CALCIUM OXIDE REMEDIATION OF ANTHROPOGENIC CONTAMINATION OF WATER AT THE GBNERR IN MISSISSIPPI.
Grand Bay National Estuarine Research Reserve (GBNERR) is an important ecosystem in the Mississippi Gulf Coast. The GBNERR may be a potential source for contamination with anthropogenic bacterial pathogens that may play a significant role in the causation of waterborne human diseases. The objective of this study was to evaluate the interaction of physicochemical and microbiological water quality parameters at the GBNERR, determine quantitative levels and establish the potential for remediation of post-contamination of water and seafood by human fecal pollution from anthropogenic sources at the reserve. Water samples were collected aseptically from Bayous Heron, Cumbest, Point Aux Chenes Bay and Bangs Lake (Pine-O-Pine). Physicochemical parameters were determined using standard protocols. Eight bacteria/parasitic species including Cryptosporidium were concentrated from water samples by membrane filtration. Water samples were tested for the presence of traditional indicator microorganisms including: heterotrophic (HPC), total coliforms (TC), fecal coliforms (FC) and enterococcus (ENT) in CFU/ml concentrations. Mean values of temperature, specific conductivity, dissolved oxygen and pH were within acceptable levels in comparison to MDEQ, USEPA and the USGS standards during the time of investigation. However, the values of turbidity in Grand Bay water exceeded USEPA recommended levels in several occasions during the investigation. Data from this study indicates significant variability (p < 0.0001) in mean bacteria concentrations between sites. The data also indicates significant impact of Calcium oxide treatment in the remediation of post contamination and survival of pathogens from the GBNERR Bayous Heron, Cumbest and Pine-O-Pine when compared with control findings. The interaction of physicochemical and microbiological parameters of water through external chemical manipulation by Calcium oxide may provide utility in the remediation of post-contamination with anthropogenic pathogens such as E. coli, Enterococci, Campylobacter, Vibrio, Giardia and Cryptosporidium. Presence of high numbers of indicator bacteria suggest public health concerns for oyster and shellfish consumers as well as other water contact activities. Hence, control strategies should be developed and implemented to prevent or remediate any future contamination of the GBNERR waters citing the economic impact of such contamination on shell fish fishing activities on the reserve.


Antigen-specific human NKT cells from tuberculosis patients produce IL-21 to help B cells for the production of immunoglobulins.
Natural killer T (NKT) cells from mouse and human play an important role in the immune responses against Mycobacterium tuberculosis. However, the function of CD3(+)TCRvβ11(+) NKT cells at the local site of M. tuberculosis infection remains poorly defined. In the present study, we found that after stimulation with M. tuberculosis antigens, NKT cells isolated from tuberculosis (TB) pleural fluid mononuclear cells (PFMCs) produced IL-21 and other cytokines including IFN-γ, TNF-α, IL-2 and IL-17. IL-21-expressing NKT cells in PFMCs displayed effector memory phenotype, expressing CD45RO(high)CD62L(low)CCR7(low). Moreover, NKT cells expressed high levels of CXCR5 and all of IL-21-expressing NKT cells co-expressed CXCR5. The frequency of BCL-6-expression was higher in IL-21-expressing but not in non-IL-21-expressing CD3(+)TCRvβ11(+) NKT cells. Sorted CD3(+)TCRvβ11(+) NKT cells from PFMCs produced IFN-γ and IL-21 after stimulation, which expressed CD40L. Importantly, CD3(+)TCRvβ11(+) NKT cells provided help to B cells for the production of IgG and IgA. Taken together, our data demonstrate that CD3(+)TCRvβ11(+) NKT cells from a local site of M. tuberculosis infection produce IL-21, express CXCR5 and CD40L, help B cells to secrete IgG and IgA, and may participate in local immune responses against M. tuberculosis infection.


Interferon-gamma-induced local leukocytoclastic vasculitis at the subcutaneous injection site.
Cutaneous reactions associated with interferons (IFNs) treatment are either localized or generalized. The most common presentation of localized reactions at IFNs injection site is usually an erythematous patch or plaque. Local leukocytoclastic vasculitis presenting with cutaneous necrosis is extremely rare. We report a 19-year-old man with hepatitis B who had local leukocytoclastic vasculitis induced by interferon-gama injection at the injection site. After changing the injection sites and using the combined treatment of prednisone and colchicine, the previous lesion healed and no other cutaneous lesion occurred. We also made a mini review of such cases.


Interleukin-1 directly stimulates the release of corticotrophin releasing factor from rat hypothalamus.
While interleukin-1 (IL-1), a monocyte-derived polypeptide, clearly stimulates the hypothalamo-pituitary-adrenal (HPA) axis, its precise site of action is controversial. In these studies, the possibility of a hypothalamic and/or a pituitary site of action was investigated in vitro, using incubated rat hypothalami and perifused dispersed pituitary cells. Both forms of IL-1, IL-1 alpha and IL-1 beta, produced a dose-dependent stimulation of CRF-41 release from incubated rat hypothalami in the dose range of 1-100 U/ml (p less than 0.01). However, concentrations of both interleukins of 1-1,000 U/ml given as 10-min infusions had no effect on ACTH release from dispersed pituitary cells. Moreover, IL-1 beta, used in the concentration range of 1-100 U/ml, was unable to potentiate CRF-41-induced ACTH release. These data therefore provide evidence that at least the acute stimulatory effects of IL-1 on the HPA axis are predominantly mediated via a direct stimulation of hypothalamic CRF-41, suggesting that the hypothalamus may provide an interface between the neuroendocrine and immune axes.


Roles of Exosome-Like Vesicles Released from Inflammatory C2C12 Myotubes: Regulation of Myocyte Differentiation and Myokine Expression.
The complicated differentiation processes of cells in skeletal muscle against inflammation that induce muscle atrophy are not fully elucidated. Given that skeletal muscle is a secretory organ, we evaluated the effects of inflammation on myogenic signals and myokine expression, and the roles of inflammatory exosomes released by myotubes in myogenic differentiation. Inflammation was induced by treatment of fully differentiated C2C12 myotubes with a cytokine mixture of TNF-α and INF-γ. Exosome-like vesicles (ELVs) were isolated from conditioned media of control or inflamed myotubes and incubated with myoblasts. The expression of molecular switches that contribute to myogenic differentiation, including several kinases, their downstream targets, and myokines, were evaluated using immunoblot analysis in inflamed myotubes and in myoblasts treated with ELVs. Inflammation activated molecular mechanisms contributing to muscle atrophy, including AMPK, p-38 MAPK and JNK, while inhibiting Akt-mediated myogenic signals. In addition, inflammation induced myostatin expression with suppression of a myostatin-counteracting myokine, decorin. Well-characterized ELVs released from inflamed myotubes induced myoblast inflammation and inhibited myogenic mechanisms while stimulating atrophic signals. Inflammation of skeletal muscle induces muscle atrophy via multiple mechanisms, including the regulation of myokines and kinases. Inflammatory ELVs are likely to contribute to inflammation-induced muscle atrophy.


Same-Sex Parents and Children's School Progress: An Association That Disappeared Over Time.
Research is divided as to whether children living in same-sex parent families achieve different outcomes compared with their peers. In this article, we improve on earlier estimates of such differences and subsequently study whether and why the association between parental union sex composition and children's school progress changed over time. Data from the American Community Survey waves 2008-2015 (N = 1,952,490 including 7,792 children living with a same-sex couple) indicate that children living with same-sex couples were historically more likely to be behind in school but that this association disappeared over time. Changes in socioeconomic characteristics of same-sex couples played a minor role. In 2008, it was only in areas with unfavorable laws and attitudes toward same-sex couples that children living with same-sex couples were more likely to be behind in school. This was especially the case for adopted children. In more recent periods, no effect of parental union sex composition on school progress is observed within any area or among any group studied. Based on where and when these changes took place, it is suggested that changing attitudes toward same-sex couples might have played an important role in equalizing school progress across groups.


Pigments induce folding of light-harvesting chlorophyll a/b-binding protein.
The conformational behaviour of the light-harvesting chlorophyll a/b-binding protein (LHCP), the apoprotein of the major light-harvesting complex (LHCII) of photosystem II in plants, has been studied. According to the circular dichroism in the ultraviolet range measured with isolated LHCII, the protein in the complex adopts a folded structure with a high content of alpha helix (about 60%), whereas the non-pigmented, solubilized protein has a less ordered structure (about 20% alpha helix). LHCP-pigment complexes that have been reconstituted from the overexpressed protein and isolated pigments in the presence of detergents display a protein CD signal similar to that of authentic LHCII, indicating that LHCP folds into the native structure during the reconstitution procedure. Renaturation of LHCP in these experiments is dependent on the presence of pigments and the formation of stable LHCP-pigment complexes. Pigment-induced engagement of LHCP in a compact structure has also been shown by two additional experimental approaches. (a) Upon complex formation, LHCP or its precursor (pLHCP) becomes resistant to trypsin digestion with the exception of an N-terminal segment of the protein; the same protection of LHCP is known to occur in intact thylakoids. (b) Pigment binding renders a cysteine residue within the N-proximal hydrophobic domain of the protein as well as a newly introduced cysteine four amino acid positions from the C terminus inaccessible to modification with a sulfhydryl-specific label whereas the N terminus stays susceptible to specific labelling. These observations support the notion that only the N terminus protrudes from a compact protein-pigment structure in LHCII. The fact that the major part of LHCP is trypsin-resistant in pigmented complexes reconstituted in the absence of a membrane or even lipids justifies caution in using protection against trypsin as a criterion for the integration of LHCP into the thylakoid membrane.


New chromogenic substrates for the assay of alpha-amylase and (1 leads to 4)-beta-D-glucanase.
New chromogenic substrates have been developed for the quantitative assay of alpha-amylase and (1 leads to 4)-beta-D-glucanase. These were prepared by chemically modifying amylose or cellulose before dyeing, to increase solubility. After dyeing, the substrates were either soluble or could be readily dispersed to form fine, gelatinous suspensions. Assays based on the use of these substrates are sensitive and highly specific for either alpha-amylase or (1 leads to 4)-beta-D-glucanase. The method of preparation can also be applied to obtain substrates for other endo-hydrolases.


