody IgA test was found to be positive in 16 siblings. CD was diagnosed in 12 siblings (10.7%) by intestinal biopsy. The prevalence of CD was found to be 10.7% in siblings of celiac patients in our study. One-third of the siblings diagnosed with CD were asymptomatic. We detected HLA-DQ alleles in 98.2% of celiac patients and 100% in siblings diagnosed with CD. In addition, 1 of the 2 siblings was diagnosed with CD 1 year later and the other 4 years later. Therefore, we suggest that siblings of celiac patients should be followed up with clinical findings as well as HLA analysis and serological examination. Since the risk of developing CD is much higher in asymptomatic siblings, we recommend that siblings should be screened for CD even if they are asymptomatic.


RNA N6-Methyladenosine Regulators Contribute to Tumor Immune Microenvironment and Have Clinical Prognostic Impact in Breast Cancer.
Purpose: This study aims to reveal the relationship between RNA N6-methyladenosine (m6A) regulators and tumor immune microenvironment (TME) in breast cancer, and to establish a risk model for predicting the occurrence and development of tumors. Patients and methods: In the present study, we respectively downloaded the transcriptome dataset of breast cancer from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database to analyze the mutation characteristics of m6A regulators and their expression profile in different clinicopathological groups. Then we used the weighted correlation network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), and cox regression to construct a risk prediction model based on m6A-associated hub genes. In addition, Immune infiltration analysis and gene set enrichment analysis (GSEA) was used to evaluate the immune cell context and the enriched gene sets among the subgroups. Results: Compared with adjacent normal tissue, differentially expressed 24 m6A regulators were identified in breast cancer. According to the expression features of m6A regulators above, we established two subgroups of breast cancer, which were also surprisingly distinguished by the feature of the immune microenvironment. The Model based on modification patterns of m6A regulators could predict the patient's T stage and evaluate their prognosis. Besides, the low m6aRiskscore group presents an immune-activated phenotype as well as a lower tumor mutation load, and its 5-years survival rate was 90.5%, while that of the high m6ariskscore group was only 74.1%. Finally, the cohort confirmed that age (p < 0.001) and m6aRiskscore (p < 0.001) are both risk factors for breast cancer in the multivariate regression. Conclusion: The m6A regulators play an important role in the regulation of breast tumor immune microenvironment and is helpful to provide guidance for clinical immunotherapy.


Type 1 Diabetes Mellitus Virtual Patient Network as a Peer Support Community: Protocol for Social Network Analysis and Content Analysis.
Type 1 Diabetes Mellitus Virtual Patient Network (T1DM-VPN) is a private Facebook group for youths with type 1 diabetes mellitus (T1DM) in Canada intended to facilitate peer-to-peer support. It was built on the finding that stigma is prevalent among youth with T1DM and impedes self-management. We aim to determine if T1DM-VPN provides support as intended and to ascertain what type of members provide support. Specifically, we will (1) identify text consistent with any one of 5 social support categories, (2) describe the network by visualizing its structure and reporting basic engagement statistics, and (3) determine whether being a designated peer leader is related to a member's centrality (ie, importance in the network) and how frequently they offer social support. We will manually extract interaction data from the Facebook group (posts, comments, likes/reactions, seen) generated from June 21, 2017 (addition of first member), to March 1, 2020. Two researchers will independently code posts and comments according to an existing framework of 5 social support categories-informational, emotional, esteem, network, and tangible-with an additional framework for nonsocial support categories. We will calculate how frequently each code is used. We will also report basic engagement statistics (eg, number of posts made per person-month) and generate a visualization of the network. We will identify stable time intervals in the history of T1DM-VPN by modeling monthly membership growth as a Poisson process. Within each interval, each member's centrality will be calculated and standardized to that of the most central member. We will use a centrality formula that considers both breadth and depth of connections (centrality = 0.8 × total No. of connections + 0.2 × total No. of interactions). Finally, we will construct multivariate linear regression models to assess whether peer leader status predicts member centrality and the frequency of offering social support. Other variables considered for inclusion in the models are gender and age at diagnosis. T1DM-VPN was launched in June 2017. As of March 1, 2020, it has 196 patient-members. This research protocol received ethics approval from the McGill University Health Centre Research Ethics Board on May 20, 2020. Baseline information about each group member was collected upon addition into the group, and collection of interaction data is ongoing as of May 2020. This content analysis and social network analysis study of a virtual patient network applies epidemiological methods to account for dynamic growth and activity. The results will allow for an understanding of the topics of importance to youth with T1DM and how a virtual patient network evolves over time. This work is intended to serve as a foundation for future action to help youth improve their experience of living with diabetes. PRR1-10.2196/18714.


Polypharmacy and mortality among nursing home residents with advanced cognitive impairment: results from the SHELTER study.
Older adults with advanced cognitive impairment have a limited life expectancy and the use of multiple drugs is of questionable benefit in this population. The aim of the present study was to assess if, in a sample of nursing home (NH) residents with advanced cognitive impairment, the effect of polypharmacy on mortality differs depending on estimated life expectancy. Data were from the Services and Health for Elderly in Long TERm care (SHELTER) project, a study collecting information on residents admitted to 57 NHs in 8 European countries. Polypharmacy was defined as the concomitant use of 10 or more drugs. Limited life expectancy was estimated based on an Advanced Dementia Prognostic Tool (ADEPT) score of 13.5 or more. A Cognitive Performance Scale score of 5 or more was used to define advanced cognitive impairment. Participants were followed for 1 year. Mean age of 822 residents with advanced cognitive impairment entering the study was 84.6 (SD 8.0) years, and 630 (86.6%) were women. Overall, 123 participants (15.0%) had an ADEPT score of 13.5 or more (indicating limited life expectancy) and 114 (13.9%) were on polypharmacy. Relative to residents with ADEPT score less than 13.5, those with ADEPT score of 13.5 or higher had a lower use of benzodiazepines, antidementia drugs, and statins but a higher use of beta-blockers, digoxin, and antibiotics. Polypharmacy was associated with increased mortality among residents with ADEPT score of 13.5 or more (adjusted hazard ratio [HR] 2.19, 95% confidence interval [CI]: 1.15-4.17), but not among those with ADEPT score less than 13.5 (adjusted HR 1.10, 95% CI: 0.71-1.71). Polypharmacy is associated with increased mortality in NH residents with advanced cognitive impairment at the end of life. These findings underline the need to assess life expectancy in older adults to improve the prescribing process and to simplify drug regimens.


Economic Burden Associated with Head Louse (Pediculus humanus capitis) Infestation in Iran.
The head louse infestation is a public health issue in the world especially, affecting most people who live in camps, school-aged children and their families. Head lice treatment has economic ramifications that often under calculated. The aim of this study was evaluation of economic burden associated with head louse infestation in Iran. In a cross-sectional study, 500,002 infestations were diagnosed among suspected head lice infested people who referred to health care system in all provinces of Iran during 2017. Direct and indirect costs related to paid by patients and government systems were extracted by referring to accounting documents and interviews with patients and experts and were recorded in researcher-made forms. Microsoft Excel 2010 software was used for economic burden calculation. The incidence rate of head lice infestation in Iran was 500,002/79,926,270 (625.5 per 100,000 populations). Economic burden of head lice in the country was calculated at 5,790,143$. Direct and indirect costs, governmental cost, out of pocket and total costs of head lice were included 3.14$, 2.84$, 5.98$, 5.60$ and 11.58$ per case respectively. The direct and indirect costs associated with treatment of infestations were relatively high. Therefore, the creation of medical facilities such as availability of diagnostic and treatment strategies can be effective in the control of infestation. The adoption of infestation prevention methods, such as health education to people at risk of infestation, reduces the incidence of head lice and imposition of related treatment costs on governmental health care system and head lice cases.


[Epidemiological and pathomorphological autopsy findings in AIDS].
The autopsy findings in 41 AIDS patients (1982-1991), including a rather large group of 8 patients without one of the classical risk factors for HIV, showed a much higher rate of opportunistic infections, especially CMV and fungal infections, as well as Kaposi's sarcoma in homosexuals than in the others. There was no decline in the incidence of Kaposi's sarcoma over the last few years. The bone marrow findings, which presented a remarkable high cellularity in these patients, well correlated with the so-called HIV-myelopathy, which is highly suggestive to represent a direct HIV-related damage of the bone marrow.


