[Effect of strontium on the anti-rickets activity of vitamin D3 and its hydroxy analogs].
Antirickets activity of vitamin D3 and of its derivatives 1 alpha- and 25-hydroxy vitamin D3 1.25- and 24,25-dihydroxy vitamin D3 and 1,24,25-trihydroxy vitamin D3 was studied in chicken maintained on a diet containing various amount (0.01-2.40 mg) of strontium. Vitamin D3 as well as its 24-hydroxy and 24,25-dihydroxy derivatives lost their antirickets activity in presence of high strontium concentrations. Under the same conditions I alpha-hydroxy, 1,25-dihydroxy and 1,24,25-trihydroxy vitamins D3 retained the ability both to induce calcium-binding protein synthesis in intestinal epithelium and to stimulate bone tissue mineralization, although to a lesser degree as compared with controls, kept on strontium-free diet. These results suggest that presence of I alpha-OH-group in the steroid molecule is necessary for expression of maximal biological activity under conditions of elevated strontium content in diet while the activity of hydroxylase is inhibited in kidney. At the same time, the vitamin D3 derivatives containing the OH-group are responsible for impairments caused by increased accumulation of strontium.


COVID-19 safety leadership, perceived severity, and emotional exhaustion: Does safety culture matter?
Emotional exhaustion is a major health-related issue that employees face, especially during crises such as pandemics. This study seeks to understand how safety leadership applied to the COVID-19 pandemic relates to emotional exhaustion, and to examine its mechanisms (i.e., perceived severity) along with its boundary condition (i.e., safety culture). A time lag study was conducted to collect data from 229 employees working in the service industry in Morocco. Data were analyzed through the Partial Least Squares Structural Equation Modeling (PLS-SEM) technique using SmartPLS 4. The results demonstrate that safety leadership is negatively related to emotional exhaustion. Additionally, they suggest that the relationship between COVID-19 safety leadership and perceived severity depends on the level of the moderating variable (i.e., safety culture). Specifically, the relationship is positive when safety culture is low, but is negative when safety culture is high. The results of this study are important as they extend our knowledge of the nature of safety leadership and emotional exhaustion, and offer managers practical implications that can help to optimize safety leadership practices.


High metal ion levels after use of the ASR™ device correlate with development of pseudotumors and T cell activation.
Pseudotumors and immunologic alterations are reported in patients with elevated metal ion levels after resurfacing arthroplasty of the hip. A direct association of increased cobalt and chromium concentrations with the development of pseudotumors has not been established. We hypothesized that (1) patients with higher blood cobalt and chromium concentrations are more likely to have pseudotumors develop, (2) elevated cobalt and chromium concentrations correlate with increased activation of defined T cell populations, and (3) elevated metal ion levels, small implant size, cup inclination angle, and patient age are risk factors for the development of pseudotumors. A single-surgeon cohort of 78 patients with 84 Articular Surface Replacement(®) implants was retrospectively investigated. Between 2006 and 2010, we performed 84 THAs using the Articular Surface Replacement(®) implant; this represented 2% (84/4950) of all primary hip replacements performed during that period. Of the procedures performed using this implant, we screened 77 patients (99%) at a mean of 43 months after surgery (range, 24-60 months). Seventy-one patients were investigated using ultrasound scanning, and cobalt and chromium concentrations in whole blood were determined by high-resolution inductively coupled plasma mass spectrometry. Differential analysis of lymphocyte subsets was performed by flow cytometry in 53 patients. Results of immunologic analyses were investigated separately for patients with and without pseudotumors. Pseudotumors were found in 25 hips (35%) and were more common in women than in men (p = 0.02). Multivariable regression analysis was performed to identify risk factors for the development of pseudotumors. Cobalt and chromium concentrations were greater in patients with pseudotumors than in those without (cobalt, median 8.3 versus median 1.0 μg/L, p < 0.001; chromium, median 5.9 versus median 1.3 μg/L, p < 0.001). The percentage of HLA-DR(+)CD4(+) T cells was greater in patients with pseudotumors than in those without (p = 0.03), and the proportion of this lymphocyte subtype was positively correlated with cobalt concentrations (r = 0.3, p = 0.02). Multivariable regression analysis indicated that increasing cobalt levels were associated with the development of pseudotumors (p < 0.001), and that patients with larger implants were less likely to have them develop (p = 0.04); age and cup inclination were not risk factors. We found a distinct association of elevated metal ion concentrations with the presence of pseudotumors and a correlation of increased cobalt concentrations with the proportion of activated T helper/regulator cells. Thus, the development of soft tissue masses after metal-on-metal arthroplasty could be accompanied by activation of T cells, indicating that this complication may be partly immunologically mediated. Further investigations of immunologic parameters in larger cohorts of patients with metal-on-metal arthroplasties are warranted. Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.


Wireless and satellite transmission of prehospital focused abdominal sonography for trauma.
As military operations become smaller and more remote and as humanitarian missions increase, ultrasound technology is emerging as a valuable asset for defining injuries in austere settings. This study evaluated the feasibility of focused abdominal sonography for trauma (FAST) examinations in a field environment with real-time images sent wireless to an antenna and over satellite. Using a 6-lb SonoSite portable ultrasound device with battery pack, FAST examinations were performed on a healthy volunteer, transferred wireless at distances of 1,000 and 1,500 feet from the receiving antenna using a vest-mounted microwave transmitter, and then redirected over satellite (INMARSAT) to a remote hospital for review by emergency physicians, and a radiologist. Real-time wireless transmissions at 1,500 feet reliably yielded images without quality or interpretability drop compared with those recorded digitally at the examination site. A 32% reduction in image quality and interpretability was seen with still images and a 42% reduction was noted with cine loops using INMARSAT. The authors did not find the upper distance limit of the wireless transmitter used. This study suggests 1) that remote FAST examinations are plausible for prehospital care and triage using new-generation portable ultrasound units, 2) that line-of-sight transmission of FAST examinations when compared with on-site images results in no degradation in image quality or interpretability at distances used, 3) that ranges greater than 1,500 feet are feasible for interpretable examinations and therefore line-of-site mass casualty or field triage sites, and 4) that real-time INMARSAT transmission of FAST examinations at 64 kbps may serve a limited role for remote clinical interpretation.


Inhibition of voltage-gated K+ current in rat intrapulmonary arterial myocytes by endothelin-1.
Although endothelin (ET)-1 is an important regulator of pulmonary vascular tone, little is known about the mechanisms by which ET-1 causes contraction in this tissue. Using the whole cell patch-clamp technique in rat intrapulmonary arterial smooth muscle cells, we found that ET-1 and the voltage-dependent K+ (Kv)-channel antagonist 4-aminopyridine, but not the Ca(2+)-activated K(+)-channel antagonist charybdotoxin (ChTX), caused membrane depolarization. In the presence of 100 nM ChTX, ET-1 (10(-10) to 10(-7) M) caused a concentration-dependent inhibition of K+ current (56.2 +/- 3.8% at 10(-7) M) and increased the rate of current inactivation. These effects of ET-1 on K+ current were markedly reduced by inhibitors of protein kinase C (staurosporine and GF 109203X) and phospholipase C (U-73122) or under Ca(2+)-free conditions and were mimicked by activators of protein kinase C (phorbol 12-myristate 13-actetate and 1,2-dioctanoyl-sn-glycerol). These data suggest that ET-1 modulated pulmonary vascular reactivity by depolarizing pulmonary arterial smooth muscle, due in part to the inhibition of Kv current that occurred via activation of the phospholipase C-protein kinase C signal transduction pathway.


Iterative Dynamic Generic Learning for Face Recognition From a Contaminated Single-Sample Per Person.
This article focuses on a new and practical problem in single-sample per person face recognition (SSPP FR), i.e., SSPP FR with a contaminated biometric enrolment database (SSPP-ce FR), where the SSPP-based enrolment database is contaminated by nuisance facial variations in the wild, such as poor lightings, expression change, and disguises (e.g., wearing sunglasses, hat, and scarf). In SSPP-ce FR, the most popular generic learning methods will suffer serious performance degradation because the prototype plus variation (P+V) model used in these methods is no longer suitable in such scenarios. The reasons are twofold. First, the contaminated enrolment samples could yield bad prototypes to represent the persons. Second, the generated variation dictionary is simply based on the subtraction of the average face from generic samples of the same person and cannot well depict the intrapersonal variations. To address the SSPP-ce FR problem, we propose a novel iterative dynamic generic learning (IDGL) method, where the labeled enrolment database and the unlabeled query set are fed into a dynamic label feedback network for learning. Specifically, IDGL first recovers the prototypes for the contaminated enrolment samples via a semisupervised low-rank representation (SSLRR) framework and learns a representative variation dictionary by extracting the "sample-specific" corruptions from an auxiliary generic set. Then, it puts them into the P+V model to estimate labels for query samples. Subsequently, the estimated labels will be used as feedback to modify the SSLRR, thus updating new prototypes for the next round of P+V-based label estimation. With the dynamic learning network, the accuracy of the estimated labels is improved iteratively by virtue of the steadily enhanced prototypes. Experiments on various benchmark face data sets have demonstrated the superiority of IDGL over state-of-the-art counterparts.


Prescription tranquilizer/sedative misuse prevalence and correlates across age cohorts in the US.
Prescription tranquilizer/sedative (e.g., alprazolam, zolpidem) misuse (i.e., use in ways not intended by the prescriber or without a prescription) is understudied, with little research identifying misuse correlates. Identification of key correlates could identify subgroups more likely to engage in misuse, allowing for targeted treatment. This work examines tranquilizer/sedative use and misuse prevalence rates and misuse correlates across U.S. age cohorts, using nationally representative data. Data were from the 2015-16 National Survey on Drug Use and Health (n = 114,043). Analyses used design-based logistic regression for past-year tranquilizer/sedative misuse correlates across participants or those engaged in past-year use; past-month misuse correlates were also examined in those with past-year misuse. Young adults (18-25 years) had the highest prevalence of past-year and past-month tranquilizer/sedative misuse, with 42.8% of those with past-year use also engaged in misuse. Mental health correlates were associated with past-year misuse, while substance use, particularly opioid misuse, was associated with both past-year and past-month misuse. Substance use correlate strength was most likely to vary by age group, with older adults (65 years and older) having fewer significant correlates overall. This work highlighted young adults and those with other substance use as most likely to engage in tranquilizer/sedative misuse. In particular, those endorsing suicidality and reporting opioid misuse are a subgroup of concern, given their especially elevated rates of misuse and the increased risk for overdose imparted by tranquilizer/sedative medication. Workplace-based interventions for young adults and school-based universal prevention may be warranted to limit tranquilizer/sedative misuse in these groups.


