Invasion, competitive dominance, and resource use by exotic and native California grassland species.
The dynamics of invasive species may depend on their abilities to compete for resources and exploit disturbances relative to the abilities of native species. We test this hypothesis and explore its implications for the restoration of native ecosystems in one of the most dramatic ecological invasions worldwide, the replacement of native perennial grasses by exotic annual grasses and forbs in 9.2 million hectares of California grasslands. The long-term persistence of these exotic annuals has been thought to imply that the exotics are superior competitors. However, seed-addition experiments in a southern California grassland revealed that native perennial species, which had lower requirements for deep soil water, soil nitrate, and light, were strong competitors, and they markedly depressed the abundance and fecundity of exotic annuals after overcoming recruitment limitations. Native species reinvaded exotic grasslands across experimentally imposed nitrogen, water, and disturbance gradients. Thus, exotic annuals are not superior competitors but rather may dominate because of prior disturbance and the low dispersal abilities and extreme current rarity of native perennials. If our results prove to be general, it may be feasible to restore native California grassland flora to at least parts of its former range.


Using crowdsourcing technology for testing multilingual public health promotion materials.
Effective communication of public health messages is a key strategy for health promotion by public health agencies. Creating effective health promotion materials requires careful message design and feedback from representatives of target populations. This is particularly true when the target audiences are hard to reach as limited English proficiency groups. Traditional methods of soliciting feedback--such as focus groups and convenience sample interviews--are expensive and time consuming. As a result, adequate feedback from target populations is often insufficient due to the time and resource constraints characteristic to public health. To describe a pilot study investigating the use of crowdsourcing technology as a method to gather rapid and relevant feedback on the design of health promotion messages for oral health. Our goal was to better describe the demographics of participants responding to a crowdsourcing survey and to test whether crowdsourcing could be used to gather feedback from English-speaking and Spanish-speaking participants in a short period of time and at relatively low costs. We developed health promotion materials on pediatric dental health issues in four different formats and in two languages (English and Spanish). We then designed an online survey to elicit feedback on format preferences and made it available in both languages via the Amazon Mechanical Turk crowdsourcing platform. We surveyed 236 native English-speaking and 163 native Spanish-speaking participants in less than 12 days, at a cost of US $374. Overall, Spanish-speaking participants originated from a wider distribution of countries than the overall Latino population in the United States. Most participants were in the 18- to 29-year age range and had some college or graduate education. Participants provided valuable input for the health promotion material design. Our results indicate that crowdsourcing can be an effective method for recruiting and gaining feedback from English-speaking and Spanish-speaking people. Compared with traditional methods, crowdsourcing has the potential to reach more diverse populations than convenience sampling, while substantially reducing the time and cost of gathering participant feedback. More widespread adoption of this method could streamline the development of effective health promotion materials in multiple languages.


Assortative mating for major psychiatric diagnoses in two population-based samples.
Previous studies on assortment for psychiatric disorders have reported discrepant findings. We aimed to test whether there is a significant association for psychiatric diagnoses, including alcoholism, generalized anxiety disorder, major depressive disorder, panic disorder and phobias between husbands and wives in two population-based samples. We further evaluated whether marital resemblance occurs primarily within or across psychiatric disorders and if assortment for psychopathology is primary or secondary to assortment for correlated variables. A model for mate selection addressed whether the correlation between mates for psychiatric disorders arises from direct assortment (primary homogamy) or through correlation with other variables for which assortment occurs (secondary homogamy) or through cross-variable assortment. The model accounted for within-person co-morbidity as well as across-spouse data. Findings suggested that a moderate degree of assortment exists both within and across psychiatric diagnoses. Only a small amount of the observed marital resemblance for mental illness could be explained by assortment for correlated variables such as age, religious attendance and education. Similar results were obtained for the two samples separately and confirmed in their joint analysis, revealing that the co-morbidity and assortment findings, except for the marital correlation for age, religious attendance and education, replicate across samples. Significant but moderate primary assortment exists for psychiatric disorders. The bias in twin studies that have ignored the small amount of assortment is negligible.


[Multicenter study of intracoronary stent implantation in Rio de Janeiro].
To evaluate retrospectively stent implantation (SI) in patients with coronary artery disease (CAD) performed in 7 hospitals in Rio de Janeiro. From June/94 to December/96 2,220 procedures were performed among which we analyzed 783 SI in 660 (29.7%) patients using coronary angiography without digital subtraction. Several types of stents were used: Palmaz-Schatz (40.9%), Gianturco-Roubin (29.1%) e NIR (22.0%). Indications for SI: 1--de novo lesion (67.9%); 2) restenotic lesion (16.0%); 3) sub-optimal results after PTCA (8.2%); 4) abrupt or threatened closure after PTCA (4.9%); 5) chronic occlusion (3.0%). All stents were implanted using high pressure balloon inflation without intracoronary ultrasound guidance. Sub-acute stent thrombosis prevention, in the majority of patients (87.8%) was done with ticlopidine and aspirin. Early outcome: a) the success rate of SI in 770 lesions was 98.0% in 646 (97.9%) patients; b) the clinical success rate in 634 patients was 96.0%; c) the major complications were acute myocardial infarction (1.1%); coronary artery bypass graft (1.4%) and death (0.8%); d) vascular complications with surgical correction and/or bleeding occurred in 3.0%. Late outcome: a) the clinical follow-up of 399 (60.4%) and the coronary angiographies of 121 patients (30.3%) showed in-stent lesion in 79 (19.8%); b) other event rates: myocardial infarction (1.5%); coronary bypass (2.3%); death: 1.0% and other PTCA or similar procedure (12.5%). This multicentric study showed that SI for CAD can be performed with safety, high early success rate, few complications and low rate of cardiac events during the late follow-up.


Racial differences in urinary potassium excretion.
Racial differences in potassium (K) intake and urinary K excretion may contribute to the higher BP observed in black compared with white individuals. Although black individuals typically consume less dietary K than white individuals, the lower urinary K excretion observed in black individuals may reflect more than differences in intake. In this study, data from the Dietary Approaches to Stop Hypertension (DASH) trial (413 white and black participants) were used to evaluate urinary K excretion in black and white individuals with similar K intake. At screening, mean urinary K excretion was higher in white than black individuals (mean Delta = 645 mg/d for white minus black individuals, adjusted for age, gender, and weight; P < 0.001). After a 3-wk run-in period during which all participants received a low-K control diet, a significant racial difference remained (mean Delta = 201 mg/d, adjusted for age, gender, and caloric intake; P < 0.001). Participants were then randomly assigned to continue the control diet or switch to a high-K diet (either a high fruit/vegetable diet or the DASH diet) for 8 wk. At the end of intervention, the mean difference in urinary K in white compared with black individuals after adjustment for age, gender, and caloric intake was -6 mg/d (P = 0.95) in the control group, 163 mg/d in the fruits/vegetables group (P = 0.39), and 903 mg/d in the DASH group (P < 0.001). Racial differences in urinary K excretion seem to reflect more than intake differences; further studies are needed to understand their potential impact on clinical outcomes.


Patients' perceptions of drug therapy counseling in Israel.
The more patients know about their medications the higher their compliance with drug therapy, reflecting an effective communication between health professionals and their patients. Numerous studies on this subject have been published, but none has been conducted in Israel. To evaluate patients' perceptions of drug counseling by health professionals--the prescribing physician and dispensing pharmacist--and to determine whether there is a difference in the patient's perception according to his or her place of birth and mother tongue. A total of 810 patients were interviewed following receipt of their medications from in-house pharmacies at two community clinics of Israel's largest sick fund. Each patient was interviewed in his or her mother tongue according to a constructed questionnaire, which included the patient's demographic background, type of medications received, the patient's perceptions of drug counseling given by both the physician and the pharmacist, and the patient's perception of non-prescription drug counseling given by the dispensing pharmacist. Of the 810 patients enrolled in this study, 32% received three or more medications at each physician visit. The main therapeutic classes of medications prescribed and dispensed were for neurological disorders, cardiovascular diseases, gastrointestinal problems and respiratory diseases. While 99% of the patients claimed that they knew how to use their medications, only 96% reported receiving an explanation from either physician or pharmacist. The quality of counseling, as evaluated by the patients, was ranked above average for 75% of the consultations with the prescribing physician and 63% with the dispensing pharmacist. Although few conclusions can be drawn from this study based on the initial statistical analysis of the data, the major findings were that patients value highly the counseling they receive and that 99% believe they have the requisite knowledge for using their medications. Compared to the international literature, our results--based on the patients' perceptions--indicate that counseling by pharmacists is a common and well-accepted activity in Israel and occurs at a high rate.


Structural and optical coherence tomography angiography in myopic choroidal neovascularization: Agreement with conventional fluorescein angiography.
To evaluate the agreement between fluorescein angiography and structural optical coherence tomography in diagnosing and monitoring the activity of myopic choroidal neovascularization and to provide a comparative analysis with optical coherence tomography angiography. Thirteen patients with active myopic choroidal neovascularization were prospectively enrolled. At the baseline, 2-month, and 6-month visits, each patient underwent a complete ophthalmological examination, including best-corrected visual acuity assessment, fundus examination, fluorescein angiography, and optical coherence tomography with structural and angiographic assessment. Sensitivity and specificity for all optical coherence tomography parameters were evaluated taking fluorescein angiography as the reference examination. At the baseline, fluorescein angiography confirmed myopic choroidal neovascularization leakage in all patients. Structural optical coherence tomography demonstrated intraretinal or subretinal fluid in 61% of cases, fuzzy borders and absence of external limiting membrane visibility in 84% of cases, and subretinal hyperreflective exudation in 53% of cases. Sensitivity to the presence of retinal fluid and subretinal hyperreflective exudation was lower than sensitivity to fuzzy borders and external limiting membrane visibility, which reached 84%. During ranibizumab therapy, external limiting membrane visibility showed a higher sensitivity (100%) compared with fuzzy borders and subretinal hyperreflective exudation (66.6%) while displaying an equal specificity of 100%. At baseline and final visit, sensitivity increased to 100% when all structural optical coherence tomography parameters were pooled. Optical coherence tomography angiography detected myopic choroidal neovascularization at baseline, 2-month, and 6-month visits in 92%, 76%, and 76% of cases, respectively. The study confirms that the new indicators of myopic choroidal neovascularization activity are more reliable than the presence or absence of retinal fluid. Optical coherence tomography angiography identified myopic choroidal neovascularization in most patients in the diagnostic phase and during treatment monitoring and could be considered as an alternative to fluorescein angiography in selected patients.


