A Fresh Start or the Devil You Know? Examining Relationships Between Release Location Choices, Community Experiences, and Recidivism for High-Risk Parolees.
This study investigated the effects of residential relocation in a sample of 282 high-risk male offenders paroled from New Zealand prisons. Initially we compared those returning to their old neighborhoods (devil you know) and those released to a new location (fresh start). This second category was then further divided: those released to a new location voluntarily (fresh start-voluntary) versus those forced to start anew at the behest of the parole board that was releasing them (fresh start-duress). All three categories were then compared on the quality of their community experiences and recidivism. Results indicated that parolees returning by choice to either their old neighborhood or a new location each were reconvicted in the first year after release at approximately the same rate; however, parolees relocating to a new area at the direction of the parole board (under duress) were reconvicted at a higher rate than those in either of the voluntary location categories. Significant group differences in ratings of community life quality were few, but there were some indications that compared with those choosing to return to a familiar location, making a voluntary residential relocation may lead to better parole experiences, particularly in terms of avoiding criminal peers, and that making a residential relocation under duress may lead to poorer parole experiences than for those returning to a familiar location.


Incorporating density dependence into the directed-dispersal hypothesis.
The directed-dispersal (DrD) hypothesis, one of the main explanations for the adaptive value of seed dispersal, asserts that enhanced (nonrandom) arrival to favorable establishment sites is advantageous for plant fitness. However, as anticipated by the ideal free distribution theory, enhanced seed deposition may impair site suitability by increasing density-dependent mortality, thus negating the advantage postulated by the DrD hypothesis. Although the role of density effects is thoroughly discussed in the seed-dispersal literature, this DrD paradox remains largely overlooked. The paradox, however, may be particularly pronounced in animal-mediated dispersal systems, in which DrD is relatively common, because animals tend to generate local seed aggregations due to their nonrandom movements. To investigate possible solutions to the DrD paradox, we first introduce a simple analytical model that calculates the optimal DrD level at which seed arrival to favorable establishment sites yields maximal fitness gain in comparison to a null model of random arrival. This model predicts intermediate optimal DrD levels that correspond to various attributes of the plants, the dispersers, and the habitat. We then use a simulation model to explore the temporal dynamics of the invasion process of the DrD strategy in a randomly dispersed population, and the resistance of a DrD population against invasion of other dispersal strategies. This model demonstrates that some properties of the invasion process (e.g., mutant persistence ratio in the population and generations until initial establishment) are facilitated by high DrD levels, and not by intermediate levels as expected from the analytical model. These results highlight the need to revise the DrD hypothesis to include the countering effects of density-dependent mortality inherently imposed by enhanced arrival of seeds to specific sites. We illustrate how the revised hypothesis can elucidate previous results from empirical studies reporting little or no support for the DrD hypothesis, and we suggest its incorporation in designing empirical studies of plant recruitment and in management practices.


Biomarker expression patterns that correlate with high grade features in treatment naive, organ-confined prostate cancer.
The early detection of prostate cancer has resulted in an increase in the number of patients with localized prostate cancer and has paralleled the reported reduction in prostate cancer mortality. The increased rate of detection of patients with localized prostate cancer may also increase the risk of potentially morbid therapy in a patient with indolent cancer. Defining the biomarker correlates of prostate cancer virulence will facilitate the appropriate application and development of therapy for patients with early disease. A 255 core prostate cancer tissue microarray (TMA) from 47 prostatectomy specimens with organ confined tumor was constructed. Prostate cancer foci of transition and peripheral zone origin were represented on the TMA. Further, replicate cores of the two Gleason grades comprising the Gleason score, representative of Gleason scores 5-9, were arrayed from each prostatectomy specimen. Standard immunohistochemical techniques were used to assess expression of nine, cell death and cell cycle regulatory proteins implicated in the pathogenesis of prostate cancer (bax, bcl-2, bcl-xL, bin1, CD95, mdm2, p21, p53, and NFkappaB). The Spearman correlation coefficient revealed a strong correlation of bax, bin1, FAS, p65 and p21 expression with Gleason grade. Spearman correlation coefficients showed that expression of, bax and bin1, bax and MDM2, Bax and p21, and bax and p65 NFkappaB was highly associated. Other significant associations were identified between bin1 and p21, bin1 and MDM2, bin1 and p65 NFkappaB and between p21 and p65 NFkappaB. A model for predicting the biological potential of Gleason score 7 prostate cancer using multivariable logistic regression methods was developed. The findings also indicate that the profile of specific markers for Gleason grade 3 prostate cancer correlates with the overall context of the Gleason score. These data support the view that important molecular differences exist among and between the Gleason scores. Furthermore, there is significant molecular heterogeneity among prostatectomy specimens containing Gleason grade 3 cancer. This observation may have broader implications regarding the determination of risk among patients with prostate cancer that is currently considered to be of either good prognosis or unclear prognosis, i.e. Gleason score 7 tumors.


DNA, but not protein vaccine based on mutated BORIS antigen significantly inhibits tumor growth and prolongs the survival of mice.
The ideal immunological target for cancer vaccine development would meet the criteria of tumor specificity, immunogenicity and vital dependency of the tumor on the functional activities of the antigenic target so as to avoid antigenic loss by mutation. Given that at face value the brother of regulator of imprinted sites (BORIS) transcription factor meets these criteria, we have developed a mutant variant of this molecule (mBORIS) that lacks tumorigenic ability, while retaining immunogenic epitopes that elicits responses against histologically irrelevant tumor cells. Here we compared vaccine strategies employing as an immunogen either mBORIS recombinant protein formulated in a strong Th1-type adjuvant, QuilA or DNA encoding this immunogen along with plasmids expressing interleukin (IL)12/IL18 molecular adjuvants. In both groups of vaccinated mice induction of tumor-specific immunity (antibody response, T-cell proliferation, cytokine production, T-cell cytotoxicity) as well as ability to inhibit growth of the aggressive breast cancer cell line and to prolong survival of vaccinated animals have been tested. We determined that DNA, but not recombinant protein vaccine, induced potent Th1-like T-cell recall responses that significantly inhibited tumor growth and prolongs the survival of vaccinated mice. These studies demonstrate that DNA immunization is superior to recombinant protein strategy and provide a clear guidance for clinical development of a cancer vaccine targeting what appears to be a universal tumor antigen.


Extrathoracic heart in northern Cameroon: a case report.
Sternal clefts, ectopia cordis, and Cantrell's pentalogy continue to be very rare congenital anomalies in pediatric surgery. The prenatal diagnosis is easily made with ultrasound by visualizing the heart outside the thoracic cavity. Ectopia cordis is frequently associated with other congenital defects involving multiple organ systems. We report a case of ectopia cordis with successful surgical correction on a 7 months old child from northern Cameroon.


Deliberation: obtaining informed input from a diverse public.
Health care decision makers require public input to incorporate diverse values into programs and policies. Deliberation, one method for obtaining input, seeks to apply inclusive principles wherein diverse groups provide perspectives to inform decisions. We evaluate whether participants of different racial, ethnic, and educational backgrounds show differences in the effect of deliberation and the value placed on deliberation participation. We surveyed 907 participants before and after deliberation. Regression models examined associations between demographics and change in knowledge and attitudes, and perceived impact. Changes in knowledge about using medical evidence in decision-making were not associated with race, ethnicity, or education. Changes in attitudes were not associated with these characteristics with one exception. African American, Hispanic, and participants with lower educational attainment reported more perceived impact. Similar results across demographic groups suggest deliberation's promise for obtaining input from a diverse public to inform health programs and policies.


[Effect of oxygen inhalation on hemodynamics in chronic thromboembolic pulmonary hypertension].
This study evaluates the haemodynamic effects of oxygen inhalation on pulmonary artery pressure and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension. In 47 patients with chronic thromboembolic pulmonary hypertension haemodynamic parameters were measured before and after oxygen inhalation. In moderately severe and severe pulmonary hypertension oxygen inhalation significantly reduced mean pulmonary artery pressure by about 11.1% and 4.6%, respectively. However, pulmonary vascular resistance was not significantly affected. Oxygen saturation improved and heart rate was reduced. Cardiac index decreased in severe pulmonary hypertension. Systemic vascular resistance increased. We conclude that oxygen inhalation reduces pulmonary artery pressure and improves oxygen supply in patients with moderately severe and severe chronic thromboembolic pulmonary hypertension.


glc locus of Escherichia coli: characterization of genes encoding the subunits of glycolate oxidase and the glc regulator protein.
The locus glc (min 64.5), associated with the glycolate utilization trait in Escherichia coli, is known to contain glcB, encoding malate synthase G, and the gene(s) needed for glycolate oxidase activity. Subcloning, sequencing, insertion mutagenesis, and expression studies showed five additional genes: glcC and in the other direction glcD, glcE, glcF, and glcG followed by glcB. The gene glcC may encode the glc regulator protein. Consistently a chloramphenicol acetyltransferase insertion mutation abolished both glycolate oxidase and malate synthase G activities. The proteins encoded from glcD and glcE displayed similarity to several flavoenzymes, the one from glcF was found to be similar to iron-sulfur proteins, and that from glcG had no significant similarity to any group of proteins. The insertional mutation by a chloramphenicol acetyltransferase cassette in either glcD, glcE, or glcF abolished glycolate oxidase activity, indicating that presumably these proteins are subunits of this enzyme. No effect on glycolate metabolism was detected by insertional mutation in glcG. Northern (RNA) blot experiments showed constitutive expression of glcC but induced expression for the structural genes and provided no evidence for a single polycistronic transcript.


