[Analysis of factors associated with the comprehensive recovery of stroke patients at acute hospital discharge].
Stroke is a public health problem of the first magnitude, being the first cause of disability in Spain. Although the fundamental role of psychophysical rehabilitation is known in patients suffering from this pathology, little is known about the integral and functional recovery of this type of patient. The Public Health Systems pay for or manage part of the treatment, but never its entirety. The aim of our study was to identify the factors that hinder access to the different treatments and care that allow the functional recovery of stroke patients. Bivariate correlational descriptive analysis was performed on a sample of 102 stroke patients, over 30 years of age, admitted to the University Clinical Hospital of Valladolid, who required comprehensive rehabilitation upon discharge from hospital. Additionally, a multivariable analysis (logistic regression) was carried out to adjust results and eliminate confusing variables. The study showed that the factors initially associated with access to total rehabilitation were age (p<0.001), place of residence (p<0.001), marital status (p=0.007) and the existence of family support (p=0.01). Sex (p=0.18) and income (p=0.62) were not statistically significant. Age and place of residence (rural or urban) were the explanatory factors for access to comprehensive rehabilitation (values adjusted for all other variables p<0.001 were obtained). The results show the existence of very unequal access variables to comprehensive rehabilitation, with the consequences of loss of quality of life and impossibility of functional recovery that this implies, both for stroke patients of advanced age and for patients residing in rural areas.


Tissue-specific deregulation of selected HDACs characterizes ALS progression in mouse models: pharmacological characterization of SIRT1 and SIRT2 pathways.
Acetylation homeostasis is thought to play a role in amyotrophic lateral sclerosis, and treatment with inhibitors of histone deacetylases has been considered a potential and attractive therapeutic approach, despite the lack of a thorough study of this class of proteins. In this study, we have considerably extended previous knowledge on the expression of 13 histone deacetylases in tissues (spinal cord and muscle) from mice carrying two different ALS-linked SOD1 mutations (G93A-SOD1 and G86R-SOD1). We have then focused on class III histone deacetylases SIRT1 and SIRT2 that are considered relevant in neurodegenerative diseases. SIRT1 decreases in the spinal cord, but increases in muscle during the progression of the disease, and a similar expression pattern is observed in the corresponding cell models (neuroblastoma and myoblasts). SIRT2 mRNA expression increases in the spinal cord in both G93A-SOD1 and G86R-SOD1 mice but protein expression is substantially unchanged in all the models examined. At variance with other sirtuin modulators (sirtinol, AGK2 and SRT1720), the well-known SIRT1 inhibitor Ex527 has positive effects on survival of neuronal cells expressing mutant SOD1, but this effect is neither mediated by SIRT1 inhibition nor by SIRT2 inhibition. These data call for caution in proposing sirtuin modulation as a target for treatment.


Current understanding of pathogenesis and treatment of TMJ osteoarthritis.
Osteoarthritis is a common disease that can cause severe pain and dysfunction in any joint, including the temporomandibular joint (TMJ). TMJ osteoarthritis (TMJOA) is an important subtype in the classification of temporomandibular disorders. TMJOA pathology is characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation in the synovial tissue. However, the exact pathogenesis and process of TMJOA remain to be understood. An increasing number of studies have recently focused on inflammation and remodeling of subchondral bone during the early stage of TMJOA, which may elucidate the possible mechanism of initiation and progression of TMJOA. The treatment strategy for TMJOA aims at relieving pain, preventing the progression of cartilage and subchondral bone destruction, and restoring joint function. Conservative therapy with nonsteroidal anti-inflammatory drugs, splint, and physical therapy, such as low-energy laser and arthrocentesis, are the most common treatments for TMJOA. These therapies are effective in most cases in relieving the signs and symptoms, but their long-term therapeutic effect on the pathologic articular structure is unsatisfactory. A treatment that can reverse the damage of TMJOA remains unavailable to date. Treatments that prevent the progression of cartilage degradation and subchondral bone damage should be explored, and regeneration for the TMJ may provide the ideal long-term solution. This review summarizes the current understanding of mechanisms underlying the pathogenesis and treatment of TMJOA.


Molecular imprinting-based micro-stir bar sorptive extraction for specific analysis of Glibenclamide in herbal dietary supplements.
A novel molecularly imprinted polymers (MIPs) coated micro-stir bar (MSB) for Glibenclamide (GM) was developed. The MIPs, with GM as template molecular and methacrylic acid as functional monomer, were synthesized at the surface of the silylated MSB that was filled with magnetic core as substrate. Computational simulation was used for the optimal selection of functional monomers and porogen. The thickness of MIPs coating for MSB was about 10 μm, the adsorption and desorption time were about 40 and 20 min, respectively. The MIPs coated MSB possessed mechanical stability, high adsorption capacity, and good selectivity for GM. To achieve the optimum extraction performance, several parameters including extraction and desorption time, stirring rate, extraction and desorption solvent were investigated. A method for the determination of GM in herbal dietary supplements by MIPs coated MSB coupled with HPLC-UV was established. The results exhibited good linear ranges of 10-6250 μg L(-1) with the low limit of detection of GM (3.05 μg L(-1)) and the good recoveries (81.9-101.4%).


Endocytosis of the synaptic vesicle protein, synaptophysin, requires the COOH-terminal tail.
Synaptic vesicles participate in a cycle of fusion with the plasma membrane and reformation by endocytosis. Endocytosis of membrane proteins by the well studied clathrin-coated vesicle pathway has been shown to involve specific sequences within the cytoplasmic tail domain. Proteins taken up by clathrin-coated vesicles are directed to early endosomes from which they may return to plasma membrane. Recent evidence suggests that the synaptic vesicle protein synaptophysin is targeted to early endosomes in transfected fibroblasts and in neuroendocrine cells. To begin to test whether sequences within the COOH-cytoplasmic domain are required for internalization we have expressed a synaptophysin molecule lacking this domain in 3T3 cells and measured its rate of internalization. While a full length synaptophysin was internalized efficiently, we could not detect internalization of the mutant construct. These data are consistent with a model in which the COOH-terminal tail is required for coated-pit localization and hence targeting of synaptophysin to early endosomes.


[Nodular lymphocyte-predominant Hodgkin lymphoma in children: clinical course, biology, and management].
Nodular lymphocyte predominant Hodgkin disease (NLPHL) differs clearly from classical Hodgkin lymphoma (cHL) by clinical presentation and more favorable outcome. Patients often present with early stage IA or IIA. Extranodal disease and B-symptoms are uncommon. Histologically, NLPHL is characterized by the presence of atypical "lymphocyte predominant cells" (LP cells) or "pop-corn" cells in a non-neoplastic and reactionnal nodular background of small mature B-lymphocytes. LP cells are negative for CD30 and positive for CD20, BCL6 and EMA (in half of the cases). FDG-PET plays an important role in evaluation of cHL and NLPHL for staging, therapy assessment and relapse. Historically, patients with NLPHL have been treated like patients with cHL, but their very favorable prognosis and the risk of late complications of chemotherapy and/or radiotherapy have led to a de-escalation in recent years. Patients with early stage could be treated by surgical adenectomy alone or associated with not intensive chemotherapy. Currently, there is no consensus regarding to the optimal treatment of patients with advanced stage. Rituximab used as monotherapy or in association with chemotherapy has achieved complete or partial responses. The outcome of NLPHL is singular by the frequent occurrence of late relapses and the risk of transformation into aggressive B lymphoma justifying an extended follow-up. Further prospective studies are needed to optimize treatment of these advanced and recurrent forms.


Hydrogen gas alleviates oxygen toxicity by reducing hydroxyl radical levels in PC12 cells.
Hyperbaric oxygen (HBO) therapy through breathing oxygen at the pressure of above 1 atmosphere absolute (ATA) is useful for varieties of clinical conditions, especially hypoxic-ischemic diseases. Because of generation of reactive oxygen species (ROS), breathing oxygen gas at high pressures can cause oxygen toxicity in the central nervous system, leading to multiple neurological dysfunction, which limits the use of HBO therapy. Studies have shown that Hydrogen gas (H2) can diminish oxidative stress and effectively reduce active ROS associated with diseases. However, the effect of H2 on ROS generated from HBO therapy remains unclear. In this study, we investigated the effect of H2 on ROS during HBO therapy using PC12 cells. PC12 cells cultured in medium were exposed to oxygen gas or mixed oxygen gas and H2 at 1 ATA or 5 ATA. Cells viability and oxidation products and ROS were determined. The data showed that H2 promoted the cell viability and inhibited the damage in the cell and mitochondria membrane, reduced the levels of lipid peroxidation and DNA oxidation, and selectively decreased the levels of •OH but not disturbing the levels of O2•-, H2O2, or NO• in PC12 cells during HBO therapy. These results indicated that H2 effectively reduced •OH, protected cells against oxygen toxicity resulting from HBO therapy, and had no effect on other ROS. Our data supported that H2 could be potentially used as an antioxidant during HBO therapy.


Phosphorylation of soybean nodulin 26 on serine 262 enhances water permeability and is regulated developmentally and by osmotic signals.
Soybean nodulin 26 is expressed and targeted to the symbiosome membrane of nitrogen-fixing nodules, where it forms an aquaporin channel with a modest water transport rate. In this study, we show that the phosphorylation of nodulin 26 on Ser-262, which is catalyzed by a symbiosome membrane-associated calcium-dependent protein kinase, stimulates its intrinsic water transport rate. Furthermore, using a phosphospecific antibody, we have elucidated the developmental appearance and regulation of nodulin 26 phosphorylation in vivo. Although nodulin 26 protein is detected first in differentiating infected cells (16 days), phosphorylated nodulin 26 does not become pronounced until infected cell maturation (25 days). Phosphorylation is sustained at steady state levels until entry into senescence. Nodulin 26 phosphorylation is enhanced further by osmotic stresses (water deprivation and salinity). Thus, the phosphorylation of nodulin 26 coincides with the establishment of mature nitrogen-fixing symbiosomes, is regulated by osmotic stresses that induce calcium-signaling pathways, and appears to be part of the adaptive responses of infected cells to osmotic challenge.


