Reversible structure transformation in ice nanocluster.
Water freezes to ice by cooling. Once ice is formed, the phase does not change unless heated over the melting point. This is a familiar phenomenon observed in our everyday life. Here, we demonstrate non-bulk-like behavior of nanosized ice by molecular-dynamics simulation using the TIP4P potential. Our 100 micros simulations reveal that the structure of the (H(2)O)(20) nanocluster reversibly changes and a variety of solidlike phases, such as bilayer structures composed of three pentagonal prisms, square and pentagonal ice nanotubes, and stuffed-fullerenelike (H(2)O)@(H(2)O)(19) structures, dynamically coexists even at 52% of the bulk melting point.


SiC Fin-Shaped Gate Trench MOSFET with Integrated Schottky Diode.
A silicon carbide (SiC) trench MOSFET featuring fin-shaped gate and integrated Schottky barrier diode under split P type shield (SPS) protection (FS-TMOS) is proposed by finite element modeling. The physical mechanism of FS-TMOS is studied comprehensively in terms of fundamental (blocking, conduction, and dynamic) performance and transient extreme stress reliability. The fin-shaped gate on the sidewall of the trench and integrated Schottky diode at the bottom of trench aim to the reduction of gate charge and improvement on the third quadrant performance, respectively. The SPS region is fully utilized to suppress excessive electric field both at trench oxide and Schottky contact when OFF-state. Compared with conventional trench MOSFET (C-TMOS), the gate charge, Miller charge, Von at third quadrant, Ron,sp·Qgd, and Ron,sp·Qg of FS-TMOS are significantly reduced by 34%, 20%, 65%, 0.1%, and 14%, respectively. Furthermore, short-circuit and avalanche capabilities are discussed, verifying the FS-TMOS is more robust than C-TMOS. It suggests that the proposed FS-TMOS is a promising candidate for next-generation high efficiency and high-power density applications.


A novel function for p53: regulation of growth cone motility through interaction with Rho kinase.
The transcription factor p53 suppresses tumorgenesis by regulating cell proliferation and migration. We investigated whether p53 could also control cell motility in postmitotic neurons. p53 isoforms recognized by phospho-p53-specific (at Ser-15) or "mutant" conformation-specific antibodies were highly and specifically expressed in axons and axonal growth cones in primary hippocampal neurons. Inhibition of p53 function by inhibitors, small interfering RNAs, or by dominant-negative forms, induced axonal growth cone collapse, whereas p53 overexpression led to larger growth cones. Furthermore, deletion of the p53 nuclear export signal blocked its axonal distribution and induced growth cone collapse. p53 inhibition-induced axonal growth cone collapse was significantly reduced by the Rho kinase (ROCK) inhibitor, Y27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide]. Our results reveal a new function for p53 as a critical regulator of axonal growth cone behavior by suppressing ROCK activity.


Promoting Adapted Physical Activity Regardless of Language Ability in Young Children With Autism Spectrum Disorder.
Purpose: There is a relationship between motor and language skills in children with Autism Spectrum Disorder (ASD), but little work addresses the ramifications of this relationship for professionals who teach motor skills to this population. Within a motor skills intervention, this study probed the importance of language skills for motor intervention. We examined the relationship between motor and language skills at baseline, and then the relationship between baseline language skills and motor improvements resulting from the intervention. Method: Twenty children aged 4-6 years with ASD participated. Eleven children received 20 hr per week of motor intervention for 8 weeks. Nine children did not receive motor intervention. Language skills (Mullen Scales of Early Learning) and motor skills (Test of Gross Motor Development - 2) were assessed at baseline and post-intervention. Spearman correlations tested the associations between baseline language and baseline motor skills. This analysis was repeated in the intervention sample to test the association between baseline language level and response to intervention (motor skill changes from baseline to post-intervention). Results: Prior to intervention, locomotor skills are positively correlated (p < .001) with both receptive (rs = 0.827) and expressive (rs = 0.722) language skills. Similarly, object-control skills are positively correlated (rs < .001) with receptive (rs = 0.779) and expressive (rs = 0.729) language skills. However, those baseline language skills do not relate to motor change in the experimental group. Conclusion: These results suggest that motor programs may improve motor skills in children with ASD when language is supported, regardless of pre-program language ability.


The use of 3D cultures of MCF-10A and MCF-12A cells by high content screening for effect-based analysis of non-genotoxic carcinogens.
The human breast epithelial cell lines MCF-10A and MCF-12A form well-differentiated acinus-like structures when grown in three-dimensional matrigel culture over a period of 20 days. In the present study, both cell lines were tested for their suitability to serve as an effect-based in vitro test system for non-genotoxic carcinogens. A software solution for automated Acinus Detection And Morphological Evaluation (ADAME) was developed to automatically acquire acinus images and to determine morphological parameters such as acinus size, lumen size, and acinus roundness. A number of test compounds were tested for their capacity to affect acinus formation and cellular differentiation. Human epidermal growth factor stimulated acinus growth for both cell lines whereas all-trans retinoic acid inhibited acinus growth. The strong estrogen 17β-estradiol had no effect on acinus formation of estrogen receptor (ER)-negative MCF-10A cells, but yielded larger MCF-12A (ER-positive) acini. Thus, the parallel use of both cell lines allows the identification of estrogenic properties of a given test compound.


