A SIMULATION OF WRIGHT'S SHIFTING-BALANCE PROCESS: MIGRATION AND THE THREE PHASES.
Wright partitioned the shifting-balance process into three phases. Phase one is the shift of a deme within a population to the domain of a higher adaptive peak from that of the historical peak. Phase two is mass selection within a deme towards that higher peak. Phase three is the conversion of additional demes to the higher peak. The migration rate between demes is critical for the existence of phases one and three. Phase one requires small effective population sizes, hence low migration rates. Phase three is optimal under high migration rates that spread the most-fit genotype from deme to deme. Thus, a population-wide peak shift requires intermediate levels of migration. By altering the rates of phases one and three, migration affects the predominant direction of mass selection within a population. This study examines the degree to which migration, through its effects on phases one and three, determines the probability of a simulated population arriving at its genotypic optimum after 12,000 generations. These simulations reveal that there is a range of migration rates for which an entire population might be expected to shift to a higher peak. Below m = 0.001 peak shifts occur frequently (phases I and II) but are not successfully exported out of subpopulations (phase III), and above 0.01 peak shifts within demes (phase I and II), required to initiate phase III, become increasingly uncommon. Because it is unlikely that real populations will have uniform migration rates from generation to generation, the probable effects of varying migration rates on broadening the range of conditions producing peak shifts are discussed.


Measurement and meaningfulness in conservation science.
Incomplete databases often require conservation scientists to estimate data either through expert judgment or other scoring, rating, and ranking procedures. At the same time, ecosystem complexity has led to the use of increasingly sophisticated algorithms and mathematical models to aid in conservation theorizing, planning, and decision making. Understanding the limitations imposed by the scales of measurement of conservation data is important for the development of sound conservation theory and policy. In particular, biodiversity valuation methods, systematic conservation planning algorithms, geographic information systems (GIS), and other conservation metrics and decision-support tools, when improperly applied to estimated data, may lead to conclusions based on numerical artifact rather than empirical evidence. The representational theory of measurement is described here, and the description includes definitions of the key concepts of scale, scale type, and meaningfulness. Representational measurement is the view that measurement entails the faithful assignment of numbers to empirical entities. These assignments form scales that are organized into a hierarchy of scale types. A statement involving scales is meaningful if its truth value is invariant under changes of scale within scale type. I apply these concepts to three examples of measurement practice in the conservation literature. The results of my analysis suggest that conservation scientists do not always investigate the scale type of estimated data and hence may derive results that are not meaningful. Recognizing the complexity of observation and measurement in conservation biology, and the constraints that measurement theory imposes, the examples are accompanied by suggestions for informal estimation of the scale type of conservation data and for conducting meaningful analysis and synthesis of this information.


Synthesis, Characterization, and Stability of Dealkylated Salen-Supported Aluminum Phosphates.
Three salen aluminum bromide compounds salen(tBu)AlBr (1) (salen = N,N'-ethylenebis(3,5-di-tert-butylsalicylideneimine)), salpen(tBu)AlBr (2) (salpen = N,N'-propylenebis(3,5-di-tert-butylsalicylideneimine)), and salophen(tBu)AlBr (3) (salophen = N,N'-o-phenylenenebis(3,5-di-tert-butylsalicylideneimine) were evaluated for their potential use as dealkylation agents with a series of organophosphates. These reactions led to the aluminum phosphate compounds containing six-coordinate aluminum centers and hydrolytically stable P-O-C bonds: 4 = [salen(tBu)AlOP(O)(OMe)2]n, 5 = [salen(tBu)AlOP(O)(OEt)2]n, 6 = [salen(tBu)AlOP(O)(OPh)2]n, 7 = [salophen(tBu)AlOP(O)(OMe)2]n, 8 = [salpen(tBu)AlOP(O)(OiPr)2]2, 9 = (salen(tBu)AlO)3PO, 10 = (salpen(tBu)AlO)3PO, 11 = (salophen(tBu)AlO)3PO. All the compounds were characterized by 1H, 13C, 27Al, and 31P NMR, IR, and mass spectrometry. Furthermore, compounds 4-8 were structurally characterized by single-crystal X-ray diffraction. The potential hydrolysis of these compounds was modeled with 4 and demonstrated the unique stability of the final product and ease of isolation.


Methotrexate inhibits effects of platelet-derived growth factor and interleukin-1β on rheumatoid arthritis fibroblast-like synoviocytes.
A key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro. Primary FLS from patients with RA or osteoarthritis were stimulated with the mitogen platelet-derived growth factor (PDGF) and the cytokine interleukin-1β (IL-1β) in the presence or absence of MTX. Cells were then subjected to qPCR for gene expression and cell cycle analysis by flow cytometry. Stimulation with PDGF and IL-1β increased the percentage of FLS in the G2/M phase and shifted the cell morphology to a dendritic shape. These effects were inhibited by MTX. Furthermore, PDGF + IL-1β reduced LBH mRNA expression. However, MTX treatment yielded significantly higher transcript levels of LBH, and of CDKN1A (p21) and TP53 (p53), compared to untreated samples upon mitogen stimulation. The expression of DNA methyltransferase-1 (DNMT1) was also higher in the presence of MTX and there was strong correlation between DNMT1 and LBH expression. Therapeutic concentrations of MTX abolish the effects of PDGF and IL-1β on tumor suppressor expression and inhibit mitogen-promoted FLS proliferation. These data demonstrate novel and important effects of MTX on pathogenic effector cells in the joint, which might involve epigenetic mechanisms.


Signatures of Conformational Dynamics and Electrode-Molecule Interactions in the Conductance Profile During Pulling of Single-Molecule Junctions.
We demonstrate that conductance can act as a sensitive probe of conformational dynamics and electrode-molecule interactions during the equilibrium and nonequilibrium pulling of molecular junctions. To do so, we use a combination of classical molecular dynamics simulations and Landauer electron transport computations to investigate the conductance of a family of Au-alkanedithiol-Au junctions as they are mechanically elongated. The simulations show an overall decay of the conductance during pulling that is due to a decrease in the through-space electrode-molecule interactions, and that sensitivity depends on the electrode geometry. In addition, characteristic kinks induced by level alignment shifts (and to a lesser extent by quantum destructive interference) were also observed superimposed to the overall decay during pulling simulations. The latter effect depends on the variation of the molecular dihedral angles during pulling and therefore offers an efficient solution to experimentally monitor conformational dynamics at the single-molecule limit.


[Effectiveness of antihypertensive conservative-free therapy with fixed combination of bimatoprost and timolol (intermediate results)].
The effects of antihypertensive therapy are often determined by patient compliance with the prescribed treatment plan. Acceptance of conservative-free forms of drugs leads to a decrease in the frequency and severity of side effects, reduces the need for the use of artificial tears, which lowers the cost of treatment for the patients. to evaluate the hypotensive effectiveness of a fixed combination of bimatoprost (0.03%) and timolol (0.5%), and its effect on the ocular surface in patients with newly diagnosed advanced glaucoma. The study was conducted during February-November 2018, and included 46 patients (76 eyes) with newly diagnosed POAG and healthy volunteers (control group). All patients underwent visometry, ICare rebound tonometry (Tiolat, Finland), elastometry with Maklakov tonometer (using 5 g, 10 g and 15 g loads), automated perimetry (AP) (Octopus-600, Haag-Streit diagnostics, Switzerland), optical coherence tomography (OCT) of the macular zone and optic nerve head, pachymetry (Spectralis OCT, Heidelberg Engineering, Germany). At the start of the study and one month after the start of treatment with the drug Ganfort (Allergan, USA), patients were examined to evaluate the state of their ocular surface: Norn's test, Schirmer's test, vital staining with lissamine green, and an OSDI questionnaire. At the start of treatment, administration of a fixed combination of bimatoprost and timolol led to a decrease in intraocular pressure by 7.9 (37.7%) mm Hg (V=271, p=5.496e-05) after 2 weeks of the use of Ganfort (Allergan, USA). During this period, the observation group did not exhibit statistically significant changes in the state of the ocular surface, which was comparable to the control group according to the data of the Norn's test, Schirmer's test, vital staining with lissamine green and the OSDI questionnaire (p>0.05). The use of a fixed combination of bimatoprost and timolol, while effectively reducing IOP, did not result in statistically significant changes in the ocular surface. Some improvement of both objective and subjective indicators of the state of ocular surface associated with the use of the Ganfort drug was noted in patients of the observation group.


Risk factors for women attending pre-pregnancy screening in selected clinics in Selangor.
The Ministry of Health is committed to achieve Millenium Development Goal (MDG) MDG 4 and 5 by 2015 and include pre-pregnancy care as a strategy. This study evaluates the risk factors detected during the pre-pregnancy screening at selected public primary care clinics in Selangor. The objectives of this study were to determine the proportion of women with risk factors receiving pre-pregnancy care in selected clinics in Selangor, their socio demographic features, the types of risk factors detected and their significance. A retrospective review using secondary data was carried out from the month of March until June 2013 in four public primary care clinics in Klang and Petaling districts of Selangor. Data were obtained through non-probability sampling, using the pre-pregnancy screening form utilised in 2012, which is a standard questionnaire to determine the presence of risk factors. Women with at least one defined risk factor were considered as being at risk of an adverse obstetric outcome. Data were analysed using SPSS version 16. A total of 840 pre-pregnancy screening forms were collected. However only 614 (73.1%) were analysed and studied. The proportion of women with at least one risk factor was 68.8% (95% CI: 65.1, 72.5). The majority was Malays who had tertiary education and earned more than RM 1000. Most were in the reproductive age group of 18-35 years old (350, 82.9%). The mean age was 28.68 + 5.78 years. Most of the women were parous (259, 65.1%) and did not practice any form of contraception (308, 80.8%) despite having risks. The percentage of those not receiving any form of immunisation was small i.e. 9.8% but it was of importance and needed to be addressed prior to the conception. This study did not reveal any person with mental disorder or those who endured domestic abuse. Additionally, 3% (12) of them had unhealthy lifestyle habits, which include smoking, alcohol and substance abuse. Approximately one-third (212, 35.2%) of the women screened were overweight and obese, putting them at risk of developing gestational diabetes mellitus, pregnancy induced hypertension or deep vein thrombosis. The mean body mass index (BMI) for those at risk was 25.36 + 5.94 compared to 21.06 ± 1.46 for those with no risk. This study also found a small percentage of women with raised blood pressure (3.9%), abnormal physical examination (1.5%) and anaemia (14.4%), which need to be investigated and treated prior to conception. More than half of the women who attended the pre-pregnancy screening were found to have at least one risk factor.


