A cautionary note regarding count models of alcohol consumption in randomized controlled trials.
Alcohol consumption is commonly used as a primary outcome in randomized alcohol treatment studies. The distribution of alcohol consumption is highly skewed, particularly in subjects with alcohol dependence. In this paper, we will consider the use of count models for outcomes in a randomized clinical trial setting. These include the Poisson, over-dispersed Poisson, negative binomial, zero-inflated Poisson and zero-inflated negative binomial. We compare the Type-I error rate of these methods in a series of simulation studies of a randomized clinical trial, and apply the methods to the ASAP (Addressing the Spectrum of Alcohol Problems) trial. Standard Poisson models provide a poor fit for alcohol consumption data from our motivating example, and did not preserve Type-I error rates for the randomized group comparison when the true distribution was over-dispersed Poisson. For the ASAP trial, where the distribution of alcohol consumption featured extensive over-dispersion, there was little indication of significant randomization group differences, except when the standard Poisson model was fit. As with any analysis, it is important to choose appropriate statistical models. In simulation studies and in the motivating example, the standard Poisson was not robust when fit to over-dispersed count data, and did not maintain the appropriate Type-I error rate. To appropriately model alcohol consumption, more flexible count models should be routinely employed.


Does daily kangaroo care provide sustained pain and stress relief in preterm infants?
1. Determine whether stress in preterm infants, measured with salivary cortisol, decreases after five days of Kangaroo Care (KC) compared to five days of Standard Care (SC). 2. To determine whether kangaroo care provides sustainable pain relief beyond the period of skin-to-skin holding. Preterm infants (n = 38) born at 27-30 weeks gestational age were randomized to either the KC or the SC group and received the allocated intervention starting on day of life (DOL) five and continuing for five days. Salivary cortisol was collected on DOL five and again on DOL ten. Differences were analyzed using repeated measures ANOVA and t tests. Pain during nasal suctioning over five days was assessed using the Premature Infant Pain Profile (PIPP). 1. Adequate saliva samples for salivary cortisol were collected for 13 KC infants and 11 SC infants. There was no main effect of group (p = 0.49), but there was a significant main effect of age (DOL five versus DOL ten), with salivary cortisol levels decreasing in both groups (p = 0.02). 2. Pain scores for both groups (n = 38) indicted mild to moderate pain during suctioning, with no significant difference in pain scores between groups. 1. KC did not affect salivary cortisol levels in preterm neonates, but levels in both the KC and SC groups decreased over time from DOL five to ten. Salivary cortisol may vary with age of infant. 2. Infants experience pain during routine suctioning and may require pain management.


Reported Prevalence and Nutritional Management of Functional Constipation among Young Children from Healthcare Professionals in Eight Countries across Asia, Europe and Latin America.
Background: The prevalence of functional constipation (FC) among children varies widely. A survey among healthcare professionals (HCPs) was conducted to better understand the HCP-reported prevalence and (nutritional) management of FC in children 12−36 months old. Methods: An anonymous e-survey using SurveyMonkey was disseminated via emails or WhatsApp among HCPs in eight countries/regions. Results: Data from 2199 respondents were analyzed. The majority of the respondents (65.9%) were from Russia, followed by other countries (Indonesia (11.0%), Malaysia (6.0%)), Mexico, KSA (5.1% (5.7%), Turkey (3.0%), Hong Kong (2.2%), Singapore (1.1%)). In total, 80% of the respondents (n = 1759) were pediatricians. The prevalence of FC in toddlers was reported at less than 5% by 43% of the respondents. Overall, 40% of the respondents reported using ROME IV criteria in > 70% of the cases to diagnose FC, while 11% never uses Rome IV. History of painful defecation and defecations < 2 x/week are the two most important criteria for diagnosing FC. In total, 33% of the respondents reported changing the standard formula to a specific nutritional solution, accompanied by parental reassurance. Conclusion: The most reported prevalence of FC in toddlers in this survey was less than five percent. ROME IV criteria are frequently used for establishing the diagnosis. Nutritional management is preferred over pharmacological treatment in managing FC.


Single-atom catalysts for the oxygen evolution reaction: recent developments and future perspectives.
Single-atom catalysts (SACs) possess the potential to achieve unique catalytic properties and remarkable catalytic mass activity by utilizing low-coordination and unsaturated active sites. However, smaller particles tend to aggregate into clusters or particles owing to their high surface energy. In addition, support materials that have strong interactions with isolated metal atoms, extremely large surface areas, and electrochemical stability are required. Therefore, sufficient information about these factors is needed to synthesize and utilize SACs. Herein, we review the recent investigations and advances in SACs for the oxygen evolution reaction (OER). We present not only the structural characterization of SACs, but also in situ/operando spectroscopic techniques and computational research for SACs to understand the mechanism and reveal the origin of their excellent OER activity. Furthermore, the OER catalytic activity and stability of SACs are summarized to evaluate the current level of SACs. Currently, research on single-atoms as OER catalysts is in the infant stage for synthesis, characterization and mechanism studies. We discuss some challenges for understanding the fundamentals of SACs and enhancing the catalytic performance of SACs for industrial applications.


Effects of a multi-component responsible beverage service programme on violent assaults in Sweden.
A multi-component Responsible Beverage Service (RBS) programme has been disseminated in Swedish municipalities. The aim of the programme is to reduce violence associated with consumption of alcohol at on-licensed premises. This study aimed to analyse the effect of the programme on police-recorded assaults after the dissemination of the programme in Swedish municipalities, 1996-2009. This study is a natural experiment that uses variation in the level of implementation of the RBS programme to predict change in the rate of police-recorded assaults. Swedish municipalities. The municipalities included in the study initiated the RBS programme no later than 2008. On-licensed premises open during the evenings must exist. Of 290 municipalities, 237 fulfilled these requirements. Programme fidelity was studied by means of several surveys. Yearly data on police-recorded assaults, per 100,000 inhabitants aged 15 and above, committed on weekend nights, were used as dependent variable. A fixed-effects panel data regression model was used to examine the effect of the programme. Each extension of the programme, by one component, was associated with a significant 3.1% reduction in assaults. However, this effect was seen mainly in smaller municipalities. Of the different components of the programme, the presence of a community coalition steering group had a significant effect on assaults. No significant effect was found regarding RBS training or supervision of on-licensed premises. Multi-component Responsible Beverage Service programmes can have a significant effect on police-recorded assaults even when implemented on a large scale in many communities.


Germ cell development in Drosophila.
More than 100 years have passed since Weismann first recognized the role of germ cells in the continuity of a species. Today, it remains unclear how a germ cell is initially set aside from somatic cells and how it chooses its unique developmental path. In this review, we address various aspects of germ cell development in Drosophila, such as germ cell determination, germ cell migration, gonad formation, sex determination, and gametogenesis. Many aspects of germ cell development, including the morphology of germ cells, their migratory behavior, as well as the processes of gonad formation and gametogenesis, show striking similarities among organisms. Considering the conservation of factors that regulate somatic development, it is likely that some aspects of germ cell development are shared not only on a morphological but also on the molecular level between Drosophila and other organisms.


Comparing the Diagnostic Accuracy of Two Cognitive Screening Instruments in Different Dementia Subtypes and Clinical Depression.
Short but accurate cognitive screening instruments are required in busy clinical practice. Although widely-used, the diagnostic accuracy of the standardised Mini-Mental State Examination (SMMSE) in different dementia subtypes remains poorly characterised. We compared the SMMSE to the Quick Mild Cognitive Impairment (Qmci) screen in patients (n = 3020) pooled from three memory clinic databases in Canada including those with mild cognitive impairment (MCI) and Alzheimer's, vascular, mixed, frontotemporal, Lewy Body and Parkinson's dementia, with and without co-morbid depression. Caregivers (n = 875) without cognitive symptoms were included as normal controls. The median age of patients was 77 (Interquartile = ±9) years. Both instruments accurately differentiated cognitive impairment (MCI or dementia) from controls. The SMMSE most accurately differentiated Alzheimer's (AUC 0.94) and Lewy Body dementia (AUC 0.94) and least accurately identified MCI (AUC 0.73), vascular (AUC 0.74), and Parkinson's dementia (AUC 0.81). The Qmci had statistically similar or greater accuracy in distinguishing all dementia subtypes but particularly MCI (AUC 0.85). Co-morbid depression affected accuracy in those with MCI. The SMMSE and Qmci have good-excellent accuracy in established dementia. The SMMSE is less suitable in MCI, vascular and Parkinson's dementia, where alternatives including the Qmci screen may be used. The influence of co-morbid depression on scores merits further investigation.


Exploring the molecular basis of dsRNA recognition by Mss116p using molecular dynamics simulations and free-energy calculations.
DEAD-box proteins are the largest family of helicase that are important in nearly all aspects of RNA metabolism. However, it is unclear how these proteins recognize and bind RNA. Here, we present a detailed analysis of the related DEAD-box protein Mss116p-RNA interaction, using molecular dynamics simulations with MM-GBSA calculations. The energetic analysis indicates that the two strands of double strands RNA (dsRNA) are recognized asymmetrically by Mss116p. The strand 1 of dsRNA provides the main binding affinity. Meanwhile, the nonpolar interaction provides the main driving force for the binding process. Although the contribution of polar interaction is small, it is vital in stabilizing the protein-RNA interaction. Compared with the wild type Mss116p, two studied mutants Q412A and D441A have obviously reduced binding free energies with dsRNA because of the decreasing of polar interaction. Three important residues Lys409, Arg415 and Arg438 lose their binding affinity significantly in mutants. In conclusion, these results complement previous experiments to advance comprehensive understanding of Mss116p-dsRNA interaction. The results also would provide support for the application of similar approaches to the understanding of other DEAD-box protein-RNA complexes.


