Ocean cleaning stations under a changing climate: biological responses of tropical and temperate fish-cleaner shrimp to global warming.
Cleaning symbioses play an important role in the health of certain coastal marine communities. These interspecific associations often occur at specific sites (cleaning stations) where a cleaner organism (commonly a fish or shrimp) removes ectoparasites/damaged tissue from a 'client' (a larger cooperating fish). At present, the potential impact of climate change on the fitness of cleaner organisms remains unknown. This study investigated the physiological and biochemical responses of tropical (Lysmata amboinensis) and temperate (L. seticaudata) cleaner shrimp to global warming. Specifically, thermal limits (CTMax), metabolic rates, thermal sensitivity, heat shock response (HSR), lipid peroxidation [malondialdehyde (MDA) concentration], lactate levels, antioxidant (GST, SOD and catalase) and digestive enzyme activities (trypsin and alkaline phosphatase) at current and warming (+3 °C) temperature conditions. In contrast to the temperate species, CTMax values decreased significantly from current (24-27 °C) to warming temperature conditions (30 °C) for the tropical shrimp, where metabolic thermal sensitivity was affected and the HSR was significantly reduced. MDA levels in tropical shrimp increased dramatically, indicating extreme cellular lipid peroxidation, which was not observed in the temperate shrimp. Lactate levels, GST and SOD activities were significantly enhanced within the muscle tissue of the tropical species. Digestive enzyme activities in the hepatopancreas of both species were significantly decreased by warmer temperatures. Our data suggest that the tropical cleaner shrimp will be more vulnerable to global warming than the temperate Lysmata seticaudata; the latter evolved in a relatively unstable environment with seasonal thermal variations that may have conferred greater adaptive plasticity. Thus, tropical cleaning symbioses may be challenged at a greater degree by warming-related anthropogenic forcing, with potential cascading effects on the health and structuring of tropical coastal communities (e.g. coral reefs).


Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy and autonomic dysfunction.
Sudomotor dysfunction may be an early detectable abnormality in diabetic small fiber neuropathy. The aim of this study was to evaluate the efficacy of Sudoscan™ (Impeto Medical, Paris, France) in detecting diabetic neuropathy (DN), in comparison with other standardized tests, in patients with diabetes mellitus (DM). Sudoscan measures electrochemical skin conductance (ESC) of hands and feet through reverse iontophoresis. We evaluated 83 DM patients with and without DN and 210 healthy controls (HCs). Neuropathy Impairment Score-Lower Legs (NIS-LL), quantitative autonomic function testing (QAFT), and quantitative sensory testing (QST) were performed. Symptomatic pain was recorded using a visual analog scale. Receiver-operator characteristic (ROC) curves were calculated to evaluate the efficacy of Sudoscan in detecting DN compared with traditional modalities. Diabetes patients with DN had significantly worse ESCs of feet and hands than DM patients without DN and HCs (respectively, 56.3±3 vs. 75.9±5.5 and 84.4±0.9 [P<0.0001] for feet and 51.9±2.4 vs. 67.5±4.3 and 73.1±0.8 [P<0.0001] for hands). Increasing NIS-LL scores were associated with decreasing ESC values. ESCs correlated significantly with clinical (NIS-LL), somatic (QST), and autonomic (QAFT) measures of neuropathy and with pain scores. ROC curve analysis showed significant results for both hands and feet ESC (area under the curve of 0.86 and 0.88, respectively; P<0.0001) with sensitivity of 78% and specificity of 92% for feet to detect DN. Sudoscan is a promising, sensitive tool to detect neuropathy in patients with DM. This is a very simple, easy-to-perform test that can be done in the clinical setting in 3-5 min.


Enforcement of tobacco purchase, use, and possession laws in four Kentucky communities.
This case study examined the implementation and enforcement of the purchase, use, and possession (PUP) laws for tobacco in four Kentucky communities. Purposive and snowball sampling were used to identify 44 adult key informants. Qualitative, semistructured phone interviews assessed knowledge about PUP laws, enforcement, effects of the laws on teen tobacco use, and perceptions about the laws. Seven themes were identified: enforcement not a priority, unaware of enforcement authority, spotty enforcement, other sources of tobacco, minimum penalties, confusion about compliance checks, and schools as de facto enforcers. One community went beyond the statutory requirements of the law and created more stringent penalties for violating the use and possession law, and it also had low illegal sales rates. These laws may be more effective if they are enforced strictly with a meaningful penalty and a clear enforcement strategy.


Splenectomy attenuates intestinal ischemia-reperfusion-induced acute lung injury.
Intestinal ischemia-reperfusion (IIR) induced acute lung injury (ALI) has been documented. Kupffer cell blockage with gadolinium chloride (GdCl(3)) has been shown to attenuate IIR-induced ALI. However, the effects of splenic monocytes/macrophages on IIR-induced ALI has not been studied previously. In the current study, the authors aimed to investigate the role of splenectomy in IIR-induced ALI. Forty-eight rats were divided randomly into 6 groups as follows: SHAM, SHAM + KCB, SHAM + SPLN, IIR, IIR + KCB, IIR + SPLN. Two hours of ischemia and 1 hour of reperfusion has been applied by clipping the SMA. GdCl3 was given 24 hours before experiment. Splenectomy was done just before SMA clipping. Lung levels of tumor necrosis-factor (TNF), interleukin (IL)-6, myeloperoxidase (MPO), and malondialdehyde (MDA) were assayed biochemically. Lung leukosequestration was determined by counting PMNLs histologically. Kruskal-Wallis and Mann-Whitney U tests were done; P values less than.003 were considered significant. Polimorphonuclear leukocyte (PMNL) counts and biochemical parameters in the IIR group were significantly higher than the other groups (P <.003). When compared with IIR group, PMNL counts and biochemical parameters were significantly decreased in the IIR+KCB and IIR+SPLN groups, respectively (P <.003). However, they were still significantly higher than their sham-operated controls (P <.003). This study documents that splenectomy attenuates ALI as well as Kupffer cell blockage. Spleen, an important component of mononuclear phagocytic system as liver Kupffer cells, might play an important role in the IIR-induced ALI.


Modified arabinoxylan rice bran (MGN-3/Biobran) enhances yeast-induced apoptosis in human breast cancer cells in vitro.
We have recently reported that phagocytosis of killed Saccharomyces cerevisiae, baker's yeast, induced apoptosis in human breast cancer cell lines MCF-7, ZR-75-1 and HCC70. In this study we have evaluated the effect of treatment with MGN-3, a modified arabinoxylan from rice bran, on phagocytosis and yeast-induced apoptosis in breast cancer cells. Cancer cells were cultured with yeast at a ratio of 1:10 in the absence or presence of MGN-3, and the percentages of phagocytic and apoptotic cancer cells were examined by flow cytometry and by cytospin preparations. Cancer cells treated with MGN-3 exhibited increased percentages of attachment (200%) and uptake of yeast (313%) by MCF-7 cells at 0.5 hr, as compared with cells without MGN-3. In addition, treatment with MGN-3 resulted in a 2 fold increase in the percentage of apoptotic MCF-7 cells, 2.5 fold for ZR-75 cells and 1.8 fold for HCC70 cells. MGN-3 effect was dose-dependent and associated with increased activation of caspases 8 and 9 in MCF-7 cells, and caspases 8, 9 and 3 in HCC70 cells. This data demonstrates that MGN-3 accelerates phagocytosis-induced apoptosis of cancer cells, which may represent a novel therapeutic strategy for the treatment of breast cancer.


Prediction of histological types of endometrial cancer by endometrial cytology.
Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC. Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest. For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002). Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC.


[Legal status of complementary medicine in Europe].
As an addition to the project on 'Complementary Medicine and Health Law' carried out within the NFP34 it became highly desirable to compare the Swiss legal situation with that of most European countries. Therefore, the project compiled and analyzed the legal status of 23 European countries concerning the licensing regulations for providers of complementary medical services and the corresponding reimbursement policies. There are considerable differences between the various countries in legal and in practical terms; for the time being a confusing situation in view of a possible European harmonization. This project is a first step in the direction of a European overview on legal preconditions for the provision of and the reimbursement for services in complementary medicine.


Required first-year generalist clinical experience courses and their relationship to career choice: the critical effect of family medicine involvement.
This study examines the relationships among the presence of a required first-year generalist clinical experience (RFGCE) course, family medicine involvement in such courses, and the percentage of 1993 medical school graduates who chose family practice as a career upon graduation. A prospective cohort study measured predictor variables in 1989, the presence of a required third-year family medicine clerkship in 1991, and the outcome variable in 1993. Data were collected from 122 US 4-year medical schools. Eighty-seven (71.3%) of 122 medical schools had RFGCE courses. In schools with courses and family medicine administrative units, family physicians were involved to some extent in most of these courses (88%). After controlling for type of medical school, the requirement of a third-year family medicine clerkship, and the involvement of a family medicine administrative unit, the presence of an RFGCE course was associated with a 3.5% increase in the number of students who selected a family practice career. This is a 28% increase on average over the mean percentage of medical students choosing a family practice career in 1993. However, in a second analysis, when all predictor variables were entered into the equation, family medicine involvement in such courses replaced the presence of such courses as a statistically significant predictor of medical students selecting family practice as a career. Family physicians are involved to some extent in the great majority of RFGCE courses. Such involvement is associated with an increase in the number of medical students selecting a family practice career upon graduation from medical school.