Species Persistence with Hybridization in Toad-Headed Lizards Driven by Divergent Selection and Low Recombination.
Speciation plays a central role in evolutionary studies, and particularly how reproductive isolation (RI) evolves. The origins and persistence of RI are distinct processes that require separate evaluations. Treating them separately clarifies the drivers of speciation and then it is possible to link the processes to understand large-scale patterns of diversity. Recent genomic studies have focused predominantly on how species or RI originate. However, we know little about how species persist in face of gene flow. Here, we evaluate a contact zone of two closely related toad-headed lizards (Phrynocephalus) using a chromosome-level genome assembly and population genomics. To some extent, recent asymmetric introgression from Phrynocephalus putjatai to P. vlangalii reduces their genomic differences. However, their highly divergent regions (HDRs) have heterogeneous distributions across the genomes. Functional gene annotation indicates that many genes within HDRs are involved in reproduction and RI. Compared with allopatric populations, contact areas exhibit recent divergent selection on the HDRs and a lower population recombination rate. Taken together, this implies that divergent selection and low genetic recombination help maintain RI. This study provides insights into the genomic mechanisms that drive RI and two species persistence in the face of gene flow during the late stage of speciation.


Subcellular localisation of Theiler's murine encephalomyelitis virus (TMEV) capsid subunit VP1 vis-á-vis host protein Hsp90.
The VP1 subunit of the picornavirus capsid is the major antigenic determinant and mediates host cell attachment and virus entry. To investigate the localisation of Theiler's murine encephalomyelitis virus (TMEV) VP1 during infection, a bioinformatics approach was used to predict a surface-exposed, linear epitope region of the protein for subsequent expression and purification. This region, comprising the N-terminal 112 amino acids of the protein, was then used for rabbit immunisation, and the resultant polyclonal antibodies were able to recognise full length VP1 in infected cell lysates by Western blot. Following optimisation, the antibodies were used to investigate the localisation of VP1 in relation to Hsp90 in infected cells by indirect immunofluorescence and confocal microscopy. At 5h post infection, VP1 was distributed diffusely in the cytoplasm with strong perinuclear staining but was absent from the nucleus of all cells analysed. Dual-label immunofluorescence using anti-TMEV VP1 and anti-Hsp90 antibodies indicated that the distribution of both proteins colocalised in the cytoplasm and perinuclear region of infected cells. This is the first report describing the localisation of TMEV VP1 in infected cells, and the antibodies produced provide a valuable tool for investigating the poorly understood mechanisms underlying the early steps of picornavirus assembly.


Effect of nedocromil sodium on adenosine- and methacholine-induced bronchospasm in asthma.
The effect of nedocromil sodium on adenosine-induced bronchospasm was investigated in eight asthmatic patients. Nedocromil sodium (4 mg) administered by aerosol 10 min before challenge, effectively inhibited adenosine-induced bronchospasm. In another group of six asthmatic patients, nedocromil sodium administered in the same way did not reduce the bronchial response to methacholine. These results support the view that adenosine-induced bronchospasm may be prevented by a membrane stabilizing drug and is not mediated through cholinergic pathways. The mechanism(s) by which nedocromil sodium inhibits adenosine-induced bronchospasm requires further investigations.


Comparative analysis of stalked and acorn barnacle adhesive proteomes.
Barnacles interest the scientific community for multiple reasons: their unique evolutionary trajectory, vast diversity and economic impact-as a harvested food source and also as one of the most prolific macroscopic hard biofouling organisms. A common, yet novel, trait among barnacles is adhesion, which has enabled a sessile adult existence and global colonization of the oceans. Barnacle adhesive is primarily composed of proteins, but knowledge of how the adhesive proteome varies across the tree of life is unknown due to a lack of genomic information. Here, we supplement previous mass spectrometry analyses of barnacle adhesive with recently sequenced genomes to compare the adhesive proteomes of Pollicipes pollicipes (Pedunculata) and Amphibalanus amphitrite (Sessilia). Although both species contain the same broad protein categories, we detail differences that exist between these species. The barnacle-unique cement proteins show the greatest difference between species, although these differences are diminished when amino acid composition and glycosylation potential are considered. By performing an in-depth comparison of the adhesive proteomes of these distantly related barnacle species, we show their similarities and provide a roadmap for future studies examining sequence-specific differences to identify the proteins responsible for functional differences across the barnacle tree of life.


Biotinyl and phosphotyrosinyl phosphoramidite derivatives useful in the incorporation of multiple reporter groups on synthetic oligonucleotides.
Non-nucleosidic phosphoramidite linker units suitable for use on commercial DNA synthesis machines have been designed for the direct incorporation of biotin and a new reporter group, phosphotyrosine, at multiple sites on synthetic oligonucleotides. The units are based on a 3-carbon glyceryl backbone where the reporter group is attached to the 2-O-position through a 3-aminopropyl spacer. 17-mer oligonucleotides were synthesized carrying at the 5'-end 1, 2, 4 or 8 biotinyl units or 1, 2, 4 or 8 phosphotyrosinyl units respectively and used for the detection of DNA on nitrocellulose filters by hybridization. Subsequent incubation of the filters with a monoclonal antibody to the reporter group followed by secondary detection using enhanced chemiluminescence (ECL) resulted in amplification of signal strengths as the number of reporter groups was increased. The results were quantitated by use of a charge couple device (CCD) camera. Spacing of biotin moieties by thymidyl residues resulted in further improvements in signal strengths, whereas similar spacing of phosphotyrosinyl units did not.


Functional responses of cougars (Puma concolor) in a multiple prey-species system.
The study of predator-prey interactions is commonly analyzed using functional responses to gain an understanding of predation patterns and the impact they have on prey populations. Despite this, little is known about predator-prey systems with multiple prey species in sites near the equator. Here we studied the functional response of cougars (Puma concolor) in relation to their main prey, armadillo (Dasypus novemcinctus), coati (Nasua narica) and white-tailed deer (Odocoileus virginianus). Between 2004 and 2010, cougar scats were collected along 5 transects to estimate the consumption of different prey species. A relative abundance index (RAI) was calculated for each prey species and cougar using 18 camera traps. We compared Holling type I, II and III functional response models to determine patterns in prey consumption based on the relative abundance and biomass of each prey species consumed. The 3 main prey species comprised 55% (armadillo), 17% (coati) and 8% (white-tailed deer) of the diet. Type I and II functional responses described consumption of the 2 most common prey species armadillos and coati similarly well, while a type I response best characterized consumption of white-tailed deer. A negative correlation between the proportions of armadillo versus coati and white-tailed deer biomass in cougar scats suggests switching to consume alternative prey, confirming high foraging plasticity of this carnivore. This work represents one of the few studies to compare functional responses across multiple prey species, combined with evidence for prey-switching at low densities of preferred prey.


Potential Effects of Digoxin on Renal Functions in Patients With Congestive Heart Failure.
Renal dysfunction is a common complication among patients with congestive heart failure (CHF) and can significantly impact their management, especially when medications like digoxin are involved. The clearance of digoxin is closely tied to the glomerular filtration rate (GFR), which suggests that the safety and efficacy of digoxin may vary with renal function. Therefore, this study aimed to assess the potential effects of digoxin on renal function in patients diagnosed with CHF at a tertiary hospital in the Asir region of Saudi Arabia. A retrospective study examined the records of 30 CHF patients treated with digoxin. Renal function markers like estimated GFR (eGFR), creatinine, blood urea nitrogen (BUN), albumin, and urine levels were compared before and after digoxin treatment. Liver enzymes and other relevant parameters were also examined. A statistical analysis using t-tests was conducted to evaluate the changes in renal function indicators before and after digoxin treatment. The mean eGFR decreased significantly from 65.4 ± 8.9 mL/min/1.73m2 before digoxin to 57.7 ± 7.8 mL/min/1.73m2 after (p = 0.001). Creatinine, BUN, albumin, and urine levels showed no significant changes. Digoxin significantly increased aspartate aminotransferase (AST) from 34.5 ± 11.6 U/L to 53.8 ± 14.6 U/L (p = 0.002), alanine aminotransferase (ALT) from 38.5 ± 12.6 U/L to 55.3 ± 17.6 U/L (p = 0.013), and creatine kinase from 117.7 ± 22.5 U/L to 133.9 ± 15.8 U/L (p = 0.012). Hemoglobin decreased significantly from 12.8 ± 1.4 g/dL to 12.1 ± 1.4 g/dL (p = 0.034). No significant changes occurred in myoglobin, troponin, bilirubin, platelets, potassium, calcium, or chloride levels. Effects on kidney function did not differ significantly by gender or age, except blood urea nitrogen was higher in patients over 50 years (8.3 ± 2.3 vs. 5.6 ± 2.7 mg/dL, p = 0.015). This study suggests digoxin may adversely affect renal function in CHF patients, as evidenced by reduced eGFR. However, the small retrospective design limits definitive conclusions. Further prospective research with larger samples is warranted to elucidate digoxin's renal effects in CHF patients.


Vanished: Is This for Real?
Spontaneous regression (SR) of lung cancer is especially rare. We report a case of an early endobronchial squamous cell carcinoma that exhibited complete radiologic and pathologic SR soon after diagnosis. The patient was monitored radiologically and bronchoscopically at regular intervals and to date, the biopsy samples have been negative. Remarkably, SR has been maintained 6 years after diagnosis, without local recurrence or distant metastases. Many hypotheses abound to explain how complete SR was achieved and maintained despite the lack of treatment.


Cancer mortality among magazine printing workers.
After an inquiry from the employees of an offset printing plant, a historical cohort study was conducted to investigate cancer mortality among these workers. The cohort comprised 262 men, who contributed 2771 person-years of observation. 16 deaths were identified during the follow up period (1980-91). Expected numbers of deaths were derived from age specific regional rates. Standardised mortality ratios (SMR) and 95% confidence intervals (95% CIs) were calculated. An increased cancer mortality was found after 10 years of employment (SMR 213, 95% CI 98 to 405, based on nine deaths), mainly due to a high mortality from lung cancer (SMR 381, 95% CI 104 to 975, four deaths), and from oesophageal cancer (SMR 1049, 95% CI 216 to 3065, three deaths). For workers with at least 20 years since the start of employment, the SMR was 262 (95% CI 105 to 540) for all cancer sites, 447 (95% CI 92 to 1306) for lung cancer, and 1094 (95% CI 132 to 3952) for oesophageal cancer. The increased cancer mortality was concentrated among pressmen. Although based on small numbers, the findings suggest an increased risk of cancer among these workers, which should be further investigated.