Job Tasks as Determinants of Thoracic Aerosol Exposure in the Cement Production Industry.
The aims of this study were to identify important determinants and investigate the variance components of thoracic aerosol exposure for the workers in the production departments of European cement plants. Personal thoracic aerosol measurements and questionnaire information (Notø et al., 2015) were the basis for this study. Determinants categorized in three levels were selected to describe the exposure relationships separately for the job types production, cleaning, maintenance, foreman, administration, laboratory, and other jobs by linear mixed models. The influence of plant and job determinants on variance components were explored separately and also combined in full models (plant&job) against models with no determinants (null). The best mixed models (best) describing the exposure for each job type were selected by the lowest Akaike information criterion (AIC; Akaike, 1974) after running all possible combination of the determinants. Tasks that significantly increased the thoracic aerosol exposure above the mean level for production workers were: packing and shipping, raw meal, cement and filter cleaning, and de-clogging of the cyclones. For maintenance workers, time spent with welding and dismantling before repair work increased the exposure while time with electrical maintenance and oiling decreased the exposure. Administration work decreased the exposure among foremen. A subjective tidiness factor scored by the research team explained up to a 3-fold (cleaners) variation in thoracic aerosol levels. Within-worker (WW) variance contained a major part of the total variance (35-58%) for all job types. Job determinants had little influence on the WW variance (0-4% reduction), some influence on the between-plant (BP) variance (from 5% to 39% reduction for production, maintenance, and other jobs respectively but an 79% increase for foremen) and a substantial influence on the between-worker within-plant variance (30-96% for production, foremen, and other workers). Plant determinants had little influence on the WW variance (0-2% reduction), some influence on the between-worker variance (0-1% reduction and 8% increase), and considerable influence on the BP variance (36-58% reduction) compared to the null models. Some job tasks contribute to low levels of thoracic aerosol exposure and others to higher exposure among cement plant workers. Thus, job task may predict exposure in this industry. Dust control measures in the packing and shipping departments and in the areas of raw meal and cement handling could contribute substantially to reduce the exposure levels. Rotation between low and higher exposed tasks may contribute to equalize the exposure levels between high and low exposed workers as a temporary solution before more permanent dust reduction measures is implemented. A tidy plant may reduce the overall exposure for almost all workers no matter of job type.


Theoretical analysis of carbon nanotube wetting in polystyrene nanocomposites.
Besides chemical functionalisation, the use of surfactants can be applied to debundle and disperse carbon nanotubes before further application in polymer nanocomposites. In this work we present a theoretical analysis of the interaction between single-walled carbon nanotubes and sodium dodecyl sulfate as surfactant and/or polystyrene as polymer matrix using semi-empirical AM1 calculations. Results indicate that the use of short potassium sulfate-terminated polystyrene chains as an extra component can help to remove the surfactant from the nanotube surface within the matrix, resulting in improved electronic properties of the nanocomposite.


NT4(Si)-p53(N15)-antennapedia induces cell death in a human hepatocellular carcinoma cell line.
To construct the recombinant lentivirus expression plasmid, pLenti6/V5-NT4 p53(N15)-antennapedia (Ant), and study its effect on HepG2 cells. Plasmid pLenti6/V5-NT4 p53(N15)-Ant was constructed incorporating the following functional regions, including signal peptide sequence and pro-region of neurotrophin 4, N-terminal residues 12-26 of p53 and 17 amino acid drosophila carrier protein, Ant. Hepatocellular carcinoma (HepG2) cells were used for transfection. 3-[4,5-dimethyl-thiazol-2yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, transmission electron microscopy (TEM) and flow cytometric analysis (FCM) were employed to investigate the effects of LV-NT4(Si)-p53(N15)-Ant in vitro on HepG2 cells. In vivo experiment was also performed to investigate the inhibitory effect of LV-NT4(Si)-p53(N15)-Ant on tumor growth in nude mice. LV-NT4(Si)-p53(N15)-Ant significantly suppressed the growth of HepG2 cells. MTT assay showed that the growth of HepG2 cells was mucj more significantly inhibited by LV-NT4(Si)-p53(N15)-Ant than by LV-EGFP. The inhibition rate for HepG2 cell growth in the two groups was 46.9% and 94.5%, respectively, 48 h after infection with LV-NT4(Si)-p53(N15)-Ant, and was 33.9% and 95.8%, respectively, 72 h after infection with LV-NT4(Si)-p53(N15)-Ant (P < 0.01). Light microscopy and TEM showed morphological changes in HepG2 cells infected with LV-NT4(Si)-p53(N15)-Ant, but no significant changes in HepG2 cells infected with LV-EGFP. Changes were observed in ultra-structure of HepG2 cells infected with LV-NT4(Si)-p53(N15)-Ant, with degraded membranes, resulting in necrosis. LDH release from HepG2 cells was analyzed at 24, 48, 72 and 96 h after infection with LV-NT4(Si)-p53(N15)-Ant and LV-EGFP, which showed that LDH release was significantly higher in LV-NT4(Si)-p53(N15)-Ant treatment group (682 IU/L) than in control group (45 IU/L, P < 0.01). The longer the time was after infection, the bigger the difference was in LDH release. FCM analysis showed that LV-NT4(Si)-p53(N15)-Ant could induce two different kinds of cell death: necrosis and apoptosis, with apoptosis being the minor type and necrosis being the main type, suggesting that LV-NT4(Si)-p53(N15)-Ant exerts its anticancer effect on HepG2 cells by inducing necrosis. The in vivo study showed that LV-NT4(Si)-p53(N15)-Ant significantly inhibited tumor growth with an inhibition rate of 66.14% in terms of tumor size and weight. LV-NT4(Si)-p53(N15)-Ant is a novel recombinant lentivirus expression plasmid and can be used in gene therapy for cancer.


Bringing ALife and Complex Systems Science to Population Health Research.
Despite tremendous advancements in population health in recent history, human society currently faces significant challenges from wicked health problems. These are problems where the causal mechanisms at play are obscured and difficult to address, and consequently they have defied efforts to develop effective interventions and policy solutions using traditional population health methods. Systems-based perspectives are vital to the development of effective policy solutions to seemingly intractable health problems like obesity and population aging. ALife in particular is well placed to bring interdisciplinary modeling and simulation approaches to bear on these challenges. This article summarizes the current status of systems-based approaches in population health, and outlines the opportunities that are available for ALife to make a significant contribution to these critical issues.


[In memoriam Vilmos Vajna: to commemorate his 155th birthday].
Vilmos Vajna was born in Transylvania. His medical education was completed at Franz Joseph University of Arts and Sciences in Kolozsvár. He studied dental sciences in Vienna and Pest. After returning to Kolozsvár he obtained his habilitation ("venia legendi") and then lectured dentistry at this university. After finishing his academic carrier he moved to Budapest in 1895. While he practiced dentistry in his private office he made several technical innovations, constructed new instruments, and invented new technologies. He was an active member of the public life of the dental community.


The Research of No-Touch Isolation Technique on the Prevention of Postoperative Recurrence and Metastasis of Hepatocellular Carcinoma after Hepatectomy.
To evaluate the efficacy of a surgical no-touch isolation technique in primary hepatocellular carcinoma patients compared with traditional hepatectomy. Eighty hepatocellular carcinoma patients were randomly divided into traditional hepatectomy (n = 40) and no-touch isolation technique groups (n = 40). We compared peripheral blood variations in alpha-fetoprotein mRNA, miRNA-221, miRNA-224, and miRNA-122 expression levels in both groups pre- and postoperatively using real-time fluorescent quantitative polymerase chain reaction. The patients in the no-touch isolation technique group had better clinical curative effect. In the traditional hepatectomy group, variations in alpha-fetoprotein mRNA copy number pre- and postoperatively indirectly indicated a significant increase in the number of exfoliated carcinoma cells induced by manipulating the liver, increasing the risk of postoperative recurrence and metastasis (P < 0.05). Traditional hepatectomy patients showed higher increases in miRNA-221 and miRNA-224 expression than those in the no-touch isolation technique group (P < 0.05). Tumor resection resulted in preoperative expression and high postoperative expression of miRNA-122. No-touch isolation technique patients showed a slight and significant increase (P < 0.01) in miRNA-122, which was positively correlated with postoperative liver function index. Conclusion: The no-touch isolation technique is more effective than traditional hepa- tectomy in tumor resection for primary hepatocellular carcinoma.