Oroxylin a Attenuates Limb Ischemia by Promoting Angiogenesis via Modulation of Endothelial Cell Migration.
Oroxylin A (OA) has been shown to simultaneously increase coronary flow and provide a strong anti-inflammatory effect. In this study, we described the angiogenic properties of OA. OA treatment accelerated perfusion recovery, reduced tissue injury, and promoted angiogenesis after hindlimb ischemia (HLI). In addition, OA regulated the secretion of multiple cytokines, including vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANG-2), fibroblast growth factor-basic (FGF-2), and platelet derived growth factor BB (PDGF-BB). Specifically, those multiple cytokines were involved in cell migration, cell population proliferation, and angiogenesis. These effects were observed at 3, 7, and 14 days after HLI. In skeletal muscle cells, OA promoted the release of VEGFA and ANG-2. After OA treatment, the conditioned medium derived from skeletal muscle cells was found to significantly induce endothelial cell (EC) proliferation. OA also induced EC migration by activating the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil kinase 2 (ROCK-II) signaling pathway and the T-box20 (TBX20)/prokineticin 2 (PROK2) signaling pathway. In addition, OA was able to downregulate the number of macrophages and neutrophils, along with the secretion of interleukin-1β, at 3 days after HLI. These results expanded current knowledge about the beneficial effects of OA in angiogenesis and blood flow recovery. This research could open new directions for the development of novel therapeutic intervention for patients with peripheral artery disease (PAD).


Activation Mechanism and Cellular Localization of Membrane-Anchored Alginate Polymerase in Pseudomonas aeruginosa.
The exopolysaccharide alginate, produced by the opportunistic human pathogen Pseudomonas aeruginosa, confers a survival advantage to the bacterium by contributing to the formation of characteristic biofilms during infection. Membrane-anchored proteins Alg8 (catalytic subunit) and Alg44 (copolymerase) constitute the alginate polymerase that is being activated by the second messenger molecule bis-(3', 5')-cyclic dimeric GMP (c-di-GMP), but the mechanism of activation remains elusive. To shed light on the c-di-GMP-mediated activation of alginate polymerization in vivo, an in silico structural model of Alg8 fused to the c-di-GMP binding PilZ domain informed by the structure of cellulose synthase, BcsA, was developed. This structural model was probed by site-specific mutagenesis and different cellular levels of c-di-GMP. Results suggested that c-di-GMP-mediated activation of alginate polymerization involves amino acids residing at two loops, including H323 (loop A) and T457 and E460 (loop B), surrounding the catalytic site in the predicted model. The activities of the respective Alg8 variants suggested that c-di-GMP-mediated control of substrate access to the catalytic site of Alg8 is dissimilar to the known activation mechanism of BcsA. Alg8 variants responded differently to various c-di-GMP levels, while MucR imparted c-di-GMP for activation of alginate polymerase. Furthermore, we showed that Alg44 copolymerase constituted a stable dimer, with its periplasmic domains required for protein localization and alginate polymerization and modification. Superfolder green fluorescent protein (GFP) fusions of Alg8 and Alg44 showed a nonuniform, punctate, and patchy arrangement of both proteins surrounding the cell. Overall, this study provides insights into the c-di-GMP-mediated activation of alginate polymerization while assigning functional roles to Alg8 and Alg44, including their subcellular localization and distribution.IMPORTANCE The exopolysaccharide alginate is an important biofilm component of the opportunistic human pathogen P. aeruginosa and the principal cause of the mucoid phenotype that is the hallmark of chronic infections of cystic fibrosis patients. The production of alginate is mediated by interacting membrane proteins Alg8 and Alg44, while their activity is posttranslationally regulated by the second messenger c-di-GMP, a well-known regulator of the synthesis of a range of other exopolysaccharides in bacteria. This study provides new insights into the unknown activation mechanism of alginate polymerization by c-di-GMP. Experimental evidence that the activation of alginate polymerization requires the engagement of specific amino acid residues residing at the catalytic domain of Alg8 glycosyltransferase was obtained, and these residues are proposed to exert an allosteric effect on the PilZAlg44 domain upon c-di-GMP binding. This mechanism is dissimilar to the proposed mechanism of the autoinhibition of cellulose polymerization imposed by salt bridge formation between amino acid residues and released upon c-di-GMP binding, leading to activation of polymerization. On the other hand, conserved amino acid residues in the periplasmic domain of Alg44 were found to be involved in alginate polymerization as well as modification events, i.e., acetylation and epimerization. Due to the critical role of c-di-GMP in the regulation of many biological processes, particularly the motility-sessility switch and also the emergence of persisting mucoid phenotypes, these results aid to reach a better understanding of biofilm-associated regulatory networks and c-di-GMP signaling and might assist the development of inhibitory drugs.


Nursing in today's multicultural society: a transcultural perspective.
The argument that nurses need to consider the different ethnic and cultural backgrounds of their patients, in order to provide effective and safe nursing care, is presented. The concept of culture is then discussed in order to provide the conceptual context for examining transcultural nursing which is described as nursing practice that accounts for patients' cultural difference. This paper also explores how transcultural nursing is the means for nurses to enable their patients to improve or sustain their health as both nurses and patients struggle with the contradictions of racism, oppression and 'caring' that co-exist in a multicultural society.


[Co-authorship and collaboration networks in Spanish research into multiple sclerosis (1996-2010)].
INTRODUCTION. Scientific collaboration is vital for to the advance of knowledge and is especially important in health sciences. The aim of this study is to identify scientific collaboration indicators and co-authorship networks of researchers and Spanish institutions that publish on multiple sclerosis (MS) during the period 1996-2010. MATERIALS AND METHODS. The analyzed papers were obtained from Web of Science and Scopus international databases, and IBECS and IME national databases, applying specific search profiles in each one of them. In order to identify collaboration networks all signed papers were quantified and co-authored measures were obtained, as the different indexes, degree, intermediation and closeness. RESULTS. 1,613 articles were published in the period 1996-2010, 92% of them in collaboration. With 10 or more works signed in collaboration, 20 Spanish research groups in MS were identified. 64.23% of the papers were published in collaboration between Spanish institutions, and 33.85% were in collaboration with foreign institutions. The institutional participation analysis has identified a large network of institutional partnerships that integrates 27 institutions, with the Hospital Vall d'Hebron in a central position. International collaboration is headed by the U.S. and European countries, most notably the UK and Italy. CONCLUSION. The most collaborative authors, institutions, and work groups in Spanish research in MS have been identified. Despite these indicators that characterize the collaboration in this area, it is necessary to enhance cooperation between them, since this collaboration is positively related to the quality and impact of research and publications.


Toward Effective and Adsorption-Based Antifouling Zipper Brushes: Effect of pH, Salt, and Polymer Design.
The undesired spontaneous deposition and accumulation of matter on surfaces, better known as fouling, is a problematic and often inevitable process plaguing a variety of industries. This detrimental process can be reduced or even prevented by coating surfaces with a dense layer of end-grafted polymer: a polymer brush. Producing such polymer brushes via adsorption presents a very attractive technique, as large surfaces can be coated in a quick and simple manner. Recently, we introduced a simple and scalable two-step adsorption strategy to fabricate block copolymer-based antifouling coatings on hydrophobic surfaces. This two-step approach involved the initial adsorption of hydrophobic-charged diblock copolymer micelles acting as a primer, followed by the complexation of oppositely charged-antifouling diblock copolymers to form the antifouling brush coating. Here, we significantly improve this adsorption-based zipper brush via systematic tuning of various parameters, including pH, salt concentration, and polymer design. This study reveals several key outcomes. First of all, increasing the hydrophobic/hydrophilic block ratio of the anchoring polymeric micelles (i.e., decreasing the hydrophilic corona) promotes adsorption to the surface, resulting in the most densely packed, uniform, and hydrophilic primer layers. Second, around a neutral pH and at a low salt concentration (1 mM), complexation of the weak polyelectrolyte (PE) blocks results in brushes with the best antifouling efficacy. Moreover, by tuning the ratio between these PE blocks, the brush density can be increased, which is also directly correlated to the antifouling performance. Finally, switching to different antifouling blocks can increase the internal density or strengthen the bound hydration layer of the brush, leading to an additional enhancement of the antifouling properties (>99% lysozyme, 87% bovine serum albumin).


Analysis of the Y402H variant of the complement factor H gene in age-related macular degeneration.
Recent studies in U.S. populations have indicated that the Y402H variant of the complement factor H (CFH) gene contains a major risk susceptibility allele for age-related macular degeneration (AMD). This study was conducted to ascertain whether this is also true in a non-U.S. population and also whether the at-risk allele is associated with the clinical phenotype of disease and the age at diagnosis. Two hundred thirty-six unrelated individuals with AMD and 144 unrelated but ethnically matched control subjects were recruited and examined. All subjects completed a standard questionnaire, were given a fundus examination, and provided a blood sample for DNA extraction. Alleles of Y402H in the CFH gene were determined by use of a MALDI-TOF-based approach followed by statistical analysis. Individuals with AMD who had at least one copy of the C allele of Y402H had an increased risk of disease (odds ratio [OR] 2.98; 95% confidence interval [CI] 1.81-4.93) compared with cases with the T allele. On subgroup analysis, this risk was found to be most significant in individuals with neovascular disease (OR 4.34; 95% CI 1.94, 9.71). In addition, individuals with neovascular disease who were homozygous CC presented with a significant 7.0-year earlier age at diagnosis relative to those individuals who were homozygous TT. The population-attributable risk for the C allele ranged between 47% to 69%, depending on the AMD disease subtype. The C allele of Y402H represents a significant risk factor in individuals with AMD, and this effect is most pronounced in individuals with neovascular disease.