[Comorbidity/polymorbidity - problems of terminology and application of index indicators (review).]
The review presents a literature analysis on controversial issues of the use of the terms polymorbidity, multimorbidity, comorbidity. Increasing publication activity on the topic of comorbidity/multimorbidity is noted. The main discussion is conducted in several areas: what term should be used - comorbidity, multimorbidity or polymorbidity; use or not use index indicators of comorbidity; if used, specifically for what purpose; what is the effectiveness of these indicators. It is concluded, that many issues have not yet been resolved and further research is needed on this issue. It is time to define terminology and specify WHERE and WHEN comorbidity/polymorbidity indexes are needed.


Robust multifunctional fluorine-free superhydrophobic fabrics for high-efficiency oil-water separation with ultrahigh flux.
The limited robustness and complex preparation process greatly hinder the large-scale use of superhydrophobic surfaces in real life. In this work, we adopt a simple method to prepare robust fluorine-free superhydrophobic cotton fabrics by a facile dip-coating method based on silica microparticles and titanium dioxide nanoparticles. Microparticles and nanoparticles are used to build a suitable rough hierarchical structure, while strong bonds are formed between fabric and particles by a silane coupling agent. The cross-linking reaction between the isocyanate group of trimers of hexamethylene diisocyanate (HDI) and the hydroxyl group of each component in the condensation reaction further increases the bonding between the coating and the cotton fabric. In addition, polydimethylsiloxane (PDMS) is used as a low-surface-energy material to modify the fabric surface. The resulting coating shows excellent superhydrophobic properties with a water contact angle of 161.7°. Meanwhile, the prepared superhydrophobic fabric exhibits excellent durability and stability after sandpaper wearing, washing, and UV radiation, as well as treatment with various organic solutions, boiling water and different pH solutions. Moreover, the superhydrophobic fabric displays excellent UV protection performance and high oil-water separation efficiency (>99% after 30 cycles) with ultrahigh flux up to 20 850 L m-2 h-1.


[Atypical ultrasound picture of pleomorphic adenoma].
Presentation of an atypical sonomorphology in a case of pleomorphic adenoma of the parotid gland. The tumour was resected and worked up for histological examination. The results emphasise the difficulty of differentiating the subtypes of parotid neoplasms by ultrasonography alone.


New horizons in therapeutic antibody discovery: opportunities and challenges versus small-molecule therapeutics.
Antibody drugs have become an increasingly significant component of the therapeutic landscape. Their success has been driven by some of their unique properties, in particular their very high specificity and selectivity, in contrast to the off-target liabilities of small molecules (SMs). Antibodies can bring additional functionality to the table with their ability to interact with the immune system, and this can be further manipulated with advances in antibody engineering. This review summarizes what antibody therapeutics have achieved to date and what opportunities and challenges lie ahead. The target landscape for large molecules (LMs) versus SMs and some of the challenges for antibody drug development are discussed. Effective penetration of membrane barriers and intracellular targeting is one challenge, particularly across the highly resistant blood-brain barrier. The expanding pipeline of antibody-drug conjugates offers the potential to combine SM and LM modalities in a variety of creative ways, and antibodies also offer exciting potential to build bi- and multispecific molecules. The ability to pursue more challenging targets can also be further exploited but highlights the need for earlier screening in functional cell-based assays. I discuss how this might be addressed given the practical constraints imposed by high-throughput screening sample type and process differences in antibody primary screening.


Apolipoprotein A-V gene polymorphism -1131T>C and Alzheimer's disease.
Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly and is also considered a progeroid genetic syndrome. The etiology of AD is complex and the mechanisms underlying its pathophysiology remain to be clarified. It has been suggested that a high serum cholesterol level is a risk factor for (AD), and that some polymorphisms of genes encoding proteins regulating cholesterol metabolism are associated with AD development. APOA5 is a recently discovered apolipoprotein involved primarily with triglyceride (TG) metabolism disorder. This study investigates the association of AD with the APOA5 gene -1131T>C polymorphisms in samples of 106 patients with Alzheimer's disease (AD), 76 elderly healthy controls and 93 young healthy controls. DNA samples were isolated from blood cells, amplified by PCR and digested with Tru1l. We observed that the genotype distributions of APOA5 variants were within Hardy-Weinberg equilibrium in all subject samples. Furthermore, chi-square test comparison for genotype distributions and allele frequencies did not reveal any significant difference among the three groups of subjects P>0.05). These results support the idea that these variants are not involved as a risk factor for developing AD.


Effect of Lung Compliance-Based Optimum Pressure Versus Fixed Positive End-Expiratory Pressure on Lung Atelectasis Assessed by Modified Lung Ultrasound Score in Laparoscopic Gynecological Surgery: A Prospective Randomized Controlled Trial.
Lung protective ventilation during the intraoperative period is now well established. However, the additional role of positive end-expiratory pressure (PEEP) during the intraoperative period remains uncertain in major laparoscopic gynecological surgery. The authors hypothesized that compliance-based optimum PEEP titration reduces postoperative lung atelectasis and improves outcomes. Patients undergoing major laparoscopic pelvic gynecological surgeries with healthy lungs were randomized to the fixed PEEP group (PEEP 5 cm H2O and recruitment maneuver {RM}) and optimum PEEP group (compliance-based PEEP and RM). Lung ultrasound and arterial blood gas analysis were performed at four time points. Modified lung ultrasound scoring was done, and the same was used as means of assessing lung aeration and the amount of lung atelectasis. Postoperative supplemental oxygen requirement and duration were also assessed and compared. Lung ultrasound score (LUS) 30 minutes after extubation in fixed (Group F) and optimum (Group O) PEEP groups were median (interquartile range {IQR}) 3 (2-3) versus 1 (1-2), p=0.0001. Ventilatory parameters between Group F and Group O after lung recruitment were tidal volume (mean 357 mL {SD: 35} versus 362 mL {SD: 22}, p=0.46), PEEP (median, 5 cm H2O {IQR: 5-5} versus median 16 cm H2O {IQR: 14-18}), peak airway pressure (median 26 cm H2O {IQR: 24-28} versus median 30 cm H2O {IQR: 28-32} p<0.0001), plateau pressure (median 22 cm H2O {IQR: 20-24} versus median 26 cm H2O {IQR: 24-28} p<0.0001), static compliance (32.07±8.36 mL cm H2O-1 versus 39.58±8.99 mL cm H2O-1, p=0.0002). The number of patients requiring postoperative oxygen therapy to maintain SpO2 >94% after extubation in postanesthesia care unit (PACU) was statistically significantly greater in group F (39/41 {95%} versus 30/41 {73%}, p=0.007). Median (IQR) duration of oxygenation therapy in the first 24 hours of the postoperative period between Group F and Group O differed with statistical significance, with the median (IQR) values being 25 (20-30) minutes versus 10 (0-15) minutes (p<0.0001). The modified lung ultrasound score significantly differed intraoperatively between the two groups, with lower scores in the optimum PEEP group. This has reflected improved postoperative outcomes in optimum PEEP group patients, with fewer patients requiring postoperative oxygen supplementation and reduced supplemental oxygen requirement duration.


Synthetic bivalent CD4-mimetic miniproteins show enhanced anti-HIV activity over the monovalent miniprotein.
HIV-1 envelope glycoprotein gp120 is displayed as a trimeric complex on the surface of virion and infected T-cells, making it a typical multivalent target. This paper describes the design and synthesis of bivalent CD4-mimetic miniproteins to target the conserved CD4-binding pockets in the trimeric gp120. Using miniprotein CD4M9 as the model inhibitor, we created bivalent inhibitors in which two CD4M9 moieties were tethered by a spacer of varied length and evaluated their anti-HIV activity using a cell culture assay. The synthetic bivalent miniproteins showed 5-21-fold enhancement in anti-HIV activity over the monovalent miniprotein. The activity enhancement is dependent on the length of the spacer. The study suggests that targeting the oligomeric gp120 complex by novel multivalent ligands offers a valuable strategy for developing highly specific and effective HIV entry inhibitors.


Idiopathic brachial neuritis.
Idiopathic brachial neuritis is a well defined clinical condition that most commonly affects young adults, seen usually by primary care physicians, neurologists or orthopaedic surgeons. Its onset is characterized by acute, aching shoulder pain lasting a few days to weeks, followed by progressive shoulder girdle and upper extremity weakness and atrophy, with a slow but progressive recovery of motor function over 6 to 18 months. Its early recognition can help avoid unnecessary and potentially harmful diagnostic and therapeutic interventions, and avoid delays in prescribing appropriate therapies that may be helpful only early in the course of the disease. We present a case of idiopathic brachial neuritis and discuss important aspects of the disease and difficulties in reaching the correct diagnosis.


What Is Engagement? Proactivity as the Missing Link in the HEXACO Model of Personality.
We tested the hypothesis that proactivity represents the engagement vector in the HEXACO model of personality. Questionnaire data were obtained in five studies, three of which consisted (mostly) of students: Study 1 (N = 188, Mage = 20.0, 89.4% women), Study 3 (N = 315, Mage = 20.4, 80.6% women), and Study 4 (N = 309 self-ratings, Mage = 20.0, 78.3% women; N = 307 other-ratings, Mage = 24.5, 62.2% women). Participants in the other two studies came from an ISO-certified representative community panel: Study 2 (N = 525, Mage = 51.2, 52.0% women) and Study 5 (N = 736, Mage = 42.2, 48.0% women). Proactive Personality and Proactivity were positively related to Extraversion, Conscientiousness, and Openness to Experience, but only weakly related or unrelated to Honesty-Humility, Emotionality, and Agreeableness, supporting the alignment of Proactive Personality/Proactivity with the hypothesized HEXACO engagement vector. Additionally, Proactivity explained incremental variance in self-rated job performance on top of the HEXACO facets that were most closely associated with Proactive Personality/Proactivity, that is, Social Boldness (an Extraversion facet), Diligence (a Conscientiousness facet), and Creativity (an Openness to Experience facet), but not in entrepreneurship and intrapreneurship. Proactivity is the missing engagement link in the HEXACO model of personality. The results are discussed in light of higher-order factors (e.g., general factor of personality and Alpha and Beta) of personality and bandwidth-fidelity controversies.


Inositol and phosphatidylinositol mediated mediated glucose derepression, gene expression and invertase secretion in yeasts.
Glucose repression occurs in many yeast species and some filamentous fungi, and it represses the expression and secretion of many intracellular and extracellular proteins. In recent years, it has been found that many biochemical reactions in yeast cells are mediated by phosphatidylinositol (PI)-type signaling pathway. However, little is known about the relationships between PI-type signaling and glucose repression, gene expression and invertase secretion in yeasts. Many evidences in our previous studies showed that glucose repression, invertase secretion, gene expression and cell growth were mediated by inositol and PI in Saccharomyces and Schizosaccharomyces. The elucidation of the new regulatory mechanisms of protein secretion, gene expression and glucose repression would be an entirely new aspect of inositol and PI-type signaling regulation in yeasts.