Comparison between iloprost and alprostadil for protection against ischemia/reperfusion injury in a rat model
Background/aim: Alprostadil and iloprost are successful agents used for both pulmonary hypertension and extremity ischemia treatment. Different systemic effects of these agents may change the preferences of clinical usage. Superiority of preventing ischemia/ reperfusion (IR) injury is a criterion for clinical preference of these agents. The present study was designed to compare the protective effects of alprostadil and iloprost in a rat model of IR injury. Materials and methods: Twenty-three male Sprague Dawley rats were used (aged 8-12 weeks, mean weight 230 ± 30 g). They were randomized into 4 groups: Group 1 (iloprost + IR), Group 2 (alprostadil + IR), Group 3 (saline + IR), and Group 4 (control). Under general anesthesia, in all groups except Group 4, the abdominal region was explored and the abdominal aorta was temporarily clamped for 60 min. After the clamp was removed, 120 min of reperfusion was applied. In Group 4, the rats were placed under general anesthesia and abdominal exploration was performed without the IR procedure. For all rats, body temperature was kept at 36 °C with a heater pad through the whole procedure. The rats were euthanized under general anesthesia to remove the kidneys and lungs for study. Histopathological and biochemical analyses were conducted with kidney and lung tissues. Histopathological scoring was done by analyzing cellular damage at tissue level. Malondialdehyde (MDA), superoxide dismutase, and glutathione levels were studied for biochemical analysis. Results: Histopathologic analysis showed that, as compared with alprostadil, iloprost provided a significantly higher level of renal protection against IR injury (P < 0.01). Renal tissue levels of MDA were significantly lower in the alprostadil group as compared to Group 3 (P < 0.05). Conclusion: Alprostadil and iloprost seem to provide protection against IR injury, with iloprost being more protective in renal tissue. Alprostadil is more effective than iloprost in protecting lung tissue against IR injury.


An enzyme-linked immunosorbent assay (ELISA) for trinitrotoluene (TNT) residue on hands.
An enzyme-linked immunosorbent assay (ELISA) developed for the detection of trinitrotoluene (TNT) in munitions wastewater has been adapted to the detection of TNT residue on hands following contact. Using the procedure developed, as little as 50 pg of TNT could be detected. Accounting for sample size and dilution, the 50 pg equates to 15 ng of TNT recovered from the hands. Following contact with TNT, amounts ranging from 53 ng to more than 1500 ng were recovered from hands. The monoclonal anti-TNT antibodies showed no cross-reactivity with several other explosives or common contaminants. These preliminary results indicate promise for the development of a simple-to-use, immunoassay-based field test kit for TNT and, ultimately, other explosives.


Angiotensin II amplification of alpha-adrenergic vasoconstriction: role of receptor reserve.
Angiotensin II (Ang II) is known to enhance the vasoconstrictor response to norepinephrine (NE). In the present study, this interaction was investigated using isolated rabbit femoral artery rings mounted in tissue baths for the measurement of isometric contraction. Exposure to 3 x 10(-10) M Ang II caused a contraction that was less than 5% of the maximal response to NE. In the presence of Ang II, the NE dose-response curve shifted to the left twofold and the maximal response was not changed. The calcium channel antagonist nifedipine, 1 x 10(-7) M, caused a modest inhibition of the response to NE in either the presence or absence of Ang II. In contrast, nifedipine abolished the leftward shift of the NE dose-response curve caused by Ang II. Femoral arteries were pretreated with benextramine to cause partial alpha-adrenoceptor inactivation. The maximal contractile response to NE in these tissues was between 20% and 40% of that in control vessels, indicating that alpha-adrenoceptor reserve had been eliminated. In benextramine-pretreated vessels, the presence of 3 x 10(-10) M Ang II caused a modest leftward shift of the NE dose-response curve but increased the maximal responses to all NE concentrations by 200% to 800%. Nifedipine caused a modest inhibition of the response to NE in the absence of Ang II. In contrast, the enhanced response to NE in the presence of Ang II was nearly abolished. These results support our conclusions that 1) Ang II enhances the vasoconstrictor response to alpha-adrenergic stimulation, 2) the magnitude of enhancement is greater under conditions of reduced alpha-receptor reserve, and 3) calcium channel activation plays a major role in the amplified response.


Imaging the adult with transposition of the great arteries.
Patients with complete and congenitally corrected transposition of the great arteries commonly survive into adulthood and present with a vast array of clinical residua. Echocardiography remains the primary imaging modality in the routine assessment of the adult with transposition of the great arteries. It provides a comprehensive anatomic and hemodynamic evaluation. Limitations to echocardiography include evaluation of the following: the systemic right ventricle, baffle patency following atrial switch procedure, coronary arteries following arterial switch procedure or Nikadoh, and multilevel right ventricular outflow tract obstruction. Each form of palliation for transposition of the great arteries results in unique long-term sequelae that affect outcomes. A multimodality approach to imaging is required for a complete evaluation.


Biosecurity in an age of open science.
The risk of accidental or deliberate misuse of biological research is increasing as biotechnology advances. As open science becomes widespread, we must consider its impact on those risks and develop solutions that ensure security while facilitating scientific progress. Here, we examine the interaction between open science practices and biosecurity and biosafety to identify risks and opportunities for risk mitigation. Increasing the availability of computational tools, datasets, and protocols could increase risks from research with misuse potential. For instance, in the context of viral engineering, open code, data, and materials may increase the risk of release of enhanced pathogens. For this dangerous subset of research, both open science and biosecurity goals may be achieved by using access-controlled repositories or application programming interfaces. While preprints accelerate dissemination of findings, their increased use could challenge strategies for risk mitigation at the publication stage. This highlights the importance of oversight earlier in the research lifecycle. Preregistration of research, a practice promoted by the open science community, provides an opportunity for achieving biosecurity risk assessment at the conception of research. Open science and biosecurity experts have an important role to play in enabling responsible research with maximal societal benefit.


Quantitative aspects of radon daughter exposure and lung cancer in underground miners.
Epidemiological studies have shown an excessive incidence of lung cancer in miners with exposure to radon daughters. The various risk estimates have ranged from six to 47 excess cases per 10(6) person years and working level month, but the effect of smoking has not been fully evaluated. The present study, among a group of iron ore miners, is an attempt to obtain quantitative information about the risk of lung cancer due to radon and its daughters among smoking and non-smoking miners. The results show a considerable risk for miners to develop lung cancer; even non-smoking miners seem to be at a rather high risk. An additive effect of smoking and exposure to radon daughters is indicated and an estimate of about 30-40 excess cases per 10(6) person years and working level month seems to apply on a life time basis to both smoking and non-smoking miners aged over 50.


Trends in acute otitis media-related health care utilization by privately insured young children in the United States, 1997-2004.
The goal was to estimate the population effect of 7-valent pneumococcal conjugate vaccine on rates of acute otitis media-related ambulatory visits and antibiotic prescriptions for <2-year-old children enrolled in private insurance plans. We performed a retrospective analysis of a defined population by using the 1997-2004 MarketScan databases, which included an average of >500,000 person-years of observations for children <2 years of age. Trends in rates of International Classification of Diseases, Ninth Revision-coded ambulatory visits and antibiotic prescriptions attributable to acute otitis media were evaluated, and the national direct medical expenditures for these outcomes were estimated. In a comparison of 2004 with 1997-1999 (baseline period), rates of ambulatory visits and antibiotic prescriptions attributable to acute otitis media decreased from 2173 to 1244 visits per 1000 person-years (42.7% reduction) and from 1244 to 722 prescriptions per 1000 person-years (41.9% reduction), respectively. Total, estimated, national direct medical expenditures for acute otitis media-related ambulatory visits and antibiotic prescriptions for children <2 years of age decreased from an average of $1.41 billion during 1997 to 1999 to $0.95 billion in 2004 (32.3% reduction). Acute otitis media-related health care utilization and associated antibiotic prescriptions for privately insured young children decreased more than expected (on the basis of efficacy estimates in prelicensure clinical trials) after the introduction of routine 7-valent pneumococcal conjugate vaccine immunization. Although other factors, such as clinical practice guidelines to reduce antibiotic use, might have contributed to the observed trend, 7-valent pneumococcal conjugate vaccine may play an important role in reducing the burden of acute otitis media, resulting in substantial savings in medical care costs.


Unusual Behavior of Donor-Acceptor Stenhouse Adducts in Confined Space of a Water-Soluble PdII8 Molecular Vessel.
Donor-acceptor Stenhouse adducts (DASA) are new-generation photochromic compounds discovered recently. DASA exist normally in open form (blue/violet) and readily convert to cyclic (light yellow/colorless) zwitterionic form reversibly in the presence of green light in toluene/dioxane. In aqueous medium, the open form is not stable and converts to the cyclic zwitterionic form irreversibly. We report here a new self-assembled Pd8 molecular vessel (MV) that can stabilize and store the open form of DASA even in aqueous medium. Reaction of the 90° acceptor cis-(tmeda)Pd(NO3)2 (M) [tmeda = N, N, N', N'-tetramethylethane-1,2-diamine] with a symmetric tetraimidazole donor (L, 3,3',5,5'-tetra(1 H-imidazol-1-yl)-1,1'-biphenyl) in a 2:1 molar ratio yielded a water-soluble [8+4] self-assembled M8L4 molecular barrel (MV). This barrel (MV) is found to be a potential molecular vessel to store and stabilize the open forms of DASA in aqueous medium over the more stable zwitterionic cyclic form, while in the absence of the barrel the same DASA exist in cyclic zwitterionic form in aqueous medium. The hydrophobic interaction between the cavity and the open form of DASA molecules benefits reaching an out-of-equilibrium or reverse equilibrium state in aqueous medium. The presence of excess MV could even drive the conversion of the stable cyclic form to the open form in aqueous medium. The host-guest complex is stable upon irradiating with green light. To the best of our knowledge, this is the first successful attempt to stabilize the open form of DASA molecules in aqueous medium and the first report on the fate of DASA in a confined space discrete molecular architecture. Furthermore, the molecular vessel has been utilized for catalytic Michael addition reactions of a series of nitrostyrene derivatives with 1,3-indandione in aqueous medium.