Separation of monosaccharides by solid-phase extraction with ionic liquid-modified microporous polymers.
Ionic liquid-modified porous polymers with large surface area and large amount of functional groups were developed and used in SPE to separate four monosaccharides. Adsorption isotherm showed that the sorbent with amino ionic liquid groups had the highest interaction with the target compounds. The mobile phase of acetonitrile/water 85:15 and 73:30 v/v can successfully separate the monosaccharides. The sorbent produced reproducible results and performed stably, demonstrating its potential applicability in the separation of extract from natural plant.


A rose by any other name is not the same: the role of orthographic knowledge in homophone confusion errors.
Homophone confusion errors were examined in a series of 6 experiments. Across a variety of tasks, readers consistently made more errors on homophone trials than on control trials. These effects were established in Experiment 1 using a semantic-decision task in which participants judged whether pairs of words were related or unrelated. For both related and unrelated trials, error rates were higher for homophones as compared with controls. Results such as these have previously been taken as evidence for the role of phonology in lexical access and reading. However, differences in orthographic knowledge (more specifically, knowledge of spelling-to-meaning correspondences) across participants and homophone items significantly predicted homophone errors across all tasks. In addition, spelling tasks and multiple-choice questionnaires revealed differences in orthographic knowledge across participants and homophone items. Although these results do not rule out a role for phonology in lexical access, they indicate that homophone confusion errors may also be due to factors other than phonology.


Investigation of Thermal and Thermomechanical Properties of Biodegradable PLA/PBSA Composites Processed via Supercritical Fluid-Assisted Foam Injection Molding.
Bio-based polymer foams have been gaining immense attention in recent years due to their positive contribution towards reducing the global carbon footprint, lightweighting, and enhancing sustainability. Currently, polylactic acid (PLA) remains the most abundant commercially consumed biopolymer, but suffers from major drawbacks such as slow crystallization rate and poor melt processability. However, blending of PLA with a secondary polymer would enhance the crystallization rate and the thermal properties based on their compatibility. This study investigates the physical and compatibilized blends of PLA/poly (butylene succinate-co-adipate) (PBSA) processed via supercritical fluid-assisted (ScF) injection molding technology using nitrogen (N₂) as a facile physical blowing agent. Furthermore, this study aims at understanding the effect of blending and ScF foaming of PLA/PBSA on crystallinity, melting, and viscoelastic behavior. Results show that compatibilization, upon addition of triphenyl phosphite (TPP), led to an increase in molecular weight and a shift in melting temperature. Additionally, the glass transition temperature (Tg) obtained from the tanδ curve was observed to be in agreement with the Tg value predicted by the Gordon⁻Taylor equation, further confirming the compatibility of PLA and PBSA. The compatibilization of ScF-foamed PLA⁻PBSA was found to have an increased crystallinity and storage modulus compared to their physically foamed counterparts.


Modifying a breast cancer risk factor survey for African American women.
To evaluate a breast cancer risk factor survey for use with African American women. Two focus groups consisting of women randomly selected from the patient population of Henry Ford Health System in Detroit, MI. A large, vertically integrated, private, nonprofit health system. Focus Group I consisted of 11 African American women aged 18-50, with a mean age of 41 years. Focus Group II consisted of nine African American women aged 51 and older, with a mean age of 60.9 years. A qualitative approach was used to gather and interpret the focus group data. Perceptions of a breast cancer risk factor survey and perceptions of breast cancer risk factors. The focus group participants suggested ways to improve the survey. Women in the younger age group appeared to lack awareness regarding breast cancer risk factors. Women in the older age group reported not knowing their family health histories. Based on comments made by the focus group participants, the survey was modified substantially. Breast cancer risk factors were perceived differently by women in the two age groups. Results of a survey of a large, ethnically diverse sample of women could inform the development of culturally and age-appropriate nursing interventions designed to address breast cancer risk perceptions and enhance the likelihood of adherence to recommended mammography screening guidelines.


Pharmacological effects of iloprost (ZK 36 374), a stable prostacyclin analogue, in man.
Iloprost, a stable analogue of carbaprostacyclin, was infused for 72 h to 9 patients with advanced obliterative arterial disease. Total peripheral and pulmonary vascular resistances and blood pressure were decreased. Cardiac output was elevated with no marked extra cardiac load. The glomerular filtration rate was increased and tubular reabsorption of sodium and water reduced. Consequently, urine excretion increased. The renin-angiotensin system was not activated but excretion of renal kallikrein was augmented. Several patients showed clinical improvement. The drug was well tolerated except for gastrointestinal side-effects with the dose of 4 ng X kg-1 X min-1 or more.