Performance, egg quality, and liver lipid reserves of free-range laying hens naturally infected with Ascaridia galli.
A study was conducted to determine the performance, egg quality, and liver lipid reserves of laying hens exposed to ranges contaminated with Ascaridia galli. Sixteen-week-old Lohmann Brown laying hens (n = 200) were divided into 4 treatments with 5 replicates containing 10 hens per pen. Hens of treatment 1 [negative control (NC)] ranged on a decontaminated area, and hens of treatments 2 (low infection) and 3 (medium infection) ranged on areas previously contaminated by hens artificially infected with 250 and 1,000 embryonated A. galli eggs, respectively. The hens of treatment 4 [positive control (PC)] ranged on areas previously contaminated by hens artificially infected with 2,500 embryonated A. galli eggs, and in addition these hens were orally inoculated with 1,000 embryonated eggs. Results indicated that hens of the medium infection group had a higher number of intestinal A. galli worms and A. galli eggs in the coprodeum excreta (43.9 ± 4.0 and 3,437 ± 459 eggs/g) compared to hens of the low infection group (23.8 ± 4.0 and 1,820 ± 450 eggs/g) (P < 0.01) and similar worm counts to PC hens (34.4 ± 4.0 and 2,918 ± 474) (P > 0.05). Egg production, egg mass, feed intake, and feed conversion ratio (FCR) were not affected by A. galli infection (P > 0.05). Egg quality parameters (egg weight, shell reflectivity, shell weight, shell thickness, shell percentage, shell breaking strength, deformation, albumen height, Haugh unit, and yolk score) were not affected by A. galli infection (P > 0.05). Highly infected hens had lower liver lipid content (2.72 ± 0.51 g) compared to uninfected hens (4.46 ± 0.58 g, P < 0.01). The results indicate that exposure to ranges contaminated with A. galli resulted in infection of the ranging hens, but this did not affect egg production or egg quality. Infection with A. galli lowered the liver lipid reserves of the host significantly, suggesting infected hens use more energy reserves for maintenance and production.


[Low influenza vaccination rates among healthcare workers. Time to take a different approach].
Despite decades of effort to encourage healthcare workers (HCWs) to be immunized against influenza, vaccination levels remain insufficient in Germany, with only one in five HCWs receiving the annual influenza vaccination. To prevent nosocomial influenza outbreaks and to ensure the protection of patients and HCWs, new approaches to increase vaccination rates are needed. The experience in the USA has shown that declination forms have increased vaccination coverage. One possible approach for Germany would be a combination of declination forms with the exclusive use of vaccinated staff in defined areas. This approach would respect a HCWs decision to refuse medical treatment, while at the same time protecting vulnerable patients. In addition, the influenza vaccination rates of HCWs should be collected in order to evaluate the implementation of vaccination policies. Similar to the setting of desired vaccination coverage for the chronically ill, a clearly defined vaccination goal should be established for HCWs.


Effects of Induced Mindfulness at Night on Repetitive Negative Thinking: Ecological Momentary Assessment Study.
Repetitive negative thinking (RNT) is a cognitive risk factor for various disorders. Although brief mindfulness-based interventions (MBIs; lasting 20-30 minutes or shorter) are effective tools to reduce RNT, the effect of a minimal (5-minute) MBI remains largely unknown. We investigated the acute changes in RNT induced by a 10-day minimal MBI (body scan before sleeping) using an ecological momentary assessment (EMA) administered during the MBI training phase. In addition, we examined longer-term effects on the postintervention and 2-month follow-up assessments for questionnaire-based RNT and psychological distress. A total of 68 participants (community sample, aged 18-55 years; n=58, 85% women) were randomly allocated to either the intervention group (n=35, 51%) or the no-training control group (n=33, 49%). Both groups completed a 10-day EMA phase of RNT, during which only the intervention group performed a daily 5-minute body scan before sleeping. The intervention group showed a significantly larger reduction in questionnaire-based RNT than the control group at the follow-up assessment (for growth-curve modeling analysis [GMA], dGMA=-0.91; P<.001), but this effect was not observed during the EMA phase or at the postintervention assessment. Furthermore, the intervention group showed significantly larger decreases in stress both at the postintervention (dGMA=-0.78; P<.001) and follow-up (dGMA=-0.60; P<.001) assessments than the control group. We found no intervention effects on depressive and anxiety symptoms. A 5-minute body scan before sleeping reduces RNT and stress when continued for at least 10 days; however, the results suggest that this effect only appears with some time lag because no acute changes during and immediately after the intervention emerged for RNT.


Heart disease prevention in women: promoting exercise.
To reinforce the importance of exercise in reducing heart disease in women and to describe motivational interviewing (MI), an effective and efficient approach to promoting exercise with women in a brief office visit with a nurse practitioner (NP). Information was obtained from a literature review. Two brief examples from clinical practice are presented. Although exercise can reduce the risk of heart disease in women, most women do not exercise enough to achieve a risk reduction. Although health promotion is a key goal of the NP, it can be difficult to incorporate in a busy practice. When time is limited, brief MI interactions can be effective in less than 10 min, and the results surpass those of the traditional advice to exercise. MI is an effective approach to exercise counseling that the NP can quickly learn and successfully conduct within the confines of a brief office visit.


Commentary: something has to give. the question is, what?
A large facet joint cyst, the size of a walnut, at L5-S1 resulted in an "emergency" laminectomy at Asheville, North Carolina's Mission Hospitals on this 79-year-old active equestrian and retired healthcare consultant, who more than a half-century earlier was formally trained in hospital administration and medical economics. While as an inpatient, he reflected broadly about today's healthcare expenditures, utilization, and quality, and speculated on possible future remedies.


Influence of thermomechanical processing on biomechanical compatibility and electrochemical behavior of new near beta alloy, Ti-20.6Nb-13.6Zr-0.5V.
This paper presents the results for the effect of different methods of thermomechanical processing on the mechanical properties and electrochemical behavior of metastable β alloy Ti-20.6Nb-13.6Zr-0.5V (TNZV). The thermomechanical processing included hot working, solution heat treatments at different temperatures, and cooling rates in addition to aging. The thermomechanical processing conditions used in the study resulted in attainment of a wide range of microstructures with varying spatial distributions and morphologies of elongated/equiaxed α, β phases, or martensite, as a result of which several tensile properties were achieved. Aging treatment led to an increase in hardness, elastic modulus, and tensile strength and a decrease in ductility (elongation). Electrochemical tests indicated that the TNZV alloy undergoes spontaneous passivation due to spontaneous formation of an oxide film in the environment of the human body. Because the air-cooled samples possessed high hardness and also a fine grain size, they showed a lower corrosion rate than the samples treated under other conditions.


Lifestyle-related factors and colorectal polyps: preliminary results from a Norwegian follow-up and intervention study.
Lifestyle-related variables are suggested to play a major role in the development of colorectal cancer (CRC). Within a 3-year follow-up and intervention study with calcium and antioxidants against growth and recurrence of colorectal polyps, supplementary studies were performed in which different aspects of lifestyle were examined. Instead of polypectomy at diagnosis, polyps <9 mm were left in situ in 116 polyp patients (50-76 years, 50% men). After 3 years, all polyps were removed and subjected to histology. Two different sets of control groups were included (all controls were age- and sex-matched and proven to be free of polyps). We applied two different methods in order to assess most exposure variables. Generally, in case-control studies, the validity of the study outcomes is high if they are similar regardless of choice of controls and methods, since bias due to these choices may affect the risk estimates. In contrast, the validity of the study outcomes is low if dependent upon these choices. Our preliminary data support the theory that different factors may be of importance in different stages of the neoplastive formation, and that lifestyle-related factors are likely to play a major role in CRC development.


The effects of active and passive participation in musical activity on the immune system as measured by salivary immunoglobulin A (SIgA).
The purposes of this study were (a) to determine if musical activity would produce a significant change in the immune system as measured by Salivary Immunoglobulin A (SIgA), and (b) to determine if active participation in musical activity had a significantly different effect on the immune system than passive participation. Thirty-three participants (28 women and 5 men) were randomly assigned to one of 3 groups, 2 experimental and 1 control. Active group participants participated in a 30-minute session where they played various percussive instruments and sang. Passive group participants listened to 30 minutes worth of live music. Saliva samples were taken before and after sessions and SIgA concentrations were determined using radial immunodiffusion technique. All groups were found to be significantly different from each other. SIgA levels of the active group showed a significantly greater increase than those of the passive group and the control group, suggesting that active participation in musical activity produces a greater effect on the immune system than passive participation.


The role of microhabitat in predation on females with alternative dorsal patterns in a small Costa Rican anole (Squamata: Dactyloidae).
Predation is one of the major selective agents influencing evolution of color patterns. Cryptic color patterns decrease detection probability by predators, but their concealing function depends on the background against which patterns are seen; therefore, habitat use and color patterns are tightly linked. In many anole species, females exhibit variation in dorsal color patterns; the drab and perhaps cryptic colors of the patterns suggest a predator avoidance function behind this polymorphism. We tested whether these different color patterns experience different predation rates depending on their microhabitat. We expected each pattern to form at least one optimal combination with a typically used micro-habitat that would result in lower predation compared to other morphs in the same micro-habitat. We tested this hypothesis for anoles at La Selva, Costa Rica, using clay models resembling a common species at this site: Norops humilis. The first experiment tested for variation in predation on various substrates. We included leaf litter, live leaves, and two size classes of woody stems, using 44 models for each pattern substrate combination. A second experiment tested effects of perch height (10 and 60cm) and diameter (< 2 cm and > 5 cm), with 50 models for each pattern perch combination. We found differences in predation rates between the morphs depending on their micro-habitat. Specifically, the striped morph had a significant advantage over the others on green leaves. In the second experiment, striped morphs showed significantly lower predation on low than on high perches, irrespective of perch diameter. Reticulated models had an advantage over other morphs on thin stems for the first experiment, where models were placed about 60cm high. Diameter did not have a significant effect on predation for reticulated morphs when height classes were combined. Dotted models did not experience an advantage over the other morphs in any of the treatments. In leaf litter and on thick perches no morph had any advantage over another, and leaf litter predation rates were generally low. These results support a role for predation in maintaining multiple female morphs within small Costa Rican anoles, such as N. humilis.


Mung bean proteins and peptides: nutritional, functional and bioactive properties.
To date, no extensive literature review exists regarding potential uses of mung bean proteins and peptides. As mung bean has long been widely used as a food source, early studies evaluated mung bean nutritional value against the Food and Agriculture Organization of the United Nations (FAO)/the World Health Organization (WHO) amino acids dietary recommendations. The comparison demonstrated mung bean to be a good protein source, except for deficiencies in sulphur-containing amino acids, methionine and cysteine. Methionine and cysteine residues have been introduced into the 8S globulin through protein engineering technology. Subsequently, purified mung bean proteins and peptides have facilitated the study of their structural and functional properties. Two main types of extraction methods have been reported for isolation of proteins and peptides from mung bean flours, permitting sequencing of major proteins present in mung bean, including albumins and globulins (notably 8S globulin). However, the sequence for albumin deposited in the UniProt database differs from other sequences reported in the literature. Meanwhile, a limited number of reports have revealed other useful bioactivities for proteins and hydrolysed peptides, including angiotensin-converting enzyme inhibitory activity, anti-fungal activity and trypsin inhibitory activity. Consequently, several mung bean hydrolysed peptides have served as effective food additives to prevent proteolysis during storage. Ultimately, further research will reveal other nutritional, functional and bioactive properties of mung bean for uses in diverse applications.