Reactions of the NO redox forms NO+, *NO and HNO (protonated NO-) with the melatonin metabolite N1-acetyl-5-methoxykynuramine.
The different NO redox forms, NO+, *NO and HNO (=protonated NO-), were compared for their capabilities of interacting with the melatonin metabolite N1-acetyl-5-methoxykynuramine (AMK), using NO+SbF6-, PAPA-NONOate and Angeli's salt as donors of the respective NO species. Particular attention was paid to stability and possible interconversions of the redox forms. *NO formation was followed by measuring the decolorization of 2-(trimethylammonio-phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (TMA-PTIO), at different pH values, at which NO+ is, in aqueous solution, either highly unstable (pH 7.4) or relatively stable (pH 2.0). *NO donation by PAPA-NONOate, as indicated by TMA-PTIO decolorization, was similar at either pH and 3-acetamidomethyl-6-methoxycinnolinone (AMMC) was formed as the major product from AMK, at pH 7.4 more efficiently than at pH 2.0. At pH 2.0, TMA-PTIO decolorization by NO+SbF6- was much weaker than by PAPA-NONOate, but AMMC was produced at substantial rates, whereas neither TMA-PTIO decolorization nor AMMC formation was observed with the NO+ donor at pH 7.4. As NO+ is also stable in organic, especially aprotic solvents, NO+SbF6- was reacted with AMK in acetonitrile, ethanol, butanol, and ethyl acetate. In all these cases, AMMC was the only or major product. In ethyl acetate, N1-acetyl-5-methoxy-3-nitrokynuramine (AMNK) was also formed, presumably as a consequence of organic peroxides emerging in that solvent. Presence of tert-butylhydroperoxide in an ethanolic solution of NO+SbF6- and AMK also resulted in AMNK formation, in addition to AMMC and two red-fluoresecent, to date unknown products. However, hydrogen peroxide enhanced *NO-dependent AMMC production from AMK and also from N1-acetyl-N2-formyl-5-methoxykynuramine. HNO donation by Angeli's salt (Na2N2O3) also caused AMMC formation from AMK at pH 7.4, with a somewhat lower efficiency than PAPA-NONOate, but no AMNK nor any other product was detected. Therefore, all three NO congeners are, in principle, capable of nitrosating AMK and forming AMMC, but in biological material the reaction with NO+ is strongly limited by the extremely short life-time of this redox form.


Perceptions of mental health nurses and patients about health promotion in mental health care: a literature review.
The aim of this review was to examine the perceptions of patients with mental disorders and mental health nurses of health promotion targeting physical activity and eating habits in mental health care. An electronic search strategy was conducted. Furthermore, references were searched by hand-searching the reference lists of the retrieved articles from the electronic databases. The literature on perceptions of health promotion and lifestyle interventions in mental health care principally consist of qualitative studies using interviews and focus groups. Positive perceptions of both mental health nurses and patients towards health promotion targeting physical activity and eating habits in mental health care were identified. Contrary, several barriers for integrating healthy lifestyles into the daily life of patients were described. Patients usually want to learn more about healthy lifestyles, but see the ability to change their physical health as beyond their control. In this sense, support from mental health nurses is considered as important. Despite the awareness of the importance of health promotion in mental health care, it appears that visions and attitudes towards the potential of health promotion are in need of change.


Membrane IL-1 induces bone resorption in organ culture.
We have studied the role of the membrane-associated form of IL-1 on bone resorption in vitro. Murine macrophages of the P388D1 cell line stimulated with LPS, subsequently fixed with paraformaldehyde, induced the proliferation of C3H/HeJ mouse thymocytes in the presence of a submitogenic concentration of Con A. Membrane IL-1 on P388D1 cells stimulated with LPS induced bone resorption in organ cultures of neonatal BALB/c mouse calvaria. Polyclonal antibodies directed against membrane IL-1 and soluble IL-1 from P388D1, and monospecific rabbit anti-murine rIL-1 alpha serum neutralized the membrane IL-1 activity, as measured by the thymocyte proliferation. In addition, these antibodies suppressed the bone resorption induced by membrane IL-1. The bone resorption induced by membrane IL-1 required direct contact between mouse calvaria and membrane IL-1. Salmon calcitonin strongly suppressed the calcium release from mouse calvaria in the presence of membrane IL-1. Indomethacin partially inhibited the bone resorption induced by membrane IL-1 on P388D1 cells. Moreover, membrane IL-1 on LPS-stimulated BALB/c mouse peritoneal macrophages or LPS-stimulated osteoblastic cells from BALB/c mouse calvaria induced bone resorption in vitro. These results suggest that membrane IL-1 on macrophages and osteoblastic cells may have a significant role in inflammatory bone resorption in vivo.


Intrinsic spinal cord lesions in 2 patients with ankylosing spondylitis.
Two men with longstanding ankylosing spondylitis (AS) developed spastic paraparesis. Extensive investigation failed to find a cause and it was concluded that some acute undetermined intrinsic spinal cord lesion had occurred. Similar descriptions in the past have been attributed to associated multiple sclerosis, but we suggest that the finding may represent a rare complication of AS with an unknown etiology.


Crystallization and preliminary crystallographic characterization of aspartic proteinase-A from baker's yeast and its complexes with inhibitors.
The aspartic proteinase from yeast vacuoles, proteinase-A, has been crystallized with and without non-hydrolysable transition-state analogue inhibitors. The native enzyme crystals belong to the space group I2(1)2(1)2(1), with two molecules per asymmetric unit. The inhibitor complex crystals are trigonal with space group P3(2)21 and with one molecule in the asymmetric unit. Preliminary X-ray analysis of both native enzyme and its complexes indicate that the complexes diffract to higher resolution than the native crystals. This is probably due to reduced flexibility in the enzyme-inhibitor complex.


Transcriptomics Reveals the Mevalonate and Cholesterol Pathways Blocking as Part of the Bacterial Cyclodipeptides Cytotoxic Effects in HeLa Cells of Human Cervix Adenocarcinoma.
The incidence of human cervix adenocarcinoma (CC) caused by papillomavirus genome integration into the host chromosome is the third most common cancer among women. Bacterial cyclodipeptides (CDPs) exert cytotoxic effects in human cervical cancer HeLa cells, primarily by blocking the PI3K/Akt/mTOR pathway, but downstream responses comprising gene expression remain unstudied. Seeking to understand the cytotoxic and anti-proliferative effects of CDPs in HeLa cells, a global RNA-Seq analysis was performed. This strategy permitted the identification of 151 differentially expressed genes (DEGs), which were either up- or down-regulated in response to CDPs exposure. Database analysis, including Gene Ontology (COG), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed differential gene expression on cancer transduction signals, and metabolic pathways, for which, expression profiles were modified by the CDPs exposure. Bioinformatics confirmed the impact of CDPs in the differential expression of genes from signal transduction pathways such as PI3K-Akt, mTOR, FoxO, Wnt, MAPK, P53, TGF-β, Notch, apoptosis, EMT, and CSC. Additionally, the CDPs exposure modified the expression of cancer-related transcription factors involved in the regulation of processes such as epigenetics, DNA splicing, and damage response. Interestingly, transcriptomic analysis revealed the participation of genes of the mevalonate and cholesterol biosynthesis pathways; in agreement with this observation, total cholesterol diminished, confirming the blockage of the cholesterol synthesis by the exposure of HeLa cells to CDPs. Interestingly, the expression of some genes of the mevalonate and cholesterol synthesis such as HMGS1, HMGCR, IDI1, SQLE, MSMO1, SREBF1, and SOAT1 was up-regulated by CDPs exposure. Accordingly, metabolites of the mevalonate pathway were accumulated in cultures treated with CDPs. This finding further suggests that the metabolism of cholesterol is crucial for the occurrence of CC, and the blockade of the sterol synthesis as an anti-proliferative mechanism of the bacterial CDPs, represents a reasonable chemotherapeutic drug target to explore. Our transcriptomic study supports the anti-neoplastic effects of bacterial CDPs in HeLa cells shown previously, providing new insights into the transduction signals, transcription factors and metabolic pathways, such as mevalonate and cholesterol that are impacted by the CDPs and highlights its potential as anti-neoplastic drugs.


Combining 3D Hydraulic Tomography with Tracer Tests for Improved Transport Characterization.
Hydraulic tomography (HT) is a method for resolving the spatial distribution of hydraulic parameters to some extent, but many details important for solute transport usually remain unresolved. We present a methodology to improve solute transport predictions by combining data from HT with the breakthrough curve (BTC) of a single forced-gradient tracer test. We estimated the three dimensional (3D) hydraulic-conductivity field in an alluvial aquifer by inverting tomographic pumping tests performed at the Hydrogeological Research Site Lauswiesen close to Tübingen, Germany, using a regularized pilot-point method. We compared the estimated parameter field to available profiles of hydraulic-conductivity variations from direct-push injection logging (DPIL), and validated the hydraulic-conductivity field with hydraulic-head measurements of tests not used in the inversion. After validation, spatially uniform parameters for dual-domain transport were estimated by fitting tracer data collected during a forced-gradient tracer test. The dual-domain assumption was used to parameterize effects of the unresolved heterogeneity of the aquifer and deemed necessary to fit the shape of the BTC using reasonable parameter values. The estimated hydraulic-conductivity field and transport parameters were subsequently used to successfully predict a second independent tracer test. Our work provides an efficient and practical approach to predict solute transport in heterogeneous aquifers without performing elaborate field tracer tests with a tomographic layout.


Craniofacial Morphology in Midline Cervical Cleft: Case Report and Review of Literature.
Congenital midline cervical cleft is a rare anomaly of the neck. This paper presents the case of a boy diagnosed with this disorder in which a preliminary orthodontic treatment was implemented. The craniofacial anomalies associated with this malformation produced a defect that could only be successfully treated through the implementation of orthodontic and surgical treatments. In this case, congenital midline cervical cleft was accompanied by certain disorders within the facial structures of the skull, primarily mandibular retrusion, flattening of the contour of the mandibular base, and a steep angle between the cranial base and the mandibular plane.


ON THE FAMILY OF ELLIPTIC CURVES X + 1/X + Y + 1/Y + t = 0.
We study various properties of the family of elliptic curves x+1/x+y+1/y+t = 0, which is isomorphic to the Weierstrass curve E t : Y 2 = X ( X 2 + ( t 2 4 - 2 ) X + 1 ) . . This equation arises from the study of the Mahler measure of polynomials. We show that the rank of E t ( Q ¯ ( t ) ) is 0 and the torsion subgroup of E t ( Q ( t ) ) is isomorphic to Z ∕ 4 Z . Over the rational field Q we obtain infinite subfamilies of ranks (at least) one and two, and find specific instances of Et with rank 5 and 6. We also determine all possible torsion subgroups of E t ( Q ) and conclude with some results regarding integral points in arithmetic progression on Et .


