A longitudinal study of respiratory symptoms in aluminum potroom workers.
The influence of occupational work exposure and host factors on the incidence of dyspnea and wheezing as reported in questionnaires was examined in 1,301 new employees in aluminum electrolytic potrooms. The incidence appeared to decrease after 2 yr of exposure, and the estimated probability of development of symptoms was nearly 20% after 4 yr. A total of 105 subjects developed dyspnea and wheezing. Of 78 symptomatic subjects who were interviewed, 76% experienced improvement or absence of symptoms when off work. In 523 subjects who were assigned to specific levels of exposure at the end of follow-up, a dose-response gradient was found between the development of symptoms and fluoride exposure. Increased risk with increasing amounts of tobacco was also observed, but childhood allergy and a family history of asthma were not significantly related to the outcome variable. We conclude that both total fluoride exposure and smoking are related to asthmatic symptoms in potroom workers, and the suggestion of a dose-response gradient was found for both variables. However, a causal relationship between fluorides and symptoms should be investigated further by specific bronchial provocation testing and by research for specific antibodies and other immunologic markers.


Colloid centrifugation selects normal spermatozoa from polymorphic bull ejaculates: a case study.
Semen from a Western Finncattle bull exhibiting a highly polymorphic spermiogram was processed by colloid centrifugation using Androcoll-B, a species-specific silane-coated silica colloid. In the first experiment, Single Layer Centrifugation (SLC) was used to identify which density colloids were needed to separate different cell populations. Colloids of the two chosen densities were then used in a density gradient resulting in two sperm subpopulations, one containing nearly all normally sized spermatozoa and the other enriched for the macrocephalic spermatozoa. Microcephalic spermatozoa did not appear in either of the selected subpopulations. Using a combination of SLC and DGC with this species-specific colloid, it was possible to separate the spermatozoa into different subpopulations, that is, a subpopulation containing nearly all normally sized spermatozoa, and another one enriched for the macrocephalic spermatozoa. Thus, colloid centrifugation could be used to select sufficient normal spermatozoa from a highly polymorphic ejaculate for AI, if desired.


Prevalence and risk factors of nonalcoholic fatty liver disease in breast cancer patients.
We aimed to evaluate the prevalence of nonalcoholic fatty liver disease (NAFLD) in breast cancer patients using liver magnetic resonance imaging (MRI), and to investigate factors associated with NAFLD. We evaluated 104 patients surgically treated for breast cancer at our hospital between September and November 2013. None of the patients had any other causes of secondary hepatic fat accumulation (such as significant alcohol consumption, use of steatogenic medication or inborn disorders). Hepatic fat accumulation was measured using liver MRI perfomed in all patients before surgical treatment. Based on the fat signal percentage from liver MRIs, 19 of 104 breast cancer patients were diagnosed with NAFLD, so the prevalence of NAFLD was 18.3%. In univariate analysis, factors associated with NAFLD were older age, high body mass index, type 2 diabetes mellitus (DM), hypertension, elevated aspartate aminotransferase, elevated alanine aminotransferase and elevated triglycerides (TG). In multivariate analysis, factors associated with NAFLD were high body mass index (BMI) (odds ratio [OR] 1.403; 95% confidence interval [CI] 1.111-1.771; p = 0.005), type 2 DM (OR 11.872; 95% CI 1.065-132.373; p = 0.044), and an elevated TG level (OR 50.267; 95% CI 4.409-573.030; p = 0.002). The prevalence of NAFLD in breast cancer patients was not different from that of the general population. High BMI, type 2 DM and an elevated serum TG level were factors associated with NAFLD.


Hyperspectral Imaging Provides Early Prediction of Random Axial Flap Necrosis in a Preclinical Model.
Necrosis remains a significant complication in cutaneous flap procedures. Monitoring, and ideally prediction, of vascular compromise in the early postoperative period may allow surgeons to limit the impact of complications by prompt intervention. Hyperspectral imaging could be a reliable, effective, and noninvasive method for predicting flap survival postoperatively. In this preclinical study, the authors demonstrate that hyperspectral imaging is able to correlate early skin perfusion changes and ultimate flap survival in a preclinical model. Thirty-one hairless, immunocompetent, adult male mice were used. Random pattern dorsal skin flaps were elevated and sutured back into place with a silicone barrier. Hyperspectral imaging and digital images were obtained 30 minutes, 24 hours, or 72 hours after flap elevation and before sacrifice on postoperative day 7. Areas of high deoxygenated hemoglobin change (124; 95 percent CI, 118 to 129) seen at 30 minutes after surgery were associated with greater than 50 percent flap necrosis at postoperative day 7. Areas demarcated by high deoxygenated hemoglobin at 30 minutes postoperatively had a statistically significant correlation with areas of macroscopic necrosis on postoperative day 7. Analysis of images obtained at 24 and 72 hours did not show similar changes. These findings suggest that early changes in deoxygenated hemoglobin seen with hyperspectral imaging may predict the region and extent of flap necrosis. Further clinical studies are needed to determine whether hyperspectral imaging is applicable to the clinical setting.


Root biomass and soil carbon distribution in hybrid poplar riparian buffers, herbaceous riparian buffers and natural riparian woodlots on farmland.
The objectives of this study were to compare coarse root (diameter > 2 mm) and fine root (diameter < 2 mm) biomass, as well as distribution of soil carbon stocks in 3 types of riparian land uses across 4 sites located in farmland of southern Québec, Canada: (1) hybrid poplar buffers (9th growing season); (2) herbaceous buffers; (3) natural woodlots (varying in tree species and age). For all land uses most of the root biomass was within the 0-20 cm depth range. Total coarse root biomass, to a 60 cm depth, ranged from 8.8-73.7 t/ha in woodlots, 0.6-1.3 t/ha in herbaceous buffers, and 9.2-27.3 t/ha in poplars. Total fine root biomass ranged from 2.68-8.64 t/ha in woodlots, 2.60-3.29 t/ha in herbaceous buffers, and 1.86-2.62 t/ha in poplars. Total root biomass was similar or higher in poplar buffers compared to a 27 year-old grey birch forest. This indicates that poplar buffers accelerated riparian soil colonisation by roots compared to natural secondary succession. Generally, fine root biomass in the surface soil (0-20 cm) was lower in poplar than in herbaceous buffers; the reverse was observed at greater depth. Highest coarse root biomass in the 40-60 cm depth range was observed in a poplar buffer, highlighting the deep rooted nature of poplars. On average, total soil C stocks (0-60 cm) were greater in woodlots than in riparian buffers. On most sites, soil C stocks tended to be lower in poplar buffers compared to adjacent herbaceous buffers, especially in surface soil, probably because of lower fine root biomass in poplar buffers. Across all sites and land uses, highest soil C stocks at the different soil depths were found in the soil layers of woodlots that also had the greatest fine root biomass. Strong positive linear relationships between fine root biomass and soil C stocks in the 0-20 cm depth range (R (2) = 0.79, p < 0.001), and in the whole soil profile (0-60 cm) (R (2) = 0.65, p < 0.01), highlight the central role of fine root biomass in maintaining or increasing soil C stocks.


Numerical integration of exchange-correlation energies and potentials using transformed sparse grids.
A new numerical integration procedure for exchange-correlation energies and potentials is proposed and "proof of principle" results are presented. The numerical integration grids are built from sparse-tensor product grids (constructed according to Smolyak's prescription [Dokl. Akad. Nauk. 4, 240 (1963)] ) on the unit cube. The grid on the unit cube is then transformed to a grid over real space with respect to a weight function, which we choose to be the promolecular density. This produces a "whole molecule" grid, in contrast to conventional integration methods in density-functional theory, which use atom-in-molecule grids. The integration scheme was implemented in a modified version of the DEMON2K density-functional theory program, where it is used to evaluate integrals of the exchange-correlation energy density and the exchange-correlation potential. Ground-state energies and molecular geometries are accurately computed. The biggest advantages of the grid are its flexibility (it is easy to change the number and distribution of grid points) and its whole molecule nature. The latter feature is potentially helpful for basis-set-free computational algorithms.


Genomic comparisons and Shiga toxin production among Escherichia coli O157:H7 isolates from a day care center outbreak and sporadic cases in southeastern Wisconsin.
Contour-clamped homogeneous electric field pulsed-field gel electrophoresis (CHEF-PFGE) was used to compare Wisconsin isolates of Escherichia coli O157:H7, including 39 isolates from a 1994 day care center outbreak, 28 isolates from 18 individuals from the surrounding geographic area with sporadic cases occurring during the 3 months before the outbreak, and 3 isolates, collected in 1995, from patients with hemolytic-uremic syndrome (HUS) who were from eastern Wisconsin counties other than those inhabited by the day care center and sporadic-case individuals. The technique of CHEF-PFGE using XbaI identified seven highly related restriction endonuclease digestion profiles (REDPs) (93 to 98% similarity) among the 39 day care center isolates and nine XbaI REDPs (63 to 93% similarity) among the 28 isolates from sporadic-case individuals, including REDP 33, which was exhibited by both day care and sporadic-case isolates. PFGE analyses of sequential E. coli O157:H7 isolates from symptomatic day care center attendees revealed that the REDPs of 25 isolates from eight patients were indistinguishable whereas the REDPs of 2 of 6 isolates from two patients differed slightly (93 to 95% similarity). The REDPs of the three isolates from 1995 HUS patients were 78 to 83% similar, with REDP 26 being exhibited by one HUS-associated isolate and an isolate from one day care attendee who did not develop HUS. The genes for both Shiga toxins I and II (stx1 and stx2, respectively) were detected in all but one isolate (sporadic case), and Shiga toxin production by the day care center isolates was not significantly different from that of the other isolates, including the three HUS-associated isolates. Analyses of E. coli O157:H7 isolates from both the day care center outbreak and sporadic cases by CHEF-PFGE permitted us to define the REDP variability of an outbreak and geographic region and demonstrated that the day care center outbreak and a HUS case in 1995 were caused by E. coli O157:H7 strains endemic to eastern Wisconsin.


The import of phosphoenolpyruvate by plastids from developing embryos of oilseed rape, Brassica napus (L.), and its potential as a substrate for fatty acid synthesis.
The plastidial phosphoenolpyruvate (PEP)/phosphate translocator (PPT) is expressed in the developing embryos of oilseed rape (Brassica napus L.). PEP can be imported by plastids isolated from embryos and used for fatty acid synthesis at rates that are sufficient to account for one-third of the rate of fatty acid synthesis in vivo. This provides the first experimental evidence for uptake of PEP and incorporation of carbon from it into fatty acids by plastids. PEP metabolism in isolated plastids is able to provide some of the ATP required for fatty acid synthesis. Expression of the PPT and related glucose 6-phosphate (Glc-6-P) translocator (GPT) is high in early embryo and leaf development and then declines. The marked decline in the abundance of PPT and GPT transcripts between the pre- and mid-oil accumulating stages of embryo development in B. napus does not correlate with the corresponding translocator activities, which both increase over the same period. This means that transcript abundance cannot be used to infer the activity of the translocators.