Cinobufocini inhibits NF-κB and COX-2 activation induced by TNF-α in lung adenocarcinoma cells.
The aim of the present study was to investigate the effects of cinobufocini on nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and the production of cytokines induced by tumor necrosis factor-α (TNF-α) in the A549 cell line. A549 cells were incubated with cinobufocini at different concentrations for 24, 48 or 72 h. Cell proliferation was examined by the WST-8 assay. The expression of NF-κB, COX-2 and inhibitor κBα (IκBα) was studied by western blotting. The NF-κB-dependent luciferase rporter (3xκB-luc) was transfected for 24 h, the cells were treated with the reagents for 24 h, and the transcriptional activity of the NF-κB promoter was detected by a luciferase assay. The levels of IL-6 and IL-8 mRNA were detected by reverse transcription-polymerase chain reaction. We found that cinobufocini inhibited NF-κB p65 expression and the transcriptional activity of the NF-κB promoter induced by TNF-α compared with the control in the nuclei of A549 cells. Moreover, induced COX-2 expression was blocked by cinobufocini and was correlated with a reduction in the activated p65 subunit of NF-κB. Additionally, the levels of IL-6 and IL-8 mRNA induced by TNF-α were significantly suppressed by the addition of cinobufocini. In conclusion, these results suggest that the anti-inflammatory effects of cinobufocini are dependent on the NF-κB/COX-2 pathway in A549 cells, thereby providing a possible anticancer mechanism for the compound.


Cortico-muscular coherence enhancement via coherent Wavelet enhanced Independent Component Analysis.
Functional coupling between the motor cortex and muscle activity is usually detected and characterized using the spectral method of cortico-muscular coherence (CMC) between surface electromyogram (sEMG) and electroencephalogram (EEG) recorded synchronously under motor control task. However, CMC is often weak and not easily detectable in all individuals. One of the reasons for the low levels of CMC is the presence of noise and components unrelated to the considered tasks in recorded sEMG and EEG signals. In this paper we propose a method for enhancing relative levels of sEMG components coherent with synchronous EEG signals via a variant of Wavelet Independent Component Analysis combined with a novel component selection algorithm. The effectiveness of the proposed algorithm is demonstrated using data collected in neurophysiologcal experiments.


Clinical assessment of nifedipine-induced gingival overgrowth in a group of brazilian patients.
Although it has been established that nifedipine is associated with gingival overgrowth (GO), there is little information on the prevalence and severity of this condition in the Brazilian population. The aim of this study was to assess the occurrence of nifedipine-induced GO in Brazilian patients and the risk factors associated using a Clinical Index for Drug Induced Gingival Overgrowth (Clinical Index DIGO). The study was carried out on 35 patients under treatment with nifedipine (test group) and 35 patients without treatment (control group). Variables such as demographic (age, gender), pharmacological (dose, time of use), periodontal (plaque index, gingival index, probing depth, clinical insertion level, and bleeding on probing), and GO were assessed. Statistical analysis showed no association between GO and demographic or pharmacological variables. However, there was an association between GO and periodontal variables, except for plaque index. According to our study, the Clinical Index DIGO can be used as a parameter to evaluate GO. Therefore, we conclude that the presence of gingival inflammation was the main risk factor for the occurrence of nifedipine-induced GO.


High-speed atomic force microscope combined with single-molecule fluorescence microscope.
High-speed atomic force microscopy (HS-AFM) and total internal reflection fluorescence microscopy (TIRFM) have mutually complementary capabilities. Here, we report techniques to combine these microscopy systems so that both microscopy capabilities can be simultaneously used in the full extent. To combine the two systems, we have developed a tip-scan type HS-AFM instrument equipped with a device by which the laser beam from the optical lever detector can track the cantilever motion in the X- and Y-directions. This stand-alone HS-AFM system is mounted on an inverted optical microscope stage with a wide-area scanner. The capability of this combined system is demonstrated by simultaneous HS-AFM∕TIRFM imaging of chitinase A moving on a chitin crystalline fiber and myosin V walking on an actin filament.


The shapes of the tibial and femoral articular surfaces in relation to tibiofemoral movement.
We report a study of the shapes of the tibial and femoral articular surfaces in sagittal, frontal and coronal planes which was performed on cadaver knees using two techniques, MRI and computer interpolation of sections of the articular surfaces acquired by a three-dimensional digitiser. The findings using MRI, confirmed in a previous study by dissection, were the same as those using the digitiser. Thus both methods appear to be valid anatomical tools. The tibial and femoral articular surfaces can be divided into anterior segments, contacting from 0 degrees to 20 +/- 10 degrees of flexion, and posterior segments, contacting from 20 +/- 10 degrees to 120 degrees of flexion. The medial and lateral compartments are asymmetrical, particularly anteriorly. Posteromedially, the femur is spherical and is located in a conforming, but partly deficient, tibial socket. Posterolaterally, it is circular only in the sagittal section and the tibia is flat centrally, sloping downwards both anteriorly and posteriorly to receive the meniscal horns. Anteromedially, the femur is convex with a sagittal radius larger than that posteriorly, while the tibia is flat sloping upwards and forwards. Anterolaterally, both the femoral and tibial surfaces are largely deficient. These shapes suggest that medially the femur can rotate on the tibia through three axes intersecting in the middle of the femoral sphere, but that the sphere can only translate anteroposteriorly and even then to a limited extent. Laterally, the femur can freely translate anteroposteriorly, but can only rotate around a transverse axis for that part of the arc, i.e., near extension, during which it comes into contact with the tibia through its flattened distal/medial surface as against its spherical posterior surface.


Electroacupuncture plus moxibustion for major depressive disorder: A randomized, sham-controlled, pilot clinical trial.
The first treatment option for major depressive disorder (MDD) is antidepressants, however, there is substantial demand for alternative therapies due to its low compliance and remission rates. This study was aimed to explore the effectiveness, safety, and feasibility of electroacupuncture plus moxibustion therapy for MDD. Thirty adults with MDD were randomly assigned to the treatment group (TG) or control group (CG). The TG was treated with electroacupuncture plus moxibustion, and the CG received sham interventions at non-acupoints for 8 weeks. The primary outcome measure was the intergroup difference of the mean change of total score of the Hamilton rating scale for depression (HRSD) between baseline and week 9. Secondary outcome measures were Beck's depression inventory, insomnia severity index, the state-trait anxiety inventory, the EuroQol-5 dimension index, the measure yourself medical outcome profile version 2, and frontal alpha asymmetry measured by electroencephalography. Adverse events (AEs) were monitored for safety assessment. The primary outcome measure was not significantly different between the two groups (p=0.2641), although the scores of HRSD in both groups improved significantly after treatment. No significant difference was identified between groups in secondary outcome measures. The incidence of AE was not significantly different between the two groups (p=0.1067). A clinical trial using electroacupuncture plus moxibustion for MDD seems feasible. However, further studies with the larger size, adopting ideal controls are warranted to provide a confirmative conclusion to the efficacy and safety of electroacupuncture plus moxibustion for MDD. The protocol was registered at Korean Clinical Trial Registry (CRIS-KCT0001810).


Blood loss and transcapillary refill in uncontrolled treated hemorrhage in dogs.
This study evaluated retroperitoneal hematomas produced by bilateral injury of iliac arteries (uncontrolled hemorrhage), blood volume loss, transcapillary refill, the effects of volume replacement on retroperitoneal bleeding and the hemodynamic changes with and without treatment. Initial blood volume was determined with Tc(99m)-labelled red cells, and bleeding was evaluated by means of a portable scintillation camera positioned over the abdomen. Previously splenectomized mongrel dogs (16.8 +/- 2.2 kg) were submitted to hemorrhage for 30 minutes and randomized into three groups: I - no treatment (n=7); II - treatment with 32 mL/kg of Lactated Ringer's for three to five minutes (n=7); and III - treatment with 4 mL/kg of 7.5% NaCl plus 6.0% dextran 70 for three to five minutes (n=7). They were studied for an additional 45 minutes. Volume replacement produced transitory recovery in hemodynamic variables, including mean pulmonary artery pressure, pulmonary capillary wedge pressure and cardiac index, with significant increase in dogs treated with 32 mL/kg of Lactated Ringer's and 7.5% NaCl plus 6.0% dextran 70 (p<0.001, against no treatment), along with a decrease (p<0.001) in the systemic vascular resistance index. Groups II and III had significant initial decreases in hematocrit and hemoglobin. The treated dogs (groups II and III) presented rebleeding, which was greater during treatment with 32 mL/kg of Lactated Ringer's (group II). Despite the rebleeding observed in treated groups, the utilization of hypertonic saline solution with dextran proved to be effective in the initial reanimation, producing evident transcapillary refill, while the Lactated Ringer's solution produced capillary extravasation and was ineffective in the initial volume replacement in this model of uncontrolled hemorrhage.