Health care providers' opinions on communication between nursing homes and emergency departments.
To characterize the beliefs and opinions of nursing home (NH) and emergency medicine providers about communication between NH and emergency departments (ED) during transitions of care of NH residents. A cross-sectional study using a mailed and Internet survey. Physicians, nurse practitioners, physicians assistants, and nurses who practice in ED settings and NH settings, affiliated with hospitals of an academic medical center in Rochester, New York. Opinions on communication; beliefs about frequency of information transmission; opinions on how often verbal communication should occur. A total of 155 nurses and medical providers participated in the survey for a response rate of 32.2% (155/481). Of the survey participants, 63.0% and 56.8% had been more than 5 years in their position and facility, respectively. Most respondents felt that important information was lost during patient transfers between NH and ED settings. Providers from ED and NH settings had different opinions on the likelihood that key information would be readily identifiable at patient transfer and that care would include requested tests and follow-up. Providers from both sites of care supported verbal communication at their position when NH residents are transferred to the other setting. Nurses and medical providers from both emergency and NH settings agree that transitional communication is poor between NHs and EDs and support a role for verbal communication during the ED transitions of care of NH residents.


Value considerations in the treatment of head and neck cancer: radiation, chemotherapy, and supportive care.
The management of head and neck cancer has advanced in many areas, including but not limited to diagnostic imaging and response assessment, radiation delivery, surgical approaches, combined-modality therapy, as well as new drug discovery. These advances have become widely used, however, the associated improvements in outcomes of interest compared with other options may at times be modest in magnitude or supported by limited data. In addition, the price tag of these advancements is often high. There is a growing mandate to look at existing data to identify insights into how to improve the value of care and to better understand the comparative effectiveness of one intervention versus another with regard to tumor control, quality of life, and other important outcomes; such insights become particularly important when considerable disparities exist in related costs. We review selected issues in radiotherapy, chemotherapy and supportive care applicable to the management of head and neck cancer and relevant to ascertaining the value of care.


[Male-to-female agonistic support for copulation in Tibetan macaques (Macaca thibetana) at Huangshan, China].
Biological market theory predicts that animals exchange the same commodities, or interchange different ones, to their mutual benefit. Using focal and behavioral sampling methods and continuous recording techniques, we studied Tibetan macaques (Macaca thibetana) in two study groups (YA1 and YA2) at Huangshan, China to see whether adults interchanged male-to-female agonistic support for copulation. Overall, male-to-female agonistic support was significantly correlated with copulation behaviors when data from both study groups were combined. For YA1, copulations in post-agonistic support observation (PO) was greater, but not significantly so, than random observation (RO) in the breeding season, and copulation in PO was significantly greater than RO in the non-breeding season. For YA2 copulations in PO were significantly greater than RO in both breeding and non-breeding seasons. These results suggest that a male who extends post-agonistic support to a female is significantly more likely to copulate with her. Our study provides evidence for the existence of a biological market involving interchanged social behaviors. Our study also illuminates the reproductive strategies of male competition and female choice in this species.


Combined effect of ozone and household air pollution on COPD in people aged less than 50 years old.
Air pollution has been suggested as an important risk factor for chronic obstructive pulmonary disease (COPD); however, evidence of interactive effects on COPD between different factors was sparse, especially for young adults. We aimed to assess the combined effects of ambient ozone (O3) and household air pollution on COPD in young individuals. We conducted a population-based study of residents aged 15-50 years in the low-income and middle-income regions of western China. We used multivariable logistic regression models to examine the associations between long-term ozone exposure and COPD in young individuals. A total of 6537 young cases were identified among the participants, with a COPD prevalence rate of 7.8 (95% CI 7.2% to 8.5%), and most young COPD individuals were asymptomatic. Exposure to household air pollution was associated with COPD in young patients after adjustment for other confounding factors (OR 1.82, 95% CI 1.41 to 2.37). We also found positive associations of COPD with O3 per IQR increase of 20 ppb (OR 1.92, 95% CI 1.59 to 2.32). The individual effects of household air pollution and O3 were 1.68 (95% CI 1.18 to 2.46) and 1.55 (95% CI 0.99 to 2.43), respectively, while their joint effect was 3.28 (95% CI 2.35 to 4.69) with the relative excess risk due to interaction of 1.05 (95% CI 0.33 to 1.78). This study concludes that exposure to ambient O3 and household air pollution might be important risk factors for COPD among young adults, and simultaneous exposure to high levels of the two pollutants may intensify their individual effects.


Development and in vitro evaluation of Chitosan-Eudragit RS 30D composite wound dressings.
The purpose of this research was to design and evaluate chitosan-based films intended for wound dressing application. Required properties for successful wound dressing, such as liquid uptake, vapor and oxygen penetration, bioadhesiveness, and film elasticity, were examined. Water uptake and vapor penetration of the films were determined gravimetrically, while oxygen penetration was determined by Winkler's method. The bioadhesive properties were determined with an in-house pulley system instrument using a pig gut model. Film elasticity was determined with a stretch test using an Instron apparatus. The results showed that pure chitosan films exhibited relatively high liquid uptake and the adsorption tended to decrease with the addition of Eudragit RS 30D. Moisture vapor and oxygen were found to be able to penetrate through all film formulations in comparable amounts. The bioadhesiveness test tended to show lower bioadhesive properties with the addition of Eudragit RS 30D. The formulation containing only chitosan exhibited low elongation of the film at 2 N, but the film elasticity increased with the addition of Eudragit RS 30D. In conclusion, the addition of Eudragit RS 30D could improve a film's mechanical properties but lower its bioadhesiveness.


Clinical significance of serum M30 and M65 levels in metastatic pancreatic adenocarcinoma.
M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin 18. This study was conducted to investigate the serum levels of M30 and M65 in patients with metastatic pancreatic adenocarcinoma (MPA) and the relationship with tumor progression and known prognostic parameters. Twenty-six patients with MPA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum M30 and M65 levels were determined using enzyme-linked immunosorbent assay. The median age at diagnosis was 59 years, range 32-80 years; 14 patients were men. All patients had metastatic stage, and most (n = 21, 81%) had hepatic metastasis. The baseline levels of both serum M30 and serum M65 were significantly higher in patients with MPA than those in the control group (p < 0.001, for both assays). Serum M65 level was only significantly higher in the patients with elevated serum LDH levels than in others with normal serum LDH levels (p = 0.03). For serum M30 levels, no correlation was found. The significant relationship was found between the serum levels of M30 and M65 (r(s) = 0. 926, n = 26, p < 0.001, Spearman's correlation). The median survival for all patients was 31.7 ± 2.2 weeks (95% CI = 27.31-36.08). Although only the serum LDH level was found to be a significant prognostic factor (p = 0.01), neither serum M30 nor serum M65 had significant effect on survival (p = 0.28 and p = 0.15, respectively). In conclusion, although both serum levels of M30 and M65 assays were found to be of diagnostic value, no predictive and prognostic values were determined in MPA patients.


Beta-adrenergic effects on transmembrane 45Ca fluxes in isolated smooth muscle cells.
The effect of the beta-adrenergic agent isoproterenol (ISO) on transmembrane fluxes of 45Ca was assessed in smooth muscle cells in suspension. Exposure of the cells to this smooth muscle relaxant provoked a large (13-fold) transient increase in 45Ca efflux from the isolated cells. This effect was blocked by the beta-adrenergic antagonist pindolol and mimicked by exposure of the cells to dibutyryl adenosine 3',5'-cyclic monophosphate. ISO had no significant effect on 45Ca binding or on 45Ca influx in those cells, thus the ISO-induced increase in 45Ca efflux appears to reflect increased Ca2+ extrusion from the smooth muscle cells. Because the ISO-induced increase in 45Ca efflux was abolished by pretreatment of the cells with the Na+-K+ pump inhibitor ouabain and by lowering extracellular Na+ levels, we propose that the increased Ca2+ extrusion in response to ISO is coupled to increased activity of the plasmalemmal Na+-K+ pump via increased Na+-Ca2+ exchange.


Tumor Necrosis Factor Receptor 2 Restricts the Pathogenicity of CD8(+) T Cells in Mice With Colitis.
Tumor necrosis factor receptor 2 (TNFR2, Tnfrsf1b) regulates multiple aspects of immune function, but little is known about its role in the immunopathogenesis of inflammatory bowel disease (IBD). We investigated whether TNFR2 restricts the activity of specific immune cell subtypes to protect against the development of colitis in mice. Tnfr2(-/-) mice were crossed with interleukin (Il) 10(-/-) mice, which spontaneously develop colitis, to generate Il10(-/-)Tnfr2(-/-) mice. Colonic tissues were collected from Il10(-/-)Tnfr2(-/-) mice along with Il10(-/-) mice (controls) and analyzed by flow cytometry and histology. Bone marrow was transplanted into Il10(-/-) and Il10(-/-)Tnfr2(-/-) mice from Il10(-/-) or Il10(-/-)Tnfr2(-/-) donors by intravenous injection. CD8(+) T cells were neutralized in Il10(-/-)Tnfr2(-/-) mice by intraperitoneal injection of anti-CD8 or isotype control antibodies. Colitis was induced in Rag2(-/-) mice by intravenous injections of naïve CD8(+) T cells isolated from C57BL/6 or Tnfr2(-/-) mice. Il10(-/-)Tnfr2(-/-) mice spontaneously developed more severe colitis compared with Il10(-/-) controls, characterized by selective expansion of colonic CD8(+) T cells. Transplantation of TNFR2-deficient bone marrow resulted in significantly increased incidence and severity of colitis. Transcriptome analyses showed that the expression of genes regulated by TNFR2 were specific to CD8(+) T cells and included genes associated with risk for IBD. Depletion of CD8(+) T cells from Il10(-/-)Tnfr2(-/-) mice prevented colonic inflammation. Adoptive transfer of TNFR2-null naïve CD8(+) T cells compared with CD8(+) T cells from control mice increased the severity of colitis that developed in Rag2(-/-) mice. TNFR2 protects mice from colitis by inhibiting the expansion of colonic CD8(+) T cells. TNFR2 regulates expression of genes that regulate CD8(+) T cells and have been associated with susceptibility to IBD. Disruption in TNFR2 signaling might therefore be associated with pathogenesis. Strategies to increase levels or activity of TNFR2 and thereby reduce the activity of CD8(+) T cells might be developed to treat IBD patients with CD8(+) T cell dysfunction.