Safety, Biodistribution, and Efficacy of an AAV-5 Vector Encoding Human Interferon-Beta (ART-I02) Delivered via Intra-Articular Injection in Rhesus Monkeys with Collagen-Induced Arthritis.
Preclinical studies to assess biodistribution, safety, and initial efficacy of ART-I02, an adeno-associated type 5 (rAAV5) vector expressing human interferon β (hIFN-β), were performed in a total of 24 rhesus monkeys with collagen-induced arthritis. All monkeys were naïve or showed limited neutralizing antibody (Nab) titers to AAV5 at the start of the study. Animals were injected with a single intra-articular dose of ART-I02 or placebo, consisting of 3.2×10(13) vg (Dose A=maximum feasible dose), 4.58×10(12) vg (Dose B), or placebo in the first affected finger joint, the ipsilateral knee, and ankle joint at the same time point. Animals were monitored for clinical parameters and well-being with a maximum of 4 weeks, with the option that the severity of arthritis could necessitate an earlier time point of sacrifice. No adverse events were noted after injection of ART-I02. No abnormalities were observed after histological evaluation of all organs. At both dose levels, immunohistochemical staining indicated expression of hIFN-β. In animals injected with Dose A, we observed stabilization or a reduction in swelling in the finger joint in which vector was administered. The highest copy numbers of vector DNA were detected in synovial tissue of the injected joint and the draining lymph node of the injected knee. High titers of Nab to rAAV5 were observed at the end of the study. Five monkeys developed an rAAV5-specific T-cell response. Two monkeys developed Nab to hIFN-β. In conclusion, intra-articular injection of ART-I02 was well-tolerated and did not induce adverse events. After administration of Dose A of ART-I02, we observed a beneficial effect on joint swelling, substantiated by decreased histological inflammation and bone erosion scores. A GMP vector for clinical application has been manufactured and is currently being tested in GLP rodent studies, with the aim to move forward to a clinical trial.


Improvement of the growth and yield of lettuce plants by non-uniform magnetic fields.
Influence of pre-sowing magnetic treatments on plant growth and final yield of lettuce (cv. Black Seeded Simpson) were studied under organoponic conditions. Lettuce seeds were exposed to full-wave rectified sinusoidal non uniform magnetic fields (MFs) induced by an electromagnet at 120 mT (rms) for 3 min, 160 mT (rms) for 1 min, and 160 mT (rms) for 5 min. Non treated seeds were considered as controls. Plants were grown in experimental stonemasons (25.2 m(2)) of an organoponic and cultivated according to standard agricultural practices. During nursery and vegetative growth stages, samples were collected at regular intervals for growth analyses. At physiological maturity, the plants were harvested from each stonemason and the final yield and yield parameters were determined. In the nursery stage, the magnetic treatments induced a significant increase of root length and shoot height in plants derived from magnetically treated seeds. In the vegetative stage, the relative growth rates of plants derived from magnetically exposed seeds were greater than those shown by the control plants. At maturity stage, all magnetic treatments increased significantly (p < 0.05)--plant height, leaf area per plant, final yield per area, and fresh mass per plant--in comparison with the controls. Pre-sowing magnetic treatments would enhance the growth and final yield of lettuce crop.


Soluble TNF and IL-2 receptors in patients with breast cancer.
Cytokines were shown both to enhance tumour growth and formation of metastases and to inhibit proliferation of tumour cells. TNF alpha may mediate apoptosis and necrosis of cancer cells, while the exact role of IL-2 remains to be elucidated. Plasma levels of TNF alpha and TNF and IL-2 soluble receptors (sTNF-R, sIL-2R) should thus be in some relation to some biological characteristics of the breast cancer. Plasma levels of TNF alpha, sTNF-R I and II and sIL-2R were measured in 31 women with different stages of breast cancer both before the institution of therapy and after 3 months of the treatment. Plasma levels of both types of sTNF-Rs were higher in patients with breast cancer than in controls (sTNF-R I--2166.6 +/- 568.9 vs. 1121.3 +/- 260.6 pg/ml, p < 0.001, sTNF-R II--3792.8 +/- 958.9 vs. 1996.2 +/- 404.3 pg/ml, p < 0.001) with no significant difference between clinical stages. Plasma levels of both sTNF-R (0.871, p < 0.001) and sIL-2R tightly correlated with each other. Plasma levels of TNF alpha decreased after treatment (from 3.92 +/- 1.86 to 3.40 +/- 1.15 pg/ml, p < 0.01), but plasma levels of sTNF-Rs and sIL-2R were not influenced by the therapy. Plasma levels of soluble TNF receptors may thus serve as a non-specific marker of the untreated breast cancer. Their relation to other biologic characteristics of this tumour is not clear. It remains also to be clarified if the long-term treatment leads to the normalization of sTNF-Rs plasma levels.


O-glycosylation of a precursor to a sweet potato vacuolar protein, sporamin, expressed in tobacco cells.
Sporamin, a vacuolar protein of the sweet potato, is synthesized as a precursor that contains signal peptide and an N-terminal propeptide that functions as a vacuolar targeting determinant. Sporamin, when expressed in tobacco cells, migrated as smeared bands on an SDS-polyacrylamide gel. The smearing was due to O-glycosylation of the precursor to sporamin. The smeared bands were stained by a glycan-specific stain but no N-glycosylation site was found in the amino acid sequence of the precursor to sporamin. The glycan attached to sporamin contained galactose and arabinose as major sugar components. Mutations that altered the Pro36 or Ser39 residue of the precursor to sporamin prevented glycosylation of the protein, and analysis by semiquantitative Edman degradation suggested that a glycan moiety was attached to Pro36 and, possibly, to Ser39. Pulse-labeling and cell-fractionation experiments revealed that the O-glycosylation of the precursor to sporamin occurred in the Golgi apparatus. Thus, this modification serves as a good marker of the transport from the endoplasmic reticulum (ER) to the Golgi apparatus of the precursor to sporamin. Treatment of transformed tobacco cells with brefeldin A (BFA) caused the intracellular accumulation of prosporamin that did not migrate as smeared bands. Thus, it appeared that BFA inhibited the transport of the precursor to sporamin to the Golgi apparatus. This result provides the first biochemical evidence that BFA inhibits transport from the ER to the Golgi apparatus in plant cells.


One-year outcome of biological and synthetic bioabsorbable meshes for augmentation of large abdominal wall defects in a rabbit model.
Long-term efficacy of biological and synthetic bioabsorbable meshes for large hernia repair is currently unclear. This rabbit study is aimed at investigating 1-y outcome of biological and synthetic bioabsorbable meshes for augmentation of large abdominal wall defects. In 46 rabbits, an 11 × 4 cm, full-thickness abdominal wall defect was repaired primarily, or with cross-linked (Permacol, Collamend) or non-cross-linked (Surgisis 4-ply, Surgisis Biodesign) biological, synthetic bioabsorbable (GORE BIO-A Tissue Reinforcement [TR], TIGR Matrix Surgical Mesh [MSM]), or polypropylene (Bard Mesh) meshes, using the underlay augmentation technique. One year after surgery, primary outcome was recurrence; secondary outcomes were tensile strength, histologic degree of tissue remodeling, and intraabdominal adhesion formation. Only two Surgisis 4-ply animals (50%) presented with a recurrent hernia. All GORE BIO-A TR meshes were completely resorbed and, as after primary repair, well-organized connective tissue without inflammation was present, with moderate adhesion formation and sufficient tensile strength. Cross-linked biological and TIGR MSM meshes demonstrated highest tensile strength but were only partially incorporated, with similar foreign body reaction and adhesion formation as polypropylene meshes in the TIGR MSM group, and minimal degradation and moderate adhesion formation in the cross-linked biological group. In the non-cross-linked biological group sufficient tensile strength and moderate adhesion formation were found, with pronounced inflammation if mesh remnants were present. Synthetic bioabsorbable GORE BIO-A TR meshes were associated with optimal tissue remodeling, with complete resorption, presence of well-organized tissue, and no inflammation. However, mesh augmentation had no advantages regarding recurrence rate versus primary repair of large abdominal wall defects.


The virulence-associated chrysobactin iron uptake system of Erwinia chrysanthemi 3937 involves an operon encoding transport and biosynthetic functions.
The iron assimilation system of Erwinia chrysanthemi 3937 is mediated by the catechol-type siderophore chrysobactin and the outer membrane transport protein Fct. We generated a variety of subclones in high- and low-copy-number vectors from a wild-type recombinant cosmid shown previously to carry the gene cluster fct-cbsA, cbsB, cbsC, cbsE encoding chrysobactin transport and biosynthetic functions, respectively. We studied their expression in Escherichia coli enterobactin-deficient entA, entB, entC, and entE mutants. This provided evidence that the fct and cbs genes are regrouped within a single genetic unit of ca. 8 kb in the following order: fct, cbsC, cbsE, cbsB, and cbsA. The gene boundaries were determined, and the various recombinant plasmids were expressed in Escherichia coli minicells: CbsA and CbsC enzymatic activities were clearly identified as polypeptides with apparent molecular masses of 32,000 and 38,000, respectively.


Ethnic differences in the prevalence and treatment of cardiovascular risk factors in US outpatients with peripheral arterial disease: insights from the reduction of atherothrombosis for continued health (REACH) registry.
Prior investigations to define ethnic-related differences in the risks, medical treatment, and outcomes of patients with peripheral arterial disease (PAD) have been limited. The impact of ethnicity on the risk factor profiles, use of evidence-based medical therapies, and 2-year cardiovascular outcomes were investigated in 2,168 individuals (blacks n = 237, Hispanics n = 115, whites n = 1,816) from the United States with PAD from the international Reduction of Atherothrombosis for Continued Health Registry. Blacks and Hispanics were more likely to have diabetes mellitus and hypertension, whereas whites had a higher rate of diagnosed hypercholesterolemia. Control of blood pressure and cholesterol levels differed significantly in the groups at baseline: elevated blood pressure was present in 55% of blacks versus 48% of Hispanics versus 38% of whites (P < .01), whereas 41% of blacks versus 31% of Hispanics versus 25% of whites had elevated total cholesterol (P < .01). Aspirin use (62% of blacks vs 68% of Hispanics vs 72% of whites, P < .01) and statin use (72% of blacks vs 68% of Hispanics vs 77% of whites, P = .03) also varied significantly. In this context, rates by ethnicity for cardiovascular death, myocardial infarction, or stroke seemed to be no different at 2 years, at 8.8% for the total population: 11.6% for blacks, 8.5% for whites, and 5.0% for Hispanics (P = .32). Fewer blacks (0.6%) had undergone peripheral arterial bypass surgery compared with whites (3.4%) and Hispanics (5.2%) (P = .02). Ethnic-related differences have been documented in the prevalence and treatment of several atherosclerotic risk factors known to be associated with PAD, including a variation in the use of surgical revascularization procedures.


Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors.
Relapse of castration-resistant prostate cancer (CRPC) that occurs after androgen deprivation therapy of primary prostate cancer can be mediated by reactivation of the androgen receptor (AR). One important mechanism mediating this AR reactivation is intratumoral conversion of the weak adrenal androgens DHEA and androstenedione into the AR ligands testosterone and dihydrotestosterone. DHEA and androstenedione are synthesized by the adrenals through the sequential actions of the cytochrome P450 enzymes CYP11A1 and CYP17A1, so that CYP17A1 inhibitors such as abiraterone are effective therapies for CRPC. However, the significance of intratumoral CYP17A1 and de novo androgen synthesis from cholesterol in CRPC, and the mechanisms contributing to CYP17A1 inhibitor resistance/relapse, remain to be determined. We report that AR activity in castration-resistant VCaP tumor xenografts can be restored through CYP17A1-dependent de novo androgen synthesis, and that abiraterone treatment of these xenografts imposes selective pressure for increased intratumoral expression of CYP17A1, thereby generating a mechanism for development of resistance to CYP17A1 inhibitors. Supporting the clinical relevance of this mechanism, we found that intratumoral expression of CYP17A1 was markedly increased in tumor biopsies from CRPC patients after CYP17A1 inhibitor therapy. We further show that CRPC cells expressing a progesterone responsive T877A mutant AR are not CYP17A1 dependent, but that AR activity in these cells is still steroid dependent and mediated by upstream CYP11A1-dependent intraturmoral pregnenolone/progesterone synthesis. Together, our results indicate that CRPCs resistant to CYP17A1 inhibition may remain steroid dependent and therefore responsive to therapies that can further suppress de novo intratumoral steroid synthesis.


Atacicept, a novel B cell-targeting biological therapy for the treatment of rheumatoid arthritis.
Recent data suggest a key role for B cells in the pathogenesis of many autoimmune diseases including rheumatoid arthritis (RA), and biological therapies targeting B cells are promising treatments for patients with RA. Atacicept inhibits B cell maturation, differentiation and survival, and immunoglobulin production by depriving B cells of growth and development signals. Therefore, atacicept may represent an effective strategy in RA treatment. To evaluate the potential value of atacicept in RA treatment based on preclinical and clinical studies. Preclinical and clinical data on atacicept were identified using PubMed and systematically reviewed. Preclinical and clinical studies show that atacicept is well tolerated, with no increased incidence of infections. Atacicept displays non-linear pharmacokinetics, with a more than dose-proportional increase in free drug and less than dose-proportional, saturated increase in atacicept-ligand complex. Overall, the pharmacokinetic profiles of atacicept were consistent, dose-related and predictable. Dose-dependent reductions in immunoglobulins and other biomarkers, including rheumatoid factor, occurred rapidly but returned to baseline after discontinuation. There was a biphasic response in B cell number, but no effect on other leucocytes. Atacicept improved the signs and symptoms of RA, although larger studies are needed to confirm its efficacy and its optimal use.


REM sleep-active MCH neurons are involved in forgetting hippocampus-dependent memories.
The neural mechanisms underlying memory regulation during sleep are not yet fully understood. We found that melanin concentrating hormone-producing neurons (MCH neurons) in the hypothalamus actively contribute to forgetting in rapid eye movement (REM) sleep. Hypothalamic MCH neurons densely innervated the dorsal hippocampus. Activation or inhibition of MCH neurons impaired or improved hippocampus-dependent memory, respectively. Activation of MCH nerve terminals in vitro reduced firing of hippocampal pyramidal neurons by increasing inhibitory inputs. Wake- and REM sleep-active MCH neurons were distinct populations that were randomly distributed in the hypothalamus. REM sleep state-dependent inhibition of MCH neurons impaired hippocampus-dependent memory without affecting sleep architecture or quality. REM sleep-active MCH neurons in the hypothalamus are thus involved in active forgetting in the hippocampus.


RNAi-mediated HuR depletion leads to the inhibition of muscle cell differentiation.
The formation of muscle fibers involves the sequential expression of many proteins that regulate key steps during myoblast-to-myotube transition. MyoD, myogenin, and the cyclin-dependent kinase inhibitor p21cip1 are major players in the initiation and maintenance of the differentiated state of mouse embryonic muscle cells (C2C12). The messenger RNAs encoding these three proteins contain typical AU-rich elements (AREs) in their 3'-untranslated regions (3'-UTRs), which are known to affect the half-life of many short-lived mRNAs. HuR, an RNA-binding protein that regulates both the stability and cellular movement of ARE-containing mRNAs, interacts and stabilizes the p21cip1 message under UV stress in human RKO colorectal carcinoma cells. Here, by the use of gel shift experiments and immunoprecipitation followed by reverse transcription-PCR analysis, we show that HuR interacts with MyoD, myogenin, and p21cip1 mRNAs through specific sequences in their 3'-UTRs. To demonstrate the implication of endogenous HuR in myogenesis, we knocked down its expression in myoblasts using RNA interference and observed a significant reduction of HuR expression, associated with complete inhibition of myogenesis. Moreover, the expression of MyoD and myogenin mRNAs, as well as proteins, is significantly reduced in the HuR knockdown C2C12 cells. We were able to completely re-establish the myogenic process of these defective cells by introducing back HuR protein conjugated to a cell-permeable peptide. Finally, HuR accumulates in the cytoplasm during myogenesis. Thus, our results clearly demonstrated that endogenous HuR plays a crucial role in muscle differentiation by regulating the expression and/or the nuclear export of ARE-containing mRNAs that are essential for this process.


FAAH Inhibition Restores Early Life Stress-Induced Alterations in PFC microRNAs Associated with Depressive-Like Behavior in Male and Female Rats.
Early life stress (ELS) increases predisposition to depression. We compared the effects of treatment with the fatty acid amide hydrolase (FAAH) inhibitor URB597, and the selective serotonin reuptake inhibitor paroxetine, on ELS-induced depressive-like behavior and the expression of microRNAs (miRs) associated with depression in the medial prefrontal cortex (mPFC), hippocampal CA1 area, lateral habenula and dorsal raphe in rats. We also examined the mRNA expression of serotonergic (htr1a and slc6a4) and endocannabinoid (cnr1, cnr2 and faah) targets in the mPFC following ELS and pharmacological treatment. Adult males and females exposed to the 'Limited Bedding and Nesting' ELS paradigm demonstrated a depressive-like phenotype and late-adolescence URB597 treatment, but not paroxetine, reversed this phenotype. In the mPFC, ELS downregulated miR-16 in males and miR-135a in females and URB597 treatment restored this effect. In ELS females, the increase in cnr2 and decrease in faah mRNAs in the mPFC were reversed by URB597 treatment. We show for the first time that URB597 reversed ELS-induced mPFC downregulation in specific miRs and stress-related behaviors, suggesting a novel mechanism for the beneficial effects of FAAH inhibition. The differential effects of ELS and URB597 on males and females highlight the importance of developing sex-specific treatment approaches.


The Evaluation of a Noninvasive Respiratory Volume Monitor in Pediatric Patients Undergoing General Anesthesia.
Pediatric patients following surgery are at risk for respiratory compromise such as hypoventilation and hypoxemia depending on their age, comorbidities, and type of surgery. Quantitative measurement of ventilation in nonintubated infants/children is a difficult and inexact undertaking. Current respiratory assessment in nonintubated patients relies on oximetry data, respiratory rate (RR) monitors, and subjective clinical assessment, but there is no objective measure of respiratory parameters that could be utilized to predict early respiratory compromise. New advances in technology and digital signal processing have led to the development of an impedance-based respiratory volume monitor (RVM, ExSpiron, Respiratory Motion, Inc, Waltham, MA). The RVM has been shown to provide accurate real-time, continuous, noninvasive measurements of tidal volume (TV), minute ventilation (MV), and RR in adult patients.In this prospective observational study, our primary aim was to determine whether the RVM accurately measures TV, RR, and MV in pediatric patients. A total of 72 pediatric patients (27 females, 45 males), ASA I to III, undergoing general anesthesia with endotracheal intubation were enrolled. After endotracheal intubation, continuous data of MV, TV, and RR were recorded from the RVM and an in-line monitoring spirometer (NM3 monitor, Phillips Healthcare). RVM and NM3 measurements of MV, TV, and RR were compared during a 10-minute period prior to the incision ("Presurgery") and a 10-minute period after the end of surgery ("Postsurgery"). Relative errors were calculated over 1-minute segment within each 10-minute period. Bias, precision, and accuracy were calculated using Bland-Altman analyses and paired-difference equivalence tests were performed. Combined across the Presurgery and Postsurgery periods, the RVM's mean measurement bias (RVM - NM3 measurement) for MV was -3.8% (95% limits of agreement) (±1.96 SD): (-19.9% to 12.2%), for TV it was -4.9 (-21.0% to 11.3%), and for RR it was 1.1% (-4.1% to 6.2%). The mean measurement accuracies for MV, TV, and RR were 11.9%, 12.0%, and 4.2% (0.6 breaths/min), respectively. Note that lower accuracy numbers correspond to more accurate RVM measurements. The equivalence tests rejected the null hypothesis that the RVM and NM3 have different mean values and conclude with 90% power that the measurements of MV, TV, and RR from the RVM and NM3 are equivalent within ±10%. Our data indicate acceptable agreement between RVM and NM3 measurements in pediatric mechanically-ventilated patients. Future studies assessing the capability of the RVM to detect respiratory compromise in other clinical settings are needed.