Liquid chromatography with electrospray ionization mass spectrometry method for the assay of glucosamine sulfate in human plasma: validation and application to a pharmacokinetic study.
A liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed and validated for the assay of glucosamine sulfate in human plasma. Plasma proteins were precipitated by acetonitrile, followed by vortex mixing and centrifugation. The supernatant was transferred and derivatized with phenyl iso-thiocyanate in acetonitrile at 60 degrees C for 40 min. Chromatographic separation was performed on a C(18) column (Inertsil ODS-3 150 x 2.1 mm i.d., 5 microm, JP) with a mobile phase gradient consisting of 0.2% acetic acid (aqueous) and methanol at a flow-rate of 0.3 mL/min. MS detection using electrospray ionization (ESI) as an interface was used in single ion monitoring mode to determine positive ions at m/z 297. This method was shown to be selective and sensitive for glucosamine sulfate. The limit of detection was 35 ng/mL for glucosamine sulfate in plasma and the linear range was 0.1-20 microg/mL in plasma with a correlation coefficient (r) of 0.9991. The relative standard deviations (RSDs) of intra-day and inter-day assays were 8.7-11.4 and 9.8-12.6%, respectively. Extraction recoveries of glucosamine sulfate in plasma were greater than 73%. This method proved to be simple, reproducible and feasible for pharmacokinetic studies of glucosamine sulfate in healthy volunteers after a single oral administration (1500 mg). The pharmacokinetic parameters and relative bioavailabilities were investigated for both domestic glucosamine sulfate tablet and capsule preparations compared with an imported capsule product.


Usefulness of fat-suppressed T1-weighted MRI using orally administered superparamagnetic iron oxide for revealing ampullary carcinomas.
To evaluate the value of adding fat-suppressed (FS) T1-weighted magnetic resonance imaging (MRI) with orally administered superparamagnetic iron oxide (SPIO) to the 3-dimensional dynamic MRI for revealing ampullary carcinomas. Twenty-five patients with ampullary carcinoma who underwent MRI with orally administered SPIO, including a FS T1-weighted fast low-angle shot (FLASH) sequence, a respiratory-triggered turbo spin-echo (RT-TSE) sequence, and the 3-phasic 3-dimensional dynamic images, were enrolled in this study. About 5 min before the examination, a mixture of 8.4 mg of SPIO and 300 mL water was administered orally to all patients. The images were compared quantitatively by measuring the tumor-pancreas (duodenum) contrast-to-noise ratio and, qualitatively, by evaluating tumor conspicuity. Three separate sets of images, that is, the dynamic set, the combination of the dynamic set, and the RT-TSE, and the combination of the dynamic set and the FLASH were analyzed by 2 observers in consensus. For the tumor-pancreas (duodenum) contrast-to-noise ratio, the FLASH was significantly higher than those of the dynamic set and RT-TSE (P < 0.05). The tumor conspicuity with the combination of the dynamic set and the FLASH was also significantly better than those of the dynamic set, and the combination of the dynamic set and RT-TSE (P = 0.001). For 15 tumors that were surgically confirmed, the combined reading of the FLASH imaging and dynamic set allowed more accurate surgical staging (14/15, 93.3%) than did the dynamic imaging set or the combined reading of the dynamic set and RT-TSE (11/15, 73.3%). Addition of the FS FLASH image using orally administered SPIO to the dynamic MRI is useful for revealing ampullary carcinoma.


First experiments on diffraction-enhanced imaging at LNLS.
Diffraction-enhanced images have been obtained using two silicon crystals in a non-dispersive set-up at the XRD2 beamline at the Brazilian Synchrotron Light Laboratory (LNLS). A first asymmetrically cut silicon crystal using the (333) reflection vertically expanded the monochromated beam from 1 mm to 20 mm allowing the imaging of the whole sample without movements. A symmetrically cut Si(333) second crystal was used as a Bragg analyzer. Images of biological samples including human tissue were recorded using a direct-conversion CCD detector resulting in enhancement of the contrast compared with absorption-contrast images.


Adenovirus E1B 55-kilodalton oncoprotein binds to Daxx and eliminates enhancement of p53-dependent transcription by Daxx.
The adenovirus E1B 55-kDa protein impairs the p53 pathway and enhances transformation, although the underlying mechanisms remain to be defined. We found that Daxx binds to the E1B 55-kDa protein in a yeast two-hybrid screen. The two proteins interact through their C termini. Mutation of three potential phosphorylation sites (S489/490 and T494 to alanine) within the E1B 55-kDa protein did not affect its interaction with Daxx, although such mutations were previously shown to inhibit E1B's ability to repress p53-dependent transcription and to enhance transformation. In addition to their coimmunoprecipitation in 293 extracts, purified Daxx interacted with the E1B 55-kDa protein in vitro, indicating their direct interaction. In 293 cells, Daxx colocalized with the E1B 55-kDa protein within discrete nuclear dots, where p53 was also found. Such structures were distinct from PML (promyelocytic leukemia protein) bodies, and it appeared that Daxx was displaced from PML bodies. Thus, the Daxx concentration was diminished in dots with a prominent presence of PML and vice versa. Indeed, PML overexpression led to dramatic redistribution of Daxx from p53-E1B 55-kDa protein complexes to PML bodies. Additionally, expression of the E1B 55-kDa protein in Saos2 osteosarcoma cells reduced the number of PML bodies. Our data suggest that E1B and PML compete for available Daxx in the cell. Surprisingly, Daxx significantly augmented p53-mediated transcription and the E1B 55-kDa protein eliminated this effect. Thus, it is likely that the E1B 55-kDa protein sequesters Daxx and p53 in specific nuclear locations, where p53 cannot activate transcription. One consequence of the Daxx-E1B interaction might be an alteration of normal interactions of Daxx, PML, and p53, which may contribute to cell transformation.


[Mendelian molecular genetics in glaucoma].
Early-onset forms of glaucoma are inherited as Mendelian-dominant or Mendelian-recessive traits. They encompass primary congenital or infantile glaucoma; juvenile primary open-angle glaucoma; development glaucomas including Rieger syndrome, glaucoma associated with nail-patella syndrome, Peters' anomaly, and nanophthalmos; and glaucoma associated with pigment dispersion syndrome. Personalized gene therapy has been proposed as an alternative therapeutic strategy for ocular diseases. This approach might be applicable in families with primary congenital glaucoma and defined mutations in the CYP1B1 gene.


Valuable online resources and outstanding nursing talent.
Welcome to the June issue of Nursing Older People. RCNi has recently launched an online frailty resource in conjunction with the RCN older people's forum. Access to this valuable resource is included in your subscription to the journal and I encourage you to visit it.


Public health consequences of a flood disaster--Iowa, 1993.
Unprecedented amounts of rain in the spring and summer of 1993 led to disastrous flooding and crop damage in nine Midwestern states. In Iowa (1990 population: 2,777,000), extensive flood damage occurred in all 99 countries. On July 11, 1993, the Iowa Department of Public Health (IDPH) requested assistance from CDC to assess the adverse public health impact of the flooding and to plan the public health response to the disaster. CDC assisted IDPH in performing an initial rapid statewide public health assessment and establishing weekly surveillance to monitor ongoing or anticipated flood-related health problems. This report summarizes the methods of the assessment and surveillance and preliminary findings.


Simultaneous detection of somatic and F-specific coliphages in different settings by Escherichia coli strain CB390.
Bacteriophages are increasingly being used as water quality indicators. Two groups of phages infecting Escherichia coli, somatic and F-specific coliphages, are being considered as indicators of fecal and viral contamination for several types of water around the world. However, some uncertainties remain regarding which coliphages to assess. Recently, E. coli strain CB390 has been reported to be suitable for simultaneous detection of both groups, which seems to be more informative than determining only one of the groups. Here, a significant number of samples from different settings, mostly those where F-specific phages have been reported to outnumber somatic coliphages, are analyzed for somatic coliphages, F-specific RNA phages by standardized methods and coliphages detected by host strain CB390. The results presented here confirm that the numbers of phages counted using CB390 are equivalent to the sum of the somatic and F-specific coliphages counted independently in all settings. Hence the usefulness of this strain for simultaneous detection of somatic and F-specific coliphages is confirmed. Also, sets of data on the presence of coliphages in reclaimed and groundwater are reported.


Continuous surveillance revealing a wide distribution of class I Newcastle disease viruses in China from 2011 to 2020.
The risk-based active surveillance for Newcastle disease virus (NDV) was carried out in China from 2011 to 2020. A total of 110,018 swabs were collected from 28 provinces. 2,389 class I NDVs were isolated and identified by RT-PCR and sequencing. The average annual positivity rate of class I NDVs from 2011 to 2020 was 2.17%. In the last 10 years, the positivity rate was highest in 2011 (4.76%), and has since decreased. Most viruses were isolated from chickens, while others were collected from ducks, geese and pigeons, as well as from the environment. The positivity rates for class I NDVs in poultry ranged from 0.55% to 2.40%. The viruses were isolated from 373 sampling sites in 24 provinces, mainly in East, Central, South and Southwest China. The positivity rates of NDVs in wholesale markets (51.58%) and retail markets (42.83%) were much higher than those in poultry farms (7.14%) and slaughterhouses (3.85%). Phylogenetic analyses showed that most isolates belonged to sub-genotype 1.1.2, while only 22 viruses belonged to sub-genotype 1.2, indicating the viruses in sub-genotype 1.1.2 were the predominant strains in China. The F and HN genes of six strains in the two sub-genotypes were sequenced and analyzed. The cleavage sites of F protein in the six viruses were 112ERQER/L117, 112ERQGR/L117 or 112GRQERL117, which were typical of low virulence NDV. Several mutations were identified in the functional domains of F and HN proteins, including fusion peptide, heptad repeat region, transmembrane domains and neutralizing epitopes. This study revealed the distribution, genetic and phylogenetic characteristics of class I NDVs in China, and could help us to better understand the epidemiological context of class I NDVs in China.