Collective dynamics and entanglement of two distant atoms embedded into single-negative index material.
We study the dynamics of two two-level atoms embedded near to the interface of paired meta-material slabs, one of negative permeability and the other of negative permittivity. This combination generates a strong surface plasmon field at the interface between the meta-materials. It is found that the symmetric and antisymmetric modes of the two-atom system couple to the plasmonic field with different Rabi frequencies. Including the Ohmic losses of the materials we find that the Rabi frequencies exhibit threshold behaviour which distinguish between the non-Markovian (memory preserving) and Markovian (memoryless) regimes of the evolution. Moreover, it is found that significantly different dynamics occur for the resonant and an off-resonant couplings of the plasmon field to the atoms. In the case of the resonant coupling, the field does not appear as a dissipative reservoir to the atoms. We adopt the image method and show that the dynamics of the two atoms coupled to the plasmon field are analogous to the dynamics of a four-atom system in a rectangular configuration. A large and long living entanglement mediated by the plasmonic field in both Markovian and non-Markovian regimes of the evolution is predicted. We also show that a simultaneous Markovian and non-Markovian regime of the evolution may occur in which the memory effects exist over a finite evolution time. In the case of an off-resonant coupling of the atoms to the plasmon field, the atoms interact with each other by exchanging virtual photons which results in the dynamics corresponding to those of two atoms coupled to a common reservoir. In addition, the entanglement is significantly enhanced.


Thermoregulation and thermography in neonatal physiology and disease.
Infrared thermal imaging, or thermography, is a technique used to measure body surface temperature in the study of thermoregulation. Researchers are beginning to use this novel methodology to study cancer, peripheral vascular disease, and wound management. The authors tested the feasibility of using an FLIR SC640 uncooled, infrared camera to measure body temperature in neonates housed in heated, humid incubators. The authors examined thermograms to analyze distributions between central and peripheral body temperature in extremely low birth weight infants. The authors have also used this technology to examine the relationship between body temperature and development of necrotizing enterocolitis in premature infants. Handheld, uncooled, infrared cameras are easy to use and produce high-quality thermograms that can be visualized in grayscale or color palettes to enhance qualitative and quantitative analyses. Future research will benefit from the use of this noninvasive, inexpensive measurement tool. Nurse researchers can use this methodology in adult and infant populations to study temperature differentials present in pathological conditions.


Accumulation of biopolymers in activated sludge biomass.
In this study, activated sludge bacteria from a conventional wastewater treatment process were induced to accumulate polyhydroxyalkanoates (PHAs) under different carbon-nitrogen (C:N) ratios. As the C:N ratio increased from 20 to 140, specific polymer yield increased to a maximum of 0.38 g of polymer/g of dry cell mass while specific growth yield decreased. The highest overall polymer production yield of 0.11 g of polymer/g of carbonaceous substrate consumed was achieved using a C:N ratio of 100. Moreover, the composition of polymer accumulated was dependent on the valeric acid content in the feed. Copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] was produced in the presence of valeric acid. The 3-hydroxyvalerate (3HV) mole fraction in the copolymer was linearly related to valeric content in the feed, which reached a maximum of 54% when valeric acid was used as sole carbon source. When the 3HV U in the polymer increased from 0-54 mol%, the melting temperature decreased from 178 degrees to 99 degrees C. Thus, the composition, and hence the mechanical properties, of the copolymer produced from activated sludge can be controlled by adjusting the mole fraction of valeric acid in the feed medium.


Survey of knowledge, beliefs, and practices of neonatal intensive care unit healthcare workers regarding nosocomial infections, central venous catheter care, and hand hygiene.
To assess the knowledge, beliefs, and practices of neonatal intensive care unit (NICU) healthcare workers (HCWs). Self-administered survey. A 55-bed NICU. NICU HCWs (N = 215). The response rate was 68%. Ninety-two percent knew central venous catheters (CVCs) should be capped, clamped, or connected to running fluids at all times. Ninety-five percent knew when to change gloves. Thirty-one percent knew the recommended duration for handwashing. Most HCWs believed sterile technique in CVC care (96%), gloves (91%), and handwashing (99%) prevent nosocomial infection (NI). Sixty-seven percent used sterile barriers to insert CVCs, 76% reported wearing gloves, 81% reported routine handwashing, 35% knew that bacterial hand counts are higher with rings, 30% knew that long fingernails are associated with higher gram-negative bacterial hand contamination, and 35% knew that artificial fingernails are associated with higher gram-negative bacterial hand contamination. Most (93%) believed HCWs can affect outcomes of patients with NIs. Fewer believed rings (40%), artificial fingernails (61%), and long fingernails (48%) play a role in NIs, or that policies concerning number of rings (50%), cutting fingernails (35%), or prohibiting artificial fingernails (47%) would prevent NIs. Sixty-one percent of HCWs regularly wore at least one ring to work, 56% wore their fingernails shorter than the fingertip, and 8% wore artificial fingernails. A disconnect existed between CVC knowledge and beliefs and practice. HCWs did not know the relationship between bacterial hand counts and rings and fingernails, and did not believe rings or long or artificial fingernails increased the risk of NIs.


Combinatorial chemistry approach to chiral catalyst engineering and screening: rational design and serendipity.
An efficient asymmetric catalyst relies on the successful combination of a large number of interrelated variables, including rational design, intuition, persistence, and good fortune-not all of which are necessarily well-understood; this renders such practice largely empirical. As a result, the possibility of using combinatorial chemistry methods in asymmetric catalysis research has been widely recognized to be highly desirable. In this account, we attempt to show the principle and application of combinatorial approach in the discovery of chiral catalysts for enantioselective reactions. The concept focuses on the strategy for the creation of a modular chiral catalyst library by two-component ligand modification of metal ions on the basis of molecular recognition and assembly. The self-assembled chiral catalyst with two different ligands indeed exhibited synergistic effects in terms of both enantioselectivity and activity in comparison with its corresponding homocombinations in many reactions. The examples described in this paper demonstrated the powerfulness of combinatorial approach for the discovery of novel chiral catalyst systems, particularly for the development of highly efficient, enantioselective, and practical catalysts for enantioselective reactions. We hope this concept will stimulate further work on the discovery of more highly efficient and enantioselective catalysts, as well as unexpected classes of catalysts or catalytic enantioselective reactions in the future with the help of a combinatorial chemistry approach.


Effective size of a wild salmonid population is greatly reduced by hatchery supplementation.
Many declining and commercially important populations are supplemented with captive-born individuals that are intentionally released into the wild. These supplementation programs often create large numbers of offspring from relatively few breeding adults, which can have substantial population-level effects. We examined the genetic effects of supplementation on a wild population of steelhead (Oncorhynchus mykiss) from the Hood River, Oregon, by matching 12 run-years of hatchery steelhead back to their broodstock parents. We show that the effective number of breeders producing the hatchery fish (broodstock parents; N(b)) was quite small (harmonic mean N(b)=25 fish per brood-year vs 373 for wild fish), and was exacerbated by a high variance in broodstock reproductive success among individuals within years. The low N(b) caused hatchery fish to have decreased allelic richness, increased average relatedness, more loci in linkage disequilibrium and substantial levels of genetic drift in comparison with their wild-born counterparts. We also documented a substantial Ryman-Laikre effect whereby the additional hatchery fish doubled the total number of adult fish on the spawning grounds each year, but cut the effective population size of the total population (wild and hatchery fish combined) by nearly two-thirds. We further demonstrate that the Ryman-Laikre effect is most severe in this population when (1) >10% of fish allowed onto spawning grounds are from hatcheries and (2) the hatchery fish have high reproductive success in the wild. These results emphasize the trade-offs that arise when supplementation programs attempt to balance disparate goals (increasing production while maintaining genetic diversity and fitness).


Conscious neurosensory mapping of the internal structures of the human knee without intraarticular anesthesia.
The conscious neurosensory characteristics of the internal components of the human knee were documented by instrumented arthroscopic palpation without intraarticular anesthesia. With only local anesthesia injected at the portal sites, the first author (SFD) had both knees inspected arthroscopically. Subjectively, he graded the sensation from no sensation (0) to severe pain (4), with a modifier of either accurate spatial localization (A) or poor spatial localization (B). The nature of the intraarticular sensation was variable, ranging from 0 on the patellar articular cartilage to 4A on the anterior synovium, fat pad, and joint capsule. The sensation arising from the cruciate ligaments ranged from 1 to 2B in the midportion, and from 3 to 4B at the insertion sites. The sensation from the meniscal cartilages ranged from 1B on the inner rim to 3B near the capsular margin. Innervation of most intraarticular components of the knee is probably crucial for tissue homeostasis. Failure of current intraarticular soft tissue reconstructions of the knee may be due, in part, to the lack of neurosensory restoration. Research studies of the knee designed to delineate factors that restore neurosensory characteristics of the musculoskeletal system may lead to techniques that result in true restoration of joint homeostasis and function.


["Bottle feeding dependency" in children with developmental retardation].
We experienced five cases of developmentally retarded children with "bottle feeding dependency", that is, refusal against entry of purees or solid foods into the mouth. All five cases had moderate to severe mental retardations (DQ: 17-37). No abnormal oral reflexes or functions were present. All had been bottle fed and rejected any purees or solid foods for a long period by turning the head, hiding the face or struggling to avoid being fed. Finally we attempted to force them to eat. Despite their initial refusal, small amounts of pureed food was forcedly pushed into their mouth. As a result, their rejecting behavior was overcome in two or three days, and food intake into the mouth markedly improved within one week. It is suspected that the rejecting behavior does not always represent aversion for solid food. We also found that termination of bottle-feeding was effective the transition to eating. Our experience indicates that forced feeding can overcome the rejecting behavior and prolonged "bottle feeding dependency" in children with developmental retardation.