Macrophage growth factor CSF-1 stimulates human monocyte production of interferon, tumor necrosis factor, and colony stimulating activity.
CSF-1, a macrophage colony stimulating factor that causes proliferation and differentiation of progenitor cells, may also have effects on mature cells. Human peripheral blood monocytes were used to examine this possibility. Monocytes, separated from normal blood by density centrifugation and adherence, were incubated for 3 days with or without CSF-1 (1,000 U/ml, purified from the MIA PaCa pancreatic carcinoma line). The two groups of cells were then washed and tested for the ability, when induced, to produce several factors. When induced for 2 days with LPS and PMA, the monocytes produced a factor that was cytotoxic to L929 cells, and this factor was completely neutralized by polyclonal antibody to tumor necrosis factor. The cells preincubated with CSF-1 consistently produced an average of 12 times more of this factor than cells not exposed to CSF-1. Monocytes induced with LPS and PMA also produced a colony stimulating activity, as measured by colony formation when using mouse bone marrow. Cells preincubated with CSF-1, washed, and induced with LPS and PMA produced more than three times as much activity compared with control monocytes. When monocytes were induced with poly-I.C, 22-fold higher levels of interferon were produced by the cells exposed to CSF-1. These results show that CSF-1 has direct stimulating effects on mature human monocytes, and suggest that the macrophage growth factor may have clinical application in the treatment of infectious diseases and cancer.


P16-positive continuous minimal deviation adenocarcinoma and gastric type adenocarcinoma in a patient with Peutz-Jeghers syndrome.
We report a case of Peutz-Jeghers syndrome (PJS) in a 33-year-old female patient with synchronous uterine cervical minimal deviation adenocarcinoma (MDA) and gastric type adenocarcinoma (GTA). The patient was diagnosed with PJS at the age of 10. At the time of consultation, she complained of watery discharge. Magnetic resonance imaging of the pelvis showed a poorly circumscribed mass in the uterine cervix. Histologically, both MDA and GTA components, as well as their transitional area, were observed. Both components were diffusely positive for MUC6, CK7 and, robustly, for p16. Moreover, the components were negative for ER, PgR and CEA, while HIK1083 and CK20 positive cells were found focally. Ki-67 labeling index in the MDA component was 5% while that in the GTA component was 50%. This case of GTA accompanied by MDA in a patient with PJS is distinct from the single previously-reported comparable case of which we are aware, with respect to the overexpression of p16 protein, an event considered rare in these tumors, and the continuity between the MDA and GTA components. This continuity favors the hypothesis that GTA arises from the dedifferentiation of MDA.


Effect of cortisol on percentage of non-sex-hormone-bound steroid: implications for distribution of steroids on binding proteins in serum.
We previously observed that in men concentrations of serum testosterone (T) not bound to sex-hormone-binding globulin (n-SHBGT) decreased as concentrations of cortisol increased in early morning. This led us to investigate in vitro the influence of several steroids on protein-bound T. Steroids were added to late-evening sera containing low concentrations of cortisol. Changes were measured in percent T or estradiol not bound to SHBG (%n-SHBGT or %n-SHBGE). Results were compared with computer simulations of a mass action model describing current understanding of steroid binding to serum proteins. In vitro measurements confirmed changes observed in vivo. Cortisol at 600 nmol/L reduced %n-SHBGT to 61% +/- 5% of basal, but this was reversed with cortisol at 2000 nmol/L. Progesterone reduced %n-SHGBT less, and dexamethasone had no effect. Free T rose with added cortisol. Increasing estradiol to 900 nmol/L caused an increase in %n-SHBGT. The %n-SHBGE rose with added cortisol (121% +/- 5% of basal with cortisol at 1000 nmol/L). Simulation predicted all behaviors except the marked initial decrease in %n-SHBGT as cortisol concentrations increased and the absolute values of %n-SHBGT and %n-SHBGE. A possible explanation for the former is that T is displaced from corticosteroid-binding globulin (CBG) by added cortisol, more T is bound to CBG than expected, and T displaced from CBG associates with SHBG rather than albumin. Alternatively, current understanding about steroid binding to serum proteins has other major deficiencies.


Hydrothermal plume measurements: a regional perspective.
An extensive deep-tow survey around an active submarine vent field was conducted to map the three-dimensional distribution of hydrothermal emissions and calculate the hydrothermal discharge of heat and manganese. Emissions from the 10-kilometer-long vent field formed a nearly isopycnal plume about 250 meters thick and elongated in the direction of the local net current. Net export of hydrothermal discharge from both point and diffuse sources was estimated from the advective transport of the plume; the heat flux was 5.8 +/- 2.9 x 10(8) watts and the dissolved manganese flux was 0.2 +/- 0.1 moles per second. Flux measurements of this type could be expanded to encompass entire ridge segments, allowing comparison with theoretical thermal and chemical process models on a common spatial scale.


Stereochemistry controlled by an asymmetric sulfur atom, and a rare example of a kryptoracemate.
The ligands 4-methylthio-6-phenyl-2,2'-bipyridine (1) and the corresponding sulfoxide (2) and sulfone (3) have been synthesized and characterized in solution, and in the solid state by single crystal X-ray diffraction. Compounds 2 and 3 crystallize in the same space group (C2/c) with similar unit cell parameters; a small increase in the unit cell volume allows for the presence of the extra oxygen atom in 3. The sulfoxide and sulfone groups adopt conformations that permit intramolecular O···HC(aryl) hydrogen bonds. The complexes [Ir(ppy)(2)L][PF(6)] with L = 1, 2 or 3 have been prepared and characterized. The asymmetric sulfur atom in ligand 2 gives rise to pairs of diastereoisomers of the complex which can be distinguished in the (1)H and (13)C NMR spectra. In solution, exchange of [PF(6)](-) by [Δ-TRISPHAT](-) gives rise to four diastereoisomers and we observed good dispersion of (1)H NMR resonances, especially for those assigned to protons close to the asymmetric sulfur atom. A single crystal X-ray diffraction study of 2{[Ir(ppy)(2)(3)][PF(6)]}·CHCl(3)·3H(2)O reveals that the complex crystallizes in the chiral space group P2(1)2(1)2(1), the asymmetric unit containing crystallographically independent Δ- and Λ-[Ir(ppy)(2)(3)](+) cations. This provides a rare example of a so-called kryptoracemate in the solid state. In MeCN solution, [Ir(ppy)(2)(1)][PF(6)], [Ir(ppy)(2)(2)][PF(6)] and [Ir(ppy)(2)(3)][PF(6)] are weakly emissive (λ(em) = 600, 647 and 672 nm, respectively) and preliminary studies of the electroluminescent properties of [Ir(ppy)(2)(2)][PF(6)] indicate that the complexes are not suitable candidates for LECs.


[A toxicological study of a phytopreparation made from an extract of alfalfa (Medicago sativa)].
A phytopreparation from lucerne (Medicago sativa) was studied with respect to the acute and chronic toxicity and the action upon the cellular genetic mechanism. It was found that the preparation belongs to the group of practically nontoxic properties.


Induced expression of the Legionella pneumophila gene encoding a 20-kilodalton protein during intracellular infection.
The eukaryotic protein synthesis inhibitor cycloheximid has been used by many investigators to selectively radiolabel intracellular bacteria. Although cycloheximide has no direct effect on bacterial gene expression, there are concerns that long-term inhibition of the host cell protein synthesis may have secondary effects on bacterial gene expression. Therefore, prior to further identification and cloning of the macrophage-induced (MI) genes of Legionella pneumophila, the effects of cycloheximide on L. pneumophila-infected U937 cells were evaluated by transmission electron microscopy. Inhibition of protein synthesis of the host cell for 6 h had no major effect on the ultrastructure of the host cell, on the formation of rough endoplasmic reticulum-surrounded replicative phagosome, or on initiation of intracellular bacterial replication. In contrast, by 15 h of cycloheximide treatment, there was profound deterioration in the host cell as well as in the phagosome. To examine protein synthesis by L. pneumophila during the intracellular infection, U937 macrophage-like cells were infected with L. pneumophila, and intracellular bacteria were radiolabeled during a 2-h cycloheximide treatment or following 12 h of cycloheximide treatment. Comparison by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the protein profile of radiolabeled in vitro-grown L. pneumophila to that of intracellularly radiolabeled bacteria showed that 23 proteins were induced in response to the intracellular environment during 2 h of inhibition of host cell protein biosynthesis. Twelve MI proteins of L. pneumophila were artifactually induced due to prolonged inhibition of the host cell protein synthesis. The gene encoding a 20-kDa MI protein was cloned by a reverse genetics technique. Sequence analysis showed that the cloned gene encoded a protein that was 80% similar to the enzyme inorganic pyrophosphatase. Studies of promoter fusion to a promoterless lacZ gene showed that compared to in vitro-grown bacteria, expression of the pyrophosphatase gene (ppa) was induced fourfold throughout the intracellular infection. There was no detectable induction in transcription of the ppa promoter during exposure to stress stimuli in vitro. The ppa gene of L. pneumophila is the first example of a regulated ppa gene which is selectively induced during intracellular infection and which may reflect enhanced capabilities of macromolecular biosynthesis by intracellular L. pneumophila. The data indicate caution in the long-term use of inhibition of host cell protein synthesis to selectively examine gene expression by intracellular bacteria.


Branching morphogenesis of the Drosophila tracheal system.
Many organs including the mammalian lung and vascular system consist of branched tubular networks that transport essential gases or fluids, but the genetic programs that control the development of these complex three-dimensional structures are not well understood. The Drosophila melanogaster tracheal (respiratory) system is a network of interconnected epithelial tubes that transports oxygen and other gases in the body and provides a paradigm of branching morphogenesis. It develops by sequential sprouting of primary, secondary, and terminal branches from an epithelial sac of approximately 80 cells in each body segment of the embryo. Mapping of the cell movements and shape changes during the sprouting process has revealed that distinct mechanisms of epithelial migration and tube formation are used at each stage of branching. Genetic dissection of the process has identified a general program in which a fibroblast growth factor (FGF) and fibroblast growth factor receptor (FGFR) are used repeatedly to control branch budding and outgrowth. At each stage of branching, the mechanisms controlling FGF expression and the downstream signal transduction pathway change, altering the pattern and structure of the branches that form. During terminal branching, FGF expression is regulated by hypoxia, ensuring that tracheal structure matches cellular oxygen need. A branch diversification program operates in parallel to the general budding program: Regional signals locally modify the general program, conferring specific structural features and other properties on individual branches, such as their substrate outgrowth preferences, differences in tube size and shape, and the ability to fuse to other branches to interconnect the network.