Prevalence of intertrigo and associated factors: A secondary data analysis of four annual multicentre prevalence studies in the Netherlands.
Intertriginous dermatitis (intertrigo) is caused by occlusive conditions in skin folds increasing local heat and moisture and skin-on-skin friction. To measure the prevalence of intertrigo in hospitals, care homes, and home care and to identify demographic and health characteristics being associated with intertrigo. Secondary data analysis of four cross-sectional multicentre prevalence studies conducted between 2013 and 2016. Care homes, hospitals, and home care in the Netherlands. Subjects being 18 years and older who underwent skin examinations for intertrigo. Pairs of two trained nurse raters per participating institution conducted head-to-toe skin examinations. Results of 40,340 subjects were included into the data analysis. The prevalence of intertrigo was highest in home care (9.6% (95% CI 8.6% to 10.6%)) followed by aged care facilities (6.7% (95% 6.4 to 7.0)) and hospitals (2% (95% CI 1.8% to 2.3%)). A high BMI, having diabetes mellitus and being care dependent was highly associated with the presence of intertrigo in all three settings. Intertrigo is a common skin condition in care homes and home care. Obese and diabetic subjects, and subjects needing help with hygiene and getting dressed are at particular high risk. Adequate skin care strategies might be helpful to prevent this skin problem.


Relationship between T-lymphocyte cytokine levels and sero-response to hepatitis B vaccines.
To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-gamma, IL-2, TNF-alpha, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers. A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-gamma, TNF-alpha and IL-10 in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response. Our findings suggest that unresponsiveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.


Reactivation of herpesvirus in neurosurgical patients.
The authors are presenting seven patients who had operations between July 1984 and July 1985 and who developed herpes infections postoperatively. Four of the patients developed their infections in a dermatomal distribution that correlated with the nerve roots manipulated at operation. A spectrum of localized herpes reactivation is demonstrated in this series. The use of corticosteroids and other associated variables are discussed. Like reactivation of herpes simplex after trigeminal nerve operation, we believe reactivation of herpes simplex and herpes zoster can occur in operation of the cervical, thoracic, or lumbosacral spine.


[Effect of immunization on functional state of thyroid gland and thyroxine binding in rat organs].
A number of modern research methods were used in experiments on 220 white rats to examine thyroid function at varying times after single immunization with typhoid vaccine. It was found that on the 1st and 2nd days of the observation period, only cAMP level of the thyroid parenchyma decreases. Three, four and seven days following immunization, thyroid function is drastically reduced, which manifests by a decrease in 131I uptake by the thyroid gland. Also decreased were the conversion ratio, the levels of thyroxine and triiodothyronine in blood serum and incorporation of labeled thyroxin by the heart, liver and spleen. During the productive phase of the immunogenesis (days 10, 15, 20 and 25), all the test indicators considerably increase. The phases of the reaction obtained seem likely to be a consequence of reciprocal relationship between the thyroid and sympathoadrenal systems (the inductive period), as well as by the feedback effect (the productive period of antibody formation). The reaction of thyroid function to immunization is regarded as a component of non-specific adaptation response of the body to an extreme irritant, that provides for metabolic reconstruction necessary for the synthesis of antibodies and formation of immune lymphocyte populations.


Inflammatory orbital pseudotumor simulating retinoblastoma in a one year old girl.
The case report of a one year old girl with a clinical diagnosis of retinoblastoma who following enucleation was histologically diagnosed as a case of inflammatory orbital pseudotumour is presented. The literature is reviewed and the conclusion is reached that inflammatory orbital pseudotumour be considered in the list of deferential diagnosis of proptosis in early childhood.


A novel "total pituitary hormone index" as an indicator of postoperative pituitary function in patients undergoing resection of pituitary adenomas.
The purpose of this study was to investigate the differences between pre- and postoperative pituitary hormone levels in patients undergoing surgical resection of pituitary adenoma and to identify factors associated with preoperative hypopituitarism. Data from 81 patients with histologically confirmed functioning and non-functioning pituitary adenomas (NFPA) who underwent transsphenoidal resection from January 2011 to December 2013 were retrospectively analyzed. Logistic regression was applied to analyze factors associated with preoperative hypopituitarism. In patients with functioning pituitary adenomas, GH and PRL levels declined after the operation; TSH, FSH and LH levels returned to preoperative values after an initial decline at postoperative day 1. In contrast, with the exception of a postoperative reduction in PRL level, NFPA patients had postoperative ACTH, TSH, FSH and LH levels at 4 months follow-up that were similar to preoperative levels. Similarly, a decrease in total hormone index was observed following surgery irrespective of NFPA type and in null-cell type NFPA patients with values increasing over the 4-month follow-up period. A higher percentage of patients receiving partial resection had high PRL levels (≥200 ng/ mL) compared to those receiving complete resection. Age (P = 0.041) and male sex (P = 0.004) were significantly associated with preoperative hypopituitarism. In conclusion, the postoperative total hormone index decreased immediately following surgery in all patients with pituitary adenoma who underwent resection, and then increased over the follow-up period. The extent of surgical resection correlated with PRL levels >200 ng/mL. Age and male sex were also independent risk factors for preoperative hypopituitarism.


Design of well-defined shell-core covalent organic frameworks/metal sulfide as an efficient Z-scheme heterojunction for photocatalytic water splitting.
Development of a covalent-organic framework (COF)-based Z-scheme heterostructure is a promising strategy for solar energy driven water splitting, but the construction of a COF-based Z-scheme heterostructure with well-defined architecture, large contact area and intimate contact interfaces is scarce. Herein, we fabricated a direct Z-scheme heterostructure COF-metal sulfide hybrid (T-COF@CdS) with shell-core architecture by self-polymerization of 1,3,5-benzenetricarboxaldehyde and 2,4,6-tris(4-aminophenyl)-1,3,5-triazine in situ on CdS. The formed C-S chemical bonding between T-COF and CdS could provide a very tight and stable interface. Owing to the properly staggered band alignment, strong interfacial interaction and large interfacial contact area between T-COF and CdS, a Z-scheme route for charge separation and transfer is realized, resulting in electron accumulation in CdS for H2O reduction. The obtained Z-scheme heterostructure T-COF@CdS-3 exhibits a high apparent quantum efficiency of 37.8% under 365 nm monochromatic light irradiation, and long-term stability arising from shell-core structures in which the T-COF shell protects the catalytic centers of CdS against deactivation, as well as acts as oxidation sites to avoid the photocorrosion of CdS. This work provides a strategy for the construction of a shell-core direct Z-scheme heterostructure photocatalyst for water splitting with high performance.


Different Types of Training Lead to Different Levels of Cardiovascular Energy Dissipation: Young Soccer Players Versus Ballet Dancers.
Arterial wall viscosity is a source of energy dissipation that takes place during mechanical transduction. In our previous studies, a "global" damping effect in endurance training athletes was introduced, verifying that endurance-athletes dissipate greater pulsatile energy in the circulation compared with healthy untrained subjects. To investigate the wall energy dissipation in the vascular bed for each beat and within the conceptual framework of ventricular-arterial coupling, in order to elucidate if different types of training could lead to differentiated levels of cardiovascular energy dissipation. Data from subjects with different kinds of training (soccer players and ballet dancers) have been collected noninvasively and compared with a control group of untrained individuals to analyse the differentiating characteristics of the subjects, especially in terms of Stroke Work Dissipation (WDIS). In the endurance-trained individuals, an enhanced WDIS has been observed compared to the untrained individuals (p<0.05). However, non-significant differences were found regarding ballet-dancers group. Changes in wall energy dissipation are developed under high intensity endurance training routines.


Predicting accurate contacts in thousands of Pfam domain families using PconsC3.
A few years ago it was shown that by using a maximum entropy approach to describe couplings between columns in a multiple sequence alignment it is possible to significantly increase the accuracy of residue contact predictions. For very large protein families with more than 1000 effective sequences the accuracy is sufficient to produce accurate models of proteins as well as complexes. Today, for about half of all Pfam domain families no structure is known, but unfortunately most of these families have at most a few hundred members, i.e. are too small for such contact prediction methods. To extend accurate contact predictions to the thousands of smaller protein families we present PconsC3, a fast and improved method for protein contact predictions that can be used for families with even 100 effective sequence members. PconsC3 outperforms direct coupling analysis (DCA) methods significantly independent on family size, secondary structure content, contact range, or the number of selected contacts. PconsC3 is available as a web server and downloadable version at http://c3.pcons.net . The downloadable version is free for all to use and licensed under the GNU General Public License, version 2. At this site contact predictions for most Pfam families are also available. We do estimate that more than 4000 contact maps for Pfam families of unknown structure have more than 50% of the top-ranked contacts predicted correctly. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Subtle neuropsychiatric sequelae of carbon monoxide intoxication: two case reports.
Carbon monoxide intoxication may result in subtle neuropsychiatric abnormalities that can be overlooked, misdiagnosed, or not fully appreciated. The author describes two patients who developed subtle but troublesome emotional cognitive problems following carbon monoxide poisoning and stresses the value of sequential neuropsychological testing and judicious psychiatric counseling in such cases.


The thiol antioxidant 1,2-dithiole-3-thione stimulates the expression of heat shock protein 70 in dopaminergic PC12 cells.
In Parkinson's disease (PD), the pathogenic factors oxidative stress and protein aggregation interact and culminate in the apoptotic death of (mainly catecholaminergic) neurons. The dithiolethiones comprise thiol antioxidants that are well known for their activation of the expression of a wide collection of cytoprotective genes, including genes coding for antioxidant enzymes. Given the observation that heat shock proteins (HSPs), in particular the heat shock protein 72 (HSP72), protects against cellular degeneration in various models of PD, the ability of the unsubstituted dithiolethione 1,2-dithiole-3-thione (D3T) to stimulate heat shock protein gene and protein expression was studied using the dopaminergic PC12 cell line. As anticipated, D3T stimulated the expression of the antioxidant enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1). Quantitative PCR analysis revealed that D3T stimulates the expression of the inducible, cytoplasmic HSP72. Moreover, D3T strongly potentiated HSP72 gene and protein expression in heat-stressed cells. Taken together, our data show that, in addition to antioxidant enzymes, D3T stimulates the expression of HSP72, a chaperone shown to be neuroprotective in various models of PD, in particular under conditions of cellular stress. Thus, the broad range manipulation of endogenous cellular defense mechanisms, through D3T, may represent an innovative approach to therapeutic intervention in PD.