Application of cardiac gated magnetic resonance imaging in murine Chagas' disease.
To evaluate the role of gated cardiac magnetic imaging resonance (MRI) in Chagas' disease, we infected mice with Trypanosoma cruzi (Brazil strain). Two models were chosen for study, the CD1 and the inducible nitric oxide synthase knockout (NOS2-/-) mice. Infection of CD1 mice was associated with a significant increase in the right ventricular inner diameter (RVID) that was reversed in some mice by verapamil. Expression of cardiac NOS2 has been associated with myocardial dysfunction. Therefore, we evaluated chagasic cardiomyopathy in NOS2-/- and syngeneic wild type (WT) mice. Infected WT mice exhibited an increase in RVID in the acute phase (< 60 days postinfection) that was more marked during chronic infection (>100 days postinfection). Chronically infected NOS2-/- mice had an increase in RVID. The RVID in infected WT mice was greater than in NOS2-/- mice. These data demonstrate that MRI is a useful tool in the serial evaluation of the heart in murine Chagas' disease. In addition, it supports the notion that the NOS2-/-/NO pathway may contribute to the pathogenesis of murine chagasic cardiomyopathy.


Protein kinase A activation enhances β-catenin transcriptional activity through nuclear localization to PML bodies.
The Protein Kinase A (PKA) and Wnt signaling cascades are fundamental pathways involved in cellular development and maintenance. In the osteoblast lineage, these pathways have been demonstrated functionally to be essential for the production of mineralized bone. Evidence for PKA-Wnt crosstalk has been reported both during tumorigenesis and during organogenesis, and the nature of the interaction is thought to rely on tissue and cell context. In this manuscript, we analyzed bone tumors arising from mice with activated PKA caused by mutation of the PKA regulatory subunit Prkar1a. In primary cells from these tumors, we observed relocalization of β-catenin to intranuclear punctuate structures, which were identified as PML bodies. Cellular redistribution of β-catenin could be recapitulated by pharmacologic activation of PKA. Using 3T3-E1 pre-osteoblasts as a model system, we found that PKA phosphorylation sites on β-catenin were required for nuclear re-localization. Further, β-catenin's transport to the nucleus was accompanied by an increase in canonical Wnt-dependent transcription, which also required the PKA sites. PKA-Wnt crosstalk in the cells was bi-directional, including enhanced interactions between β-catenin and the cAMP-responsive element binding protein (CREB) and transcriptional crosstalk between the Wnt and PKA signaling pathways. Increases in canonical Wnt/β-catenin signaling were associated with a decrease in the activity of the non-canonical Wnt/Ror2 pathway, which has been shown to antagonize canonical Wnt signaling. Taken together, this study provides a new understanding of the complex regulation of the subcellular distribution of β-catenin and its differential protein-protein interaction that can be modulated by PKA signaling.


On the filling in of the visual blind spot: some rules of thumb.
In monocular viewing there is a region in the peripheral visual field that is blind owing to the absence of photoreceptors at the site where the optic nerve exits the eye. This region, like certain other blind spots, nonetheless appears filled in. Several novel demonstrations of filling in at the blind spot have recently been reported. Here the implications of many of these effects are critically reevaluated. Specifically, it is argued that many blind-spot phenomena taken to support early filling in (eg pop out and alteration in apparent motion) are actually consistent with the thesis that the visual blind spot is treated by early perceptual processing as a region of reduced or absent information. In support of this, it is shown that many perceptual effects observed in blindspot completion are similar in detail to the amodally perceived completion of partly occluded objects viewed somewhat peripherally. The goals were to point out striking similarities between blind-spot completion and the amodal completion of occluded parts of surfaces, and to provide a common theoretical framework for understanding these phenomena in the context of surface segregation and perceptual interpolation.


Auriculotherapy fails to relieve chronic pain. A controlled crossover study.
Enthusiastic reports of the effectiveness of electrical stimulation of the outer ear for the relief of pain ("auriculotherapy") have led to increasing use of the procedure. In the present study, auriculotherapy was evaluated in 36 patients suffering from chronic pain, using a controlled crossover design. The first experiment compared the effects of stimulation of designated auriculotherapy points, and of control points unrelated to the painful area. A second experiment compared stimulation of designated points with a no-stimulation placebo control. Pain-relief scores obtained with the McGill Pain Questionnaire failed to show any differences in either experiment. It is concluded that auriculotherapy is not an effective therapeutic procedure for chronic pain.


Association between oral health status and oral food intake level in subacute stroke patients admitted to a convalescent rehabilitation unit.
Stroke patients often suffer from dysphagia during their recovery. We hypothesised that subacute stroke patients with dysphagia had more deteriorated oral health status including muscle strength and motor function. Quantitatively investigate oral health status and identify associations with oral feeding status in stroke patients admitted to a convalescent rehabilitation unit. We prospectively recruited 187 stroke patients admitted to a convalescent rehabilitation unit. Oral feeding status was examined using the Functional Oral Intake Scale (FOIS), and the cohort was divided into three groups based on FOIS score as non-oral feeding (FOIS-123; 22 patients), dysphagic diet (FOIS-45; 74 patients), and regular diet (FOIS-67; 91 patients) groups. Activities of daily living (ADL) were assessed with the Functional Independence Measure (FIM). Oral health status was measured quantitatively in six oral function parameters and Oral Health Assessment Tool (OHAT), and differences according to the FOIS, age and FIM were statistically tested. In bivariate analysis, two parameters, tongue pressure and tongue-lip motor functions were significantly higher in the regular diet group than in the other groups (P < .01). Gross OHAT score was also significantly better in the regular diet group than in the other groups (P < .01). These significant associations mostly remained in the multiple model after adjusting for age and FIM. This study suggests that, amongst oral health status, tongue strength and motor function, as well as OHAT score, may have strong associations with oral feeding status in subacute stroke patients at convalescent rehabilitation units regardless of ADL levels.


Urinary tract infection.
The approach to urinary tract infection remains a difficult and sometimes controversial issue. One area in particular is accurate diagnosis. In a recent article it was suggested utilizing the "enhanced" urinalysis, not as a replacement to culture but as a potential sensitive predictor to allow therapy to be given while awaiting culture results. Another difficult area is the issue of radiologic evaluation for underlying urologic abnormalities following a urinary tract infection. Previous discussion on this topic has pointed to early evaluation, even after the first urinary tract infection. There now seems to be some reconsideration of when to evaluate children following urinary tract infection. Some reviews, however point to a less aggressive approach. Another area of discussion is the evaluation of siblings of index cases with reflux. Here there is new data suggesting that evaluation of young siblings (under 6 years of age) may yield a relatively high incidence of reflux whereas evaluation of siblings over 6 years of age yields a small percentage of patients with reflux. The question of circumcision is another area of long-term interest in the study of urinary tract infections. Still more data published recently suggests that uncircumcised males have a higher incidence of urinary tract infection. However, this continues to be a point of controversy.


Interaction of Aqueous Extract of Pleurotus pulmonarius (Fr.) Quel-Champ. with Glyburide in Alloxan Induced Diabetic Mice.
Mushrooms are low calorie food with very little fat and are highly suitable for obese persons. With no starch and very low sugars, they are the 'delight of the diabetics'. Combination of herbal drugs (or isolated phytochemicals) is found to be beneficial in certain diseases when given along with conventional drugs. The aim of the present study was to evaluate the effects of aqueous extract of Pleurotus pulmonarius (Lentinaceae) (called as PP-aqu) and its interaction with glyburide in alloxan induced diabetic mice. The diabetic mice treated were with PP-aqu (500 mg/kg, p.o.) alone or combination with glyburide (10 mg/kg, p.o.) for 28 days. Blood samples were collected by orbital sinus puncture using heparinized capillary glass tubes and were analyzed for serum glucose on 0, 7th, 14th, 21st and 28th days. Body weights and mortality were noted during the study period. In oral glucose tolerance test (OGTT), glucose (2.5 g/kg, p.o.) was administered with either vehicle, PP-aqu alone or in combination with glyburide and serum glucose level analyzed at 0, 30, 60 and 120 min after drug administration. Administration of PP-aqu (500 mg/kg) and its combination with glyburide (10 mg/kg) significantly (P < 0.001) decreased serum glucose level in diabetic mice. In OGTT, glyburide or PP-aqu treatment alone or their combination produced significant (P < 0.001) increase in glucose threshold. Thus we suggest that P. pulmonarius showed potent and synergistic antihyperglycemic effect in combination with glyburide.


The effects of acute or chronic cadmium exposure on the adult mouse CNS: a freeze-fracture study.
The effect of acute Cd exposure (0.5-12 mg CdCl2/kg body wt. for six hours) or chronic Cd exposure (40 ppm in the drinking water for 3 weeks) on the CNS of adult mice was investigated quantitatively by the use of the freeze-fracture technique to examine the nuclear membrane of cells from the cerebral cortex. Intramembrane particle density and nuclear pore density was determined for both the P face of the inner membrane and the E face of the outer membrane from control and experimental animals. The changes observed for both groups of experimental animals were similar in that particle numbers for both P and E faces were significantly increased over control values while nuclear pore numbers were unaffected. For the acute doses the increases were dose-dependent.


Two very long chain fatty acid acyl-CoA synthetase genes, acs-20 and acs-22, have roles in the cuticle surface barrier in Caenorhabditis elegans.
In multicellular organisms, the surface barrier is essential for maintaining the internal environment. In mammals, the barrier is the stratum corneum. Fatty acid transport protein 4 (FATP4) is a key factor involved in forming the stratum corneum barrier. Mice lacking Fatp4 display early neonatal lethality with features such as tight, thick, and shiny skin, and a defective skin barrier. These symptoms are strikingly similar to those of a human skin disease called restrictive dermopathy. FATP4 is a member of the FATP family that possesses acyl-CoA synthetase activity for very long chain fatty acids. How Fatp4 contributes to skin barrier function, however, remains to be elucidated. In the present study, we characterized two Caenorhabditis elegans genes, acs-20 and acs-22, that are homologous to mammalian FATPs. Animals with mutant acs-20 exhibited defects in the cuticle barrier, which normally prevents the penetration of small molecules. acs-20 mutant animals also exhibited abnormalities in the cuticle structure, but not in epidermal cell fate or cell integrity. The acs-22 mutants rarely showed a barrier defect, whereas acs-20;acs-22 double mutants had severely disrupted barrier function. Moreover, the barrier defects of acs-20 and acs-20;acs-22 mutants were rescued by acs-20, acs-22, or human Fatp4 transgenes. We further demonstrated that the incorporation of exogenous very long chain fatty acids into sphingomyelin was reduced in acs-20 and acs-22 mutants. These findings indicate that C. elegans Fatp4 homologue(s) have a crucial role in the surface barrier function and this model might be useful for studying the fundamental molecular mechanisms underlying human skin barrier and relevant diseases.