A new strategy to determine the actual protein content of poly(lactide-co-glycolide) microspheres.
Bovine serum albumin, lysozyme, and trypsin inhibitor were first encapsulated into poly-d,l-lactide-co-glycolide (PLGA) microspheres and then a new strategy was used to quantitate the actual levels of proteins in the microspheres. The proper combination of water-miscible dimethyl sulfoxide and 0.05 N-NaOH containing 0.5% sodium dodecyl sulfate (SDS) made it possible to solubilize both PLGA microspheres and proteins in a single phase. A total protein assay conveniently provided accurate information on the amount of protein encapsulated into the microspheres. In contrast to conventional techniques making use of acetonitrile, dichloromethane, and SDS extraction methods, this new method did not necessitate polymer precipitation, filtration, and protein extraction into other phases. These features were a great advantage in recovering proteins without any loss due to experimental processes. As a consequence, the new method reported in this study provided accurate data for the actual level of protein in PLGA microspheres, regardless of the pattern of protein distribution inside microspheres or the characteristics of microspheres. The experiment relying on the use of a radiolabeled protein also validated the reliability of this new method.


Impact of urban wastewater discharges on the sediments of a small Mediterranean river and associated coastal environment: assessment of estrogenic and dioxin-like activities.
The Mediterranean region includes many small coastal rivers about which little is known concerning organic contaminant loads in their sediment. This study was designed to assess organic contamination in one of these small coastal rivers (Lez River) and associated coastal sediments. Levels of alkylphenols (APs), polycylic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were measured in sediments of the Lez River and two coastal lagoons impacted by wastewater discharges. In parallel, sediment surrounding a recently built submarine outfall that discharges treated wastewater, from an area encompassing some 450,000 inhabitants, into the sea was monitored a year after the beginning of emission via the outfall. Finally, these sediments were characterized by screening estrogenic, PAH-like and dioxin-like activities using in vitro bioassays. Both chemical analyses and bioassays revealed that wastewater inputs were a source of organic contamination of sediments from the Lez and lagoons, which still persisted 2 years after the discharges were stopped. APs could explain a small proportion of the overall estrogenic activities (up to 31%), suggesting that other estrogenic compounds were also present in the sediments. PAHs explained a great share (83% on average) of the EROD induction potency of the extracts. This survey should be the first step in the long-term monitoring of these sites.


Defining the molecular components of calcium transport regulation in a reconstituted membrane system.
Using a chemically defined reconstitution system, we performed a systematic study of key factors in the regulation of the Ca-ATPase by phospholamban (PLB). We varied both the lipid/protein and PLB/Ca-ATPase ratios, determined the effects of PLB phosphorylation, and compared the regulatory effects of several PLB mutants, as a function of Ca concentration. The reconstitution system allowed us to determine accurately not only the PLB effects on K(Ca) (Ca concentration at half-maximal activity) of the Ca-ATPase, but also the effects on V(max) (maximal activity). Wild-type PLB (WT-PLB) and two gain-of-function mutants, N27A-PLB and I40A-PLB, showed not only the previously reported increase in K(Ca), but also an increase in V(max). Specifically, V(max) increases linearly with the intramembrane PLB concentration, and is approximately doubled when the sample composition approaches that of cardiac SR. Upon phosphorylation of PLB at Ser-16, the K(Ca) effects were almost completely reversed for WT- and N27A-PLB but were only partially reversed for I40A-PLB. Phosphorylation induced a V(max) increase for WT-PLB, and a V(max) decrease for N27A- and I40A-PLB. We conclude that PLB and PLB phosphorylation affect V(max) as well as K(Ca), and that the magnitude of both effects is sensitive to the PLB concentration in the membrane.


Detection of Pancreatic Cancer-Induced Cachexia Using a Fluorescent Myoblast Reporter System and Analysis of Metabolite Abundance.
The dire effects of cancer-induced cachexia undermine treatment and contribute to decreased survival rates. Therapeutic options for this syndrome are limited, and therefore efforts to identify signs of precachexia in cancer patients are necessary for early intervention. The applications of molecular and functional imaging that would enable a whole-body "holistic" approach to this problem may lead to new insights and advances for diagnosis and treatment of this syndrome. Here we have developed a myoblast optical reporter system with the purpose of identifying early cachectic events. We generated a myoblast cell line expressing a dual tdTomato:GFP construct that was grafted onto the muscle of mice-bearing human pancreatic cancer xenografts to provide noninvasive live imaging of events associated with cancer-induced cachexia (i.e., weight loss). Real-time optical imaging detected a strong tdTomato fluorescent signal from skeletal muscle grafts in mice with weight losses of only 1.2% to 2.7% and tumor burdens of only approximately 79 to 170 mm(3). Weight loss in cachectic animals was also associated with a depletion of lipid, cholesterol, valine, and alanine levels, which may provide informative biomarkers of cachexia. Taken together, our findings demonstrate the utility of a reporter system that is capable of tracking tumor-induced weight loss, an early marker of cachexia. Future studies incorporating resected tissue from human pancreatic ductal adenocarcinoma into a reporter-carrying mouse may be able to provide a risk assessment of cachexia, with possible implications for therapeutic development.


Studies on immune cellular injury. II. Functional role of C'1 esterase in immune cytotoxicity.
An initial separation of reaction stages in immune cytoxicity is described. Primary isolates of normal human amnion cells were reacted first with specific rabbit gamma(2)-globulin antibody, then with human C'1 esterase in the presence of Ca(++), and finally with human C'2, C'3, and C'4 in the presence of Mg(++). Cytotoxicity, as measured by uptake of trypan blue, occurred only when these reactions were performed in the order given and did not occur when any of the constituents was omitted. Inhibition of immune cytotoxicity was achieved with partially purified preparations of human serum inhibitor of C'1 esterase under certain experimental conditions. The data are discussed in relation to the role of C'1 esterase in initiating complement action and the partial biochemical definition of an early event in immune cytotoxicity.


Investigating Stochastic Differential Equations Modelling for Levodopa Infusion in Patients with Parkinson's Disease.
Levodopa concentration in patients with Parkinson's disease is frequently modelled with ordinary differential equations (ODEs). Here, we investigate a pharmacokinetic model of plasma levodopa concentration in patients with Parkinson's disease by introducing stochasticity to separate the intra-individual variability into measurement and system noise, and to account for auto-correlated errors. We also investigate whether the induced stochasticity provides a better fit than the ODE approach. In this study, a system noise variable is added to the pharmacokinetic model for duodenal levodopa/carbidopa gel (LCIG) infusion described by three ODEs through a standard Wiener process, leading to a stochastic differential equations (SDE) model. The R package population stochastic modelling (PSM) was used for model fitting with data from previous studies for modelling plasma levodopa concentration and parameter estimation. First, the diffusion scale parameter (σw), measurement noise variance, and bioavailability are estimated with the SDE model. Second, σw is fixed to certain values from 0 to 1 and bioavailability is estimated. Cross-validation was performed to compare the average root mean square errors (RMSE) of predicted plasma levodopa concentration. Both the ODE and the SDE models estimated bioavailability to be approximately 75%. The SDE model converged at different values of σw that were significantly different from zero. The average RMSE for the ODE model was 0.313, and the lowest average RMSE for the SDE model was 0.297 when σw was fixed to 0.9, and these two values are significantly different. The SDE model provided a better fit for LCIG plasma levodopa concentration by approximately 5.5% in terms of mean percentage change of RMSE.


Endothelial deficiency of L1 reduces tumor angiogenesis and promotes vessel normalization.
While tumor blood vessels share many characteristics with normal vasculature, they also exhibit morphological and functional aberrancies. For example, the neural adhesion molecule L1, which mediates neurite outgrowth, fasciculation, and pathfinding, is expressed on tumor vasculature. Here, using an orthotopic mouse model of pancreatic carcinoma, we evaluated L1 functionality in cancer vessels. Tumor-bearing mice specifically lacking L1 in endothelial cells or treated with anti-L1 antibodies exhibited decreased angiogenesis and improved vascular stabilization, leading to reduced tumor growth and metastasis. In line with these dramatic effects of L1 on tumor vasculature, the ectopic expression of L1 in cultured endothelial cells (ECs) promoted phenotypical and functional alterations, including proliferation, migration, tubulogenesis, enhanced vascular permeability, and endothelial-to-mesenchymal transition. L1 induced global changes in the EC transcriptome, altering several regulatory networks that underlie endothelial pathophysiology, including JAK/STAT-mediated pathways. In particular, L1 induced IL-6-mediated STAT3 phosphorylation, and inhibition of the IL-6/JAK/STAT signaling axis prevented L1-induced EC proliferation and migration. Evaluation of patient samples revealed that, compared with that in noncancerous tissue, L1 expression is specifically enhanced in blood vessels of human pancreatic carcinomas and in vessels of other tumor types. Together, these data indicate that endothelial L1 orchestrates multiple cancer vessel functions and represents a potential target for tumor vascular-specific therapies.


Community-Acquired Pneumonia.
Community-acquired pneumonia is an important cause of morbidity and mortality. It can be caused by bacteria, viruses, or fungi and can be prevented through vaccination with pneumococcal, influenza, and COVID-19 vaccines. Diagnosis requires suggestive history and physical findings in conjunction with radiographic evidence of infiltrates. Laboratory testing can help guide therapy. Important issues in treatment include choosing the proper venue, timely initiation of the appropriate antibiotic or antiviral, appropriate respiratory support, deescalation after negative culture results, switching to oral therapy, and short treatment duration.


Development of RT-multiplex PCR assay for detection of adenovirus and group A and C rotaviruses in diarrheal fecal specimens from children in China.
Rotavirus, adenovirus, norovirus, sapovirus and astrovirus are considered to be significant global enteropathogens associated with sporadic cases and outbreaks of acute gastroenteritis. Therefore, a rapid and sensitive assay is preferred to screen for the presence of these viruses in diarrheal fecal specimens. In a previous study, we developed a reverse transcription single-round multiplex polymerase chain reaction (RT-smPCR) assay for the simultaneous detection of norovirus (genogroup I, genogroup II), sapovirus and astrovirus in fecal specimens (Yan et aL, 2003). Recently, we developed another RT multiplex PCR for one-step amplification of all subgenera A to F adenoviruses, and group A and C rotaviruses. In this study, a total of 207 fecal specimens collected from children with acute gastroenteritis between December 2001 and April 2003 in Yunnan Province, China were examined for the presence of adenoviruses, and group A and C rotaviruses, by RT-multiplex PCR. The detection rate of these three viruses was 55.1% (114 out of 207 specimens), among which adenovirus and group A and C rotaviruses were identified in 11, 101 and 1 fecal specimen, respectively. Furthermore, one specimen was found to be positive for co-infection with adenovirus and group A rotavirus. An epidemic of acute gastroenteritis was also identified as peaking mainly in October and November. Taken together, our results clearly indicate that this novel assay provides a potentially rapid and convenient tool for epidemiologic investigation of diarrhea caused by adenovirus and group A and C rotaviruses.