The joint evolution of lifespan and self-fertilization.
In Angiosperms, there exists a strong association between mating system and lifespan. Most self-fertilizing species are short-lived, and most predominant or obligate outcrossers are long-lived. This association is generally explained by the influence of lifespan on the evolution of the mating system, considering lifespan as fixed. Yet, lifespan can itself evolve, and the mating system may as well influence the evolution of lifespan, as is suggested by joint evolutionary shifts of lifespan and mating system between sister species. In this paper, we build modifier models to study the joint evolution of self-fertilization and lifespan, including both juvenile and adult inbreeding depression. We show that provided that inbreeding depression affects adult survival, self-fertilization is expected to promote evolution towards shorter lifespan, and that the range of conditions under which selfing can evolve rapidly shrinks as lifespan increases. We study the effects of inbreeding depression affecting various steps in the life cycle and discuss how extrinsic mortality conditions are expected to affect evolutionary associations. In particular, we show that selfers may sometimes remain short-lived even in a very stable habitat, as a strategy to avoid the deleterious effects of inbreeding.


The study of intercalated cells using ex vivo techniques: primary cell culture, cell lines, kidney slices, and organoids.
This review summarizes methods to study kidney intercalated cell (IC) function ex vivo. While important for acid-base homeostasis, IC dysfunction is often not recognized clinically until it becomes severe. The advantage of using ex vivo techniques is that they allow for the differential evaluation of IC function in controlled environments. Although in vitro kidney tubular perfusion is a classical ex vivo technique to study IC, here we concentrate on primary cell cultures, immortalized cell lines, and ex vivo kidney slices. Ex vivo techniques are useful in evaluating IC signaling pathways that allow rapid responses to extracellular changes in pH, CO2, and bicarbonate (HCO3-). However, these methods for IC work can also be challenging, as cell lines that recapitulate IC do not proliferate easily in culture. Moreover, a "pure" IC population in culture does not necessarily replicate its collecting duct (CD) environment, where IC are surrounded by the more abundant principal cells (PC). It is reassuring that many findings obtained in ex vivo IC systems signaling have been largely confirmed in vivo. Some of these newly identified signaling pathways reveal that IC are important for regulating NaCl reabsorption, thus suggesting new frontiers to target anti-hypertensive treatments. Moreover, recent single-cell characterization studies of kidney epithelial cells revealed a dual developmental origin of IC, as well as the presence of novel CD cell types with certain IC characteristics. These exciting findings present new opportunities for the study of IC ex vivo, and will likely rediscover the importance of available tools in this field.


Mapping of quantitative trait loci for cholesterol, LDL, HDL, and triglyceride serum concentrations in pigs.
The fine mapping of polymorphisms influencing cholesterol (CT), triglyceride (TG), and lipoprotein serum levels in human and mouse has provided a wealth of knowledge about the complex genetic architecture of these traits. The extension of these genetic analyses to pigs would be of utmost importance since they constitute a valuable biological and clinical model for the study of coronary artery disease and myocardial infarction. In the present work, we performed a whole genome scan for serum lipid traits in a half-sib Duroc pig population of 350 individuals. Phenotypic registers included total CT, TG, and low (LDL)- and high (HDL)-density lipoprotein serum concentrations at 45 and 190 days of age. This approach allowed us to identify two genomewide significant quantitative trait loci (QTL) for HDL-to-LDL ratio at 45 days (SSC6, 84 cM) and for TG at 190 days (SSC4, 23 cM) as well as a number of chromosomewide significant QTL. The comparison of QTL locations at 45 and 190 days revealed a notable lack of concordance at these two time points, suggesting that the effects of these QTL are age specific. Moreover, we have observed a considerable level of correspondence among the locations of the most significant porcine lipid QTL and those identified in humans. This finding might suggest that, in mammals, diverse polymorphisms located in a common set of genes are involved in the genetic variation of serum lipid levels.


Application of ADM1 model to a full-scale anaerobic digester under dynamic organic loading conditions.
The IWA Anaerobic Digestion Model No. 1 (ADM1) was used to simulate the full-scale anaerobic sludge digester of Ankara Central Wastewater Treatment Plant. The digester is a completely mixed, once through continuous flow type which is being fed with a primary and secondary sludge mixture. The variability and unpredicted nature of the primary sludge composition was expected to challenge the model. A one-year dynamic data set from the digester was used for model calibration and validation in the study. The standard ADM1 model was corrected in the study with regard to nitrogen and carbon mass balances. A good correlation between the measured and simulated data was obtained for biogas yield, total volatile fatty acids and pH after heuristically calibrating stoichiometric and kinetic parameters of the ADM1 model. The simulation is sensitive to influent composition.


An adenoviral vector expressing interleukin-4 modulates tumorigenicity and induces regression in a murine breast-cancer model.
Anti-tumor activity of a recombinant adenovirus expressing murine IL-4 (AdCAIL-4) was investigated in a murine model of mammary adenocarcinoma. Primary tumor cells derived from mammary adenocarcinomas induced in transgenic mice by the middle T antigen gene of polyomavirus were infected with AdCAIL-4 and injected into syngeneic non-tumor bearing recipients. Expression of IL-4 by AdCAIL-4 transduced tumor cells significantly prolonged survival of all animals and prevented tumor development in 61% of recipient mice. When tumor bearing animals were injected intra-tumorally with AdCAIL-4, all animals survived at least 8 to 10 weeks longer than controls, and 50% of treated animals underwent complete tumor regression. Both en: vivo and in vivo treatment with AdCAIL-4 resulted in infiltration by eosinophils in and around the tumor site. Animals which had undergone complete tumor regression were protected from a second challenge suggesting that immunotherapy with Ad vectors expressing cytokines may protect from metastatic disease.


The association between childhood maltreatment and internet addiction among Chinese junior middle school students: prospective cohort study.
Childhood maltreatment is associated with internet addiction, but most evidence is from retrospective studies. We aimed to investigate the relationship between childhood maltreatment and internet addiction through a prospective cohort design. In a prospective cohort study, self-reported data on childhood maltreatment (Childhood Trauma Questionnaire - Short Form) at baseline, and internet addiction (Revised Chinese Internet Addiction Scale) at baseline and 6-month follow-up, were collected online from 756 Chinese junior middle school students aged 11-15 years and residing in Changsha, Hunan Province. Demographic data and covariates such as depression, anxiety, stress (Depression, Anxiety, and Stress Scale 21) and insomnia (Athens Insomnia Scale) were also surveyed at baseline. Logistic regression analysis measured the association between childhood maltreatment and internet addiction, and gender-related differences. Childhood maltreatment was prevalent in Chinese junior middle school students (37.83%), and the incidence rate of internet addiction was 9.26% at the 6-month follow-up. Emotional abuse was a significant risk factor for internet addiction (adjusted odds ratio 2.618, 95% CI 1.194-5.738; P = 0.016) in both males and females. This study suggests a high prevalence of childhood maltreatment in Chinese junior middle school students, and that emotional abuse plays a significant role in internet addiction. More attention should be paid to parenting style and adolescents' mental health.


Study of coumarin-resveratrol hybrids as potent antioxidant compounds.
In the present work we synthesized a selected series of hydroxylated 3-phenylcoumarins 5-8, with the aim of evaluating in detail their antioxidant properties. From an in depth study of the antioxidant capacity data (ORAC-FL, ESR, CV and ROS inhibition) it was concluded that these derivatives are very good antioxidants, with very interesting profiles in all the performed assays. The study of the effect of the number and position of the hydroxyl groups on the antioxidant activity was the principal aim of this study. In particular, 7-hydroxy-3-(3'-hydroxy)phenylcoumarin (8) proved to be the most active and effective antioxidant of the selected series in four of the performed assays (ORAC-FL = 11.8, capacity of scavenging hydroxyl radicals = 54%, Trolox index = 2.33 and AI30 index = 0.18). However, the presence of two hydroxyl groups on this molecule did not increase greatly the activity profile. Theoretical evaluation of ADME properties of all the derivatives was also carried out. All the compounds can act as potential candidates for preventing or minimizing the free radical overproduction in oxidative-stress related diseases. These preliminary findings encourage us to perform a future structural optimization of this family of compounds.


A Retrospective, Epidemiological Review of Type 2 Diabetes Mellitus in a Military Population.
Examine incidence rates of Type 2 Diabetes Mellitus (T2DM) in a military population over a tenyear period and whether demographic characteristics differ within the same population. Diagnostic data and demographic variables from 23,821 active duty service members between 2006 and 2015 were analyzed from the Defense Medical Epidemiological Database. The incidence rates of new onset cases ranged from .22 (per 1,000 service members) in 2015 to a high of 1.46 (per 1,000 service members) in 2006 for T2DM without complications and .00 (per 1,000 service members) in 2007 to a high of .29 (per 1,000 service members) in 2015 for T2DM with complications. The one-sample chi-square test showed the observed, and expected frequencies differed significantly for all demographic variables tested. Although there was a significant increase in the diagnosis of T2DM with complications in 2015, the overall downtrend is similar to that of the general US population. Older age and higher rank were more likely to be associated with the diagnosis of T2DM with and without complications, again suggestive of similar trends with the general US population. Continued efforts towards early diagnosis and treatment of these service members are needed to address this problem regarding military readiness.