Intestinal coinfection with numerous Giardia trophozoites and Vibrio cholerae in hospitalized children with watery diarrhea.
During the recent cholera epidemic which affected Peru and other Latin American countries, fresh stool samples of 100 hospitalized children were assessed February through April 1991. The children had been admitted because of profuse watery diarrhea. The microbiologic study of wet mount preparations showed curved bacteria suspicious for cholera agent and confirmed afterward to be Vibrio cholerae 01 scrotype Inaba. In 30% of such cases, besides the curved bacteria, a strikingly large number of trophozoites of Giardia intestinalis were observed. The same samples studied by permanent stains confirmed the presence of Giardia trophozoites. To our knowledge, the association of Giardia with serious epidemic cholera infection has not been previously described. All patients were admitted because of severe dehydration requiring intravenous fluid replacement, which might suggest a synergistic role for the above-noted coinfection. Adequately designed case-control studies are needed to ascertain the frequency and the pathophysiologic and clinical significance of such an unusual association.


Viscosity effect on the ultrafast bond twisting dynamics in an amyloid fibril sensor: thioflavin-T.
The femtosecond fluorescence upconversion technique is used to study the effect of viscosity on the excited state relaxation dynamics of an amyloid fibril sensor, thioflavin-T, in different solvent media. The excited state decay in all of the solvents is seen to be dependent on the emission wavelength. From the constructed time-resolved emission spectra, it is seen that the present system shows dynamic Stokes' shift as well as an appreciable increase in the spectral width with time. These temporal spectral characteristics of time-resolved emission spectra have been assigned to the formation of a new emissive species from the locally excited state of the thioflavin-T molecule. The formation of the new emissive state from the locally excited state is also supported by the fact that an iso-emissive point appears in the time-resolved area normalized emission spectra. From the detailed study on the excited state dynamics of thioflavin-T as a function of solvent viscosity, it is concluded that the new emissive state is formed due to the twisting around the central C-C single bond in the excited state of thioflavin-T. The formation rate of the twisted emissive state from the locally excited state is found to be nicely correlated with the viscosity of the medium.


Y chromosomal evidence on the origin of northern Thai people.
The Khon Mueang represent the major group of people present in today's northern Thailand. While linguistic and genetic data seem to support a shared ancestry between Khon Mueang and other Tai-Kadai speaking people, the possibility of an admixed origin with contribution from local Mon-Khmer population could not be ruled out. Previous studies conducted on northern Thai people did not provide a definitive answer and, in addition, have largely overlooked the distribution of paternal lineages in the area. In this work we aim to provide a comprehensive analysis of Y paternal lineages in northern Thailand and to explicitly model the origin of the Khon Mueang population. We obtained and analysed new Y chromosomal haplogroup data from more than 500 northern Thai individuals including Khon Mueang, Mon-Khmer and Tai-Kadai. We also explicitly simulated different demographic scenarios, developed to explain the Khon Mueang origin, employing an ABC simulation framework on both mitochondrial and Y microsatellites data. Our results highlighted a similar haplogroup composition of Khon Mueang and Tai-Kadai populations in northern Thailand, with shared high frequencies of haplogroups O-PK4, O-M117 and O-M111. Our ABC simulations also favoured a model in which the ancestors of modern Khon Mueang originated recently after a split from the other Tai-Kadai populations. Our different analyses concluded that the ancestors of Khon Mueang are likely to have originated from the same source of the other Tai-Kadai groups in southern China, with subsequent admixture events involving native Mon-Khmer speakers restricted to some specific populations.


Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer.
We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk. Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays. Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-related genes, and with lower expression of estrogen receptor (ER) -related genes. In 82 independent patients treated with neoadjuvant paclitaxel and doxorubicin, DNA microarray data were available for 79 of the 86 genes. In univariate analysis, 24 genes correlated with pCR with P < .05 (false discovery, four genes) and 32 genes showed correlation with P < .1 (false discovery, eight genes). The Recurrence Score was positively associated with the likelihood of pCR (P = .005), suggesting that the patients who are at greatest recurrence risk are more likely to have chemotherapy benefit. Quantitative expression of ER-related genes, proliferation genes, and immune-related genes are strong predictors of pCR in women with locally advanced breast cancer receiving neoadjuvant anthracyclines and paclitaxel.


Hyperpolarized [U-(2) H, U-(13) C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells.
A resonance at ∼181 ppm in the (13) C spectra of tumors injected with hyperpolarized [U-(2) H, U-(13) C]glucose was assigned to 6-phosphogluconate (6PG), as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak assignments were investigated here using measurements of 6PG and 3PG (13) C-labeling using liquid chromatography tandem mass spectrometry (LC-MS/MS) METHODS: Tumor-bearing mice were injected with (13) C6 glucose and the (13) C-labeled and total 6PG and 3PG concentrations measured. (13) C MR spectra of glucose-6-phosphate dehydrogenase deficient (zwf1Δ) and wild-type yeast were acquired following addition of hyperpolarized [U-(2) H, U-(13) C]glucose and again (13) C-labeled and total 6PG and 3PG were measured by LC-MS/MS RESULTS: Tumor (13) C-6PG was more abundant than (13) C-2PG/3PG and the resonance at ∼181 ppm matched more closely that of 6PG. (13) C MR spectra of wild-type and zwf1Δ yeast cells showed a resonance at ∼181 ppm after labeling with hyperpolarized [U-(2) H, U-(13) C]glucose, however, there was no 6PG in zwf1Δ cells. In the wild-type cells 3PG was approximately four-fold more abundant than 6PG CONCLUSION: The resonance at ∼181 ppm in (13) C MR spectra following injection of hyperpolarized [U-(2) H, U-(13) C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells.


Home treatment with enzyme replacement therapy for mucopolysaccharidosis type I is feasible and safe.
Intravenous enzyme replacement therapy (ERT) with recombinant alpha-L-iduronidase may ameliorate the non-neurological symptoms in patients with mucopolysaccharidosis type I (MPS I). Since home-based ERT for Gaucher and Fabry diseases has been reported to be safe and successful, we investigated the feasibility and safety of home therapy in patients with MPS I. This two-centre study included 17 ERT-treated MPS I patients between 1 and 35 years of age. A patient was allowed to transfer to home treatment after a minimum period of 6 months of in-hospital administration of ERT and after a self- or home nurse-supported home setting was arranged. Thirteen out of 17 patients transferred to home treatment with a median time to transfer of 13 months (range 7-40 months). Two patients preferred to continue ERT in the hospital, whereas for two other patients the transfer to home was hampered for practical reasons. All patients who received ERT at home were assisted by either a relative or a nurse. In total over 1000 home infusions were performed and no serious complications were observed. Two infusion-associated reactions were observed, both within the first 3 months of in-hospital administration of ERT. All patients except one developed antibodies against the recombinant enzyme, but this was not associated with the development of hypersensitivity reactions. ERT for MPS I applied at home is safe and might alleviate the burden of life-long intravenous treatment in these patients.


Recurrence of post traumatic stress disorder.
Traumatic events can have an enduring effect on an individual's wellbeing, even causing a recurrence of trauma-related stress symptoms 50 years later. This lasting impact means that those working with older people need an awareness of those symptoms and education in their management.


Use of weighted vests in pediatric occupational therapy practice.
The aim of this study was to investigate pediatric occupational therapists' general experience and practice with weighted vests and their impressions about whether weighted vests are effective in changing specific behaviors of children with whom they have used weighted vests. A survey was mailed to a random sample of 514 pediatric occupational therapists who belonged to the School-Based Systems Special Interest Section or the Sensory Integration Special Interest Section of the American Occupational Therapy Association. The response rate was 68%. The survey included 43 items which covered therapist opinions, procedures, behavioral observations and knowledge about weighted vests, in addition to demographic information. Respondents who use weighted vests were more likely to have advanced degrees or certifications and more years of experience as pediatric therapists. They reported using weighted vests with preschool and young elementary school-aged children with the diagnoses of autism or attention deficit disorder. Staying on task, staying in seat and attention span were the most common behaviors that therapists reported improving when weighted vests were used.


Pyridostigmine cotreatment for controlled ovarian hyperstimulation in low responders undergoing in vitro fertilization-embryo transfer.
To investigate the effect of pyridostigmine, an acetylcholinesterase inhibitor, as cotreatment for controlled ovarian hyperstimulation (COH) in low responders. Randomized, double-blind, placebo-controlled study. A reproductive medicine unit in a university hospital. Seventy infertile women with a history of low ovarian response to COH using a GnRH agonist as part of a long stimulation protocol in previous IVF-ET cycles. Sixty milligrams of pyridostigmine or placebo was administered orally twice daily from the first day of COH until the day of hCG injection in patients undergoing IVF-ET cycles. In vitro fertilization results, pregnancy outcome, and serum and intrafollicular concentrations of GH and insulin-like growth factor-1. Pyridostigmine cotreatment was associated with significant decreases in the amount of gonadotropins and the duration of stimulation required. The clinical pregnancy rate was higher in the pyridostigmine group, but this difference was not statistically significant (25.7% vs. 11.4%). The serum GH level on the day of hCG injection was significantly higher in the pyridostigmine group than in the placebo group. Follicular fluid concentrations of GH and insulin-like growth factor-1 were significantly higher in the pyridostigmine group. This study suggests that pyridostigmine cotreatment for COH could affect the serum and intrafollicular GH and insulin-like growth factor-1 concentrations and, hence, improve the ovarian response to COH and the results of IVF in low responders undergoing IVF-ET.


Is there a future for topological analysis in experimental charge-density research?
Topological analysis using Bader and co-worker's Atoms in Molecules theory has seen many applications in theoretical chemistry and experimental charge-density research. A brief overview of successful early developments, establishing topological analysis as a research tool for characterizing intramolecular chemical bonding, is provided. A lack of vision in many `descriptive but not predictive' subsequent studies is discussed. Limitations of topology for providing accurate energetic estimates of intermolecular interaction energies are put into perspective. It is recommended that topological analyses of well understood bonding situations are phased out and are only reported for unusual bonding. Descriptive studies of intermolecular interactions should have a clear research focus.