Hydration of CO2 by carbonic anhydrase: intramolecular proton transfer between Zn2+-bound H2O and histidine 64 in human carbonic anhydrase II.
The energy barrier for the intramolecular proton transfer between zinc-bound water and His 64 in the active site of human carbonic anhydrase II (HCA II) has been studied at the partial retention of diatomic differential overlap (PRDDO) level. The most important stabilizing factor for the intramolecular proton transfer is the zinc ion, which lowers the pKa of zinc-bound water and electrostatically repels the proton. The energy barrier of 127.5 kcal/mol for proton transfer between a water dimer is completely removed in the presence of the zinc ion. The zinc ligands, which donate electrons to the zinc ion, raise the barrier slightly to 34 kcal/mol for a 4-coordinated zinc complex including three imidazole ligands from His 94, His 96, and His 119 and to 54 kcal/mol for the 5-coordinated zinc complex including the fifth water ligand. A few model calculations indicate that these energy barriers are expected to be reduced to within experimental range (approximately 10 kcal/mol) when large basis set, correlation energies, and molecular dynamics are considered. The proton-transfer group, which functions as proton receiver in the intramolecular proton transfer, helps to attract the proton; and the partially ordered active site water molecules are important for proton relay function.


Most effective colon cancer chemopreventive agents in rats: a systematic review of aberrant crypt foci and tumor data, ranked by potency.
Potential chemopreventive agents for colorectal cancer are assessed in rodents. We speculated that the magnitude of the effect is meaningful and ranked all published agents according to their potency. Data were gathered systematically from 137 articles with the aberrant crypt foci (ACF) end point and from 146 articles with the tumor end point. The potency of each agent to reduce the number of ACF is listed in one table and the potency of each agent to reduce the tumor incidence in another table. Both tables are shown in this review and on a website with sorting abilities (http://www.inra.fr/reseau-nacre/sci-memb/corpet/indexan.html). Potency was estimated as the ratio of the value in control rats to the value in treated rats. From each article, only the most potent agent was kept, except in articles reporting the effect of more than seven agents. Among the 186 agents in the ACF table, the median agent reduced the number of ACF by one-half. The most potent agents to reduce azoxymethane-induced ACF were Pluronic, polyethylene glycol, perilla oil with beta-carotene, and sulindac sulfide. Among the 160 agents in the tumor table, the median agent reduced the tumor incidence in rats by one-half. The most potent agents to reduce the incidence of azoxymethane-induced tumors were celecoxib, a protease inhibitor from soy, difluoromethylornithine with piroxicam, polyethylene glycol, and a thiosulfonate. For the 57 agents present in both tables, a significant correlation (r) was found between the potencies against ACF and tumors (r = 0.45, P < 0.001); without celecoxib, a major outlying point in the correlation, r = 0.68 (P < 0.001, n = 56). In conclusion, this review gathers most known chemopreventive agents, ranks the most promising agents against colon carcinogenesis in rats or mice, and further supports the use of ACF as a surrogate end point for tumors in rats.


Toxicokinetics of propylene glycol mono-t-butyl ether following intravenous or inhalation exposure in rats and mice.
Propylene glycol mono-t-butyl ether (PGMBE) is a widely used solvent in industry and in consumer products, posing a potential for human exposure via inhalation or dermal routes. Toxicokinetic studies were conducted on F344/N rats and B6C3F1 mice of both sexes to evaluate single or repeated dose, species, and/or sex differences in PGMBE elimination kinetics following intravenous or inhalation exposure. In the first study, rats and mice received a single intravenous dose of 15 or 200 mg PGMBE/kg and serial blood samples were collected and analyzed for PGMBE. In the second study, rats and mice received a single 6-h whole-body inhalation exposure to 75, 300, or 1200 ppm PGMBE and serial blood samples were collected and analyzed for PGMBE. In the third study, rats and mice received whole-body inhalation exposures to 75, 300, or 1200 ppm PGMBE for 6 h/day, 5 days/wk for 14 (rats) or 16 (mice) wk. Serial blood samples were analyzed for PGMBE after 2, 6, 14 (rats), and 16 (mice) wk on study. Urine samples were also collected for 16 h postexposure and analyzed for creatinine and PGMBE sulfate and PGMBE glucuronide conjugates. These studies revealed that: (1) PGMBE was eliminated from blood following concentration-dependent nonlinear kinetics in both species; (2) saturable Michaelis-Menten kinetics were clearly exhibited following a single inhalation exposure at 1200 ppm, but were less obvious following repeated exposures; (3) mice were more efficient in eliminating PGMBE from blood at lower exposure concentrations (i.e., < or = 300 ppm), but at exposure concentrations potentially exceeding their elimination capacity, mice had a greater concentration-dependent decrease in PGMBE elimination than rats; (4) there were minimal but consistent sex differences in PGMBE elimination profiles for rats, with females having higher blood concentrations at all exposure concentrations and sampling times; and (5) sex differences in PGMBE elimination were in part associated with differences in urinary excretion of PGMBE metabolites.