High-protein nutrition during pregnancy and lactation programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.
Maternal low-protein diet during pregnancy is a risk factor for cardiovascular disease of the offspring in later life. The impact of high-protein diet during pregnancy on the cardiovascular phenotype of the offspring, however, is still unknown. We examined the influence of a high-protein diet during pregnancy and lactation on the renal, hemodynamic, and metabolic phenotype of the F1 generation. Female Wistar rats were either fed a normal protein diet (20% protein: NP) or an isocaloric high-protein diet (40% protein: HP) throughout pregnancy and lactation. At weaning, the offspring were fed with standard diet, and they were allocated according to sex and maternal diet to four groups: normal-protein male (NPm, n = 25), normal-protein female (NPf, n = 19), high-protein male (HPm, n = 24), high-protein female (HPf, n = 29). During the experiment (22 wk), the animals were characterized by repeated measurement of body weight, food intake, blood pressure, glucose tolerance, energy expenditure, and kidney function. At the end of the study period histomorphological analyses of the kidneys and weight measurement of reproductive fat pads were conducted. There were no differences in birth weight between the study groups. No influence of maternal diet on energy expenditure, glucose tolerance, and plasma lipid levels was detected. Blood pressure and glomerulosclerosis were elevated in male offspring only, whereas female offspring were characterized by an increased food efficiency, higher body weight, and increased fat pads. Our study demonstrates that a high-protein diet during pregnancy and lactation in rats programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.


Self-assembly of laminin induced by acidic pH.
The supramolecular architecture of the basement membrane is provided by two enmeshed networks of collagen IV and laminin. The laminin network is maintained exclusively by interactions among individual laminin molecules and does not depend on the presence of other extracellular matrix components. Laminin polymers can be obtained in vitro either in solution or in association with the surface of bilayers containing acidic lipids. In this work, we have tested the hypothesis that the negative charges present on acidic lipids establish an acid microenvironment that is directly responsible for inducing laminin aggregation. Using light-scattering measurements, we show that laminin does not aggregate on vesicles of neutral lipids, whereas instantaneous aggregation occurs to progressively greater extents as the proportion of acidic phospholipids in the vesicles is increased. Aggregation of laminin induced by vesicles containing acidic phospholipids occurs very rapidly, so that maximal aggregation for each condition is reached within 1 min after laminin dilution. Aggregation depends on the presence of Ca(2+) ions, is reversed by increasing ionic strength, and can be detected at laminin concentrations as low as 6 nM. In addition, we show that, in the absence of vesicles, acidification of the bulk solution can also induce laminin self-polymerization through a process that exhibits the same properties as lipid-induced polymerization. The fact that there is a correspondence between the processes of self-polymerization of laminin in acidic medium and in neutral medium but in the presence of vesicles containing negatively charged lipids leads us to propose that the microenvironment of an acidic surface may trigger the assembly of laminin networks. In vivo, such an acidic microenvironment would be provided by negatively charged sialic acid and sulfate groups present in the glycocalyx surrounding the cells.


Regulation of transcription factors by heterotrimeric G proteins.
Lessons from viral hijacks of cells and cancer biology suggest that the activation of G protein-coupled receptors (GPCRs) often results in the modulation of various transcription factors and cofactors. Since drugs acting on GPCRs represent a significant portion of therapeutic agents currently in use, it is important to understand the actions of GPCRs on gene expression. GPCRs and their associated heterotrimeric G proteins are known to regulate gene transcription through complex signaling networks. The G protein-mediated signaling cascades have been extensively studied and accumulating evidence indicates that the four subfamilies of G proteins may utilize both common and unique pathways for transcriptional regulation. This review aims to provide a contemporary account of our understanding on the regulation of transcription factors by GPCRs, with a special emphasis on specific regulations of transcription factors such as STAT3 and NF-kappaB by individual G protein subfamilies. Functional impacts of the signal integration between different pathways and the contributions by other GPCR-interacting molecules will also be briefly discussed.


Vaccine Hesitancy and the Green Digital Pass: A Study on Adherence to the Italian COVID-19 Vaccination Campaign.
In July 2021, the vaccination campaign in Italy suffered a sudden setback, and the number of vaccine administrations decreased dramatically. On 20 July 2021, the obligation of the Green Digital Pass came into force in order to access work and leisure places, penalizing those who had not been vaccinated. The purpose of this work was to investigate the phenomenon of vaccination hesitancy and the underlying reasons, as well as any changes to the membership following the obligation of the Green Pass. A total of 83 subjects (45.8% F; mean age 22.24 ± 4.308) participated in the survey during the post-vaccine observation phase at the Vaccinal Center of the University Hospital "San Giovanni di Dio e Ruggi d'Aragona" (Salerno, Italy). The questionnaire collected anamnestic information, as well as data on state anxiety (STAI-Y), perception of quality of life (SF-12), perception of COVID-19 risks, and vaccine hesitancy. Among participants, 19.3% reported hesitation. The most common concerns about the COVID-19 vaccine concerned safety and efficacy (4.9%) and the obligation of the Green Pass (4.9%). Findings suggest that delving into the phenomenon of vaccine hesitancy can help to enhance vaccination strategies in order to gain widespread acceptance, a key path to ensuring a quick way out of the current pandemic emergency.


Influence of adsorption thermodynamics on guest diffusivities in nanoporous crystalline materials.
Published experimental data, underpinned by molecular simulations, are used to highlight the strong influence of adsorption thermodynamics on diffusivities of guest molecules inside ordered nanoporous crystalline materials such as zeolites, metal-organic frameworks (MOFs), and zeolitic imidazolate frameworks (ZIFs). For cage-type structures (e.g. LTA, CHA, DDR, and ZIF-8), the variation of the free energy barrier for inter-cage hopping across the narrow windows, -δFi, provides a rationalization of the observed strong influence of pore concentrations, ci, on diffusivities. In open structures with large pore volumes (e.g. FAU, IRMOF-1, CuBTC) and within channels (MFI, BEA, MgMOF-74, MIL-47, MIL-53), the pore concentration (ci) dependence of the self- (Di,self), Maxwell-Stefan (Đi), and Fick (Di) diffusivities are often strongly dictated by the inverse thermodynamic correction factor, 1/Γi≡∂ln ci/∂ln pi; the magnitudes of the diffusivities are dictated by the binding energies for adsorption. For many guest-host combinations Đi-ci dependence is directly related to the 1/Γivs. ci variation. When molecular clustering occurs, we get 1/Γi > 1, causing unusual Đivs. ci dependencies. The match, or mis-match, between the periodicity of the pore landscape and the conformations of adsorbed chain molecules often leads to non-monotonic variation of diffusivities with chain lengths.


The forensic pathology of nonagenarians and centenarians: do they die of old age? (The Auckland experience).
The aim of this study is to provide awareness of the common causes of death and their associated trends in the very aged. Forensic autopsies on patients aged >90 years were reviewed. The study lasted from January 1, 1988 to December 11, 1998 and was done in Auckland, New Zealand, the population of which is 1.3 million. Cases were divided into natural or unnatural deaths. Of the total of 319 cases, 272 (85%) deaths were natural. Of those, only 13 (5%) were "written off" as being attributed to old age or senile debility. The most common causes of death were ischemic heart disease (IHD), 74 cases (23%); bronchopneumonia, 37 cases (12%); fractures, 28 cases (9%); acute myocardial infarction, 25 cases (8%); cerebrovascular accident, 19 cases (6%); and ruptured aneurysm, 17 cases (5%); 61 (19%) deaths were multifactorial. Fractures, either as the primary cause of death or as a complicating factor, accounted for 29 cases, third only to IHD and bronchopneumonia. Forty-seven deaths (15%) were unnatural; of those, 43 were accidents, 3 were suicides, and 1 was a homicide. From these results it is clear that the very elderly succumb to disease; they do not often die of old age.


On the redox control of B lymphocyte differentiation and function.
On the one hand, redox emerges as a key mechanism in regulating intra- and intercellular signaling and homeostatic systems. On the other hand, cells of the B lineage provide powerful systems to unravel the intra- and intercellular mechanisms that coordinate the processes of development and terminal differentiation. This essay summarizes a few paradigmatic examples of redox regulation and signal modulation that emerged from, or were confirmed by, studies on the development, differentiation and function of B cells. While a role for intra- and intercellular redox signaling has been firmly established for differentiating B cells, many fundamental questions remain open, including the cellular sources of reactive oxygen species (ROS), the spatial and temporal constraints of ROS signaling, and the functional role of the antioxidant response. Given their robustness and biotechnological and clinical interest, cells of the B lineage continue to be fruitful goldmines from which redox biologists can dig novel mechanistic knowledge of general relevance.