Hospitals adopt intensive programs for diabetic patients to avoid high inpatient costs.
Just over a year ago, a 24-year-old man walked into a free health screening at Palmyra Medical Centers in Albany, Ga., complaining of weight loss, unending thirst and frequent urination. A quick blood test revealed the man was diabetic, with an alarming hemoglobin A1c level of 20.1. After six months of intervention, the man's hemoglobin dropped to an excellent rating of 7.1 and his physician is now ready to take him off insulin, said Layne Cox, program manager of the Diabetes Treatment Center at Palmyra, a Columbia/HCA hospital. While health fairs of yesterday were used to attract patients into the hospital, today's outreach programs are measured by success stories such as this. The goal now is to keep patients healthy and out of the hospital to reduce costs to managed care plans and health-care providers at risk through capitation contracts.


Asymmetric reassociation of calf spleen NAD+ glycohydrolase into liposomes.
NAD+ glycohydrolase (NAD+ nucleosidase, EC 220.127.116.11) can be solubilized from calf spleen microsomes (microsomal fractions) by steapsin or by detergents to yield respectively a hydrophilic (i.e. water-soluble) and a hydrophobic form of the enzyme. The detergent-solubilized enzyme was successfully reassociated into phosphatidylcholine liposomes either by a cholate-dialysis or by a gel-filtration procedure. In both cases the incorporation of NAD+ glycohydrolase was found to be completely asymmetric, i.e. the active site of the enzyme was exposed only at the outer surface of the vesicles. By contrast, as judged by flotation experiments, the hydrophilic form of NAD+ glycohydrolase could not be reassociated into liposomes. These results are in agreement with the hypothesis that calf spleen NAD+ glycohydrolase is an amphipathic protein. When incorporated into large unilamellar vesicles composed of phosphatidylcholine, NAD+ glycohydrolase was not found to catalyse vectorial transfer of NAD+ by transglycosidation with nicotinamide as acceptor.


Adaptive oscillators support Bayesian prediction in temporal processing.
Humans excel at predictively synchronizing their behavior with external rhythms, as in dance or music performance. The neural processes underlying rhythmic inferences are debated: whether predictive perception relies on high-level generative models or whether it can readily be implemented locally by hard-coded intrinsic oscillators synchronizing to rhythmic input remains unclear and different underlying computational mechanisms have been proposed. Here we explore human perception for tone sequences with some temporal regularity at varying rates, but with considerable variability. Next, using a dynamical systems perspective, we successfully model the participants behavior using an adaptive frequency oscillator which adjusts its spontaneous frequency based on the rate of stimuli. This model better reflects human behavior than a canonical nonlinear oscillator and a predictive ramping model-both widely used for temporal estimation and prediction-and demonstrate that the classical distinction between absolute and relative computational mechanisms can be unified under this framework. In addition, we show that neural oscillators may constitute hard-coded physiological priors-in a Bayesian sense-that reduce temporal uncertainty and facilitate the predictive processing of noisy rhythms. Together, the results show that adaptive oscillators provide an elegant and biologically plausible means to subserve rhythmic inference, reconciling previously incompatible frameworks for temporal inferential processes.


A riot on campus: The effects of social identity complexity on emotions and reparative attitudes after ingroup-perpetrated violence.
When a group commits a transgression, members who identify closely with the group often engage in defensive strategies in which they are less likely to experience guilt and shame in response to the transgression than are less identified group members. Subsequently, highly identified group members are often less willing to offer reparations to the injured parties. Because appropriate emotional responses and reparations are critical to community reconciliation, the present investigation examined whether social identity complexity-the degree to which individuals perceive their multiple social identities as interrelated-reduced these defensive responses. In the aftermath of a campus riot, emotional responses and reparative attitudes of undergraduate students were assessed. Results indicated that individuals who closely identified with the university were in fact capable of experiencing guilt and shame, but only if they also had complex social identities. A path model indicated that emotional responses, in turn, predicted willingness to provide reparations to the campus community. Accordingly, social identity complexity provides a new approach to understanding responses to ingroup-perpetrated violence.


Revisiting the Link between Job Satisfaction and Life Satisfaction: The Role of Basic Psychological Needs.
The link between job satisfaction and life satisfaction has been extensively explored in the relevant literature. However, the great majority of past research has been carried out using cross-sectional analyses, and almost exclusively in the Western world. Moreover, the underlying psychological mechanisms explaining the link are not yet completely understood. Thus, we report the first research to date which uses both cross-sectional and longitudinal data among workers in Chile-a fast-developing Latin American economy-and which aims to tackle previous limitations. Three studies consistently support a positive link between the constructs. Study 1 (N = 636) found that higher job satisfaction predicted higher life satisfaction both contemporaneously and longitudinally, and vice versa, above and beyond several key control variables. Study 2 (N = 725) and Study 3 (N = 703) replicated Study 1 results, but tested for the first time the role of satisfaction of basic psychological needs (as stated by self-determination theory) in the job-life satisfaction link. This is the most novel contribution of our paper. Key implications not only for individual quality of life, but also for companies' human resource practices emerge from our findings.


Complex formation of Vipp1 depends on its alpha-helical PspA-like domain.
Vipp1 (vesicle-inducing protein in plastids 1) is found in Cyanobacteria and chloroplasts of photosynthetic eukaryotes where it is essential for the formation of the thylakoid membrane. Vipp1 is closely related to the phage shock protein A (PspA), a bacterial protein induced under diverse stress conditions. Vipp1 proteins differ from PspA by an additional C-terminal domain that is required for Vipp1 function in thylakoid biogenesis. We show here that in Cyanobacteria, green algae, and vascular plants, Vipp1 is part of a high molecular mass complex. The complex is formed by multiple copies of Vipp1, and complex formation involves interaction of the central alpha-helical domain that is common to Vipp1 as well as to PspA proteins. In chloroplasts of vascular plants, the Vipp1 complex can be visualized by green fluorescent protein fusion in discrete locations at the inner envelope. Green fluorescent protein fusion analysis furthermore revealed that complex formation is important for proper positioning of Vipp1 at the inner envelope of chloroplasts.


[Changes in the vegetative status and excretion of catecholamines during lateral therapy for essential hypertension].
In 30 patients with stage II essential hypertension a spectral analysis of the heart's rhythm was done together with measuring the urine excretion of catecholamines before and after a session of lateral light therapy. There has been noted a decrease in power of the ranges 0.08-0.15 and 0.15-0.5 Hz of the spectrogram and an appreciable rise in excretion of dofamine. The investigators have reached the conclusion that under the exposure to lateral light therapy there occurs a decrease in the baroreflex and vagus tone. A suggestion is made to the effect that dofamine may have its part in the antihypertensive effect of lateral therapy.


Epigenetic modifying enzyme expression in asthmatic airway epithelial cells and fibroblasts.
Recognition of the airway epithelium as a central mediator in the pathogenesis of asthma has necessitated greater understanding of the aberrant cellular mechanisms of the epithelium in asthma. The architecture of chromatin is integral to the regulation of gene expression and is determined by modifications to the surrounding histones and DNA. The acetylation, methylation, phosphorylation, and ubiquitination of histone tail residues has the potential to greatly alter the accessibility of DNA to the cells transcriptional machinery. DNA methylation can also interrupt binding of transcription factors and recruit chromatin remodelers resulting in general gene silencing. Although previous studies have found numerous irregularities in the expression of genes involved in asthma, the contribution of epigenetic regulation of these genes is less well known. We propose that the gene expression of epigenetic modifying enzymes is cell-specific and influenced by asthma status in tissues derived from the airways. Airway epithelial cells (AECs) isolated by pronase digestion or endobronchial brushings and airway fibroblasts obtained by outgrowth technique from healthy and asthmatic donors were maintained in monolayer culture. RNA was analyzed for the expression of 82 epigenetic enzymes across 5 families of epigenetic modifying enzymes. Western blot and immunohistochemistry were also used to examine expression of 3 genes. Between AECs and airway fibroblasts, we identified cell-specific gene expression in each of the families of epigenetic modifying enzymes; specifically 24 of the 82 genes analyzed showed differential expression. We found that 6 histone modifiers in AECs and one in fibroblasts were differentially expressed in cells from asthmatic compared to healthy donors however, not all passed correction. In addition, we identified a corresponding increase in Aurora Kinase A (AURKA) protein expression in epithelial cells from asthmatics compared to those from non-asthmatics. In summary, we have identified cell-specific variation in gene expression in each of the families of epigenetic modifying enzymes in airway epithelial cells and airway fibroblasts. These data provide insight into the cell-specific variation in epigenetic regulation which may be relevant to cell fate and function, and disease susceptibility.


The benefits of group occupational therapy for patients with Parkinson's disease.
The medical treatment of idiopathic Parkinson's disease has improved the quality of life and increased survival of patients with Parkinson's disease. However, as the illness progresses, impairments in daily living activities occur. A clinical trial for a group rehabilitation program was initiated to maintain the functional status of these patients. The research protocol consisted of a pretreatment evaluation, random assignment to experimental or control groups, and posttreatment evaluations after therapy, at 6 months and at 1 year. The results showed that the subjects of the treated experimental group maintained their functional status after 1 year, demonstrated a significant decrease of bradykinesia, and perceived a significant improvement in their psychological well-being. This study confirms the value of an occupational therapy group approach and its benefits to the functional independence, to the improvement of physical and motor symptoms, and to the quality of life of persons with Parkinson's disease.


Structure, nutritional composition, and functionality of xylanase/microwave radiation-pretreated tiger nut.
In this study, tiger nut was pretreated with xylanase (Xyl), microwave radiation (MW), and a combination of both (MW + Xyl). The structure, nutritional composition, technofunctional, and antioxidant properties of the pretreated and untreated (control) tiger nut flour (TNF) were investigated. The Fourier transform infrared spectroscopic and X-ray diffractrometric spectra of the control and the pretreated samples are similar; however, there was a slight change in some peaks in the pretreated samples, indicating structural re-organization of macromolecules. Scanning electron microscopic images show reductions of surface erosion and formation of clusters in the MW + Xyl-treated TNF compared to the other pretreated samples. Pretreatment increased the protein, Ca, total phenolic content, and swelling capacity of TNF by 3.71-7.31%, 29.41-32.35%, 4.39-9.65%, and 1.59-6.75%, respectively. Meanwhile, 45.52-58.78% and 11.54-15.38% reductions in fat content and water absorption capacity, respectively, were recorded. Pretreatment of TNF with Xyl and MW + Xyl increased its soluble dietary fiber by 26.84% and 64.34%, respectively; however, a 3.31% reduction was recorded following MW treatment. The highest 2, 2-diphenyl-1-picrylhydrazyl scavenging activity (53.20%) was recorded in the MW + Xyl-treated TNF. These findings proved that pretreating TNF with microwave radiation and Xyl could improve its technological and nutritional qualities, enhancing its applicability in food systems.