Random effects models in clinical research.
In clinical trials a fixed effects research model assumes that the patients selected for a specific treatment have the same true quantitative effect and that the differences observed are residual error. If, however, we have reasons to believe that certain patients respond differently from others, then the spread in the data is caused not only by the residual error but also by between-patient differences. The latter situation requires a random effects model. To explain random effects models in analysis of variance and to give examples of studies qualifying for them. If in a particular study the data are believed to be different from one assessing doctor to the other, and if we have no prior theory that 1 or 2 assessing doctors produced the highest scores, but rather expect there may be heterogeneity in the population of doctors at large, then a random effects model will be appropriate. For that purpose between-doctor variability is compared to within-doctor variability. If the data of 2 separate studies of the same new treatment are analyzed simultaneously, it will be safe to consider an interaction effect between the study number and treatment efficacy. If the interaction is significant, a random effects model with the study number as random variable, will be adequate. For that purpose the treatment effect is tested against the interaction effect. In a multicenter study the data are at risk of interaction between centers and treatment efficacy. If this interaction is significant, a random effects model with the health center as random variable, will be adequate. The treatment effect is tested not against residual but against the interaction. If in a crossover study a treatment difference is not observed, this may be due to random subgroup effects. A post-hoc random effects model, with patients effect as random variable, testing the treatment effect against treatments x patients interaction, will be appropriate. Random effects research models enable the assessment of an entire sample of data for subgroup differences without need to split the data into subgroups. Clinical investigators, in general, are hardly aware of this possibility and, therefore, wrongly assess random effects as fixed effects leading to a biased interpretation of the data.


The Association of Mindful Parenting with Glycemic Control and Quality of Life in Adolescents with Type 1 Diabetes: Results from Diabetes MILES-The Netherlands.
The objective of this study was to examine associations between the mindful parenting style of parents of adolescents (aged 12-18) with type 1 diabetes mellitus (T1DM), and the glycaemic control and quality of life (QoL) of the adolescents. Chronic health conditions, such as T1DM, that require demanding treatment regimens, can negatively impact adolescents' quality of life. Therefore, it is important to determine whether mindful parenting may have a positive impact in these adolescents. Age, sex and duration of T1DM were examined as potential moderators. Parents (N = 215) reported on their own mindful parenting style (IM-P-NL) and the adolescents' glycaemic control. Parents and the adolescents with T1DM (N = 129) both reported on adolescents' generic and diabetes-specific QoL (PedsQL™). The results showed that a more mindful parenting style was associated with more optimal hemoglobin A1c (HbA1c) values for boys. For girls, a more mindful parenting style was associated with not having been hospitalized for ketoacidosis. For both boys and girls, a more mindful parenting style was associated with better generic and diabetes-specific proxy-reported QoL. In conclusion, mindful parenting style may be a factor in helping adolescents manage their T1DM. Mindful parenting intervention studies for parents of adolescents with T1DM are needed to examine the effects on adolescents' glycaemic control and their quality of life.


Circum-menopausal changes in women's preferences for sexually dimorphic shape cues in peer-aged faces.
Recent studies suggest that post-menopausal women demonstrate stronger preferences for feminine characteristics in male and female faces than do pre-menopausal women, potentially reflecting stronger preferences for healthy men and greater derogation of attractive women among more fertile women. A limitation of this work was that it assessed circum-menopausal women's face preferences using images of young adults only. Here, we found that post-menopausal women demonstrated stronger preferences for feminine characteristics in male and female peer-aged faces that did pre-menopausal women. These data present novel evidence for circum-menopausal variation in face perception and confirm that the circum-menopausal variation in face preferences observed previously was not an artefact of the young faces employed as stimuli.


Hypoxia induces changes in phospholipase A2 in rat proximal tubules: evidence for multiple forms.
Increased free fatty release during hypoxia is believed to contribute to cell injury. This phenomenon is likely to be mediated through activation of specific isoforms of phospholipase A2 (PLA2). In this study, PLA2 enzymatic activity was measured in cell-free extracts prepared from rat renal proximal tubules. Both soluble and membrane-associated PLA2 activity were detected. All PLA2 activity detected during normoxia was Ca2+ dependent. Fractionation of cytosolic extracts by gel filtration revealed three peaks of PLA2 activity. Exposure of tubules to hypoxia resulted in stable activation of soluble PLA2 activity, which correlated with disappearance of the highest molecular mass form (> 100 kDa) and appearance of a low-molecular-mass form (approximately 15 kDa) of PLA2. Hypoxia also resulted in release of a low-molecular-mass form of PLA2 into the extracellular medium. Pretreatment of tubules with glycine before hypoxia blocked this release of PLA2 but not activation of soluble PLA2 activity. These studies provide direct evidence for PLA2 activation during hypoxia and suggest that multiple mechanisms regulate free fatty acid release associated with hypoxia injury.


Lactobacilli differently regulate expression and secretion of CXCL8 in urothelial cells.
Modulation of the immune response is an established feature of certain lactobacilli. CXCL8 is an inflammatory chemokine released by the urinary tract mucosa after contact with uropathogenic Escherichia coli during urinary tract infection and is crucial for proper infiltration of immune cells. Nevertheless, persistently high levels of CXCL8 are associated with pathogenicity and malignancy. In this study, we tested twelve Lactobacillus strains for their ability to influence CXCL8 release from urothelial cells. We evaluated how strains from different Lactobacillus species could regulate CXCL8 in human 5637 urothelial cells, either resting cells or cells concomitantly challenged with heat-killed E. coli. A majority of the tested species altered CXCL8 release from the urothelial cells after 24 hours of stimulation. Most species increased CXCL8 release, whereas a few lactobacilli efficiently suppressed CXCL8 secretion from E. coli-challenged cells. While strong CXCL8 modulators such as Lactobacillus reuteri and Lactobacillus delbrueckii were unable to degrade CXCL8 in the extracellular environment, effects on IL8 transcription were evident for selected lactobacilli. Although IL8 transcription was affected by lactobacilli, the influence on mRNA transcript did not correlate to the impact on CXCL8 release. Phylogenetic analysis based on a 16S rRNA dendrogram of the tested lactobacilli and their effect on CXCL8 revealed some linkage to specific Lactobacillus groups. Testing the immunomodulatory nature of lactobacilli can prove important when selecting new probiotic microbes. Moreover, we believe that phylogenetic and phenotypic similarities could be used to analyse the traits governing such modulation.


Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.
Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-β1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs.


Invasive Intraductal Papillary Mucinous Neoplasms: CT Features of Colloid Carcinoma Versus Tubular Adenocarcinoma of the Pancreas.
OBJECTIVE. The purpose of this study is to compare the CT features of colloid carcinoma and tubular adenocarcinoma of the pancreas arising in association with intraductal papillary mucinous neoplasms (IPMNs). MATERIALS AND METHODS. The preoperative CT images of 85 patients with histopathologically proven IPMNs and associated invasive adenocarcinoma located next to each other were retrospectively reviewed. Twenty-nine patients (34.1%; 19 men and 10 women; mean [± SD] age, 68.0 ± 9.5 years) had invasive colloid carcinoma, and 56 patients (65.9%; 31 men and 25 women; mean age, 70.8 ± 10.6 years) had invasive tubular adenocarcinoma. We compared the following CT features between the two groups: IPMN type, main pancreatic duct (MPD) and common bile duct diameters, diameter and characteristics of the largest cystic lesion for branch duct and mixed-type IPMNs, presence of an extracystic or extraductal solid mass next to the cystic lesion or MPD, morphologic features of the upstream MPD in relation to the cystic lesion or solid mass, and presence of a fistula to the adjacent organs. RESULTS. An MPD size of 9.5 mm or greater, a largest cystic lesion diameter of 28 mm or greater, location in the head or neck, septation, calcification, presence of a mural nodule(s) within a cystic lesion or MPD, and presence of a fistula were all more commonly associated with colloid carcinoma. In contrast, presence of an extracystic or extraductal solid mass and an abrupt change in the caliber of the dilated MPD were associated with tubular adenocarcinoma. The best CT feature for differentiating between the two groups was the morphologic features of the upstream MPD in relation to the cystic lesion or solid mass (sensitivity, 81.3%; specificity, 92.3%). CONCLUSION. Preoperative CT is helpful in differentiating two types of invasive carcinoma arising in association with IPMNs. These findings are clinically important because prognosis is better for colloid carcinoma than for tubular adenocarcinoma.


Hydration recommendations for sport 2008.
Fluid replacement remains an important strategy for preserving exercise performance as dehydration in excess of 2% of body weight consistently impairs aerobic exercise performance. Too much of a good thing, however, can have negative health consequences as persistent drinking in excess of sweating rate can induce symptomatic exercise associated hyponatremia. This short review highlights new position stands and/or policy statements regarding fluid replacement for sport, evidence that laboratory findings translate to team sport performance, and current hydration practices of athletes. It is culminated with practical strategies for drinking appropriately during physical activity.


Generalization of associations of kidney-related genetic loci to American Indians.
CKD disproportionally affects American Indians, who similar to other populations, show genetic susceptibility to kidney outcomes. Recent studies have identified several loci associated with kidney traits, but their relevance in American Indians is unknown. This study used data from a large, family-based genetic study of American Indians (the Strong Heart Family Study), which includes 94 multigenerational families enrolled from communities located in Oklahoma, the Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a population-based study of cardiovascular disease in American Indians. This study selected 25 single nucleotide polymorphisms in 23 loci identified from recently published kidney-related genome-wide association studies in individuals of European ancestry to evaluate their associations with kidney function (estimated GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study. This study also examined the association of single nucleotide polymorphisms in the APOL1 region with estimated GFR in 1121 Strong Heart Family Study participants. GFR was estimated using the abbreviated Modification of Diet in Renal Disease Equation. Additive genetic models adjusted for age and sex were used. This study identified significant associations of single nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2, PIP5K1B, and WDR72 (P<2.1 × 10(-3) to account for multiple testing). Single nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total variance and 2.9% of its heritability. An intronic variant of BCAS3 was significantly associated with urinary albumin to creatinine ratio. APOL1 single nucleotide polymorphisms were not associated with estimated GFR in a single variant test or haplotype analyses, and the at-risk variants identified in individuals with African ancestry were not detected in DNA sequencing of American Indians. This study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries.