Nonselective destruction of murine neoplastic cells by syngeneic tumoricidal macrophages.
The purpose of these studies was to select in vitro tumor cells that were resistant to macrophage-mediated lysis. Seven different heterogeneous murine neoplasms (four fibrosarcomas, a melanoma, a rhabdomyosarcoma, and an osteogenic sarcoma) and one cloned line of a fibrosarcoma were incubated in vitro with syngeneic tumoricidal macrophages. Surviving tumor cells were recovered and expanded to undergo subsequent interaction with tumoricidal macrophages. After six sequential interactions, all cell lines were examined for their susceptibility to lysis mediated by murine peritoneal exudate macrophages activated with liposomes containing muramyl tripeptide phosphatidylethanolamine. In all eight systems, no significant differences were detected between the parent tumor cells and cells that survived the sequential interactions. Neither macrophage infiltration into s.c. tumors nor the experimental or spontaneous metastatic potentials of the parental tumors differed from the lines established by cells surviving macrophage-mediated lysis. Collectively, the data suggest that tumor cell destruction by activated macrophages is nonselective and does not lead to the development of resistant tumor cells nor to cells with altered metastatic properties.


Rapid killing of actinomycin D-treated tumor cells by human monocytes. II. Cytotoxicity is independent of secretion of reactive oxygen intermediates and is suppressed by protease inhibitors.
Pretreatment with Actinomycin D (ActD, 1 microgram/ml for 3 hr) rendered WEHI 164 tumor cells susceptible to killing by human monocytes in a 6-hr 51Cr release assay. The present study was designed to elucidate the role of reactive oxygen intermediates (ROI) and of proteolytic enzymes in this reactivity. ActD-treated WEHI 164 cells did not trigger any measurable release of O-2 or H2O2 from monocytes. Monocytes exposed to phorbol-12-myristate-13-acetate, which enhanced release of ROI, did not show augmented killing of ActD-treated tumor cells. Scavengers of oxygen metabolites (catalase, superoxide dismutase, gluthatione, and mannitol), which inhibited ROI-mediated PMA-induced monocyte cytotoxicity against erythrocytes, did not affect monocyte killing of ActD-treated WEHI 164 cells. Enzymatically generated ROI with xanthine/xanthine-oxidase glucose/glucose-oxidase did not show preferential killing of ActD-treated WEHI 164 cells. Two patients with chronic granulomatous disease had normal levels of monocyte cytotoxicity against ActD-treated tumor cells. To determine the possible role of proteolytic enzymes in mediating this reactivity, we studied various antiproteases. Organophosphorous agents (DFP and PMSF), chloromethyl-ketone derivatives of tosylamino acids (TLCK and TPCK), Actinomyces products (pepstatin and chymostatin), and the synthetic protease substrate TAME inhibited monocyte-mediated cytotoxicity against ActD-treated WEHI 164 cells. The macromolecular protease inhibitors alpha-1 antitrypsin, bovine pancreatic trypsin inhibitor (BPTI), soybean trypsin inhibitor, and the synthetic protease substrate ATEE had little effect on monocyte cytotoxicity. When monocytes were preincubated with drugs for 1 hr and washed, TLCK, TPCK, and PMSF inhibited cytolysis, whereas the less effective chymostatin and TAME and the inactive BPTI had no effect under these conditions. Inhibition by preincubation with TLCK, PMSF, and TPCK was completely reversed after 6 hr of culture. Supernatants of monocyte cultures had lytic activity against ActD-treated WEHI 164 but not against untreated cells. Antiproteases inhibited the lytic activity of monocyte supernatants. These results strongly suggest that ROI do not play a critical role in monocyte-mediated rapid killing of drug-treated tumor cells, and that proteolytic enzymes are involved in this reactivity.


Macro- and Micro-heterogeneity in Pituitary and Urinary Follicle-Stimulating Hormone Glycosylation.
FSH glycosylation macroheterogeneity in pituitary and urinary hFSH samples was evaluated by Western blotting. Microheterogeneity in two highly purified urinary and pituitary hFSH preparations was evaluated by nano-electrospray mass spectrometry of peptide-N-glycanase-released oligosaccharides. An age-related loss of hypo-glycosylated hFSH in individual female pituitaries was indicated by progressively reduced abundance of hFSH21 relative to hFSH24. Urinary hFSH was evaluated as a potentially non-invasive indicator of glycoform abundance, as the only way for pituitary FSH to reach the urine is through the blood. Both highly purified and crude postmenopausal urinary hFSH preparations possessed the same amount of hFSH21 as postmenopausal pituitary gland FSH. Considerable microheterogeneity was encountered in both pituitary and urinary hFSH glycan populations, as 84 pituitary hFSH glycan ions were observed as compared with 68 urinary hFSH glycans. The biggest quantitative differences between the two populations were reduced abundance of bisecting GlcNAc-containing and fucosylated glycans, along with sulfated glycans in the urinary hFSH glycan population. The relative abundance of sialic acid and glycan antenna did not rationalize the retarded electrophoretic mobilities of the urinary hFSHβ21- and α-subunit bands relative to the corresponding pituitary hFSH bands, as the most abundant glycans in the former possessed only 2 more branches and the same sialic content as in the latter. Site-specific glycosylation information will probably be necessary.


Hereditary angioedema due to C1 - inhibitor deficiency in Switzerland: clinical characteristics and therapeutic modalities within a cohort study.
Registration of trigger factors, prodromal symptoms, swelling localization, therapeutic behavior and gender-specific differences of the largest cohort of patients with hereditary angioedema due to C1-Inhibitor deficiency (C1-INH-HAE) in Switzerland. Questionnaire survey within a cohort study: Consenting eligible patients with diagnosed HAE according to clinical history, physical examination and laboratory results, including plasma values for C1-INH and C4 were selected. To each participant we sent a questionnaire assessing patients' birthday, sex, date of first symptoms and diagnosis, trigger factors, prodromal symptoms, frequency and localization of angioedema, medication use and co-morbidities. Clinical information was collected in each center and then transmitted to the cohort database. Frequencies and distributions were summarized. Associations between gender and trigger factors or prodromal symptoms or localization of angioedema were assessed in multivariate analyses correcting for patients' age. Of 135 patients, data from 104 patients (77%) were available for analysis. Fifty- four percent were female, mean age at diagnosis was 19.5 years (SD 14.1), Mean age when completing the questionnaire was 44.0 (SD 19.8). More women than men were symptomatic (44/57 vs. 36/47; p = 0.005). This association remained when correcting for age at diagnosis (16.10. 95%CI (5.17 to 26.70); p = 0.004). Swelling episodes ranged between 1 and 136 episodes/year. Swelling was more common among female than among male (-13.15 (95% CI; -23.10 to -3.22), p = 0.010). Age at diagnosis was inversely associated with the total number of attacks 0.50 (-0.88 to -.011); p = 0.012). One third of patients were on danazol prophylaxis. We found large differences of HAE in male and female both in terms of symptom number and swelling episodes. Women are more affected by intensity and frequency of angioedema episodes than men. Danazol treatment remains widely used as effective prophylaxis despite its side effects. New therapies which selectively influence the hormonal estrogen balance could open new therapeutic options mainly for women and maybe also for men.


Altered regulation of cytochrome P-450 enzymes in choline-deficient cirrhotic male rat liver: impaired regulation and activity of the male-specific androst-4-ene-3,17-dione 16 alpha-hydroxylase, cytochrome P-450UT-A, in hepatic cirrhosis.
Total microsomal cytochrome P-450 levels were decreased, to about 50% of control, in liver of male rats made cirrhotic by the prolonged intake of a choline-deficient diet. We have suggested previously that this decrease in cytochrome P-450 levels is not a generalized one, but is selective for certain forms of the enzyme. In the present study, levels of six cytochrome P-450 forms including the sex-specific cytochrome P-450 forms, P-450UT-A, P-450PCN-E, and P-450UT-l, were quantitated immunochemically in hepatic microsomes prepared from control and cirrhotic male rats and were related to changes in the regioselectivity of cytochrome P-450-mediated androst-4-ene-3,17-dione hydroxylation in these fractions. The principal finding of this study was that the male-specific androst-4-ene-3,17-dione 16 alpha-hydroxylase was decreased in cirrhotic microsomes to about 20% of control. The content of P-450UT-A decreased concurrently from about 0.40 to less than 0.01 nmol/mg of microsomal protein. Other pathways of androst-4-ene-3,17-dione hydroxylation were also affected, but to different extents than the 16 alpha-hydroxylase. 6 beta-Hydroxylation decreased in cirrhotic microsomes to about 45% of control, despite a marked decrease in P-450PCN-E from 0.27 to less than 0.002 nmol/mg of microsomal protein. The rate of androst-4-ene-3,17-dione 7 alpha-hydroxylation underwent a less pronounced reduction in cirrhosis to about two-thirds of control microsomal activity, and levels of the cytochrome P-450 associated with this activity, P-450UT-F, were decreased in proportion with the decrease in total microsomal cytochrome P-450. 16 beta-Hydroxylase activity was unaffected by the cirrhotogenic process. From spectral binding studies it was apparent that androst-4-ene-3,17-dione elicited a high affinity type I interaction in control microsomal fractions (Ks = 4.5 microM), whereas no interaction was apparent in cirrhotic liver microsomes. Levels of three other forms of cytochrome P-450--P-450PB-C (a constitutive form inducible by phenobarbital), P-450ISF-G (a major isosafrole-inducible form), and P-450UT-I (the major female sexually-differentiated isozyme)--were apparently unaltered in cirrhosis. These findings are consistent with the assertion that specific forms of cytochrome P-450 are subject to altered regulation in hepatic cirrhosis.