Ultrasonography and diagnosis of venous thromboembolism.
Venous thromboembolism (VTE) consists of two related conditions: pulmonary embolism (PE) and deep vein thrombosis (DVT). Objective testing for VTE is crucial because the clinical diagnosis is nonspecific and insensitive, and the consequences of a missed diagnosis are serious. The purpose of this review is to discuss the utility of venous ultrasonography as the foundation for diagnosis of acute lower extremity DVT. The effectiveness and practicality of venous ultrasonography as a stand-alone examination versus theoretically attractive, but perhaps less practical, combined approaches of ultrasonography with clinical probability assessment and D-dimer testing in the diagnosis of acute DVT is also addressed. Finally, the role of venous ultrasonography in a diagnostic algorithm for suspected PE is discussed.


BRDT is an essential epigenetic regulator for proper chromatin organization, silencing of sex chromosomes and crossover formation in male meiosis.
The double bromodomain and extra-terminal domain (BET) proteins are critical epigenetic readers that bind to acetylated histones in chromatin and regulate transcriptional activity and modulate changes in chromatin structure and organization. The testis-specific BET member, BRDT, is essential for the normal progression of spermatogenesis as mutations in the Brdt gene result in complete male sterility. Although BRDT is expressed in both spermatocytes and spermatids, loss of the first bromodomain of BRDT leads to severe defects in spermiogenesis without overtly compromising meiosis. In contrast, complete loss of BRDT blocks the progression of spermatocytes into the first meiotic division, resulting in a complete absence of post-meiotic cells. Although BRDT has been implicated in chromatin remodeling and mRNA processing during spermiogenesis, little is known about its role in meiotic processes. Here we report that BRDT is an essential regulator of chromatin organization and reprograming during prophase I of meiosis. Loss of BRDT function disrupts the epigenetic state of the meiotic sex chromosome inactivation in spermatocytes, affecting the synapsis and silencing of the X and Y chromosomes. We also found that BRDT controls the global chromatin organization and histone modifications of the chromatin attached to the synaptonemal complex. Furthermore, the homeostasis of crossover formation and localization during pachynema was altered, underlining a possible epigenetic mechanism by which crossovers are regulated and differentially established in mammalian male genomes. Our observations reveal novel findings about the function of BRDT in meiosis and provide insight into how epigenetic regulators modulate the progression of male mammalian meiosis and the formation of haploid gametes.


[ST-segment depression and elevation during supraventricular tachycardias].
Three electrocardiograms with repolarisation abnormalities (ST-segment depression and elevation) during supraventricular tachycardias are presented. In all three cases the subjects were young and otherwise healthy. Despite this in one of these cases an acute coronary syndrome was erroneously diagnosed on the basis of pronounced ST-segment depression in several leads and troponin I elevation. Coronary angiogram and echocardiogram in this case was normal. Diagnostic value and aetiology of repolarisation abnormalities during supraventricular tachycardias are discussed.


Comparison of the nucleic acid sequence of anglerfish and mammalian insulin mRNA's from cloned cDNA's.
Anglerfish (Lophius americanus) insulin complementary DNA was cloned in bacterial plasmids, and its sequence was determined. Fish insulin messenger RNA is larger (1.5 times) than the messenger RNA encoding mammalian (rat and human) insulin, in part because of a larger C peptide (an additional six amino acids or 18 nucleotides in length) but mainly because of increases in the 5' and 3' untranslated regions. Comparison of the fish, rat, and human insulin messenger RNA (from the complementary DNA) reveals that, in addition to the regions coding for the A and B peptides, sequence conservation is limited to a segment within the 5' untranslated region which may be involved in ribosomal binding, two small segments of the signal peptide, and two stretches of sequence in the 3' untranslated region.


Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010.
Time trends in cancer incidence rates (IR) are important to measure the changing burden of cancer on a population over time. The overall IR of cancer in the United States is declining. Although central nervous system tumors (CNST) are rare, they contribute disproportionately to mortality and morbidity. In this analysis, the authors examined trends in the incidence of the most common cancers and CNST between 2000 and 2010. The current analysis used data from the United States Cancer Statistics publication and the Central Brain Tumor Registry of the United States. Age-adjusted IR per 100,000 population with 95% confidence intervals and the annual percent change (APC) with 95% confidence intervals were calculated for selected common cancers and CNST overall and by age, sex, race/ethnicity, selected histologies, and malignancy status. In adults, there were significant decreases in colon (2000-2010: APC, -3.1), breast (2000-2010: APC, -0.8), lung (2000-2010: APC, -1.1), and prostate (2000-2010: APC, -2.4) cancer as well as malignant CNST (2008-2010: APC, -3.1), but a significant increase was noted in nonmalignant CNST (2004-2010: APC, 2.7). In adolescents, there were significant increases in malignant CNST (2000-2008: APC, 1.0) and nonmalignant CNST (2004-2010: APC, 3.9). In children, there were significant increases in acute lymphocytic leukemia (2000-2010: APC, 1.0), non-Hodgkin lymphoma (2000-2010: APC, 0.6), and malignant CNST (2000-2010: APC, 0.6). Surveillance of IR trends is an important way to measure the changing public health and economic burden of cancer. In the current study, there were significant decreases noted in the incidence of adult cancer, whereas adolescent and childhood cancer IR were either stable or increasing.


Extremely Low-Frequency Magnetic Fields and the Risk of Childhood B-Lineage Acute Lymphoblastic Leukemia in a City With High Incidence of Leukemia and Elevated Exposure to ELF Magnetic Fields.
It is important to study the relationship between extremely low-frequency magnetic fields (ELF-MFs) and childhood leukemia, particularly in locations with a high incidence of this neoplasm in children and an elevated exposure to ELF-MF, such as Mexico City. The aim was to investigate the association between ELF-MF exposure and the risk of B-lineage acute lymphoblastic leukemia (B-ALL). A case-control study was conducted in Mexico City during the period from 2010 to 2011. Residential 24-h ELF-MF measurements were obtained for 290 incident B-ALL patients and 407 controls, aged less than 16 years. Controls were frequency-matched by sex, age (±18 months), and health institution. The adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated. ELF-MF exposure at <0.2 μT was used to define the reference group. ELF-MF exposure at ≥0.3 μT was observed in 11.3% of the controls. Different ELF-MF intensity cutoff values were used to define the highest exposure category; the highest exposure category for each cutoff value was associated with an increased risk of B-ALL compared with the corresponding lower exposure categories. The aORs were as follows: ≥0.2 μT = 1.26 (95% CI: 0.84-1.89); ≥0.3 μT = 1.53 (95% CI: 0.95-2.48); ≥0.4 μT = 1.87 (95% CI: 1.04-3.35); ≥0.5 μT = 1.80 (95% CI 0.95-3.44); ≥0.6 μT = 2.32 (95% CI: 1.10-4.93). ELF-MF exposure as a continuous variable (per 0.2 μT intervals) was associated with B-ALL risk (aOR = 1.06; 95% CI: 1.01-1.12). In the present study, the proportion of children exposed to ≥0.3 μT is among the highest reported worldwide. Additionally, an ELF-MF exposure ≥0.4 μT may be associated with the risk of B-ALL. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.


Patient Characteristics and Causes of Facial Fractures in the State of California.
Each year, more than 400,000 emergency department (ED) visits in the United States are due to facial fractures. To inform targeted interventions to prevent facial fractures, the purpose of this study was to identify patient characteristics associated with causes of facial fractures in California. The 2005 to 2011 California State Emergency Department Database was used for this cross-sectional study. The study population was composed of all ED visits for facial fractures. The primary outcome was cause of injury: fall, firearm injury, motor vehicle traffic accident, pedal cycle accident, pedestrian accident, transport accident, and assault. Predictor variables included patient characteristics, such as age, gender, insurance type, and race and ethnicity. Multivariable logistic regression models were used. There were 198,870 ED visits for facial fractures from 2005 to 2011. The patients' average age was 35.7 years. Most ED visits were by male patients (71%), privately insured patients (35%), and white patients (52%). Approximately 65% of visits were on weekdays and 93% were routinely discharged. Closed fractures of nasal bones, other facial bones, orbital floor, malar and maxillary bones, and mandible were the most prevalent (91%) facial fractures. Assaults (44%), falls (24%), and motor vehicle traffic crashes (6%) were the top 3 causes of facial fractures. Elderly patients (odds ratio [OR] = 6.17), female patients (OR = 2.25), and Medicare enrollees (OR = 1.51) were statistically more likely to have fall-related fractures than patients 45 to 64 years old, male patients, and privately insured patients. Blacks (OR = 0.46) and micropolitan residents (OR = 0.76) were statistically less likely to have fall-related fractures than whites and metropolitan residents. Violence among youth and falls among the elderly are predominant causes of facial fractures. The uninsured contribute to more than one fourth of ED visits for facial fractures. Interventions targeted at these population groups can curb the prevalence of these fractures.