Possible role of SCN4A skeletal muscle mutation in apnea during seizure.
SCN4A gene mutations cause a number of neuromuscular phenotypes including myotonia. A subset of infants with myotonia-causing mutations experience severe life-threatening episodic laryngospasm with apnea. We have recently identified similar SCN4A mutations in association with sudden infant death syndrome. Laryngospasm has also been proposed as a contributory mechanism to some cases of sudden unexpected death in epilepsy (SUDEP). We report an infant with EEG-confirmed seizures and recurrent apneas. Whole-exome sequencing identified a known pathogenic mutation in the SCN4A gene that has been reported in several unrelated families with myotonic disorder. We propose that the SCN4A mutation contributed to the apneas in our case, irrespective of the underlying cause of the epilepsy. We suggest this supports the notion that laryngospasm may contribute to some cases of SUDEP, and implicates a possible shared mechanism between a proportion of sudden infant deaths and sudden unexpected deaths in epilepsy.


[Identification and antibiotic susceptibility of viridans group streptococci isolates recovered from patients hospitalized at a teaching hospital in Buenos Aires City].
Members of the viridans group streptococci (VGS) are the cause of local and invasive infections. Due to the severity of these infections and taking into account that reports regarding epidemiological aspects are scarce, the aims of this work were the identification and the study of the antibiotic susceptibility profiles of the isolates recovered from patients that were hospitalized in order to find out about the resistance level and the epidemiology of infections in which VGS are involved. A hundred and thirty two isolates identified as VGS were isolated at Hospital de Clínicas «José de San Martín» during the period 2011-2015. The identification was performed by biochemical test and mass spectrometry by Matrix Assisted Laser Desorption Ionization -Time of Flight Mass Spectrometry. Streptococcus anginosus group was prevalent (42%) followed by Streptococcus mitis group (33%). In the latter, isolates of Streptococcus pneumoniae were excluded. All the VGS isolates were susceptible to ertapenem, meropenem, linezolid and vancomycin; 25.8% were resistant (I+R) to penicillin, being prevalent in the S. mitis group. Regarding ceftriaxone and cefepime 96.9% of the isolates were susceptible. Only two isolates were resistant to levofloxacin, 27.2% to tetracycline and it was not found high level resistance to gentamycin (MIC range 0.5-32μg/ml). Resistance to erythromycin was 17.4% with no significant difference between M and MLS phenotypes. The most active antibiotics were in addition to ceftriaxone and cefepime, vancomycin, ertapenem, meropenem and linezolid. These results highlight the importance of the continuous surveillance of the infections caused by VGS in order to predict a correct antibiotic therapy.


Evaluating the capacity of heavy metal pollution enrichment in green vegetation in the industrial zone, Northwest China.
It focused on heavy metal pollution of green vegetation in Tuokexun County, Xinjiang Northwest China's suburban industrial area, using inductively coupled plasma emission spectrometer to analyze the samples for Mn, Ni, Zn, Cd, Hg, Pb, As, Cu, and Cr contents. The soil's heavy metal content in the study area indicated a minor level of pollution overall (P = 1.77), with the most severe contamination being Hg, which is more likely to be caused by human activities. Heavy metal elements in trees have the most stable composition in comparison to grass and shrubs, with varying concentrations across different vegetation. The concentrations of Mn, Cd and Hg were highest in the Haloxylon ammodendron, Ni in Morus alba, Pb, As and Cu in Nitraria tangutorums, and Cr in Phragmites australis. Heavy metal restoration is most effectively performed by shrubs, and there are disparities in heavy metal enrichment among various vegetation. No significant difference was found in heavy metal enrichment between the aboveground and underground parts of vegetation. Based on the average of the membership function, Tamarix exhibits the strongest ability to enrich heavy metals, while Nitraria tangutorum comes in second, and Cynanchum chinense R.Br. is the least effective among all plant species. Morus alba is recommended as the primary planting species in the area. Nitraria tangutorum and Haloxylon ammodendron have good potential for Cd and As restoration and can be used as supporting vegetation.


[Evaluation of the mutagenic properties of nanomaterials].
Nanomaterials have properties showing their possible mutagenic activity. The review analyzes the currently available studies evaluating the mutagenic properties of nanomaterials. The studies have been conducted using limited quantities of nanomaterials and mainly in in vitro experiments. But they also suggest that nanomaterials are able to induce DNA damages, chromosomal aberrations, micronuclei, and aneuploidy. Single studies have revealed consequences due to the genotoxic effect of nanomaterials: rat lung cancer. There is a need for developing a system to evaluate the mutagenic properties of nanomaterials, the basis of which may be a polyorgan micronuclear test, by taking the indicators of proliferation and apoptosis into account.


Defective inflammatory monocyte development in IRF8-deficient mice abrogates migration to the West Nile virus-infected brain.
IRF8 (interferon-regulatory factor-8) plays a critical role in regulating myeloid cell differentiation. However, the role of this transcription factor in the development of Ly6C+ inflammatory monocytes and their migration to the infected brain has not been examined. We have previously shown that West Nile virus (WNV) infection of wild-type (WT) mice triggers a significant increase in numbers of Ly6C+ monocytes in the bone marrow. These cells traffic via the blood to the infected brain, where they give rise to proinflammatory macrophages. Here, we show that WNV-infected IRF8-deficient (IRF8-/-) mice had significantly reduced numbers of Ly6C+ monocytes in the periphery, with few of these cells found in the blood. Furthermore, low numbers of inflammatory monocyte-derived macrophages were observed in the brains of IRF8-/- mice throughout infection. Adoptive transfer of IRF8-/- Ly6C+ monocytes demonstrated that these cells were intrinsically unable to traffic to the inflamed brain. Low expression of the chemokine receptor CCR2 and integrin VLA-4 by IRF8-/- monocytes likely contributed to this defect, as the interactions between these proteins and their ligands are critical for monocyte egress and migration to inflammatory foci. These data highlight a critical role for IRF8 in inflammatory monocyte differentiation and migration during WNV infection.


PHOTOLITHOGRAPHY-FREE LASER-PATTERNED HF ACID-RESISTANT CHROMIUM-POLYIMIDE MASK FOR RAPID FABRICATION OF MICROFLUIDIC SYSTEMS IN GLASS.
Excellent chemical and physical properties of glass, over a range of operating conditions, make it a preferred material for chemical detection systems in analytical chemistry, biology, and the environmental sciences. However, it is often compromised with SU8, PDMS, or Parylene materials due to the sophisticated mask preparation requirements for wet etching of glass. Here, we report our efforts toward developing a photolithography-free laser-patterned hydrofluoric acid-resistant chromium-polyimide tape mask for rapid prototyping of microfluidic systems in glass. The patterns are defined in masking layer with a diode-pumped solid-state laser. Minimum feature size is limited to the diameter of the laser beam, 30 μm; minimum spacing between features is limited by the thermal shrinkage and adhesive contact of the polyimide tape to 40 μm. The patterned glass substrates are etched in 49% hydrofluoric acid at ambient temperature with soft agitation (in time increments, up to 60 min duration). In spite of the simplicity, our method demonstrates comparable results to the other current more sophisticated masking methods in terms of the etched depth (up to 300 μm in borosilicate glass), feature under etch ratio in isotropic etch (~1.36), and low mask hole density. The method demonstrates high yield and reliability. To our knowledge, this method is the first proposed technique for rapid prototyping of microfluidic systems in glass with such high performance parameters. The proposed method of fabrication can potentially be implemented in research institutions without access to a standard clean-room facility.


Control of the pattern of perithecium development in Sordaria fimicola on agar medium.
In a Sordaria fimicola (Rob.) Ces. and de Not. colony grown on agar medium in a petri plate, perithecia developed in a narrow band around the plate edge after the colony margin reached the edge. Physical wounding of the colony carried out shortly before or during the time perithecia were developing around the plate edge stimulated perithecium development in the wound area. Diffusion barriers were created by cutting small trenches in the agar parallel to the plate edge. The trenches were made at several different positions between the plate center and edge using cultures of several different ages, and the resultant distribution of perithecia along the trench edges suggested that the colony center and periphery produce diffusible inhibitors of perithecium development. These inhibitors may be responsible, in part, for the observed pattern of perithecium development in the colony.


The impact of social structure on breeding strategies in an island bird.
The social environment is a key factor determining fitness by influencing multiple stages of reproduction, including pair formation, mating behavior and parenting. However, the influence of social structure across different aspects of breeding is rarely examined simultaneously in wild populations. We therefore lack a consolidation of the mechanisms by which sociality impacts reproduction. Here we investigate the implications of the social environment before and during breeding on multiple stages of reproduction in an island population of the ground nesting shorebird, the Kentish plover (Charadrius alexandrinus). We utilise information on mating decisions, nest locations and nesting success across multiple years in combination with social network analysis. Sociality before breeding was connected with patterns of pair formation. In addition, site fidelity and personal breeding experience was associated with the spatial organisation of breeding pairs. Our results provide evidence that, while differential social interactions at localised scales influence patterns of reproductive pairing, site fidelity and personal breeding experience influence the structure of populations at the landscape scale. Our results underline the tight link between the social structure of populations and patterns of mating, while revealing that the relative influence of sociality, breeding experience and local ecology are dynamic across different facets of reproduction.


[Prospective analysis of clinical course and outcomes in silicosis patients].
The authors revealed features of clinical course and outcomes in patients with silicosis and silicotuberculosis, who worked on iron industry enterprise. The article covers comparative analysis of survival rate and mortality among silicosis patients over 14 years of observation.