Influence of anabolic steroids on body composition, blood pressure, lipid profile and liver functions in body builders.
The effects of anabolic steroids on body composition, blood pressure, lipid profile and liver functions were studied in male body builders who received a weekly i.m. injection of nandrolone-decanoate (100 mg) or placebo for 8 weeks in a double blind way. In addition, 5 body builders received the same dosage of nandrolone-decanoate or placebo, in a double blind cross-over design during two 8-week periods, interspersed by 12 weeks. Anabolic steroids induced a 25-27% decrease in HDL-cholesterol, which was virtually reversed 6 weeks after cessation of drug use. In the SAD group an increase in diastolic blood pressure was observed, which returned to pre-anabolic values approximately 6 weeks after cessation of drug administration. No deleterious effects of anabolic drugs on plasma activity of liver enzymes were found. Increases in lean body mass were found in all groups, though the increase in the subjects who received anabolic steroids was superior to that in the placebo-treated subjects. The increase in lean body mass suggests increases in muscle mass.


Presynaptic actions of carbachol and adenosine on corticostriatal synaptic transmission studied in vitro.
The purpose of this study was to identify, in the in vitro rat neostriatal slice preparation, an electrophysiological response corresponding to the activation of striatal neurons by cortical afferents, and to study the actions of a variety of putative neurotransmitters on modulating synaptic transmission at this synapse. Local stimulation of the neostriatal slice evokes a field potential composed of 2 prominent negativities. Experiments using calcium antagonists and tetrodotoxin indicate that the first negativity (N1) reflects the direct activation of intrinsic neurons and axons, while the second negativity (N2) is synaptically mediated. The afferent fibers eliciting the second negativity have not previously been identified because of the mixing of afferents within the striatum. However, similar field potential responses are elicited by stimulation of the corpus callosum, in which the only striatal afferents are crossed corticostriatal fibers. Kynurenate, gamma-D-glutamylglycine, and piperidine dicarboxylate all reversibly reduced or abolished N2, suggesting that the transmitter generating the response is an excitatory amino acid. Together, these results strongly suggest that N2 reflects activation of striatal neurons by corticostriatal afferents. Three putative striatal neurotransmitters, dopamine, acetylcholine and adenosine, were studied with respect to their ability to modulate the corticostriatal response. Dopamine had minimal effects on the waveform of the field potential. In contrast, carbachol or adenosine consistently reversibly reduced or eliminated N2. Atropine blocked carbachol's actions, while theophylline blocked adenosine's actions, indicating that the compounds were acting on muscarinic and adenosine receptors, respectively. To test whether these were primarily pre- or postsynaptic actions, we recorded the response to ionophoretically applied glutamate while simultaneously recording the synaptically evoked field potential from the same location.(ABSTRACT TRUNCATED AT 250 WORDS)


Armed conflict and maternal mortality: A micro-level analysis of sub-Saharan Africa, 1989-2013.
There is existing country-level evidence that countries with more severe armed conflict tend to have higher Maternal Mortality Rates (MMR). However, during armed conflict, the actual fighting is usually confined to a limited area within a country, affecting a subset of the population. Hence, studying the link between country-level armed conflict and MMR may involve ecological fallacies. We provide a more direct, nuanced test of whether local exposure to armed conflict impacts maternal mortality, building on the so-called "sisterhood method". We combine geo-coded data on different types of violent events from the Uppsala Conflict Data Program with geo-referenced survey data from the Demographic and Health Surveys (DHS) on respondents' reports on sisters dying during pregnancy, childbirth, or the puerperium. Our sample covers 1,335,161 adult sisters aged 12-45 by 539,764 female respondents in 30 countries in sub-Saharan Africa. Rather than aggregating the deaths of sisters to generate a maternal mortality ratio, we analyze the sisters' deaths at the individual level. We use a sister fixed-effects analysis to estimate the impact of recent organized violence events within a radius of 50 km of the home of each respondent on the likelihood that her sister dies during pregnancy, childbirth, or the puerperium. Our results show that local exposure to armed conflict events indeed increases the risk of maternal deaths. Exploring potential moderators, we find larger differences in rural areas but also in richer and more educated areas.


A worldwide survey of genome sequence variation provides insight into the evolutionary history of the honeybee Apis mellifera.
The honeybee Apis mellifera has major ecological and economic importance. We analyze patterns of genetic variation at 8.3 million SNPs, identified by sequencing 140 honeybee genomes from a worldwide sample of 14 populations at a combined total depth of 634×. These data provide insight into the evolutionary history and genetic basis of local adaptation in this species. We find evidence that population sizes have fluctuated greatly, mirroring historical fluctuations in climate, although contemporary populations have high genetic diversity, indicating the absence of domestication bottlenecks. Levels of genetic variation are strongly shaped by natural selection and are highly correlated with patterns of gene expression and DNA methylation. We identify genomic signatures of local adaptation, which are enriched in genes expressed in workers and in immune system- and sperm motility-related genes that might underlie geographic variation in reproduction, dispersal and disease resistance. This study provides a framework for future investigations into responses to pathogens and climate change in honeybees.


Vitamin B12 deficiency in untreated celiac disease.
Iron and folate malabsorption are common in untreated celiac disease as the proximal small intestine is predominantly affected. Vitamin B12 deficiency is thought to be uncommon, as the terminal ileum is relatively spared. This study aims to investigate the prevalence of vitamin B12, deficiency in patients with untreated celiac disease. Prospective study of 39 consecutive biopsy-proven celiac disease patients (32 women, seven men; median age 48 yr, range 22-77 yr) between September 1997 and February 1999. The full blood count, serum vitamin B12, red blood cell folate, and celiac autoantibodies (IgA antigliadin and IgA antiendomysium antibodies) were measured before and after a median of 4 months (range 2-13 months) of treatment with a gluten-free diet. In vitamin B12-deficient patients, intrinsic factor antibodies and a Schilling test, part 1, were performed. A total of 16 (41%) patients were vitamin B12 deficient (<220 ng/L) and 16 (41%) patients (11 women and live men) were anemic. Concomitant folate deficiency was present in only 5/16 (31%) of the vitamin B12 patients. The Schilling test, performed in 10 of the vitamin B12-deficient patients, showed five low and five normal results. Although only five patients received parenteral vitamin B12, at follow-up the vitamin B12 results had normalized in all patients. Acral paraesthesia at presentation in three vitamin B12-deficient patients resolved after vitamin B12 replacement. Vitamin B12 deficiency is common in untreated celiac disease, and concentrations should be measured routinely before hematinic replacement. Vitamin B12 concentrations normalize on a gluten-free diet alone, but symptomatic patients may require supplementation.


Reliability of serum iron, ferritin, nitrite, and association with risk of renal cancer in women.
Reliability of serum levels of iron, ferritin and nitrite (NO(2)(-)) over a 2-year period were evaluated in 40 healthy women (20 pre-menopausal and 20 post-menopausal), ages 39-65 years, from the New York University Women's Health Study (NYUWHS). Three blood samples per woman collected at yearly intervals were analyzed. Reliability coefficients (RCs) of serum iron, ferritin, and nitrite were 0.03 (95% confidence interval (CI), 0-0.33), 0.90 (95% CI, 0.79-0.95), and 0.72 (95% CI, 0.50-0.86), respectively, for pre-menopausal women, and 0.26 (95% CI, 0-0.56), 0.77 (95% CI, 0.59-0.89), and 0.55 (95% CI, 0.30-0.77), respectively, for post-menopausal women. In a case-control study nested within NYUWHS cohort, serum levels of nitrite, ferritin, and iron were measured in women apparently healthy at the time of blood donation but diagnosed with renal cancer 1.8-12.2 years later (n=24) and in individually matched controls (two per case). The results suggest that high serum levels of ferritin and nitrite may be associated with a decreased risk of renal cancer (odds ratio (OR), 0.55, 95% CI, 0.15-2.01 for ferritin, and OR, 0.52, 95% CI, 0.17-1.60 for nitrite in women with above median level as compared to women with below median level). The possible role of ferritin and nitrite in renal cancer is discussed.


Adoption of a research-based program for neck disorders implemented in primary care physiotherapy: a short- and long-term follow-up survey study.
Neck disorders are common in primary health care (PHC) physiotherapy. A neck-specific exercise program based on research findings was implemented among physiotherapists in Swedish PHC. The aim of the study was to evaluate the adoption of the program. We invited PHC physiotherapists to an educational session including theoretical information and practical training. Before the educational session the participants (n = 261) completed a baseline questionnaire. After 3 and 12 months, we distributed surveys to identify changes in practice and in confidence regarding diagnosis and treatment. We compared data from 3-months and 12-months follow-up, respectively, with baseline data. Self-reported frequency of most of the included assessment methods was unchanged after 12 months. Frequency of assessment of neck proprioception had increased significantly. Specific neck muscle exercise for treatment of whiplash associated disorders was applied more frequently after 3 and after 12 months than at baseline. Frequency of other treatment methods remained unchanged. Confidence in diagnosis and treatment increased significantly, particularly among women. The program was not adopted as expected, but resulted in increased confidence regarding diagnosis and treatment. The provision of a short educational session seemed not to be sufficient to obtain a sustained change in practice.


[Method of exposing cells to ultrasound].
A simple chamber for studying the influence of ultrasound on low quantities of cell suspension is suggested. It consists of an organic glass cylinder, which is placed on the head of the apparatus YTP-1, the surface of which forms the floor of the chamber. Thanks to this, the loss of ultrasonic energy is eliminated, and a possibility of a rather exact determination of the intensity of ultrasound, which influences the suspension cells, is attained.