Conivaptan (Yamanouchi).
Yamanouchi is developing conivaptan, an orally active vasopressin V1A and V2 antagonist for the potential treatment of heart failure, edema and hyponatremia. The company anticipated launch of the product for hyponatremia in 2002 [362201]. By May 2001, Yamanouchi was continuing phase II trials in Japan for hyponatremia and heart failure, and in the US and Europe for heart failure, and phase III trials in the US and Europe for hyponatremia [411763]. In July 2000, it had been reported that conivaptan was undergoing phase III trials in both the US and Europefor hyponatremia and heart failure [377561]. In April 1998, Warner-Lambert (now Pfizer) acquired the rights to YM-087 for US, South America, Europe and Africa, while Yamanouchi retains copromotion rights, but by November 2000, Pfizer had cancelled its licensing contract to market the drug in the US [397901]. In September 2001, analysts at Morgan Stanley predicted launch of conivaptan for hyponatremia in the US between 2004 and 2005 [422782]. In October 2001, analysts at Credit Suisse First Boston predicted that an NDA would be filed in 2002 followed by launch in 2003, with peak annual sales of $50 million and $300 million for hyponatremia and heart failure, respectively [427028].


Recombination sequences in plant mitochondrial genomes: diversity and homologies to known mitochondrial genes.
Several plant mitochondrial genomes contain repeated sequences that are postulated to be sites of homologous intragenomic recombination (1-3). In this report, we have used filter hybridizations to investigate sequence relationships between the cloned mitochondrial DNA (mtDNA) recombination repeats from turnip, spinach and maize and total mtDNA isolated from thirteen species of angiosperms. We find that strong sequence homologies exist between the spinach and turnip recombination repeats and essentially all other mitochondrial genomes tested, whereas a major maize recombination repeat does not hybridize to any other mtDNA. The sequences homologous to the turnip repeat do not appear to function in recombination in any other genome, whereas the spinach repeat hybridizes to reiterated sequences within the mitochondrial genomes of wheat and two species of pokeweed that do appear to be sites of recombination. Thus, although intragenomic recombination is a widespread phenomenon in plant mitochondria, it appears that different sequences either serve as substrates for this function in different species, or else surround a relatively short common recombination site which does not cross-hybridize under our experimental conditions. Identified gene sequences from maize mtDNA were used in heterologous hybridizations to show that the repeated sequences implicated in recombination in turnip and spinach/pokeweed/wheat mitochondria include, or are closely linked to genes for subunit II of cytochrome c oxidase and 26S rRNA, respectively. Together with previous studies indicating that the 18S rRNA gene in wheat mtDNA is contained within a recombination repeat (3), these results imply an unexpectedly frequent association between recombination repeats and plant mitochondrial genes.


Highly enantioselective cyclizations of conjugated trienes with low catalyst loadings: a robust chiral N-heterocyclic carbene enabled by acetic acid cocatalyst.
Densely functionalized cyclopentenones are useful synthetic intermediates. We report herein a new method to synthesize this important class of compounds through a highly enantioselective (98 → 99% ee) triene cyclization that is cocatalyzed by acetic acid and a chiral N-heterocyclic carbene (NHC). We discovered that acetic acid not only could coexist with NHCs but also could greatly stabilize the active catalyst, which enables a long-lived catalyst with high reactivity and selectivity.


A gas chromatographic analysis of fecal short-chain fatty acids, using the direct injection method.
A simple, reproducible, and rapid gas chromatographic method for short-chain fatty acid determination in human feces was developed. It involves direct injection of fecal supernatants into the gas chromatograph, without any pretreatment. Contamination of the gas chromatographic column with nonvolatile fecal material was prevented by the use of a glass liner in the injector. This liner, which acted as a precolumn, was stoppered with a glass wool plug at the lower end of the liner. Injection was performed against the glass wall of the liner, ensuring an immediate contact of the injected sample with the hot glass wall. More than 100 injections of fecal supernatants could be carried out before the liner had to be replaced by a new one. Peak tailing and ghosting was prevented by the use of formic acid in the fecal samples. The method gave sharp peaks with baseline separation for all the fatty acids.


Ultrasound Examination of the Lymphatic Drainage Area and Regional Lymph Nodes in Melanoma Patients with In-Transit Metastases.
In-transit metastases (ITMs) are cutaneous or subcutaneous regional metastases that may occur in patients with melanoma. ITMs are often multiple and new lesions tend to appear over time. Ultrasonography can detect impalpable subcutaneous tumors. The aim of this study was to assess the value of ultrasound examination in detecting additional, non-palpable ITMs and to determine their relevance. Melanoma patients with ITMs who underwent regional ultrasound examination of the skin and subcutaneous tissue between the wide excision scar of the primary melanoma and the regional lymph node field were identified. In most, ultrasound assessment also included the regional lymph node field. Relevant data were collected and analyzed. Twenty-eight patients presenting with a total of 40 ITMs were included. Ultrasound examination identified additional ITMs in 15 patients (54%). No nodal recurrences were detected. Most additional lesions were found closer to the regional lymph nodes than the original ITMs. Management was influenced by the ultrasound findings in nine patients (32%), five of whom had more extensive surgery, three received systemic drug therapy instead of surgery, and in one patient surgery was delayed and follow-up intensified. In one patient, only subcutaneous fat was found in the excised specimen and the ultrasound was classified as false-positive. In melanoma patients with ITMs, ultrasonography of the lymphatic drainage area provided valuable information, as additional ITMs were identified in more than half of these patients and management was influenced in one-third.