Beneficial effects of melatonin on bovine oocytes maturation: a mechanistic approach.
This study was performed to investigate the effect of melatonin on bovine oocyte maturation and subsequent embryonic development in vitro. The endogenous melatonin concentration in bovine follicular fluid is approximately 10(-11) M. To examine the potential beneficial effects of melatonin on bovine oocyte maturation in vitro, germinal vesicle (GV) oocytes were incubated with different concentrations of melatonin (10(-11), 10(-9), 10(-7), 10(-5), 10(-3) M). Melatonin supplementation at suitable concentrations significantly promoted oocyte maturation. The development of embryos and the mean cell number/blastocyst produced after in vitro fertilization were remarkably improved. The most effective melatonin concentrations obtained from the studies ranged from 10(-9) to 10(-7) M. The expression of melatonin receptor MT1 and MT2 genes was identified in cumulus cells, granulosa cells, and oocytes using reverse transcription PCR, immunofluorescence, and Western blot. The mechanistic studies show that the beneficial effects of melatonin on bovine oocyte maturation are mediated via melatonin membrane receptors as the melatonin receptor agonist (IIK7) promotes this effect while the melatonin receptor antagonist (luzindole) blocks this action. Mechanistic explorations revealed that melatonin supplementation during bovine oocyte maturation significantly up-regulated the expressions of oocyte maturation-associated genes (GDF9, MARF1, and DNMT1a) and cumulus cells expansion-related gene (PTX3, HAS1/2) and that LHR1/2, EGFR are involved in signal transduction and epigenetic reprogramming. The results obtained from the studies provide new information regarding the mechanisms by which melatonin promotes bovine oocyte maturation in vitro and provide an important reference for in vitro embryo production of bovine and the human-assisted reproductive technology.


Epinephrine impairs insulin release by a mechanism distal to calcium mobilization. Similarity to lipoxygenase inhibitors.
The mechanisms that enable epinephrine (EPI) and lipoxygenase inhibitors to impede insulin secretion are unknown. We examined the possibility that EPI inhibits Ca2+ fluxes as its major mechanism by studying 45Ca efflux from prelabeled, intact rat islets. EPI (2.5 x 10(-7) to 1 x 10(-5) M) inhibited insulin release induced by the influx of extracellular Ca2+ (46 mM K+) or the mobilization of intracellular Ca2+ stores (2 mM Ba2+), but it did not reduce the 45Ca efflux stimulated by either agonist. EPI also nullified insulin release induced by isobutylmethylxanthine or dibutyryl cAMP, with minimal or no effects on 45Ca efflux, and blocked the insulinotropic effects of 12-O-tetradecanoylphorbol-13-acetate (a direct activator of protein kinase C), which is believed primarily to sensitize the exocytotic apparatus to Ca2+ without mobilizing additional Ca2+. Previously we reported that similar effects were induced by inhibitors of pancreatic islet lipoxygenase. In this study, however, pretreatment with either the alpha 2-adrenergic antagonist yohimbine or pertussis toxin did not block the effects of lipoxygenase inhibitors, although either agent did block the effects of EPI. Thus, EPI, via an alpha 2-receptor mechanism, is able to reduce exocytosis largely distal to, or independent of, changes in Ca2+ flux, cAMP formation or its Ca2+-mobilizing action, or generation of protein kinase C activators. Therefore, EPI may reduce the sensitivity of the exocytotic apparatus to Ca2+. Inhibition of islet lipoxygenase may have a similar effect; however, in this case, the effect would have to be unrelated, or distal, to stimulation of alpha 2-receptors.


Epigenetics and gestational diabetes: a review of epigenetic epidemiology studies and their use to explore epigenetic mediation and improve prediction.
Epigenetics encapsulates a group of molecular mechanisms including DNA methylation, histone modification and microRNAs (miRNAs). Gestational diabetes (GDM) increases the risk of adverse perinatal outcomes and is associated with future offspring risk of obesity and type 2 diabetes. It has been hypothesised that epigenetic mechanisms mediate an effect of GDM on offspring adiposity and type 2 diabetes and this could provide a modifiable mechanism to reduce type 2 diabetes in the next generation. Evidence for this hypothesis is lacking. Epigenetic epidemiology could also contribute to reducing type 2 diabetes by identifying biomarkers that accurately predict risk of GDM and its associated future adverse outcomes. We reviewed published human studies that explored associations between any of maternal GDM, type 2 diabetes, gestational fasting or post-load glucose and any epigenetic marker (DNA methylation, histone modification or miRNA). Of the 81 relevant studies we identified, most focused on the potential role of epigenetic mechanisms in mediating intrauterine effects of GDM on offspring outcomes. Studies were small (median total number of participants 58; median number of GDM cases 27) and most did not attempt replication. The most common epigenetic measure analysed was DNA methylation. Most studies that aimed to explore epigenetic mediation examined associations of in utero exposure to GDM with offspring cord or infant blood/placenta DNA methylation. Exploration of any causal effect, or effect on downstream offspring outcomes, was lacking. There is a need for more robust methods to explore the role of epigenetic mechanisms as possible mediators of effects of exposure to GDM on future risk of obesity and type 2 diabetes. Research to identify epigenetic biomarkers to improve identification of women at risk of GDM and its associated adverse (maternal and offspring) outcomes is currently rare but could contribute to future tools for accurate risk stratification.


Factors associated with 30-day mortality and morbidity in patients undergoing emergency colorectal surgery.
The 30-day period following emergency colorectal surgery (ECRS) is associated with high mortality and morbidity. There is a lack of data assessing factors associated with outcomes of ECRS in the Saudi population. Assess factors associated with 30-day postoperative mortality and complications following ECRS. Retrospective cohort study. Single tertiary care center, Riyadh, Saudi Arabia. Demographic characteristics (age, sex, diagnosis, American Society of Anesthesiologists classification, pre-operative septic state, smoking, and comorbidities), operative characteristics (urgency, diverting ostomy, and procedure performed), and postoperative characteristics (length of stay, 30-day mortality, intensive care unit [ICU] admission, ICU length of stay, surgical site infection [SSI], readmission, reoperation, and complications) were collected from electronic medical records. Univariate logistic regression was used to evaluate association with the outcome measures (30-day mortality and postoperative complications). Multivariate logistic regression was applied to evaluate independent variables. Thirty-day postoperative mortality and morbidity. 241 patients. Among 241 patients, 145 (60.2%) were men, and 80 (33.2%) patients were between 50-64 years of age. The most common indication for surgery was malignancy 138 (57%). The overall complication rate was 26.6% and the 30-day mortality rate was 11.2%. Left hemicolectomy was the most commonly performed procedure, performed in 69 (28.6%) patients. Patients between the age of 65-74 had an increased odds of death within 30 days (OR 5.25 [95% CI 1.03-26.5]) on univariate analysis. Preoperative sepsis was associated with a fourfold increase in the likelihood of 30-day mortality (OR 4.44, 95% CI 1.21-16.24, P=.024) on multivariate analysis. The likelihood of hospital re-admission increased by fivefold in patients who developed a postoperative complication (OR 5.33, 95% CI 1.30-21.78, P=.02). Preoperative sepsis was independently associated with 30-day mortality in patients undergoing ECRS, while the likelihood of hospital readmission increased in patients with postoperative complications. Expeditious control of sepsis in the emergency surgical setting by both surgical and medical interventions may reduce the likelihood of postoperative mortality. Establishing discharge protocols for postoperative ECRS patients is advocated. Retrospective design, small sample size, and single setting.


Readmission to the acute care unit and functional outcomes in patients with severe brain injury during rehabilitation.
Medical and surgical complications are common after brain lesions and may require acute care unit readmission (ACUR) during the rehabilitation stay. This clinical phenomenon has not been explored in subjects with severe brain injury (sBI). Because sBI patients come from the intensive care unit (ICU), patients may be transferred to rehabilitation before complete clinical stabilization. We investigated ACUR and causes as well as whether those who required ACUR had different functional outcomes. Prospective cohort study. Dedicated rehabilitation setting. Adult subjects with sBI causing a disorder of consciousness graded 3-8 on the Glasgow Coma Scale admitted to a dedicated rehabilitative setting were prospectively enrolled from January 2014 to December 2015. Functional outcome was investigated using the Rancho Los Amigos Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS), in subjects with and without ACUR, at admission and discharge. Mortality and length of stay (LOS) were recorded. One hundred-thirty (53 F, 77 M; mean age: 55.7±17.8) subjects were admitted to the rehabilitation setting, and 97 were enrolled (43 F, 54 M; mean age: 54.7±18.2). Thirty-six ACUR were detected that involved 29 (29.8%) patients. There were 20 and 16 referrals to acute medical and surgical care, respectively. Significant functional outcomes in all assessment measures were observed after rehabilitation, but subjects without ACUR showed significant improvement in all measurements: LCF (P=0.001), DRS (P<0.001), GOS (P=0.003), and mRS (P<0.001), compared to those who required ACUR. At baseline, patients with ACUR were more disabled than those without ACUR, and they had significant lower LCF scores: 2.60 (95% CI: 2.15-3.14) and 3.47 (95% CI: 3.07-3.91) (P=0.013), respectively. Significant longer LOS was observed in subjects with ACUR as compared to those without ACUR: 120 (q1-q3:93-165) vs. 63 (q1-q3: 38-93) days (P<0.001), respectively. The intra-hospital mortality rate was higher in patients who required ACUR (8.1 events per 100 person-months) as compared to those who did not require ACUR (2.8 events per 100 person-months). Readmission to acute care was common in subjects with sBI during rehabilitation. Subjects who required ACUR had poorer functional outcomes, higher risk of mortality and longer LOS than subjects without ACUR. Careful control of these subjects and more strict collaboration and communication among physicians on the rehabilitative team are required to plan proper care pathways.


Ethylene regulates root growth through effects on auxin biosynthesis and transport-dependent auxin distribution.
In plants, each developmental process integrates a network of signaling events that are regulated by different phytohormones, and interactions among hormonal pathways are essential to modulate their effect. Continuous growth of roots results from the postembryonic activity of cells within the root meristem that is controlled by the coordinated action of several phytohormones, including auxin and ethylene. Although their interaction has been studied intensively, the molecular and cellular mechanisms underlying this interplay are unknown. We show that the effect of ethylene on root growth is largely mediated by the regulation of the auxin biosynthesis and transport-dependent local auxin distribution. Ethylene stimulates auxin biosynthesis and basipetal auxin transport toward the elongation zone, where it activates a local auxin response leading to inhibition of cell elongation. Consistently, in mutants affected in auxin perception or basipetal auxin transport, ethylene cannot activate the auxin response nor regulate the root growth. In addition, ethylene modulates the transcription of several components of the auxin transport machinery. Thus, ethylene achieves a local activation of the auxin signaling pathway and regulates root growth by both stimulating the auxin biosynthesis and by modulating the auxin transport machinery.