Strengthening couples' relationships with education: social policy and public health perspectives.
There is some evidence that skill-based couples relationship education (CRE) enhances couples' maintenance of healthy, committed relationships. This article analyzes issues in the balancing of a limited but growing knowledge base on the effects of CRE with current social policy that is creating an impetus for widespread dissemination of CRE. It is suggested that enough is known to act now, and that by doing so, the field has a unique opportunity to substantially (and rapidly) add to the existing knowledge base. Specifically, there can be expansion of knowledge of the efficacy of CRE with diverse populations and service delivery contexts, as well as the influences on the reach of CRE to populations at high risk of future relationship difficulties. While the current article focuses on CRE, the issues discussed have relevance to warrant dissemination to many areas of family psychology intervention.


Metagenomics uncovers dietary adaptations for chitin digestion in the gut microbiota of convergent myrmecophagous mammals.
Myrmecophagous mammals are specialized in the consumption of ants and/or termites. They do not share a direct common ancestor and evolved convergently in five distinct placental orders raising questions about the underlying adaptive mechanisms involved and the relative contribution of natural selection and phylogenetic constraints. Understanding how these species digest their prey can help answer these questions. More specifically, the role of their gut microbial symbionts in the digestion of the insect chitinous exoskeleton has not been investigated in all myrmecophagous orders. We generated 29 new gut metagenomes from nine myrmecophagous species to reconstruct more than 300 bacterial genomes in which we identified chitin-degrading enzymes. Studying the distribution of these chitinolytic bacteria among hosts revealed both shared and specific bacteria between ant-eating species. Overall, our results highlight the potential role of gut symbionts in the convergent dietary adaptation of myrmecophagous mammals and the evolutionary mechanisms shaping their gut microbiota.


Light-Augmented Multi-ion Interaction in MXene Membrane for Simultaneous Water Treatment and Osmotic Power Generation.
The mixing of wastewater and natural water releases abundant osmotic energy. Harvesting this energy could significantly reduce the energy and economic cost of water treatment, leading to sustainable wastewater treatment technology. Yet, such energy harvesting is highly challenging because it requires a material that is highly permeable to nontoxic ions while rejecting toxic ions in wastewater to reach high power density and prevent environmental pollution. In this work, we demonstrate that a light-augmented biomimetic multi-ion interaction in an MXene membrane can simultaneously realize high permeability of Na+ ions for enhanced osmotic power generation and high selectivity to heavy metal ions up to a ratio of 2050 for wastewater treatment. The Na+ permeability is enhanced by the photothermal effect of the MXene membrane. The transport of heavy metal ions, however, is suppressed because, under angstrom-confinement, heavy metal ions are strongly electrostatically repelled by the increased number of permeating Na+ ions. As a result, the membrane can stably generate osmotic power from simulated industrial wastewater, and the power density can be enhanced by 4 times under light illumination of approximate 1 sun intensity. This work highlights the importance of multi-ion interaction for the transport properties of ionic materials, which remains rarely investigated and poorly understood in previous studies.


Surgical resection is sufficient for incidentally discovered solitary pulmonary nodule caused by nontuberculous mycobacteria in asymptomatic patients.
Incidentally discovered solitary pulmonary nodules (SPN) caused by nontuberculous mycobacteria (NTM) is uncommon, and its optimal treatment strategy remains uncertain. This cohort study determined the clinical characteristics and outcome of asymptomatic patients with NTM-SPN after surgical resection. Resected SPNs with culture-positive for NTM in six hospitals in Taiwan during January, 2010 to January, 2017 were identified. Asymptomatic patients without a history of NTM-pulmonary disease (PD) or same NTM species isolated from the respiratory samples were selected. All were followed until May 1, 2019. A total of 43 patients with NTM-SPN were enrolled. Mycobacterium avium complex (60%) and M. kansasii (19%) were the most common species. The mean age was 61.7 ± 13.4. Of them, 60% were female and 4% had history of pulmonary tuberculosis. The NTM-SPN was removed by wedge resection in 38 (88%), lobectomy in 3 (7%) and segmentectomy in 2 (5%). Caseating granuloma was the most common histologic feature (58%), while chronic inflammation accounts for 23%. Mean duration of the follow-up was 5.2 ± 2.8 years (median: 4.2 years [2.5-7.0]), there were no mycobacteriology recurrence or NTM-PD development. In conclusion, surgical resection is likely to curative for incidentally discovered NTM-SPN in asymptomatic patients without culture evidence of the same NTM species from respiratory specimens, and routine mycobacterium culture for resected SPN might be necessary for differentiating pulmonary tuberculosis and NTM because further treatment differs.


Hierarchical Convolutional Neural Networks for Segmentation of Breast Tumors in MRI With Application to Radiogenomics.
Breast tumor segmentation based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a challenging problem and an active area of research. Particular challenges, similarly as in other segmentation problems, include the class-imbalance problem as well as confounding background in DCE-MR images. To address these issues, we propose a mask-guided hierarchical learning (MHL) framework for breast tumor segmentation via fully convolutional networks (FCN). Specifically, we first develop an FCN model to generate a 3D breast mask as the region of interest (ROI) for each image, to remove confounding information from input DCE-MR images. We then design a two-stage FCN model to perform coarse-to-fine segmentation for breast tumors. Particularly, we propose a Dice-Sensitivity-like loss function and a reinforcement sampling strategy to handle the class-imbalance problem. To precisely identify locations of tumors that underwent a biopsy, we further propose an FCN model to detect two landmarks located at two nipples. We finally selected the biopsied tumor based on both identified landmarks and segmentations. We validate our MHL method on 272 patients, achieving a mean Dice similarity coefficient (DSC) of 0.72 which is comparable to mutual DSC between expert radiologists. Using the segmented biopsied tumors, we also demonstrate that the automatically generated masks can be applied to radiogenomics and can identify luminal A subtype from other molecular subtypes with the similar accuracy with the analysis based on semi-manual tumor segmentation.


Bilateral blindness secondary to optic nerve ischemia from severe amlodipine overdose: a case report.
Calcium channel blockers are commonly prescribed medications; calcium channel blocker overdose is becoming increasingly prevalent. The typical presentation of a calcium channel blocker overdose is hypotension and decreased level of consciousness. We describe a case of a calcium channel blocker overdose that led to bilateral cortical blindness, a presentation that has not previously been reported. A 49-year-old white woman with known bilateral early optic atrophy presented to our hospital with hypotension and obtundation following a known ingestion of 150 mg of amlodipine. She was transferred to our intensive care unit where she was intubated, mechanically ventilated, and required maximal vasopressor support (norepinephrine 40 mcg/minute, epinephrine 40 mcg/minute, and vasopressin 2.4 units/hour) along with intravenously administered crystalloid boluses. Despite these measures, she continued to deteriorate with persistent hypotension and tachycardia, as well as anuria. Intralipid emulsion therapy was subsequently administered to which no initial response was observed. A chest X-ray revealed diffuse pulmonary edema; intravenous diuresis as well as continuous renal replacement therapy was initiated. Following the initiation of continuous renal replacement therapy, her oxygen requirements as well as urine output began to improve, and 3 days later she was liberated from mechanical ventilation. Following extubation, she complained of new onset visual impairment, specifically seeing only red-green colors, but no objects. An ophthalmologic examination revealed that this was due to bilateral optic atrophy from prolonged hypotension during the first 24 hours after the overdose. Persistent hypotension in the setting of a calcium channel blocker overdose can lead to worsening optic atrophy resulting in bilateral cortical blindness.


Silymarin and management of liver function in non-alcoholic steatohepatitis: a case report.
Non-alcoholic fatty liver disease (NAFLD) and its progressive form (non-alcoholic steatohepatitis; NASH) are the main reason for chronic liver disease in the general population, characterized by fat accumulation in hepatocytes (steatosis) and anomalies in liver biochemical analyses. To date, no pharmacological agents have been approved for NAFLD or NASH treatment. However, silymarin, the active ingredient in milk thistle, has been used in the last decades for the treatment of several liver diseases. In this case report, treatment with silymarin 140 mg three-times daily highlighted moderate efficacy and a good safety profile in the management of NASH and liver function, as it decreased serum AST and ALT levels over the treatment period with no side-effects, supporting silymarin as a promising supplemental intervention that can normalize liver activity in NAFLD and NASH. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series. Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.


Context influences conscious appraisal of cross situational statistical learning.
Previous research in cross-situational statistical learning has established that people can track statistical information across streams in order to map nonce words to their referent objects (Yu and Smith, 2007). Under some circumstances, learners are able to acquire multiple mappings for a single object (e.g., Yurovsky and Yu, 2008). Here we explore whether having a contextual cue associated with a new mapping may facilitate this process, or the conscious awareness of learning. Using a cross-situational statistical learning paradigm, in which learners could form both 1:1 and 2:1 word-object mappings over two phases of learning, we collected confidence ratings during familiarization and provided a retrospective test to gage learning. In Condition 1, there were no contextual cues to indicate a change in mappings (baseline). Conditions 2 and 3 added contextual cues (a change in speaker voice or explicit instructions, respectively) to the second familiarization phase to determine their effects on the trajectory of learning. While contextual cues did not facilitate acquisition of 2:1 mappings as assessed by retrospective measures, confidence ratings for these mappings were significantly higher in contextual cue conditions compared to the baseline condition with no cues. These results suggest that contextual cues corresponding to changes in the input may influence the conscious awareness of learning.