ROS-mediated Therapeutics Combined with Metal-based Porphyrin Nanoparticles and their Applications in Tumor Treatment.
High concentrations of reactive oxygen species (ROS) can disrupt cell structure and induce apoptosis and necrosis of tumor cells. Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are two cancer treatments mediated by reactive oxygen species. Oxygen molecules (O2 ) are one of the indispensable factors in PDT and hypoxic tumor sites limit its application. However, another ROS-mediated method, CDT, can generate •OH and O2 in situ by Fenton reaction or Fenton-like reaction. Synergistic PDT/CDT therapy is a strategy to overcome the limitations of tumor microenvironment therapy. In this review, PDT and CDT therapies are briefly introduced, with an emphasis on metal-basrd porphyrin nanoparticles constructed in different ways for PDT/CDT dual-mode therapy. By introducing the history and latest design schemes of the treatment model, it provides ideas for researchers engaged in ROS-mediated cancer therapies.


Relationship of depression, disability, and family caregiver attitudes to the quality of life of Kuwaiti persons with multiple sclerosis: a controlled study.
Assessment of subjective quality of life (QOL) of persons with multiple sclerosis (MS) could facilitate the detection of psychosocial aspects of disease that may otherwise go unrecognized. The objectives of the study were to (i) compare the QOL ratings of relapsing remitting (RRMS) and progressive (PMS) types of MS with those of a general population group and the impression of their family caregivers; and (ii) assess the association of demographic, clinical, treatment, depression, and caregiver variables with patients' QOL. Consecutive clinic attendees at the national neurology hospital were assessed with the 26 -item WHOQOL Instrument, Beck's Depression Inventory and Expanded Disability Scale. Caregivers rated their impression of patients' QOL and attitudes to patients' illness. The 170 patients (60 m, 109 f) consisted of 145(85.3%) with RRMS and 25 with PMS, aged 32.4(SD 8.8), age at onset 27.1(7.7), EDSS score 2.9 (1.8), and 76% were employed. The patients were predominantly dissatisfied with their life circumstances. The RRMS group had higher QOL domain scores (P < 0.001), and lower depression(P > 0.05) and disability (P < 0.0001) scores than the PMS group. Patients had significantly lower QOL scores than the control group (P < 0.001). Caregiver impression was significantly correlated with patients' ratings. Depression was the commonest significant covariate of QOL domains. When we controlled for depression and disability scores, differences between the two MS groups became significant for only one (out of 6) QOL domains. Patients who were younger, better educated, employed, felt less sick and with lesser side effects, had higher QOL. The predictors of patients' overall QOL were disability score, caregiver impression of patients' QOL, and caregiver fear of having MS. Our data indicate that MS patients in stable condition and with social support can hope to have better QOL, if clinicians pay attention to depression, disability, the impact of side effects of treatment and family caregiver anxieties about the illness. The findings call for a regular program of psychosocial intervention in the clinical setting, to address these issues and provide caregiver education and supports, in order to enhance the quality of care.


New-onset diabetes mellitus after solid organ transplantation.
New-onset diabetes mellitus is a common complication of solid organ transplantation and is likely to become even more common with the current epidemic of obesity in some countries. It has become clear that both new-onset diabetes and prediabetic states (impaired fasting glucose and impaired glucose tolerance) negatively influence graft and patient survival after transplantation. This observation forms the basis for recommending meticulous screening for glucose intolerance before and after transplantation. Although a number of clinical factors including age, weight, ethnicity, family history, and infection with hepatitis C are closely associated with the new-onset diabetes mellitus, immunosuppression with corticosteroids, calcineurin inhibitors and possibly sirolimus plays a dominant role in its pathogenesis. Management of new-onset diabetes after transplantation generally conforms to the guidelines for treatment of type 2 diabetes mellitus in the general population. However, further studies are needed to determine the optimal immunosuppressive regimens for patients with this disorder.


Thermodynamic Hydricities of Biomimetic Organic Hydride Donors.
Thermodynamic hydricities (Δ GH-) in acetonitrile and dimethyl sulfoxide have been calculated and experimentally measured for several metal-free hydride donors: NADH analogs (BNAH, CN-BNAH, Me-MNAH, HEH), methylene tetrahydromethanopterin analogs (BIMH, CAFH), acridine derivatives (Ph-AcrH, Me2N-AcrH, T-AcrH, 4OH, 2OH, 3NH), and a triarylmethane derivative (6OH). The calculated hydricity values, obtained using density functional theory, showed a reasonably good match (within 3 kcal/mol) with the experimental values, obtained using "potential p Ka" and "hydride-transfer" methods. The hydride donor abilities of model compounds were in the 48.7-85.8 kcal/mol (acetonitrile) and 46.9-84.1 kcal/mol (DMSO) range, making them comparable to previously studied first-row transition metal hydride complexes. To evaluate the relevance of entropic contribution to the overall hydricity, Gibbs free energy differences (Δ GH-) obtained in this work were compared with the enthalpy (Δ HH-) values obtained by others. The results indicate that, even though Δ HH- values exhibit the same trends as Δ GH-, the differences between room-temperature Δ GH- and Δ HH- values range from 3 to 9 kcal/mol. This study also reports a new metal-free hydride donor, namely, an acridine-based compound 3NH, whose hydricity exceeds that of NaBH4. Collectively, this work gives a perspective of use metal-free hydride catalysts in fuel-forming and other reduction processes.


Influence of molybdenum and sulfate supplementation and withdrawal of diets containing high copper broiler litter on tissue copper levels in ewes.
Thirty-six mature, nongestating, crossbred ewes were allotted randomly to three diets for 140 d: basal (six ewes); 50% basal and 50% broiler litter, dry basis (24 ewes) and 50% basal and 50% deep stacked broiler litter with the addition of 25 ppm molybdenum (Mo) and 5 g sulfate (SO4)/kg feed (six ewes). The control diet and the broiler litter contained 8 and 257 ppm Cu, dry basis, respectively. Liver samples from six ewes in each group were obtained by biopsy initially and at 40, 80 and 120 d and at slaughter (140 d). The remaining 18 litter-fed ewes were fed the basal diet after 140 d and six were slaughtered after 30-, 60- and 120-d. Liver Cu content continually increased (P less than .01) by feeding broiler litter (404 vs 1,543 ppm, dry basis), and was decreased (962 ppm) by supplementing Mo and SO4. During the withdrawal period, liver and duodenum Cu levels were not reduced (P greater than .05). A linear increase (P less than .001) in serum glutamic oxalacetic transaminase (SGOT) was observed with time during the withdrawal period. Serum Cu decreased at 30-d withdrawal and increased thereafter (quadratic effect (P less than .05). Hepatic Cu-metallothionein levels increased 15-fold above control values in the litter-fed ewes (P less than .05).


Use of dynamic capillaroscopy for studying cutaneous microcirculation in patients with diabetes mellitus.
To investigate the relationship between cutaneous microcirculation and retinopathy in diabetes mellitus, we studied by dynamic capillaroscopy 35 diabetes mellitus patients, including 10 patients without retinopathy, 10 patients with background retinopathy, and 15 patients with proliferative retinopathy. We found that (1) cutaneous and retinal microcirculation in diabetes mellitus in long-term diabetes mellitus, regressional rather than proliferational changes occurred in skin vasculature as compared to that in retina; (2) functional impairments of cutaneous microcirculation, that is, decreased resting capillary blood cell velocity, peak blood cell velocity, and prolonged time to peak capillary blood cell velocity by dynamic capillaroscopy, could be detected in diabetes mellitus patients without retinopathy; (3) the degree of tortouosity of capillaries, impairment in peak capillary blood cell velocity, and time to peak capillary blood cell velocity of cutaneous microcirculation were significantly correlated with the gravity of retinopathy in diabetes mellitus patients; (4) abnormal leakage of fluorescence in cutaneous microcirculation appeared in diabetes mellitus patients with or without abnormal fluorescein angiography in retina. In conclusion, dynamic capillaroscopy used in concert with ophthalmoscopy and fluorescein angiography can facilitate a comprehensive examination of vasculopathy in diabetes mellitus.


Mitogenomes of genus Pristipomoides, Lutjanus and Pterocaesio confirm Caesionidae nests in Lutjanidae.
In this study, the complete mitochondrial genome of Goldbanded jobfish (Perciformes: Lutjanidae: Etelinae: Pristipomoides multidens) was sequenced using long-PCR amplification (Accession No.: KF430626). The mitochondrial genome is highly homologous to those of other teleosts. Consensus tree based on phylogeny analysis of nucleotide sequences using the protein-coding regions combined sequences (apart from ND6) in 11 species supports the fact that Pristipomoides multidens of Etelinae and the cluster of Subfamily Lutjaninae remain the sister relationship, consistent with the traditional taxonomy, while the fusiliers (Pterocaesio tile) of family Caesionidae nested within the genus Lutjanus of family Lutjanidae and showed more closely relationship with the non-reddish snappers cluster including L. russellii and L. argentimaculatus. Conclusively, this mitogenomic phylogeny indicates that the Caesionidae is a synonym of family Lutjanidae. Given the morphologic and feeding diversity, we hypothesize that the variation of feeding systems of genus Lutjanus may drive the speciation of snappers and fusiliers.


Considerations in Patients With Cardiac Implantable Electronic Devices at End of Life.
Since the introduction of implantable cardiac pacemakers in 1958 and implantable cardioverter-defibrillators in 1980, these devices have been proven to save and prolong lives. Pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy are deemed life-sustaining therapies. Despite these life-saving technologies, all patients ultimately will reach the end of their lives from either their heart disease or development of a terminal illness. Clinicians may be faced with patient and family requests to withdraw these life-sustaining therapies. The purpose of this article is to educate clinicians about the legal and ethical principles that underlie withdrawal of life-sustaining therapies such as device deactivation and to highlight the importance of proactive communication with patients and families in these situations.