Two unusual types of syndactyly in the same family; Cenani-Lenz type and "new" type versus severe type I syndactyly?
Cenani-Lenz syndactyly is a very rare syndrome where the syndactyly is totally disorganized with abnormal development of pattern formation of the hand. We report here an additional case of Cenani-Lenz syndactylism in a woman who has congenital cataract and an unusual type of duplication of big toes not described so far. She had a half cousin who had an unusual new type or severe type I syndactyly. It is not clear whether these two types of syndactyly present in this family may be coincidental or not.


hdac4 mediates perichondral ossification and pharyngeal skeleton development in the zebrafish.
Histone deacetylases (HDACs) are epigenetic factors that function to repress gene transcription by removing acetyl groups from the N-terminal of histone lysines. Histone deacetylase 4 (HDAC4), a class IIa HDAC, has previously been shown to regulate the process of endochondral ossification in mice via repression of Myocyte enhancer factor 2c (MEF2C), a transcriptional activator of Runx2, which in turn promotes chondrocyte maturation and production of bone by osteoblasts. In this study, we generated two zebrafish lines with mutations in hdac4 using CRISPR/Cas9 and analyzed mutants for skeletal phenotypes and expression of genes known to be affected by Hdac4 expression. Lines have insertions causing a frameshift in a proximal exon of hdac4 and a premature stop codon. Mutations are predicted to result in aberrant protein sequence and a truncated protein, eliminating the Mef2c binding domain and Hdac domain. Zygotic mutants from two separate lines show a significant increase in ossification of pharyngeal ceratohyal cartilages at 7 days post fertilization (dpf) (p < 0.01, p < 0.001). At 4 dpf, mutant larvae have a significant increase of expression of runx2a and runx2b in the ceratohyal cartilage (p < 0.05 and p < 0.01, respectively). A subset of maternal-zygotic (mz) mutant and heterozygote larvae (40%) have dramatically increased ossification at 7 dpf compared to zygotic mutants, including formation of a premature anguloarticular bone and mineralization of the first and second ceratobranchial cartilages and symplectic cartilages, which normally does not occur until fish are approximately 10 or 12 dpf. Some maternal-zygotic mutants and heterozygotes show loss of pharyngeal first arch elements (25.9% and 10.2%, respectively) and neurocranium defects (30.8% and 15.2%, respectively). Analysis of RNA-seq mRNA transcript levels and in situ hybridizations from zygotic stages to 75-90% epiboly indicates that hdac4 is highly expressed in early embryos, but diminishes by late epiboly, becoming expressed again in larval stages. Loss of function of hdac4 in zebrafish is associated with increased expression of runx2a and runx2b targets indicating that a role for hdac4 in zebrafish is to repress activation of ossification of cartilage. These findings are consistent with observations of precocious cartilage ossification in Hdac4 mutant mice, demonstrating that the function of Hdac4 in skeletal development is conserved among vertebrates. Expression of hdac4 mRNA in embryos younger than 256-512 cells indicates that there is a maternal contribution of hdac4 to the early embryo. The increase in ossification and profound loss of first pharyngeal arch elements and anterior neurocranium in a subset of maternal-zygotic mutant and heterozygote larvae suggests that maternal hdac4 functions in cartilage ossification and development of cranial neural crest-derived structures.


Cortisol is significantly correlated with cardiovascular responses during high levels of stress in critical care personnel.
Everyday stressors elicit adaptive changes in the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system. Data on the relationship between these two systems under real-life conditions are sparse. We, therefore, sought to examine the association between HRV and salivary cortisol, which were recorded simultaneously in a stress-exposed, prospective, occupational cohort. The study population comprised 88 nurses. We recorded heart rate (HR) and HRV during 301 working shifts. Participants provided salivary cortisol samples at the beginning of their work shift and every 2 hours thereafter. Samples were collected during three investigation periods spread over 9 months. Change scores for cortisol were calculated as deviations from the expected circadian baseline. Change scores from the grand diurnal mean in the time domain-based root mean square of successive differences served to index alterations in HRV. To account for the temporal delay between changes in HR/HRV and changes in salivary cortisol, the latter were compared with the changes in HR/HRV observed 15 minutes to 45 minutes before the cortisol sampling. During periods of high stress as indexed by high cortisol levels, we found significant associations between cortisol levels and HR (r = .48, p < .001) and HRV (r = -.28, p = .05). However, during low stress periods, these associations were attenuated and became nonsignificant. These data suggest a relative independence in the regulation of the HPA axis and the autonomic nervous system in response to everyday stressors but synchrony of both systems in highly stressful situations.


The effect of posture and abdominal binding on respiratory pressures.
We examined the effect of posture on the generation of respiratory pressures in 6 highly trained subjects. Transdiaphragmatic pressure was measured at FRC during bilateral percutaneous phrenic nerve stimulation (twitch Pdi) and maximal sniffs (sniff Pdi), with the abdomen bound and unbound. Maximum static inspiratory (PImax) and expiratory (PEmax) mouth pressures were measured with the abdomen unbound. Three postures were examined: seated (Se), semi-supine (30s), and supine (Su). Changes of posture did not significantly alter twitch Pdi. By contrast, sniff Pdi and static mouth pressures were significantly reduced in the Su posture. Abdominal binding significantly increased twitch Pdi only. We conclude that voluntary respiratory manoeuvres requiring activation, recruitment and coordination of different muscle groups are performed better in the Se position. We suggest that posture be standardised for serial comparative measurements of voluntary respiratory pressures in a given subject.


Confinement of p-Xylene in the Pores of a Bilanthanide Metal-Organic Framework for Highly Selective Recognition.
The rapid and accurate sensing of p-xylene, an essential raw material with a multi-billion-dollar market, in xylene mixture is of great significance in industry; however, the highly similar molecular structures, energy levels, and spectral characteristics of xylene isomers make the selective recognition extremely challenging. Metal-organic frameworks (MOFs) exhibiting tailorable pores and potential binding sites provide prospects for xylene sensing but a comprehensive understanding of the pore effect is still elusive, primarily due to the intricacies involved in the sensing process. Herein, we reported a robust bilanthanide MOF NKU-999-EuTb with precisely engineered pores to accommodate p-xylene, of which the binding sites were confirmed by single crystal X-ray diffraction and dynamic magnetic susceptibilities. NKU-999-EuTb exhibits high-performance in selective recognition for p-xylene towards its isomers. Through a systematical study, it was revealed that absorbing p-xylene into the pores governs the sensing performance. This work provides insights for developing advanced sensing materials for complex isomers.


Outcome of patients with multiple myeloma and renal failure on novel regimens.
Renal involvement occurs in 20-40% of newly diagnosed multiple myeloma (MM) patients, and diagnosis of myeloma is frequently made after investigation for unexplained renal disease. This is a retrospective study between 2006 and 2013 in which 57 consecutive patients seen at the Nephrology Unit with diagnosis of MM were enrolled. MM was diagnosed for the first time because of renal dysfunction and/or proteinuria in these patients. The mean age of the patients (65% male) was 58.3 ± 12.7 years. The median baseline serum creatinine was 3.5 mg/dL (1.4-14.5). Anemia (hemoglobin <12 g/dL) was noted in 88% and hypercalcemia (calcium >10.5 mg/dL) in 35% of patients. Early hemodialysis was started in 28 patients (49%). Thalidomide plus dexamethasone (16% on bortezomib) were the main therapeutic regimens. Three patients (5%) underwent autologous stem cell transplantation. Twenty-six patients (45.6%) died during a median follow-up of 25 months (1-90). The mean age of patients who died was significantly higher than the age in patients who were alive (62.2 ± 12.7 vs. 55.2 ± 11.9 years, respectively; P = 0.037). Early hemodialysis had no significant effect on mortality rate. The one-, three and five year patient survival was 71%, 54%, and 41%, respectively. The median overall survival of patients was 50 months. Prolonged patient survival can be expected in myeloma patients with renal failure or on dialysis by applying novel therapeutic agents.


Safety and efficacy of adapalene gel 0.1% in acne vulgaris: results of a post-marketing surveillance study.
Adapalene is a novel retinoid indicated for the topical treatment of acne vulgaris. The drug was introduced in India in 2001. A post-marketing surveillance study was conducted to assess the safety and efficacy of adapalene gel 0.1% when used as monotherapy or in combination with other anti-acne agents in Indian patients of acne vulgaris. A 12-week, multicentre, open-label, non-comparative study involving 571 patients from 21 centers across India was conducted between January and September of 2002. Concomitant prescription of other anti-acne drugs was permitted, if needed. Of the 571 patients, 441 completed the treatment as per protocol. At the end of therapy, 96.3% of patients showed an improvement in their acne from baseline, with greater than 75% improvement seen in two-thirds of patients. Adverse events were reported in 24% of the patients, none of which were serious. The tolerability of therapy was rated as excellent/good in 81% of patients by physicians and in 78% by the patients. Adapalene gel 0.1% is a safe and effective topical agent in the treatment of mild to moderate acne vulgaris in Indian patients. It may be safely combined with other topical and oral anti-acne agents.


[Tetanus, an infectious disease still topical in Lome (Togo)].
Tetanus still remains a public health problem in Togo despite the existence of the Expanded Program on Immunization. A retrospective and descriptive cohort study was performed from January 1, 2008 to December 31, 2018 in the infectious and tropical diseases department of Sylvanus Olympio teaching hospital of Lome (Togo) on tetanus cases. We included 208 tetanus cases accounting for 6.5% of the whole hospitalizations in the infectious and tropical diseases department at this hospital. The median age of the patients was 23 [13-38 years] with male predominance (81.2%). The patients were workers (63.5%) and came mainly from urban areas (65.9%). Tetanus vaccination was only up to date in 9.3% of patients. Gateways were dominated by skin wounds (66.8%). Antitetanus serum was administered in 191 patients (91.8%) mainly through intrathecal route (189 patients (91.1%)). Complications were marked by superinfection of the wound (n=8), septic shock (n=3), acute respiratory failure and skin necrosis in 1 case respectively. The lethality was 27.4%. The morbidity of tetanus, in particular juvenile morbidity, remains high with significant lethality. It is therefore important to place particular emphasis on the vaccine booster component.


The fetal Doppler mechanical PR interval: a validation study.
To evaluate the accuracy of pulsed Doppler-derived fetal PR interval measurements obtained by physicians participating in a multicenter prospective fetal echocardiographic study. Echocardiograms on healthy fetuses were performed and evaluated by 15 pediatric cardiologists/perinatologists across the United States who are participating in a larger clinical trial involving fetuses at risk for autoantibody-associated congenital heart block. Prior to enrolling women in the main trial, each physician was provided with a teaching tape to demonstrate how the pulsed Doppler-derived PR interval is measured. The procedure involves placing a gated pulsed Doppler sample volume in the left ventricle at the junction of the anterior leaflet of the mitral valve and the left ventricular outflow tract in an apical 5-chamber view, and simultaneously obtaining left ventricular filling and emptying. Time intervals are measured from the onset of the mitral A wave (atrial systole) to the onset of the aortic pulsed Doppler tracing (ventricular systole). This represents the mechanical PR interval. Each physician measured the pulsed Doppler-derived fetal PR interval on 5 different subjects recruited from the physician's specific site. To validate each physician's technique, the tapes were sent to a central facility and the same intervals were remeasured by an experienced central reader (D.M.F.). A physician was determined to have adequate ability to measure the fetal PR interval if all 5 measurements were within +/- 30 ms of the central reader's measurements, where 30 ms corresponds to 25% of the mean observed in normative PR interval data. This difference was deemed to be the minimum clinically important difference in Doppler PR interval. Fourteen of the 15 physicians were considered to have adequate ability to measure the fetal PR interval according to our established criterion. The overall mean difference between the physicians and the central reader's measurements was -0.26 +/- 11.04 ms (p = 0.84). In addition, 95% of the observed differences were included in the interval (-22.23 to 21.81), which is well within our clinically acceptable range of +/- 30 ms. The pulsed Doppler assessment of the mechanical PR interval in the fetus can be accurately performed after minimal training. This technique may be a valuable tool for identification of early and potentially reversible conduction abnormalities in fetuses at risk for more advanced and permanent forms of heart block associated with maternal antibodies to SSA/Ro-SSB/La.