Human exposures to monomers resulting from consumer contact with polymers.
Many consumer products are composed completely, or in part, of polymeric materials. Direct or indirect human contact results in potential exposures to monomers as a result of migrations of trace amounts from the polymeric matrix into foods, into the skin or other bodily surfaces. Typically, residual monomer levels in these polymers are <100 p.p.m., and represent exposures well below those observable in traditional toxicity testing. These product applications thus require alternative methods for evaluating health risks relating to monomer exposures. A typical approach includes: (a) assessment of potential human contacts for specific polymer uses; (b) utilization of data from toxicity testing of pure monomers, e.g. cancer bioassay results; and (c) mathematical risk assessment methods. Exposure potentials are measured in one of two analytical procedures: (1) migration of monomer from polymer into a simulant solvent (e.g. alcohol, acidic water, vegetable oil) appropriate for the intended use of the product (e.g. beer cans, food jars, packaging adhesive, dairy hose); or (2) total monomer content of the polymer, providing worse-case values for migratable monomer. Application of toxicity data typically involves NOEL or benchmark values for non-cancer endpoints, or tumorigenicity potencies for monomers demonstrated to be carcinogens. Risk assessments provide exposure 'safety margin' ratios between levels that: (1) are projected to be safe according to toxicity information, and (2) are potential monomer exposures posed by the intended use of the consumer product. This paper includes an example of a health risk assessment for a chewing gum polymer for which exposures to trace levels of butadiene monomer occur.


Production of Galacto-oligosaccharides by the β-Galactosidase from Kluyveromyces lactis : comparative analysis of permeabilized cells versus soluble enzyme.
The transgalactosylation activity of Kluyveromyces lactis cells was studied in detail. Cells were permeabilized with ethanol and further lyophilized to facilitate the transit of substrates and products. The resulting biocatalyst was assayed for the synthesis of galacto-oligosaccharides (GOS) and compared with two soluble β-galactosidases from K. lactis (Lactozym 3000 L HP G and Maxilact LGX 5000). Using 400 g/L lactose, the maximum GOS yield, measured by HPAEC-PAD analysis, was 177 g/L (44% w/w of total carbohydrates). The major products synthesized were the disaccharides 6-galactobiose [Gal-β(1→6)-Gal] and allolactose [Gal-β(1→6)-Glc], as well as the trisaccharide 6-galactosyl-lactose [Gal-β(1→6)-Gal-β(1→4)-Glc], which was characterized by MS and 2D NMR. Structural characterization of another synthesized disaccharide, Gal-β(1→3)-Glc, was carried out. GOS yield obtained with soluble β-galactosidases was slightly lower (160 g/L for Lactozym 3000 L HP G and 154 g/L for Maxilact LGX 5000); however, the typical profile with a maximum GOS concentration followed by partial hydrolysis of the newly formed oligosaccharides was not observed with the soluble enzymes. Results were correlated with the higher stability of β-galactosidase when permeabilized whole cells were used.


Influenza vaccination status and influenza-related perspectives and practices among US physicians.
The influenza vaccination rate among US healthcare workers (HCWs) remains low. This survey was designed to assess influenza vaccination status and related knowledge, attitudes, and beliefs among a national sample of primary care physicians and subspecialists likely to see patients at high risk for complications from influenza. We used a mail survey of a national random sample of 495 family physicians (FPs), 491 internists (IMs), 498 geriatricians (GERs), and 497 pulmonologists (PUDs). The overall response rate was 38%. Almost all respondents (87%) reported receiving an influenza vaccine during the 2003-2004 influenza season, with no significant difference across specialty groups (84% FPs, 87% IMs, 87% GERs, 91% PUDs). In a multivariate model, adjusted for physician specialty and age group, significant predictors of vaccination were: strong agreement that HCWs have professional responsibility to be vaccinated, access to vaccination on site and free of charge, strong worksite recommendation for HCWs to be vaccinated, and strong agreement that benefits of vaccination outweigh risk of side effects. Physicians reported a high influenza vaccination rate. To improve these rates further, with likely benefits for other HCWs, worksite policies that facilitate access to vaccination and documentation of reductions in nosocomial influenza associated with HCW vaccination should continue to be pursued.


Differentiation of membrane IgE+ rat B cells into IgE-secreting cells.
Rat spleen cells were stimulated with pokeweed mitogen (PWM) and the IgM and IgE responses were assessed. An enrichment of the cell suspension with IgE-bearing cells before stimulation resulted in an increase in the number of IgE-secreting cells. A decrease of the number of IgE-secreting cells was found after depletion of IgE- or IgM-bearing cells, but not those bearing IgD molecules on their membranes, before stimulation. Moreover, the stimulation of membrane IgE on B cells with anti-IgE antibodies was shown to increase the number of IgE-secreting cells after PWM-induced differentiation in vitro. In vivo, it was also observed that a single injection of anti-IgE antibodies can induce the differentiation of IgE-secreting cells. These results demonstrate the presence of IgE(+)-IgM (+)-IgD- B cells in the rat that are responsive to PWM-induced differentiation into IgE-secreting cells. They indicate a pre-commitment of these cells at a stage where they still express IgM on their surface. IgE molecules on the cell membranes play a role in their differentiation.