Advancing Research: An Examination of Differences in Characteristics of Sexual and Non-Sexual Offense Recidivism Using a 10-Year Follow-Up.
In this article, we examine our current understanding of adverse childhood experiences (ACEs) and the intersection of mental health challenges and substance use on sexual and non-sexual recidivism. This study uses administrative data and comprehensive case files of a sample of 626 individuals who were incarcerated for a sexual offense. Each case was standardized to a 10-year post-release follow-up time for criminal history review. Findings reveal that ACEs, mental health challenges, and substance use disorder, along with a variety of other factors, affect the pathway to re-offending differently. Interestingly, despite the recent legislative push to utilize one standardized predictor of risk, individuals who commit sexual offenses (ICSOs) had very different re-offending patterns based on historic life events. This research will inform the current legislative debate by providing relevant empirical data on a large sample of ICSOs followed for a substantial period of time.


Photosensitized breakage and damage of DNA by CdSe-ZnS quantum dots.
Strand breakages and nucleobase damages in plasmid DNA (pDNA) by CdSe-ZnS quantum dots (QDs) are investigated under different conditions of photoactivation. Here, streptavidin functionalized CdSe-ZnS QDs are conjugated to biotinylated pDNA, and photosensitized strand breakages and nucleobase damages in the conjugates are investigated using atomic force microscopy (AFM) imaging, gel electrophoreses analyses, and assay of reactive oxygen intermediates (ROI). Also, reactions of photoactivated pDNA-QD conjugates with base excision repair enzymes such as formamidopyrimidine glycosylase (Fpg) and endonuclease III (Endo III) show damages of purine and pyrimidine bases. The base excision repair enzymes recognize and remove the damaged bases. The base excision reactions of photoactivated pDNA-QD conjugates resulted in pDNA strand breakages, which appeared as sheared bands in agarose gel images. On the basis of AFM imaging, reactions of Fpg and Endo III with damaged pDNA, ROI assay, and literature reports, we attribute the breakage and damage of pDNA to its reactions with ROI. The production of ROI by photoactivated QDs is confirmed by nitroblue tetrazolium (NBT) assay. The current work shows that photoactivation of QD-conjugated nucleic acids for an extended period of time is not favorable for their stability. On the other hand, photoinduced production of ROI by QDs is an emerging research area with potential applications in the photodynamic therapy of cancer. In this regard, photosensitized damage of pDNA observed in the current work shows possibilities of QDs in nucleus-targeted photodynamic therapy.


Reducing Hospitalization Rates for Children With Anaphylaxis.
Most children with anaphylaxis in the emergency department (ED) are hospitalized. Opportunities exist to safely reduce the hospitalization rate for children with anaphylaxis by decreasing unnecessary hospitalizations. A quality improvement (QI) intervention was conducted to improve care and reduce hospitalization rates for children with anaphylaxis. We used the Model for Improvement and began with development and implementation in 2011 of a locally developed evidence-based guideline based on national recommendations for the management of anaphylaxis. Guideline adoption and adherence were supported by interval reminders and feedback to providers. Patients from 2008 to 2014 diagnosed with anaphylaxis were identified, and statistical process control methods were used to evaluate change in hospitalization rates over time. The balancing measure was any return visit to the ED within 72 hours. To control for secular trends, hospitalization rates for anaphylaxis at 34 US children's hospitals over the same time period were analyzed. Over the study period, there were 1169 visits for children with anaphylaxis, of which 731 (62%) occurred after the QI implementation. The proportion of children hospitalized decreased from 54% to 36%, with no increase in the 72-hour ED revisit rate. The hospitalization rate across 34 other US pediatric hospitals remained static at 52% over the study period. We safely reduced unnecessary hospitalizations for children with anaphylaxis and sustained the change over 3 years by using a QI initiative that included evidence-based guideline development and implementation, reinforced by provider reminders and structured feedback.


[The TLR3 induction increases content of interferons in rat's brain by TRAIL signaling during long-term alcoholization].
The pathogenetic mechanisms associated with alcohol use include dysregulation of the innate immune system mechanisms in the brain. TLR3 expression is increased in the postmortem material of the prefrontal cortex of humans. An increase in the TLR3 signaling activity leads to the induction of interferons (IFN). IFN are associated with depressive symptoms and, therefore, may play a role in the pathogenesis of alcoholism; however, the exact mechanisms of intracellular signaling mediated by the influence of ethanol are not fully elucidated and their study was the purpose of this work. The experimental results showed that ethanol and the TLR3 agonist Poly (I:C) increased the content of TLR3, IFNβ, and IFNγ mRNA in the prefrontal cortex. In addition, expression of the TRAIL encoding gene also increased, and this increase positively correlaed with the mRNA content of TLR3, IFNβ and IFNγ both under alcoholization conditions and after injections of the TLR3 agonist. The data obtained may indicate that alcoholization is able to activate TLR3-TRAIL-IFN-signaling in the prefrontal cortex of the brain.


D-serine Measurements in Brain Slices or Other Tissue Explants.
D-serine is an atypical amino acid present in the mammalian body (most amino acids in the mammalian body are L-isomers) that is mostly known in neuroscience for its role as a co-agonist controlling the N-methyl D-aspartate receptor (NMDAR). D-serine levels are decreased in patients with schizophrenia and this is thought to mediate, at least in part, the hypofunction of NMDARs that is central to the glutamate hypothesis for the etiology of this neuropsychiatric disorder. D-serine detection was first established using high performance liquid chromatography, a costly and complex technique that requires high levels of expertise. But with the increasing interest in this unconventional amino acid, there is an increasing need for easier, cheaper and more accessible detection methods. Here we describe the amperometric, biosensor-based method we employed in a recent publication (Papouin et al., 2017b). It allows reliable measurement of D-serine levels from fresh tissue, such as acute brain slices, for concentrations higher than 100 nM, with minimal technical requirements.


The rho-guanine nucleotide exchange factor domain of obscurin regulates assembly of titin at the Z-disk through interactions with Ran binding protein 9.
Obscurin is an approximately 800-kDa protein composed of structural and signaling domains that organizes contractile structures in striated muscle. We have studied the Rho-GEF domain of obscurin to understand its roles in morphogenesis and signaling. We used adenoviral overexpression of this domain, together with ultrastructural and immunofluorescence methods, to examine its effect on maturing myofibrils. We report that overexpression of the Rho-GEF domain specifically inhibits the incorporation of titin into developing Z-disks and disrupts the structure of the Z-disk and Z/I junction, and alters features of the A/I junction. The organization of other sarcomeric markers, including alpha-actinin, was not affected. We identified Ran binding protein 9 (RanBP9) as a novel ligand of the Rho-GEF domain and showed that binding is specific, with an apparent binding affinity of 1.9 microM. Overexpression of the binding region of RanBP9 also disrupted the incorporation of titin into developing Z-disks. Immunofluorescence localization during myofibrillogenesis indicated that the Rho-GEF domain assembles into sarcomeres before RanBP9, which first occurs in myonuclei and later in development translocates to the myoplasm, where it colocalizes with obscurin. Both the Rho-GEF domain and its binding region on RanBP9 bind directly to the N-terminal Ig domains of titin, which flank the Z-disk. Our results suggest that the Rho-GEF domain interacts with RanBP9 and that both can interact with the N-terminal region of titin to influence the formation of the Z-disk and A/I junction.


Zerumbone attenuates the excessive proliferation of keratinocytes in psoriasis mice through regulating NLRP3/NF-κB pathway.
Psoriasis is a common chronic disease, and existing treatment regimens often exhibit certain toxicities and side effects. Zerumbone (Zer) may possess therapeutic effect, and the objective of this study is to investigate the effect of Zer on psoriasis. A mouse model of psoriasis was established using imiquimod cream, and the role of Zer on the pathological alterations in psoriatic mouse skin was evaluated by psoriasis area and severity index (PASI) score; the effect of Zer on keratinocyte proliferation was evaluated via hematoxylin and eosin staining, Zen image analysis, and immunofluorescence; Immunohistochemistry and enzyme-linked immunoassay were used to evaluate the effect of Zer on tissue inflammatory responses, while malondialdehyde (MDA) and glutathione (GSH) levels were measured to elucidate the role of Zer in modulating oxidative stress; the signaling pathway regulated by Zer was evaluated by western blotting. The results demonstrated that Zer could alleviate the pathological manifestations of psoriasis, reduce PASI score, reduce skin pathological damage and epidermal hyperplasia, diminish the number of CD8+ T cells and cytokine expression levels, decrease the level of MDA and GSH and increase the expression of Nrf and HO-1. Zer was found to regulate the NLRP3/nuclear factor-kappa B (NF-κB) signaling pathway. In conclusion, Zer ameliorated the symptoms of psoriasis in mice, suppressed the keratinocyte hyperproliferation, and mitigates inflammation and oxidative stress in psoriatic skin tissue by regulating the NLRP3/NF-κB pathway.


Synthesis, X-ray characterization and DFT analysis of dicyanidoaurate telluronium salts: on the importance of charge assisted chalcogen bonds.
In this manuscript we report the synthesis and X-ray characterization of two cyanidoaurate telluronium salts, namely (3-fluorophenyl)(methyl)(phenyl)telluronium dicyanidoaurate [(3-F-Ph)(Me)(Ph)Te][Au(CN)2] (1) and methyldiphenyltelluronium dicyanidoaurate [(Me)(Ph)2Te][Au(CN)2] (2). In the solid state, the tellurium atom establishes three concurrent and directional chalcogen bonds (ChBs) with the adjacent anions, in both compounds. These charge-assisted ChBs (CAChBs) have been analyzed using DFT calculations and several computational tools. The MEP surface analysis discloses the existence of three σ-holes at the Te-atoms capable of establishing strong CAChBs with the counter-ions. In addition, significant charge transfer from the lone pair orbital at the N-atom of the anion to the antibonding σ*(Te-C) orbital of the cation is observed in some cases.


Successful conversion of TandemHeart left ventricular assist device to right ventricular assist device after implantation of a HeartMate XVE.
A 60-year-old man with end-stage ischemic cardiomyopathy (ejection fraction, 10%) was admitted in cardiogenic shock, which was unresponsive to maximum inotropes and an intraaortic balloon pump. The TandemHeart (TH) left ventricular assist device (Cardiac Assist Inc, Pittsburgh, PA) was placed in the standard percutaneous transseptal configuration with improved hemodynamics. The HeartMate XVE (Thoratec Corp, Pleasanton, CA) implantation was performed as a bridge to transplant 5 days after TandemHeart insertion. The TandemHeart was converted to a temporary right ventricular assist device during the HeartMate XVE (Thoratec Corp) implantation due to right ventricular failure. The right ventricular assist device was weaned 3 days later. This strategy was useful, technically easy, and cost effective.