[Autonomous space and own role: nurses' representation in collective health-hospital context].
This study has the objective of analzying the social representation structure of professional authonomy. It is a Qualitative research based on Social Representations and developed with 83 nurses in a city of Rio de Janeiro State, Brazil. In order to collect data it was used free evocation to expressions like professional authonomy and nursing and to analyse them EVOC software was used. The nucleous of representation to authonomy expression is build by knowledge, achievement and responsibility, whereas in nursing expression it is possible to observe love and dedication. It can be notice the presence of representational dimensions connected to the person of the professionals and to their feelings. It can be concluded that exposed representational structures show an achievement process of professional authonomy.


Noninvasive measurement of extraction fraction and single-kidney glomerular filtration rate with MR imaging in swine with surgically created renal arterial stenoses.
To test whether magnetic resonance (MR) imaging enables accurate measurement of extraction fraction (EF) in swine with unilateral renal ischemia and to evaluate effects of renal arterial stenosis on EF and single-kidney glomerular filtration rate. High-grade unilateral renal arterial stenoses were surgically created in eight pigs. Direct measurements of renal venous and arterial inulin concentration provided reference standard estimates of single-kidney EF. Pigs were imaged with a 1.5-T imager to estimate EF, renal blood flow, and glomerular filtration rate. A breath-hold inversion-recovery spiral sequence was used to measure T1 of blood in the infrarenal inferior vena cava and renal veins after intravenous administration of gadopentetate dimeglumine, and these data were used to calculate EF. Cine-phase contrast material-enhanced imaging of the renal arteries provided quantitative renal blood flow measurements. Bilateral single-kidney glomerular filtration rate was then determined: glomerular filtration rate = renal blood flow x (1 - hematocrit level) x EF. A statistically significant linear correlation was found between EF, as determined with MR imaging, and inulin (r = 0.77). As compared with kidneys without renal arterial stenosis, kidneys with renal arterial stenosis showed 50% (0.14/0.28) EF reduction (P <.01) and 59% glomerular filtration rate reduction (P <.01). MR imaging shows promise for in vivo measurement of EF and glomerular filtration rate, which may be useful in assessing the clinical importance of renal arterial stenosis.


Hydrothermal Sterilization Improves Initial Osteoblast Responses on Sandpaper-Polished Titanium.
Hydrocarbon contamination accumulated on titanium (Ti) implant surfaces during storage and sterilization is unavoidable and difficult to remove. It impairs the bioactivity of implants, restricts initial interactions between implants and the surrounding biological environment, and has become a common challenge for Ti implants. To overcome this problem, sterilization was considered as the final surface modification and a novel method, hydrothermal sterilization (HS), was proposed. Briefly, stored sandpaper-polished Ti specimens were sterilized in a glass container with pure water at 121 °C for 20 min and kept in the same water until utilization. As a control, another group of specimens was sterilized with conventional autoclaving (AC) at 121 °C for 20 min and stored in sterilization pouches after being dried at 60 °C. Compared with AC, HS deposited numerous nano-sized particles on the substrates, reduced the atomic percentage of the surface carbon, and transformed the Ti surface to a super hydrophilic status. HS also increased the attachment rate, spread, proliferation, and the mineralized nodule areas of rat bone marrow-derived osteoblasts. These results suggest that HS enhances the bioactivity of Ti implants for osteoblasts, and that this biofunctionalization was attributed to nanostructure construction, hydrophilic conversion, and the effective removal of hydrocarbons. Hydrothermal sterilization is proposed to be used as a universal sterilization method for all kinds of titanium implants without apatite coating.


Granular measures of agricultural land use influence lake nitrogen and phosphorus differently at macroscales.
Agricultural land use is typically associated with high stream nutrient concentrations and increased nutrient loading to lakes. For lakes, evidence for these associations mostly comes from studies on individual lakes or watersheds that relate concentrations of nitrogen (N) or phosphorus (P) to aggregate measures of agricultural land use, such as the proportion of land used for agriculture in a lake's watershed. However, at macroscales (i.e., in hundreds to thousands of lakes across large spatial extents), there is high variability around such relationships and it is unclear whether considering more granular (or detailed) agricultural data, such as fertilizer application, planting of specific crops, or the extent of near-stream cropping, would improve prediction and inform understanding of lake nutrient drivers. Furthermore, it is unclear whether lake N and P would have different relationships to such measures and whether these relationships would vary by region, since regional variation has been observed in prior studies using aggregate measures of agriculture. To address these knowledge gaps, we examined relationships between granular measures of agricultural activity and lake total phosphorus (TP) and total nitrogen (TN) concentrations in 928 lakes and their watersheds in the Northeastern and Midwest U.S. using a Bayesian hierarchical modeling approach. We found that both lake TN and TP concentrations were related to these measures of agriculture, especially near-stream agriculture. The relationships between measures of agriculture and lake TN concentrations were more regionally variable than those for TP. Conversely, TP concentrations were more strongly related to lake-specific measures like depth and watershed hydrology relative to TN. Our finding that lake TN and TP concentrations have different relationships with granular measures of agricultural activity has implications for the design of effective and efficient policy approaches to maintain and improve water quality.


Loss of M2 muscarinic receptor function inhibits development of hypoxic bradycardia and alters cardiac beta-adrenergic sensitivity in larval zebrafish (Danio rerio).
Fish exposed to hypoxia develop decreased heart rate, or bradycardia, the physiological significance of which remains unknown. The general muscarinic receptor antagonist atropine abolishes the development of this hypoxic bradycardia, suggesting the involvement of muscarinic receptors. In this study, we tested the hypothesis that the hypoxic bradycardia is mediated specifically by stimulation of the M(2) muscarinic receptor, the most abundant subtype in the vertebrate heart. Zebrafish (Danio rerio) were reared at two levels of hypoxia (30 and 40 Torr PO(2)) from the point of fertilization. In hypoxic fish, the heart rate was significantly lower than in normoxic controls from 2 to 10 days postfertilization (dpf). At the more severe level of hypoxia (30 Torr PO(2)), there were significant increases in the relative mRNA expression of M(2) and the cardiac type beta-adrenergic receptors (beta1AR, beta2aAR, and beta2bAR) at 4 dpf. The hypoxic bradycardia was abolished (at 40 Torr PO(2)) or significantly attenuated (at 30 Torr PO(2)) in larvae experiencing M(2) receptor knockdown (using morpholino antisense oligonucleotides). Sham-injected larvae exhibited typical hypoxic bradycardia in both hypoxic regimens. The expression of beta1AR, beta2aAR, beta2bAR, and M(2) mRNA was altered at various stages between 1 and 4 dpf in larvae experiencing M(2) receptor knockdown. Interestingly, M(2) receptor knockdown revealed a cardioinhibitory role for the beta(2)-adrenergic receptor. This is the first study to demonstrate a specific role of the M(2) muscarinic receptor in the initiation of hypoxic bradycardia in fish.


Validation of analytic methods for biomarkers used in drug development.
The role of biomarkers in drug discovery and development has gained precedence over the years. As biomarkers become integrated into drug development and clinical trials, quality assurance and, in particular, assay validation become essential with the need to establish standardized guidelines for analytic methods used in biomarker measurements. New biomarkers can revolutionize both the development and use of therapeutics but are contingent on the establishment of a concrete validation process that addresses technology integration and method validation as well as regulatory pathways for efficient biomarker development. This perspective focuses on the general principles of the biomarker validation process with an emphasis on assay validation and the collaborative efforts undertaken by various sectors to promote the standardization of this procedure for efficient biomarker development.


Is there unmet need for implantable cardioverter defibrillators? Findings from a post-mortem series of sudden cardiac death.
To establish whether sudden cardiac death (SCD) victims could have been identified prior to their event and considered for an implantable cardioverter defibrillators (ICDs). Consecutive post-mortem cases of adult SCDs presumed to be caused by a ventricular arrhythmia over 12 months (2002-03) from a defined catchment population, Southampton, UK (n = 443 824 adults aged >or=16 years). Pathological data were extracted from the post-mortem reports. Hospital and general practice (GP) notes provided data on previous symptoms, investigations, and cardiac disease history. Two electrophysiologists judged the appropriateness of each case for an ICD against National Guidance. Two hundred and fifteen cases met the inclusion criteria and lived within the catchment area. Agreement between experts on appropriateness for an ICD in those aged <80 years was good (kappa score of 0.64). Only one case (<1%) was considered appropriate for an ICD without requirement for further investigation. Forty-nine per cent of cases were considered to have required further cardiac investigations to determine appropriateness; these were mainly heart failure patients who had suffered a myocardial infarction (MI). Forty per cent of cases had no previous clinical evidence of confirmed or suspected heart disease. However, pathological data showed that 51% of cases had suffered a previous MI. Two-fifths of SCD victims had no recorded health service contact that would indicate increased risk of SCD within their lifetime. A large number of patients suffered previous cardiac events or symptoms suggestive of increased SCD risk but were not referred for further investigations. There is a need for better care pathways for patients post-MI to identify those requiring an ICD. The impact on the ICD rate of undertaking these extra investigations is uncertain.