Radioiodination of humic substances via azocoupling with 3-[125I] iodoaniline.
A new method is described for radiolabeling humic substances (HS) with iodine radioisotopes. The method radiolabels the electron-rich aromatic moieties of HS with the 3-[125I]iodobenzenediazonium ion via azocoupling. The method uses four steps: (i) 3-aminobenzenetrimethylstannane is synthesized and isolated by using a silica gel column, (ii) 3-[125I]iodoaniline is synthesized and isolated by HPLC, with radiochemical yields of up to 60%, (iii) 3-[125I]iodobenzenediazonium chloride is synthesized, and the reaction mixture from this step is used in step iv to radioiodinate HS with radiochemical yields of up to 95% (with reference to 3-[125I]iodoaniline). The advantage of this method is that it is selective radiolabeling, placing the radiolabel in a specific site (the 3-position of the phenyl ring) within HS molecules, which minimizes unwanted secondary chemical interactions. Investigations of the stability of the radiolabel and the effect of photoreductive dehalogenation showed that there was a negligible release of 125I. The production of radiolabeled HS using this method allows the sensitive detection of HS in laboratory and field studies. In addition, the method offers the possibility of using different iodine radioisotopes simultaneously in investigations using HS.


Agonist-induced localized Ca2+ spikes directly triggering exocytotic secretion in exocrine pancreas.
We investigated how agonist-induced patterned rises in cytosolic Ca2+ concentration ([Ca2+]i) regulate exocytotic secretion in the rat pancreatic acinar cell. The distribution of [Ca2+]i was visualized with a confocal microscope, which revealed that a Ca2+ ionophore, A23187, induced slow and homogeneous [Ca2+]i rises, while acetylcholine (ACh) always triggered primary Ca2+ spikes at the granular area which bears secretory granules. Secretion was monitored by measuring capacitance with the patch clamp method. Errors in the estimates of membrane capacitance (C) due to changes in conductance (G) were experimentally as well as theoretically evaluated to be one-tenth of the actual signals. We found that A23187 raised G without changing C at a low concentration, while it triggered asynchronous rises in G and C with lags in C, at a high concentration. By contrast, ACh triggered simultaneous rapid rises in G and C. Our results support the hypothesis that exocytotic secretion is less sensitive to Ca2+ than to ion channels and is directly caused by agonist-induced primary Ca2+ spikes at the granular area. It is therefore suggested that spatio-temporal patterns of Ca2+ oscillations could play a key role in exocytotic secretion from the exocrine acinar cell.


Morphological, biological, and biochemical characteristics of a benign human trichilemmoma cell line in vivo and in vitro.
A cell line of a benign tumor, trichilemmoma, was established in vitro and has been maintained in culture for 1.5 years with more than 30 passages. Plating efficiency was less than 0.1%, and population doubling time was 10 days. Saturation density was 10(5) cells/sq cm at the time of a monolayer with 98% cell viability. Ultrastructurally, tissue-cultured trichilemmoma cells showed desmosome-tonofilament complexes at cell-to-cell junctions. The tissue-cultured cells synthesized abundant glycogen (50 to 100 microgram/10(6) cells) e was 10 days. Saturation density was 10(5) cells/sq cm at the time of a monolayer with 98% cell viability. Ultrastructurally, tissue-cultured trichilemmoma cells showed desmosome-tonofilament complexes at cell-to-cell junctions. The tissue-cultured cells synthesized abundant glycogen (50 to 100 microgram/10(6) cells) e was 10 days. Saturation density was 10(5) cells/sq cm at the time of a monolayer with 98% cell viability. Ultrastructurally, tissue-cultured trichilemmoma cells showed desmosome-tonofilament complexes at cell-to-cell junctions. The tissue-cultured cells synthesized abundant glycogen (50 to 100 microgram/10(6) cells) as observed in vivo. Gas chromatographic analysis revealed that extracted glycogen was composed of glucose alone. Chromosome analyses with trypsin-Giemsa banding showed an abnormal karyotype with hypodiploid modal numbers of 44 and 45. There were four marker chromosomes observed in 100% of cells in 100 metaphase cells examined. Cells did not grow on fibroblast monolayers or in soft agar in vitro but did induce tumors in athymic nude mice (12 of 15) after the s.c. injection of tissue-cultured cells (2.5 x 10(6) to 4.5 x 10(7) cells/mouse). The histological characteristics of the tumors in nude mice were similar to those of the original tumor. This is the first time, to our knowledge, that a benign human tumor cell line has been established in vitro which can induce tumors in nude mice.


How strategists really think. Tapping the power of analogy.
Leaders tend to be so immersed in the specifics of strategy that they rarely stop to think how much of their reasoning is done by analogy. As a result, they miss useful insights that psychologists and other scientists have generated about analogies' pitfalls. Managers who pay attention to their own analogical thinking will make better strategic decisions and fewer mistakes. Charles Lazarus was inspired by the supermarket when he founded Toys R Us; Intel promoted its low-end chips to avoid becoming like U.S. Steel; and Circuit City created CarMax because it saw the used-car market as analogous to the consumer-electronics market. Each example displays the core elements of analogical reasoning: a novel problem or a new opportunity, a specific prior context that managers deem to be similar in its essentials, and a solution that managers can transfer from its original setting to the new one. Analogical reasoning is a powerful tool for sparking breakthrough ideas. But dangers arise when analogies are built on surface similarities (headlong diversification based on loose analogies played a role in Enron's collapse, for instance). Psychologists have discovered that it's all too easy to overlook the superficiality of analogies. The situation is further complicated by people's tendency to hang on to beliefs even after contrary evidence comes along (a phenomenon known as anchoring) and their tendency to seek only the data that confirm their beliefs (an effect known as the confirmation bias). Four straightforward steps can improve a management team's odds of using an analogy well: Recognize the analogy and identify its purpose; thoroughly understand its source; determine whether the resemblance is more than superficial; and decide whether the original strategy, properly translated, will work in the target industry.


Effects of tamoxifen on cardiovascular risk factors in postmenopausal women after 5 years of treatment.
Adjuvant tamoxifen therapy for breast cancer has been given for a period of several years. Cardiovascular diseases increased in incidence rapidly in women older than 60 years. Favorable changes in cardiovascular risk factors have been seen with 2 years of tamoxifen therapy, and lower rates of myocardial infarction and of hospitalization for heart disease have been observed in tamoxifen-treated women. We sought to evaluate changes in risk factors for cardiovascular diseases in postmenopausal women after therapy with tamoxifen for 5 years. Five years after their initial entry in a 2-year randomized, placebo-controlled toxicity study, we re-examined 62 of the original 140 disease-free, axillary node-negative postmenopausal breast cancer patients. These 62 patients were women available for study because they had not suffered major illness and had continued on either the tamoxifen or no-tamoxifen regimen to which they had been originally randomly assigned for the entire 5 years. Patient and control blood samples were analyzed for total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and subfractions, triglycerides, apolipoprotein AI, apolipoprotein B, lipoprotein(a), fibrinogen, glucose, and platelets. At base line for all measurements except atherogenic lipoprotein [lipoprotein(a)], the 30 long-term tamoxifen recipients and the 32 long-term no-tamoxifen recipients were not significantly different. After 5 years, levels of total serum cholesterol (P < .001), LDL cholesterol (P < .001), and lipoprotein(a) (P = .001) were significantly lower, and apolipoprotein AI levels were significantly higher (P < .001) in the tamoxifen-treated group compared with the no-tamoxifen group. Apolipoprotein B levels increased to a greater extent in the no-tamoxifen than in the tamoxifen group (P < .001). After 5 years, fibrinogen level decrease and triglyceride level increases in the tamoxifen group compared with the no-tamoxifen group were of borderline statistical significance and HDL cholesterol levels were not different in the two groups. Favorable changes in lipid, lipoprotein, and fibrinogen levels seen early in tamoxifen therapy in postmenopausal women persist with treatment of 5 years. The types and magnitude of changes in cardiovascular risk factors seen here with tamoxifen are similar to a certain extent with those seen with estrogen supplements. Further risk-factor and ethnic-group data are needed to estimate the magnitude of expected benefits of tamoxifen treatment on incidence of heart disease.


Peri-implant health and disease. A systematic review of current epidemiology.
To develop preventive strategies addressing peri-implant diseases, a thorough understanding of the epidemiology is required. The aim was to systematically assess the scientific literature in order to evaluate the prevalence, extent and severity of peri-implant diseases. Data were extracted from identified studies. Meta-analyses for prevalence of peri-implant mucositis and peri-implantitis were performed. The effect of function time and disease definition on the prevalence of peri-implantitis was evaluated by meta-regression analyses. Data on extent and severity of peri-implant diseases were estimated if not directly reported. Fifteen articles describing 11 studies were included. Case definitions for mucositis and peri-implantitis varied. The prevalence of peri-implant mucositis and peri-implantitis ranged from 19 to 65% and from 1 to 47%, respectively. Meta-analyses estimated weighted mean prevalences of peri-implant mucositis and peri-implantitis of 43% (CI: 32-54%) and 22% (CI: 14-30%), respectively. The meta-regression showed a positive relationship between prevalence of peri-implantitis and function time and a negative relationship between prevalence of peri-implantitis and threshold for bone loss. Extent and severity of peri-implant diseases were rarely reported. Future studies on the epidemiology of peri-implant diseases should consider (i) applying consistent case definitions and (ii) assessing random patient samples of adequate size and function time.


Fluorescent protein tagging of adenoviral proteins pV and pIX reveals 'late virion accumulation compartment'.
The human adenovirus type 5 (HAdV5) causes disease of the upper and lower respiratory tract. The early steps of HAdV5 entry up to genome replication in the host nucleus have been extensively studied. However, late stages of infection remain poorly understood. Here, we set out to elucidate the spatiotemporal orchestration of late adenovirus nuclear remodeling in living cells. We generated virus mutants expressing fluorescently tagged protein IX (pIX) and protein V (pV), a capsid and viral genome associated protein, respectively. We found that during progeny virion production both proteins localize to a membrane-less, nuclear compartment, which is highly impermeable such that in immunofluorescence microscopy antibodies can hardly penetrate it. We termed this compartment 'late virion accumulation compartment' (LVAC). Correlation between light- and electron microscopy revealed that the LVAC contains paracrystalline arrays of viral capsids that arrange tightly packed within a honeycomb-like organization of viral DNA. Live-cell microscopy as well as FRAP measurements showed that the LVAC is rigid and restricts diffusion of larger molecules, indicating that capsids are trapped inside.