Tracheostomy timing and the duration of weaning in patients with acute respiratory failure.
The effect of various airway management strategies, such as the timing of tracheostomy, on liberation from mechanical ventilation (MV) is uncertain. We tested the hypothesis that tracheostomy, when performed prior to active weaning, does not influence the duration of weaning or of MV in comparison with a more selective use of tracheostomy. In this observational prospective cohort study, surgical patients requiring >or= 72 hours of MV were followed prospectively. Patients undergoing tracheostomy prior to any active weaning attempts (early tracheostomy [ET]) were compared with patients in whom initial weaning attempts were made with the endotracheal tube in place (selective tracheostomy [ST]). We compared the duration of weaning, the total duration of MV and the frequency of fatigue and pneumonia. Seventy-four patients met inclusion criteria. Twenty-one patients in the ET group were compared with 53 patients in the ST group (47% of whom ultimately underwent tracheostomy). The median duration of weaning was shorter (3 days versus 6 days, P = 0.05) in patients in the ET group than in the ST group, but the duration of MV was not (median [interquartile range], 11 days [9-26 days] in the ET group versus 13 days [8-21 days] in the ST group). The frequencies of fatigue and pneumonia were lower in the ET group patients. Determining the ideal timing of tracheostomy in critically ill patients has been difficult and often subjective. To standardize this process, it is important to identify objective criteria to identify patients most likely to benefit from the procedure. Our data suggest that in surgical patients with resolving respiratory failure, a patient who meets typical criteria for a trial of spontaneous breathing but is not successfully extubated within 24 hours may benefit from a tracheostomy. Our data provide a framework for the conduct of a clinical trial in which tracheostomy timing can be assessed for its impact on the duration of weaning. Tracheostomy prior to active weaning may hasten liberation from ventilation and reduce complications. However, this does not reduce the overall duration of MV.


Factors affecting phosphate uptake by Aerobacter aerogenes in a system relating cell numbers to 32P uptake.
The uptake of phosphate, from media limited in this ion, by resting cells of Aerobacter aerogenes has been investigated and shown to be dependent upon several factors. An incubation medium composed of 10(-2)m K(+), 5 x 10(-3)m Mg(2+), 1 mg of glucose per ml, and 1 muCi of (32)PO(4) (3-) per ml, buffered at pH 6.55 with 0.05 mN-2-hydroxyethyl-piperazine-N'-2-ethanesulfonic acid (HEPES), was found to stimulate optimum accumulation of (32)P-orthophosphate. The temperature of incubation, incubation time, the concentration of unlabeled orthophosphate, as well as arsenate, and several metabolic inhibitors were found to affect the accumulation. The labeled cells were collected on a membrane filter, which had been previously boiled in glass-distilled water, for measurement of the radioactivity accumulated. Under optimum conditions, as few as 20,000 cells were capable of accumulating detectable amounts of (32)P-orthophosphate in 1 hr of incubation.


Epilepsy-Heart Syndrome: Incidence and Clinical Outcomes of Cardiac Complications in patients with Epilepsy.
The risks of cardiovascular events (CVEs) in people with epilepsy (PWE) are not well understood. To establish the short- and long-term burden of CVEs in PWE. Electronic health records from a global federated health research network (TriNetX) were used to establish a cohort of PWE. Primary outcomes were: (1) the proportion of people experiencing a composite outcome of cardiac arrest, acute heart failure (HF), acute coronary syndrome (ACS), atrial fibrillation (AF), severe ventricular arrhythmia or all-cause death within 30 days of a seizure; and (2) the 5-year risk for a composite outcome of ischemic heart diseases, stroke, hospitalization, or all-cause death in the PWE experiencing early CVEs. Cox-regression analyses with propensity score matching was used to produce hazard ratios (HRs) and 95% confidence intervals (CI). In 271,172 PWE (mean age 50 ± 20 years; 52% females), the 30-day risk of CVEs following seizure was: 8.7% for the composite outcome, 0.9% for cardiac arrest, 0.8% for HF, 1.2% for ACS, 4.1% for AF, 0.7% for severe ventricular arrhythmias, and 1.6% for all-cause death. For the 15,120 PWE experiencing CVEs within 30 days of seizure, the 5-year adjusted risks for all composite outcomes measured were significantly increased (overall HR: 2.44, 95% CI 2.37-2.51), ischemic heart diseases HR 3.23 (95% CI 3.10-3.36), stroke HR 1.56 (95% CI 1.48-1.64), hospitalization HR 2.03 (95% CI 1.97-2.10), and all-cause death HR 2.75 (95% CI 2.61-2.89). The large proportions of PWE with active disease that experience CVEs and the poor long-term outcome associated suggest the existence of an "epilepsy-heart syndrome."


Periodontitis and Risk of Diabetes in the Atherosclerosis Risk In Communities (ARIC) Study: A BMI-Modified Association.
To determine whether periodontal disease is positively associated with incident diabetes across the continuum of body mass levels (BMI) and test the hypothesis that the periodontal risk for incident diabetes is modified by BMI. We included 5569 diabetes-free participants from Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities study and followed them until 2018. Periodontal disease status was classified by periodontal profile class (PPC)-Stages , and incident diabetes was based on participant report of physician diagnosis. We estimated the hazard ratios (HR) for diabetes using a competing risk model for each PPC-Stage. We assessed multiplicative interactions between periodontal disease and BMI (as a continuous variable) on risk of diabetes. During a median time of 19.4 years of follow-up, 1348 incident diabetes cases and 1529 deaths occurred. Compared to the "Health/Incidental Disease" stage, participants with PPC "Severe Periodontal Disease" or "Severe Tooth Loss" stage and lower BMI had elevated risk for diabetes adjusting for demographic, smoking, education, and biological variables when accounting for death as a competing risk with HRs of 1.76 (95% CI 1.10-2.80) and 2.11 (95% CI 1.46-3.04), respectively. The interaction between PPC-Stages and BMI was significant (P = 0.01). No significant associations of PPC-Stages with incident diabetes were present when BMI was above 31 kg/m2. Periodontal disease was associated with incident diabetes, especially in nonobese participants. Dentists should be aware that periodontal disease is associated with incident diabetes but the association may be modified for patient's at higher BMI levels.


Chemical states of trace elements in sewage sludge incineration ash by using x-ray absorption fine structure.
In this study, the chemical states of chromium (Cr), arsenic (As), and selenium (Se) in sewage sludge incineration ash were determined by X-ray absorption fine structure (XAFS) spectroscopy. Sewage sludge incineration ash was sampled from several facilities, and XAFS measurements were carried out with a beam line BL01B1 at the SPring-8 facility. Cr K-edge X-ray absorption near-edge structure (XANES) spectra suggested that Cr compounds were predominantly speciated as Cr(III) and the fraction of Cr(VI) was very minor. Compared to the reference materials, Cr XANES spectra of the incineration ashes were similar to those of FeCr2O4, Cr(OH)3, and CaCr2O4. As K-edge XANES spectra indicated that As(V) compounds were present in incineration ashes. Because the chemical state of As in sewage sludge was As3+ in our previous study, we speculated that the chemical state of As changed into As(V) during the incineration process. According to Se K-edge XANES spectra, Se compounds were predominantly Se(IV), and a slight difference was observed in the chemical states amongst facilities using inorganic or organic coagulants in the dewatering process.


Cancer stem cell targeting: the next generation of cancer therapy and molecular imaging.
Cancer stem cells (CSCs) have the capacity to generate the heterogeneous lineages of all cancer cells comprising a tumor and these populations of cells are likely to be more relevant in determining prognosis. However, these cells do not operate in isolation, but instead rely upon signals co-opted from their microenvironment, making the targeting and imaging of CSCs within a cancer mass a daunting task. A better understanding of the molecular cell biology underlying CSC pathology will facilitate the development of new therapeutic targets and novel strategies for the successful eradication of cancer. In addition, the continued investigation of sensitive molecular-imaging modalities will enable more accurate staging, treatment planning and the ability to monitor the effectiveness of CSC-targeted therapies in vivo. In this review, we explore the possibilities and limitations of CSC-directed therapies and molecular imaging modalities.


Leopard seal diets in a rapidly warming polar region vary by year, season, sex, and body size.
Resolving the preferred prey items and dietary proportions of leopard seals is central to understanding food-web dynamics in the rapidly-warming Antarctic Peninsula region. Previous studies have identified a wide range of prey items; however, due to anecdotal or otherwise limited information, leopard seal diets remain unresolved by seal sex, individual, body size, region, and season. Over the 2013, 2014, and 2017 field seasons we collected scat, tissue samples (red blood cells and plasma; n = 23) for stable isotope analyses, and previously-reported animal-borne video from 19 adult leopard seals foraging near mesopredator breeding colonies at Cape Shirreff, Livingston Island. We summarized a priori diet information from scat and video analysis and applied a three-isotope (δ13C, δ15N, δ34S), four-source (fish, fur seal, krill, penguin) Bayesian mixing model to examine temporal variability in both prey sources and leopard seal tissues. The austral spring diets of males and females focused on Antarctic krill (31.7-38.0%), notothen fish (31.6-36.5%), and penguin (24.4-26.9%) and were consistent across all 3 years. Several lines of evidence suggest the transition to summer foraging was distinct for males and females. Female diets transitioned rapidly to higher δ15N values (+2.1‰), indicating increased consumption of penguin (29.5-46.2%) and energy-dense Antarctic fur seal pup (21.3-37.6%). The seasonal increase in leopard seal δ15N values, and thus fur seal in their diet, was predictably related to larger body size; it may also be forcing reductions to the largest Antarctic fur seal colony in the Antarctic Peninsula. Our ensemble sampling approach reduces historical biases in monitoring marine apex predator diets. Further, our results are necessary to best inform regional fisheries management planning.


Relationships between nonverbal IQ and brain size in right and left-handed men and women.
This study was designed to evaluate the relationship between nonverbal IQ and brain size in men and women. A significant correlation was found between IQ and brain size in total subjects. There was no significant correlation between these variables in women; men exhibited only a weak relation of brain size to IQ. In both left-handed men and women significant correlations were found between IQ and brain size. The results supported the hypothesis about the relation of IQ to brain size, suggesting that the sex difference in the cranial capacity and cerebral asymmetry might contribute to the diversity in cognitive functions.


Alternative reproductive tactics in male freshwater fish influence the accuracy of species recognition.
Sexual conflict can result in coercive mating. Because males bear low costs of heterospecific mating, coercive males may engage in misdirected mating attempts toward heterospecific females. In contrast, sexual selection through consensual mate choice can cause mate recognition cues among species to diverge, leading to more accurate species recognition. Some species show both coercive mating and mate choice-associated courtship behaviors as male alternative reproductive tactics. We hypothesized that if the selection pressures on each tactic differ, then the accuracy of species recognition would also change depending on the mating tactic adopted. We tested this hypothesis in the guppy (Poecilia reticulata) and mosquitofish (Gambusia affinis) by a series of choice experiments. Poecilia reticulata and G. affinis males both showed imperfect species recognition and directed all components of mating behavior toward heterospecific females. They tended to direct courtship displays more frequently toward conspecific than heterospecific females. With male P. reticulata, however, accurate species recognition disappeared when they attempted coercive copulation: they directed coercions more frequently toward heterospecific females. We also found that heterospecific sexual interaction had little effect on the fecundity of gravid females, which suggests that prepregnancy interactions likely underpin the exclusion of G. affinis by P. reticulata in our region.