Hexanuclear Platinum(II) Thiolate Macrocyclic Host: Charge-Transfer-Driven Inclusion of a Ag(I) Ion Guest.
The inclusion of a Ag(I) ion by a hexanuclear platinum(II) thiolate macrocycle in solution was demonstrated, and the inclusion structure was determined by X-ray crystallography. Unique host-guest intermetallic interactions driven by charge transfer were elucidated by optical absorption spectroscopy and theoretical calculations.


Respiratory mechanics during high-frequency oscillatory ventilation: a physical model and preterm infant study.
Accurate mechanics measurements during high-frequency oscillatory ventilation (HFOV) facilitate optimizing ventilator support settings. Yet, these are influenced substantially by endotracheal tube (ETT) contributions, which may dominate when leaks around uncuffed ETT are present. We hypothesized that 1) the effective removal of ETT leaks may be confirmed via direct comparison of measured vs. model-predicted mean intratracheal pressure [mPtr (meas) vs. mPtr (pred)], and 2) reproducible respiratory system resistance (Rrs) and compliance (Crs) may be derived from no-leak oscillatory Ptr and proximal flow. With the use of ETT test-lung models, proximal airway opening (Pao) and distal (Ptr) pressures and flows were measured during slow-cuff inflations until leaks are removed. These were repeated for combinations of HFOV settings [frequency, mean airway pressure (Paw), oscillation amplitudes (ΔP), and inspiratory time (%t(I))] and varying test-lung Crs. Results showed that leaks around the ETT will 1) systematically reduce the effective distending pressures and lung-delivered oscillatory volumes, and 2) derived mechanical properties are increasingly nonphysiologic as leaks worsen. Mean pressures were systematically reduced along the ventilator circuit and ETT (Paw > Pao > Ptr), even for no-leak conditions. ETT size-specific regression models were then derived for predicting mPtr based on mean Pao (mPao), ΔP, %t(I), and frequency. Next, in 10 of 11 studied preterm infants (0.77 ± 0.24 kg), no-to-minimal leak was confirmed based on excellent agreement between mPtr (meas) and mPtr (pred), and consequently, their oscillatory respiratory mechanics were evaluated. Infant resistance at the proximal ETT (R(ETT); resistance airway opening = R(ETT) + Rrs; P < 0.001) and ETT inertance (P = 0.014) increased significantly with increasing ΔP (50%, 100%, and 150% baseline), whereas Rrs showed a modest, nonsignificant increase (P = 0.14), and Crs was essentially unchanged (P = 0.39). We conclude that verifying no-leak conditions is feasible by comparison of model-derived vs. distending mPtr (meas). This facilitated the reliable and accurate assessment of physiologic respiratory mechanical properties that can objectively guide ventilatory management of HFOV-treated preterm infants.


Cytofluorographic identification of activated T-cell subpopulations in the semen of men with spinal cord injuries.
The semen of most men with spinal cord injury (SCI) contains an abundance of leukocytes. It is not known if this leukocytospermia contributes to the abnormally low sperm motility observed in many of these men. Our study used flow cytometry to identify the leukocyte population in the semen of 12 men with SCI compared to 8 healthy age-matched control subjects. The results showed that, compared to control subjects, the semen of men with SCI had increased numbers of mature granulocytes and lymphocytes. The largest proportion of the leukocytes consisted of lymphocytes, and immunophenotypic analysis showed that the greater fraction were T cells, many of which coexpressed human leukocyte antigen HLA-DR and CD25, suggesting they were in an "activated" state. No significant B-cell population was evident. Our finding of immunologically active leukocytes is a significant step in understanding the relationship of leukocytospermia and decreased sperm motility in the semen of men with SCI.


Effect of blood transfusion on acid base, glucose and electrolyte status in very low birth weight infants.
The effect of citrate phosphate dextrose (CPD) blood transfusion on the acid base, glucose and electrolyte status of VLBW infants was studied in infants aged 1-7, 8-20 and greater than 20 days; a 4th group composed of infants greater than 20 days subjected to a second transfusion was also studied. All the infants remained clinically well during and after the transfusion. Only the infants in the group 1-7 days experienced a significant fall in ionic Ca and PO2. No significant change in all the other parameters studied was observed. In the other groups of infants studied, the changes observed were not significant, and became less with increasing age and repeat transfusion. VLBW infants apparently tolerate CPD blood transfusion well.


The role of family history and its influence on the onset time in female pattern hair loss.
Female pattern hair loss (FPHL) is one of the most common causes of hair loss in women. Genetics plays an important role in the development of the disease, but the etiopathogenesis and the inheritance pattern in women remain unexplained. To determine the extent to which FPHL is of genetic origin in women from the Polish population and whether a positive family history is a risk factor for its earlier onset. Family histories of 111 unrelated female patients with FPHL and 129 female patients without hair thinning were analysed. FPHL was diagnosed based on a detailed medical history, the clinical picture and trichoscopic features. A positive family history was noted in 69 (62.2%) patients with FPHL. In 32 (28.8%) patients from that group, more than one person in the family suffered from hair loss, whereas in the healthy group, the same was true of only 4 patients (3.1%) (p < 0.0001). A positive family history on the mother's side proved statistically significant for FPHL patients. In the case of 20 (18%), hair loss had been identified in their grandparents, while the healthy group had a negative history in that respect. A positive family history of hair loss in grandparents was three times more frequent in the group of patients with the disease onset before 40. A positive history on the mother's side may be of great significance for FPHL development. Hair loss in more than one family member and in one's grandparents may also indicate a higher risk of disease development.


Transforming glucose into fluorescent graphene quantum dots via microwave radiation for sensitive detection of Al3+ ions based on aggregation-induced enhanced emission.
This paper initially describes a nanosensor for fluorescence detection of Al3+ ions by using graphene quantum dots (GQDs) that are synthesized via microwave-assisted single-step ring-closure condensation of glucose molecules. The one-pot synthesis strategy based on the microwave radiation could be finished in several minutes and no post-modification of the GQDs was required. In particular, the GQD nanoprobes showed a sensitive and specific fluorescence enhancement response to Al3+. The involved mechanism might be the Al3+-mediated aggregation of the GQDs leading to aggregation-induced enhanced emission (AIEE). Under optimal conditions, this new fluorescent nanosensor was able to quantitatively detect Al3+ in a linear concentration range of 0.4-500 μM. The limit of detection was estimated to be ∼59.8 nM according to the 3σ rule, which made it be among the most sensitive systems currently available for sensing the target ion. Moreover, satisfactory recovery results (ranging from 96.8 to 109.7%) of analyzing a set of real water examples additionally validated its accuracy for practical applications. Considering its simplicity, high sensitivity and specificity, low cost, and good reliability, the developed fluorescent nanosensing system for Al3+ holds great promise for broad uses in water safety, environmental monitoring, and waste management.


In vitro activity of ceftriaxone and amikacin against Pseudomonas aeruginosa.
Ceftriaxone and amikacin were combined at ratios of 1:1, 5:1, and 10:1 and tested in vitro against Pseudomonas aeruginosa. The activity was determined using the Steers-Foltz replicator and the agar dilution technique with Mueller-Hinton agar. Under all conditions tested, including those simulating severe infection (10(5) to 10(6) colony-forming units per spot), the organisms were more susceptible to the combination than to the single agents. With a conventional inoculum of 10(4) colony-forming units per spot, the combinations gave 97-100% coverage against P. aeruginosa. The increased activity of the combinations resulted in MIC90 values which were below the expected serum/plasma levels for significantly longer time periods than the MIC90 values observed with the individual agents.