Tumor-associated serpin, squamous cell carcinoma antigen stimulates matrix metalloproteinase-9 production in cervical squamous cell carcinoma cell lines.
Squamous cell carcinoma antigen (SCCA) is clinically used as a tumor marker for patients with squamous cell carcinoma of various organs. SCCA1 and its highly homologous molecule, SCCA2, belong to the serine proteinase inhibitors (serpins) family, suggesting that these proteins may be involved in the malignant behavior of squamous cell carcinoma cells. The aim of this study is to functionally characterize these tumor-associated serpins regarding the potential to influence the production of matrix metalloproteinases (MMPs), which play a key role in tumor cell invasion and metastasis. Cervical squamous cell carcinoma cell lines, CaSki cells and SKG-IIIa cells were incubated with SCCA1 or SCCA2 and MMP production was analyzed by gelatin zymography. Both SCCA1 and SCCA2 significantly increased production of proMMP-9, but not proMMP-2. These stimulatory effects were still observed when cells were treated with SCCA mutants lacking the proteinase inhibitory activity of serpins. Furthermore, treatments with various forms of SCCAs, which are generated by interacting with their target proteinases, diminished the stimulatory effect of SCCAs, implying the importance of the conformational structure of SCCAs in the stimulatory effects of SCCAs on proMMP-9 production. In addition, in vitro invasion assay showed that SCCA1 and SCCA2 significantly promoted the activity of cell invasion. It is concluded that SCCAs can alter the invasive phenotype of cervical squamous cell carcinoma cells, probably by stimulating proMMP-9 production, and that intact conformational structure of SCCAs, but not proteinase inhibitory activity of serpins, is required for its stimulatory activity on proMMP-9 production.


Ectoparasitism in Black-and-White Ruffed Lemurs ( Varecia variegata) in Southeastern Madagascar.
We documented ectoparasites found on wild black-and-white ruffed lemurs ( Varecia variegata) in the southeastern rain forests of Madagascar and describe trends in parasitism. In this study, 235 mesostigmatid mites (1 male, 87 females, 147 nymphs) identified as Liponyssella sp., in the acarine family Macronyssidae, were collected during 87% (34/39) of lemur examinations (mean number/host=7.9). The only other ectoparasite collected was the louse fly ( Allobosca crassipes; 3 males, 8 females) in the dipteran family Hippoboscidae, which was collected during 26% (10/39) of lemur examinations (mean number/host=1.1). The lemur most heavily parasitized by mites was an adult female with 29 adult females and 17 nymphs, all collected from the face.


The modification of gastrointestinal tolerance and responses to abdominal irradiation by chemotherapeutic agents.
Groups of male DBA/2 mice were irradiated with partial abdominal exposures of x radiation ranging from 100 to 1,600 rads. Concomitant with radiation exposure and at 1 or 4 hours prior to, and at 1, 6, 24, or 48 hours after irradiation, various chemotherapeutic agents were administered, i.e., methotrexate, Cytoxan, adriamycin and BCNU. The results suggest that excessive gastrointestinal toxicity may result if aggressive chemotherapy is closely spaced with radiation exposure for the treatment of abdominal neoplasms. However, adjustment of dose and time patterns based on the proliferative responses of the mucosa may circumvent such toxicity to a large extent.


Critical components of reflective supervision: responses from expert supervisors in the field.
This article offers a brief review of the history of supervision, defines reflective supervision, and reports the results of a Delphi study designed to identify critical components of reflective supervision. Academicians and master clinicians skilled in providing reflective supervision participated in a three-phase survey to elicit beliefs about best practice when engaging in reflective supervision. The process yielded consensus descriptions of optimal characteristics and behaviors of supervisors and supervisees when entering into supervisory relationships that encourage reflective practice. These results, although preliminary, suggest that it is possible to identify elements that are integral to effective reflective supervision. These initial findings may be used for future study of the reflective supervisory process.


A comparative transcriptome analysis of two sets of backcross inbred lines differing in lint-yield derived from a Gossypium hirsutum × Gossypium barbadense population.
Upland cotton (Gossypium hirsutum L.) is the most important fiber crop, and its lint-yield improvement is impeded due to its narrow genetic base and the lack of understanding of the genetic basis of yield. Backcross inbred lines (BILs) or near-isogenic lines (NILs) in the same genetic background differing in lint yield, developed through advanced backcrossing, provide an important genomic resource to study the molecular genetic basis of lint yield. In the present study, a high-yield (HY) group and a low-yield (LY) group each with three BILs were selected from a BIL population between G. hirsutum and G. barbadense. Using a microarray-based comparative transcriptome analysis on developing fibers at 10 days post-anthesis (DPA) between the two groups, 1486 differentially expressed genes (DEGs) were identified. A total of 212 DEGs were further mapped in the regions of 24 yield QTL and 11 yield trait QTL hotspots as reported previously, and 81 DEGs mapped with the 7 lint-yield QTL identified in the BIL population from which the two sets of BILs were selected. Gene Ontology annotations and Blast-Mapping-Annotation-KEGG analysis via Blast2GO revealed that more DEGs were associated with catalytic activity and binding, followed by transporters, nucleic acid binding transcription factors, structural molecules and molecular transducer activities. Six DEGs were chosen for a quantitative RT-PCR assay, and the results were consistent with the microarray analysis. The development of DEGs-based markers revealed that 7 single strand conformation polymorphism-based single nucleotide polymorphic (SSCP-SNP) markers were associated with yield traits, and 3 markers with lint yield. In the present study, we identified a number of yield and yield component QTL-co-localizing DEGs and developed several DEG-based SSCP-SNP markers for the traits, thereby providing a set of candidate genes for molecular breeding and genetic manipulation of lint yield in cotton.


Dendritic cells administered intrarectally penetrate the intestinal barrier to break intestinal tolerance via Th2-medeiated colitis in mice.
Intestinal lamina propria dendritic cells (LPDCs) in mice are known to extend dendrites between the intestinal epithelia and the luminal side when processing luminal antigens. We conducted intrarectal cell transfer experiments of bone marrow-derived dendritic cells (BMDCs) in mice to assess dendritic cell penetration of the intestine. Intrarectally administered GFP(+) BMDCs localized in the colonic LP within 3h and the spleen within 12h after administration. 72h after administration, recipient C57BL/6 mice showed acute diarrhea, and administration of BMDCs (once weekly for 3 weeks) induced intestinal inflammation with increased numbers of recipient macrophages and CD4(+) T cells exhibiting a Th2-mediated immune response. These results demonstrate that DCs actively communicate across the intestinal barrier, and highlight a potential technique for controlling colonic immune tolerance.


Severe dysphagia associated with major tranquillizer treatment.
A 56 year old patient with psychiatric complications of systemic lupus erythematosus developed severe dysphagia complicated by weight loss and aspiration. Following investigation it was concluded that the addition of haloperidol to her treatment was the major precipitating cause and withdrawal of the drug was followed by an objective improvement in swallowing. Patients taking major transquillizers may be at increased risk of severe dysphagia; regular observation of swallowing is suggested as a useful addition to the clinical examination of these patients.


[The synergy between quality approach and health promotion: synergy between quality approach and health promotion: example of the Ile-de-France/Outre-Mer Legal Protection of Youth].
Legal Protection of Youth is responsible for the education of juvenile offenders, and for the inspection and assessment of the bodies that supervise them. The objective of this project is to promote and strengthen the synergy between the quality approach and health promotion in the missions of the Ile-de-France/ Outre-Mer Inter-regional Directorate of Legal Protection of Youth. A participatory and cross-sectional methodology was used to study two strategies designed to integrate existing prevention and health promotion actions into a quality approach and to include prevention and health promotion in the existing quality approach. Three reference frameworks were constructed: a guide for the analysis of prevention and health promotion actions implemented by associations financed by the Ile-de-France Regional Health Agency; a guide for internal evaluation for health promotion in educational bodies; a technical data sheet proposing audit references for health promotion. The results of the project contributed to achieving the initial objective. The frameworks and tools should now be compared with prevention and health promotion actions, and activities and services provided by educational bodies, in order to measure their usefulness to improve quality.


The influence of pregnancy on heterotopic ossification post-displaced acetabular fractures surgical repair.
Pregnancy is associated with maternal bone mineral density loss and modulation of calcium metabolism. We hypothesized that pregnancy may decrease the risk of heterotopic ossification (HO) after trauma. This is a single-institution, University of Mississippi Medical Center, retrospective study investigating the effect of pregnancy on the incidence HO after surgical repair (SR) of displaced acetabular fractures. Between January 1998 and 2010, 257 non-pregnant women (Group A) and 16 pregnant women (Group B) were identified. All the non-pregnant women received radiation therapy (RT) ± indomethacin. None of the pregnant women in group B received any prophylaxis. After a median follow-up of 6.6 years the incidence of HO in all patients was 27% (75/273). In Group A, non-pregnant, women who received RT ± indomethacin, 29% developed HO; HO risk was 0.4. In Group B, 16 pregnant patients, only one developed HO (6%); HO risk was 0.06. Thus, the risk of HO appears to be nearly six-fold higher in non-pregnant women despite prophylactic RT ± indomethacin. Our data suggest that pregnancy may be associated with a reduced risk of HO after SR of displaced acetabular fractures. Further analysis with a larger pregnant patient sample is necessary to confirm this finding.


Changes in Nutritional and Functional Status in Longer Stay Patients Admitted to a Geriatric Evaluation and Management Unit.
Malnutrition and functional decline are common in older inpatients admitted to subacute care settings. However the association between changes in nutritional status and relevant functional outcomes remains under-researched. This study examined changes in nutritional status, function and mobility in patients admitted to a Geriatric Evaluation and Management (GEM) unit who had a length of stay (LOS) longer than 21 days. A prospective, observational study. Two GEM units at St Vincent's Hospital Melbourne, Australia. Patients admitted to the GEM units who stayed longer than 21 days were included in the study. Patients were assessed on admission and prior to discharge using the Subjective Global Assessment (SGA), Functional Independence Measure (FIM) motor domain and the Modified Elderly Mobility Scale (MEMS). Fifty-nine patients (Mean age 84.0 ± 7 years) met the required length of stay and were included in the study. Fifty-four per cent (n=32) were malnourished on admission (SGA B/C) and 44% (n=26) were malnourished on discharge. Twenty-two per cent (n=13) improved SGA category, 75% remained stable (n=44) and 3% deteriorated (n=2) from admission to discharge. Total Motor FIM scores significantly increased from admission to discharge in both the improved (p<0.001) and stable or deteriorated (p<0.001) nutritional status groups. Subjects who improved in nutritional status had a significantly higher MEMS score at discharge (p<0.001). On admission to the GEM unit, just over half the included patients were rated as malnourished defined by SGA category. Nearly one quarter of the sample had improved their nutritional status at the time of discharge. Improvement in nutritional status was associated with greater improvement in mobility scores. Further studies are required to investigate the effectiveness of nutrition interventions, which will inform models of care aiming to optimise nutritional, functional, and associated clinical outcomes in patients admitted to GEM units.