Severe and common mental disorders and risk of emergency hospital admissions for ambulatory care sensitive conditions among the UK Biobank cohort.
People with mental disorders have worse physical health compared with the general population, which could be attributable to receiving poorer quality healthcare. To examine the relationship between severe and common mental disorders and risk of emergency hospital admissions for ambulatory care sensitive conditions (ACSCs), and factors associated with increased risk. Baseline data for England (N = 445 814) were taken from UK Biobank, which recruited participants aged 37-73 years during 2006-2010, and linked to hospital admission records up to 31 December 2019. Participants were grouped into those with a history of either schizophrenia, bipolar disorder, depression or anxiety, or no mental disorder. Survival analysis was used to assess the risk of hospital admission for ACSCs among those with mental disorders compared with those without, adjusting for factors in different domains (sociodemographic, socioeconomic, health and biomarkers, health-related behaviours, social isolation and psychological). People with schizophrenia had the highest (unadjusted) risk of hospital admission for ACSCs compared with those with no mental disorder (hazard ratio 4.40, 95% CI 4.04-4.80). People with bipolar disorder (hazard ratio 2.48, 95% CI 2.28-2.69) and depression or anxiety (hazard ratio 1.76, 95% CI 1.73-1.80) also had higher risk. Associations were more conservative when including all admissions, as opposed to first admissions only. The observed associations persisted after adjusting for a range of factors. People with severe mental disorders have the highest risk of preventable hospital admissions. Ensuring people with mental disorders receive adequate ambulatory care is essential to reduce the large health inequalities they experience.


Khat Chewing Practice and Associated Factors among Adults in Ethiopia: Further Analysis Using the 2011 Demographic and Health Survey.
Khat chewing has become a highly prevalent practice and a growing public health concern in Ethiopia. Although there have been many small scale studies, very limited national information has been available in the general population. This study aimed to identify factors associated with khat chewing practice among Ethiopian adults. The study used the 2011 Ethiopian demographic and health survey data. The survey was cross-sectional by design and used a multistage cluster sampling procedure. Bivariate and multivariable logistic regression models with adjusted odds ratio (AOR) and their 95% confidence intervals (CI) were used to quantify the predictors. The overall khat chewing prevalence was 15.3% (95% CI: 14.90-15.71). Regional variation was observed with the highest in Harari [(53.2% (95% CI: 43.04-63.28)] and lowest in Tigray regional state [(1.1% (95% CI: 0.72-1.66)]. Multivariable analysis showed that Islam followers were 23.8 times more likely to chew khat as compared to Orthodox followers. Being a resident in Oromiya, South Nation, Nationalities and People (SNNP), Gambella, Harari and Dire Dawa regions had 1.9, 1.6, 3.1, 5.2 and 3.5 times higher odds of chewing khat as compared to Addis Ababa residents, respectively. Adults in the age group 45-49 years were 3.6 times more likely to chew khat as compared to 15-19 years. The middle and richest wealth quintiles were 1.3 and 1.5 times more likely to chew khat, respectively, as compared to the poorest category. Rural residents had 1.3 odds of chewing khat than urban residents. Those individuals who had occupation in sales, agriculture, service sector, skilled and unskilled manual workers were 1.6, 1.3, 2.4, 1.7 and 2.3 times more likely to chew khat, respectively, as compared to those who have no occupation. Females were 77% less likely to chew khat as compared to males. Formerly married and those experienced in child death had 1.4 and 1.2 times higher odds to chew khat as compared with those never married and never had child death, respectively. Those who attended mass media were 1.4 times more likely to chew khat compared with not attended. Khat chewing is a public health concern in Ethiopia. The highest wealth quintiles, older age group, rural residence, child death, formerly married, males, regions of Oromiya, SNNP, Gambella, Harari and Dire Dawa and Islamic followers had statistically significant association with khat chewing. Due attention needs to be given for these factors in any intervention procedures.


Tone perception ability of Cantonese-speaking children.
Studies have shown that while children acquire all Cantonese tones by age two, they are not able to label them reliably until approximately age 10. One possible explanation for the large age discrepancy may be the different methodologies used. This study aimed to (1) investigate a new research design for the collection of reliable tone perception data from young children; (2) compare lexical and nonlexical items for testing tone perception ability; and (3) identify the relative ease of perceiving the three basic tone contrasts in Cantonese, that is, high level/high rising (T1/T2), high level/low falling (T1/T4), and, high rising/low falling tones (T2/T4). The three tone pairs were presented to 31 children in the form of word and nonword stimuli. It was found that the research design could be used to assess the tone perception knowledge of children as young as 2;09. Significant differences were found between word and nonword stimuli and also in the identification of the T2/T4 contrast in comparison with the other two pairs. Children's overall tone perception abilities are discussed in detail with reference to the role of lexical knowledge and the potential for tone perception confusions arising from differences in fundamental frequencies for tone onset and offset.


High-Temperature Polymer Dielectrics Designed Using an Invertible Molecular Graph Generative Model.
Generating new molecules with the desired physical or chemical properties is the key challenge of computational material design. Deep learning techniques are being actively applied in the field of data-driven material informatics and provide a promising way to accelerate the discovery of innovative materials. In this work, we utilize an invertible graph generative model to generate hypothetical promising high-temperature polymer dielectrics. A molecular graph generative model based on the invertible normalizing flow is trained on a data set containing 250k polymer molecular graphs (mostly generated by an RNN-based generative model) to learn the invertible transformations between latent distributions and molecular graph structures. When generating molecular graphs, a sample vector is drawn from the latent space, and then an adjacency tensor and node attribute matrix are generated through two invertible flows in two steps and assembled into a molecular graph. The model has the merits of exact likelihood training and an efficient one-shot generation process. The learned latent space is used to generate polymers with a high glass-transition temperature (Tg) and a wide band gap (Eg) for the application of high-temperature energy storage film capacitors. This work contributes to the efficient design of high-temperature polymer dielectrics by using deep generative models.


Struggling in silence.
Women who have been treated for breast cancer can experience an early menopause or the return of symptoms such as hot flushes years after they have been through the menopause. Grateful to have survived cancer, they may be reluctant to seek help for menopausal symptoms. A breast cancer menopause clinic is providing tailored support.


Identification of pathognomonic purine synthesis biomarkers by metabolomic profiling of adolescents with obesity and type 2 diabetes.
The incidence of type 2 diabetes is increasing more rapidly in adolescents than in any other age group. We identified and compared metabolite signatures in obese children with type 2 diabetes (T2D), obese children without diabetes (OB), and healthy, age- and gender-matched normal weight controls (NW) by measuring 273 analytes in fasting plasma and 24-hour urine samples from 90 subjects by targeted LC-MS/MS. Diabetic subjects were within 2 years of diagnosis in an attempt to capture early-stage disease prior to declining renal function. We found 22 urine metabolites that were uniquely associated with T2D when compared to OB and NW groups. The metabolites most significantly elevated in T2D youth included members of the betaine pathway, nucleic acid metabolism, and branched-chain amino acids (BCAAs) and their catabolites. Notably, the metabolite pattern in OB and T2D groups differed between urine and plasma, suggesting that urinary BCAAs and their intermediates behaved as a more specific biomarker for T2D, while plasma BCAAs associated with the obese, insulin resistant state independent of diabetes status. Correlative analysis of metabolites in the T2D signature indicated that betaine metabolites, BCAAs, and aromatic amino acids were associated with hyperglycemia, but BCAA acylglycine derivatives and nucleic acid metabolites were linked to insulin resistance. Of major interest, we found that urine levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) were increased in diabetic youth, identifying urine SAICA-riboside as a potential biomarker for T2D.


Transcriptional analysis of genes associated with stress and adhesion in Lactobacillus acidophilus NCFM during the passage through an in vitro gastrointestinal tract model.
The aim of the present study was to investigate the transcription of genes associated with stress and adhesion in Lactobacillus acidophilus NCFM during the passage through an in vitro gastrointestinal tract model. As acidified milk exerted a protective effect on the bacteria leading to increased survival, the gene expression studies were carried out with pre-inoculation of L. acidophilus NCFM in acidified milk. The induction of the genes encoding the stress-related proteins GroEL, DnaK and ClpP, and adhesion-related genes encoding mucin-binding proteins, fibronectin-binding protein and S-layer was analyzed by real-time PCR. The genes encoding GroEL, DnaK and ClpP were significantly up-regulated (9- to 16-fold) during gastric digestion and declined upon subsequent duodenal digestion. The genes encoding mucin-binding proteins and fibronectin-binding protein were not influenced by saliva and gastric juice, but they were significantly upregulated during incubation in duodenal juice and bile (6- to 7-fold). A significant induction of the gene encoding the S-layer protein was not detected. Our results give a better understanding of the functionality of L. acidophilus NCFM and other probiotics during passage through the gastrointestinal tract; hence, they provide an implementable basis for the selection of prospective probiotic candidates.


Coiling of elastic rods on rigid substrates.
We investigate the deployment of a thin elastic rod onto a rigid substrate and study the resulting coiling patterns. In our approach, we combine precision model experiments, scaling analyses, and computer simulations toward developing predictive understanding of the coiling process. Both cases of deposition onto static and moving substrates are considered. We construct phase diagrams for the possible coiling patterns and characterize them as a function of the geometric and material properties of the rod, as well as the height and relative speeds of deployment. The modes selected and their characteristic length scales are found to arise from a complex interplay between gravitational, bending, and twisting energies of the rod, coupled to the geometric nonlinearities intrinsic to the large deformations. We give particular emphasis to the first sinusoidal mode of instability, which we find to be consistent with a Hopf bifurcation, and analyze the meandering wavelength and amplitude. Throughout, we systematically vary natural curvature of the rod as a control parameter, which has a qualitative and quantitative effect on the pattern formation, above a critical value that we determine. The universality conferred by the prominent role of geometry in the deformation modes of the rod suggests using the gained understanding as design guidelines, in the original applications that motivated the study.


A prospective evaluation of computed tomography and ultrasound of the pancreas.
A prospective cooperative study was performed to assess the relative efficacy of computed tomography (CT) and ultrasound in detecting and identifying pancreatic lesions. Of the 279 patients in the study, 146 were found to have a normal pancreas, and 133 had an abnormal pancreas. All patients underwent both CT and ultrasound examinations. Forty-four ultrasound examinations were technically unsatisfactory. When these suboptimal examinations were excluded, CT had a sensitivity of 0.87 and a specificity of 0.90 in detecting an abnormal pancreas. Ultrasound had a sensitivity of 0.69 and a specificity of 0.82. In detecting a lesion and identifying it as malignant or inflammatory, CT had a sensitivity of 0.84 and ultrasound had a sensitivity of 0.56. It is concluded that CT is the method of choice for detecting a pancreatic lesion, assessing its extent, and defining its etiology.