Ammonium-Chloride-Potassium Lysing Buffer Treatment of Fully Differentiated Cells Increases Cell Purity and Resulting Neotissue Functional Properties.
Juvenile and fetal, primary, fully differentiated cells are widely considered to be ideal cell types for tissue engineering applications. However, their use in tissue engineering may be hindered through contamination by undesirable cell types. These include blood-associated cells as well as unwanted resident cell types found both in healthy and pathologic donor tissues. Ammonium-chloride-potassium (ACK) lysing buffer is used to lyse red blood cells (RBCs) during the isolation of stem cell populations, but has not been explored for the purification of fully differentiated cells. This study sought to investigate the effect of ACK buffer treatment of freshly isolated, fully differentiated cells to increase cell purity and enhance the formation of biofunctional engineered neotissues; this was tested in the well-established cartilage tissue engineering model of the self-assembling process using fetal ovine articular chondrocytes (foACs) and juvenile bovine articular chondrocytes (jbACs). ACK buffer treatment of foACs and jbACs decreased the number of contaminating RBCs by over 60% and additionally reduced the number of apoptotic chondrocytes in the cell isolates. Reducing the number of contaminating RBCs removed cellular detractors to the self-assembling process and eliminated an apoptotic stimulus, thus improving neocartilage homogeneity, chondrocyte distribution, and extracellular matrix deposition within the neotissues. For example, in foAC neocartilage, ACK buffer treatment ultimately led to a 170% increase in compressive aggregate modulus, a 130% increase in shear modulus, an 80% increase in tensile modulus, and a 130% increase in ultimate tensile strength of the neocartilage. This work represents the first time that ACK buffer has been used to purify fully differentiated cells and subsequently increase the functional properties of neotissue.


Section II: General orthopaedics. Anterior cervical fusion for trauma.
Anterior bone grafts of 24 injured cervical spines were reviewed with respect to early postoperative instability and eventual malunion. Spinal redislocation or graft extrusion occurred in 21% representing failure to attain early stability. In 38%, the late complication of kyphotic malunion occurred, averaging 21%. The Yale instability criteria were fulfilled in 15 cases and mechanical complications developed in 87% of these. When posterior instability was present, the mechanical complication rate rose to 92%. Early stabilization of most neck injuries is not achieved by the anterior bone graft and its use as a means of "stabilization" is unsubstantiated by clinical experience.


A comprehensive study on the fire resistance properties of ultra-fine ceramic waste-filled high alkaline white cement paste composites for progressing towards sustainability.
The most practical sustainable development options to safeguard the local ecology involve reducing the use of raw materials and guaranteeing proper recycling of the principal destroyed solid wastes. Preventing the creation of hazardous waste and the subsequent pollution that results from improper disposal is a top priority. Based on this, the study's authors recommend reusing the ultra-fine ceramic shards (CW). High-alkaline white cement (WC) has been partially replaced by ultra-fine CW because it is a cheaper, more abundant, and more lasting environmental material used in the production of trendy blended white cement pastes composites. In this context, we look at ultra-fine CW, a material that has been suggested for use as a hydraulic filler due to its high performance, physicomechanical qualities, and durability. XRF, XRD, FTIR, and SEM measurements are used to characterize the microstructure, thermal characteristics, and thermodynamics. Because of the effect of ultra-fine ceramic waste, the firing test reduces the mechanical strength by default, but with active filler, decreases slowly and increase its physicomechanical features and compressive strength compared to the control sample (WC), setting a new benchmark. The maximum amount of crystallization formed in the presence of ultra-fine ceramic waste in WC-matrix, resulting in a decrease in total porosity and early cracking. Together, the improved workability and energy-saving features of cement blends with ultra-fine ceramic waste, reflect their economic and environmental benefits, which may reduce building costs and boost the durability of the raw materials used in the mix.


Tongue-operated assistive technology with access to common smartphone applications via Bluetooth link.
Tongue Drive System (TDS) is a wireless and wearable assistive technology (AT) that enables people with severe disabilities to control their computers, wheelchairs, and electronic gadgets using their tongue motion. We developed the TDS to control smartphone's (iPhone/iPod Touch) built-in and downloadable apps with a customized Bluetooth mouse module by emulating finger taps on the touchscreen. The TDS-iPhone Bluetooth mouse interface was evaluated by four able-bodied subjects to complete a scenario consisting of seven tasks, which were randomly ordered by using touch on the iPhone screen with index finger, a computer mouse on iPhone, and TDS-iPhone Bluetooth mouse interface with tongue motion. Preliminary results show that the average completion times of a scenario with touch, mouse, and TDS are 165.6 ± 14.50 s, 186.1 ± 15.37 s, and 651.6 ± 113.4 s, respectively, showing that the TDS is 84.37% and 81.16% slower than touch and mouse for speed of typing with negligible errors. Overall, considering the limited number of commands and unfamiliarity of the subjects with the TDS, we achieved acceptable results for hands-free functionality.


Regulatory monoubiquitination of phosphoenolpyruvate carboxylase in germinating castor oil seeds.
Phosphoenolpyruvate carboxylase (PEPC) is a tightly regulated enzyme situated at the core of plant C-metabolism. Although its anaplerotic role and control by allosteric effectors, reversible phosphorylation, and oligomerization have been well documented in the endosperm of developing castor oil seeds (COS), relatively little is known about PEPC in germinating COS. The initial phase of COS germination was accompanied by elevated PEPC activity and accumulation of comparable amounts of pre-existing 107-kDa and inducible 110-kDa immunoreactive PEPC polypeptides (p107 and p110, respectively). A 440-kDa PEPC heterotetramer composed of an equivalent ratio of non-phosphorylated p110 and p107 subunits was purified from germinated COS. N-terminal microsequencing, mass spectrometry, and immunoblotting revealed that both subunits arose from the same gene (RcPpc3) that encodes the p107 subunit of a phosphorylated 410-kDa PEPC homotetramer in developing COS but that p110 is a monoubiquitinated form of p107. Tandem mass spectrometry sequencing of a diglycinated tryptic peptide identified Lys-628 as p110's monoubiquitination site. This residue is conserved in vascular plant PEPCs and is proximal to a PEP-binding/catalytic domain. Incubation with a human deubiquitinating enzyme (USP-2 core) converted the p110:p107 PEPC heterotetramer into a p107 homotetramer while significantly reducing the enzyme's K(m)(PEP) and sensitivity to allosteric activators (hexose-Ps, glycerol-3-P) and inhibitors (malate, aspartate). Monoubiquitination is a non-destructive and reversible post-translational modification involved in the control of diverse processes such as transcription, endocytosis, and signal transduction. The current study demonstrates that tissue-specific monoubiquitination of a metabolic enzyme can also occur and that this modification influences its kinetic and regulatory properties.


An aged rat model of partial androgen deficiency: prevention of both loss of bone and lean body mass by low-dose androgen replacement.
The aim of this study was to evaluate the effects of different doses of androgen replacement, both on body composition and bone, in an aged male orchidectomized rat model. Testosterone was administered by 0.5, 1, and 2.5-cm sc SILASTIC implants (release of, respectively, 11.5, 23, and 55 microg/day) to aged (12 months old, +/- 550 g) male orchidectomized Wistar rats during a 15-week experimental period. T 0.5 only partially prevented decrease of ventral prostate and seminal vesicle weight, compared with an intact group that received an empty implant (Intact). The 1-cm implant (T 1) completely prevented decrease of both seminal vesicles and ventral prostate weight. The 2.5-cm implant (T 2.5) was clearly supraphysiological, as demonstrated by significant hypertrophy of both androgen-sensitive organs. Serum testosterone was lower in T 0.5 and T 1 (0.38 +/- 0.06 ng/ml and 0.92 +/- 0.06 ng/ml, respectively) and higher in T 2.5 (2.4 +/- 0.28. ng/ml), compared with both Intact (1.6 +/- 0.23 ng/ml) and the baseline group(1.6 +/- 0.11 ng/ml). As expected, orchidectomized rats that received an empty SILASTIC implant had significantly lower bone mineral content (-7.9%), apparent density (-5.7%), and lean body mass (-10.8%), as measured by dual-energy x-ray absorptiometry, without significant changes in body weight and fat mass, compared with Intact. Also, cancellous (-50.3%) and cortical (-1.8%) volumetric density, as measured by peripheral quantitative computed tomography, were decreased in the tibia. Bone turnover, as measured by serum osteocalcin and urinary deoxypyridinoline excretion, was increased in orchidectomized rats that received an empty SILASTIC implant. T 0.5 prevented all changes, not only in bone mineral content, density, and turnover but also in lean body mass. Moreover, there were no significant differences, for all these parameters, between the different doses of testosterone replacement. In conclusion, low-dose androgen replacement does not lead to lower bone mineral density, higher bone turnover, and lower lean body mass in aged male rats, whereas complete androgen deficiency does. Therefore, the threshold concentration of testosterone necessary for prevention of both bone and lean body mass loss in aged male rats is clearly lower than for prostate and seminal vesicles.


Effect of experimental diabetes on rat cardiac cAMP, phosphorylase, and inotropy.
The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the effect of isoproterenol on adenosine 3',5'-cyclic monophosphate (cAMP) content, inotropy, and phosphorylase activity. Experimental diabetes was induced by intravenous injection of either alloxan (40 mg/kg) or streptozotocin (50 mg/kg). There were no changes in either basal cAMP levels or in isoproterenol-induced cAMP levels in hearts from diabetic rats at either 3 days or 100-120 days after induction of diabetes. Maximum changes produced by isoproterenol in positive and negative dP/dt developments of diabetic rat hearts were also not different from control at either time point. However, phosphorylase was activated to a significantly greater extent by isoproterenol in hearts obtained from acute as well as chronic diabetic rats. Chronic diabetic rat hearts exhibited significantly higher total phosphorylase activity. Diabetic rat hearts had slightly but not significantly higher basal phosphorylase a activity. Furthermore, prostaglandin E1 activated phosphorylase in diabetic rat hearts but not in control rat hearts. Acute metabolic derangements and alterations in Ca2+ homeostasis caused by diabetes could be the underlying causes for this phosphorylase response. Thyroid hormone levels were depressed in diabetic rats. However, hypothyroidism is probably not responsible for the alterations in phosphorylase activity.