Cardiotoxicity of de Gramont's regimen: incidence, clinical characteristics and long-term follow-up.
The incidence of 5-fluorouracil (5-FU)-related cardiotoxicity seems to be dosage and schedule dependent. It was reported as 1.6-3% with earlier bolus regimens whereas this increased up to 7.6-18% with prolonged (4-5 days) infusion regimens. Knowledge of the cardiotoxicity incidence in patients treated with the widely used de Gramont's regimen (2 days infusional 5-FU) and the long-term follow-up of affected patients is still limited. We investigated the incidence and clinical characteristics of the cardiotoxicity of de Gramont's regimen and long-term follow-up of the affected patients. Nine of a total of 231 patients receiving de Gramont's regimen experienced cardiac events, revealing an overall incidence of 3.9%. Four (2.5%) cases were receiving de Gramont's regimen only. Cardiac manifestations were acute coronary syndrome (n = 6), congestive heart failure (n = 2) and atrial fibrillation (n = 1). Cardiotoxicity occurred in the first cycle in eight patients, and in the second cycle in one. The median onset day was day 2. Cardiac symptoms occurred mostly at night time (seven patients) and the onset was a few hours after the bolus part of the regimen in four out of seven patients. After the cardiotoxicity, treatments were continued safely without 5-FU. de Gramont's regimen has a lower incidence of cardiotoxicity compared with more prolonged 5-FU-based infusion regimens. Nevertheless, patients should still be carefully monitored especially in the first cycles and at night time.


Gene targeting at the mouse cytokeratin 10 locus: severe skin fragility and changes of cytokeratin expression in the epidermis.
Bullous congenital ichthyosiform erythroderma (BCIE) is a dominantly inherited blistering skin disorder caused by point mutations in the suprabasal cytokeratins 1 or 10. Targeting the murine cytokeratin 10 gene in ES cells resulted in mice with different phenotypes in the homozygotes and heterozygotes; both of which exhibit similarities to specific clinical characteristics of BCIE. Homozygotes suffered from severe skin fragility and died shortly after birth. Heterozygotes were apparently unaffected at birth, but developed hyperkeratosis with age. In both genotypes, aggregation of cytokeratin intermediate filaments, changes in cytokeratin expression, and alterations in the program of epidermal differentiation were observed. In addition we demonstrate, for the first time, the existence of the murine equivalent of human cytokeratin 16.


Intrinsic impairment of CD4(+)CD25(+) regulatory T cells in acquired aplastic anemia.
Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure attacked by autoreactive effector T cells and BM is the main target organ. CD4(+)CD25(+) regulatory T cells (Tregs) were believed to control development and progression of autoimmunity by suppressing autoreactive effector T cells, but little was known regarding the function of Tregs in AA. Our study demonstrated that both peripheral blood (PB) and BM had decreased frequencies of Tregs, accompanied with a reversed lower ratio of Treg frequencies between BM and PB in AA. PB Tregs in AA had impaired migratory ability because of lower CXCR4 (but not for CXCR7) expression. Interestingly, we first showed that impairment of Treg-mediated immunosuppression was intrinsic to Tregs, rather than resistance of effector T cells to suppression in AA by coculture assays and criss-cross experiments in vitro. Furthermore, Tregs in AA were less able to inhibit interferon-γ production by effector T cells. Defective immunosuppression by Tregs could contribute to impaired hematopoiesis conducted by effector T cells in vitro. Our study provided powerful evidence that impairment of Tregs played a critical role in the pathophysiology of AA. Thus, patients with AA might greatly benefit from a Treg-oriented immunosuppressive strategy.


Invasive (solid) Papillary Carcinoma of the Breast: A Report of Two Cases.
Papillary carcinoma is a rare malignant tumour of the breast with an incidence of 1-2% in the general population. The clinical behaviour of solid papillary carcinomas is generally indolent unless it is associated with invasion. Here, we are reporting two cases of solid invasive papillary carcinomas of the breast, who were 2 female patients aged 44 years and 55 years., with breast masses which were diagnosed by FNAC and confirmed by histopathology. The exact incidence and the clinical behaviours of such cases need to be ascertained by further research.


Estimating the US pericarditis prevalence using national health encounter surveillance databases.
To obtain a nationally representative annualized estimate of the prevalence of pericarditis (inflammation of the pericardium) in the United States (US) in order to better understand the potential burden on the health care system. Three nationally representative datasets were used to estimate the annualized period prevalence and prevalence rate of pericarditis from 2007 to 2016: the National Ambulatory Medical Care Survey (NAMCS), the National Hospital Ambulatory Medical Care Survey (NHAMCS), and the Nationwide Inpatient Sample (NIS). Across all data sources, ICD-9/10 codes were used to identify healthcare encounters with ≥1 primary or secondary diagnosis related to pericarditis irrespective of duration or etiology. The prevalence of pericarditis in 2020 was extrapolated by multiplying the average annualized prevalence rate from 2007 to 2016 by the total US population as of March 2020. Data from NAMCS/NHAMCS (2007-2016) yielded an average annualized estimate of 125,209 patients with pericarditis, resulting in a pooled average annualized prevalence estimate of 40 patients with pericarditis per 100,000 persons. Data from NIS (2007-2016) yielded an average annualized estimate of 34,441 patients with pericarditis, resulting in a pooled average annualized prevalence estimate of 11 hospitalized patients with pericarditis per 100,000 persons. Extrapolation of these results based on the March 2020 population estimates from the US Census Bureau of 329,436,928 resulted in an estimated US prevalence of pericarditis to be approximately160,000. Despite certain methodologic limitations, our analysis of data from nationally representative sources support that pericarditis is a rare disease affecting substantially fewer than 200,000 persons in the US.


Rapid evolution through gene duplication and subfunctionalization of the testes-specific alpha4 proteasome subunits in Drosophila.
Gene duplication is an important mechanism for acquiring new genes and creating genetic novelty in organisms. Evidence suggests that duplicated genes are retained at a much higher rate than originally thought and that functional divergence of gene copies is a major factor promoting their retention in the genome. We find that two Drosophila testes-specific alpha4 proteasome subunit genes (alpha4-t1 and alpha4-t2) have a higher polymorphism within species and are significantly more diverged between species than the somatic alpha4 gene. Our data suggest that following gene duplication, the alpha4-t1 gene experienced relaxed selective constraints, whereas the alpha4-t2 gene experienced positive selection acting on several codons. We report significant heterogeneity in evolutionary rates among all three paralogs at homologous codons, indicating that functional divergence has coincided with genic divergence. Reproductive subfunctionalization may allow for a more rapid evolution of reproductive traits and a greater specialization of testes function. Our data add to the increasing evidence that duplicated genes experience lower selective constraints and in some cases positive selection following duplication. Newly duplicated genes that are freer from selective constraints may provide a mechanism for developing new interactions and a pathway for the evolution of new genes.


Facilitated saliva secretion and reduced oral inflammation by a novel artificial saliva system in the treatment of salivary hypofunction.
Saliva substitutes and/or lubricants are commonly employed to lessen dry mouth symptoms by stimulating and/or substituting for the secretion of saliva. In this study, a novel artificial saliva containing inorganic salts, including sodium chloride and potassium chloride, and bactericidal agents, including potassium thiocyanate and lactoperoxidase, was formulated in the form of a solution (DM-sol) or gel (DM-gel). Those in vivo therapeutic efficacies were assessed in terms of saliva secretion and anti-inflammatory activity in rats and mice, respectively. Salivary secretion was promoted by mucosal application of DM-formulations in normal rats. In particular, DM-gel resulted in 2.5- and 1.9-fold greater salivary flow rates compared to normal saline and DM-sol, respectively. In an in vivo efficacy evaluation in diabetic mice with salivary hypofunction, repeated application of DM-formulations alleviated histopathological changes in the buccal mucosa in terms of atrophy and thinning of the epithelium, compared to vehicle, after 4 weeks. Moreover, the DM-sol and DM-gel were comparably effective for relieving periodontal gingivitis, reducing infiltration of inflammatory cells, and normalizing the neutrophil level in the gingival gingiva, after 4 weeks. Therefore, the novel artificial saliva is expected to facilitate salivary secretion and restore physiological conditions in the mouth of patients with salivary hypofunction.


Suppression of azoxymethane-induced aberrant crypt foci in rat colon by nimesulide, a selective inhibitor of cyclooxygenase 2.
Non-steroidal anti-inflammatory drugs, such as piroxicam and sulindac, are known to inhibit development of aberrant crypt foci (ACF) and cancer in the colon. However, these agents cause gastrointestinal side-effects. Nimesulide is a selective inhibitor of cyclooxygenase 2 and has been shown to have a more potent anti-inflammatory action than piroxicam, but be less ulcerogenic and, therefore, a potentially more useful chemopreventive agent. To assess this possibility the inhibitory effects of nimesulide on the formation of ACF induced by azoxymethane in rat colon were investigated, and compared with those of piroxicam and sulindac. Male F344 rats were treated s.c. with 15 mg/kg body weight azoxymethane once a week for 2 weeks and given 50, 100 or 200 ppm nimesulide, 200 ppm piroxicam, or 200 ppm sulindac in their diet from the day before the first carcinogen treatment until the end of the experiment at week 4. At this time, nimesulide at doses of 50, 100 and 200 ppm had reduced the numbers of azoxymethane-induced ACF to 75%, 71% and 65% respectively compared to the control. The number of azoxymethane-induced ACF per colon in the group given 200 ppm nimesulide was almost the same as in those given 200 piroxicam, and lower than that in the group given 200 ppm sulindac. These results suggest that nimesulide, a selective cyclooxygenase 2 inhibitor, warrants attention as a candidate for chemopreventive agent with low toxicity, active against colon carcinogenesis.


[Characteristics of a new aromatic heptaenic antibiotic, flavumycin A].
The study of the products of alkaline and acid hydrolysis showed that flavumycin A included mycosamine, an aminosugar and n-aminoacetophen, an aromatic fragment. The main functional groups of the antibiotics aglicone were determined.