Performance assessment of a glucose control protocol in septic patients with an automated intermittent plasma glucose monitoring device.
The optimal level and modality of glucose control in critically ill patients is still debated. A protocolized approach and the use of nearly-continuous technologies are recommended to manage hyperglycemia, hypoglycemia and glycemic variability. We recently proposed a pato-physiology-based glucose control protocol which takes into account patient glucose/carbohydrate intake and insulin resistance. Aim of the present investigation was to assess the performance of our protocol with an automated intermittent plasma glucose monitoring device (OptiScanner™ 5000). OptiScanner™ was used in 6 septic patients, providing glucose measurement every 15' from a side-port of an indwelling central venous catheter. Target level of glucose was 80-150 mg/dL. Insulin infusion and kcal with nutritional support were also recorded. 6 septic patients were studied for 319 h (1277 measurements); 58 [45-65] hours for each patient (measurements/patient: 231 [172-265]). Blood glucose was at target for 93 [90-98]% of study time. Mean plasma glucose was 126 ± 11 mg/dL. Only 3 hypoglycemic episodes (78, 78, 69 mg/dL) were recorded. Glucose variability was limited: plasma glucose coefficient of variation was 11.7 ± 4.0% and plasma glucose standard deviation was 14.3 ± 5.5 mg/dL. The local glucose control protocol achieved satisfactory glucose control in septic patients along with a high degree of safeness. Automated intermittent plasma glucose monitoring seemed useful to assess the performance of the protocol.


Involvement of p27KIP1 in G1 arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody.
Activation of the cyclin dependent kinases (CDK4/CDK6 and CDK2) is required for G1 phase progression and entry into S-phase. The activation of these kinases is regulated by checkpoints that monitor environmental and intracellular conditions. Progression into S-phase is controlled, in part, by the availability of growth factors, and we have investigated the relationship between growth factor availability and the activation of the CDK kinases. Blocking activation of epidermal growth factor (EGF) receptor tyrosine kinase with anti-EGF receptor monoclonal antibody (mAb) 225 induces G1 phase cell cycle arrest in DiFi human colon adenocarcinoma cells. When DiFi cells are treated with mAb 225 for 24 h, we observe marked decreases in the activities of CDK2 kinase and cyclin E-associated CDK kinase which are not accompanied by reduced levels of cyclin E and CDK2 proteins. However, the amount of cyclin/CDK kinase inhibitor p27KIP1 increases in the mAb-treated cells and p27KIP1 is bound to CDK2 in increasing amounts. Immunodepletion of p27KIP1 removes an inhibitory activity from lysates of mAb-treated cells: the immunodepleted and heated lysates lose the capacity to inhibit cyclin E/CDK2 activity in an in vitro assay. The results suggest that G1 arrest in the cell cycle induced by EGF receptor blockade involves p27KIP1.


Small variant STEVOR antigen is uniquely located within Maurer's clefts in Plasmodium falciparum-infected red blood cells.
Malaria parasite antigens encoded by multigene families are important factors in virulence and in disease pathology. In Plasmodium falciparum, the virulence factor PfEMP-1 is encoded by the var multigene family and is exposed at the infected erythrocyte surface. PfEMP-1 is clonally variant, allowing the parasite to evade host immunity. The recently identified P. falciparum stevor multigene family and its products also have the potential to be involved in similar important aspects of host-parasite interactions. Here, we show tightly regulated stage-specific transcription of stevor occurring over just a few hours of the asexual parasite life cycle. Only a subset of stevor genes are transcribed in parasite populations maintained in cultures and in single micromanipulated parasites. Antibodies against STEVOR recognize proteins of the expected size (approximately 37 kDa) and localize STEVOR in Maurer's clefts, unique membranous structures located in the cytoplasm of infected erythrocytes. The fact that the timing of stevor expression and the location of STEVOR are clearly distinct from those of other parasite variant antigens suggests that this gene family may have a novel role in P. falciparum biology.


Heterogeneity of lung volume reduction surgery outcomes in patients selected by use of evidence-based criteria.
Despite its benefit, lung volume reduction surgery (LVRS) is underused, partially because of the heterogeneous responses and lack of recent outcomes data. Data from 59 consecutive emphysema patients who underwent LVRS were analyzed. The proportion of patients responding based on 6-minute walk distance (6-MWD), exercise capacity (watts), and forced expiratory volume in 1 second (FEV1) were calculated. Baseline variables were correlated with improvements in 6-MWD, maximal watts, and FEV1. Eighty-eight percent of patients responded to LVRS, with a higher proportion of FEV1 and 6-MWD responders in our cohort compared with similar patients from the National Emphysema Treatment Trial. Significant associations existed between lower baseline 6-MWD and increased 6-MWD after operation (r = -0.423), more extensive emphysema and increased FEV1 (r = 0.491), and hyperinflation and increased maximal watts (r = 0.438). The probability of survival was 0.93 at 90 days, 0.90 at 1 year, and 0.80 (3 years). The lowest exercise group (<20 watts on baseline testing) had an increased risk for death (RR 13.3, p = 0.001). There were durable improvements in FEV1 and exercise capacity in patients meeting the National Emphysema Treatment Trial criteria. Survival was comparable to that in similar patients from the National Emphysema Treatment Trial; response rates were higher in our cohort for FEV1 and 6-MWD. Those with lower 6-MWD, more emphysema, and more hyperinflation at baseline were most likely to respond to LVRS. Those with lowest exercise capacity at baseline may have a higher risk of death after LVRS.


Acoustic neuromas: Gd-DTPA enhancement in MR imaging.
Magnetic resonance (MR) imaging examinations were performed in ten patients with 12 acoustic neuromas before and after intravenous administration of 0.1 mmol/kg body weight gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). The degree of enhancement was greatest with the inversion recovery sequence 1,500/500/44 (repetition time [TR]/inversion time/echo delay time [TE]), followed by spin-echo (SE) 544/44 (TR/TE) sequences, then by SE 1,500/44 and SE 1,500/80 sequences. After enhancement there was a 50% reduction for measured T1 values, 33% for T2, and no significant change for proton density. There were no toxic effects on patients. Enhanced CT scans failed to demonstrate lesions in six of 12 cases. Air-CT technique improved sensitivity in four of five cases. Enhanced MR imaging added significant clinical information in two small intracanalicular tumors and in one recurrent tumor.


Doping control analysis for adrafinil and its major metabolites in human urine.
A new and reliable two-step liquid chromatography/tandem mass spectrometry (LC/MS/MS) method in combination with gas chromatography/mass spectrometry (GC/MS) for the screening and confirmation of adrafinil and its major metabolites, modafinil and modafinil acid, in human urine has been developed and validated. The method involved reversed-phase C18 solid-phase extraction (SPE) cartridge extraction and MS analysis by means of LC/MS/MS and GC/MS. The study illustrated that the ESI capillary temperature played a key role in the formation of the protonated molecule. The limits of detection (LODs) of the developed method for the three compounds were lower than the minimum required performance limit (MRPL) of the World Anti-Doping Agency (WADA). The human urine samples obtained after the oral administration of modafinil and from the Beijing 2008 Olympic Games were analyzed by using the described method, which has also been successfully applied to routine analyses and the WADA Proficiency Test.


Frost, Abscisic Acid, and Desiccation Hasten Embryo Development in Brassica napus.
Seed development in canola (Brassica napus) following a mild nonlethal freeze was examined with respect to abscisic acid (ABA) levels, desiccation, and expression of LEA.76 and isocitrate lyase (ICL) transcripts. Plants with seed of 70 and 55% moisture contents were frozen to -5 degrees C for 3 hours, and seed development followed after thawing. In addition, similar processes were compared during induction of extreme desiccation tolerance by application of ABA in Brassica microspore-derived haploid embryos in culture. A mild freeze/thaw caused a premature switch in seed developmental direction from predesiccation to desiccation as indicated by an immediate and accelerated loss of seed moisture to levels similar to the mature seed in 7 instead of 35 days, and by elevated ABA levels and induction of low levels of LEA.76 and ICL transcripts. Similarly, addition of ABA to haploid embryos in culture resulted in the induction of desiccation tolerance and low levels of late embryogenesis-abundant (LEA) but not ICL transcripts. In contrast, normal seed development and desiccation of ABA-treated (desiccation-tolerant) embryos resulted in the induction of ICL and very high levels of LEA.76 transcripts. Similarly, desiccation of control (desiccation-sensitive) embryos resulted in very high levels of LEA.76 transcripts. These results indicate that although LEA-type proteins have been implicated in the development of desiccation tolerance, high transcript levels of LEA.76 were not observed in the induction of desiccation tolerance either by a hastening of the maturation process in the developing Brassica seed, or by the exogenous application of ABA to Brassica haploid embryos in culture.