Cutaneous syndromes of non-X histiocytosis. A review of the macrophage-histiocyte diseases of the skin.
The bone marrow and blood monocytes are precursor cells to the macrophage-histiocyte, the Langerhans cell, the indeterminate cell, the interdigitating cell, and the dendritic cell in the thymus, lymph node, and skin. While there are many histologic and functional similarities in these cell types, some differences do occur. A notable difference is the minimal phagocytosis by the Langerhans cell and the histiocytosis X cell. Non-X histiocytosis is represented by a series of cutaneous disease patterns characterized by localized, nonaggressive, histioxanthomatous skin and mucous membrane lesions, with a tendency to self-heal, Eruptive histiocytoma, juvenile xanthogranuloma, reticulohistiocytoma cutis, papular xanthoma, necrobiotic xanthogranuloma with paraproteinemia, and xanthoma disseminatum are cutaneous patterns of non-X histiocytosis that suggest the possibility of at least two patterns of peripheral macrophage differentiation and pathologic change.


Role of the maternal organism in transplacental carcinogenesis.
The maternal organism plays a highly important role in transplacental carcinogenesis, since for carcinogens in the bloodstream of the mother to reach the fetus, they must cross several barriers, the first of which is the placenta. Some types of compounds require metabolic activation in the maternal organism, in the fetus and even sometimes in the placenta. Thus, four main pathways can be hypothesized by which substances exert a carcinogenic effect on the fetus. Most carcinogens can cross the placenta; data confirm that this process consists of simple diffusion or - in the case of high doses - facilitated diffusion. That carcinogens may be detoxified in the maternal organism is confirmed by experiments on activation of enzyme systems and on caesarean deliveries. Species and strain specificities are characteristic of transplacental carcinogenesis and are manifested in organotropism. Organotropism in transplacental carcinogenesis is determined by genetic predisposition, cell differentiation and proliferative activity in the target tissues. For indirect carcinogens, the level of metabolizing enzymes is also important.


The co-localization of neuropeptides in the submucosa of the small intestine of normal Wistar and non-diabetic BB rats.
Immunocytochemical double and triple staining techniques were employed on whole mounts of the submucosal plexus from normal Wistar and non-diabetic BB rat jejunum and ileum, to determine the patterns of co-localization of vasoactive intestinal polypeptide-, peptide histidine-isoleucine-, somatostatin-, neuropeptide Y-, calcitonin gene-related peptide-, substance P-, and galanin-immunoreactive nerves. Neuropeptide Y immunoreactivity was found in 38% of submucosal plexus neurons, within the same neuronal elements as vasoactive intestinal polypeptide immunoreactivity (39% of submucosal plexus neurons) and peptide histidine-isoleucine immunoreactivity. A small population (1% of submucosal plexus neurons) containing vasoactive intestinal polypeptide- and peptide histide isoleucine-like immunoreactivity without NPY-like immunoreactivity was also observed. A significant population of fibers containing vasoactive intestinal polypeptide and galanin immunoreactivity were observed in the mucosa and submucosa, although no cell bodies were detected which contained both neuropeptides. Galanin-like immunoreactivity was seen in a small (2% of submucosal plexus neurons) population, not co-localized with any of the other neuropeptides examined. All somatostatin-immunoreactive neuronal elements (18% of submucosal plexus neurons) contained calcitonin gene-related peptide immunoreactivity, just over half of which also contained substance P immunoreactivity. An additional 25% of submucosal plexus neurons contained calcitonin gene-related peptide- without somatostatin-like immunoreactivity and 28% of submucosal plexus neurons contained substance P without somatostatin-like immunoreactivity. Some degree of co-localization was seen between calcitonin gene-related peptide- and substance P-like immunoreactivity, however, this could not be directly quantified.(ABSTRACT TRUNCATED AT 250 WORDS)


Loss of the imprinted, non-coding Snord116 gene cluster in the interval deleted in the Prader Willi syndrome results in murine neuronal and endocrine pancreatic developmental phenotypes.
Global neurodevelopmental delay is a prominent characteristic of individuals with Prader-Willi syndrome (PWS). The neuromolecular bases for these delays are unknown. We identified neuroanatomical changes in the brains of mice deficient for a gene in the minimal critical deletion region for PWS (Snord116p-/m+). In Snord116p-/m+ mice, reduced primary forebrain neuron cell body size is apparent in embryonic day 15.5 fetuses, and persists until postnatal day 30 in cerebellar Purkinje neurons. Snord116 is a snoRNA gene cluster of unknown function that can localize to the nucleolus. In cerebellar Purkinje neurons from postnatal day 30 Snord116p-/m+ mice the reduction in neuronal cell body size was associated with decreased neuronal nucleolar size. We also identified developmental changes in the endocrine pancreas of Snord116p-/m+ animals that persist into adulthood. Mice lacking Snord116 have smaller pancreatic islets; within the islet the percentage of δ-cells is increased, while the percentage of α-cells is reduced. The α-cell markers, Sst and Hhex, are upregulated in Snord116p-/m+ isolated islets while Ins1, Ins2, Pdx1, Nkx6-1, and Pax6 are downregulated. There is a 3-fold increase in the percentage of polyhormonal cells in the neonatal pancreata of Snord116p-/m+ mice, due primarily to an increase in cells co-positive with somatostatin. Snord116 may play a role in islet cell lineage specification. The Snord116 gene cluster is important for developmental processes in the brain as well as the endocrine pancreas.


Construction and characterization of an HIV-1 group O infectious molecular clone and analysis of vpr- and nef-negative derivatives.
In this report, we describe the construction and characterization of the first full-length infectious molecular clone from the Cameroonian HIV-1 group O primary isolate MVP8913. Virus obtained after transfection of the proviral clone pCMO2.3 replicated to levels comparable to its parental isolate in the human T-cell line PM-1, although replication was reduced by fivefold in peripheral blood mononuclear cells (PBMC) and was barely detectable in primary monocyte-derived macrophages (MDM). Phylogenetic analysis of the complete proviral sequence revealed a closer relationship to ANT70 than to MVP5180, the two prototypic group O primary isolates. All reading frames for structural and accessory genes were open except for vpr that contained an in-frame stop codon. In the nef gene, a mutation disrupting the functionally important myristoylation signal was observed. Repairing the defect in nef enhanced replication in PBMC and MDM, although repairing the vpr defect only affected replication in MDM, consistent with the known phenotypes of vpr and nef mutants in HIV-1 group M viruses. Repairing both vpr and nef showed an additive effect, but the resulting virus was still impaired compared to the parental isolate. This defect was overcome when the gag-pol coding region was exchanged for that from another O-type isolate giving rise to the proviral clone pCMO2.5. Virus obtained from pCMO2.5 replicated with similar kinetics as the parental O-type isolate in both PBMC and MDM, making this proviral clone a valuable tool for further studies on functional characteristics of HIV-1 group O viruses.


Specialized transducing phages derived from phage P22 that carry the pro AB region of the host, Salmonella typhimurium: genetic evidence for their structure and mode of transduction.
Two independently isolated specialized transducing phages, P22pro-1 and P22pro-3, have been studied. Lysates of P22pro-1 contain a majority of transducing phages which can go through the lytic cycle only in mixed infection; these defective phages transduce by lysogenization in mixed infection and by substitution in single infection. A few of the transducing phages in P22pro-1 lysates appear to be non-defective, being able to form plaques and to transduce by lysogenization in single infection. Transduction by P22pro-3 lysates is effected by non-defective transducing phages, which transduce by lysogenization; these lysates also contain a majority of defective phages which do not co-operate in mixed infection. The P22pro-1 genome is thought to contain an insertion of bacterial DNA longer than the terminal repetition present in P22 wild type, so that at maturation a population of differently defective phages is produced. The exact structure of the P22pro-3 genome is open to conjecture, but it seems clear that the insertion of bacterial DNA is smaller than that in P22pro-1. Both P22pro-1 and P22pro-3 are defective in integration at ataA under non-selective conditions, although both integrate on medium that lacks proline.


Sustained effect of an intervention to limit ordering of emergency department lumbosacral spine films.
Attempts at modification of test-ordering practices among housestaff demonstrate reversion to prior behavior after relaxation of surveillance. To test the hypothesis that use of pre-specified criteria for obtaining emergency department (ED) lumbosacral spine (LSS) films would reduce LSS utilization, we designed a cross-sectional observational study, with 1-year follow-up. The primary endpoint was estimate of efficacy, expressed as a proportionate change in LSS films from 1982 to 1992, adjusted for ED volume. The secondary endpoint was estimate of safety of this protocol. We found a 28% proportionate decrease in LSS films from 1982 to 1992. Among 520 patients with back complaints not meeting criteria for films, 4 had serious back pathology on follow-up that may have been detected on the index ED visit if LSS films had been ordered. All four were HIV(+), three of whom initially denied, then subsequently admitted, to active intravenous drug use. We conclude that use of a simple requisition form is associated with a quantitatively and statistically significant sustained reduction in utilization of ED LSS radiography. This protocol appears to provide a safe, cost-efficient means of limiting LSS film ordering by housestaff, with the possible exception of HIV(+) individuals. Because the association between HIV and radiographic abnormalities may be confounded by intravenous drug use, we cannot determine, on the basis of our data, whether HIV(+) status should be considered an independent criterion for obtaining LSS films.


First in vivo evaluation of liposome-encapsulated 223Ra as a potential alpha-particle-emitting cancer therapeutic agent.
Liposomes carrying chemotherapeutics have had some success in cancer treatment and may also be suitable carriers for therapeutic radionuclides. This study was designed to evaluate the biodistribution and to estimate the radiation doses of the alpha emitter 223Ra loaded into pegylated liposomes in selected tissues. 223Ra was encapsulated in pegylated liposomal doxorubicin (PLD) by ionophore-mediated loading. The biodistribution of liposomal 223Ra was compared to free cationic 223Ra in Balb/C mice. Liposomal 223Ra circulated in the blood with an initial half-life in excess of 24 hours, which agreed well with that reported for PLD in rodents, while the blood half-life of cationic 223Ra was considerably less than an hour. When liposomal 223Ra was catabolized, the released 223Ra was either excreted or taken up in the skeleton. This skeletal uptake increased up to 14 days after treatment, but did not reach the level seen with free 223Ra. Pre-treatment with non-radioactive PLD 4 days in advance lessened the liver uptake of liposomal 223Ra. Dose estimates showed that the spleen, followed by bone surfaces, received the highest absorbed doses. Liposomal 223Ra was relatively stable in vivo and may have potential for radionuclide therapy and combination therapy with chemotherapeutic agents.