Spatiotemporal heterogeneity in precipitation patterns explain population-level germination strategies in an edaphic specialist.
Many locally endemic species in biodiversity hotspots are restricted to edaphic conditions that are fixed in the landscape, limiting their potential to track climate change through dispersal. Instead, such species experience strong selection for germination strategies that can track suitable conditions through time. Germination strategies were compared among populations across the geographic range of a California vernal pool annual, Lasthenia fremontii Local germination strategies were tested to determine the associations with geographic variation in precipitation patterns. This study evaluated patterns of seed germination, dormancy and mortality in response to simulated variation in the timing, amount and duration of the first autumn precipitation event using seeds from six populations that span a geographic gradient in precipitation. Next, it was tested whether the germination strategies of different populations can be predicted by historical precipitation patterns that characterize each site. A significant positive relationship was observed between the historical variability in autumn precipitation and the extent of dormancy in a population. Marginal populations, with histories of the most extreme but constant autumn precipitation levels, expressed the lowest dormancy levels. Populations from sites with historically higher levels of autumn precipitation tended to germinate faster, but this tendency was not statistically significant. Germination in L. fremontii is cued by the onset of the first rains that characterize the beginning of winter in California's Great Central Valley. However, populations differ in how fast they germinate and the fraction of seeds that remain dormant when germination cues occur. The results suggest that seed dormancy may be a key trait for populations to track increasingly drier climates predicted by climate change models. However, the low dormancy and high mortality levels observed among seeds of the southernmost, driest populations make them most vulnerable to local extinction.


[Role of "Health" National project in improvement of health parameters in working population].
The author analyzed results of "Health" National project accomplishment in Rostov region over 2006-2009. Findings are that quality of primary medical care has improved, material and technical basis of municipal health care institutions has progressed, salary of primary health care division specialists has increased. Over this period, infant mortality and mortality among able-bodied population in the region has decreased, birth rate has increased, coefficient of natural loss of population has reduced, life expectancy has increased.


The association of type 1, type 2A and type 2B phosphatases with the human T lymphocyte plasma membrane.
Several putative plasma-membrane-associated components of the T-lymphocyte signal-transduction pathway are phosphorylated during the initial events of cellular activation. Little is known about the control of dephosphorylation of these components. We have shown by immunoblotting that the type 1 phosphatase, the type 2A phosphatase and type 2B phosphatase (calcineurin) are associated with the plasma membrane of normal human T lymphoblasts and the human T leukaemic cell line Jurkat 6. The type 1 phosphorylase phosphatase activity is present in a latent form which can be stimulated synergistically by deinhibitor and p-nitrophenyl phosphate. The PCSH form of the type 2A phosphatase appears to be the predominant oligomer in the plasma-membrane fraction. All three phosphatases can be extracted from membranes with Nonidet P40, but whereas the type 1c and type 2Ac phosphatases separate into the detergent-poor phase of Triton X-114, calcineurin separates into both detergent-rich and -poor phases. It is probable that one or more of these three plasma-membrane-associated phosphatases play regulatory roles in determining the phosphorylation state of membrane-bound proteins involved in human T-cell activation.


Direct visualization of the enzymatic digestion of a single fiber of native cellulose in an aqueous environment by atomic force microscopy.
Atomic force microscopy (AFM) was used to study native cellulose films prepared from a bacterial cellulose source, Acetobacter xylinum, using a novel application of the Langmuir-Blodgett technique. These films allowed high-resolution AFM images of single fibers and their microfibril structure to be obtained. Two types of experiments were performed. First, the fibers were characterized using samples that were dried after LB deposition. Next, novel protocols that allowed us to image single fibers of cellulose in films that were never dried were developed. This procedure allowed us to perform in situ AFM imaging studies of the enzymatic hydrolysis of single cellulose fibers in solution using cellulolytic enzymes. The in situ degradation of cellulose fibers was monitored over a 9 h period using AFM. These studies provided the first direct, real-time images of the enzymatic degradation of a single cellulose fiber. We have demonstrated the tremendous potential of AFM to study the mechanism of the enzymatic digestion of cellulose and to identify the most effective enzymes for the digestion of various cellulose structures or isomorphs.


Children's identification of consonants in a speech-shaped noise or a two-talker masker.
To evaluate child-adult differences for consonant identification in a noise or a 2-talker masker. Error patterns were compared across age and masker type to test the hypothesis that errors with the noise masker reflect limitations in the peripheral encoding of speech, whereas errors with the 2-talker masker reflect target-masker confusions within the central auditory system. A repeated-measures design compared the performance of children (5-13 years) and adults in continuous speech-shaped noise or a 2-talker masker. Consonants were identified from a closed set of 12 using a picture-pointing response. In speech-shaped noise, children under age 10 years performed more poorly than adults, but performance was adultlike for 11- to 13-year-olds. In the 2-talker masker, significant child-adult differences were observed in even the oldest group of children. Systematic clusters of consonant errors were observed for children in the noise masker and for adults in both maskers, but not for children in the 2-talker masker. These results suggest a more prolonged time course of development for consonant identification in a 2-talker masker than in a noise masker. Differences in error patterns between the maskers support the hypothesis that errors with the 2-talker masker reflect failures of sound segregation.


Heat shock protein 72 (HSPA1B) gene polymorphism and Toll-like receptor (TLR) 4 mutation are associated with increased risk of urinary tract infection in children.
Innate immunity and urinary tract response play a central role in the development of urinary tract infection (UTI). Heat shock protein (HSP) 72 and Toll-like receptor (TLR) 4 are among the key elements of innate defence mechanisms. This study assesses the role of HSPA1B A(1267)G and TLR4 A(896)G polymorphisms using allele-specific polymerase chain reaction in 103 patients treated with recurrent UTI. Allelic prevalence was compared with reference values of 235 healthy controls. Clinical data were also statistically evaluated. TLR4 (896)AG genotype and TLR4 (896)G allele had also higher prevalence in UTI patients versus controls (p = 0.031 and 0.041, respectively). Our data indicates a relationship between the carrier status of HSPA1B (1267)G and TLR4 (896)G alleles and the development of recurrent UTI in childhood independently of other renal abnormalities, while raising further questions about the clinical and therapeutic relevance of these polymorphisms in everyday pediatric nephrology.


The whole-genome landscape of medulloblastoma subtypes.
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.


8-oxoguanine in a quadruplex of the human telomere DNA sequence.
8-Oxoguanine is a ubiquitous oxidative base lesion. We report here on the effect of this lesion on the structure and stability of quadruplexes formed by the human telomeric DNA sequence 5'-dG(3)(TTAG(3))(3) in NaCl and KCl. CD, PAGE and absorption-based thermodynamic stability data showed that replacement of any of the tetrad-forming guanines by 8-oxoguanine did not hinder the formation of monomolecular, antiparallel quadruplexes in NaCl. The modified quadruplexes were, however, destabilized in both salts, the extent of this depending on the position of the lesion. These results and the results of previous studies on guanine-to-adenine exchanges and guanine abasic lesions in the same quadruplex show a noticeable trend: it is not the type of the lesion but the position of the modification that determines the effect on the conformation and stability of the quadruplex. The type of lesion only governs the extent of changes, such as of destabilization. Most sensitive sites were found in the middle tetrad of the three-tetrad quadruplex, and the smallest alterations were observed if guanines of the terminal tetrad with the diagonal TTA loop were substituted, although even these substitutions brought about unfavorable enthalpic changes. Interestingly, the majority of these base-modified quadruplexes did not adopt the rearranged folding induced in the unmodified dG(3)(TTAG(3))(3) by potassium ions, an observation that could imply biological relevance of the results.


Drug preferences in humans.
In animals, self-administration procedures have been used to assess reinforcing properties of drugs and predict abuse liability. In humans, subjective effect have been used. In the present studies, there two approaches were combined in human subjects. During the first four sessions of a nine-session experiment, subjects were given opportunities to ingest two drugs. After ingestion, subjects were free to leave. Mood questionnaires were filled out before ingestion and 1, 3, and 6 h later. During the last five sessions, subjects chose which drug to ingest. In study I, subjects chose 5 mg d-amphetamine over placebo. Subjective effects were typical of amphetamines but were not correlated with amount of amphetamine preference. In study II this same comparison was repeated three times. The preference for amphetamine decreased but subjective effects did not change. In study III, subjects tended to prefer 5 mg d-amphetamine to 20 mg fenfluramine. Subjective effects after amphetamine were similar to those in study I but those after fenfluramine did not differ from placebo. In study IV, subjects preferred placebo to 5 or 10 mg diazepam. The subjective effects of diazepam were typical of sedatives. These results indicate that drug self-administration procedures with humans can be useful for testing abuse liability and that subjective measures do not always correlate with drug preference.


Hydrogen sulfide is endogenously generated in rat skeletal muscle and exerts a protective effect against oxidative stress.
Skeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide (H2S) is endogenously produced in mammalian tissues and participates in a number of physiological and pathophysiological processes. We aimed to verify whether H2S could be endogenously generated and released by rat skeletal muscle, and determine the biological effects of H2S in rat skeletal muscle. The study was divided into two parts: detection of endogenous H2S generation and release in rat skeletal muscle and determination of antioxidative activity of skeletal muscle-derived H2S. H2S content and production in tissues were detected by sensitive sulfur electrode method. The expressions of H2S producing enzymes cystathionine β-synthase, cystathionine γ-lyase and mercaptopyruvate sulfurtransferase were detected by real-time PCR and western blotting and their tissue distributions were observed by immunohistochemical and immunofluorescent analysis. Rat skeletal muscular ischemia-reperfusion (I-R) injury model was created and evaluated by histological analysis under microscope. The malondialdehyde (MDA) contents, hydrogen peroxide levels, superoxide anion and superoxide dismutase (SOD) activities were detected using spectrophotometer. H2S could be endogenously generated and released by skeletal muscle of Sprague-Dawley rats (H2S content: (2.06 ± 0.43) nmol/mg; H2S production: (0.17 ± 0.06) nmol×min(-1)×mg(-1)). Gene and protein expressions of the three H2S producing enzymes were detected in skeletal muscle, as well as the liver and kidney. Endogenous H2S content and production were decreased in skeletal muscles of rats with I-R skeletal muscle injury (P < 0.05). Furthermore, H2S significantly protected rat skeletal muscle against I-R injury and resulted in decreased MDA content, reduced hydrogen peroxide and superoxide anion levels, but increased SOD activity and protein expression in skeletal muscles (all P < 0.01). H2S generation pathway exists in rat skeletal muscle and it acts as an antioxidant in skeletal muscle.