The Strange Case of Jekyll and Hyde: Parallels Between Neural Stem Cells and Glioblastoma-Initiating Cells.
During embryonic development, radial glial precursor cells give rise to neural lineages, and a small proportion persist in the adult mammalian brain to contribute to long-term neuroplasticity. Neural stem cells (NSCs) reside in two neurogenic niches of the adult brain, the hippocampus and the subventricular zone (SVZ). NSCs in the SVZ are endowed with the defining stem cell properties of self-renewal and multipotent differentiation, which are maintained by intrinsic cellular programs, and extrinsic cellular and niche-specific interactions. In glioblastoma, the most aggressive primary malignant brain cancer, a subpopulation of cells termed glioblastoma stem cells (GSCs) exhibit similar stem-like properties. While there is an extensive overlap between NSCs and GSCs in function, distinct genetic profiles, transcriptional programs, and external environmental cues influence their divergent behavior. This review highlights the similarities and differences between GSCs and SVZ NSCs in terms of their gene expression, regulatory molecular pathways, niche organization, metabolic programs, and current therapies designed to exploit these differences.


Cloning and characterization of GLOSSY1, a maize gene involved in cuticle membrane and wax production.
The cuticle covering the aerial organs of land plants plays a protective role against several biotic and abiotic stresses and, in addition, participates in a variety of plant-insect interactions. Here, we describe the molecular cloning and characterization of the maize (Zea mays) GLOSSY1 (GL1) gene, a component of the pathway leading to cuticular wax biosynthesis in seedling leaves. The genomic and cDNA sequences we isolated differ significantly in length and in most of the coding region from those previously identified. The predicted GL1 protein includes three histidine-rich domains, the landmark of a family of membrane-bound desaturases/hydroxylases, including fatty acid-modifying enzymes. GL1 expression is not restricted to the juvenile developmental stage of the maize plant, pointing to a broader function of the gene product than anticipated on the basis of the mutant phenotype. Indeed, in addition to affecting cuticular wax biosynthesis, gl1 mutations have a pleiotropic effect on epidermis development, altering trichome size and impairing cutin structure. Of the many wax biosynthetic genes identified so far, only a few from Arabidopsis (Arabidopsis thaliana) were found to be essential for normal cutin formation. Among these is WAX2, which shares 62% identity with GL1 at the protein level. In wax2-defective plants, cutin alterations induce postgenital organ fusion. This trait is not displayed by gl1 mutants, suggesting a different role of the maize and Arabidopsis cuticle in plant development.


Diffuse astrocytoma initially presenting as a massive intracerebral hemorrhage: case report.
We report the case of a 58-year-old woman with low-grade astrocytoma, who developed massive intracranial hemorrhage as the first presentation of this disease, and become comatose and subsequently underwent an emergency craniotomy. A small amount of tumor-like tissue was observed on the wall of the hematoma cavity. Histological analysis of the resected specimen indicated diffuse astrocytoma [World Health Organization (WHO) grade II]. The patient was discharged without neurological deficits 2 weeks after the operation. A non-enhanced tumor-like nodule was observed on magnetic resonance imaging 3 months after the operation, which was monitored carefully but was not treated by adjuvant therapy. The tumor grew gradually, and a second operation was performed 3 years after the first, in which the tumor was completely resected. Histological analysis of the resected specimen again indicated diffuse astrocytoma (WHO grade II). Although rare, brain tumors, including low-grade astrocytoma, should be considered a possible cause of subcortical hemorrhage in patients without risk factors for intracranial hemorrhage.


Pharmacological activities of dehydroepiandrosterone: A review.
Dehydroepiandrosterone (DHEA) is a steroidal hormone secreted by Zonareticularis of the adrenal cortex with a characteristic age related pattern of secretion. These hormones are inactive precursors that are transformed into active sex steroids in peripheral target tissues. These hormones are used for the energy, vitality and the natural support of most bodily functions that involve the endocrine system. DHEA is a 19 carbon steroid hormone, is lipophilic, and can be converted to DHEAs by activity of the enzyme sulphotransferasein the liver and adrenal glands. These are naturally synthesized in our body through cholesterol- pregnenolone pathway and can also be synthesized from various other sources like diosgenin, geniestein, wild yam, soy and cholesterol in laboratory. It serves as an indirect precursor to estrogen and testosterone and other steroid hormones. This hormone progressively declines at the rate of 2% per year. DHEA evidence a large variety of pharmacological activities like antidiabetic, anticancer, anti-allergic, obesity treatment and cardiovascular property. It is beneficial in autoimmune disorders like lupus erythematosus, immune modulation, muscle building and hormonal problems. DHEA is known as an anti-ageing hormone, in osteoporosis and in dementia. It can also be used as a supplement as directed by the physician in various condition.


A survey of nitrate and nitrite concentrations in conventional and organic-labeled raw vegetables at retail.
A national survey of the nitrate ( NO3(-)) and nitrite ( NO2(-)) concentrations in raw and highly consumed vegetables available at retail in the United States was conducted. A total of 194 samples of fresh broccoli, cabbage, celery, lettuce, and spinach categorized as conventional or organic by label were collected from 5 major cities in different geographic regions of the United States and analyzed to determine NO3(-) and NO2(-) concentrations. There were no differences in the mean NO2(-) values of conventional compared with organic vegetables taken from the 5 metropolitan areas. However, significant differences in mean pairwise comparisons between some conventional and organic vegetables for NO3(-) content were observed. The mean NO2(-) concentration of both conventional and organic vegetables ranged between 0.1 and 1.2 mg/kg of fresh weight (FW) with the exception of conventional spinach that contained 8.0 mg/kg FW. Mean NO3(-) contents of conventional broccoli, cabbage, celery, lettuce, and spinach were 394, 418, 1496, 851, and 2797 mg/kg FW, respectively, while their organic-labeled counterparts averaged 204, 552, 912, 844, and 1318 mg/kg FW. In most cases, organic vegetables were numerically lower in NO3(-) content than their conventional counterparts. Based on survey results, the finding that low NO3(-) levels were observed in some organic vegetables in different cities may warrant further study to determine if true differences exist, due to production practices, seasonal differences, and the magnitudes of those differences. Furthermore, the geographic differences in NO3(-) content of vegetables may flaw estimates of daily NO2(-) and NO3(-) exposure.


Selected Texan K-12 Educators' Perceptions of Youth Suicide Prevention Training.
K-12 school personnel may be frontline responders for youth contemplating suicide or other harmful behaviors. Therefore, the purpose of this preliminary study was to determine selected K-12 educators' perceptions of youth suicide prevention (YSP) training. A longitudinal trend survey with repeated measures and proportionally stratified random samples of K-12 personnel from nine Texas independent school districts provided data. Participants' perceived knowledge of the YSP content showed significant appreciative gains between pre- and follow-up post-tests. Likewise, their confidence levels for helping students at risk of suicide and approaching other adults to talk about students at risk of suicide rose significantly between pretests and follow-up post-tests. This preliminary study reinforces the value of training educators to acquire content knowledge and confidence boosting opportunities for engagement in difficult dialogue about suicidality. YSP training helped improve educators' confidence to engage with others about students' mental health concerns, calling attention to the importance of identifying early warning signs that may aid in early support and prevention of youth mental health concerns.


Demystifying the practice of khafd in the Dawoodi Bohra community: A commentary on the WeSpeakOut report from India.
In this commentary, we critique a recent report on female genital cutting (FGC) in the Indian Dawoodi Bohra community titled "The Clitoral hood a contested site: Khafd or female genital mutilation/cutting (FGM/C) in India." Published against the backdrop of possible legislation against FGC in India, the report makes good recommendations and is a useful addition to global literature on FGC. We critique specific sections of the document using relevant literature and informal conversations with the Bohra community in Pakistan, thereby highlighting both its strengths and weaknesses. We also attempt to show that criminalising khafd by conflating it with more drastic forms of cutting may be counterproductive. In conclusion, education and activism from within the community may be more fruitful than the imposition of a law banning khafd.


Bilateral multipartite patellae avulsions associated with a unilateral quadriceps tendon rupture.
Multipartite (or bipartite) patella is a developmental anomaly that occurs in 2%-6% of individuals. In 50%, the variant is bilateral. Multipartite patella is usually an asymptomatic condition. Quadriceps tendon rupture is also a rare entity occurring mostly in men aged >40 years and usually results from an acute eccentric quadriceps contracture. The authors present a case of a patient with bilateral multipartite patellae that sustained bilateral multipartite avulsions as well as an associated unilateral quadriceps tendon rupture. This constellation of injuries has never been reported in the literature. The patient was treated with excision of the multipartite patella fragments and quadriceps tendon repair on the side with the extensor mechanism disruption. He was treated non-operatively for the contralateral lower extremity multipartite patella avulsion. This report, along with a thorough review of the literature, serves to demonstrate the clinical and radiographic characteristics of this unusual injury.