Patterns of Care Among Patients Referred to Rheumatologists in Ontario, Canada.
Our aim was to characterize referrals to rheumatologists, the early care management of patients with rheumatic diseases, and timeliness of care and treatment. We conducted a retrospective observational study involving patients with first-time rheumatology referrals between 2000 and 2013 in the primary care Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Referrals were characterized in terms of diagnoses, patient demographics, diagnostic tests, treatment initiated by family physicians and rheumatologists, and other specialists seen prior to rheumatology consultation. Timeliness of referrals, rheumatologist consultations, and treatment were determined overall and for each diagnostic category. Among 2,430 patients referred to a rheumatologist, 69% were female, with an average age of 53 years. The principal diagnosis associated with the referral included osteoarthritis (32%), systemic inflammatory rheumatic diseases (31%), regional musculoskeletal conditions (16%), chronic pain conditions (14%), osteoporosis (2%), and other/miscellaneous (5%). Family physicians most frequently prescribed nonsteroidal antiinflammatory drugs/cyclooxygenase 2 inhibitors (38%), and their pre-referral diagnostic testing practice varied considerably. The duration of time from symptom onset to rheumatology consultation varied by diagnoses, with the shortest being for patients with systemic rheumatic diseases; for rheumatoid arthritis (RA), the median time to consultation was 327 days. Most of the delay occurred prior to referral; 36% of RA patients initiated a disease-modifying antirheumatic drug within 6 months of symptom onset. Approximately 1 in 3 referrals to rheumatologists were for a systemic inflammatory rheumatic disease. We observed substantial delays to rheumatology consultations and variations in patterns of care that could be amenable to quality improvement interventions.


Birdsong: is it music to their ears?
Since the time of Darwin, biologists have wondered whether birdsong and music may serve similar purposes or have the same evolutionary precursors. Most attempts to compare song with music have focused on the qualities of the sounds themselves, such as melody and rhythm. Song is a signal, however, and as such its meaning is tied inextricably to the response of the receiver. Imaging studies in humans have revealed that hearing music induces neural responses in the mesolimbic reward pathway. In this study, we tested whether the homologous pathway responds in songbirds exposed to conspecific song. We played male song to laboratory-housed white-throated sparrows, and immunolabeled the immediate early gene product Egr-1 in each region of the reward pathway that has a clear or putative homologue in humans. We found that the responses, and how well they mirrored those of humans listening to music, depended on sex and endocrine state. In females with breeding-typical plasma levels of estradiol, all of the regions of the mesolimbic reward pathway that respond to music in humans responded to song. In males, we saw responses in the amygdala but not the nucleus accumbens - similar to the pattern reported in humans listening to unpleasant music. The shared responses in the evolutionarily ancient mesolimbic reward system suggest that birdsong and music engage the same neuroaffective mechanisms in the intended listeners.


The falling rate of positive penicillin skin tests from 1995 to 2007.
Data on the rate of positive penicillin skin test (PenST) results over time in large populations are rare. The factors that influence positive PenST results are incompletely understood. We sought to correlate demographic variables to the rate of positive PenST results over time in a large group of patients with a history of penicillin allergy. RESULTS from the first test for all patients tested for penicillin allergy in the Kaiser Permanente Health Care Program in San Diego County, CA, between 1995 and 2007 are reported. All patients were tested with penicillin, penicilloyl-poly-lysine, penilloate, penicilloate, and amoxicillin. There were 255 positive PenST results in 3469 individuals. The rate of positive PenST results declined from >10% to <5% during the 13 years studied. The positive PenST result rate could be accounted for by the year of testing (R(2) = 0.56; p = 0.003) without any significant contribution from the patient's age or the time since reaction (TSR). If the TSR was ≤13 years, the relative risk of a positive PenST result was 2.1 (95% confidence interval = 1.6-2.8). If the study subject's age was ≤38 years, the relative risk of a positive PenST result was 2.1 (95% confidence interval = 1.6-2.7). Females reported higher rates of penicillin allergy history than males did (11% compared with 6.6%; p < 0.0001), but there were no significant sex differences in the rate of positive PenST results. There has been a steady decline in the proportion of positive PenST results between 1995 and 2007, independent of study subject age and TSR. Increasing age and increasing TSR were associated with a lower rate of positive PenST results.


An improved platform for functional assessment of large protein libraries in mammalian cells.
Multiplex genetic assays can simultaneously test thousands of genetic variants for a property of interest. However, limitations of existing multiplex assay methods in cultured mammalian cells hinder the breadth, speed and scale of these experiments. Here, we describe a series of improvements that greatly enhance the capabilities of a Bxb1 recombinase-based landing pad system for conducting different types of multiplex genetic assays in various mammalian cell lines. We incorporate the landing pad into a lentiviral vector, easing the process of generating new landing pad cell lines. We also develop several new landing pad versions, including one where the Bxb1 recombinase is expressed from the landing pad itself, improving recombination efficiency more than 2-fold and permitting rapid prototyping of transgenic constructs. Other versions incorporate positive and negative selection markers that enable drug-based enrichment of recombinant cells, enabling the use of larger libraries and reducing costs. A version with dual convergent promoters allows enrichment of recombinant cells independent of transgene expression, permitting the assessment of libraries of transgenes that perturb cell growth and survival. Lastly, we demonstrate these improvements by assessing the effects of a combinatorial library of oncogenes and tumor suppressors on cell growth. Collectively, these advancements make multiplex genetic assays in diverse cultured cell lines easier, cheaper and more effective, facilitating future studies probing how proteins impact cell function, using transgenic variant libraries tested individually or in combination.


Essential functional modules for pathogenic and defensive mechanisms in Candida albicans infections.
The clinical and biological significance of the study of fungal pathogen Candida albicans (C. albicans) has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved in C. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI) networks for both C. albicans and zebrafish were constructed. By comparing PPI networks at the early and late stages of the infection process, several critical functional modules were identified in both pathogenic and defensive mechanisms. Functional modules in C. albicans, like those involved in hyphal morphogenesis, ion and small molecule transport, protein secretion, and shifts in carbon utilization, were seen to play important roles in pathogen invasion and damage caused to host cells. Moreover, the functional modules in zebrafish, such as those involved in immune response, apoptosis mechanisms, ion transport, protein secretion, and hemostasis-related processes, were found to be significant as defensive mechanisms during C. albicans infection. The essential functional modules thus determined could provide insights into the molecular mechanisms of host-pathogen interactions during the infection process and thereby devise potential therapeutic strategies to treat C. albicans infection.


Systematic review with meta-analysis: the risk of mother-to-child transmission of hepatitis B virus infection in sub-Saharan Africa.
The risk of mother-to-child transmission of hepatitis B virus (HBV) has been quoted as 70-90% among women positive for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), and 5-30% among HBsAg-positive HBeAg-negative women. These risks are derived from Asia; little is known about sub-Saharan Africa. To determine the risk of mother-to-child transmission in sub-Saharan Africa, according to maternal HBeAg and type of prophylaxis. We searched Medline, Global Health, Embase, African Journals Online and African Index Medicus. We included observational or interventional studies that enrolled infants of HBV-infected women, and that tested for HBsAg or HBV DNA between 3 and 12 months of age. Fifteen articles from 11 African countries were included. Among HBeAg-positive women, the pooled risk was 38.3% (95% CI: 7.0-74.4%) without prophylaxis, which was significantly lower than the lower bound of 70-90% risk in the literature (P = 0.007). Among HBeAg-negative women, the pooled risk was 4.8% (95% CI: 0.1-13.3%) without prophylaxis, which lays within the lower range of the 5-30% risk in Asia. By extrapolating the pooled transmission risks to the number of births to infectious mothers, an estimated 1% of newborns (n = 367 250) are annually infected with HBV at birth in sub-Saharan Africa. Compared to Asia, the risk of mother-to-child transmission is low in sub-Saharan Africa. However, the annual number of infants perinatally infected with HBV is twice the number of incident paediatric HIV infections in sub-Saharan Africa (n = 190 000). This highlights the importance of preventing mother-to-child transmission of HBV in sub-Saharan Africa, which has been long neglected.


Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats.
While many experiment with drugs, relatively few individuals develop a true addiction. We hypothesized that, in rats, such individual differences in the actions of addictive drugs might be determined by postnatal rearing conditions. To test this idea, we investigated whether stimulant- and stress-induced activation of nucleus accumbens dopamine transmission and dopamine-dependent behaviours might differ among adults rats that had been either repeatedly subjected to prolonged maternal separation or a brief handling procedure or left undisturbed (non-handled) during the first 14 days of life. We found that, in comparison with their handled counterparts, maternally separated and non-handled animals are hyperactive when placed in a novel setting, display a dose-dependent higher sensitivity to cocaine-induced locomotor activity and respond to a mild stressor (tail-pinch) with significantly greater increases in nucleus accumbens dopamine levels. In addition, maternally separated animals were found to sensitize to the locomotor stimulant action of amphetamine when repeatedly stressed under conditions that failed to sensitize handled and non-handled animals. Finally, quantitative receptor autoradiography revealed a lower density of nucleus accumbens-core and striatal dopamine transporter sites in maternally separated animals. Interestingly, we also found greatly reduced D(3) dopamine receptor binding and mRNA levels in the nucleus accumbens-shell of handled animals. Together, these findings provide compelling evidence that disruptions in early postnatal rearing conditions can lead to profound and lasting changes in the responsiveness of mesocorticolimbic dopamine neurons to stress and psychostimulants, and suggest a neurobiological basis for individual differences in vulnerability to compulsive drug taking.


Crystal structure of the 1: 1 complex of 5-fluorouracil and 9-ethylhypoxanthine.
9-Ethylhypoxanthine and 5-fluorouracil form a 1 : 1 crystalline complex. The structure of this complex has been solved by x-ray diffraction analysis. The molecules crystallize in a monoclinic lattice and form a sheet structure in which pairs of fluorouracil molecules are held together by two hydrogen bonds. The 9-ethylhypoxanthine residues fill up the rest of the molecular sheet by forming single hydrogen bonds with each uracil pair.