Structural and dynamic characteristics in monolayer square ice.
When water is constrained between two sheets of graphene, it becomes an intriguing monolayer solid with a square pattern due to the ultrahigh van der Waals pressure. However, the square ice phase has become a matter of debate due to the insufficient experimental interpretation and the slightly rhomboidal feature in simulated monolayer square-like structures. Here, we performed classical molecular dynamics simulations to reveal monolayer square ice in graphene nanocapillaries from the perspective of structure and dynamic characteristics. Monolayer square-like ice (instantaneous snapshot), assembled square-rhombic units with stacking faults, is a long-range ordered structure, in which the square and rhombic units are assembled in an order of alternative distribution, and the other rhombic unit forms stacking faults (polarized water chains). Spontaneous flipping of water molecules in monolayer square-like ice is intrinsic and induces transformations among different elementary units, resulting in the structural evolution of monolayer square ice in dynamics. The existence of stacking faults should be attributed to the spontaneous flipping behavior of water molecules under ambient temperature. Statistical averaging results (thermal average positions) demonstrate the inherent square characteristic of monolayer square ice. The simulated data and insight obtained here might be significant for understanding the topological structure and dynamic behavior of monolayer square ice.


Diffusion-perfusion MRI for triaging transient ischemic attack and acute cerebrovascular syndromes.
Time from symptom onset to treatment is considered to be the key variable that influences the indication of recanalization therapy for treatment of acute brain infarction. Symptom duration less than 24 h defines transient ischemic attack (TIA). The evolution of multimodal brain MRI demonstrates that neuroimaging findings of tissue injury may be more important predictors of clinical outcomes than arbitrary time thresholds. Preliminaries studies suggest that stroke victims with a significant penumbra estimated by the diffusion/perfusion mismatch on MRI benefit from thrombolysis beyond the currently recommended time window of 4.5 h. New software programs can automatically produce reliable perfusion and diffusion maps for use in clinical practice. Combined diffusion and perfusion MRI reveals an acute ischemic lesion in about 60% of TIA patients. Patients with transient symptoms and a restricted diffusion lesion on MRI are considered by the American Heart Association (AHA) scientific committee to have suffered a brain infarction and have a very high risk of early stroke recurrence. Multimodal MRI provides critical real-time information about ongoing tissue injury as well as the risk of additional ischemic damage. It is becoming an essential tool for the diagnosis, management and triage of acute TIA and brain infarction.


The Effect of Static and Dynamic Stretching Exercises on Sprint Ability of Recreational Male Volleyball Players.
The aim of the present trial was to investigate the effect of two stretching programs, a dynamic and a static one, on the sprint ability of recreational volleyball players. The sample consisted of 27 male recreational volleyball players (age 21.6 ± 2.1 years, mean ± standard deviation, body mass 80.3 ± 8.9 kg, height 1.82 ± 0.06 m, body mass index 24.3 ± 2.5 kg.m-2, volleyball experience 7.7 ± 2.9 years). Participants were randomly divided into three groups: (a) the first performing dynamic stretching exercises three times per week, (b) the second following a static stretching protocol on the same frequency, and (c) the third being the control group, abstaining from any stretching protocol. The duration of the stretching exercise intervention period was 6 weeks, with all groups performing baseline and final field sprinting tests at 4.5 and 9 m. The post-test sprint times were faster in both the 4.5 (p = 0.027, η2 = 0.188) and 9 m tests (p < 0.001, η2 = 0.605) compared to the pre-test values. A large time × group interaction was shown in both the 4.5 (p = 0.007, η2 = 0.341) and 9 m tests (p = 0.004, η2 = 0.363) with the static and dynamic stretching groups being faster in the post-test than in the pre-test, whereas no change was found in the control group. The percentage change in the 4.5 m sprint time correlated with volleyball experience (r = -0.38, p = 0.050), i.e., the longer the volleyball experience, the larger the improvement in the 4.5 m sprint. Thus, it is concluded that both stretching techniques have a positive effect on the velocity of recreational male volleyball players, when performed at a frequency of three times per week for 6 weeks under the same conditions as defined in the study protocol.


3DCNAS: A universal method for predicting the location of fluorescent organelles in living cells in three-dimensional space.
Cellular biology research relies on microscopic imaging techniques for studying the complex structures and dynamic processes within cells. Fluorescence microscopy provides high sensitivity and subcellular resolution but has limitations such as photobleaching and sample preparation challenges. Transmission light microscopy offers a label-free alternative but lacks contrast for detailed interpretation. Deep learning methods have shown promise in analyzing cell images and extracting meaningful information. However, accurately learning and simulating diverse subcellular structures remain challenging. In this study, we propose a method named three-dimensional cell neural architecture search (3DCNAS) to predict subcellular structures of fluorescence using unlabeled transmitted light microscope images. By leveraging the automated search capability of differentiable neural architecture search (NAS), our method partially mitigates the issues of overfitting and underfitting caused by the distinct details of various subcellular structures. Furthermore, we apply our method to analyze cell dynamics in genome-edited human induced pluripotent stem cells during mitotic events. This allows us to study the functional roles of organelles and their involvement in cellular processes, contributing to a comprehensive understanding of cell biology and offering insights into disease pathogenesis.


Genetic trade-offs underlie divergent life history strategies for local adaptation in white clover.
Local adaptation is common in plants, yet characterization of its underlying genetic basis is rare in herbaceous perennials. Moreover, while many plant species exhibit intraspecific chemical defence polymorphisms, their importance for local adaptation remains poorly understood. We examined the genetic architecture of local adaptation in a perennial, obligately-outcrossing herbaceous legume, white clover (Trifolium repens). This widespread species displays a well-studied chemical defence polymorphism for cyanogenesis (HCN release following tissue damage) and has evolved climate-associated cyanogenesis clines throughout its range. Two biparental F2 mapping populations, derived from three parents collected in environments spanning the U.S. latitudinal species range (Duluth, MN, St. Louis, MO and Gainesville, FL), were grown in triplicate for two years in reciprocal common garden experiments in the parental environments (6,012 total plants). Vegetative growth and reproductive fitness traits displayed trade-offs across reciprocal environments, indicating local adaptation. Genetic mapping of fitness traits revealed a genetic architecture characterized by allelic trade-offs between environments, with 100% and 80% of fitness QTL in the two mapping populations showing significant QTL×E interactions, consistent with antagonistic pleiotropy. Across the genome there were three hotspots of QTL colocalization. Unexpectedly, we found little evidence that the cyanogenesis polymorphism contributes to local adaptation. Instead, divergent life history strategies in reciprocal environments were major fitness determinants: selection favoured early investment in flowering at the cost of multiyear survival in the southernmost site versus delayed flowering and multiyear persistence in the northern environments. Our findings demonstrate that multilocus genetic trade-offs contribute to contrasting life history characteristics that allow for local adaptation in this outcrossing herbaceous perennial.


Pregnancy, birth, and disability: women's health care experiences.
This qualitative study examined the pregnancy, birth and postpartum experiences of 12 women with mobility-limiting physical disabilities. Analysis of semi-structured interviews of one to two hours revealed that the women's experiences were influenced by their own perspectives and the characteristics of health care system within which they were treated. The woman's experience included the effect of her disability, her resources, and her personality and approach. Health care system factors included provider attitudes, knowledge about disability and structural and political factors. Implications for health care providers are described.


Recruitment strategies and colony size in ants.
Ants use a great variety of recruitment methods to forage for food or find new nests, including tandem running, group recruitment and scent trails. It has been known for some time that there is a loose correlation across many taxa between species-specific mature colony size and recruitment method. Very small colonies tend to use solitary foraging; small to medium sized colonies use tandem running or group recruitment whereas larger colonies use pheromone recruitment trails. Until now, explanations for this correlation have focused on the ants' ecology, such as food resource distribution. However, many species have colonies with a single queen and workforces that grow over several orders of magnitude, and little is known about how a colony's organization, including recruitment methods, may change during its growth. After all, recruitment involves interactions between ants, and hence the size of the colony itself may influence which recruitment method is used--even if the ants' behavioural repertoire remains unchanged. Here we show using mathematical models that the observed correlation can also be explained by recognizing that failure rates in recruitment depend differently on colony size in various recruitment strategies. Our models focus on the build up of recruiter numbers inside colonies and are not based on optimality arguments, such as maximizing food yield. We predict that ant colonies of a certain size should use only one recruitment method (and always the same one) rather than a mix of two or more. These results highlight the importance of the organization of recruitment and how it is affected by colony size. Hence these results should also expand our understanding of ant ecology.


Intra-islet insulin permits glucose to directly suppress pancreatic A cell function.
Inhibition of pancreatic glucagon secretion during hyperglycemia could be mediated by (a) glucose, (b) insulin, (c) somatostatin, or (d) glucose in conjunction with insulin. To determine the role of these factors in the mediation of glucagon suppression, we injected alloxan while clamping the arterial supply of the pancreatic splenic lobe of dogs, thus inducing insulin deficiency localized to the ventral lobe and avoiding hyperglycemia. Ventral lobe insulin, glucagon, and somatostatin outputs were then measured in response to a stepped IV glucose infusion. In control dogs glucagon suppression occurred at a glucose level of 150 mg/dl and somatostatin output increased at glucose greater than 250 mg/dl. In alloxan-treated dogs glucagon output was not suppressed nor did somatostatin output increase. We concluded that insulin was required in the mediation of glucagon suppression and somatostatin stimulation. Subsequently, we infused insulin at high rates directly into the artery that supplied the beta cell-deficient lobe in six alloxan-treated dogs. Insulin infusion alone did not cause suppression of glucagon or stimulation of somatostatin; however, insulin repletion during glucose infusions did restore the ability of hyperglycemia to suppress glucagon and stimulate somatostatin. We conclude that intra-islet insulin permits glucose to suppress glucagon secretion and stimulate somatostatin during hyperglycemia.