Biomarker alterations produced in rat lung by intratracheal instillations of air particulate extracts and chemoprevention with oral N-acetylcysteine.
Organic matter extracts were obtained from particulates recovered from 10,000-m3 air samples collected in Sicily (Italy). The overall concentrations of acenaphthene, benzo(a)pyrene, phenanthrene, anthracene, fluoranthene, and pyrene were 526 ng/m3 air in a highly polluted urban area and 48 ng/m3 in a rural area affected by motor vehicle traffic pollution. After metabolic activation, both samples were mutagenic in Salmonella typhimurium his(-) strains of the TA and YG series, with potencies in TA100 of 140.7 and 11.8 revertants/m3 air, respectively. The samples, resuspended in tricaprylin, were instilled intratracheally in Sprague-Dawley rats for 5 consecutive days, accounting for a cumulative dose in each animal of the organic fractions extracted from 400 m3 air, which corresponds approximately to the volume of air inhaled by a man in 1 month. Treatment with the rural area sample and, at higher levels, with the urban area sample resulted in the formation of adducts to lung DNA, as assessed both by synchronous fluorescence spectrophotometry and by 32P postlabeling, which showed the appearance of up to six individual adducts emerging from diffuse diagonal radioactive zones. The adducts were more efficiently detected by extraction with butanol than by digestion with nuclease P1. DNA binding of air particulate extracts was followed by alterations of early damage biomarkers only in the rats treated with the urban area sample. Repair of DNA damage in lung cells was inferred from a significant stimulation of the nuclear enzyme poly(ADP-ribose) polymerase compared with that in sham-exposed rats. Among the cells recovered by bronchoalveolar lavage, an increase in polymorphonucleate leukocytes and cells of the ciliated respiratory epithelium was accompanied by a relative decrease in pulmonary alveolar macrophages. The frequency of micronuclei was significantly enhanced both in epithelial cells and alveolar macrophages, and binucleated macrophages were also more frequent in treated rats. The thiol N-acetylcysteine, one of the most promising cancer chemopreventive agents, was administered with drinking water to a group of animals receiving the air particulate polycyclic aromatic hydrocarbon fraction from the urban area. N-acetylcysteine prevented or considerably attenuated the alterations of all monitored parameters. These findings provide evidence that, even under outstandingly high exposure conditions, it is possible to protect the respiratory tract from DNA-binding and DNA-damaging air particulate carcinogens.


Picoliter nDEP traps enable time-resolved contactless single bacterial cell analysis in controlled microenvironments.
We present a lab-on-a-chip device, the Envirostat 2.0, which allows for the first time contactless cultivation of a single bacterial cell by negative dielectrophoresis (nDEP) in a precisely controllable microenvironment. Stable trapping in perfusing growth medium was achieved by a miniaturization of octupole electrode geometries, matching the dimensions of bacteria. Temperature sensitive fluorescent measurements showed that these reductions of microelectrode distances led to reduced Joule heating during cell manipulation. The presented miniaturization is not possible with conventional manufacturing processes. Therefore, we present a novel bonding technology, which permits miniaturization of 3D octupole electrode geometry with biocompatible materials. To exclude the influence of other cells and to enable sampling of perfusion medium from the isolated living bacterium under study, computer aided flow simulations were used to develop a microfluidic nDEP isolation procedure. The developed microchannel and microelectrode design integrates for the first time well characterized nDEP cell sorting mechanisms and time-resolved contactless single bacterial cell cultivation in a 1.7 picoliter bioreactor system. The cell type independent trapping is demonstrated with singularized Bacillus subtilis, Escherichia coli, Corynebacterium glutamicum and other industrially relevant microbes. The static and precisely controlled microenvironment resulted in a consistent and significant faster growth compared to maximal growth rates observed on population level. Preventing the influence of surfaces and cell-cell interactions, the Envirostat 2.0 chip permits total microenvironmental control by the experimenter and therefore provides major opportunities for microfluidic based cell analysis of bacteria and small eukaryotes.


Evaluation of individually ventilated cage systems for laboratory rodents: cage environment and animal health aspects.
The use of individually ventilated cage (IVC) systems has become an attractive housing regime of laboratory rodents. The benefits of IVC systems are, reportedly, a high degree of containment combined with relative ease of handling, and a high degree of protection from allergenes. In the present study we tested whether two IVC systems (BioZone VentiRack, IVC1 and Techniplast SealSafe, IVC2S), in which we held mature male NMRI mice, were constructed to maintain a constant differential pressure, positive or negative, during a prolonged period of time. We also measured ammonia (NH3) concentrations after about 2 weeks of use, and CO2 build-up during a 60 min simulated power failure situation. In addition, animal weight development and bite-wound frequency were recorded (Renström et al. 2000). From the present study it is concluded that the IVC1 air handling system provides a more uniform and balanced differential pressure than the IVC2S. Both systems effectively scavenge NH3 when bedding material is not soaked by urine. Although the IVCs are dependent on the continual function of the fans to work properly, it seems unlikely that CO2 concentrations increase to hazardous levels, as a result of a one hour power failure, with the type of cages used in this study. Differences in weight development and bite-wound occurrence were noted between the two IVC systems. Causes for these differences could not be established and need more investigation.


Transfer of training effects in stroke patients with apraxia: an exploratory study.
The goal of the present study was to examine the transfer of the effects of cognitive strategy training for stroke patients with apraxia from trained to non-trained tasks. In strategy training, the occurrence of transfer is expected as the training programme is aimed, not at relearning specific tasks, but at teaching patients new ways to handle the problems resulting from the impairment. Exploratory analyses were conducted on data previously collected in a randomised controlled trial on the efficacy of the strategy training. A total of 113 left hemisphere stroke patients were randomly assigned to a strategy training group and a group receiving occupational therapy as usual. Assessment of apraxia, motor functioning and activities of daily living (ADL) took place at baseline, after an eight-week treatment period, and five months after baseline. The primary outcome measure consisted of standardised ADL observations of trained and non-trained tasks. The analyses showed that in both treatment groups, the scores on the ADL observations for non-trained tasks improved significantly after eight weeks of training as compared with the baseline score. Change scores of non-trained activities were larger in the strategy training group as compared with the usual treatment group. By using previously collected data we are able to illustrate the potential transfer of treatment effects in a large sample of stroke patients. We found indications for the occurrence of transfer, although the study was not originally designed for the purpose of evaluating transfer. Therefore these results are worth exploring more profoundly. We will further investigate our preliminary conclusions in a new prospective study which is specifically designed to examine the transfer of training effects.


Synthesis and reactivity of aza-dipyrrin alkali metal salts.
We report the lithium, sodium and potassium salts of aza-dipyrrins and detail their use as anionic aza-dipyrrinato ligand sources in complexation. Of the three types of alkali salts studied, those of lithium are found to be most useful as synthetic precursors. For example, they selectively afford heteroleptic aza-dipyrrinato zinc complexes which can be further modified via ligand exchange.


Influence of glutathione S-transferase polymorphisms on genotoxic effects induced by tobacco smoke.
Genotoxicity of tobacco smoke has long been investigated and tobacco smoke is considered to be one of the principal human carcinogens. Although its role in DNA-damage induction and cancer development has been documented, the mechanisms by which this happens are not well understood. Many chemical constituents of tobacco smoke are enzymatically metabolized by phase-I and phase-II enzymes, but modifications in coding and regulating sequences of these genes could influence their ability to detoxify these compounds. In this work, we studied several enzymes involved in the metabolism of xenobiotics, viz. the glutathione S-transferases (GST) M1, T1, P1 and A1, with respect to their influence on the genotoxic effects induced by cigarette smoking. We assessed the genotoxic effects of tobacco smoke on peripheral blood lymphocytes of 72 healthy caucasians by use of the chromosomal aberration (CA) assay and the micronucleus (MN) test. Genotypes of GST M1, T1, P1 and A1 were determined by means of the polymerase chain reaction and methods based on restriction fragment length polymorphism (RFLP). We found that smoke and gender are the two variables that most influence the DNA damage. In particular, we observed that female smokers seem to be more sensitive than male smokers, having a significantly higher frequency of CAs. Moreover, a significant increase in frequency of micronuclei in bi-nucleated cells (BNMN) was found in smokers, but not in non-smokers. This increase seems to be influenced not only by age and gender, but also by genetic constitution. Subjects carrying GSTM1-null genotype seemed to have an higher susceptibility to DNA damage induced by tobacco smoke than GSTM1-positive ones. When considering a combination of GST genotypes, we found a lower BNMN frequency in subjects with GSTP1 variant allele plus GSTM1-positive genotypes, while the most damaged cells are found in subjects bearing GSTM1-null plus GSTP1-wild type. Our results suggest that investigation of the association between several gene polymorphisms and important endpoints of DNA damage could contribute to better understanding the role of gene-gene interaction.


AMEE Medical Education Guide No. 23 (Part 1): Curriculum, environment, climate, quality and change in medical education-a unifying perspective.
This paper looks at five focal terms in education - curriculum, environment, climate, quality and change - and the interrelationships and dynamics between and among them. It emphasizes the power and utility of the concept of climate as an operationalization or manifestation of the curriculum and the other three concepts. Ideas pertaining to the theory of climate and its measurement can provide a greater understanding of the medical curriculum. The learning environment is an important determinant of behaviour. Environment is perceived by students and it is perceptions of environment that are related to behaviour. The environment, as perceived, may be designated as climate. It is argued that the climate is the soul and spirit of the medical school environment and curriculum. Students' experiences of the climate of their medical education environment are related to their achievements, satisfaction and success. Measures of educational climate are reviewed and climate measures for medical education are discussed. These should take account of current trends in medical education and curricula. Measures of the climate may subdivide it into different components giving, for example, a separate assessment of so-called Faculty Press, Student Press, Administration Press and Physical or Material Environmental Press. Climate measures can be used in different modes with the same stakeholders. For example, students may be asked to report, first, their perceptions of the actual environment they have experienced and, second, to report on their ideal or preferred environment. The same climate index can be used with different stakeholders giving, for example, staff and student comparisons. In addition to the educational climate of the environment that students inhabit, it is important to consider the organizational climate of the work environment that staff inhabit. This organizational climate is very significant, not only for staff, but for their students, too. The medical school is a learning organization evolving and changing in the illuminative evaluation it makes of its environment and its curriculum through the action research studies of its climate. Considerations of climate in the medical school, along the lines of continuous quality improvement and innovation, are likely to further the medical school as a learning organization with the attendant benefits. Unless medical schools become such learning organizations, their quality of health and their longevity may be threatened.