Methotrexate osteopathy: five cases and systematic literature review.
Methotrexate (MTX)-related osteopathy is rare, defined by the triad of pain, osteoporosis, and "atypical fractures" when it was first described in the 1970s in children treated with high doses MTX for acute leukemia. Since then, several cases have been reported in patients treated with low-dose MTX for inflammatory diseases. A systematic research of cases of MTX-related osteopathy was performed in records of Rheumatology Department of Rennes University Hospital. Data collection focused on demographic data, corticosteroid doses, MTX doses and intake method, cumulative doses, year of diagnosis, fracture location, bone densitometry value, and osteoporosis treatment if necessary. A literature review was also conducted to identify other cases in literature and try to understand the pathophysiological mechanisms of this rare entity. We report 5 cases identified between 2011 and 2019, which represents the largest cohort described excluding oncology cases. Fracture locations were atypical for osteoporotic fractures. All patients improved in the following months with MTX withdrawal. All patients except one were treated with antiresorptives (bisphosphonates, denosumab). Two patients, treated with bisphosphonates, had a recurrence of fracture, once again of atypical location. Twenty-five cases were collected in literature with similar clinical presentation. The cellular studies that investigated the bone toxicity of MTX mainly showed a decrease in the number of osteoblasts, osteocytes, and chondrocytes in the growth plate and an increase in the number and activity of osteoclasts. In vitro, consequences of mechanical stimulation on human trabecular bone cells in the presence of MTX showed an alteration in mechano-transduction, with membrane hyperpolarization, acting on the integrin pathway. In contrast with our report, the cases described in the literature were not consistently associated with a decrease in bone mineral density (BMD). MTX osteopathy while rare must be known by the rheumatologist, especially when using this treatment for inflammatory conditions. The mechanisms are still poorly understood, raising the question of a possible remnant effect of MTX on osteo-forming bone cells, potentially dose-dependent. Methotrexate (MTX) osteopathy, described as a clinical triad, pain, osteoporosis, and atypical stress fractures, while rare, must be known by the rheumatologist. Our cohort of 5 cases represent the largest series of the literature. Pathophysiological studies raised the question of a dose-dependent remnant effect of MTX on osteo-forming bone cells.


Utility of Urinary Biomarkers Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 as a Marker for Diagnosing the Presence of Renal Scar in Children with Vesicoureteral Reflux (VUR): A Cross-Sectional Study.
To explore the possibility of using urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assess the presence of renal scars in children with Vesicoureteric Reflux (VUR). This cross-sectional study was conducted in 94 children aged 0-16 years diagnosed with VUR in the Department of Pediatric Surgery, JIPMER. Urinary biomarkers were measured using the enzyme-linked immunosorbent assay kits, normalized with urinary creatinine (Cr) and compared with severity of VUR (low grade [I and II] and high grade [III, IV, and V]), presence or absence of renal scar in VUR patients and severity of renal scar. Independent Student's t-test, Mann-Whitney U-test, and analysis of variance Kruskal-Wallis test were used for comparison, and receiver operating characteristic (ROC) curve analysis for predicting the accuracy of biomarkers in detecting the presence of renal scars. The median urinary NGAL (uNGAL) value was higher in children with renal scar (1.49 ng/mL) than those without renal scar (0.58 ng/mL) and was statistically significant (<0.001). Whereas median uNGAL/Cr was higher in children with renal scar (0.07) than those without renal scar (0.03) but was not statistically significant (P = 0.06). Urinary KIM-1 and urinary KIM-1/urinary Cr (uKIM-1/Cr) was not found to be a significant predictor of renal scar. The difference of uNGAL/Cr was comparable between the grades of renal scar but was not statistically significant. On ROC curve analysis, uNGAL had area under the ROC curve (AUC) of 0.769 with 71% of both specificity and sensitivity, whereas uNGAL/Cr was found to be a poor predictor of renal scar with AUC of 0.611, 60% sensitivity, and 61.2% specificity. uNGAL can serve as a noninvasive marker for diagnosing the presence of renal scar in children with VUR and a multicentric more extensive cohort study may be needed to strengthen or negate its role.


Transcriptomic analysis reveals the GRAS family genes respond to gibberellin in Salvia miltiorrhiza hairy roots.
Salvia miltiorrhiza is one of the most important traditional Chinese medicinal plants with high medicinal value. Gibberellins are growth-promoting phytohormones that regulate numerous growth and developmental processes in plants. However, their role on the secondary metabolism regulation has not been investigated. In this study, we found that gibberellic acid (GA) can promote hairy roots growth and increase the contents of tanshinones and phenolic acids. Transcriptomic sequencing revealed that many genes involved in the secondary metabolism pathway were the GA-responsive. After further analysis of GA signaling pathway genes, which their expression profiles have significantly changed, it was found that the GRAS transcription factor family had a significant response to GA. We identified 35 SmGRAS genes in S. miltiorrhiza, which can be divided into 10 subfamilies. Thereafter, members of the same subfamily showed similar conserved motifs and gene structures, suggesting possible conserved functions. Most SmGRAS genes were significantly responsive to GA, indicating that they may play an important role in the GA signaling pathway, also participating in the GA regulation of root growth and secondary metabolism in S. miltiorrhiza.


Honeycomb-like structure of the intermediate layers of the rat superior colliculus, with additional observations in several other mammals: AChE patterning.
The aim of the present study was to reinvestigate the stereometric pattern of acetylcholinesterase (AChE) activity staining in the intermediate layers of the superior colliculus in several mammalian species. A pioneering study in the cat and the monkey by Graybiel (1978) stressed the regular arrangement of AChE staining in the deep collicular layers. According to her description, made in the frontal plane, the enzyme was arranged in a mediolateral series of patches, the cores of which tended to line up in the longitudinal axis of the structure, so they formed roughly parallel bands. As exhaustive a description as possible of the AChE distribution was undertaken in the rat by compiling observations in the frontal, sagittal, and tangential planes. It emerged that AChE-positive elements are organized in the form of a conspicuous honeycomb-like network that is divided into about 100 rounded compartments, over virtually the full extent of the intermediate layers. The generality of the rat model was then tested in other rodents such as mouse and hamster and also in cat and monkey. For these species we resorted to a single tangential cutting plane, which proved to be more appropriate for disclosing such a modular arrangement. The data revealed that in all species AChE staining followed the same architectural plan and identified the striking similarity in the number of compartments that compose the various honeycomb-like lattices. In conclusion, the present findings support a unified model of the AChE arrangement within the intermediate layers of the mammalian colliculus; the model comprehensively incorporates the classical description of the patchy and stripy features of the enzyme distribution. We hypothesize here that the modular AChE arrangement might be the anatomical basis for collicular vectorial encoding of orienting movements.


Ecology of Listeria monocytogenes in the environment of raw poultry meat and raw pork meat processing plants.
The zoonotic Listeria monocytogenes is mainly transmitted to humans by the food-borne route. This bacterium was often found in the environment of food processing plants. Therefore the aims of this study were (i) the identification of environmental factors associated with L. monocytogenes contamination on working and non-working surfaces in poultry or pork processing plants and (ii) the understanding of its survival in such environments. The physicochemical risk profiles showed that a surface in resin or plastic, rather than uneven, with organic residues, with a neutral pH, a low temperature and a high hygrometry was associated with L. monocytogenes contamination.


Preparation of holographic gratings of liquid crystals dispersed in polyurethane acrylates under controlled reaction conditions.
Transmission gratings of holographic polymer-dispersed liquid crystals (HPDLC) are prepared under controlled reaction conditions by adding various amounts of chain-transfer agent (CTA). The resulting films have a higher gel content with lower cross-link density, less dark reaction, less grating shrinkage with much smoother LC/polymer interfaces, smaller induction period, and fast saturation of diffraction efficiency, which shows a maximum of 95 % with 1 % CTA. An optimum LC content of 35 % is verified on the basis of morphology and reaction kinetics.