Analysis of the influence of host lifestyle (coffee consumption, drinking, and smoking) on Korean oral microbiome.
If a DNA sample collected in the field is old or degraded, short tandem repeat analysis is difficult to perform, a representative analysis method currently used for individual identification. Given that microorganisms exist everywhere and within the human body, in similar amounts to human cells, microbial analysis could be used to identify individuals even in cases in which human DNA-based identification is difficult. Research has demonstrated that the types of microorganisms within the human body differ depending on various internal or external factors, such as body part or bodily fluid type, lifestyle, geographical area of residence, sex, and age. In this study, we aimed to examine the relationship between lifestyle factors and the composition and diversity of the oral microbiome in individuals living in Korea. We collected 43 saliva samples from Korean individuals and analyzed the oral microbiome and its variations due to external factors, such as coffee consumption, drinking, and smoking. Linear discriminant analysis effect size revealed that Oribacterium, Campylobacter, and Megasphaera were abundant in coffee consumers, whereas Saccharimonadales, Clostridia, and Catonella were abundant in alcohol non-drinkers. We found increased levels of Stomatobaculum in the saliva of smokers, compared with that of non-smokers. Thus, our analysis revealed characteristic microorganisms for each parameter that was evaluated (coffee consumption, smoking, drinking). Consequently, our study provides insight into the oral microbiome in the Korean population and lays the foundation for developing the Korean Forensic Microbiome Database.


Investigation of the relationship between the metabolic profile of tobacco leaves in different planting regions and climate factors using a pseudotargeted method based on gas chromatography/mass spectrometry.
An improved pseudotargeted method using gas chromatography/mass spectrometry (GC/MS) was developed to investigate the metabolic profile of tobacco leaves from three planting regions (Yunnan, Guizhou, and Henan provinces). The analytical characteristics of the method with regard to reproducibility, precision, linearity, and stability were satisfactory for metabolic profiling study. Partial least-squares-discriminant analysis and hierarchical cluster analysis demonstrated that the metabolic profiles of tobacco from the Yunnan and Guizhou regions were different from that from the Henan province. The amino acid (e.g., phenylalanine, leucine, and tyrosine) and carbohydrate (e.g., fructose, trehalose, and sucrose) contents were the highest in Henan tobacco. The highest contents of organic acids (e.g., isocitrate, citrate, and fumarate) of the TCA cycle and antioxidants (e.g., quinate, chlorogenic acid, and ascorbate) were found in Guizhou tobacco. The correlation coefficients between metabolite content and climate factors (rainfall, sunshine, and temperature) demonstrated that drought facilitated the accumulation of sugars and amino acids. The content of TCA cycle intermediates could be influenced by multiple climate factors. This study demonstrates that the pseudotargeted method with GC/MS is suitable for the investigation of the metabolic profiling of tobacco leaves and the assessment of differential metabolite levels related to the growing regions.


Transepithelial invasion and intramesenchymal infiltration of the chick embryo chorioallantois by tumor cell lines.
The ability of cultured tumor cell lines to invade across epithelia was studied by placing 10(4) to 10(6) dispersed cells on the chorionic epithelium (CE) of the chorioallantoic membrane of the 10-day chick embryo. Tumor lines included Walker carcinosarcoma, F87 cl 6T2 and B16-BL6 melanomas, and KiSV-NIH, 3B77SC4, and HT 1080 sarcomas. The CE is a bilayer of cells with a superficial periderm overlying a basal layer. Invasion across an intact CE was very weak (limited to the formation of "microtumors" by a small fraction of the inoculated cells in 5 to 50% of the embryos) but was massive (most or all of the inoculated cells invaded in over 99% of the embryos) if the chorioallantoic membrane was traumatized in a fashion which disrupted the periderm but left the basal layer intact. Normal fibroblasts also invaded across the traumatized CE. The histological picture of invasion suggests that cells inoculated on the traumatized CE induced large-scale active retraction of the basal layer, resulting in the formation of large gaps in its continuity. Migration into the subjacent mesoderm occurred through these gaps. The nodules formed by both tumorigenic and normal cells became extensively vascularized within 3 days.


Reciprocal subsidies and food web pathways leading to chum salmon fry in a temperate marine-terrestrial ecotone.
Stable isotope analysis was used to determine the relative proportions of terrestrial and marine subsidies of carbon to invertebrates along a tidal gradient (low-intertidal, mid-intertidal, high-intertidal, supralittoral) and to determine the relative importance of terrestrial carbon in food web pathways leading to chum salmon fry Oncorhynchus keta (Walbaum) in Howe Sound, British Columbia. We found a clear gradient in the proportion of terrestrially derived carbon along the tidal gradient ranging from 68% across all invertebrate taxa in the supralittoral to 25% in the high-intertidal, 20% in the mid-intertidal, and 12% in the low-intertidal. Stable isotope values of chum salmon fry indicated carbon contributions from both terrestrial and marine sources, with terrestrially derived carbon ranging from 12.8 to 61.5% in the muscle tissue of chum salmon fry (mean 30%). Our results provide evidence for reciprocal subsidies of marine and terrestrially derived carbon on beaches in the estuary and suggest that the vegetated supralittoral is an important trophic link in supplying terrestrial carbon to nearshore food webs.


SNP Discovery and Genetic Variation of Candidate Genes Relevant to Heat Tolerance and Agronomic Traits in Natural Populations of Sand Rice (Agriophyllum squarrosum).
The extreme stress tolerance and high nutritional value of sand rice (Agriophyllum squarrosum) make it attractive for use as an alternative crop in response to concerns about ongoing climate change and future food security. However, a lack of genetic information hinders understanding of the mechanisms underpinning the morphological and physiological adaptations of sand rice. In the present study, we sequenced and analyzed the transcriptomes of two individuals representing semi-arid [Naiman (NM)] and arid [Shapotou (SPT)] sand rice genotypes. A total of 105,868 pairwise single nucleotide polymorphisms (SNPs) distributed in 24,712 Unigenes were identified among SPT and NM samples; the average SNP frequency was 0.3% (one SNP per 333 base pair). Characterization of gene annotation demonstrated that variations in genes involved in DNA recombination were associated with the survival of the NM population in the semi-arid environment. A set of genes predicted to be relevant to heat stress response and agronomic traits was functionally annotated using the accumulated knowledge from Arabidopsis and several crop plants, including rice, barley, maize, and sorghum. Four candidate genes related to heat tolerance (heat-shock transcription factor, HsfA1d), seed size (DA1-Related, DAR1), and flowering (early flowering 3, ELF3 and late elongated hypocotyl, LHY) were subjected to analysis of the genetic diversity in 10 natural populations, representing the core germplasm resource across the area of sand rice distribution in China. Only one SNP was detected in each of HsfA1d and DAR1, among 60 genotypes, with two in ELF3 and four in LHY. Nucleotide diversity ranged from 0.00032 to 0.00118. Haplotype analysis indicated that the NM population carried a specific allele for all four genes, suggesting that divergence has occurred between NM and other populations. These four genes could be further analyzed to determine whether they are associated with phenotype variation and identify alleles favorable for sand rice breeding.


Immune checkpoint inhibitors as adjuvant therapy in patients with completely resected nonsmall cell lung cancer.
The purpose of the review is to summarize the current status of immune checkpoint inhibitors as adjuvant therapy in patients with resected nonsmall cell lung cancer (NSCLC). The IMpower010 phase 3 trial demonstrated improved disease-free survival and, in case of PD-L1 at least 50%, also improved overall survival for atezolizumab compared to best supportive care among patients with completely resected stage II-IIIA NSCLC. The PEARLS/KEYNOTE-091 trial showed increased disease-free survival for pembrolizumab among patients with stage IB-IIIA NSCLC. Trials with nivolumab and durvalumab are ongoing. Atezolizumab or pembrolizumab have become options for adjuvant therapy in patients with completely resected NSCLC.


Clonidine-displacing substance from bovine brain binds to imidazoline receptors and releases catecholamines in adrenal chromaffin cells.
Identification of nonadrenergic binding sites for clonidine and related imidazolines in brain and peripheral tissues and partial purification of an endogenous ligand for these sites have led to the postulation of a novel transmitter/receptor system. The receptors seem to be present in adrenal medulla and to regulate chromaffin cell function. The present study was undertaken to test the ability of the putative endogenous ligand clonidine-displacing substance (CDS) to displace [3H]idazoxan binding to adrenal chromaffin cell membranes and to release catecholamines from cultured chromaffin cells. CDS potently displaces [3H]idazoxan binding to chromaffin cell membranes, with an IC50 of 5 units. The displacement of [3H]idazoxan binding by CDS was not modified by guanosine 5'-(beta, gamma-imido)triphosphate, suggesting that the imidazoline binding sites may not be GTP-binding protein-coupled receptors. CDS produced a large release of catecholamines from chromaffin cells, and the release was partially blocked by cobalt, a calcium channel blocker. The calcium-dependent release reached a plateau above 5 units of CDS, with a maximal response at 15 min. It is concluded that endogenous CDS, prepared from brain, regulates the secretion of catecholamines from adrenal chromaffin cells, probably by activating imidazole receptors.


[Isokinetic assessment and mid-term work reincorporation of patients surgically treated with the shoulder Latarjet technique].
We studied a group of 12 subjects with chronic posttraumatic scapulo-humeral instability who underwent arthroscopic coracoid transposition using Latarjet's technique. All patients were followed-up after the operation for a mean of 1.7 years (minimum 1 year, maximum 3 years). The follow-ups consisted of a clinico-functional evaluation with a apprehension test and isokinetic studies of strength and joint movements during internal and external rotation of the abducted shoulder, both on the healthy side and on the operated side. The isokinetic evaluation consisted of 5 repetitions of internal-external rotation at ana angular velocity of 60 degrees/sec. The results showed that the operated shoulder was slightly weaker than the healthy one, but that the difference was not statistically significant according to Student's t test for paired data. The profile of the trace did not show macroscopic differences between the two sides. At clinical assessment 11 of 12 patients reported a good-excellent outcome of the operation with complete recovery of shoulder function and return to previously performed sporting activities. In conclusion, this technique is shown to have a good medium-term outcome. Although there have been no complications in our series, a longer follow-up to evaluate possible complications would be advisable.