A tyrosine motif in the cytoplasmic domain of mason-pfizer monkey virus is essential for the incorporation of glycoprotein into virions.
Mason-Pfizer monkey virus (M-PMV) encodes a transmembrane (TM) glycoprotein with a 38-amino-acid-long cytoplasmic domain. After the release of the immature virus, a viral protease-mediated cleavage occurs within the cytoplasmic domain, resulting in the loss of 17 amino acids from the carboxy terminus. This maturational cleavage occurs between a histidine at position 21 and a tyrosine at position 22 in the cytoplasmic domain of the TM protein. We have demonstrated previously that a truncated TM glycoprotein with a 21-amino-acid-long cytoplasmic tail showed enhanced fusogenicity but could not be incorporated into virions. These results suggest that postassembly cleavage of the cytoplasmic domain removes a necessary incorporation signal and activates fusion activity. To investigate the contribution of tyrosine residues to the function of the glycoprotein complex and virus replication, we have introduced amino acid substitutions into two tyrosine residues found in the cytoplasmic domain. The effects of these mutations on glycoprotein biosynthesis and function, as well as on virus infectivity, have been examined. Mutation of tyrosine 34 to alanine had little effect on glycoprotein function. In contrast, substitutions at tyrosine 22 modulated fusion activity in either a positive or negative manner, depending on the substituting amino acid. Moreover, any nonaromatic substitution at this position blocked glycoprotein incorporation into virions and abolished infectivity. These results demonstrate that M-PMV employs a tyrosine signal for the selective incorporation of glycoprotein into budding virions. Antibody uptake studies show that tyrosine 22 is part of an efficient internalization signal in the cytoplasmic domain of the M-PMV glycoprotein that can also be positively and negatively influenced by changes at this site.


Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes.
Unstimulated peripheral blood mononuclear cells (PBMCs) from corticosteroid-resistant (CR) but not corticosteroid-sensitive (CS) asthmatics demonstrate increased activating peptide-1 (AP-1)- and decreased glucocorticoid receptor (GR)-DNA binding. We test whether these abnormalities are associated with excessive generation of c-fos, the inducible component of AP-1. The c-fos transcription rate, mRNA and protein levels, and GR-DNA binding were quantitated in PBMCs, T cells, and monocytes from CS, CR, and nonasthmatic subjects. There was a 1.7-, 4.2-, and 2.3-fold greater increase in the baseline c-fos transcription rate, mRNA expression, and protein levels, respectively, in PBMCs derived from CR compared with CS patients. At optimal stimulation with PMA, there was a 5.7-, 3.4-, and 2-fold greater increase in the c-fos transcription rate, mRNA accumulation, and protein levels, respectively, in CR compared with CS PBMCs. These abnormalities were detected in both the T cell and monocyte subpopulations. PMA stimulation converted PBMCs from a CS to a CR phenotype and was associated with direct interaction between c-Fos and the GR. Pretreatment of PBMCs from CR patients with c-fos antisense oligonucleotides enhanced GR-DNA binding activity in CR PBMCs stimulated with dexamethasone. We suggest that increased c-fos synthesis provides a major mechanism for the increased AP-1- and decreased GR- DNA binding seen in CR asthma.


Roux limb volvulus after pancreas transplantation: an unusual cause of pancreatic graft loss.
Pancreas transplantation with enteric drainage avoids the long-term urological complications of bladder drainage. Increasing use of this technique raises the possibility of complications from the enteric reconstruction. This report describes a patient five yr after left-sided pancreas transplant with Roux-en-Y enteric drainage, presenting with abdominal pain, leukocytosis and radiological evidence of bowel obstruction. Exploration revealed a volvulus of the Roux limb as it passed through the mesocolon, with necrosis of the allograft duodenum and marked congestion of the pancreas. This is the first report of pancreas graft loss due to this entity, which should be recognized as an unusual cause of abdominal pain after pancreas transplantation. Potential bowel complications related to the sigmoid mesentery in left-sided pancreas transplantation are additional reasons for right-sided placement of the pancreas allograft.


Vasoactive intestinal peptide control of cyclic adenosine 3':5'-monophosphate levels in seven human colorectal adenocarcinoma cell lines in culture.
This study was undertaken to assess the role of vasoactive intestinal peptide (VIP) in the control of cyclic adenosine 3':5'-monophosphate production in colonic tumor cells. Seven human colorectal adenocarcinoma cell lines in culture were investigated (HT-29, HRT-18, SW-480, Caco-2, CO-115, CO-125, and HCT-8R). These cell-lines had a cyclic adenosine 3':5'-monophosphate production system which was very sensitive to VIP but less so to prostaglandin E1 and/or isoproterenol. Nonintestinal human malignant epithelial cells, such as HeLa (cervix) and Caki-1 and Caki-2 (kidney), by contrast, did not respond to VIP. The dose-response relationships of malignant colorectal cells were compared to those obtained with epithelial cells of normal human colon and showed that: (a) maximal responses were observed with 0.1 micro M VIP in both malignant and normal cells; (b) half-maximal responses were elicited by VIP concentrations in the 0.3 to 2 nM range in malignant cells (1.2 nM in normal cells), thus indicating the high apparent affinity of the cells to VIP; and (c) the magnitudes of the responses (stimulated:basal ratios) were highly variable in malignant cells, ranging from 225 in HT-29 cells to 3.5 in Caco-2 cells, but were more constant, in the order of 25, in normal cells. Secretin, a VIP agonist in intestinal tissue, stimulated cyclic adenosine 3':5'-monophosphate accumulation in all colorectal cells, but with a 1000- to 5000-fold lower potency than did VIP. These results show that the VIP-sensitive adenylate cyclase system operates in malignant as well as in normal colon epithelial cells.


Obesity is associated with increased risk of gastrointestinal symptoms: a population-based study.
Perception of sensations arising from the gastrointestinal tract may be diminished in obese subjects and thus facilitate overeating. Alternatively, excess food intake may cause gastrointestinal (GI) symptoms in obese patients. We evaluated the relationship between body mass index (BMI) and specific GI symptoms in the community. Residents of Olmsted County, MN were selected at random to receive by mail one of two validated questionnaires. The association of reported GI symptoms with BMI (kg/m(2)) was assessed using a logistic regression analysis adjusting for age, gender, psychosomatic symptom score, and alcohol and tobacco use. Response rate was 74% (1,963 of 2,660). The prevalence of obesity (BMI > or = 30 kg/m(2)) was 23%. There was a positive relationship between BMI and frequent vomiting (p= 0.02), upper abdominal pain (p= 0.03), bloating (p= 0.002), and diarrhea (p= 0.01). The prevalence of frequent lower abdominal pain, nausea, and constipation was increased among obese (BMI > or = 30 kg/m(2)) compared to normal weight participants, however, no significant association was found between BMI and these symptoms. In the community, increasing BMI is associated with increased upper GI symptoms, bloating, and diarrhea. Clarification of the cause-and-effect relationships and the mechanisms of these associations require further investigation.


Shift work, sleep, and sleepiness - differences between shift schedules and systems.
In this narrative review, we examined what level of research evidence is available that shift workers' sleep-wake disturbances can be minimized through ergonomic shift scheduling. We classified the pertinent studies conducted on real shift workers in field conditions by the type of shift system and study design (ie, whether the shift systems were modified or not - "treatment" versus "no treatment"). The results of the observational studies in which no changes to the shift system were made (ie, no treatment) showed that, irrespective of the shift system, night and early-morning shifts and quick returns are associated with short sleep and increases in sleepiness. The same is true for very long shifts (>16 hours) and extremely long weekly working hours (>55 hours). For all categories of shift systems, there was a lack of controlled intervention studies, limiting the possibility to provide solution-focused recommendations for shift scheduling. Most of the controlled intervention studies had been conducted on workers under regular 3-shift systems. These studies suggested that a change from slowly backward-rotating shifts to rapidly forward-rotating shifts is advantageous for alertness and, to some degree, sleep. We also found that a change from an 8- to 12-hour shift system does not necessarily result in impairments in the sleep-wake pattern. The level of research evidence was affected by many of the studies' frequent methodological limitations in measuring sleep and sleepiness. In all, to have reliable and solution-focused recommendations for shift scheduling, methodologically sound controlled intervention studies are required in different categories of shift systems.


On the pH regulation of plant aquaporins.
The majority of plants are unable to evade unfavorable conditions such as flooding, salinity, or drought. Therefore, a fine-tuned water homeostasis appears to be of crucial importance for plant survival, and it was assumed that aquaporins play a significant role in these processes. Regulation of plant aquaporin conductivity was suggested to be achieved by a gating mechanism that involves protein phosphorylation under drought stress conditions and protonation after cytosolic acidification during flooding. The effect of protein phosphorylation or protonation of aquaporins was studied on two plasma membrane intrinsic proteins, NtPIP2;1 and NtAQP1 from tobacco, which were heterologously expressed in yeast. Our results on mutated aquaporins with serine-to-alanine exchange indicate that phosphorylation of the two key serine residues did not affect the pH-dependent modification of water permeability. Protonation on a conserved histidine residue decreased water conductivity of NtPIP2;1. Although cells expressing NtPIP2;1 with a replacement of the histidine by an alanine were found to be pH-insensitive with regard to water permeability, these maintain high water transport rates, similar to those obtained under acidic conditions. The data clearly support the role of histidine at 196 as a component of pH-dependent modification of aquaporin-facilitated water transport. The predictions of combined effects from phosphorylation at conserved serines and histidine protonation were not supported by the results of functional analysis. The obtained results challenge the gating model as a general regulation mechanism for plant plasma membrane aquaporins.


Current preventive policies and practices against Vaccine-Preventable Diseases and tuberculosis targeted for workers from hospitals of the Sardinia Region, Italy.
Health care Workers are exposed to infectious diseases more than the general population. Many of these infections are preventable by vaccination. The objective in this study is to investigate whether, how, and which vaccination underwent Sardinia Health Care Workers (HCWs) and the variability of policies in different Hospital Health Managements of the whole region. In March 2013, we enrolled the Hospital Health Management of all the 32 Sardinia hospitals. We investigate on immunity against vaccine-preventable diseases and education campaigns about recommended vaccinations for HCWs. Flu, hepatitis B, measles-mumps-rubella, varicella and tuberculosis were the objects of our research. In most of the hospitals, influenza vaccination coverage among HCWs is less than 6%. Hepatitis B antibody assay was performed in all the respondent hospitals but only 14 had available data as collected electronically. Most of the hospitals did not perform serological tests for the evaluation of antibodies against Varicella, Measles, Mumps and Rubella in their HCWs. In 30 hospitals Mantoux test was replaced or integrated by "in vitro" test for health surveillance protocols. This method produced a large amount of data in small time and at a low cost. Sending back data to respective Hospital Health Management (HHM) we took a step towards greater awareness of the issue of biological risks of HCWs and of vaccine coverage.