Tuberous sclerosis mimicking adult polycystic kidney disease.
Tuberous sclerosis is a recognised cause of renal disease, usually angiomyolipomas but also cysts; it usually presents in childhood. A father and son are reported with familial tuberous sclerosis presenting in adulthood and mimicking polycystic kidney disease.


Inhibition of Nek2 by small molecules affects proteasome activity.
Nek2 is a serine/threonine kinase localized to the centrosome. It promotes cell cycle progression from G2 to M by inducing centrosome separation. Recent studies have shown that high Nek2 expression is correlated with drug resistance in multiple myeloma patients. To investigate the role of Nek2 in bortezomib resistance, we ectopically overexpressed Nek2 in several cancer cell lines, including multiple myeloma lines. Small-molecule inhibitors of Nek2 were discovered using an in-house library of compounds. We tested the inhibitors on proteasome and cell cycle activity in several cell lines. Proteasome activity was elevated in Nek2-overexpressing cell lines. The Nek2 inhibitors inhibited proteasome activity in these cancer cell lines. Treatment with these inhibitors resulted in inhibition of proteasome-mediated degradation of several cell cycle regulators in HeLa cells, leaving them arrested in G2/M. Combining these Nek2 inhibitors with bortezomib increased the efficacy of bortezomib in decreasing proteasome activity in vitro. Treatment with these novel Nek2 inhibitors successfully mitigated drug resistance in bortezomib-resistant multiple myeloma. Nek2 plays a central role in proteasome-mediated cell cycle regulation and in conferring resistance to bortezomib in cancer cells. Taken together, our results introduce Nek2 as a therapeutic target in bortezomib-resistant multiple myeloma.


Quantitative neurotoxicology: Potential role of artificial intelligence/deep learning approach.
Neurotoxicity studies are important in the preclinical stages of drug development process, because exposure to certain compounds that may enter the brain across a permeable blood brain barrier damages neurons and other supporting cells such as astrocytes. This could, in turn, lead to various neurological disorders such as Parkinson's or Huntington's disease as well as various dementias. Toxicity assessment is often done by pathologists after these exposures by qualitatively or semiquantitatively grading the severity of neurotoxicity in histopathology slides. Quantification of the extent of neurotoxicity supports qualitative histopathological analysis and provides a better understanding of the global extent of brain damage. Stereological techniques such as the utilization of an optical fractionator provide an unbiased quantification of the neuronal damage; however, the process is time-consuming. Advent of whole slide imaging (WSI) introduced digital image analysis which made quantification of neurotoxicity automated, faster and with reduced bias, making statistical comparisons possible. Although automated to a certain level, simple digital image analysis requires manual efforts of experts which is time-consuming and limits analysis of large datasets. Digital image analysis coupled with a deep learning artificial intelligence model provides a good alternative solution to time-consuming stereological and simple digital analysis. Deep learning models could be trained to identify damaged or dead neurons in an automated fashion. This review has focused on and discusses studies demonstrating the role of deep learning in segmentation of brain regions, toxicity detection and quantification of degenerated neurons as well as the estimation of area/volume of degeneration.


Relative contributions of excitatory and inhibitory neuronal activity to alkaline transients evoked by stimulation of Schaffer collaterals in the rat hippocampal slice.
1. The neuronal basis of alkaline shifts in extracellular pH (pHo) evoked by stimulation of Schaffer collaterals was studied by means of double-barreled H(+)-selective microelectrodes in the area CA1 of rat hippocampal slices. 2. Alkaline transients in stratum pyramidale evoked by stimulation at a low frequency (5-10 Hz) were enhanced by pentobarbital sodium (100 microM). In the absence of the drug, inhibition of extracellular carbonic anhydrase (CAo) by benzolamide or by prontosildextran 5000 (PD 5000) resulted in an increase in the alkaline shifts. In contrast to this, alkaloses evoked by low-frequency stimulation in the presence of pentobarbital were attenuated by a subsequent inhibition of CAo. 3. Blockade of gamma-aminobutyric acid-A (GABAA) receptors with picrotoxin (PiTX; 100 microM) resulted in an enhancement of alkaline transients in s. pyramidale evoked by low-frequency stimulation (10 Hz) but suppressed alkaline shifts evoked by brief high-frequency (1 s, 100 Hz) trains of stimuli. 4. Application of trains of stimuli consisting of a constant number of pulses (50 or 100) revealed a striking dependence of the effect of benzolamide on stimulation frequency (10-200 Hz) in s. pyramidale: the enhancement of the alkaloses seen upon inhibition of CAo became progressively smaller with an increase in frequency, and at 100-200 Hz benzolamide produced a suppression or a complete block of the alkaline transients. However, alkaline transients evoked with the use of a constant train duration (5 s) were enhanced by benzolamide at all stimulation frequencies examined (5-200 Hz).(ABSTRACT TRUNCATED AT 250 WORDS)