A mixed-methods study to explore the supportive care needs of breast cancer survivors.
Needs assessment is the essence of quality cancer survivorship care. The aim of this study was to explore the supportive care needs of breast cancer survivors (BCS) in the first 5 years post treatment. A mixed-methods approach was employed. A quantitative study included a Supportive Care Needs Survey, which was completed by 250 BCS to identify the level of their needs for help. The quantitative data informed semistructured qualitative interviews undertaken with 60 BCS to explore in detail their posttreatment needs and experiences. 32.4% and 16.8% reported 1 to 5 and greater than or equal to 6 needs for help, respectively. The regression analyses revealed that women within 2 years posttreatment and with higher educational level had higher levels of Psychological and Health Care System/Information needs. The qualitative data revealed "continuity of care" and "lifestyle advice and self-management" as prominent survivorship concerns. It was shown that determination to continue normal life, social support, and feeling overwhelmed by information were all experienced as important influences on survivors' need for help. Posttreatment needs vary with BCS characteristics and to the domains concerned. The approach to posttreatment care needs to be personalized and viable.


Early appearance of germinal center-derived memory B cells and plasma cells in blood after primary immunization.
Immunization with a T cell-dependent antigen elicits production of specific memory B cells and antibody-secreting cells (ASCs). The kinetic and developmental relationships between these populations and the phenotypic forms they and their precursors may take remain unclear. Therefore, we examined the early stages of a primary immune response, focusing on the appearance of antigen-specific B cells in blood. Within 1 wk, antigen-specific B cells appear in the blood with either a memory phenotype or as immunoglobulin (Ig)G1 ASCs expressing blimp-1. The memory cells have mutated V(H) genes; respond to the chemokine CXCL13 but not CXCL12, suggesting recirculation to secondary lymphoid organs; uniformly express B220; show limited differentiation potential unless stimulated by antigen; and develop independently of blimp-1 expression. The antigen-specific IgG1 ASCs in blood show affinity maturation paralleling that of bone marrow ASCs, raising the possibility that this compartment is established directly by blood-borne ASCs. We find no evidence for a blimp-1-expressing preplasma memory compartment, suggesting germinal center output is restricted to ASCs and B220(+) memory B cells, and this is sufficient to account for the process of affinity maturation.


A study of activity in the home environment among individuals with disability following a stroke.
An ethnographic approach (Fetterman DM. Ethnography Step by Step. Applied Social Research Methods Series, Vol. 17. London, New Delhi, SAGA Publication, 1990) with thematic interviews, participatory observations, the 'activity log' (Yerxa EJ, Baum S. Engagement in daily occupations and life satisfaction among people with spinal cord injuries. Occup Ther J Res 1986;(6)4;318-326), and the 'satisfaction with performance scaled questionnaire' (Yerxa EJ, Burnett-Beaulieu SE, Stocking S, Azen SP. Development of the satisfaction with performance scaled questionnaire (SPSQ). Am J Occup Ther 1988;42:215-221) were used to investigate, in their homes, the performance of occupation/activity in 15 stroke victims dependent in activities of daily living. The data were categorised according to Spradley (Participants Observation. USA, Holt, Rinehart and Winston, 1980). The study describes the activities performed by the individuals themselves, activities done for them, patterns of activity over time and the individuals' satisfaction with, and feelings about, each activity.


Theoretical investigation on the linear and nonlinear susceptibilities of urea crystal.
The linear and second-order nonlinear susceptibilities of the urea crystal have been evaluated by applying the supermolecule approach. Calculations performed at the time-dependent Hartree-Fock (TDHF) level using the Austin model (AM1) semiempirical Hamiltonian have first demonstrated the almost additive character of the essential polarizability and first hyperpolarizability components. In fact, the only exception concerns the chi(cc) ((1)) component when stacking urea molecules along the c axis, i.e., the axis of the hydrogen bonds. This behavior has been confirmed by ab initio calculations on small clusters. The macroscopic quantities have then been determined by adopting the multiplicative scheme and by correcting the TDHF/AM1 values for missing electron correlation by means of density functional theory and coupled cluster method. The reliability of the multiplicative scheme was demonstrated for clusters as large as 3ax3bx3c. While the electron correlation correction factors are similar for a single molecule and different small clusters, the global performance of the scheme differs for the linear and nonlinear responses. For the second-order nonlinear susceptibility, our predictions are in good agreement with experiment, while for the linear susceptibility and the associated refractive index, our predictions underestimate the experimental values. The limitations of our approach may be attributed to its inability to account for more subtle cooperative effects, like those associated with a network of hydrogen bonds. Together with other works, the supermolecule calculations confirm that the sign of chi(abc) ((2)) is negative, contrary to an estimate from band structure calculation.


A review. Lessons from an animal model of intra-abdominal sepsis.
Intra-abdominal sepsis that involves multiple aerobic and anaerobic bacteria derived from the colonic flora was studied in Wistar rats to determine the relative roles of various microbial species. The rats challenged with pooled colonic contents showed a biphasic disease. Initially, there was acute peritonitis, Escherichia coli bacteremia, and high mortality. In rats that survived this acute peritonitis stage, intra-abdominal abscesses developed, and anaerobic bacteria were the preponderant organisms. Subsequent experiments showed that antibiotics directed against coliforms prevented mortality, whereas agents active against anaerobes reduced the incidence of abscesses. Challenges with Escherichia coli alone produced bacteremia and death, whereas pure cultures of Bacteroides fragilis caused intra-abdominal abscesses. These observations suggest that both coliforms and anaerobes are important pathogens in intra-abdominal sepsis, although the different types of microbes appear to play distinctive roles in the sequence of pathological events.


The hydrogenation of gamma-linolenic acid by pure cultures of two rumen bacteria.
Two species of rumen bacteria that have been previously shown to partially hydrogenate alpha-linolenic acid have been examined for their ability to hydrogenate gamma-linolenic acid. Free gamma-linolenic acid is hydrogenated in vitro to stearic acid by a rumen Fusocillus sp. (N.C.I.B. 11026), but only to cis,trans-octadec-6,11-enoic acid by a Butyrivibrio sp. The sequential hydrogenations are preceded by a delta 12-cis-delta 11-trans isomerization identical with that observed in the hydrogenation of alpha-linolenic acid and linoleic acid.


On-Reading (Chinese-Style Pronunciation) Predominance Over Kun-Reading (Native Japanese Pronunciation) in Japanese Semantic Dementia.
Japanese kanji (morphograms) have two ways of reading: on-reading (Chinese-style pronunciation) and kun-reading (native Japanese pronunciation). It is known that some Japanese patients with semantic dementia read kanji with on-reading but not with kun-reading. To characterize further reading impairments of patients with semantic dementia, we analyzed data from a total of 9 patients who underwent reading and writing tests of kanji and kana (Japanese phonetic writing) and on-kun reading tests containing two-character kanji words with on-on reading, kun-kun reading, and specific (so-called Jukujikun or irregular kun) reading. The results showed that on-reading preceding (pronouncing first with on-reading) and kun-reading deletion (inability to recall kun-reading) were observed in nearly all patients. In the on-kun reading test, on-reading (57.6% correct), kun-reading (46.6% correct), and specific-reading (30.0% correct) were more preserved in this decreasing order (phonology-to-semantics gradient), although on-reading and kun-reading did not significantly differ in performance, according to a more rigorous analysis after adjusting for word frequency (and familiarity). Furthermore, on-substitution (changing to on-reading) errors in kun-reading words (27.0%) were more frequent than kun-substitution (changing to kun-reading) errors in on-reading words (4.0%). These results suggest that kun-reading is more predominantly disturbed than on-reading, probably because kun-reading and specific-reading are closely associated with the meaning of words.


Clinical response to hormone therapy correlated with estrogen receptor analyses. Biochemical v histochemical methods.
Estrogen receptor (ER) analysis by sucrose density gradient analysis (SDGA) was compared with histochemical localization of estrogen binding using 6-carbomethoxy-bovine serum albumin-fluorescein isothiocyanode-estradiol (E2-6-CMO-BSA-FITC) (6FE), 17-thiosemicarbozene-BSA-FITC-estrogen (E-17-TSC-BSA-FITC) (17FE), and polyestradiol phosphate-antiestradiol antibody-FITC (PEP) on serial frozen sections of metastatic breast cancer lesions from 72 patients treated with hormonal therapy. A comparison of assays to clinical responses gave the following sensitivities: ER-SDGA, 90%; 6FE, 50%; 17FE, 55%; and PEP, 58%. Specificities were as follows: ER-SDGA, 81%; 6FE, 47%; 17FE, 41%; and PEP, 59%. The SDGA gave the highest predictive value for clinical response, while the predictive value for each of the three histologic techniques approximated that predicted by chance alone. These selected histochemical techniques for ER localization, despite impressive cytologic localization patterns, therefore, do not correlate with clinical response.


Canadian high arctic ice core records of organophosphate flame retardants and plasticizers.
Organophosphate esters (OPEs) have been used as flame retardants, plasticizers, and anti-foaming agents over the past several decades. Of particular interest is the long range transport potential of OPEs given their ubiquitous detection in Arctic marine air. Here we report 19 OPE congeners in ice cores drilled on remote icefields and ice caps in the Canadian high Arctic. A multi-decadal temporal profile was constructed in the sectioned ice cores representing a time scale spanning the 1970s to 2014-16. In the Devon Ice Cap record, the annual total OPE (∑OPEs) depositional flux for all of 2014 was 81 μg m-2, with the profile dominated by triphenylphosphate (TPP, 9.4 μg m-2) and tris(2-chloroisopropyl) phosphate (TCPP, 42 μg m-2). Here, many OPEs displayed an exponentially increasing depositional flux including TCPP which had a doubling time of 4.1 ± 0.44 years. At the more northern site on Mt. Oxford icefield, the OPE fluxes were lower. Here, the annual ∑OPEs flux in 2016 was 5.3 μg m-2, dominated by TCPP (1.5 μg m-2) but also tris(2-butoxyethyl) phosphate (1.5 μg m-2 TBOEP). The temporal trend for halogenated OPEs in the Mt. Oxford icefield is bell-shaped, peaking in the mid-2000s. The observation of OPEs in remote Arctic ice cores demonstrates the cryosphere as a repository for these substances, and supports the potential for long-range transport of OPEs, likely associated with aerosol transport.