Subcellular localization and adaptive up-regulation of the System A (SAT2) amino acid transporter in skeletal-muscle cells and adipocytes.
The recently cloned amino acid transporter SAT2 is ubiquitously expressed and confers Na(+)-dependent transport of short-chain neutral amino acids, characteristics of the functionally defined System A transporter. Here we report the presence of SAT2 mRNA and protein in both skeletal muscle and adipocytes, and the characterization of polyclonal antibodies directed against this transporter. SAT2 protein was present in both plasma-membrane and internal-membrane fractions derived from rat skeletal muscle and adipose tissue, L6 myotubes and 3T3-L1 adipocytes, having a localization similar to that of the glucose transporter GLUT4. Moreover, consistent with the adaptive up-regulation of System A activity following chronic amino acid deprivation, a time-dependent increase in SAT2 protein abundance was observed in amino-acid-deprived L6 myotubes and 3T3-L1 adipocytes. These studies provide the first evidence regarding the subcellular distribution and adaptive up-regulation of SAT2 protein and the characterization of molecular probes for this physiologically important transporter, the function of which is altered in several disease states.


[Differential indicators of loneliness among elderly. The importance of type of partner relationship, partner history, health, socioeconomic status and social relations].
Using data from the 1992 NESTOR-survey 'Living arrangements and social networks of older adults' (N = 4494), the aim of the present study is to identify specific categories of older adults who are most vulnerable to loneliness. By looking at different types of partner relationships (first, second, and third marriages; consensual unions; partners who are not household members) and at partner histories (never married, ever divorced, ever widowed, remarried), this study elaborates on previous research which has tended to look only at the presence versus the absence of partner relationships. Findings indicate that different types of partner relationships provide differential protection against loneliness. There appears to be a 'shadow of the past' of a previous divorce or widowhood in second and third partnerships, which accounts for generally higher levels of loneliness. Single men tend to be more lonely than single women. Moreover, there are no differences in loneliness between men who have always been single and those previously married. Among single women, differences in partner history are relevant: never married single women tend to be least vulnerable to loneliness. The differences in loneliness between older adults with different types of partner relationships and partner histories are only partially attributable to network and social participation differences. The latter independently contribute to the explanation of loneliness. The role of non-social determinants (health and socioeconomic position) is also examined. The results underscore the socially isolating effects of sensory impairments. Older adults with functional limitations, and those with visual or auditory problems tend to be more lonely, findings which are only partially attributable to differences in the number and quality of social relationships. Socioeconomic circumstances primarily have an indirect influence on loneliness. Those with higher levels of educational attainment and higher incomes tend to have more extensive social networks and are therefore less prone to loneliness.


Embryonal rhabdomyosarcoma (botryoid type) of the uterine corpus and cervix in adult women: report of a case series and review of the literature.
In its classical form, embryonal rhabdomyosarcoma (ERMS, botryoid type) is a vaginal neoplasm occurring in infants and young girls and is often not considered in the differential diagnosis of uterine corpus and cervical spindle cell tumors in adult women. Clinicopathologic and immunohistochemical features of 25 cases of ERMS in women 20 years of age or older were analyzed. Patient age ranged from 20 to 89 years (mean, 44.4 y; median, 46 y), with 8 patients aged 20 to 39 years, 14 patients aged 40 to 59 years, and 3 patients older than 60 years of age. Tumors originated in the cervix in 20 cases and in the uterine corpus in 5. They were characterized by an edematous hypocellular spindle cell proliferation, typically with cellular condensation beneath epithelial surfaces (cambium layer), in which tightly packed hypercellular foci were scattered. Neoplastic cells had hyperchromatic nuclei and minimal cytoplasm, usually with delicate cytoplasmic processes. Occasionally, elongated or globular cells with eosinophilic cytoplasm (rhabdomyoblasts) were evident, but cytoplasmic cross-striations were only rarely identified. Apoptotic bodies and mitotic figures were usually identified in the hypercellular foci. Hemorrhage was common, often making recognition of the hypercellular foci difficult. Desmin and myogenin were coexpressed in 22 of 23 (95.6%) tumors evaluated. Proliferative activity, as assessed by Ki-67 expression, was notably elevated in all tumors evaluated, typically concentrated in the hypercellular foci. Estrogen and progesterone receptors were expressed focally in only 3 of 12 (25%) and 1 of 8 (12.5%) tumors evaluated, respectively. Follow-up was available in 7 cases. Five patients were alive without evidence of disease with follow-up of 3 to 8 years, and 1 patient was alive with disease at 5 months. One patient died at 5 months with pulmonary nodules, but it was not determined whether this was due to metastatic ERMS or the patient's known ductal breast carcinoma. ERMS has a broader clinical profile than classically expected and should be considered in the differential diagnosis of a uterine corpus or cervical spindle cell tumor, regardless of patient age. Recognition can be rendered difficult by the hypocellular background, which can suggest a benign polyp or low-grade tumor, and hemorrhage, which can obscure the characteristic hypercellular foci. Identification of hypercellular foci in which mitotic activity and apoptotic bodies are found, desmin and myogenin are coexpressed, proliferative activity is notably elevated, and hormone receptor expression is usually absent is very useful for establishing the diagnosis.


Dual-Energy CT for Abdominal and Pelvic Trauma.
Computed tomography (CT) is key to the assessment of hemodynamically stable patients with blunt or penetrating trauma to the abdomen and pelvis. Dual-energy (DE) CT is a technology that allows acquisition of data at both high and low kilovolt peaks, allowing materials that have different x-ray absorption behaviors as a function of kilovolt peak (such as iodine) to be differentiated and quantified. DE CT has a variety of postprocessing applications that may be helpful in abdominal and pelvic trauma, including iodine-selective imaging, virtual monenergetic imaging, and virtual noncalcium imaging. Both iodine-selective imaging and virtual monoenergetic imaging can increase the conspicuity of traumatic solid-organ and hollow visceral injuries, making injuries easier to detect and categorize. Iodine-selective imaging, through the use of iodine maps and virtual noncontrast images, can assist in the evaluation of active contrast extravasation. Virtual noncalcium images can unmask bone marrow edema, improving detection of subtle fractures. The purpose of this review article is to familiarize radiologists with the basic physics and technical principles of DE CT, common postprocessing techniques, and the potential added value of DE CT in patients with abdominal and pelvic trauma. The technical limitations of DE CT are also reviewed, as are diagnostic pitfalls and common challenges in interpretation. ©RSNA, 2018.


[Bronchoplasty in tumor surgery (author's transl)].
A series of 80 bronchial resections and other broncho-plasties is presented; 60 operations were performed on the right side, while only 20 on the left side. The most frequent variation was the "sleeve lobectomy" (upper lobe with main bronchus). The attention is called to other possibilities so as: the reinplantation of the middle lobe after removal of the lower lobe and the intermede bronchus, the anastomosis between the left main bronchus and the upper lobe bronchus when the dividsion of the main bronchus must be removed together with the lower lobe, the repair of the continuity on the right side by means of a double anastomosis etc. Lethal postoperative complications occurred in 7 cases; 29 patients died in consequence of recidives or metastases and 44 are alive (22 more than 3 years, 8 more than 5 years). These procedures may significantly enlarge the resectability of the cancer in old patients and in those with limited respiratory reserve.


Topoisomerase involvement in multiplicity reactivation of phage T4.
The products of phage T4 genes 39, 52 and probably 60 have been previously characterized as forming a type II DNA topoisomerase. Other evidence suggested that this topoisomerase promotes normal initiation of DNA replication, and that when it is defective its loss is partially compensated for by the host gyrase. We present evidence here that mutants defective in genes 39, 52 and 60 have reduced ability to carry out multiplicity reactivation (MR, a form of recombinational repair) of phage DNA damaged either by mitomycin C (MMC) or psoralen plus near-UV light (PUVA). We also observed that there is not extensive superhelicity in the intracellular phage DNA either in the presence or absence of the phage topoisomerase. This tends to rule out the possibility that the topoisomerase influences MR by controlling the general superhelicity of the phage DNA. The dependence of MR on topoisomerase could occur in several possible ways. However, we favor the explanation that the lesions are bypassed by a postreplication recombinational repair process that is influenced by the topoisomerase through its role in initiating replication.


[Late development of tumors in the liver of dogs after long-term external gamma-radiation].
Development of tumors in the liver of dogs exposed to gamma-quanta for 3 and 6 years at dose--rates of 0.0006, 0.0017 and 0.0034 Gy/day was studied 1-10 years after termination of the exposure. The results are summarized in this work. Tumors were found in 27 out of 89 dogs. The number of benign and malignant tumors was virtually the same (13 and 14). In the first place were hepatoma, among benign neoplasms (9 out of 13), and liver cancer, among malignant tumors (12 out of 14). Neoplasms were more frequent (32%) in exposed animals than in the controls (19%). Tumors were almost two times more frequent and developed earlier after 6 year- than after-3-year-irradiation.


CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database.
The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD's Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.


Tear Film Characteristics During Wear of Daily Disposable Contact Lenses.
To evaluate changes induced over time by three daily disposable (DD) contact lenses on tear meniscus height (TMH), pre-lens non-invasive break-up time (pre-lens NIBUT), tear film osmolarity (TO) and objective quality of vision (OQV). Forty-six subjects enrolled in this prospective open-label unmasked non-randomized simultaneous comparative cross-over study. For the first week of the study, subjects wore a nesofilcon A lens in the right eye and a delefilcon A lens in the left eye. After 3 days of washout, for the second week, subjects wore a nesofilcon A lens in the left eye and a stenfilcon A lens in the right eye. TMH, pre-lens NIBUT, TO and OQV were measured before contact lens fitting and for each contact lens combination on day 1 at 20 minutes and on day 7 after ≥8 hours of wear. OQV measurement included the changes of objective scatter index (OSI), the stability index (SI) and the fluctuation index (FI) calculated in a range of time of 20 s from a blink. TMH was unchanged at 20 minutes wear of all lenses but was significantly reduced after 8 or more hours wear (on day 7) of delefilcon A and stenfilcon A, respectively. Pre-lens NIBUT was significantly reduced with all lenses, while no significant change in TO was observed with any lens. SI and FI increased significantly for all lenses at both wear times. While the presence of any contact lens on the eye challenges the tear film, nesofilcon A contact lenses, despite their high water content, compared to delefilcon A and stenfilcon A contact lenses, showed a lower overall effect. We speculate that superior tear film behavior while wearing nesofilcon A lenses may translate to improved subjective comfort, but this remains to be evaluated.