Impacts of gene essentiality, expression pattern, and gene compactness on the evolutionary rate of mammalian proteins.
Understanding the determinants of the rate of protein sequence evolution is of fundamental importance in evolutionary biology. Many recent studies have focused on the yeast because of the availability of many genome-wide expressional and functional data. Yeast studies revealed a predominant role of gene expression level and a minor role of gene essentiality in determining the rate of protein sequence evolution. Whether these rules apply to complex organisms such as mammals is unclear. Here we assemble a list of 1,138 essential and 2,341 nonessential mouse genes based on targeted gene deletion experiments and report a significant impact of gene essentiality on the rate of mammalian protein evolution. Gene expression level has virtually no effect, although tissue specificity in expression pattern has a strong influence. Unexpectedly, gene compactness, measured by average intron size and untranslated region length, has the greatest influence. Hence, the relative importance of the various factors in determining the rate of mammalian protein evolution is gene compactness > gene essentiality approximately tissue specificity > expression level. Our results suggest a considerable variation in rate determinants between unicellular organisms such as the yeast and multicellular organisms such as mammals.


[Analysis of the effects of selected polymers on morpho-dynamic features of rat hepatocytes].
The thesis shows the results of the research on the influence of the film-form polymers on the hepatocytes in rats. The polymers were composed of polyethylene (PE), polyvinyl chlorides (P-25, P-47), polyesters (A, B, E) and irradiated L7 collagen. The aim of the research was to establish whether the changes in the specific morpho-dynamic characteristics-which prove the changes in the hepatocyte metabolic activity in rats-could be used to assess the usability of the above mentioned polymers for medicine. The evaluation of the research findings was analysed on the basic of the stereometric methods and factor analysis. On the basic of the obtained results, polyvinyl chlorides P-25 and P-47 have been evaluated most favourably as far as their possible application in medicine is concerned, whereas polyester E shows the most negative characteristics for such an application.


Vertical transmission of HIV-an update.
One of the greatest successes in AIDS research to date has by far been the discovery of successful interventions that interrupt the transmission of HIV from mother to child. It is however important to note that these successes have occurred largely in countries with great resources and the least burden of perinatal transmission of HIV. In the developing world wherein currently 95% of vertical transmission of HIV occurs, it is highly condemnable that still every minute an infected infant is said to be born in spite of the fact that vertical transmission is largely preventable, mainly because translating knowledge into practice is not always possible or feasible; This has led to a continuous growing numbers of children with HIV, thereby making pediatric HIV a looming problem rapidly draining the already burdened health care system of these countries. It is the need of the hour to appropriately address the challenges to achieve zero percent transmission of HIV from an infected mother to her child thereby giving a hope for an AIDS-free new generation worldwide.


[Creation of emergency care services in developing countries: luxury or necessity?].
Organization of emergency care services prior to hospital admission has progressed at a satisfactory pace in developed countries. A performance model in this field is the French emergency service called service d'aide médicale d'urgence (SAMU). Socioeconomic conditions prevailing in developing countries have pushed authorities to give priority to preventive medicine. However numerous patients especially young people and women during childbirth die as a result of inadequate facilities for transportation from hospitals and dwellings in outlying areas to major medical centers where the best medical equipment and staff are available. As a result, it may be asked if emergency care services is really a luxury. The authors base their conclusion on analysis of the conditions and outcome of emergency patient care in three African countries in which it is essentially a requirement.


Nanodiamonds and Their Applications in Cells.
Diamonds owe their fame to a unique set of outstanding properties. They combine a high refractive index, hardness, great stability and inertness, and low electrical but high thermal conductivity. Diamond defects have recently attracted a lot of attention. Given this unique list of properties, it is not surprising that diamond nanoparticles are utilized for numerous applications. Due to their hardness, they are routinely used as abrasives. Their small and uniform size qualifies them as attractive carriers for drug delivery. The stable fluorescence of diamond defects allows their use as stable single photon sources or biolabels. The magnetic properties of the defects make them stable spin qubits in quantum information. This property also allows their use as a sensor for temperature, magnetic fields, electric fields, or strain. This Review focuses on applications in cells. Different diamond materials and the special requirements for the respective applications are discussed. Methods to chemically modify the surface of diamonds and the different hurdles one has to overcome when working with cells, such as entering the cells and biocompatibility, are described. Finally, the recent developments and applications in labeling, sensing, drug delivery, theranostics, antibiotics, and tissue engineering are critically discussed.