A 437-base-pair deletion at the beginning of the latency-associated transcript promoter significantly reduced adrenergically induced herpes simplex virus type 1 ocular reactivation in latently infected rabbits.
In this study we used a herpes simplex virus type 1 (HSV-1) deletion mutant to identify a segment of the genome necessary for epinephrine-induced reactivation in the rabbit eye model of herpetic recurrent disease. In HSV-1 latently infected neural tissue, the only abundant viral products are the latency-associated transcripts (LATs). At least one promoter of LAT has been identified, and mutations in the LAT domain have been used to investigate HSV-1 reactivation. We used an ocular rabbit model of epinephrine-induced HSV-1 reactivation to study the effects of deleting a 437-bp region beginning 796 bp upstream of the LAT CAP site. Specifically, the 437-bp deletion is located between genomic positions 118006 and 118443 of the parent 17Syn+, and the construct is designated 17 delta S/N. This region also controls a portion of the genome encoding two transcripts (1.1 and 1.8 kb) from the LAT domain. A rescuant, 17 delta S/N-Res, was constructed from 17 delta S/N. Following ocular infection, all three viruses produced similar acute dendritic lesions in rabbits. Five weeks after infection, rabbits received transcorneal iontophoresis of epinephrine. The parent, 17Syn+, and the rescuant, 17 delta S/N-Res, underwent a high frequency of HSV-1 ocular reactivation as determined by recovery of infectious virus in the tear film. Rabbits infected with 17 delta S/N had a significantly lower frequency of ocular reactivation. Analysis of the trigeminal ganglia from all three groups of latently infected rabbits revealed (i) similar amounts of HSV DNA (genomic equivalents), (ii) accumulation of 2.0- and 1.45-kb LATs, and (iii) explant reactivation at the same high frequency. Therefore, these studies indicate that the 437-bp deleted region in 17 delta S/N is essential for epinephrine-induced reactivation and could implicate the 1.1- and 1.8-kb transcripts in the mechanisms controlling HSV-1 reactivation.


Disparities among 2009 pandemic influenza A (H1N1) hospital admissions: a mixed methods analysis--Illinois, April-December 2009.
During late April 2009, the first cases of 2009 pandemic influenza A (H1N1) (pH1N1) in Illinois were reported. On-going, sustained local transmission resulted in an estimated 500,000 infected persons. We conducted a mixed method analysis using both quantitative (surveillance) and qualitative (interview) data; surveillance data was used to analyze demographic distribution of hospitalized cases and follow-up interview data was used to assess health seeking behavior. Invitations to participate in a telephone interview were sent to 120 randomly selected Illinois residents that were hospitalized during April-December 2009. During April-December 2009, 2,824 pH1N1 hospitalizations occurred in Illinois hospitals; median age (interquartile range) at admission was 24 (range: 6-49) years. Hospitalization rates/100,000 persons for blacks and Hispanics, regardless of age or sex were 2-3 times greater than for whites (blacks, 36/100,000 (95% Confidence Interval ([95% CI], 33-39)); Hispanics, 35/100,000 [95%CI,32-37] (; whites, 13/100,000[95%CI, 12-14); p<0.001). Mortality rates were higher for blacks (0.9/100,000; p<0.09) and Hispanics (1/100,000; p<0.04) when compared with the mortality rates for whites (0.6/100,000). Of 33 interview respondents, 31 (94%) stated that they had heard of pH1N1 before being hospitalized, and 24 (73%) did not believed they were at risk for pH1N1. On average, respondents reported experiencing symptoms for 2 days (range: 1-7) before seeking medical care. When asked how to prevent pH1N1 infection in the future, the most common responses were getting vaccinated and practicing hand hygiene. Blacks and Hispanics in Illinois experienced disproportionate pH1N1 hospitalization and mortality rates. Public health education and outreach efforts in preparation for future influenza pandemics should include prevention messaging focused on perception of risk, and ensure community wide access to prevention messages and practices.


Statistical analysis of the spatial-temporal distribution of aerosol extinction retrieved by micro-pulse lidar in Kashgar, China.
The spatial-temporal distribution of dust aerosol is important in climate model and ecological environment. An observation experiment of the aerosol vertical distribution in the low troposphere was made using the micro-pulse lidar system from Sept. 2008 to Aug. 2009 at the oasis city Kashgar, China, which is near the major dust source area of the Taklimakan desert. The monthly averaged temporal variation of aerosol extinction profiles are given in the paper. The profile of aerosol extinction coefficient suggested that the dust aerosol could be vertically transported from the ground level to the higher altitude of above 5 km around the source region, and the temporal distribution showed that the dust aerosol layer of a few hundred meters thick appeared in the seasons of early spring and summer near the ground surface.


[Asthma prevalence in adolescents. Relation to sex and active smoking].
Asthma prevalence in adolescents appears to be increasing and determinants are not well established. To determine the association between sex and active smoking with asthma prevalence in adolescents. In this cross-sectional study 6,922 students, ages 12 to 18 years, residents in an area of northeastern Mexico, were included. We developed a questionnaire based on The International Study of Asthma and Allergies in Childhood (ISAAC) and on The European Community Respiratory Health Survey (ECRHS). The association between sex and active smoking with asthma prevalence was determined using a logistic regression model. Of the total population, 46.3% were males, 7.3% suffered from asthma and 17.3% were cigarette smokers. We found that sex (OR = 0.55; CI 95%: 0.48-0.63) and active smoking (adjusted OR = 1.12; CI 95%: 0.89-1.42) were not associated with asthma prevalence. Females (OR = 1.44; CI 95%: 1.13-1.84) and active smoking (adjusted OR = 1.38; CI 95%: 1.15-1.67) were associated with prevalence of wheezing in the last 12 months, and with prevalence of dry cough at night (OR = 1.53; CI 95%: 1.34-1.76). Teenager males and active smoking were not associated with asthma prevalence. Females had an association with wheezing in the last 12 months and dry cough at night.


Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely diagnosed.
Articles in the literature on alpha-1 antitrypsin (AAT) deficiency have been interpreted as indicating that AAT deficiency is a rare disease that affects mainly Caucasians (whites) from northern Europe. In a recent publication on the worldwide racial and ethnic distribution of AAT deficiency, new data were presented demonstrating that it is also found in various populations of African blacks; Arabs and Jews in the Middle East; and Central, Far East, and Southeast Asians, as well as whites in Australia, Europe, New Zealand, and North America. The new data on the prevalence of AAT deficiency in other major racial groups worldwide will affect the standards for the diagnosis of AAT deficiency by the medical community, with the realization that is not a rare disease of whites in northern Europe and immigrants from these countries in the New World. In a total population of 4.4 billion in the 58 countries surveyed, there are at least 116 million carriers (those with Pi phenotypes PiMS and PiMZ) and 3.4 million with deficiency allele combinations (phenotypes PiSS, PiSZ, and PiZZ) for the two most prevalent deficiency alleles PiS and PiZ; therefore, the new data suggest that AAT deficiency may be one of the most common serious single-locus genetic diseases in the world. Particularly important is the unique susceptibility of AAT-deficient individuals to exposure to chemical and particulate environmental agents. Such exposures are known to result in both lung and liver disease as well as other adverse health effects.


Salmonella spp. and antibiotic-resistant strains in wild mammals and birds in north-western Italy from 2002 to 2010.
Salmonella is an important zoonotic pathogen of economic importance. In Europe, salmonellosis is the second food-borne infection, in Italy, Salmonella is still the major cause of food-borne outbreaks. In Europe, there are many Salmonella surveillance plans on farmed animals, while Salmonella survey of wild animals is occasionally performed. The aim of this study was to investigate the presence of Salmonella including the antibiotic-resistant strains in wild animals. Between 2002 and 2010, 2,713 wild animals (canids, mustelids, birds, rodents, ungulates), were collected in north-western Italy and tested for Salmonella by classical microbiological culture method followed by serological and biochemical typing. One hundred and seventeen wild animals (63 canids, 25 mustelids, 24 birds, 5 ungulates) were found positive for Salmonella (4.3%). One hundred and thirty strains, belonging to several serotypes were isolated, and S. Typhimurium was the most common serotype found. Antibiotic susceptibility was tested by disk-diffusion test on 88 strains. Almost all the analyzed strains (97.7%) showed resistance/intermediate resistance to at least one class of antibiotics and the highest resistance values were observed for the tetracycline class. In conclusion, zoonotic and antibiotic-resistant serotypes were found in many species of wildlife.


Western Australian schools access to dentally optimal fluoridated water.
This study examined water fluoride levels at schools across Western Australia. The aim was to identify schools where levels of water fluoride appeared to be below dental health thresholds (0.5-1.0 mg/L) as recommended by the National Health and Medical Research Council (NHMRC). The objective is to provide health organizations with the knowledge for a more targeted approach to schools with greater risk of decay. Population data, school location, enrolment data and water quality data were integrated into geographic databases for analysis using Quantum GIS, Lisboa 1.8. The results indicated that 46% of school attendees in the northern half of Western Australia were at schools where there was the potential that the water was not dentally optimally fluoridated while in the southern half of Western Australia this was about 10%. Of these attendees (north and south), 45% were at primary school. Similarly, there was an association between socio-economic decile and proportion of school attendees in non-dentally optimally fluoridated schools. Lower deciles (i.e. poorer attendees) had a greater risk of being in schools outside dentally optimally fluoridated areas. This study clearly highlights areas where more prevention (and probably) treatment needs are present and provides a framework for targeted service planning.