"Giant" terminal myelocystocele: A rare variant of spinal dysraphism.
Terminal myelocystocele (TMC) is a rare form of spinal dysraphism. They constitute approximately 5% of skin covered lumbosacral masses. The TMC is composed of a low-lying conus medullaris with cystic dilatation of caudal central canal and a surrounding meningocele that extends from the conus to the skin. A 2-year-old female child presented with a large lumbosacral mass and weakness of both lower limbs since birth. Magnetic resonance imaging revealed a giant TMC. The child was operated on successfully. This is an interesting and rare case of "giant" TMC with partial sacral agenesis.


Cellular and molecular mechanisms of systolic and diastolic dysfunction in an avian model of dilated cardiomyopathy.
We investigated the cellular and molecular mechanisms of systolic and diastolic dysfunction in a furazolidone (Fz)-induced model of dilated cardiomyopathy (DCM) in turkey poults. Serial echocardiograms disclosed marked systolic dysfunction in the Fz-treated poults, and ventricular weight and left ventricular (LV)/body weight ratio were significantly increased. Isolated heart experiments were performed to determine LV pressure-volume (P-V) relationships. In addition, LV sarcomere lengths (SLs) were measured after hearts had been fixed, and wall stress (sigma)-SL relationships were determined. When compared to control hearts, LV chamber volume in DCM hearts was approximately 3-fold increased, the active or developed LV P-V relationship was markedly depressed, the passive or diastolic P-V relationship was steeper, and SLs were significantly shorter. However, the developed sigma-SL relationships of DCM and control hearts were not different indicating that intrinsic myocardial capacity to generate active force is unaffected in this model of DCM. In contrast, passive sigma, and passive tension in trabecular muscle preparations increased much more steeply with SL in DCM than normal hearts. Trabecular muscle experiments disclosed that the increase in passive myocardial stiffness was primarily collagen based. Titin, the giant sarcomeric molecule, which is an important determinant of passive myocyte properties in normal myocardium, did not contribute significantly to increased passive myocardial stiffness in DCM. We conclude that increased collagen-based passive myocardial stiffness is the major cause of the steeper passive or diastolic P-V relationship in DCM. Further, altered passive myocardial properties and ventricular geometry in DCM play a critical role to reduce ventricular systolic function by limiting SL extension during diastole, thereby limiting the use of the myocardial length-tension relationship.


The relation of poor mastication with cognition and dementia risk: a population-based longitudinal study.
We investigated the effect of poor masticatory ability on cognitive trajectories and dementia risk in older adults. 544 cognitively intact adults aged ≥50 were followed for up to 22 years. Cognitive domains (verbal, spatial/fluid, memory, and perceptual speed) were assessed at baseline and follow-ups. Dementia was ascertained according to standard criteria. Masticatory ability was assessed using the Eichner Index and categorized according to the number of posterior occlusal zones: A (all four), B (3-1), and C (none).At baseline, 147 (27.0%) participants were in Eichner category A, 169 (31.1%) in B and 228 (41.9%) in C. After the age of 65, participants in Eichner category B and C showed an accelerated decline in spatial/fluid abilities (β: -0.16, 95% CI: -0.30 to -0.03) and (β: -0.15, 95% CI: -0.28 to -0.02), respectively. Over the follow-up, 52 incident dementia cases were identified. Eichner categories B or C were not associated with an increased risk of dementia, compared to category A (Hazard Ratio [HR]: 0.83, 95% CI: 0.39 to 1.76 and HR: 0.63, 95% CI: 0.30 to 1.29, respectively).Poor masticatory ability is associated with an accelerated cognitive decline in fluid/spatial abilities, however it was not related to a higher risk of dementia.


Quantitative Cross-Sectional Study About the Prevalence of Depression Among Epileptic Patients in Saudi Arabia.
There are high prevalence of mental health co-morbidities in people with epilepsy, with major depressive disorder being the most common among them. This study aims to investigate the prevalence of depression among epileptic patients in Saudi Arabia. We also explored some of the sociodemographic and clinical variables associated with depression in epilepsy. This was a cross-sectional analysis executed across the four geographical regions of Saudi Arabia and the sample size is calculated to be 358. Data collection was facilitated through a digital self-administered questionnaire, which consisted of three parts: patients' sociodemographic variables, clinical variables, and patient health questionnaire (PHQ-9) depression score. Data processing and analytical procedures are undertaken using the SPSS software. Of the participants, 311 responded: 65.6% were females, and 34.4% were males. Approximately 50.5% had a confirmed epilepsy diagnosis and were included in the PHQ-9 depression score analysis. Notably, 84.7% manifested depressive symptoms, with the severe category being predominant at 84.7% and moderate at 3.8%. An intriguing observation was the heightened prevalence among the younger demographic (16 to 24 years), registering at 34.4%, a figure nearly 3% superior to older age brackets. The majority of participants manifested depressive symptoms, with a significant association noted between medication quantity and depression prevalence in epilepsy. It is imperative to broaden the scope of research, encompassing varied methodologies and spanning multiple urban centers, to procure more robust and generalizable conclusions.


Leukocyte adhesion defect: An uncommon immunodeficiency.
Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency disorder with autosomal recessive inheritance which is characterized by presence of a defect of phagocytic function resulting from a lack of leukocyte cell surface expression of b2 integrin molecules (CD11 and CD18) that are essential for chemotaxis. The classic symptoms of the disease are failure of separation of the umbilical cord and recurrent bacterial infections, which continue throughout life. We describe here two cases of infants who presented with characteristic history of recurrent infections, delayed separation of umbilical cord and marked leukocytosis.


Kidney transplantation from small pediatric donors may be feasible to those who developed chronic refractory dialysis hypotension: a single-center experience.
Chronic refractory dialysis hypotension (CRDH) is a serious issue in dialysis patients waiting for transplants. It leads to fatal clinical outcomes and disqualification from kidney transplantation. Kidney transplantation from pediatric donor to adult patient with lower blood pressure (BP) may be an option. No related study has been reported and we conducted this study to first evaluate the effect of pediatric donor kidney transplantation in CRDH recipients. Ten single-kidney transplantations from small pediatric donors after cardiac death in our center between August 2016 and April 2018 were described. Half were CRDH recipients (group A) with intradialytic and interdialytic systolic blood pressure (SBP) below 100 mmHg. Each was paired with no-CRDH recipient (control, group B) from the same donor. The operation method of vascular anastomosis and ureterocystoneostomy was the same as that of adult donors. Clinical characteristics, post-operative treatment and outcomes of all recipients were retrieved. Postoperative BP, graft function and size were compared between two groups. The follow-up time was up to April 2019. There was no acute rejection (AR), graft loss or death in all recipients after transplantation. Their renal function was recovered despite three transient delayed graft function (DGF). There was no significant difference in serum creatinine (SCr) or graft size (P=0.84, 0.94) after transplantation between two groups. For all CRDH recipients, the postoperative SBP was above 100 mmHg (except one, 90-130 mmHg). The BP one year after transplantation was maintained at 110-125/70-85 mmHg. kidney transplantation from small pediatric donors may be feasible to CRDH recipients and their BP may return to normal after transplantation.


Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis.
Glioblastoma multiforme (GBM) universally recurs with dismal prognosis. We evaluated the efficacy of standard treatment strategies for patients with recurrent GBM (rGBM). From two centers in the Netherlands, 299 patients with rGBM after first-line treatment, diagnosed between 2005 and 2014, were retrospectively evaluated. Four different treatment strategies were defined: systemic treatment (SYST), re-irradiation (RT), re-resection followed by adjuvant treatment (SURG) and best supportive care (BSC). Median OS for all patients was 6.5 months, and median PFS (excluding patients receiving BSC) was 5.5 months. Older age, multifocal lesions and steroid use were significantly associated with a shorter survival. After correction for confounders, patients receiving SYST (34.8%) and SURG (18.7%) had a significantly longer survival than patients receiving BSC (39.5%), 7.3 and 11.0 versus 3.1 months, respectively [HR 0.46 (p < 0.001) and 0.36 (p < 0.001)]. Median survival for patients receiving RT (7.0%) was 9.2 months, but this was not significantly different from patients receiving BSC (p = 0.068). Patients receiving SURG compared to SYST had a longer PFS (9.0 vs. 4.3 months, respectively; p < 0.001), but no difference in OS was observed. After adjustments for confounders, patients with rGBM selected for treatment with SURG or SYST do survive significantly longer than patients who are selected for BSC based on clinical parameters. The value of reoperation versus systemic treatment strategies needs further investigation.


Comparison of laparoscopic imaging systems and conditions using a knot-tying task.
Pilot experiments to determine the important factors in the engineering of laparoscopic (videoscopic) imaging systems are described in this paper. In the first set of experiments, three videoscopic systems were compared by using a knot-tying task: monoscopic, monoscopic with digital contrast enhancement, and stereoscopic. Direct viewing was used as a control. In both experienced and novice subject groups, no difference was found in completion time or errors between the videoscopic conditions. Performance with direct viewing was significantly better, however, indicating that there are factors in videoscopic imaging that degrade perception or distort the relationship between vision and motor response. In the second set of experiments, the effects of contrast and spatial resolution were examined by varying working distance and camera exposure while experienced subjects tied knots on high- and low-contrast surfaces. Good contrast was found to be most important at longer working distances. This result shows that performance of knot tying, a complex task, is affected by contrast sensitivity, which is a fundamental property of human vision.