Simulated sunlight photocatalytic degradation of aqueous p-nitrophenol and bisphenol A in a Pt/BiOBr film-coated quartz fiber photoreactor.
Pt/BiOBr film-coated quartz fiber bundles were prepared by dip-coating combined with photodeposition, and their phase and chemical structures, electronic and optical properties, textural properties as well as morphologies were well-characterized. The simulated sunlight photocatalytic performance including activity and stability of the as-prepared Pt/BiOBr film was evaluated in a self-made quartz fiber photoreactor by selecting two typical light-insensitive organic pollutants, p-nitrophenol (PNP) and bisphenol A (BPA), as the target compounds. Since the quartz fiber bundles served as both the support for Pt/BiOBr films and the medium of light propagation, Pt/BiOBr film-coated quartz fiber bundles exhibited excellent photocatalytic activity due to their enhanced light harvesting ability. In addition, the enhanced photocatalytic activity of the Pt/BiOBr film is explained based on the results of photoelectrochemistry and free radical and hole scavenging experiments.


Impact of early-season thrips management on reducing the risks of spotted wilt virus and suppressing aphid populations in Flue-cured tobacco.
The influence of tray drench (TD) treatments, with and without foliar applications of the plant activator acibenzolar-S-methyl (Actigard), was examined in replicated field plots in 2000--2002. TD treatments of Actigard, imidacloprid (Admire), and these two products combined had little effect on seasonal mean thrips populations; however, thrips densities were lower in the Admire-treated plots at 4 and 5 wk after transplanting. Actigard and Admire TD treatments significantly reduced the seasonal incidence of tomato spotted wilt virus (TSWV) symptomatic plants in 2 yr in the study. The combination of both products was better in reducing TSWV than Actigard alone. Three early-season foliar sprays of Actigard had no effect on thrips population densities, but they did reduce TSWV incidence. The tobacco thrips, Frankliniella fusca (Hinds), comprised 92-95% of the thrips complex each year. Other thrips collected on tobacco foliage at very low densities included Haplothrips spp., Chirothrips spp., Limothrips cerealium (Haliday), other Frankliniella spp. and other unidentified species. Using nonstructural TSWV protein enzyme-linked immunosorbent assay, 1.5-2.3% of the F. fusca tested positive for nonstructural TSWV protein. Cured yields were higher in the TD treatments and the Actigard foliar treatments in the years with high TSWV in the untreated plots. The TD treatments and foliar Actigard had little impact on plant height or grade index; however, TD treatments with Admire had low tobacco aphid, Myzus nicotianae Blackman, populations through 10 wk after transplanting. The early-season Actigard and Admire treatment options are management decisions that can effectively reduce the risks of TSWV incidence in flue-cured tobacco.


Towards socially inclusive research: an evaluation of telephone questionnaire administration in a multilingual population.
Missing data may bias the results of clinical trials and other studies. This study describes the response rate, questionnaire responses and financial costs associated with offering participants from a multilingual population the option to complete questionnaires over the telephone. Before and after study of two methods of questionnaire completion. Seven hundred and sixty five pregnant women from 25 general practices in two UK inner city Primary Care Trusts (PCTs) taking part in a cluster randomised controlled trial of offering antenatal sickle cell and thalassaemia screening in primary care. Two hundred and four participants did not speak English. Sixty one women were offered postal questionnaire completion only and 714 women were offered a choice of telephone or postal questionnaire completion. (i) Proportion of completed questionnaires, (ii) attitude and knowledge responses obtained from a questionnaire assessing informed choice. The response rate from women offered postal completion was 26% compared with 67% for women offered a choice of telephone or postal completion (41% difference 95% CI Diff 30 to 52). For non-English speakers offered a choice of completion methods the response rate was 56% compared with 71% for English speakers (95% CI Diff 7 to 23). No difference was found for knowledge by completion method, but telephone completion was associated with more positive attitude classifications than postal completion (87 vs 96%, 95% CI diff 0.006 to 15). Compared with postal administration the additional costs associated with telephone administration were pound3.90 per questionnaire for English speakers and pound71.60 per questionnaire for non English speakers. Studies requiring data to be collected by questionnaire may obtain higher response rates from both English and non-English speakers when a choice of telephone or postal administration (and where necessary, an interpreter)is offered compared to offering postal administration only. This approach will, however, incur additional research costs and uncertainty remains about the equivalence of responses obtained from the two methods.


Assessment of the effects of subthalamic stimulation in Parkinson disease patients by artificial neural network.
This study aims at using a probabilistic neural network (PNN) for discriminating between normal and Parkinson disease (PD) subjects using as input the principal components (PCs) derived from vertical component of the ground reaction force (vGRF). The trained PNN was further used for evaluating the effects of deep brain stimulation of the subthalamic nucleus (STN DBS) on PD, with and without medication. A sample of 45 subjects (30 normal and 15 PD subjects who underwent STN DBS) was evaluated by gait analysis. PD subjects were assessed under four test conditions: without treatment (mof-sof), only with stimulation (mof-son) or medication (mon-sof), and with combined treatments (mon-son). PC analysis was applied on vGRF, where six PC scores were chosen by the broken stick test. Using a bootstrap approach for the PNN model, and the area under the receiver operating characteristic curve (AUC) as performance measurement, the first three and fifth PCs were selected as input variables. The PNN presented AUC = 0.995 for classifying controls and PD subjects in the mof-sof condition. When applied to classify the PD subjects under treatment, the PNN indicated that STN DBS alone is more effective than medication, and further vGRF enhancement is obtained with combined therapies.


Health technology assessment in Australia: the role of AHTAC. Australian Health Technology Advisory Committee.
This paper outlines and discusses the field of medical technology assessment and the role of the Australian Health Technology Advisory Committee (AHTAC) in that process. Developments in medical technologies have altered the way in which health care is practised and delivered. The policy task is a complex one; attempting to balance the need for cost containment whilst at the same time ensuring that the processes of innovation into Australia, and diffusion occur in a manner which maximises the benefit and minimises any harm to the Australian community.


Spatial variations in the associations of term birth weight with ambient air pollution in Georgia, USA.
Birth weight is an important indicator of overall infant health and a strong predictor of infant morbidity and mortality, and low birth weight (LBW) is a leading cause of infant mortality in the United States. Numerous studies have examined the associations of birth weight with ambient air pollution, but the results were inconsistent. In this study, a spatial statistical technique, geographically weighted regression (GWR) is applied to explore the spatial variations in the associations of birth weight with concentrations of ozone (O3) and fine particulate matter (PM2.5) in the State of Georgia, USA adjusted for gestational age, parity, and six other socioeconomic, behavioral, and land use factors. The results show considerable spatial variations in the associations of birth weight with both pollutants. Significant positive, non-significant, and significant negative relationships between birth weight and concentrations of each air pollutant are all found in different parts of the study area, and the different types of the relationships are affected by the socioeconomic and urban characteristics of the communities where the births are located. The significant negative relationships between birth weight and O3 indicate that O3 is a significant risk factor of LBW and these associations are primarily located in less-urbanized communities. On the other hand, PM2.5 is a significant risk factor of LBW in the more-urbanized communities with higher family income and education attainment. These findings suggest that environmental and health policies should be adjusted to address the different effects of air pollutants on birth outcomes across different types of communities to more effectively and efficiently improve birth outcomes.


Declining coral skeletal extension for forereef colonies of Siderastrea siderea on the Mesoamerican Barrier Reef System, Southern Belize.
Natural and anthropogenic stressors are predicted to have increasingly negative impacts on coral reefs. Understanding how these environmental stressors have impacted coral skeletal growth should improve our ability to predict how they may affect coral reefs in the future. We investigated century-scale variations in skeletal extension for the slow-growing massive scleractinian coral Siderastrea siderea inhabiting the forereef, backreef, and nearshore reefs of the Mesoamerican Barrier Reef System (MBRS) in the western Caribbean Sea. Thirteen S. siderea cores were extracted, slabbed, and X-rayed. Annual skeletal extension was estimated from adjacent low- and high-density growth bands. Since the early 1900s, forereef S. siderea colonies have shifted from exhibiting the fastest to the slowest average annual skeletal extension, while values for backreef and nearshore colonies have remained relatively constant. The rates of change in annual skeletal extension were -0.020±0.005, 0.011±0.006, and -0.008±0.006 mm yr⁻¹ per year [mean±SE] for forereef, backreef, and nearshore colonies respectively. These values for forereef and nearshore S. siderea were significantly lower by 0.031±0.008 and by 0.019±0.009 mm yr⁻¹ per year, respectively, than for backreef colonies. However, only forereef S. siderea exhibited a statistically significant decline in annual skeletal extension over the last century. Our results suggest that forereef S. siderea colonies are more susceptible to environmental stress than backreef and nearshore counterparts, which may have historically been exposed to higher natural baseline stressors. Alternatively, sediment plumes, nutrients, and pollution originating from watersheds of Guatemala and Honduras may disproportionately impact the forereef environment of the MBRS. We are presently reconstructing the history of environmental stressors that have impacted the MBRS to constrain the cause(s) of the observed reductions in coral skeletal growth. This should improve our ability to predict and potentially mitigate the effects of future environmental stressors on coral reef ecosystems.