Gastroduodenal motility--a comparison between domperidone and metoclopramide.
Domperidone (Motilium) speeds the emptying rate of the smallest particle size of a digestible solid (radioactive cubed liver) but has no effect on the emptying rate of 400 ml of 5% dextrose in the normal canine stomach. Conversely, metoclopramide (Maxolon) speeds the emptying of the liquid, but slows the emptying rate of the digestible solid. The effect of domperidone on canine gastric electrical activity is to increase the frequency and strength of action potentials in the stomach after fasting and to slow the rate of discharge of the pacesetter potential, an effect similar to that seen after feeding.


The impacts of prosthetic interventions on mastication predominance in Kennedy Class Ⅱ patients.
Purpose The purpose of this study was to investigate the effects of prosthetic interventions in patients with Kennedy Class Ⅱ (unilateral missing posterior teeth) on mastication predominance.Methods The subjects comprised patients with Kennedy Class II and healthy dentate volunteers (HD group). The subjects were asked to freely chew the test foods (chewing gum, beef jerky, and peanuts). Electromyographic activity of the bilateral masseter muscles was recorded twice (before and after prosthetic intervention). The chewing side (right or left) was judged by the level of the root mean square electromyographic amplitude. Mastication predominance was assessed using the mastication predominance index (MPI; range 0-100%). Each patient was restored with a removable partial denture (RPD) or an implant-supported fixed prosthesis (IFP). The effects of prosthetic interventions were statistically evaluated by the differences between MPI before and after prosthetic interventions (pre-MPI and post-MPI , respectively).Results There was a significant difference between pre-MPI of patients with Kennedy Class II and MPI of the HD group (HD-MPI) for all test foods (P < 0.0001). Statistical analysis also demonstrated a significant difference between pre-MPI and post-MPI measured with each of the three food items in both the RPD and IFP groups (P < 0.0001). Multiple comparisons revealed that post-MPI in the IFP group, but not in the RPD group, was statistically comparable with HD-MPI, although there were no significant differences among the three groups when MPIs were calculated using peanuts.Conclusions Prosthetic interventions improved mastication predominance in patients with Kennedy Class Ⅱ patients. Depending on the food type, IFP might contribute to better improvement of mastication predominance than RPD depending on food.


Genome Evolution in Bacteria Isolated from Million-Year-Old Subseafloor Sediment.
Beneath the seafloor, microbial life subsists in isolation from the surface world under persistent energy limitation. The nature and extent of genomic evolution in subseafloor microbes have been unknown. Here, we show that the genomes of Thalassospira bacterial populations cultured from million-year-old subseafloor sediments evolve in clonal populations by point mutation, with a relatively low rate of homologous recombination and elevated numbers of pseudogenes. Ratios of nonsynonymous to synonymous substitutions correlate with the accumulation of pseudogenes, consistent with a role for genetic drift in the subseafloor strains but not in type strains of Thalassospira isolated from the surface world. Consistent with this, pangenome analysis reveals that the subseafloor bacterial genomes have a significantly lower number of singleton genes than the type strains, indicating a reduction in recent gene acquisitions. Numerous insertion-deletion events and pseudogenes were present in a flagellar operon of the subseafloor bacteria, indicating that motility is nonessential in these million-year-old subseafloor sediments. This genomic evolution in subseafloor clonal populations coincided with a phenotypic difference: all subseafloor isolates have a lower rate of growth under laboratory conditions than the Thalassospira xiamenensis type strain. Our findings demonstrate that the long-term physical isolation of Thalassospira, in the absence of recombination, has resulted in clonal populations whereby reduced access to novel genetic material from neighbors has resulted in the fixation of new mutations that accumulate in genomes over millions of years. IMPORTANCE The nature and extent of genomic evolution in subseafloor microbial populations subsisting for millions of years below the seafloor are unknown. Subseafloor populations have ultralow metabolic rates that are hypothesized to restrict reproduction and, consequently, the spread of new traits. Our findings demonstrate that genomes of cultivated bacterial strains from the genus Thalassospira isolated from million-year-old abyssal sediment exhibit greatly reduced levels of homologous recombination, elevated numbers of pseudogenes, and genome-wide evidence of relaxed purifying selection. These substitutions and pseudogenes are fixed into the population, suggesting that the genome evolution of these bacteria has been dominated by genetic drift. Thus, reduced recombination, stemming from long-term physical isolation, resulted in small clonal populations of Thalassospira that have accumulated mutations in their genomes over millions of years.


Calculations for new prescribers.
Mistakes in calculation can lead to potentially dangerous prescribing errors. This article takes the nurse prescriber through some basic calculations and points out the possible pitfalls.


[Syphilis in 2008: practical aspects and controversies].
Rising incidence rate of syphilis is observed in economically advanced countries, particularly among homosexual men and subpopulation with low socioeconomic status. The various clinical presentations are divided into early and late stages, including neurosyphilis. The latter can occur during any stage of the disease, leading to the question "when to perform lumbar puncture", particularly in HIV positive patients. Penicillin continues to be the first-line therapy for all stages of syphilis. An alternative treatment should be considered as an exemption, after advice from a specialist. All patients require prolonged clinical and serological follow-up after treatment to rule out relapse or re-infection. The diagnosis of syphilis is an opportunity to search and treat other sexually transmitted diseases in patients and their sexual partner(s).


A service for women with schizophrenia.
A program for women with schizophrenia that combines inpatient, outpatient, and outreach services is described. The program was established at the Clarke Institute of Psychiatry at the University of Toronto in 1995. Services include a comprehensive patient and family assessment, with subsequent recommendations to the treating clinician about differential diagnosis, psychopharmacologic and psychosocial treatments, and patient management during pregnancy and early parenthood. Other components of the program are home-based outreach services, substance abuse counseling, instruction of new mothers and parenting training, sex education, relationship-focused groups, and self-protection in an urban environment to prevent victimization. The clinic has established liaisons with pediatricians and gynecologists in the community to provide care to clinic patients. Linkages have also been established with agencies and facilities to fill gaps in the service spectrum, such as fitness programs and leisure activities and children's aid and protection.


The effects of clozapine on tardive dyskinesia.
This article reviews eight published studies that describe clozapine's effects on TD and examines the outcome of 30 patients with TD treated with clozapine for up to 36 months. These data indicate that TD response to clozapine is variable but that approximately 43% of cases, particularly those with dystonic features, improved after clozapine treatment. Methodological limitations of the studies described, however, preclude definitive conclusions, which must await appropriately controlled trials.


Precautions and Procedures for Coronary and Structural Cardiac Interventions During the COVID-19 Pandemic: Guidance from Canadian Association of Interventional Cardiology.
The globe is currently in the midst of a COVID-19 pandemic, resulting in significant morbidity and mortality. This pandemic has placed considerable stress on health care resources and providers. This document from the Canadian Association of Interventional Cardiology- Association Canadienne de Cardiologie d'intervention, specifically addresses the implications for the care of patients in the cardiac catheterization laboratory (CCL) in Canada during the COVID-19 pandemic. The key principles of this document are to maintain essential interventional cardiovascular care while minimizing risks of COVID-19 to patients and staff and maintaining the overall health care resources. As the COVID-19 pandemic evolves, procedures will be increased or reduced based on the current level of restriction to health care services. Although some consistency across the country is desirable, provincial and regional considerations will influence how these recommendations are implemented. We believe the framework and recommendations in this document will provide crucial guidance for clinicians and policy makers on the management of coronary and structural procedures in the CCL as the COVID-19 pandemic escalates and eventually abates.


The Fundamentals Behind the Use of Flow Reactors in Electrochemistry.
In the past decade, research into continuous-flow chemistry has gained a lot of traction among researchers in both academia and industry. Especially, microreactors have received a plethora of attention due to the increased mass and heat transfer characteristics, the possibility to increase process safety, and the potential to implement automation protocols and process analytical technology. Taking advantage of these aspects, chemists and chemical engineers have capitalized on expanding the chemical space available to synthetic organic chemists using this technology. Electrochemistry has recently witnessed a renaissance in research interests as it provides chemists unique and tunable synthetic opportunities to carry out redox chemistry using electrons as traceless reagents, thus effectively avoiding the use of hazardous and toxic reductants and oxidants. The popularity of electrochemistry stems also from the potential to harvest sustainable electricity, derived from solar and wind energy. Hence, the electrification of the chemical industry offers an opportunity to locally produce commodity chemicals, effectively reducing inefficiencies with regard to transportation and storage of hazardous chemicals. The combination of flow technology and electrochemistry provides practitioners with great control over the reaction conditions, effectively improving the reproducibility of electrochemistry. However, carrying out electrochemical reactions in flow is more complicated than just pumping the chemicals through a narrow-gap electrolytic cell. Understanding the engineering principles behind the observations can help researchers to exploit the full potential of the technology. Thus, the prime objective of this Account is to provide readers with an overview of the underlying engineering aspects which are associated with continuous-flow electrochemistry. This includes a discussion of relevant mass and heat transport phenomena encountered in electrochemical flow reactors. Next, we discuss the possibility to integrate several reaction steps in a single streamlined process and the potential to carry out challenging multiphase electrochemical transformations in flow. Due to the high control over mass and heat transfer, electrochemical reactions can be carried out with great precision and reproducibility which provide opportunities to enhance and tune the reaction selectivity. Finally, we detail on the scale-up potential of flow electrochemistry and the importance of small interelectrode gaps on pilot and industrial-scale electrochemical processes. Each principle has been illustrated with a relevant organic synthetic example. In general, we have aimed to describe the underlying engineering principles in simple words and with a minimum of equations to attract and engage readers from both a synthetic organic chemistry and a chemical engineering background. Hence, we anticipate that this Account will serve as a useful guide through the fascinating world of flow electrochemistry.