Purification and structural characterization of LFA-1, a lymphocyte function-associated antigen, and Mac-1, a related macrophage differentiation antigen associated with the type three complement receptor.
LFA-1, an antigen associated with antigen-specific T lymphocyte-mediated killing, and Mac-1, a macrophage differentiation antigen associated with type three complement receptor function, contain alpha chains of Mr = 180,000 and 170,000, respectively, and beta chains of Mr = 95,000. The monoclonal antibodies defining these antigens do not cross-react. The LFA-1 and Mac-1 beta chains are highly homologous or identical, whereas the alpha chains are highly different by tyrosyl tryptic peptide mapping (Kürzinger, K., Ho, M. K., and Springer, T. A. (1982) Nature (Lond.) 296, 668-670). T lymphoma cell lines express LFA-1 but not Mac-1 as shown by immunofluorescence and immunoprecipitation. Conversely, some macrophage-like lines express Mac-1 but not LFA-1. Other macrophage-like lines co-express Mac-1 and small amounts of LFA-1. Mac-1 and LFA-1 are present as separate molecules in these cells. [35S]Methionine and [[3H]glucosamine are incorporated into both alpha and beta chains of Mac-1 and LFA-1, showing both chains are endogenously synthesized and are glycoproteins. Cross-linking and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments show that in both Mac-1 and LFA-1 the alpha and beta chains are noncovalently associated in alpha 1 beta 1 quaternary structures. By quantitative immunofluorescence flow cytometry, the EL-4 T lymphoma and P388D1 macrophage-like lines were estimated to express 10(5) LFA-1 and 1.6 x 10(5) Mac-1 molecules/cell, respectively. From these sources the antigens have been purified to homogeneity in 200-400-micrograms quantities by monoclonal antibody affinity chromatography. The purified antigens contain only the alpha and beta subunits.


Verapamil prevents silent myocardial perfusion abnormalities during exercise in asymptomatic patients with hypertrophic cardiomyopathy.
Recent studies indicate that reversible 201Tl perfusion defects, compatible with silent myocardial ischemia, commonly develop during exercise in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy (HCM). To determine whether this represents a dynamic process that may be modified favorably by medical therapy, we studied 29 asymptomatic or minimally symptomatic patients with HCM, aged 12-55 years (mean, 28), with exercise 201Tl emission computed tomography under control conditions and again after 1 week of oral verapamil (mean dosage, 453 mg/day). Treadmill time increased slightly during verapamil (21.0 +/- 3.6 to 21.9 +/- 2.7 minutes, p less than 0.005), but peak heart rate-blood pressure product was unchanged (26.3 +/- 6.0 X 10(3) compared with 25.0 +/- 6.4 X 10(3). Two midventricular short-axis images per study were divided into five regions each, and each of these 10 regions was then analyzed on a 0-2 scale by three observers blinded with regard to the patients' therapy. Average regional scores of 1.5 or less were considered to represent perfusion defects, and a change in regional score of 0.5 or more was considered to constitute a significant change. During control studies, 15 patients (52%) developed perfusion defects with exercise (average, 3.7 regions per patient). In 14 of these patients, all perfusion defects completely reversed after 3 hours of rest; one patient had fixed defects. After administration of verapamil, exercise perfusion scores improved in 10 of the 14 patients (71%) with reversible defects; there was overall improvement in 34 of 50 (68%) regions with initially reversible perfusion defects.(ABSTRACT TRUNCATED AT 250 WORDS)


Clathrin and caveolin-1 expression in primary pigmented rabbit conjunctival epithelial cells: role in PLGA nanoparticle endocytosis.
The internalization of poly (dl-lactide-co-glycolide, PLGA) nanoparticles in rabbit conjunctival epithelial cells (RCEC) was previously shown to occur by an endocytic process, as evidenced its energy-dependence, inhibition by the vesicle formation blocker cytochalasin D, and by the characteristic display of punctate distribution under confocal microscopy. In addition, clathrin protein was implicated in the endocytosis of these nanoparticles in vascular smooth muscle cells. We sought to examine the expression of clathrin and caveolin-1 in RCECs and to determine whether they play a role in PLGA nanoparticle endocytosis. PLGA (50:50) nanoparticles (100 nm in diameter) containing 6-coumarin (fluorescent marker, 0.05% w/v) were used in this study. The effect of pharmacological treatments aimed at disrupting formation of clathrin-coated vesicles (hypertonic challenge and intracellular K+ depletion) and caveolae (nystatin and filipin) on apical uptake of nanoparticles in primary cultured RCEC was investigated. Transferrin was chosen as a marker for clathrin-dependent endocytosis from the basolateral aspect, whereas cholera toxin B subunit was chosen as a marker for caveolae-mediated endocytosis. The staining pattern of nanoparticles in RCECs was compared with that of clathrin heavy chain (HC) and caveolin-1 under fluorescent confocal microscopy to examine possible colocalization using clathrin HC and caveolin-1 mouse monoclonal antibodies (mAb). Two pairs of primers were designed (based on conserved regions of clathrin and caveolin-1 gene in different species) to amplify a 744-bp and 152-bp fragment of clathrin HC and caveolin-1 gene, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) to detect the message for clathrin HC and caveolin-1 was performed using total RNA prepared from freshly isolated RCECs. HEK293 cells were used as positive control for clathrin gene expression, whereas rabbit heart muscle and HEK cells were used as positive control for caveolin-1 gene expression. The RT-PCR products were separated using 2% agarose gel electrophoresis. Western blot analysis was performed to detect the expression of both clathrin and caveolin-1 proteins in RCECs using mouse mAbs. HeLa cells and A431 epidermoid cells were used as positive controls. The effect of transfection of RCECs (using Lipofectamine 2000TM reagent) with specific antisense oligonucleotides designed against the rabbit clathrin isoform on clathrin protein expression and PLGA nanoparticle uptake was investigated. Apical uptake of nanoparticles in primary cultured RCECs was decreased by 45% and 35%, respectively, as a result of K+ depletion and hypertonic media treatments. Likewise, the same treatments significantly decreased the basolateral uptake of FITC-transferrin by 50%. In contrast, nystatin and filipin had no effect on apical uptake of nanoparticles and cholera toxin B subunit in RCECs, suggesting a lack of the involvement of caveolae in the internalization of these two agents. Confocal microscopy showed fluorescent staining of cell membrane in the presence clathrin mAb, but not in the presence of caveolin-1 mAb, with partial overlap with a nanoparticle staining pattern. RT-PCR confirmed the presence of the clathrin HC gene, but not the caveolin-1 gene, in RCECs as indicated by a 744-bp fragment of the gene. However, caveolin-1 gene was detected in other rabbit tissues such as the epithelium of the cornea and trachea, and heart muscle, as indicated by a 152-bp fragment of the gene. Western blot analysis revealed a clathrin HC band (180 kDa) in RCEC culture and HeLa cells. However, caveolin-1 protein (22 kDa) was not detected in RCEC culture, but was detected in A431 cells. Transfection of RCECs with antisense oligonuceotide directed against clathrin HC resulted in knockdown of the clathrin HC protein in a concentration dependent manner. However, clathrin HC protein knockdown had no effect on apical uptake of nanoparticles in RCECs. Our findings indicate that endocytosis of nanoparticles in primary cultured RCECs occurs mostly independently of clathrin- and caveolin-1-mediated pathways. In addition, the gene and protein expression of clathrin HC, but not caveolin-1, was identified in rabbit conjunctival epithelial cells.


Soil biogeochemical responses to multiple co-occurring forms of human-induced environmental change.
Human activities cause a multitude of environmental issues, including increased temperatures and altered precipitation patterns associated with climate change, air pollution, and other impacts of urbanization. One area highly affected by these issues is the Sonoran Desert, specifically the Phoenix metropolitan area where urbanization is among the most rapid in the United States. Most studies investigate these multiple environmental change factors independently or sometimes in pairs, but rarely all together as co-occurring forms of change. We examined how the simultaneous manipulation of increasing temperatures, altered precipitation patterns, nitrogen deposition, and urbanization influenced soil respiration and mineral N pools in the Sonoran Desert. Soil was collected from urban and exurban sites, from both nitrogen-fertilized and control plots. To simulate projected climate change, the soils were incubated in microcosm at the annual average Phoenix temperature as well a 2 ℃ increase under a factorial precipitation treatment of decreased frequency and increased pulse size. Our results show that C and N dynamics were altered by all four forms of environmental change. However, the dominance of significant 3- and 4-way interactions among the four environmental factors for both respiration and mineral N pools demonstrates that the impact of any given form of environmental change will depend on the levels of the other environmental factors. In other words, the cumulative effect of altered precipitation, fertilization, temperature, and urbanization on soil biogeochemical processes is not necessarily predictable from their individual impact.


Medicine and aviation: a review of the comparison.
This paper aims to understand the nature of medical error in highly technological environments and argues that a comparison with aviation can blur its real understanding. This study is a comparative study between the notion of error in health care and aviation based on the author's own ethnographic study in intensive care units and findings from the research literature on errors in aviation. Failures in the use of medical technology are common. In attempts to understand the area of medical error, much attention has focused on how we can learn from aviation. This paper argues that such a comparison is not always useful, on the basis that (i) the type of work and technology is very different in the two domains; (ii) different issues are involved in training and procurement; and (iii) attitudes to error vary between the domains. Therefore, it is necessary to look closely at the subject of medical error and resolve those questions left unanswered by the lessons of aviation.


Treatment and Survival Disparities of Colon Cancer in the Texas-Mexico Border Population: Cancer Disparities in Border Population.
Previous studies have reported healthcare disparities in the Texas-Mexico border population. Our aim was to evaluate treatment utilization and oncologic outcomes of colon cancer patients in this vulnerable population. Patients with localized and regional colon cancer (CC) were identified in the Texas Cancer Registry (1995-2016). Clinicopathological data, hospital factors, receipt of optimal treatment, and overall survival (OS) were compared between Texas-Mexico Border (TMB) and the Non-Texas-Mexico Border (NTMB) cohorts. Multivariable analysis was performed to identify risk factors associated with decreased survival. We identified 43,557 patients with localized/regional CC (9% TMB and 91% NTMB). TMB patients were more likely to be Hispanic (73% versus 13%), less likely to have private insurance (13% versus 21%), were more often treated at safety net hospitals (82% versus 22%) and less likely at ACS-CoC accredited hospitals (32% versus 57%). TMB patients were more likely to receive suboptimal treatment (21% versus 16%) and had a lower median OS for localized (8.58 versus 9.58 y) and regional colon cancer (5.75 versus 6.18 y, all P < 0.001). In multivariable analysis, TMB status was not associated with worse OS. Factors associated with worse survival included receipt of suboptimal treatment, Medicare/insured status, and treatment in safety net and non-accredited ACS-CoC hospitals (all P < 0.001) CONCLUSIONS: While TMB CC patients had worse OS, TMB status itself was not found to be a risk factor for decreased survival. This survival disparity is likely associated with higher rate of suboptimal treatment, Medicare/Uninsured status, and decreased access to ACS-CoC accredited hospitals.