Synthesis, Spectroscopic, Thermal, and Catalytic Properties of Eight New Complexes of Metal(II) Formates or Propionates with Imidazole; Relationship between the Carbon Chain Length and Catalytic Activity.
In one of our previously published articles, we reported the synthesis, spectroscopic, thermal, and catalytic properties of four new M(II) acetate (where M = Co, Ni, Cu, Zn) complexes with imidazole. Presented compounds exhibited activity in the reaction on catalytic oxidation of styrene. In this study we have synthesized and investigated properties of analogous compounds, however using formates or propionates of mentioned metal cations instead of acetates. Such an approach allowed us to draw valuable conclusions concerning the relationship between the carbon chain length and catalytic activity, which is an important factor for catalyst modeling. Synthesized compounds have been thoroughly investigated using appropriate analytic techniques: AAS (Atomic Absorption Spectrometry), FTIR (Fourier-Transform Infrared Spectroscopy), and TGA (Thermogravimetric Analysis). Catalytic properties have been studied under the same previous conditions, using GC-FID (GC-chromatograph equipped with FID detector).


A new species of Proegernia from the Namba Formation in South Australia and the early evolution and environment of Australian egerniine skinks.
The diverse living Australian lizard fauna contrasts greatly with their limited Oligo-Miocene fossil record. New Oligo-Miocene fossil vertebrates from the Namba Formation (south of Lake Frome, South Australia) were uncovered from multiple expeditions from 2007 to 2018. Abundant disarticulated material of small vertebrates was concentrated in shallow lenses along the palaeolake edges, now exposed on the western of Lake Pinpa also known from Billeroo Creek 2 km northeast. The fossiliferous lens within the Namba Formation hosting the abundant aquatic (such as fish, platypus Obdurodon and waterfowl) and diverse terrestrial (such as possums, dasyuromorphs and scincids) vertebrates and is hereafter recognized as the Fish Lens. The stratigraphic provenance of these deposits in relation to prior finds in the area is also established. A new egerniine scincid taxon Proegernia mikebulli sp. nov. described herein, is based on a near-complete reconstructed mandible, maxilla, premaxilla and pterygoid. Postcranial scincid elements were also recovered with this material, but could not yet be confidently associated with P. mikebulli. This new taxon is recovered as the sister species to P. palankarinnensis, in a tip-dated total-evidence phylogenetic analysis, where both are recovered as stem Australian egerniines. These taxa also help pinpoint the timing of the arrival of scincids to Australia, with egerniines the first radiation to reach the continent.


The importance of the library in medical education.
The medical library assumes increasing importance to teaching and research. While funds for research, medical education, and improved facilities for patients have been increasing and are relatively easy to obtain, however, it has been extraordinarily difficult to obtain funds for the building and maintenance of medical libraries. The National Library of Medicine is attempting to preserve the record of medical knowledge and by means of mechanization provide more efficient service to physicians and scientists, but one, or a few, great libraries cannot serve the medical interests of the country. Federal support such as the program of grants in the proposed Medical Library Assistance Act is needed to assist local and regional efforts to improve library service.


Bone apatite composition of necrotic trabecular bone in the femoral head of immature piglets.
Ischemic osteonecrosis of the femoral head (IOFH) can lead to excessive resorption of the trabecular bone and collapse of the femoral head as a structure. A well-known mineral component to trabecular bone is hydroxyapatite, which can be present in many forms due to ionic substitution, thus altering chemical composition. Unfortunately, very little is known about the chemical changes to bone apatite following IOFH. We hypothesized that the apatite composition changes in necrotic bone possibly contribute to increased osteoclast resorption and structural collapse of the femoral head. The purpose of this study was to assess the macroscopic and local phosphate composition of actively resorbed necrotic trabecular bone to isolate differences between areas of increased osteoclast resorption and normal bone formation. A piglet model of IOFH was used. Scanning electron microscopy (SEM), histology, X-ray absorbance near edge structure (XANES), and Raman spectroscopy were performed on femoral heads to characterize normal and necrotic trabecular bone. Backscattered SEM, micro-computed tomography and histology showed deformity and active resorption of necrotic bone compared to normal. XANES and Raman spectroscopy obtained from actively resorbed necrotic bone and normal bone showed increased carbonate-to-phosphate content in the necrotic bone. The changes in the apatite composition due to carbonate substitution may play a role in the increased resorption of necrotic bone due to its increase in solubility. Indeed, a better understanding of the apatite composition of necrotic bone could shed light on osteoclast activity and potentially improve therapeutic treatments that target excessive resorption of bone.


Differential Effects of Workaholism and Work Engagement on the Interference Between Life and Work Domains.
This study analyzed the differences between workaholism and work engagement in relation to their influence on work-life interference. Workaholism is an addiction to work, characterized by obsessive attitude towards job, whereas work engagement concerns a positive pattern of thoughts and feelings about one's job; these two constructs thus represent pathological and healthy forms of heavy work investment, respectively. As a consequence, it was expected that workaholism and work engagement would have different effects on perceived interference between work and life domains. We assessed levels of workaholism, work engagement, work-to-life interference, and life-to-work interference in a sample of 212 Italian workers. Results from structural equation modeling showed an inverse symmetry involving patterns and magnitudes of the relations observed: work engagement was more negatively related to life-to-work interference than work-to-life interference, whereas workaholism was more positively related to work-to-life interference than life-to-work interference. Implications about findings of the study are discussed.


Cloning and sequencing of protein kinase cDNA from harbor seal (Phoca vitulina) lymphocytes.
Protein kinases (PKs) play critical roles in signal transduction and activation of lymphocytes. The identification of PK genes provides a tool for understanding mechanisms of immunotoxic xenobiotics. As part of a larger study investigating persistent organic pollutants in the harbor seal and their possible immunomodulatory actions, we sequenced harbor seal cDNA fragments encoding PKs. The procedure, using degenerate primers based on conserved motifs of human protein tyrosine kinases (PTKs), successfully amplified nine phocid PK gene fragments with high homology to human and rodent orthologs. We identified eight PTKs and one dual (serine/threonine and tyrosine) kinase. Among these were several PKs important in early signaling events through the B- and T-cell receptors (FYN, LYN, ITK and SYK) and a MAP kinase involved in downstream signal transduction. V-FGR, RET and DDR2 were also expressed. Sequential activation of protein kinases ultimately induces gene transcription leading to the proliferation and differentiation of lymphocytes critical to adaptive immunity. PKs are potential targets of bioactive xenobiotics, including persistent organic pollutants of the marine environment; characterization of these molecules in the harbor seal provides a foundation for further research illuminating mechanisms of action of contaminants speculated to contribute to large-scale die-offs of marine mammals via immunosuppression.


Environmental assessment of three egg production systems--Part II. Ammonia, greenhouse gas, and particulate matter emissions.
As an integral part of the Coalition for Sustainable Egg Supply (CSES) Project, this study simultaneously monitored air emissions of 3 commercially operated egg production systems at the house level and associated manure storage over 2 single-cycle flocks (18 to 78 wk of age). The 3 housing systems were 1) a conventional cage house (CC) with a 200,000-hen capacity (6 hens in a cage at a stocking density of 516 cm2/hen), 2) an enriched colony house (EC) with a 50,000-hen capacity (60 hens per colony at a stocking density of 752 cm2/hen), and 3) an aviary house (AV) with a 50,000-hen capacity (at a stocking density of 1253 to 1257 cm2/hen). The 3 hen houses were located on the same farm and were populated with Lohmann white hens of the same age. Indoor environment and house-level gaseous (ammonia [NH3] and greenhouse gasses [GHG], including carbon dioxide [CO2], methane [CH4], and nitrous oxide [N2O]) and particulate matter (PM10, PM2.5) emissions were monitored continually. Gaseous emissions from the respective manure storage of each housing system were also monitored. Emission rates (ERs) are expressed as emission quantities per hen, per animal unit (AU, 500 kg live BW), and per kilogram of egg output. House-level NH3 ER (g/hen/d) of EC (0.054) was significantly lower than that of CC (0.082) or AV (0.112) (P<0.05). The house-level CO2 ER (g/hen/d) was lower for CC (68.3) than for EC and AV (74.4 and 74.0, respectively), and the CH4 ER (g/hen/d) was similar for all 3 houses (0.07 to 0.08). The house-level PM ER (mg/hen/d), essentially representing the farm-level PM ER, was significantly higher for AV (PM10 100.3 and PM2.5 8.8) than for CC (PM10 15.7 and PM2.5 0.9) or EC (PM10 15.6 and PM2.5 1.7) (P<0.05). The farm-level (house plus manure storage) NH3 ER (g/hen/d) was significantly lower for EC (0.16) than for CC (0.29) or AV (0.30) (P<0.05). As expected, the magnitudes of GHG emissions were rather small for all 3 production systems. Data from this study enable comparative assessment of conventional vs. alternative hen housing systems regarding air emissions and enhance the U.S. national air emissions inventory for farm animal operations.


Metacognition in Community-Dwelling Older Black and African American Adults During the COVID-19 Pandemic.
Cognitive assessment of older adults typically includes symptom reports and objective evaluations. However, there is often poor agreement between these measures. Cultural norms, stress, and anxiety may also influence cognitive self-appraisal and performance. Little research describes how other factors affect the self-report/objective test discrepancies noted in the literature. This study investigated whether the disparity between subjective cognitive concerns and objective cognitive performance is related to measures of anxiety and stress in older Black and African American adults. Telephone screenings were administered to 206 older adults (ages 64-94) during the first year of the pandemic. Demographic data, objective memory (Telephone Interview for Cognitive Status [TICS-m]), an adaptation of the subjective memory measure, the Cognitive Change Questionnaire, emphasizing executive functioning in everyday life [CCQ-e]), Generalized Anxiety Disorder-7 (GAD-7), and Perceived Stress Scale-4 (PSS4) were measured. Metacognition Discrepancy Index (MDI) was calculated from the standardized residual after regressing TICS-m on CCQ-e scores to quantify the discrepancy between cognitive self-appraisal and objective cognitive functioning. Neither GAD-7 nor PSS-4 moderated the relationship between TICS-m and CCQ-e, and TICS-m scores weakly predicted subjective CCQ-e scores (F(1, 197)=4.37, p = 0.038, R2 = 0.022). The MDI correlated with stress and anxiety (rs = 0.294, 0.396, ps < 0.001). Discrepancies exist between objectively measured and self-evaluated cognition. Elevations in stress and anxiety are associated with greater overestimation of cognitive difficulties relative to objective performance. Pandemic-related stressors may have worsened anxiety and diminished self-appraisal of cognitive abilities for some individuals, while others may remain reluctant to acknowledge impairments. Social and emotional factors are meaningful considerations in assessing cognitive difficulties.