Integrating primary health care and mental health services--a successful rural linkage.
The local delivery of human services is currently receiving national emphasis. The expectation is that community-based services shall be provided with a minimum of duplication and with maximum efficiency, achieved partly by interdisciplinary and interorganizational cooperation. This emphasis was appropriately facilitated in the mid-1970s through the availability of the Mental Health Initiative grants. The grants, initiated by the Bureau of Community Health Services in conjunction with the National Institute of Mental Health, Public Health Service, promoted the increased availability of mental health services through formal linkages between community mental health centers and primary health care programs. One such successful linkage was between a small primary health care center and a nonfederally funded, multicounty, mental health center in northwest Illinois. Initiated in September 1980, the services of the linkage project included direct clinical mental health services delivered at the primary health care center site, consultation and education activities, and the coordination of interagency services. The project patients differed from the general clients of the mental health center in demographic characteristics, source of referral, and diagnoses. The key elements in successful linkages and the achievement of goals are analyzed. The experience of the linkage project is relevant to the 1980s. The project was prematurely ended after 14 months. Reduction in Federal funds severely cut support for the primary health care center, and the depressed local economy could not match the withdrawn Federal funds.


Launching Effectiveness Research to Guide Practice in Neurosurgery: A National Institute Neurological Disorders and Stroke Workshop Report.
This workshop addressed challenges of clinical research in neurosurgery. Randomized controlled clinical trials (RCTs) have high internal validity, but often insufficiently generalize to real-world practice. Observational studies are inclusive but often lack sufficient rigor. The workshop considered possible solutions, such as (1) statistical methods for demonstrating causality using observational data; (2) characteristics required of a registry supporting effectiveness research; (3) trial designs combining advantages of observational studies and RCTs; and (4) equipoise, an identified challenge for RCTs. In the future, advances in information technology potentially could lead to creation of a massive database where clinical data from all neurosurgeons are integrated and analyzed, ending the separation of clinical research and practice and leading to a new "science of practice."


Phase separation reduces cell-to-cell variability of translational bursting.
Gene expression is a stochastic and noisy process often occurring in "bursts". Experiments have shown that the compartmentalization of proteins by liquid-liquid phase separation is conducive to reducing the noise of gene expression. Therefore, an important goal is to explore the role of bursts in phase separation noise reduction processes. We have established a coupled model that includes phase separation and a two-state gene expression process. Using the timescale separation method, we obtained approximate solutions for the expectation, variance, and noise strength of the dilute phase. It was found that a higher burst frequency weakens the ability of noise reduction by phase separation, but as the burst size increases, this ability first increases and then decreases. This study provides a deeper understanding of phase separation to reduce noise in the stochastic gene expression with burst kinetics.


Successful percutaneous coronary intervention for acute and chronic occlusion of the left main coronary artery: report of two cases and review of the literature.
Total occlusion of the left main coronary artery (LMCA) is a rare but clinically serious event due to its poor prognosis. While coronary artery bypass grafting (CABG) is currently recommended for treatment of these patients, recent studies support the feasibility of treatment by percutaneous intervention (PCI). Here, we report the diagnoses and treatment of two cases of total occlusion of the LMCA. One patient presented with acute myocardial infarction complicated by cardiogenic shock resulting from acute occlusion of the LMCA, and the other patient presented with unstable angina pectoris resulting from chronic occlusion of the LMCA. Both cases were successfully treated with PCI. Our results in these cases suggest that PCI may be a safe and effective alternative to CABG for treatment of LMCA occlusion.


Congenital Tufting Enteropathy-Associated Mutant of Epithelial Cell Adhesion Molecule Activates the Unfolded Protein Response in a Murine Model of the Disease.
Congenital tufting enteropathy (CTE) is a rare chronic diarrheal disease of infancy caused by mutations in epithelial cell adhesion molecule (EpCAM). Previously, a murine CTE model showed mis-localization of EpCAM away from the basolateral cell surface in the intestine. Here we demonstrate that mutant EpCAM accumulated in the endoplasmic reticulum (ER) where it co-localized with ER chaperone, GRP78/BiP, revealing potential involvement of ER stress-induced unfolded protein response (UPR) pathway in CTE. To investigate the significance of ER-localized mutant EpCAM in CTE, activation of the three UPR signaling branches initiated by the ER transmembrane protein components IRE1, PERK, and ATF6 was tested. A significant reduction in BLOS1 and SCARA3 mRNA levels in EpCAM mutant intestinal cells demonstrated that regulated IRE1-dependent decay (RIDD) was activated. However, IRE1 dependent XBP1 mRNA splicing was not induced. Furthermore, an increase in nuclear-localized ATF6 in mutant intestinal tissues revealed activation of the ATF6-signaling arm. Finally, an increase in both the phosphorylated form of the translation initiation factor, eIF2α, and ATF4 expression in the mutant intestine provided support for activation of the PERK-mediated pathway. Our results are consistent with a significant role for UPR in gastrointestinal homeostasis and provide a working model for CTE pathophysiology.


The ocular pathology of trisomy 22: report of two cases and review.
Two cases of full trisomy 22 with the associated gross and microscopic pathology are reported. These cases demonstrate the typical craniofacial and organ system anomalies previously reported in trisomy 22 but also exhibit uveal colobomas that, within the spectrum of chromosome 22 anomalies, are usually restricted to the so-called "cat eye" syndrome. The attendant microscopic ocular findings represent, the best of our knowledge, the first such report in the literature.


A standard muscle-sparing utility thoracotomy for VATS procedures.
Improvements in surgical equipment have rendered video-assisted thoracic surgery (VATS) an effective device for thoracic surgeons and nowadays several intrathoracic diseases can benefit from this approach. This development has expanded potential use and recently the technical feasibility of major lung resections by VATS has been demonstrated. The authors present their experience with a standard muscle-sparing utility thoracotomy (UT) utilized for all VATS procedures, including major lung resections. From November 1996 to October 1997, 30 patients were operated on. There were 22 males and 8 females (medium age 58 years; range 24-78). There were 13 anatomical lung resections (i.e.: 11 lobectomies, 1 left pneumonectomy, 1 segmental resection), 8 wedge resections, 3 lung biopsies, 2 debridements of pleural empyema, 2 mediastinal nodes biopsies, 1 esophageal resection for leiomyoma, 1 excision of benign mediastinal cyst. No mortality or major morbidity were recorded, as well as no rib fractures due to the rib spreader. Two patients suffered from prolonged air-leaks after respectively left upper lobectomy and lung biopsy and required prolonged chest drainage. Concerning anatomic major lung resections the medium hospital stay was 7.9 days and medium chest tube time was 5.6 days. The utility thoracotomy through the auscultatory triangle proved to be a safe approach and confirmed the technical feasibility of various type of surgical procedures with results comparable to standard open thoracotomy. Our data shows that VATS approach did not seriously affect the duration of hospital stay, chest tube time, the overall morbidity or lung function. As the real benefit of this approach remains controversial, the majority of the studies comparing the VATS approach to conventional muscle-sparing thoracotomy neither nor prospective nor randomized, and several parameters are difficult to evaluate in the literature further study are mandatory.


Reduction of MR imaging time by the hybrid fast-scan technique.
The time taken to collect high-resolution and high signal-to-noise (S/N) data in magnetic resonance (MR) imaging may be the limiting factor in patient throughput and in reducing patient motion. A hybrid fast-scan technique combining static and oscillatory phase-encoding gradients from two-dimensional Fourier transform (2DFT) and echo-planar imaging can reduce the time needed to collect data at the expense of loss in S/N. The flexibility of this technique is that any amplitude or frequency of oscillation of the phase-encoding gradient can be used. The technique was used for different frequencies and amplitudes, and images are presented that were acquired in one-half and one-quarter the time required with standard 2DFT techniques. The images illustrate that the hybrid and 2DFT techniques produce comparable resolution and contrast under identical conditions.


E6/E7 and E6* From HPV16 and HPV18 Upregulate IL-6 Expression Independently of p53 in Keratinocytes.
Keratinocyte infection with high-risk human papillomavirus genotypes has been linked to cancer development. In cervix, the alpha HPV16 and HPV18 have been reported as the mayor causative agents of cervical cancer. Oncogenic progression and chronic inflammation are closely related processes, with IL-6 as one of the main pro-inflammatory cytokines involved. However, there are limited studies about the regulation of IL-6 by low and high risk HPVs and the HPV proteins implicated in this modulation. In this work, we report the overexpression of IL-6 in HPV infected cervical cancer derived cell lines (HeLa and SiHa) compared to non-tumorigenic keratinocytes (HaCaT), and in Cervical Intraepithelial Neoplasia grade 1 HPV16 and HPV18 positive cervical samples compared to HPV negative samples without lesions. Moreover, we generated HaCaT keratinocytes that express E5, E6, and E7 from high risk (16 or 18) or low risk (62 and 84) HPVs. E5 proteins do not modify IL-6 expression, while E7 modestly increase it. Interestingly, E6 proteins in HaCaT cells upregulate IL-6 mRNA expression and protein secretion. Indeed, in HaCaT cells that express high risk HPV16E6 or HPV18E6 proteins, only the truncated E6* isoforms were expressed, showing the stronger IL-6 overexpression, while in HaCaT cells that express low risk HPV62 and HPV84 full length E6 proteins, IL-6 was also upregulated but not so drastically. Since HaCaT cells have a mutated p53 form that is not degraded by the introduction of E6 or E6/E7, it seems that E6/E7 regulate IL-6 by an additional mechanism independent of p53. In addition, basal keratinocytes showed a strong expression of IL-6R using immunohistochemistry, suggesting an autocrine mechanism over proliferative cells. Altogether, IL-6 cytokine expression in keratinocytes is upregulated by E6 and E7 proteins from HPVs 16, 18, 62, and 84, especially by high risk HPV16 and HPV18 E6*, which may contribute to promote a pro-inflammatory and highly proliferative microenvironment that can persist over time and lead to cervical tumorigenesis.