Suramin, an antiparasitic drug, stimulates adipocyte differentiation and promotes adipogenesis.
Previous studies demonstrated that mast cells with their degranulated component heparin are the major endogenous factors that stimulate preadipocyte differentiation and promote fascial adipogenesis, and this effect is related to the structure of heparin. Regarding the structural and physiological properties of the negatively charged polymers, hexasulfonated suramin, a centuries-old medicine that is still used for treating African trypanosomiasis and onchocerciasis, is assumed to be a heparin-related analog or heparinoid. This investigation aims to elucidate the influence of suramin on the adipogenesis. To assess the influence exerted by suramin on adipogenic differentiation of primary white adipocytes in rats, this exploration was conducted both in vitro and in vivo. Moreover, it was attempted to explore the role played by the sulfonic acid groups present in suramin in mediating this adipogenic process. Suramin demonstrated a dose- and time-dependent propensity to stimulate the adipogenic differentiation of rat preadipocytes isolated from the superficial fascia tissue and from adult adipose tissue. This stimulation was concomitant with a notable upregulation in expression levels of pivotal adipogenic factors as the adipocyte differentiation process unfolded. Intraperitoneal injection of suramin into rats slightly increased adipogenesis in the superficial fascia and in the epididymal and inguinal fat depots. PPADS, NF023, and NF449 are suramin analogs respectively containing 2, 6, and 8 sulfonic acid groups, among which the last two moderately promoted lipid droplet formation and adipocyte differentiation. The number and position of sulfonate groups may be related to the adipogenic effect of suramin. Suramin emerges as a noteworthy pharmaceutical agent with the unique capability to significantly induce adipocyte differentiation, thereby fostering adipogenesis.


A new role of vemurafenib as a neoadjuvant treatment of axillary and brain melanoma metastases.
Vemurafenib is approved by the FDA for the management of unresectable or metastatic melanoma. However, its role as a neoadjuvant therapy has not been determined. We present the first documented case in which vemurafenib induced complete tumor necrosis of both lymph node and brain metastases within one month or less, an outcome that indicated that the patient was a good candidate for excisional surgery.


Cellular stress amplifies TLR3/4-induced CXCL1/2 gene transcription in mononuclear phagocytes via RIPK1.
The impact of environmental stressors on the magnitude of specific chemokine gene expression was examined in mouse bone marrow-derived macrophages stimulated through various TLRs. Levels of TLR-stimulated CXCL1 and CXCL2 but not CXCL10 or CCL5 mRNAs were selectively enhanced (>10-fold) in stressed macrophages. The amplification was also manifested for other proinflammatory cytokines, including TNF-α, IL-1α, and IL-6. Responses through TLR3 and TLR4 exhibited the greatest sensitivity, reflecting a requirement for Toll/IL-IR domain-containing adaptor-inducing IFN-β (TRIF), the adaptor protein selectively associated with these TLRs. IFN regulatory factor 3, a transcription factor that is downstream of TLR4/TRIF signaling, was not required for sensitivity to stress-induced chemokine amplification. c/EBP homologous protein and X box binding protein 1 have been reported to enhance inflammatory cytokine responses but are not required for amplification of TLR3/4-induced CXCL1 expression. Rather, receptor-interacting protein kinase 1, a kinase also linked with TLR3/4/TRIF signaling, is required and involves a stress-dependent increase in its abundance and ubiquitination. Whereas NF-κB activation is necessary for TLR-induced chemokine gene transcription, this factor does not appear to be the primary mechanistic target of environmental stress. The application of stress also enhanced chemokine expression in macrophages infiltrating the peritoneal cavity but was not observed in the resident peritoneal cells or in the liver. These findings identify novel mechanisms for modulating the magnitude and duration of selective TLR-induced chemokine and cytokine gene expression and further establish the importance of cell stress pathways in coordinating the outcomes of cellular and tissue injury.


Vagal Tone and Children's Delay of Gratification: Differential Sensitivity in Resource-Poor and Resource-Rich Environments.
Children from different socioeconomic backgrounds have differing abilities to delay gratification, and impoverished children have the greatest difficulties in doing so. In the present study, we examined the role of vagal tone in predicting the ability to delay gratification in both resource-rich and resource-poor environments. We derived hypotheses from evolutionary models of children's conditional adaptation to proximal rearing contexts. In Study 1, we tested whether elevated vagal tone was associated with shorter delay of gratification in impoverished children. In Study 2, we compared the relative role of vagal tone across two groups of children, one that had experienced greater impoverishment and one that was relatively middle-class. Results indicated that in resource-rich environments, higher vagal tone was associated with longer delay of gratification. In contrast, high vagal tone in children living in resource-poor environments was associated with reduced delay of gratification. We interpret the results with an eye to evolutionary-developmental models of the function of children's stress-response system and adaptive behavior across varying contexts of economic risk.


When your heart wants to remember: person centred dementia care.
The traditional approach to dementia care was essentially based around the view that so long as people with dementia were kept 'fed', clean and dry, that was all they needed. This minimalistic approach to care arose, not because of any intention to harm or to deprive people from care, but because of established knowledge, values and beliefs about dementia that have developed in UK society over the past 100 years (Harding and Palfrey 1997). This learning unit aims to enable nurses to develop a better understanding of person centred dementia care so that they might reflect more critically on their working with, and promote wellbeing for, people with dementia. It is necessary to watch the entire video before starting work on this Nursing Update workbook.


Amplified fragment length polymorphism (AFLP) versus randomly amplified polymorphic DNA (RAPD) as new tools for inter- and intra-species differentiation within Bordetella.
Automated amplified fragment length polymorphism (AFLP) and randomly amplified polymorphic DNA (RAPD) techniques with fluorescently labelled primers were used to track differences among isolates of the eight known species of the Bordetella genus. Eighty-one representative strains of these species from international and Polish bacterial collections were genotyped according to RAPD protocols using primer 1254 or 1247, and AFLP involving EcoRI/MseI or newly designed SpeI/ApaI restriction/ligation/amplification procedures. By comparing AFLP and RAPD data, it was concluded that the discriminatory power of AFLP is higher in comparison with RAPD for both intra- and inter-species differentiation of isolates of the Bordetella genus. The most precise level of inter-species discrimination and the highest level of intra-species discrimination of the Bordetella isolates of the eight species were observed in the AFLP EcoRI/MseI and SpeI/ApaI sets, respectively. Both techniques might provide alternative tools for the identification of Bordetella at the genomic species and strain levels, and thus may be valuable in human and veterinary diagnostics as well as in epidemiology. By applying the AFLP technique presented in this article, more precise data on the emergence of newly acquired and/or on expanded clones and transmission routes of isolates of the Bordetella genus in the human and animal environments might be obtained.


Modeling Dravet syndrome using induced pluripotent stem cells (iPSCs) and directly converted neurons.
Severe myoclonic epilepsy of infancy (SMEI, also known as Dravet syndrome) and genetic epilepsy with febrile seizures plus (mild febrile seizures) can both arise due to mutations of SCN1A, the gene encoding alpha 1 pore-forming subunit of the Nav1.1 voltage-gated sodium channel. Owing to the inaccessibility of patient brain neurons, the precise mechanism of mild febrile seizures and SMEI remains elusive, and there is no effective pharmacotherapy. Induced pluripotent stem cells (iPSCs) and induced neurons (iNs) have been successfully generated from patients and applied for modeling various neuronal diseases. In this study, we established iPSC lines from one SMEI patient and one mild febrile seizures patient, respectively. Functional glutamatergic neurons were subsequently differentiated from these iPSCs. Electrophysiological analysis of patient iPSC-derived glutamatergic neurons revealed a hyperexcitable state of enlarged and persistent sodium channel activation, more intensive evoked action potentials and typical epileptic spontaneous action potentials. In consistent with the severity of the symptoms, the hyperexcitability of the neurons derived from SMEI patient was more serious than that of mild febrile seizures patient. Furthermore, the hyperexcitability of the neurons can be alleviated by treatment with phenytoin, a conventional antiepileptic drug. In parallel, iNs were directly converted from patient fibroblasts which also showed a delayed inactivation of sodium channels. Our results demonstrate that both iPSC-derived neurons and iNs from mild febrile seizures and SMEI patients exhibited a hyperexcitable state. More importantly, patient iPSC-derived neurons can recapitulate the neuronal pathophysiology and respond to drug treatment, indicating that these neurons can be potentially used for screening appropriate drugs for personalized therapies.


Fertility of women after exposure to internal and external radiation.
Fertility was examined in 199 women exposed to internal and external radiation while employed in the radium watch-dial painting industry in Illinois between 1916 and 1929. In women with at least one live birth, mean log live-birth rate was significantly lower in the highest (estimated) ovarian-dose group (i.e., greater than or equal to 20 rem) than in the lowest group (< 5 rem). In multiple regression analysis, intake dose (proportional to alpha-particle dose to ovaries) but not duration of employment (relevant to external gamma-ray dose to ovaries) was a statistically significant predictor of log live-birth rate. There was no evidence for an increase in fetal deaths with increasing ovarian dose level (rem). This suggests that the findings on live-birth rate may not involve post-implantation dominant lethal mutations, but preimplantation losses could not be evaluated. Some possible explanations for these findings are discussed.


Healthcare-seeking behaviour for common infectious disease-related illnesses in rural Kenya: a community-based house-to-house survey.
Community surveys of healthcare-use determine the proportion of illness episodes not captured by health facility-based surveillance, the methodology used most commonly to estimate the burden of disease in Africa. A cross-sectional survey of households with children aged less than five years was conducted in 35 of 686 census enumeration areas in rural Bondo district, western Kenya. Healthcare sought for acute episodes of diarrhoea or fever in the past two weeks or pneumonia in the past year was evaluated. Factors associated with healthcare-seeking were analyzed by logistic regression accounting for sample design. In total, 6,223 residents of 981 households were interviewed. Of 1,679 children aged less than five years, 233 (14%) had diarrhoea, and 736 (44%) had fever during the past two weeks; care at health facilities was sought for one-third of these episodes. Pneumonia in the past year was reported for 64 (4%) children aged less than five years; 88% sought healthcare at any health facility and 48% at hospitals. Seeking healthcare at health facilities was more likely for children from households with higher socioeconomic status and with more symptoms of severe illness. Health facility and hospital-based surveillance would underestimate the burden of disease substantially in rural western Kenya. Seeking healthcare at health facilities and hospitals varied by syndrome, severity of illness, and characteristics of the patient.