Incidence and characteristics of antibiotic use in aged nursing home patients.
To measure the prevalence, incidence, types, and certain characteristics of antibiotics prescribed in nursing homes. Periodic survey over 1 year of patient charts in 53 stratified, randomly selected nursing homes in the state of Maryland. All patients 65 years of age or more residing in these nursing homes on the first day of study. Of 4,165 patients in 53 nursing homes, records over the year were satisfactory in 3,899 patients in 52 nursing homes. The prevalence of antibiotic use on the first day of the study was 8%. Over the next 12 months, observations of more than one million patient-days revealed an incidence of 0.46 antibiotic courses/100 patient-days; 54% of the 3,899 patients received at least one antibiotic course. For presumed active infections, beta lactam antibiotics were the most commonly used, 54% of antibiotic orders. For all antibiotics, urinary tract infection was the most common indication, eliciting 36% of orders including 9% for asymptomatic bacteriuria. Skin, lower respiratory, and upper respiratory infections comprised 14%-17% each. Physicians prescribed 94% of courses but documented examinations of only 44% of patients at the outset of these courses. Consensus criteria for minimal diagnostic evaluation of four selected infections were met in only 11% of episodes of infection. Although the most serious infections tended to be better evaluated than others, 31% of the former were not noted to have been examined by a physician. Three percent of orders were for prophylaxis and two-thirds of these antibiotics were administered for more than 2 days. Antibiotics are frequently prescribed for aged nursing home patients, often in the absence of a physician's examination and other features commonly performed in evaluation of specific infectious diseases. More than one-fifth of antibiotics prescribed by presumed active infections were for two infections usually thought not to require antibiotic therapy, "viral" upper respiratory infection (13%) and asymptomatic bacteriuria (9%). To optimize antibiotic use in nursing homes, greater attention should be directed to appropriate durations of prophylaxis for urologic, dental, and minor surgical procedures; to standards for diagnostic evaluations of common infections; and to the roles of antibiotics in upper respiratory infections and in asymptomatic bacteriuria.


Automatic calculation of symmetry-adapted tensors in magnetic and non-magnetic materials: a new tool of the Bilbao Crystallographic Server.
Two new programs, MTENSOR and TENSOR, hosted on the open-access website known as the Bilbao Crystallographic Server, are presented. The programs provide automatically the symmetry-adapted form of tensor properties for any magnetic or non-magnetic point group or space group. The tensor is chosen from a list of 144 known tensor properties gathered from the scientific literature or, alternatively, the user can also build a tensor that possesses an arbitrary intrinsic symmetry. Four different tensor types are considered: equilibrium, transport, optical and nonlinear optical susceptibility tensors. For magnetically ordered structures, special attention is devoted to a detailed discussion of the transformation rules of the tensors under the time-reversal operation 1'. It is emphasized that for non-equilibrium properties it is the Onsager theorem, and not the constitutive relationships, that indicates how these tensors transform under 1'. In this way it is not necessary to restrict the validity of Neumann's principle. New Jahn symbols describing the intrinsic symmetry of the tensors are introduced for several transport and optical properties. In the case of some nonlinear optical susceptibilities of practical interest, an intuitive method is proposed based on simple diagrams, which allows easy deduction of the action of 1' on the susceptibilities. This topic has not received sufficient attention in the literature and, in fact, it is usual to find published results where the symmetry restrictions for such tensors are incomplete.


Exploring the association between anticipated and actual responses to disclosures of intimate partner violence and sexual assault.
Victims of intimate partner violence (IPV) and sexual assault (SA) commonly disclose their experiences to friends or family members, or within other personal relationships. Disclosure recipients' responses to these disclosures are associated with victims' mental health. Previous research has separately measured both actual responses to IPV/SA and anticipated responses to IPV/SA (e.g., response to a hypothetical scenario) from the perspective of disclosure recipients. Yet, little research has described the association between disclosure recipients' anticipated and actual responses. The aim of the current paper was to use a prospective design to examine the association between disclosure recipients' anticipated and actual responses to IPV/SA, including positive and negative social reactions, perceptions of victim responsibility, empathy, and confusion and ineffectiveness about how to respond. Participants (N = 126 college students aged 18-23; 70.6% women) answered questions about their anticipated responses to a hypothetical IPV/SA disclosure scenario, and then six months later answered the same questions about their actual responses to an actual disclosure of IPV/SA. Although most anticipated and actual responses were significantly associated, associations were moderate in size. Some associations were stronger for participants with a closer relationship to the victim, for participants who had their own victimization history, for women, and for men. Individuals can predict their responses to some degree, but are not totally accurate in doing so.


Diversity and physiology of polyhydroxyalkanoate-producing and -degrading strains in microbial mats.
Photosynthetic microbial mats are sources of microbial diversity and physiological strategies that reflect the physical and metabolic interactions between their resident species. This study focused on the diversity and activity of polyhydroxyalkanoate-producing and -degrading bacteria and their close partnership with cyanobacteria in an estuarine and a hypersaline microbial mat. The aerobic heterotrophic population was characterized on the basis of lipid biomarkers (respiratory quinones, sphingoid bases), polyhydroxyalkanoate determination, biochemical analysis of the isolates, and interaction assays. Most of the polyhydroxyalkanoate-producing isolates obtained from an estuarine mat belonged to the Halomonas and Labrenzia genera, while species of Sphingomonas and Bacillus were more prevalent in the hypersaline mat. Besides, the characterization of heterotrophic bacteria coisolated with filamentous cyanobacteria after selection suggested a specific association between them and diversification of the heterotrophic partner belonging to the Halomonas genus. Preliminary experiments suggested that syntrophic associations between strains of the Pseudoalteromonas and Halomonas genera explain the dynamics of polyhydroxyalkanoate accumulation in some microbial mats. These metabolic interactions and the diversity of the bacteria that participate in them are most likely supported by the strong mutual dependence of the partners.


Inherited, early onset, insulin-requiring diabetes mellitus of Keeshond dogs.
Spontaneous diabetes mellitus has been characterized in a line of nonobese purebred keeshond dogs as an insulin-requiring hereditary disorder with onset at between 2 and 6 mo of age. Diabetic dogs developed cataracts, became ketotic, hyperglycemic, hypercholesterolemic, lipemic, and hypoinsulinemic. Basal glucagon, cortisol, and T4 serum concentrations and responses to ACTH, TSH, and arginine were normal. Light microscopic studies of the pancreas by immunocytochemical procedures revealed the absence of islet B cells, the presence of A cells, and solitary B cells. Diabetic dogs had poor fecundity, and a single puberal diabetic male had poor semen quality and was unable to sire pups. Parents of diabetics and nondiabetic siblings were normal. This spontaneous form of diabetes mellitus, with similar lesions to the insulin-dependent diabetes of people, will be a valuable aid to comparative biomedical research of diabetes mellitus.


Synthesis and characterization of biobased isosorbide-containing copolyesters as shape memory polymers for biomedical applications.
Novel biobased isosorbide-containing copolyesters (PBISI copolyesters) with both biocompatibility and sustainability were synthesized by using commercially available biobased diols and diacids. Due to the presence of itaconate in copolyesters, it can be readily crosslinked by peroxide into a crystallizable network. The structure and thermal properties of PBISI copolyesters were determined by 1H NMR, FTIR, DSC, and WAXD. The chain composition, melting point and crystallinity of the PBISI copolyesters can be tuned continuously by changing the content of isosorbide. The crosslinked copolyester is demonstrated to be a promising shape memory polymer (SMP) with excellent shape memory properties including shape fixity and shape recovery rate close to 100%. The switching temperatures of PBISI-based SMPs can be tuned between 26 °C and 54 °C by altering the composition of PBISI copolyesters and curing extent. Cell adhesion and proliferation were adopted to evaluate the potential biocompatibility of PBISI-based SMPs, and the results indicated that all the PBISI-based SMPs were essentially noncytotoxic, making them suitable for fabricating biomedical devices.


Risk factors for poor outcome in community-onset Clostridium difficile infection.
A substantial portion of Clostridium difficile infection (CDI) cases occur in communities, and community-onset CDI (CO-CDI) can lead to serious complications including mortality. This study aimed to identify the risk factors for a poor outcome in CO-CDI. We performed a retrospective review of all inpatients with CDI, in a 1300-bed tertiary-care hospital in Korea, from 2008 through 2015. CO-CDI was defined as CDI occurring within 48 h of admission. Poor outcome was defined as follows: 1) all-cause 30-day mortality, 2) in-hospital mortality, or 3) surgery due to CDI. Of a total 1256 CDIs occurring over 8 years, 152 (12.1%) cases were classified as CO-CDI and 23 (15.1%) had a poor outcome, including 22 (14.5%) cases of mortality and 2 (1.3%) cases of surgery. Patients with a poor outcome had a higher mean age than those without a poor outcome (75.8 vs. 69.6 years, p = 0.03). The proportion of men and prior proton pump inhibitor (PPI) use were significantly higher in the poor outcome group (65.2% vs. 41.9%, p = 0.04; 39.1% vs. 17.6%, p = 0.02, respectively). Multivariate binary logistic model showed that PPI use and anemia (hemoglobin < 10 g/dL) at presentation were significantly associated with a poor outcome (adjusted odds ratio [aOR], 3.76; 95% confidence interval [95CI], 1.26-11.21, aOR, 4.67; 95CI, 1.52-14.34, respectively). Clinicians should not only be aware of the possibility of CDI in the community setting but also pay more attention to PPI-using elderly patients with anemia in consideration of a poor outcome.


Immune response in sows given transmissible gastroenteritis virus or canine coronavirus.
Twelve pregnant sows were inoculated oral-nasally 8 weeks before farrowing with attenuated transmissible gastroenteritis virus (TGEV), tissue culture-adapted canine coronavirus (CCV), or fluids from mock-infected culture (controls). A 2nd dose of the same inoculum, one-half oral-nasally and one-half intramammarily, was given 6 weeks later. Neutralizing antibodies for TGEV and CCV were demonstrated in sera, colostrum, and milk whey from the virus-vaccinated sows. Homologous geometric mean neutralizing titers were generally 4-fold higher than were heterologous titers. After challenge exposure of the nursing pigs with virulent TGEV, average morbidity and mortality for the pigs were 81% and 34% (mortality range = 11% to 63%), respectively, in the TGEV-vaccinated group; 83% and 39% (mortality range = 15% to 83%), respectively, in the CCV-vaccinated group; and 97% and 84% (mortality range = 78% to 100%), respectively, in the controls. Seemingly, sera from swine exposed to CCV could test serologically positive for TGEV-neutralizing antibody, and TGEV and CCV share at least 1 common neutralizing determinant that may be involved in protection.