Comparison of the dental arch changes in patients with different malocclusions.
To evaluate the pre-treatment and post-treatment dental arch changes in both upper and lower arches in orthodontic patients treated with extraction of first premolar teeth. Measurements were made on casts of 50 post treated cases in the age group of 12-30 years for individual tooth measurements, width of the arches (inter-incisal, inter-canine, inter-premolar and inter-molar) arch length (both right and left sides, anterior segment, posterior segment and total arch length for both for the maxillary and mandibular dental casts. Kolmogorov-Smirnov test for Normality, Regression Analysis was done as variables were tested and proved to follow normality. Statistical software Statistical Package for the Social Sciences version 18 (SPSS Inc.; Chicago, Illinois, USA) was used for data analysis. Descriptive statistics and paired t-tests were used to compare the changes in the Class I and Class II div 1 groups. There was a significant increase in the inter-incisor and inter-canine width post-treatment in the Class I and Class II div 1 subjects in the upper arch but no significant change in inter-incisor width in the lower arch in class I subjects. A significant decline in the inter-molar arch width in both the groups were seen. The inter-premolar arch width declined significantly in Class I cases while it increased significantly in Class II div 1 subjects. There was a significant increase in anterior arch length and a significant decrease in posterior arch length in all subjects. The findings of this original clinical research should significantly help the orthodontists in orthodontic treatment planning in patients requiring extractions of premolars.


Very high frequency of lymphoma induction by a chemical carcinogen in pim-1 transgenic mice.
Infection of mice with Moloney murine leukaemia virus (MuLV) induces T-cell lymphomas after an average latency period of 150 days. In these lymphomas the MuLV DNA is frequently integrated into the mouse chromosomal DNA in the vicinity of the pim-1 oncogene. Transgenic mice overexpressing the pim-1 oncogene are predisposed to develop T-cell lymphomas, but only to the extent that approximately 10% of the mice develop a lymphoma within 240 days. When these mice are infected with MuLV, lymphomas develop in all mice in only 50-60 days. In these lymphomas MuLV DNA is integrated near either the c-myc or N-myc gene, suggesting that pim-1 and myc synergize in lymphomagenesis. To determine whether this system has a more general application, we have now tested the susceptibility of pim-1 transgenic mice to N-ethyl-N-nitrosourea (ENU), a chemical carcinogen. With a single low dose of ENU, nearly all pim-1 transgenic mice, but only 15% of non-transgenic mice, develop T-cell lymphomas within 200 days. All ENU-induced lymphomas in both pim-1 transgenic and non-transgenic mice express high levels of c-myc messenger RNA, supporting the notion that pim-1 and c-myc synergize in lymphoma induction. We propose that pim-1 transgenic mice could be used to test the oncogenic potential of other chemical compounds.


Screening for the protective effect target of deproteinized extract of calf blood and its mechanisms in mice with CCl4-induced acute liver injury.
Liver injury is a common pathological basis of various liver diseases, and long-term liver injury is often an important initiation factor leading to liver fibrosis and even liver cirrhosis and hepatocellular carcinoma (HCC). It has been reported that deproteinized extract of calf blood (DECB) can inhibit the replication of hepatitis B virus and confers a protective effect on the liver after traumatic liver injury. However, few studies on the regulatory factors and mechanisms of DECB have been reported. In this current study, an acute mouse liver injury model was established with carbon tetrachloride (CCl4). The differentially expressed genes and related cell signal transduction pathways were screened using mRNA expression microarray. STEM software V1.3.6 was used for clustering gene functions, and the DAVID and KEGG databases were applied for the analysis. A total of 1355 differentially expressed genes were selected, among which nine were validated by RT-qPCR. The results showed that the Fas, IL1b, Pik3r1, Pik3r5, Traf2, Traf2, Csf2rb2, Map3k14, Pik3cd and Ppp3cc genes were involved in the regulation of DECB in an acute mouse liver injury model. Targets of the protective effects of DECB and its related mechanisms were found in mice with acute liver injury induced by carbon tetrachloride, which may provide an important theoretical basis for further DECB research.


Mortality associated with congenital syphilis in the United States, 1992-1998.
To summarize national trends in the incidence of congenital syphilis (CS) and associated mortality. We analyzed CS surveillance data reported to the Centers for Disease Control and Prevention by 50 states and the District of Columbia from 1992-1998. From 1992-1998, 942 deaths, including 760 stillbirths, were reported among 14 627 cases of CS, yielding a case fatality ratio (stillborns and deaths/all cases) of 6.4%. Untreated, inadequately treated, or undocumented treatment of syphilis during pregnancy accounted for 87.4% of reported cases. Among CS cases, there was an inverse relationship between the number of prenatal care visits (0, 1-4, 5-9, >/=10) and risk of fatal outcome. Among deaths, 52% of deliveries occurred by 30 weeks' gestation. Among live born infants with CS, death occurred more often in infants for whom no radiograph or cerebrospinal fluid evaluation was reported. Although both cases and deaths from CS declined from 1992-1998, there was no significant change in the case fatality ratio. Mortality associated with CS continues to be an important public health problem that will resurge if adult syphilis rates increase. Because a large proportion of deaths occur at low gestational age, earlier diagnosis and treatment of maternal syphilis may substantially reduce the case fatality ratio.


Gene therapy research in Asia.
Gene therapy has shown great potential for the treatment of diseases that previously were either untreatable or treatable but not curable with conventional schemes. Recent progress in clinical gene therapy trials has emerged in various severe diseases, including primary immunodeficiencies, leukodystrophies, Leber's congenital amaurosis, haemophilia, as well as retinal dystrophy. The clinical transformation and industrialization of gene therapy in Asia have been remarkable and continue making steady progress. A total of six gene therapy-based products have been approved worldwide, including two drugs from Asia. This review aims to highlight recent progress in gene therapy clinical trials and discuss the prospects for the future in China and wider Asia.


Increasing the energy yield of mechanochemical transformations: selected case studies.
The products of mechanical treatment are surface atoms or molecules, substances with a crystal structure different from their initial one (another polymorph, amorphous), point or linear defects, radicals and new chemical substances. It is often assumed, that to increase the yield of the products of a mechanical treatment, it is necessary to increase the treatment time and the mechanical power input. In view of the low energy yield of many mechanochemical transformations, this leads to high power consumption and contamination of the matter under treatment with the wear products of the material of a mill or reactor, in which the mechanical treatment is carried out. As a result, the technological attractiveness of mechanochemical processes is reduced, so that many mechanochemical transformations that have been discovered recently do not reach the stage of commercialization. In the present paper we describe different examples of increasing successfully the energy yield of mechanochemical processes, by a factor of several times to several orders of magnitude, for inorganic and organic substances. An increase in the energy yield of mechanochemical transformations opens new possibilities for their practical usage. In particular, the methods of preliminary treatment and the modes of conducting enzymatic processes that may find application in the production of second-generation biofuels are discussed using lignocellulose materials as examples.


[Regulatory volume decrease and its mechanism in nasopharyngeal epithelial cells].
To investigate regulatory volume decrease (RVD) and its mechanism in primary-culturing fetal human nasopharyngeal epithelial cells, living cell imaging technique was employed to detect the volume changes following exposure to hypotonic solution, and blockage of Cl- channels was used to clarify the role of Cl- channels in RVD. The results showed that extracellular hypotonic treatment swelled the cells and induced RVD. 47% hypotonic solution (160 mOsmol/L) swelled the cell by 144.7% and induced 38.7% recovery of cell volume within 20 min. RVD was correlated negatively to the extracellular osmolarity (r=-0.99, P<0.05) and positively to the swelling volume(r=0.99, P<0.05) in "S" shape, respectively. Chloride channel blockers, tamoxfen (20 micromol/ L), ATP (10 mmol/L) and NPPB (100 micromol/L), inhibited RVD by 100%, 76.3% and 62.7% (P< 0.01), respectively. The results indicated that primary-culturing fetal human nasopharyngeal epithelial cells are capable of RVD. Cl- efflux through Cl- channels is the key mechanism of RVD.


van der Waals screening by single-layer graphene and molybdenum disulfide.
A sharp tip of atomic force microscope is employed to probe van der Waals forces of a silicon oxide substrate with adhered graphene. Experimental results obtained in the range of distances from 3 to 20 nm indicate that single-, double-, and triple-layer graphenes screen the van der Waals forces of the substrate. Fluorination of graphene, which makes it electrically insulating, lifts the screening in the single-layer graphene. The van der Waals force from graphene determined per layer decreases with the number of layers. In addition, increased hole doping of graphene increases the force. Finally, we also demonstrate screening of the van der Waals forces of the silicon oxide substrate by single- and double-layer molybdenum disulfide.


Rhanterium epapposum Oliv. essential oil: Chemical composition and antimicrobial, insect-repellent and anticholinesterase activities.
The essential oil (EO) of the aerial parts of Rhanterium epapposum Oliv. (Asteraceae), was obtained by hydrodistillation. The oil was subsequently analyzed by both GC-FID and GC-MS, simultaneously. Forty-five components representing 99.2% of the oil composition were identified. The most abundant compounds were camphene (38.5%), myrcene (17.5%), limonene (10.1%) and α-pinene (8.7%). Referring to the ethnobotanical utilization, an insecticidal assay was performed, where the oil repelled the yellow fever mosquito Aedes aegypti L. at a minimum effective dose (MED of 0.035 ± 0.010 mg/cm2) compared to the positive control DEET (MED of 0.015 ± 0.004 mg/cm2). Additionally, the in vitro antimicrobial activity against a panel of pathogens was determined using a microdilution method. The acetyl- and butyrylcholine esterase inhibitory activities were measured using the colorimetric Ellman method. The bioassay results showed that the oil was rather moderate in antimicrobial and cholinesterase inhibitions when compared to the standard compounds.


The bees of the genus Colletes (Hymenoptera: Apoidea: Colletidae) from China.
Available information about the bees of the genus Colletes from China is summarized. Currently, 66 species are recorded from China, of which two species, Colletes linzhiensis sp. nov. and C. spinatus sp. nov., are described as new. Type specimens are deposited in the Insect Collection of the Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Thirteen species are recorded for China for the first time: C. edentuloides Kuhlmann, 2011, C. pauljohni Kuhlmann, 2002, C. tuberculatus Morawitz, 1894, C. annapurnensis Kuhlmann, 2002, C. laevigena Noskiewicz, 1936, C. annejohnae Kuhlmann, 2003, C. eous Morice, 1904, C. squamosus Morawitz, 1879, C. wollmanni Noskiewicz, 1936, C. bhutanicus Kuhlmann, 2003, C. kaszabi Kuhlmann, 2002, C. uralensis Noskiewicz, 1936, and C. dorni Kuhlmann, 2002. The male of C. edentuloides Kuhlmann, 2011 and the female of C. pseudolaevigena Kuhlmann, 2002 are described for the first time. Colletes dudgeonii Bingham, 1897 was erroneously recorded from China and is removed from the list of Chinese species.