Retinal sphingolipids and their very-long-chain fatty acid-containing species.
Recent evidence suggests that ceramide metabolism plays an important role in retinal photoreceptor cell survival and apoptosis. The purpose of this study was to characterize sphingolipids in the retina with special emphasis on the very-long-chain-containing saturated (VLC-FA) and polyunsaturated (VLC-PUFA) fatty acid-containing species. The VLC-FAs and VLC-PUFAs are synthesized by the ELOVL4 protein, which is involved in human Stargardt's macular dystrophy type 3 (STGD3). Total lipids were extracted from retina and other tissues, and different sphingolipid classes were isolated and purified using various combinations of liquid- and solid-phase separation. Purified sphingolipids were analyzed by high-performance thin layer chromatography (HPTLC), gas chromatography (GC), and GC-MS (GC-mass spectrometry). Nonsialylated sphingolipids (NSLs) comprised approximately 3.5% of total retinal lipids of which 70% was sphingomyelin. Ceramide and glycosylceramides (GCs) constituted<or=1% of total retinal lipids. Gangliosides (GGs), on the other hand, comprised approximately 3.0% of total retinal lipids. Fatty acid analysis of retinal NSLs indicated an abundance of saturated fatty acids, with the presence of VLC-FAs but not of VLC-PUFAs beyond 24 carbons. However, GG had significant levels of unsaturated, polyunsaturated, and VLC-PUFAs. Retinal rod outer segments (ROS) contained approximately 1% each of NSL and GG, and their fatty acid profile was not very different from whole retinal NSL and GG, respectively. Retina has a total of 6% to 7% fatty acids that are N-linked to a sphingosine, which would be 11 to 13 mole % in comparison to phospholipids. The presence of VLC-FAs and VLC-PUFAs in retinal sphingolipids indicates that they may play role in ELOVL4-mediated Stargardt 3.


Invasiveness of Aeromonas spp. in relation to biotype, virulence factors, and clinical features.
Of 69 fecal isolates of Aeromonas spp., 18 had the ability to invade HEp-2 cells. Invasiveness correlated with biotype; of the 18 invasive strains, 16 were A. sobria and 2 were A. hydrophila. No invasive strains were found among the A. caviae. Of the 18 invasive strains, 13 were enterotoxigenic. Of the enterotoxigenic and invasive strains, 12 were A. sobria, but enterotoxicity was also more common among noninvasive strains of A. sobria. Fucose-resistant hemagglutination was also more common in A. sobria, but invasive strains were equally divided between fucose-resistant hemagglutination and other patterns. Detailed clinical information was available for 27 of the 69 strains. All 15 strains of A. sobria or A. hydrophila associated with diarrhea were enterotoxigenic; 6 of the 10 strains of A. sobria were also invasive. Blood was present in the stool samples of five of the six patients with invasive A. sobria and in none of the patients with noninvasive strains. Although limited, these observations suggest that dysenteric symptoms may be produced by invasive Aeromonas spp.


A comparative study of the binding characteristics of ceftriaxone, cefoperazone and cefsulodin to human serum albumin.
The binding to human serum albumin of three cephalosporins of pharmacological interest: cefoperazone, ceftriaxone and cefsulodin was studied by ultrafiltration and differential scanning calorimetry methods. The identification of the binding sites in albumin was also performed using probes for the so-called sites I, II, bilirubin and fatty acids binding sites. Albumin showed two types of binding sites for cefoperazone and ceftriaxone, while for cefsulodin it showed a single type of binding site. The affinity values were: 5.6 10(4) M-1 and 3.1 10(4) M-1 for cefoperazone and ceftriaxone respectively, while cefsulodin showed low affinity (3.8 10(2) M-1). It was found that only cefoperazone interacted in a slight way with site I on serum albumin, while site II and the bilirubin binding site have capacity of binding the three cephalosporins assayed. Ceftriaxone and cefoperazone showed capacity to bind to the fatty acids binding site on albumin. These cephalosporins increased the thermal stability of the protein, suggesting that these ligands are favouring the compact structure of the native form of the protein more than the unfolded form.


Overcoming aggregation in indium salen catalysts for isoselective lactide polymerization.
A methodology for controlling aggregation in highly active and isoselective indium catalysts for the ring opening polymerization of racemic lactide is reported. A series of racemic and enantiopure dinuclear indium ethoxide complexes bearing salen ligands [(ONNOR)InOEt]2 (R = Br, Me, admantyl, cumyl, t-Bu) were synthesized and fully characterized. Mononuclear analogues (ONNOR)InOCH2Pyr (R = Br, t-Bu, SiPh3) were synthesized by controlling aggregation with the use of chelating 2-pyridinemethoxide functionality. The nuclearity of metal complexes was confirmed using PGSE NMR spectroscopy. Detailed kinetic studies show a clear initiation period for these dinuclear catalysts, which is lacking in their mononuclear analogues. The polymerization behavior of analogous dinuclear and mononuclear compounds is identical and consistent with a mononuclear propagating species. The isotacticity of the resulting polymers was investigated using direct integration and peak deconvolution methodologies and the two were compared.


[Characteristics of goiter endemic in Kuzbass].
The purpose of the present study was to comprehensively assess goiter endemia in Kuzbass. The spread of goiter was examined in its population. The severity and intensity of goiter endemia were assessed. Its causes and risk factors were revealed. The Kemerovo region was found to be an area of moderate goiter endemia with a tendency for its severity. The wide spread of iodine deficiency in the population, which is associated with low dietary iodine intake, is a cause of goiter endemia in Kuzbass.


Homoplasy-Based Partitioning Outperforms Alternatives in Bayesian Analysis of Discrete Morphological Data.
Bayesian analysis of morphological data is becoming increasingly popular mainly (but not only) because it allows for time-calibrated phylogenetic inference using relaxed morphological clocks and tip dating whenever fossils are available. As with molecular data, recent studies have shown that modeling among-character rate variation (ACRV) in morphological matrices greatly improves phylogenetic inference. In a likelihood framework this may be accomplished, for instance, by employing a hidden Markov model to assign characters to rate categories drawn from a (discretized) $\Gamma$ distribution and/or by partitioning data sets according to rate heterogeneity and estimating per-partition branch lengths, conditioned on a single topology. While the first approach is available in many phylogenetic analysis software, there is still no clear consensus on how to partition data, except perhaps in the simplest cases (e.g., "by codon" partitioning of coding sequences). Additionally, there is a trade-off between improvement in likelihood scores and the number of free parameters in the analysis, which rises quickly with the number of partitions. This trade-off may be dealt with by employing statistics that penalize overfitting of complex models, such as Akaike or Bayesian information criteria, or the more recently introduced stepping-stone method for marginal likelihood approximation. We applied the latter to three distinct matrices of discrete morphological data and demonstrated that sorting characters by homoplasy scores (obtained from implied weighting parsimony analysis) outperformed other partitioning strategies (anatomically-based and PartitionFinder2). The method was in fact so efficient in segregating characters by rates of evolution that no within-partition ACRV modeling was necessary, while among-partition rate variation was adequately accommodated by rate multipliers. We conclude that partitioning by homoplasy is a powerful and easy-to-implement strategy to address ACRV in complex data sets. We provide some guidelines focusing on morphological matrices, although this approach may be also applicable to molecular data sets.


Assessment of choroidal osteoma complicating choroidal neovascularization by optical coherence tomography angiography.
Choroidal osteoma (CO) frequently leads to progressive visual loss due to complications of secondary choroidal neovascularization (CNV).We report herein the function of optical coherence tomography angiography (OCTA) in observation of CO complicating CNV. A 25-year-old female presented to our hospital with chief complaint of sudden unilateral visual acuity decrease for one week, with metamorphopsia in the left eye. Her best corrected visual acuity was 0.12 in the left eye. Then complete ophthalmological examinations including fundus photography, B-scan ultrasound, fundus fluorescent angiography, and spectral-domain optical coherence tomography (SD-OCT) were performed. She was diagnosed as CO on the basis of these results. But the diagnosis could not explain the sudden visual loss and submacular hyperreflective lesion by SD-OCT. Furthermore, she underwent OCTA and indocyanine green angiography. A diagnosis of classic juxtafoveal CNV secondary to CO was made eventually. Then she was treated with an intravitreous injection of ranibizumab twice. The visual acuity got better and better during the treatment, and the efficacy was stable, giving rise to both subjective and anatomic improvement. Optical coherence tomography angiography has the advantage of varying the segmentation and scrolling through the different retinal layers, and layer-specific observation of blood flow in each layer. In addition, OCTA can measure the vessel area change of CNV and provide a better appreciation of CNV, observing the efficacy more elaboratively and quantizedly. OCTA makes promising noninvasive identification of the CO-related CNV.


Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease.
Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders. NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD. The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated cannabinoid receptors and ligands have mechanistic and therapeutic implications in metabolic derangements and specifically in NAFLD. Cannabinoid receptor 1 antagonism has demonstrated promising effects with increased resistance to hepatic steatosis, reversal of hepatic steatosis, and improvements in glycemic control, insulin resistance, and dyslipidemia. Literature regarding the role of cannabinoid receptor 2 in NAFLD is controversial. Exocannabinoids and endocannabinoids have demonstrated some therapeutic impact on metabolic derangements associated with NAFLD, although literature regarding direct therapeutic use in NAFLD is limited. Nonetheless, the properties of the endocannabinoid system, its receptors, substrates, and ligands remain a significant arena warranting further research, with potential for a pharmacologic intervention for a disease with an anticipated increase in economic and clinical burden.