Endothelium-dependent induction of vasorelaxation by Melissa officinalis L. ssp. officinalis in rat isolated thoracic aorta.
In the current study, vasorelaxant effect produced by the aqueous extract of Melissa officinalis L. ssp. officinalis (MOO) (Lamiaceae) and its possible mechanism in isolated rat aortic rings precontracted with phenylephrine were examined. In the first series of experiments, effect of MOO on the baseline and phenylephrine (10(-5)M) precontracted arteries was investigated, while in the second group of experiments, endothelium intact or endothelium denuded effect was determined. The agents used were N(omega)-nitro-L-arginine (L-NAME), an irreversible inhibitor of nitric oxide (NO) synthase, indomethacin (10 microM), a cyclooxygenase (COX) inhibitor, and glibenclamide (10 microM), an ATP-sensitive potassium channel blocker. The extract was found to exert a vasorelaxant effect and rosmarinic acid quantity, the characteristic compound of the plant, was analyzed by reversed-phase high-performance liquid chromatography (18.75%), and was further confirmed by LC-MS analysis giving a prominent [M(+1)] molecular ion peak at m/z 365. Total phenol amount in the extract was determined using Folin-Ciocalteau reagent (0.284 mg/mg extract). Vasorelaxant effect of the extract was entirely dependent on the presence of endothelium and was abolished by pretreatment with L-NAME, whereas pretreatment with indomethacin and glibenclamide reduced the relaxation to a minor extent. Rosmarinic acid was also tested in the same manner as the extract and was found to exert vasorelaxant effect. These results suggest that the aqueous extract of MOO vasodilates via nitric oxide pathway with the possible involvement of prostacycline and endothelium-derived hyperpolarizing factor (EDHF) pathways as well.


[Effect of the exogenous tryptophan on biosynthesis of ergot alkaloids in Penicillium sizovae].
Various concentrations of exogenous L and D-tryptophan as well as of their analogue D,L-6-methyltryptophan were added to the growth medium of Penicillium sizovae during its inoculation and after the active growth of the fungus was over. The authors studied the effect of these compounds on the accumulation of exocellular alkaloids and biomass as well as on the synthesis of proteins, the content of free tryptophan in the cells, and the activity of tryptophan synthetase. As was shown in experiments using labeled tryptophan, this amino acid is a direct precursor of alkaloids in the culture.


Posterior dislocation of the elbow with fractures of the radial head and coronoid.
Posterior dislocation of the elbow with associated fractures of the radial head and the coronoid process of the ulna has been referred to as the "terrible triad of the elbow" because of the difficulties encountered in its management. However, there are few published reports on this injury. Eleven patients with this pattern of injury were evaluated after a minimum of two years. The radial head fracture had been repaired in five patients, and the radial head had been resected in four. None of the coronoid fractures had been repaired, and the lateral collateral ligament had been repaired in only three patients. All eleven patients returned for clinical examination, functional evaluation, and radiographs. Seven elbows redislocated in a splint after manipulative reduction. Five, including all four treated with resection of the radial head, redislocated after operative treatment. At the time of final follow-up, three patients were considered to have a failure of the initial treatment. One of them had recurrent instability, which was treated with a total elbow arthroplasty after multiple unsuccessful operations; one had severe arthrosis and instability resembling neuropathic arthropathy; and one had an elbow flexion contracture and proximal radioulnar synostosis requiring reconstructive surgery. The remaining eight patients, who were evaluated at an average of seven years after injury, had an average of 92 degrees (range, 40 degrees to 130 degrees ) of ulnohumeral motion and 126 degrees (range, 40 degrees to 170 degrees ) of forearm rotation. The average Broberg and Morrey functional score was 76 points (range, 34 to 98 points), with two results rated as excellent, two rated as good, three rated as fair, and one rated as poor. Overall, the result of treatment was rated as unsatisfactory for seven of the eleven patients. All four patients with a satisfactory result had retained the radial head, and two had undergone repair of the lateral collateral ligament. Seven of the ten patients who had retained the native elbow had radiographic signs of advanced ulnohumeral arthrosis. Elbow fracture-dislocations that involve a fracture of the coronoid process in addition to a fracture of the radial head are very unstable and prone to numerous complications. Identification of the coronoid fracture is therefore important, and computed tomography should be used if there is uncertainty. With operative treatment, the surgeon should attempt to restore stability by providing radiocapitellar contact (preserving the radial head when possible and replacing it with a prosthesis otherwise), repairing the lateral collateral ligament, and perhaps performing internal fixation of the coronoid fracture.


Herpes simplex virus-2 glycoprotein interaction with HVEM influences virus-specific recall cellular responses at the mucosa.
Infection of susceptible cells by herpes simplex virus (HSV) requires the interaction of the HSV gD glycoprotein with one of two principal entry receptors, herpes virus entry mediator (HVEM) or nectins. HVEM naturally functions in immune signaling, and the gD-HVEM interaction alters innate signaling early after mucosal infection. We investigated whether the gD-HVEM interaction during priming changes lymphocyte recall responses in the murine intravaginal model. Mice were primed with attenuated HSV-2 expressing wild-type gD or mutant gD unable to engage HVEM and challenged 32 days later with virulent HSV-2 expressing wild-type gD. HSV-specific CD8(+) T cells were decreased at the genital mucosa during the recall response after priming with virus unable to engage HVEM but did not differ in draining lymph nodes. CD4(+) T cells, which are critical for entry of HSV-specific CD8(+) T cells into mucosa in acute infection, did not differ between the two groups in either tissue. An inverse association between Foxp3(+) CD4(+) regulatory T cells and CD8(+) infiltration into the mucosa was not statistically significant. CXCR3 surface expression was not significantly different among different lymphocyte subsets. We conclude that engagement of HVEM during the acute phase of HSV infection influences the antiviral CD8(+) recall response by an unexplained mechanism.


The underlying mechanism of metabolic syndrome on benign prostatic hyperplasia and prostate volume.
To investigate the potential mechanism of the effect of metabolic syndrome (MetS) on prostate volume (PV) and the risk of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and the relationships of MetS and the major pathogenic factors of MetS with the clinical progression of BPH/LUTS in older Chinese men. We analyzed clinical data obtained from 506 ostensibly healthy men who underwent routine health check-ups and recruited 415 subjects from a group of previously studied men after 4 years. We evaluated the associations of major pathological factors of MetS, including insulin resistance, subclinical inflammatory state, and sex hormone changes, with PV, the risk of BPH and the clinical progression of BPH/LUTS by using multiple linear regression and logistic regression. After adjustment for age, insulin, HOMA (homeostatic model assessment) index, leptin, resistin, adiponectin, C-reactive protein, tumor necrosis factor-α (TNF-α), sex hormone-binding globulin, and testosterone levels were significantly associated with PV (all P < .05), and in the age-adjusted logistic regression model, positive associations of resistin and TNF-α with BPH/LUTS were found (OR, 1.662, P = .007 and OR, 1.044, P < .001, respectively). Predictors of BPH/LUTS clinical progression were significantly correlated with MetS and TNF-α. The group with higher TNF-α levels had a higher rate of newly diagnosed BPH (9.5% vs 19.1%, P = .006) and a greater increase in PV levels (0.61 ± 0.08 vs 1.09 ± 0.35 cm3 , P <.001) after 4 years. MetS and its pathological factors were associated with an increased PV and an increased risk of BPH/LUTS that is more prone to clinical progression. TNF-α may serve as an early biological indicator to identify which patients with BPH/LUTS are at higher risk of unfavorable outcomes.


Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine.
Using tissue-engineering techniques, we have developed a neointestine that regenerates the structural and dynamic features of native small intestine. In this study, we tested neointestinal responsiveness to glucagon-like peptide 2 (GLP-2). Neointestinal cysts were engineered by seeding biodegradable polymers with neonatal rat intestinal organoid units. The cysts were matured and anastomosed to the native jejunum of syngeneic adult recipients. Animals were treated with GLP-2 [Gly2] (twice daily, 1 microg/g body wt) or vehicle alone (control) for 10 days. Rats were then killed, and tissues were harvested for analysis. Na+-glucose cotransporter (SGLT1) mRNA expression was assessed with Northern blotting and in situ hybridization. SGLT1 protein was localized by using immunofluorescence. GLP-2 administration resulted in 1.8- and 1.7-fold increases (P < 0.05) in neointestinal villus height and crypt depth, respectively. GLP-2 administration also resulted in a 2.4-fold increase (P < 0.01) in neomucosal SGLT1 mRNA expression. SGLT1 mRNA expression was localized to enterocytes throughout the villi, and SGLT1 protein was localized to the brush border of enterocytes along the entire length of villi from the neointestine of GLP-2-treated animals. The response of tissue-engineered neointestine to exogenous GLP-2 includes mucosal growth and enhanced SGLT1 expression. Therefore, tissue-engineering principles may help in dissecting the regulatory mechanisms mediating complex processes in the intestinal epithelium.


Mechanisms of salinity tolerance.
The physiological and molecular mechanisms of tolerance to osmotic and ionic components of salinity stress are reviewed at the cellular, organ, and whole-plant level. Plant growth responds to salinity in two phases: a rapid, osmotic phase that inhibits growth of young leaves, and a slower, ionic phase that accelerates senescence of mature leaves. Plant adaptations to salinity are of three distinct types: osmotic stress tolerance, Na(+) or Cl() exclusion, and the tolerance of tissue to accumulated Na(+) or Cl(). Our understanding of the role of the HKT gene family in Na(+) exclusion from leaves is increasing, as is the understanding of the molecular bases for many other transport processes at the cellular level. However, we have a limited molecular understanding of the overall control of Na(+) accumulation and of osmotic stress tolerance at the whole-plant level. Molecular genetics and functional genomics provide a new opportunity to synthesize molecular and physiological knowledge to improve the salinity tolerance of plants relevant to food production and environmental sustainability.