HeartMate II Left Ventricular Assist Device Geometry on Chest Radiograph Does Not Correlate with Risk of Pump Thrombosis.
Pump thrombosis (PT) is a common and potentially life-threatening complication among HeartMate II (HMII; Thoratec, Pleasanton, CA) patients. There have been efforts to correlate HMII geometry with higher risk of PT. The aim of this study was to test the validity of using HMII inflow cannula angle (ICA) and pump pocket depth (PPD) to predict PT. We performed a retrospective analysis of patients implanted with HMII left ventricular assist devices (LVADs) from January 2011 to March 2014 at our institution. Three blinded reviewers measured ICA and PPD from chest x-rays at postimplantation and most recent follow-up time points. The diagnosis of PT was visually confirmed upon device explantation by benchtop evaluation. HeartMate II was implanted in 90 patients. Sixteen (20%) patients experienced PT. There was no statistical difference between PT and non-PT patients in their initial ICAs (56.0° ± 10.1 vs. 54.6° ± 10.8, p = 0.63) and PPD (86.7 ± 24.9 mm vs. 81.1 ± 32.2 mm, p = 0.46). Prediction of PT using ICA and PPD by receiving operating characteristic was negative (area under curve (AUC) = 0.54 and 0.55, respectively). Changes in HMII geometry were measured over 112.5 (interquartile range = 34.3-337.3) days. A decrease in PPD was observed (p = 0.0001). Initial ICA was a significant predictor of future angle change and suggested a convergence toward the mean (55.4°) (analysis of variance p = 0.002). Pump thrombosis recurred in four (25%) patients. Postoperative ICA and PPD do not appear to predict PT in HMII patients in our experience. HeartMate II geometry changes over time secondary to remodeling with a decrease in PPD and a convergence toward the median in ICAs. Further investigation into the role of geometric ventricular assist device conformation postimplant may be warranted.


Exploiting endogenous opioids: Lessons learned from endomorphin 2 in the female rat.
Effective management of chronic pain is demanded by ethical as well as medical considerations. Although opioid analgesics remain among the most effective pharmacotherapies for ameliorating many types of pain, their use is clouded by concerns regarding their addictive properties, underscored by the current epidemic of prescription opioid abuse and attendant deaths. Medicinal harnessing of endogenous opioid antinociception could provide a strategy for continuing to take advantage of the powerful antinociceptive properties of opioids while avoiding their abuse potential. Based on our studies of endogenous mechanism that suppress and facilitate spinal endomorphin 2 antinociception over the rat reproductive cycle, we identified multiple signaling molecules that could serve as targets for activating endogenous opioid analgesia for chronic pain management in women. Our findings emphasize the need for a precision medicine approach that includes stage of menstrual cycle as an important determinant of drug targets for (activating/harnessing) endogenous opioid antinociceptive systems/ capabilities. Utilization of drugs that harness endogenous opioid antinociception in accordance with varying physiological states represents a novel approach for effective pain management.


The tradition algorithm approach underestimates the prevalence of serodiagnosis of syphilis in HIV-infected individuals.
Currently, there are three algorithms for screening of syphilis: traditional algorithm, reverse algorithm and European Centre for Disease Prevention and Control (ECDC) algorithm. To date, there is not a generally recognized diagnostic algorithm. When syphilis meets HIV, the situation is even more complex. To evaluate their screening performance and impact on the seroprevalence of syphilis in HIV-infected individuals, we conducted a cross-sectional study included 865 serum samples from HIV-infected patients in a tertiary hospital. Every sample (one per patient) was tested with toluidine red unheated serum test (TRUST), T. pallidum particle agglutination assay (TPPA), and Treponema pallidum enzyme immunoassay (TP-EIA) according to the manufacturer's instructions. The results of syphilis serological testing were interpreted following different algorithms respectively. We directly compared the traditional syphilis screening algorithm with the reverse syphilis screening algorithm in this unique population. The reverse algorithm achieved remarkable higher seroprevalence of syphilis than the traditional algorithm (24.9% vs. 14.2%, p < 0.0001). Compared to the reverse algorithm, the traditional algorithm also had a missed serodiagnosis rate of 42.8%. The total percentages of agreement and corresponding kappa values of tradition and ECDC algorithm compared with those of reverse algorithm were as follows: 89.4%,0.668; 99.8%, 0.994. There was a very good strength of agreement between the reverse and the ECDC algorithm. Our results supported the reverse (or ECDC) algorithm in screening of syphilis in HIV-infected populations. In addition, our study demonstrated that screening of HIV-populations using different algorithms may result in a statistically different seroprevalence of syphilis.


An externally brooding acorn worm (Hemichordata, Enteropneusta, Torquaratoridae) from the Russian arctic.
A single specimen of a previously undescribed acorn worm in the family Torquaratoridae was trawled from a bottom depth of about 350 m in the Kara Sea (Russian Arctic). The new species is the shallowest of the exclusively deep-sea torquaratorids found to date, possibly an example of high-latitude emergence. On the basis of ribosomal DNA sequences and morphology, the worm is described here as the holotype of Coleodesmium karaensis n. gen., n. sp. It is most similar in overall body shape to the previously described enteropneust genus Allapasus, but is uniquely characterized by a tubular component of the proboscis skeleton ensheathing the collar nerve cord. Additionally, within the proboscis, the sparseness of the musculature of C. karaensis clearly distinguishes it from the much more muscular members of Allapasus. The holotype is a female bearing about a dozen embryos on the surface of her pharyngeal region, each recessed within a shallow depression in the dorsal epidermis. The embryos, ranging from late gastrula to an early stage of coelom formation, are a little more than 1 mm in diameter and surrounded by a thin membrane. Each embryo comprises an external ectoderm of monociliated cells (not arranged in obvious ciliated bands) and an internal endo-mesoderm; the blastopore is closed. In the most advanced embryos, the anterior coelom is starting to constrict off from the archenteron. Coleodesmium karaensis is the first enteropneust (and indeed the first hemichordate) found brooding embryos on the surface of the mother's body.


[Isolated rupture of the interventricular septum after blunt chest trauma (author's transl)].
The mechanism, symptoms and treatment of traumatic ventricular septal defect are discussed on the basis of an own observation. To the best of our knowledge this is the first report of a rupture of the membranous septum, involving the portion between the left ventricle and the right atrium. An attempt is made to explain the mechanism of isolated traumatic ventricular septal rupture on the basis of embryological considerations. The patient died on the 11th postoperative circulatory status and inspite rather prompt diagnosis and operative treatment.


Global biodiversity and the ancient carbon cycle.
Paleontological data for the diversity of marine animals and land plants are shown to correlate significantly with a concurrent measure of stable carbon isotope fractionation for approximately the last 400 million years. The correlations can be deduced from the assumption that increasing plant diversity led to increasing chemical weathering of rocks and therefore an increasing flux of carbon from the atmosphere to rocks, and nutrients from the continents to the oceans. The CO(2) concentration dependence of photosynthetic carbon isotope fractionation then indicates that the diversification of land plants led to decreasing CO(2) levels, while the diversification of marine animals derived from increasing nutrient availability. Under the explicit assumption that global biodiversity grows with global biomass, the conservation of carbon shows that the long-term fluctuations of CO(2) levels were dominated by complementary changes in the biological and fluid reservoirs of carbon, while the much larger geological reservoir remained relatively constant in size. As a consequence, the paleontological record of biodiversity provides an indirect estimate of the fluctuations of ancient CO(2) levels.


Adverse neurodevelopmental effects and hearing loss in children associated with manganese in well water, North Carolina, USA.
Heavy metals such as manganese, arsenic and lead can act as neurotoxins. There have been few human studies of neurobehavioral/neurodevelopmental effects of arsenic and manganese on children in the United States. Since 1998, North Carolina has tested all new private wells for manganese, arsenic and lead. This study was conducted to evaluate adverse neurodevelopmental effects (delayed milestones, speech/language disorders and hearing loss) in children and metal concentrations in well water. A quasi-regression model of the number of children (0-35 months of age) with adverse neurodevelopmental effects as outcome measures and aggregate mean metal concentration (arsenic, lead, and manganese) in private well water in each county as exposures. Over 70,000 private well water samples from 1998 to 2011 were analyzed for metal content. From 2008 to 2011, an average of 17,000 children was enrolled in the Infant Toddler Program. On average, 1.7% of children in this age range in each county had a speech/language disorder, 0.24% had a diagnosis of delayed milestones, and 0.026% had a diagnosis of hearing loss. The county mean manganese concentration was significantly and positively associated with the prevalence of delayed milestones and hearing loss in the children. No association was found for metal concentrations and speech/language disorders. This ecological study indicates that further investigation of manganese in well water and associated neurodevelopmental health outcomes in children is needed.


The LINE-1 DNA sequences in four mammalian orders predict proteins that conserve homologies to retrovirus proteins.
Recent work suggests that one or more members of the highly repeated LINE-1 (L1) DNA family found in all mammals may encode one or more proteins. Here we report the sequence of a portion of an L1 cloned from the domestic cat (Felis catus). These data permit comparison of the L1 sequences in four mammalian orders (Carnivore, Lagomorph, Rodent and Primate) and the comparison supports the suggested coding potential. In two separate, noncontiguous regions in the carboxy terminal half of the proteins predicted from the DNA sequences, there are several strongly conserved segments. In one region, these share homology with known or suspected reverse transcriptases, as described by others in rodents and primates. In the second region, closer to the carboxy terminus, the strongly conserved segments are over 90% homologous among the four orders. One of the latter segments is cysteine rich and resembles the putative metal binding domains of nucleic acid binding proteins, including those of TFIIIA and retroviruses.