Alterations in aldosterone biosynthesis in essential hypertensives.
We studied hypertensives with decreased adrenal responsiveness to infused angiotensin II (AII) to assess their responsiveness to other aldosterone secretagogues, ACTH and potassium, which are thought to stimulate aldosterone synthesis in sites different from one another and from AII. All subjects, following sodium restriction, received an infusion of AII in increasing doses (0.1-3 ng/kg per min). The increment in aldosterone between control and the highest infusion dose divided by the increment in plasma AII was used as the index of adrenal responsiveness. All normotensive controls (NC) had a ratio greater than 0.5. Hypertensives with a normal ratio were designated normal responders (NR) and those with a lower ratio were abnormal responders (AbR). The slope of the regression line between aldosterone and AII was significantly less for the AbR (0.02 +/- 0.04) than for the NR (1.20 +/- 0.02, P less than 0.001) and the NC (1.00 +/- 0.03, P less than 0.001) groups. During infusion of cosyntropin in increasing doses (0.05-1.5 mIU/kg per 30 min), the aldosterone response of the AbR was significantly less than that of the NR (P less than 0.016) or the NC (P less than 0.05) groups. Similarly, after infusion of potassium (0.33 mEq/min), the increment in aldosterone in the AbR group (7.6 +/- 2.2 ng/dl) was significantly less than that in the NR (14.2 +/- 2.5 ng/dl, P less than 0.05) and the NC (18 +/- 5 ng/dl, P less than 0.05) groups. Thus hypertensives with decreased aldosterone responsiveness to infused AII also had decreased responsiveness to infused ACTH and potassium, suggesting that their defect lies in the intracellular aldosterone biosynthetic pathway.


Chiral sculptured thin films for circular polarization of mid-wavelength infrared light.
Being an assembly of identical upright helices, a chiral sculptured thin film (CSTF) exhibits the circular Bragg phenomenon and can therefore be used as a circular polarization filter in a spectral regime called the circular Bragg regime. This has been already demonstrated in the near-infrared and short-wavelength infrared regimes. If two CSTFs are fabricated in identical conditions to differ only in the helical pitch, and if both are made of a material whose bulk refractive index is constant in a wide enough spectral regime, then the center wavelengths of the circular Bragg regimes of the two CSTFs must be in the same ratio as their helical pitches by virtue of the scale invariance of the frequency-domain Maxwell postulates. This theoretical result was confirmed by measuring the linear transmittance spectra of two zinc-selenide CSTFs with helical pitches in the ratio 1:7.97. The center wavelengths were found to be in the ratio 1:7.1, and the deviation from the ratio of helical pitches is explainable at least in part because the bulk refractive index of zinc selenide decreases a little with wavelength. We concluded that CSTFs can be fabricated to function as circular polarization filters in the mid-wavelength infrared regime.


Distance-Delivered Parent Training for Childhood Disruptive Behavior (Strongest Families™): a Randomized Controlled Trial and Economic Analysis.
Disruptive behavior disorders are prevalent in youth, yet most children with disruptive behavior do not have access to timely, effective treatment. Distance-delivered service (e.g., via telephone, Internet) can overcome several barriers to care. This study tested the effectiveness of a 12-week parent training program, Strongest Families™ Parenting the Active Child, delivered via written material, skill-based videos, and telephone coaching sessions, as compared to usual care in reducing child externalizing behavior. Participants were 172 primary caregivers of a 6- to 12-year-old (29% girls; M age = 8.5 years) recruited from community children's mental health clinics. Participants were randomized to either Strongest Families™ or usual care and completed measures of child externalizing behavior, parenting practices, parent distress, and intervention services consumed at baseline and 5-, 10-, 16-, and 22-months post-baseline. Growth curve analysis showed significant reductions in externalizing behavior in both conditions over time. Improvements were significantly greater at 10 months in the Strongest Families™ condition (d = 0.43). At 22 months, however, the differences were not significant and small in magnitude (d = -0.05). The intervention decreased inconsistent discipline significantly more than usual care. Parents in both conditions showed significant reductions in distress. We also conducted a cost-effectiveness analysis to assess the value for money of the Strongest Families™ program versus usual care. Distance parent training is a promising way to increase access to, and reduce costs associated with, mental health care for families with a child with disruptive behavior.


Metabolic kinetics of pulmonary surfactant in newborn infants using endogenous stable isotope techniques.
We compared kinetic indices of pulmonary surfactant metabolism in premature infants (n = 41) with respect to i) tracer ([1-(13)C1]acetate, [U-(13)C6]glucose, and [1,2,3,4-(13)C4] palmitate), ii) phospholipid (PL) pool (total PLs or disaturated PLs), or iii) instrumentation [gas chromatography/mass spectrometry (GC/MS) or GC-combustion-isotope ratio mass spectometry (GC-C-IRMS)]. Tracer incorporation was measured in PLs extracted from serial tracheal aspirates after a 24 h tracer infusion. The fractional catabolic rate (FCR), representing the total fractional turnover from all sources of surfactant production, was independent of tracer. The fractional synthesis rate of surfactant PL from plasma palmitate was significantly higher than that from palmitate synthesized de novo from acetate, and these two sources of palmitate together accounted for only half of the total surfactant production in preterm infants. [U-(13)C6]glucose showed significant recycling of the (13)C label in intermediary metabolism, distinguishable by GC-MS but not by GC-C-IRMS, resulting in a slower apparent FCR when GC-C-IRMS was used. The extracted PL pool did not affect the surfactant metabolic indices. We suggest that FCR should be used as a primary measure of surfactant turnover kinetics and that tracers labeling both de novo synthesis (acetate and glucose) and preformed pathways (plasma palmitate) can be used to partition the fractional contribution of each pathway to total production.


[Phospholipid methylation in fibroblasts of patients with trisomy 21].
Comparative studies of phospholipid methylation in normal and Down syndrome (trisomy 21) fibroblasts were performed on a series of 7 pairs. Two patients showed an increased phospholipid methylation pathway as compared to the appropriate controls; one patient showed a decreased pathway; and in four patients there was no significant difference. The phospholipid methylation pathway appears to be a minor pathway, as compared to the choline pathway of phosphatidylcholine synthesis and thus does not allow the detection of an eventual disturbance of monocarbon metabolism in Down syndrome.


Clinical comparison of borreliacidal-antibody test with indirect immunofluorescence and enzyme-linked immunosorbent assays for diagnosis of Lyme disease.
To compare the clinical results with the borreliacidal-antibody test (BAT) and two standard screening serologic tests for Lyme disease (LD)-the indirect immunofluorescence assay (IFA) and the enzyme-linked immunosorbent assay (ELISA). The medical records of patients from an endemic LD area, who had been serologically tested during the summer of 1992, were retrospectively categorized by clinical diagnoses without results of serologic tests. Serologic testing, which included control serum samples from patients from a nonendemic LD area, was performed in a blinded fashion, and the results were compared with the clinical categories. Medical records of 307 patients who had been serologically tested for LD were reviewed. We found untreated, active LD in 43 patients (early-localized LD, 21; early-disseminated LD, 14; and late-disseminated LD, 8) and treated LD in 33. Non-LD cases were categorized into acute or chronic conditions of unknown or known cause. Overall, the BAT had a sensitivity of 11% in active LD and did not correlate with results of other conventional surface antibody assays. The IFA and ELISA were more sensitive (67 to 93%), but false-positive results frequently were noted (20 to 40%) in acute and chronic non-LD inflammatory conditions. The specificity of the BAT, IFA, and ELISA in the control group was 96%, 93%, and 97%, respectively. Until the sensitivity, as measured by prospective clinical studies, is improved without loss of specificity, the BAT should not be used clinically for the diagnosis of LD. Suspected cases of LD with atypical clinical manifestations should have positive ELISA and IFA results confirmed with a standardized immunoblot assay.


Clinical and laboratory factors associated with the presence of dysmorphic oocytes in intracytoplasmic sperm injection cycles.
This study investigated the clinical and laboratory factors associated with the presence of dysmorphic oocytes in intracytoplasmic sperm injection (ICSI) cycles. The study involved 200 ICSI cycles, performed from 2020 to 2021, that yielded at least one mature oocyte. Clinical characteristics and ovarian stimulation methods were compared between 68 cycles with at least one dysmorphic oocyte (the dysmorphic group) and 132 cycles with normal-form oocytes only (the non-dysmorphic group). Dysmorphic oocytes were characterized by dark cytoplasm, cytoplasmic granularity, cytoplasmic vacuoles, refractile bodies in the cytoplasm, smooth endoplasmic reticulum in the cytoplasm, an oval shape, an abnormal zona pellucida, a large perivitelline space, debris in the perivitelline space, or an abnormal polar body. The ages of the women, indications for in vitro fertilization, serum anti-Müllerian hormone levels, and rates of current ovarian endometrioma were similar between the dysmorphic and non-dysmorphic groups. In both groups, the three ovarian stimulation regimens, two types of pituitary suppression, and total gonadotropin dose were employed similarly. However, the dual-trigger method was used more frequently in the dysmorphic group (67.6% vs. 50%, p=0.024). The dysmorphic group contained significantly more immature oocytes and exhibited significantly lower oocyte maturity (50% vs. 66.7%, p=0.001) than the non-dysmorphic cycles. Within the dysmorphic group, significantly lower oocyte maturity was found in the cycles using a dual-trigger, but not in those with a human chorionic gonadotropin trigger. ICSI cycles with dysmorphic oocytes are closely associated with reduced oocyte maturity. This association was observed exclusively in dual-trigger cycles.


Advances in vascular brachytherapy over the last 10 years: focus on femoropopliteal applications.
Restenosis and the need for repeated interventions after percutaneous transluminal angioplasty (PTA) remain major drawbacks limiting a widespread application of this minimally invasive technique in the femoropopliteal segment. During the last decade, vascular brachytherapy (BT) emerged as a promising, novel technology with the potential to reduce the rates of restenosis. Meanwhile, several randomized controlled trials have suggested beneficial short and midterm effects of BT in the femoropopliteal arteries. However, despite substantial advances, many questions remain regarding the utility of vascular BT and its dissemination as a practical tool to prevent restenosis. The risk of complications, such as late stent thrombosis, edge effect, catch-up late restenosis, and potential aneurysm formation, as well as the logistical issues associated with the use of this technology in the catheterization laboratory, are delaying the acceptance of BT for routine use. This article reviews the developments of BT for restenosis prevention during the past decade, focusing on implications for peripheral endovascular treatment.