Efficacy of nasal high flow therapy on the coordination between breathing and swallowing of saliva during daytime nap in chronic obstructive pulmonary disease patients: A single center, randomized crossover controlled study.
There are some clinical reports on dysphagia in patients with chronic obstructive pulmonary disease (COPD); however, its pathophysiology remains largely unknown.Changes in respiratory function occur in patients with COPD causing a decrease in tidal volume and an increase in respiratory rate (tachypnea). In addition, it leads to lack of coordination between respiration and swallowing.A new treatment called nasal high flow (NHF) has been introduced for patients with COPD, replacing the traditional non-invasive ventilation (NIV) procedure. The NHF therapy involves inhalation of high flow of humidified air, which reduces respiratory effort in patients with COPD. Furthermore, NHF therapy facilitates swallowing of saliva even during respiratory management. A recent clinical study reported that high-flow nasal cannula oxygen therapy for 6 weeks improved the health-related quality of life and reduced hypercapnia in patients with stable COPD. Taken together, NHF therapy is gaining attention in the clinical management of patients with COPD.Therefore, in this study, we aim to examine the efficacy of NHF therapy on the coordination between breathing and swallowing of saliva during daytime nap in patients with COPD. This open-label, investigator-initiated, single center study will evaluate the efficacy of NHF therapy on the coordination between breathing and swallowing of saliva during the daytime nap in COPD patients with forced expiratory volume in 1 second (FEV1%) of <70% during treatment at the Nagasaki University Hospital Respiratory Rehabilitation Center. Evaluations will be performed during the 90 to 180 minute "daytime nap" in the measurement room of the hospital. The primary endpoint will be the rate of appearance of the expiratory phase after swallowing of saliva and the frequency of swallowing during the measurement period. The purpose of this study is to obtain evidence regarding the utility of NHF as a potential therapeutic device for COPD patients to prevent aspiration of saliva during the sleep stage of daytime nap. The utility will be assessed by comparing the decrease in incidence rates of the expiratory phase after swallowing of saliva in the NHF device group and the control group, wherein this device was not used.


Richard, Richard! Despite a new president, the American Hospital Association hopes the secret to continued success is staying the same.
Richard Umbdenstock arrives at his new position at the American Hospital Association with a definite agenda: Stay the course. "Continuity is a priority of the first order," says Umbdenstock, left, who was the only candidate considered for the president's job. "One of the reasons he was selected was because we felt the AHA was on the right path and doing well and we wanted the course to stay the same," says AHA Chairman-elect Kevin Lofton.


Widespread abundance of functional bacterial amyloid in mycolata and other gram-positive bacteria.
Until recently, extracellular functional bacterial amyloid (FuBA) has been detected and characterized in only a few bacterial species, including Escherichia coli, Salmonella, and the gram-positive organism Streptomyces coelicolor. Here we probed gram-positive bacteria with conformationally specific antibodies and revealed the existence of FuBA in 12 of 14 examined mycolata species, as well as six other distantly related species examined belonging to the phyla Actinobacteria and Firmicutes. Most of the bacteria produced extracellular fimbriae, sometimes copious amounts of them, and in two cases large extracellular fibrils were also produced. In three cases, FuBA was revealed only after extensive removal of extracellular material by saponification, indicating that there is integrated attachment within the cellular envelope. Spores of species in the genera Streptomyces, Bacillus, and Nocardia were all coated with amyloids. FuBA was purified from Gordonia amarae (from the cell envelope) and Geodermatophilus obscurus, and they had the morphology, tinctorial properties, and beta-rich structure typical of amyloid. The presence of approximately 9-nm-wide amyloids in the cell envelope of G. amarae was visualized by transmission electron microscopy analysis. We conclude that amyloid is widespread among gram-positive bacteria and may in many species constitute a hitherto overlooked integral part of the spore and the cellular envelope.


Convergent validity of the Agnew Relationship Measure and the Working Alliance Inventory.
The convergent validity of the Agnew Relationship Measure (ARM) and the Working Alliance Inventory (WAI) was assessed in samples drawn from 2 comparative clinical trials of time-limited psychotherapies for depression. In 1 sample, clients (n = 18) and therapists (n = 4) completed self-report versions of both measures after every session (n = 198). In the other sample, clients (n = 39) and therapists (n = 6) completed the ARM, and observers subsequently rated selected audiotaped sessions (n = 78) using the WAI. In both samples, the ARM's core alliance scales (Bond, Partnership, and Confidence) were correlated with the WAI's scales (Bond, Tasks, and Goals) strongly when assessed within client and therapist perspectives and, with some qualifications, moderately when assessed between client, therapist, and observer perspectives, supporting the assumption that the ARM and the WAI measure some of the same core constructs.


Associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and changes in tibiofemoral joint structures in patients with knee osteoarthritis.
To describe the longitudinal associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and joint structural changes in tibiofemoral compartments in patients with knee osteoarthritis (OA). The participants were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) study. PTFJ morphological parameters were measured on coronal and sagittal MRI. The contacting area (S) of PTFJ and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ), and coronal plane (posterior stress-bolstering area, Sυ) were assessed. Knee structural abnormalities, including cartilage defects, bone marrow lesions (BMLs), and cartilage volume, were evaluated at baseline and after 2 years. Log binominal regression models and linear regression models were used to assess the associations between PTFJ morphological parameters and osteoarthritic structural changes. In the longitudinal analyses, the S (RR: 1.45) and Sτ (RR: 1.55) of PTFJ were significantly and positively associated with an increase in medial tibial (MT) cartilage defects. The Sτ (β: - 0.07), Sυ (β: - 0.07), and S (β: - 0.06) of PTFJ were significantly and negatively associated with changes in MT cartilage volume. The Sτ (RR: 1.55) of PTFJ was positively associated with an increase in MT BMLs, and Sφ (RR: 0.35) was negatively associated with an increase in medial femoral BMLs. This longitudinal study suggests that higher load-bearing area of PTFJ could be a risk factor for structural changes in medial tibiofemoral (MTF) compartment in knee OA. Clinicaltrials.gov Identifier: NCT01176344 Anzctr.org.au Identifier: ACTRN12610000495022 Date of registration: 7 May 2010.


Plasticity of CYP2B enzymes: structural and solution biophysical methods.
In the past three years, major advances in understanding cytochrome P450 2B (CYP2B) structure-function relationships have been made through determination of multiple ligand-bound and one ligand-free X-ray crystal structure of CYP2B4 and one ligand-bound X-ray crystal structure of CYP2B6. These structures have provided insight into the features that provide the high degree of plasticity of the enzymes. A combination of a phenylalanine cluster that allows for concerted movement of helices F through G and a conserved set of electrostatic interactions involving Arg(262) facilitates movement of this region to accommodate binding of ligands of various sizes without perturbing most of the P450 fold. Integrating solution based techniques such as NMR or deuterium exchange mass spectrometry (DXMS) with computational methods including molecular docking has provided further insight into enzyme behavior upon ligand binding. In addition, extended molecular dynamics simulations have provided a link between an open and a closed conformation of ligand-free CYP2B4 found in crystal structures. Other studies revealed the utility of rational engineering in improving stability of P450s to facilitate structural studies. The solution and computational results combined with the X-ray crystal structures yield a comprehensive picture of how these enzymes adopt different conformations to bind various ligands.


Tobacco-related cancers in Poland in 1963-1989.
"In this paper we are presenting an epidemiological analysis of tobacco-related cancer risk in Poland in 1963-1989 and, in addition, etiological characteristics of the cancers." Data are from official sources. The results indicate that "standardized mortality rates had significantly increased for all tobacco-related cancer sites in 1963-1989."


Privileged substructure-based diversity-oriented synthesis pathway for diverse pyrimidine-embedded polyheterocycles.
A new diversity-oriented synthesis pathway for the fabrication of a pyrimidine-embedded polyheterocycles library was developed for potential interactions with diverse biopolymers. Five different pyrimidine-embedded core skeletons were synthesized from ortho-alkynylpyrimidine carbaldehydes by a silver- or iodine-mediated tandem cyclization strategy. The resulting polyheterocycles possess diverse fused ring sizes and positions with potential functionalities for further modification.


Potential new drug treatments for congestive heart failure.
The prevalence of heart failure (HF) has increased globally in recent decades. Advances in our understanding of underlying pathophysiologic mechanisms have given rise to new therapies for treating the growing HF population. Nonetheless, morbidity and mortality associated with HF and its financial implications are daunting. Thus, novel therapies that can improve the natural history of HF patients are urgently needed. This article reviews new investigational drugs being developed for the treatment of both acute decompensated heart failure (ADHF) and chronic heart failure with reduced ejection fraction (HFrEF). It presents the background of these drugs with a focus on their mechanism of action, their pharmacology, evidence from clinical studies and their potential role in HF management. The mortality benefit associated with serelaxin treatment in the RELAX-HF trial is being tested in RELAX-AHF II, while two other drugs, ularitide and TRV027, are also being evaluated in ADHF patients. Two new agents for the treatment of chronic HFrEF, LCZ696 and ivabradine, have been recently been approved for use by the FDA and four novel agents which have shown considerable promise in early studies, omecamtiv mecarbil, vericiguat, finerenone, and neuregulin, are currently being evaluated in late-phase clinical trials.