Knee power is an important parameter in understanding medial knee joint load in knee osteoarthritis.
To determine the extent to which knee extensor strength and power explain variance in knee adduction moment (KAM) peak and impulse in clinical knee osteoarthritis (OA). Fifty-three adults (mean ± SD age 61.6 ± 6.3 years, 11 men) with clinical knee OA participated. The KAM waveform was calculated from motion and force data and ensemble averaged from 5 walking trials. The KAM peak was normalized to body mass (Nm/kg). The mean KAM impulse reflected the mean total medial knee load during stride (Nm × seconds). For strength, the maximum knee extensor moment attained from maximal voluntary isometric contractions (MVIC) was normalized to body mass (Nm/kg). For power, the maximum knee extensor power during isotonic contractions, with the resistance set at 25% of MVIC, was normalized to body mass (W/kg). Covariates included age, sex, knee pain on the Knee Injury and Osteoarthritis Outcome Score, gait speed, and body mass index (BMI). Relationships of the KAM peak and impulse with strength and power were examined using sequential stepwise forward linear regressions. Covariates did not explain variance in the KAM peak. While extensor strength did not, peak knee extensor power explained 8% of the variance in the KAM peak (P = 0.02). Sex and BMI explained 24% of the variance in the KAM impulse (P < 0.05). Sex, BMI, and knee extensor power explained 31% of the variance in the KAM impulse (P = 0.02), with power contributing 7% (P < 0.05). Knee extensor power was more important than isometric knee strength in understanding medial knee loads during gait.


Reducing gunshot victimization in high-risk social networks through direct and spillover effects.
More than 60,000 people are victimized by gun violence each year in the United States. A large share of victims cluster in bounded and identifiable social networks. Despite a growing number of violence reduction programmes that leverage networks to broaden programmatic effects, there is little evidence that reductions in victimization are achieved through spillover effects on the peers of participants. This study estimates the direct and spillover effects of a gun violence field intervention in Chicago. Using a quasi-experimental design, we test whether a desistance-based programme reduced gunshot victimization among 2,349 participants. The study uses co-arrest network data to further test spillover effects on 6,132 non-participants. Direct effects were associated with a 3.2-percentage point reduction in victimization among seeds over two years, while potential spillover was associated with a 1.5-percentage point reduction among peers. Findings suggest that peer influence and the structure of networks might be leveraged to amplify gun violence reduction efforts.


Ocular manifestations of pituitary adenomas.
Fifty patients with pituitary adenomas were evaluated preoperatively by an ophthalmologist; of these, 68% had visual field defects, the most common (25%) a superior bitemporal depression and 16%, bitemporal hemianopsia. Almost 60% of patients with field defects had visual complaints; 38% had visual acuity in one eye of 20/60 or less. Patients with larger, nonsecreting tumors had more visual defects than patients with secreting pituitary adenomas.


Association of maturation period blood pressure with dialysis access patency.
Problematic dialysis vascular access is a major health issue. The purpose of this study was to evaluate for potentially modifiable factors associated with access patency, particularly, the association of early postoperative, or maturation period, blood pressure with patency. A retrospective review was performed of patients who had undergone placement of an arteriovenous fistula or graft. Demographic, operative, and postoperative factors were evaluated for possible association with access primary patency using univariate and multivariate Cox regression analyses. Seventy-three patients over a 3-year review period were examined. Overall analysis showed a significant association of absence of peripheral vascular disease, aspirin use, and absence of previous permanent dialysis access with higher primary patency rates. Fistula subgroup analysis showed that higher blood pressure during the maturation period relative to preoperative blood pressure was associated with lower patency rates. For grafts, race was significantly associated with patency, with blacks having higher patency rates than whites. Multiple clinical factors were found to have a significant association with dialysis access primary patency. The finding of an association of maturation period blood pressure with fistula patency suggests that the maturation period environment, specifically hemodynamics during this time, may play an important role in dialysis access patency.


Obesity in Hispanic Americans.
The prevalence of obesity among Hispanic American populations is generally greater than among white populations in the United States. Among Mexican Americans, the prevalence of obesity was higher than among either Cuban Americans or Puerto Ricans. It is well known that the prevalence of diabetes increases with increasing levels of obesity or body mass index. However, it does not appear that the high prevalence of obesity in Mexican Americans completely accounts for the higher prevalence of diabetes seen in this ethnic group. Among Mexican Americans, the association of selected cardiovascular disease risk factors, high-density lipoprotein cholesterol subfractions and systolic blood pressure, was similar to that seen among other U.S. populations. Individuals with diabetes had higher values than seen among those without diabetes. In a comparison of nutrient intake in two Mexican-American populations, one rural and one urban, there were no major differences other than higher calorie intakes in the rural population compared with the urban population. In addition, the diet in the rural population, based on higher levels of the Keys score, was more atherogenic than that of the urban population.


Parents and carers' choice of drinks for infants and toddlers, in areas of social and economic disadvantage.
Sugar rich drinks are a recognised risk factor in early childhood caries. Currently, in depth knowledge of factors influencing parents' choice of infant drinks is incomplete. This study investigated parents and carers understanding of feeding practices potentially detrimental to oral health; barriers to adopting safe feeding practices and commercial factors influencing feeding bottle and cup contents. A qualitative approach using semi-structured interviews was employed. Interviews were conducted by an experienced researcher and tape recorded. Following full transcription, emerging themes were identified, systematically explored and validated within the verbatim accounts. Thirty-three parents/carers of children aged three years and under, resident in areas of high caries prevalence in Cardiff, Wales, were interviewed. Overall understanding of the prolonged effect of exposure to sugared drinks in feeding bottles and cups was poor. Greater concern was expressed over the use of bottles on the development of the occlusion. Milk was viewed as a food rather than as a drink. Many barriers to giving water were described: children reject it; mothers don't like it; it was 'cruel' to offer water instead of sweet drinks; water in feeding bottles or cups was seen as a sign of poverty. Commercial influences on choices were strong. Products offered by baby food manufacturers were viewed as safe, but a recently marketed "Toothsafe" drink was viewed with suspicion. There are significant barriers to adopting the traditional oral health education message, that only milk and water are truly safe for teeth. Future oral health education and promotion programmes must recognise and account for these factors.


Excellent prognosis of patients with nonhereditary medullary thyroid carcinoma with ultrasonographic findings of follicular tumor or benign nodule.
Medullary thyroid carcinoma (MTC) accounts for only 1.4% of all thyroid malignancies in Japan. Generally, MTC shows ultrasonographic findings typical of thyroid carcinoma. However, in our experience, some MTC may be diagnosed as a follicular tumor or a benign nodule on ultrasonography because ultrasonographic findings of malignancy are lacking. In this study we investigated differences in biological behavior between these two types of MTC. Seventy-seven patients with nonhereditary MTC who underwent surgery in our department between 1988 and 2007 were enrolled in this study. Of these patients, 54 were diagnosed as having thyroid carcinoma (malignant, or M-type) but the remaining 23 were diagnosed as having follicular tumor or benign nodule (benign, or B-type) on ultrasonography. Clinically apparent lateral node metastasis, extrathyroid extension, and extranodal tumor extension were observed in 37%, 17%, and 11% of M-type patients, respectively, but none of the B-type patients showed any of these features. All B-type patients but only 59% of M-type patients were biochemically cured. Lymph node metastasis was pathologically confirmed in 38 and 65% of B-type and M-type patients, respectively. Eight patients showed recurrence and three have died of carcinoma to date; all of these patients were M-type patients. B-type MTC is highly indolent and shows an excellent prognosis. However, thyroidectomy and lymph node dissection for B-type MTC should be the same as for M-type MTC because 38% of B-type MTC showed pathologic node metastasis.


Albumin-Based Liver Reserve Models vs. MELD 3.0 in Prognostic Prediction for Hepatocellular Carcinoma Patients with Renal Insufficiency.
The severity of liver functional reserve is an important prognostic predictor in hepatocellular carcinoma (HCC). The albumin-bilirubin (ALBI), easy (EZ)-ALBI, platelet-albumin-bilirubin (PALBI), platelet-albumin (PAL) score, and MELD 3.0 score are used to evaluate the severity of liver dysfunction. However, their prognostic role in HCC patients, specifically with renal insufficiency (RI), is unclear. We aimed to investigate the predictive accuracy of the five models in these patients. A total of 1120 newly diagnosed HCC patients with RI were enrolled. A multivariate Cox proportional analysis was used to identify independent predictors associated with survival. In the Cox model, older age, an α-fetoprotein ≥20 ng/mL, vascular invasion, a medium and high tumor burden score, poor performance status, a higher ALBI grade, an EZ-ALBI grade, a PALBI grade, a PAL grade, and MELD 3.0 score were all independently associated with decreased overall survival (all p < 0.001). Among the five liver reserve models, the ALBI grade is the best surrogate marker to represent liver functional reserve in terms of outcome prediction. The albumin-based liver reserve models (ALBI, EZ-ALBI, PALBI, and PAL) and MELD 3.0 are all feasible prognostic markers to indicate liver injury, specifically in HCC patients with RI. Among them, the ALBI grade is the most robust tool for survival prediction in these patients.


Effects of dietary concentrate composition and linseed oil supplementation on the milk fatty acid profile of goats.
Milk fat composition can be modulated by the inclusion of lipid supplements in ruminant diets. An interaction between the lipid supplement and the forage to concentrate ratio or the type of forage in the rations may affect milk fat composition. However, little is known about the effects of the starch-to-non-forage NDF ratio in the concentrate and lipid supplementation of goat diets. The aim of this work was to determine the role of dietary carbohydrates in goats rations supplemented with linseed oil on animal performance and milk fatty acid (FA) profile. A total of 16 dairy goats were allocated to two simultaneous experiments (two treatments each), in a crossover design with four animals per treatment and two experimental periods of 25 days. In both experiments alfalfa hay was the sole forage and the forage to concentrate ratio (33:67) remained constant. The concentrate in experiment 1 consisted of barley, maize and soybean meal (concentrate rich in starch), whereas it included soybean hulls replacing 25% of barley and 25% maize in experiment 2 (concentrate rich in NDF). As a result, the starch-to-non-forage NDF ratio was 3.1 in experiment 1 and it decreased to 0.8 in experiment 2. Both concentrates were administered either alone or in combination with 30 g/day of linseed oil. Animal performance parameters were not affected by experimental treatments. In contrast, major changes were observed in milk FA profile due to lipid supplementation and the type of concentrate. Linseed oil significantly raised vaccenic and rumenic acids as well as α-linolenic acid and its biohydrogenation intermediates while decreased medium-chain saturated FA (12:0 to 16:0) in milk fat. Milk fat contents of odd and branched-chain FA and trans-10 18:1 responded differently to linseed oil supplementation according to the concentrate fed.