Correlation of estrogen receptor level and lipid staining in breast carcinoma.
Intracytoplasmic lipid was demonstrated in 10% or more of the cells in 13 (26%) of 50 estrogen receptor (ER)-positive breast carcinomas and in four (14.8%) of 27 ER-negative breast carcinomas. Thus, proportionately more positive tumors contained significant amounts of intracytoplasmic lipid. The difference, however, was not statistically significant. Furthermore, the presence of lipid as a test to predict the ER status is not useful because of its low efficiency and predictive value.


Impacts of COVID-19 on sexual behaviour in Britain: findings from a large, quasi-representative survey (Natsal-COVID).
Physical restrictions imposed to combat COVID-19 dramatically altered sexual lifestyles but the specific impacts on sexual behaviour are still emerging. We investigated physical and virtual sexual activities, sexual frequency and satisfaction in the 4 months following lockdown in Britain in March 2020 and compared with pre-lockdown. Weighted analyses of web panel survey data collected July/August 2020 from a quota-based sample of 6654 people aged 18-59 years in Britain. Multivariable regression took account of participants' opportunity for partnered sex, gender and age, to examine their independent associations with perceived changes in sexual frequency and satisfaction. Most participants (86.7%) reported some form of sex following lockdown with physical activities more commonly reported than virtual activities (83.7% vs 52.6%). Altogether, 63.2% reported sex with someone ('partnered sex') since lockdown, three-quarters of whom were in steady cohabiting relationships. With decreasing relationship formality, partnered sex was less frequently reported, while masturbation, sex toy use and virtual activities were more frequently reported. Around half of all participants perceived no change in partnered sex frequency compared with the 3 months pre-lockdown, but this was only one-third among those not cohabiting, who were more likely to report increases in non-partnered activities than those cohabiting. Two-thirds of participants perceived no change in sexual satisfaction; declines were more common among those not cohabiting. Relationship informality and younger age were independently associated with perceiving change, often declines, in sexual frequency and satisfaction. Our quasi-representative study of the British population found a substantial minority reported significant shifts in sexual repertoires, frequency and satisfaction following the introduction of COVID-19 restrictions. However, these negative changes were perceived by some more than others; predominantly those not cohabiting and the young. As these groups are most likely to experience adverse sexual health, it is important to monitor behaviour as restrictions ease to understand the longer term consequences, including for health services.


Anal sphincter EMG does not distinguish between multiple system atrophy and Parkinson's disease.
Clinical distinction of multiple system atrophy (MSA) from Parkinson's disease (PD) is often difficult. Several recent reports indicate that objective classification may be accomplished using electromyographic (EMG) testing of the anal or urethral sphincters, but some authors have found that these tests are not reliable for this purpose. We studied 13 patients with PD and 10 with probable MSA, as diagnosed by consensus of four movement disorders specialists, according to accepted clinical criteria. Anal sphincter EMG was performed blind to the clinical diagnosis. We found no significant differences in the mean duration of motor unit potentials (MUPs), mean MUP amplitude, or prevalence of polyphasic potentials, satellite potentials, very long duration MUPs, or spontaneous activity between the two groups. Thus, anal sphincter EMG does not differentiate between PD and MSA.


Antihypertensive drug therapy in USAF flying personnel.
The reviewed data concerns hypertensive USAF aircrew members, as available from the WAVR File (July 1973) and the records of the Aeromedical Consultation Service at USAFSAM (1 July 1972-30 June 1973). Of over 6,500 entries in the WAVR File, hypertension was listed as a diagnosis for 754 individuals. Drug therapy had been instituted in 379 cases (50.3%) of the total. Statistics regarding ranks, age groups, and aeronautical ratings are presented. The group included 520 pilots, of whom 268 were receiving drug therapy. Associated medical conditions, e.g., abnormal EKG findings, carbohydrate intolerance, and hyperuriciemia, are presented. Similar data are reviewed for the 84 patients evaluated on the Aeromedical Consultation Service (USAFSAM).


The importance of considering the neglected intestinal protozoan parasite Dientamoeba fragilis.
Dientamoebiasis is globally distributed and detected in a large number of subjects with diarrhea, abdominal discomfort, flatulence, fatigue and loss of appetite. The life cycle and transmission of Dientamoeba fragilis are poorly understood. Microscopic examination of permanent stained smears is traditionally employed to diagnose the infection. However, this approach is time-consuming and the success in detecting D. fragilis depends on the microscopist's experience. Hence, only a few laboratories routinely carry out tests for D. fragilis. Consequently, the prevalence of D. fragilis infection is probably underestimated. Although novel, rapid and more sensitive diagnostic tests are becoming available for detecting intestinal parasites, they also possess some limitations. The aim of this study was to emphasize the importance of performing microscopic examination of permanent stained smears from at least one fresh stool specimen after sample arrival at the laboratory, as a mandatory practice for the diagnosis of dientamoebiasis, particulary where it is not possible to perform molecular assays.


Development of acute inhalation reference exposure levels (RELs) to protect the public from predictable excursions of airborne toxicants.
Uniform guidelines have been developed for the derivation of 1-h acute inhalation reference exposure levels (RELs) applicable to the general public exposed routinely to hazardous substances released into the environment. Existing acute exposure guidance values developed by other organizations have been examined, and strengths and weaknesses in these existing guidelines have been identified. The results of that examination have led to the development of a reproducible and resource-intensive methodology to calculate acute inhalation RELs for 41 prioritized chemicals. Approaches to estimating levels protective against mild and severe acute effects are discussed in this report. The default methodology is the no-observed-adverse-effect level (NOAEL)/uncertainty factor (UF) approach using mainly reports in the peer-reviewed toxicological and medical literature. For two well-studied chemicals, ammonia and formaldehyde, the data allowed a benchmark dose (or concentration) methodology, as a departure from the default options, to be used. However, better human dose-response data from, for example, improved workplace monitoring correlated with symptoms, and more extensive epidemiological studies are needed before the departure from default approaches can be expanded to more substances.


T-cell rosette test in squamous cell carcinoma of the head and neck.
The percentage of total T-lymphocytes was measured in 38 patients with histologically diagnosed squamous cell carcinoma of the head and neck. This measure of cellular immunity, which appears to be important in tumor-cell destruction, is demonstrably lowered in advanced stages of this disease. With the use of this test, the effect of a combined chemoimmunotherapeutic regimen consisting of methotrexate sodium, isoniazid, and BCG vaccine was sutdied. In this small series, no decrease of the T-cell count following treatment by methotrexate was demonstrated, except when a high dosage followed by leucovorin calcium was used. The BCG vaccine appeared to enhance T-cell counts, and one patient who was treated with cryosurgery had a dramatic increase in circulating T-lymphocytes. The T-cell test may be of clinical importance in the development of treatment sequences that provide maximum reduction of tumor cell mass while preserving host T cells.


Real-world effectiveness of pneumococcal vaccination in older adults: Cohort study using the UK Clinical Practice Research Datalink.
The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for UK older adults, but how age moderates effectiveness is unclear. Three annual cohorts of primary-care patients aged≥65y from the Clinical Practice Research Datalink selected from 2003-5 created a natural experiment (n = 324,804), reflecting the staged introduction of the vaccine. The outcome was symptoms consistent with community-acquired pneumococcal pneumonia (CAP) requiring antibiotics or hospitalisation. We used the prior event rate ratio (PERR) approach to address bias from unmeasured confounders. Vaccinated patients had higher rates of CAP in the year before vaccination than their controls, indicating the potential for confounding bias. After adjustment for confounding using the prior event rate ratio (PERR) method, PPV23 was estimated to be effective against CAP for two years after vaccination in all age sub-groups with hazard ratios (95% confidence intervals) of 0.86 (0.80 to 0.93), 0.74 (0.65 to 0.85) and 0.65 (0.57 to 0.74) in patients aged 65-74, 75-79 and 80+ respectively in the 2005 cohort. Age moderated the effect of vaccination with predicted risk reductions of 8% at 65y and 29% at 80y. PPV23 is moderately effective at reducing CAP among UK patients aged≥65y, in the two years after vaccination. Vaccine effectiveness is maintained, and may increase, in the oldest age groups in step with increasing susceptibility to CAP.


Disperse distribution of cationic amino acids on hydrophilic surface of helical wheel enhances antimicrobial peptide activity.
The antimicrobial action of amphipathic antimicrobial peptides (AMPs) generally depends on perturbation of the bacterial membrane via electrostatic interactions promoting initial binding to the surface and hydrophobic interactions for pore formation into the membrane. Several studies have focused on the structure-activity relationship (SAR) of AMPs by modulation of structural parameters. However, modulation of one parameter commonly induces simultaneous changes in other parameters, making it difficult to investigate the specific influence of a single variable. In the present work, we investigated the distribution effect of cationic amino acids on the hydrophilic surface of the helical wheel using model AMPs composed of only lysine (K) and leucine (L) as representative cationic and hydrophobic residues, respectively, under conditions in which other parameters are fixed. Based on SAR analyses of alpha-helical KL model AMPs displaying different cationic distributions, we propose that the dispersity of cationic amino acids on the hydrophilic surface is a factor that contributes to the antimicrobial activity of AMP. Moreover, antimicrobial activity is enhanced by rearrangement of cationic amino acids to promote dispersed distribution. We confirmed the cationic distribution effect using natural AMP-derived alpha-helical CRAMP18 and its analogs. Our data show that accumulation of lysine shifts in the CRAMP18 analog leads to higher dispersion, and subsequently to improved antimicrobial activity. Therefore, we propose that the cationic distribution effect can be applied for the rational redesign of amino acid sequences to improve the antimicrobial activities of natural alpha-helical AMPs, in combination with regulation of other known structural parameters.