Snake venomics of Crotalus tigris: the minimalist toxin arsenal of the deadliest Nearctic rattlesnake venom. Evolutionary Clues for generating a pan-specific antivenom against crotalid type II venoms [corrected].
We report the proteomic and antivenomic characterization of Crotalus tigris venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7-8 gene products from 6 toxin families; the presynaptic β-neurotoxic heterodimeric PLA(2), Mojave toxin, and two serine proteinases comprise, respectively, 66 and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1-2 PIII-SVMPs each represent 0.1-5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A-subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend toward neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by pedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, Crotalus horridus , Crotalus oreganus helleri, Crotalus scutulatus scutulatus, and Sistrurus catenatus catenatus indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South and North American Crotalus species.


Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.
Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).


GTP cyclohydrolase 1 inhibition attenuates vasodilation and increases blood pressure in rats.
GTP cyclohydrolase 1 is the rate-limiting enzyme in production of tetrahydrobiopterin, a necessary cofactor for endothelial nitric oxide synthase. We tested the hypothesis that inhibition of tetrahydrobiopterin synthesis impairs endothelium-dependent relaxation and increase blood pressure in rats. 2,4-Diamino-6-hydroxypyrimidine (DAHP), a GTP cyclohydrolase 1 inhibitor, was given in drinking water (approximately 120 mg.kg(-1).day(-1)) to male Sprague-Dawley rats for 3 days. Systolic blood pressures were measured (tail-cuff procedure) for 3 days before and each day during DAHP treatment. Blood pressure was significantly increased after DAHP treatment (122 +/- 2 vs. 154 +/- 3 mmHg before and after DAHP, respectively; P < 0.05). Endothelium-intact aortic segments from pentobarbital sodium-anesthetized rats were isolated and hung in organ chambers for measurement of isometric force generation. Aortas from DAHP-treated rats exhibited a decreased maximal relaxation to ACh compared with controls [% relaxation from phenylephrine (10-7 M)-induced contraction: DAHP 57 +/- 6% vs. control 79 +/- 4%; P < 0.05]. Relaxation responses to A-23187 were also decreased in aortas from DAHP-treated rats compared with controls. Incubation with sepiapterin (10-4 M, 1 h), which produces tetrahydrobiopterin via a salvage pathway, restored relaxation to ACh in aortas from DAHP-treated rats. Superoxide dismutase significantly increased ACh-induced relaxation in aortas from DAHP-treated rats, whereas catalase had no effect. Endothelium-independent relaxation to sodium nitroprusside in aortas from DAHP-treated rats was not different from control rats; however, nitric oxide synthase inhibition increased sensitivity to sodium nitroprusside in aortas from DAHP-treated rats. These results support the hypothesis that GTP cyclohydrolase 1 inhibition decreases relaxation and increases blood pressure in rats.


Formation and detection of oxidant-generated tryptophan dimers in peptides and proteins.
Free radicals are produced during physiological processes including metabolism and the immune response, as well as on exposure to multiple external stimuli. Many radicals react rapidly with proteins resulting in side-chain modification, backbone fragmentation, aggregation, and changes in structure and function. Due to its low oxidation potential, the indole ring of tryptophan (Trp) is a major target, with this resulting in the formation of indolyl radicals (Trp•). These undergo multiple reactions including ring opening and dimerization which can result in protein aggregation. The factors that govern Trp• dimerization, the rate constants for these reactions and the exact nature of the products are not fully elucidated. In this study, second-order rate constants were determined for Trp• dimerization in Trp-containing peptides to be 2-6 × 108M-1s-1 by pulse radiolysis. Peptide charge and molecular mass correlated negatively with these rate constants. Exposure of Trp-containing peptides to steady-state radiolysis in the presence of NaN3 resulted in consumption of the parent peptide, and detection by LC-MS of up to 4 different isomeric Trp-Trp cross-links. Similar species were detected with other oxidants, including CO3•- (from the HCO3- -dependent peroxidase activity of bovine superoxide dismutase) and peroxynitrous acid (ONOOH) in the presence or absence of HCO3-. Trp-Trp species were also isolated and detected after alkaline hydrolysis of the oxidized peptides and proteins. These studies demonstrate that Trp• formed on peptides and proteins undergo rapid recombination reactions to form Trp-Trp cross-linked species. These products may serve as markers of radical-mediated protein damage, and represent an additional pathway to protein aggregation in cellular dysfunction and disease.


Pharmacokinetics of budesonide in children with asthma.
The pharmacokinetics of the glucocorticoid budesonide was studied in 6 children with asthma after i.v. injection of 0.5 mg and oral inhalation of 1 mg as an aerosol. Budesonide is a 1:1 mixture of the epimers 22 S and 22 R, which were assayed separately by HPLC combined with RIA. All pharmacokinetic parameters of the epimers differed except the half-life of about 1.5 h. It was significantly shorter than that reported in adults. Plasma clearance averaged 103 l X h-1 for epimer 22 R and 74 l X h-1 for epimer 22 S; calculated per kg body weight these values were about 50% higher than in adults. The difference was about 40% when calculated per m2 of body surface area. Since budesonide is a high-clearance drug, the data indicate higher liver blood flow X kg-1 body weight and m2 of body surface area in children. The systemic availability of the aerosol was approximately 30% of nominal dose, i.e. the same as in adults. The high clearance and short half-life of budesonide in children are advantageous in reducing the risk of possible systemic side-effects of prophylactic treatment of asthma in childhood.


An autoregressive model approach to two-dimensional shape classification.
In this paper, a method of classifying objects is reported that is based on the use of autoregressive (AR) model parameters which represent the shapes of boundaries detected in digitized binary images of the objects. The object identification technique is insensitive to object size and orientation. Three pattern recognition algorithms that assign object names to unlabelled sets of AR model parameters were tested and the results compared. Isolated object tests were performed on five sets of shapes, including eight industrial shapes (mostly taken from the recognition literature), and recognition accuracies of 100 percent were obtained for all pattern sets at some model order in the range 1 to 10. Test results indicate the ability of the technique developed in this work to recognize partially occluded objects. Processing-speed measurements show that the method is fast in the recognition mode. The results of a number of object recognition tests are presented. The recognition technique was realized with Fortran programs, Imaging Technology, Inc. image-processing boards, and a PDP 11/60 computer. The computer algorithms are described.


Senescence of maternal effects: aging influences egg quality and rearing capacities of a long-lived bird.
Senescence could depress prenatal and postnatal capacities of mothers to invest in offspring. Longitudinal observations on the blue-footed booby (Sula nebouxii) revealed a quadratic effect of female age on fledgling production and cohort differences in rate of reproductive decline. By swapping clutches between females of different ages, we tested whether reproductive senescence is due to decline in egg quality or capacity to care. As laying mothers aged, egg size, ulna length of 5-day-old chicks, and ulna growth of second chicks up to age 30 days declined, and as rearing mothers aged, ulna growth and cellular mediated immune response of second chicks diminished. Oddly, senescent females (>11 years) produced more fledglings when rearing offspring of middle-aged females (8-11 years) than when rearing offspring of senescent or young females. Thus, senescence reduced egg quality and rearing capacities, and reproductive success of senescent mothers depended on prenatal effects associated with the age of the laying mother. Reproductive senescence of boobies may involve constraints on resources allocated to reproduction as well as adaptive adjustment of provision and care according to offspring value, implying that negative effects of senescence on offspring survival can be ameliorated by plasticity in postlaying or postnatal care.


The challenge to delivering oral health services in rural America.
This review identifies the challenges to oral health in rural America and describes areas of innovation in prevention, delivery of dental services, and workforce development that may improve oral health for rural populations. This descriptive article is based on literature reviews and personal communications. Rural populations have lower dental care utilization, higher rates of dental caries, lower rates of insurance, higher rates of poverty, less water fluoridation, fewer dentists per population, and greater distances to travel to access care than urban populations. Improving the oral health of rural populations requires practical and flexible approaches to expand and better distribute the rural oral health workforce, including approaches tailored to remote areas. Solutions that involve mass prevention/public health interventions include increasing water fluoridation, providing timely oral health education, caries risk assessment and referral, preventive services, and offering behavioral interventions such as smoking and tobacco cessation programs. Solutions that train more providers prepared to work in rural areas include recruiting students from rural areas, training students in rural locations, and providing loan repayment and scholarships. Increasing the flexibility and capacity of the oral health workforce for rural areas could be achieved by creating new roles for and new types of providers. Solutions that overcome distance barriers include mobile clinics and telehealth technology. Rural areas need flexibility and resources to develop innovative solutions that meet their specific needs. Prevention needs to be at the front line of rural oral health care, with systematic approaches that cross health professions and health sectors.


Conduction and Gating Properties of the TRAAK Channel from Molecular Dynamics Simulations with Different Force Fields.
In recent years, the K2P family of potassium channels has been the subject of intense research activity. Owing to the complex function and regulation of this family of ion channels, it is common practice to complement experimental findings with the atomistic description provided by computational approaches such as molecular dynamics (MD) simulations, especially, in light of the unprecedented timescales accessible at present. However, despite recent substantial improvements, the accuracy of MD simulations is still undermined by the intrinsic limitations of force fields. Here, we systematically assessed the performance of the most popular force fields employed to study ion channels at timescales that are orders of magnitude greater than the ones accessible when these energy functions were first developed. Using 32 μs of trajectories, we investigated the dynamics of a member of the K2P ion channel family, the TRAAK channel, using two established force fields in simulations of biological systems: AMBER and CHARMM. We found that while results are comparable on the nanosecond timescales, significant inconsistencies arise at microsecond timescales.