The endothelial surface and responses to injury.
Pulmonary microvascular endothelial cells are known to play an active role in the events that lead to vascular damage in the inflammatory response. The endothelial surface, normally immunologically privileged and very actively antithrombogenic, can respond to certain stimuli, generally injurious, by becoming strongly procoagulant and by expressing Fc and C3b receptors. Like macrophages, activated endothelial cells can provide a common source and substratum for combined hemostatic and complement-linked reactions. Such transformations of endothelial functions may involve alterations in the endothelial glycocalyx and, in addition, may be important for the entrapment and disposal of phagocytosed particulates. What is clear is that it is not simply absence of endothelium that has a bearing on the outcome of inflammatory stimuli but that structural and functional responses of the endothelial surface to injury, resulting in altered expression of hemostatic and immunologic potential, may have an important bearing on the role of the endothelium in the regulation of microvascular permeability.


Effect of Fragment 1 on the Binding of Epigallocatechin Gallate to the PD-L1 Dimer Explored by Molecular Dynamics.
Blocking the interaction between programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) by directly targeting the PD-L1 dimer has emerged as a hot topic in the field of cancer immunotherapy. Epigallocatechin gallate (EGCG), a natural product, has been demonstrated binding to the PD-L1 dimer in our previous study, but has a weaker binding capacity, moreover, EGCG is located at the end of the binding pocket of the PD-L1 dimer. The inhibitor fragment 1 (FRA) lies at the other end. So, we proposed that the introduction of FRA might be able to improve the binding ability. To illuminate this issue, molecular dynamics (MD) simulation was performed in the present study. Binding free energy calculations show that the binding affinity is significantly increased by 17 kcal/mol upon the introduction of FRA. It may be due to the energy contributions of emerging key residues ATyr56, AMet115, BTyr123, AIle54 and the enhanced contributions of initial key residues ATyr123 and BVal68. Binding mode and non-bonded interaction results indicate that FRA_EGCG (EGCG in combination with FRA) binds to the C-, F- and G-sheet of the PD-L1 dimer. Importantly, the introduction of FRA mainly strengthened the nonpolar interactions. The free energy landscape and secondary structure results further show that FRA_EGCG can interact with the PD-L1 dimer more stably. These data demonstrated here provide the theoretical basis for screening two or more natural products with additive inhibitory effect on this pathway and therefore exerting more effective anticancer immunity.


Associated factors for falls among the community-dwelling older people assessed by annual geriatric health examinations.
Falls are very common among the older people. Nearly one-third older people living in a community fall each year. However, few studies have examined factors associated with falls in a community-dwelling population of older Taiwanese adults. To identify the associated factors for falls during the previous 12 months among the community-dwelling Taiwanese older people receiving annual geriatric health examinations. People aged sixty-five years or older, living in the community, assessed by annual geriatric health examinations 1377 community-dwellers aged ≥65 years who received annual geriatric health examinations at one hospital in northern Taiwan between March and November of 2008. They were asked about their history of falls during the year prior to their most recent health examination. The average age of the 1377 participants was 74.9±6.8 years, 48.9% of which were women. Three-hundred and thirteen of the participants (22.7%) had at least one fall during the previous year. Multivariate analysis showed that odds ratio for the risk of falling was 1.94 (95% CI 1.36-2.76) when the female gender group is compared with the male gender group. The adjusted odds ratios of age and waist circumference were 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 1.01-1.05) respectively. The adjusted odds ratios of visual acuity, Karnofsky scale, and serum albumin level were 0.34 (95% CI 0.15-0.76), 0.94 (95% CI 0.89-0.98), and 0.37 (95% CI 0.18-0.76) respectively. Larger waist circumference, older age, female gender, poorer visual acuity, lower score on the Karnofsky Performance Scale, and lower serum albumin level were the independent associated factors for falls. In addition to other associated factors, waist circumference should be included as a novel risk factor for falls.


Timing of onset of contraceptive effectiveness in Norplant implant users. Part I. Changes in cervical mucus.
To provide scientific data regarding the changes in cervical mucus within the first hours to days after Norplant implant insertion and to estimate when the cervical mucus is hostile enough to suggest a contraceptive effect. Multicenter, clinical descriptive study. Family planning clinics. Forty-two women who were between days 8 and 13 of their menstrual cycle and who had requested Norplant implants were admitted to the study. Cervical mucus and blood samples were obtained. Cervical mucus scores, sperm penetration distances, and serum levels of progesterone, estradiol, and levonorgestrel. The median cervical mucus score observed at baseline was 6 ("fair"), indicating that the mucus was already somewhat hostile before insertion of the Norplant implants. The median scores declined to 5 at 12 and 24 hours and continued to decrease through day 7 to 2 ("poor"), a score that is judged as hostile to sperm penetration. Overall, 73% of all subjects had a poor cervical mucus score by 3 days after insertion; at 7 days after insertion, 90% exhibited poor mucus and none had a good score. There was a substantial drop in the overall median distance traveled by the vanguard sperm after 12 hours for each cervical mucus score grouping. The distance traveled decreased rapidly between 12 and 24 hours to < 0.5 cm in subjects with fair and poor mucus, and by day 3, 91% of the subjects exhibited poor sperm penetration. On the basis of our findings, deterioration of the quality of the cervical mucus and sperm penetration is evident by 24 hours after insertion, although not to a level that would suggest adequate protection until 72 hours after insertion. Therefore, we are confident in recommending that backup methods of contraception (e.g, condoms) need not be used for more than 3 days after insertion, even when the implants are inserted close to ovulation. These findings provide policy makers, clinic managers, and clinicians with important information about how they can improve client access to Norplant implants.


PDI-Based Organic Small Molecule Regulated by Inter/Intramolecular Interactions for Efficient Solar Vapor Generation.
Organic small molecules with processing feasibility, structural diversity, and fine-tuned properties have the potential applications in solar vapor generation. However, the common defects of narrow solar absorption, low photothermal conversion efficiency, and photobleaching result in limited materials available and unsatisfactory evaporation performance. Herein, the perylene diimide (PDI) derivatives are exploited as stable sunlight absorbers for solar vapor generation. Particularly, the N,N'-bis(3,4,5-trimethoxyphenyl)-3,4,9,10-perylenetetracarboxylic diimide (PDI-DTMA) is well-designed with donor-acceptor-donor configuration based on plane rigid PDI core. The efficient photothermal conversion is enabled through strong intermolecular π-π stacking and intramolecular charge transfer, as revealed by experimental demonstration and theoretical calculation. The PDI-DTMA with a narrow band gap of 1.17 eV exhibits expanded absorption spectrum and enhanced nonradiative transition capability. The 3D hybrid hydrogels (PPHs) combining PDI-DTMA and polyvinyl alcohol are constructed. With the synergistic effect of solar-to-heat conversion, thermal localization management, water activation, and unobstructed water transmission of PPHs, the high water evaporation rates can reach 3.61-10.07 kg m-2 h-1 under one sun. The hydrogels also possess great potential in seawater desalination and sewage treatment. Overall, this work provides valuable insights into the design of photothermal organic small molecules and demonstrates their potentials in solar water evaporation.


Population-genomic variation within RNA viruses of the Western honey bee, Apis mellifera, inferred from deep sequencing.
Deep sequencing of viruses isolated from infected hosts is an efficient way to measure population-genetic variation and can reveal patterns of dispersal and natural selection. In this study, we mined existing Illumina sequence reads to investigate single-nucleotide polymorphisms (SNPs) within two RNA viruses of the Western honey bee (Apis mellifera), deformed wing virus (DWV) and Israel acute paralysis virus (IAPV). All viral RNA was extracted from North American samples of honey bees or, in one case, the ectoparasitic mite Varroa destructor. Coverage depth was generally lower for IAPV than DWV, and marked gaps in coverage occurred in several narrow regions (< 50 bp) of IAPV. These coverage gaps occurred across sequencing runs and were virtually unchanged when reads were re-mapped with greater permissiveness (up to 8% divergence), suggesting a recurrent sequencing artifact rather than strain divergence. Consensus sequences of DWV for each sample showed little phylogenetic divergence, low nucleotide diversity, and strongly negative values of Fu and Li's D statistic, suggesting a recent population bottleneck and/or purifying selection. The Kakugo strain of DWV fell outside of all other DWV sequences at 100% bootstrap support. IAPV consensus sequences supported the existence of multiple clades as had been previously reported, and Fu and Li's D was closer to neutral expectation overall, although a sliding-window analysis identified a significantly positive D within the protease region, suggesting selection maintains diversity in that region. Within-sample mean diversity was comparable between the two viruses on average, although for both viruses there was substantial variation among samples in mean diversity at third codon positions and in the number of high-diversity sites. FST values were bimodal for DWV, likely reflecting neutral divergence in two low-diversity populations, whereas IAPV had several sites that were strong outliers with very low FST. This initial survey of genetic variation within honey bee RNA viruses suggests future directions for studies examining the underlying causes of population-genetic structure in these economically important pathogens.


S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis via NLRP3/IL-1β.
Metastasis is the primary cause of cancer death. The inflammatory tumor microenvironment contributes to metastasis, for instance, by recruiting blood and lymph vessels. Among tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) take a center stage in promoting both tumor angiogenesis and metastatic spread. We found that genetic deletion of the S1P receptor 1 (S1pr1) alone in CD11bhi CD206+ TAMs infiltrating mouse breast tumors prevents pulmonary metastasis and tumor lymphangiogenesis. Reduced lymphangiogenesis was also observed in the nonrelated methylcholanthrene-induced fibrosarcoma model. Transcriptome analysis of isolated TAMs from both entities revealed reduced expression of the inflammasome component Nlrp3 in S1PR1-deficient TAMs. Macrophage-dependent lymphangiogenesis in vitro was triggered upon inflammasome activation and required both S1PR1 signaling and IL-1β production. Finally, NLRP3 expression in tumor-infiltrating macrophages correlated with survival, lymph node invasion, and metastasis of mammary carcinoma patients. Conceptually, our study indicates an unappreciated role of the NLRP3 inflammasome in promoting metastasis via the lymphatics downstream of S1PR1 signaling in macrophages.