Strain-Specific Differences in Survival of Campylobacter spp. in Naturally Contaminated Turkey Feces and Water.
Campylobacter jejuni and Campylobacter coli are leading causes of human foodborne illness, with poultry as a major vehicle. Turkeys are frequently colonized with Campylobacter, but little is known about Campylobacter survival in turkey feces, even though fecal droppings are major vehicles for Campylobacter within-flock transmission as well as for environmental dissemination. Our objective was to examine survival of Campylobacter, including different strains, in freshly excreted feces from naturally colonized commercial turkey flocks and in suspensions of turkey feces in water from the turkey house. Fecal and water suspensions were stored at 4°C, and Campylobacter populations were enumerated on selective media at 48-h intervals. C. jejuni and C. coli isolates were characterized for resistance to a panel of antibiotics, and a subset was subtyped using multilocus sequence typing. Campylobacter was recovered from feces and water for up to 16 days. Analysis of 548 isolates (218 C. jejuni and 330 C. coli) revealed that C. jejuni survived longer than C. coli in feces (P = 0.0005), while the reverse was observed in water (P < 0.0001). Strain-specific differences in survival were noted. Multidrug-resistant C. jejuni isolates of sequence type 1839 (ST-1839) and the related ST-2935 were among the longest-surviving isolates in feces, being recovered for up to 10 to 16 days, while multidrug-resistant C. coli isolates of ST-1101 were recovered from feces for only up to 4 days. Data on Campylobacter survival upon excretion from the birds can contribute to further understanding of the transmission dynamics of this pathogen in the poultry production ecosystem.IMPORTANCECampylobacter jejuni and Campylobacter coli are leading foodborne pathogens, with poultry as a major reservoir. Due to their growth requirements, these Campylobacter spp. may be unable to replicate once excreted by their avian hosts, but their survival in feces and the environment is critical for transmission in the farm ecosystem. Reducing the prevalence of Campylobacter-positive flocks can have major impacts in controlling both contamination of poultry products and environmental dissemination of the pathogens. However, understanding the capacity of these pathogens to survive in transmission-relevant vehicles such as feces and farmhouse water remains poorly understood, and little information is available on species- and strain-associated differences in survival. Here, we employed model conditions to investigate the survival of C. jejuni and C. coli from naturally colonized turkey flocks, and with diverse genotypes and antimicrobial resistance profiles, in turkey feces and in farmhouse water.


Occupational and environmental exposures associated with testicular germ cell tumours: systematic review of prenatal and life-long exposures.
Testicular germ cell tumours (TGCT) are the most common cancers in men aged between 15 and 44 years and the incidence has increased steeply over the past 30 years. The rapid increase in the incidence, the spatial variation and the evolution of incidence in migrants suggest that environmental risk factors play a role in TGCT aetiology. The purpose of our review is to summarise the current state of knowledge on occupational and environmental factors thought to be associated with TGCT. A systematic literature search of PubMed. All selected articles were quality appraised by two independent researchers using the 'Newcastle-Ottawa Quality Assessment Scale'. After exclusion of duplicate reports, 72 relevant articles were selected; 65 assessed exposure in adulthood, 7 assessed parental exposures and 2 assessed both. Associations with occupation was reported for agricultural workers, construction workers, firemen, policemen, military personnel, as well as workers in paper, plastic or metal industries. Electromagnetic fields, PCBs and pesticides were also suggested. However, results were inconsistent and studies showing positive associations tended to had lower quality ranking using the assessment scale (p=0.02). Current evidence does not allow concluding on existence of any clear association between TGCT and adulthood occupational or environmental exposure. The limitations of the studies may partly explain the inconsistencies observed. The lack of association with adulthood exposure is in line with current hypotheses supporting the prenatal origin of TGCT. Future research should focus on prenatal or early life exposure, as well as combined effect of prenatal and later life exposure. National and international collaborative studies should allow for more adequately powered epidemiological studies. More sophisticated methods for assessing exposure as well as evaluating gene-environment interactions will be necessary to establish clear conclusion.


Glacial history affected phenotypic differentiation in the alpine plant, Campanula thyrsoides.
Numerous widespread Alpine plant species show molecular differentiation among populations from distinct regions. This has been explained as the result of genetic drift during glacial survival in isolated refugia along the border of the European Alps. Since genetic drift may affect molecular markers and phenotypic traits alike, we asked whether phenotypic differentiation mirrors molecular patterns among Alpine plant populations from different regions. Phenotypic traits can be under selection, so we additionally investigated whether part of the phenotypic differentiation can be explained by past selection and/or current adaptation. Using the monocarpic Campanula thyrsoides as our study species, a common garden experiment with plants from 21 populations from four phylogeographic groups located in regions across the Alps and the Jura Mountains was performed to test for differentiation in morphological and phenological traits. Past selection was investigated by comparing phenotypic differentiation among and within regions with molecular differentiation among and within regions. The common garden results indicated regional differentiation among populations for all investigated phenotypic traits, particularly in phenology. Delayed flowering in plants from the South-eastern Alps suggested adaptation to long sub-mediterranean summers and contrasted with earlier flowering of plants experiencing shorter growing seasons in regions with higher elevation to the West. Comparisons between molecular and phenotypic differentiation revealed diversifying selection among regions in height and biomass, which is consistent with adaptation to environmental conditions in glacial refugia. Within regions, past selection acted against strong diversification for most phenotypic traits, causing restricted postglacial adaptation. Evidence consistent with post-glacial adaptation was also given by negative correlation coefficients between several phenotypic traits and elevation of the population's origin. In conclusion, our study suggests that, irrespective of adaptation of plants to their current environment, glacial history can have a strong and long-lasting influence on the phenotypic evolution of Alpine plants.


Actin is part of pre-initiation complexes and is necessary for transcription by RNA polymerase II.
Actin is abundant in the nucleus and has been implicated in transcription; however, the nature of this involvement has not been established. Here we demonstrate that beta-actin is critically involved in transcription because antibodies directed against beta-actin, but not muscle actin, inhibited transcription in vivo and in vitro. Chromatin immunoprecipitation assays demonstrated the recruitment of actin to the promoter region of the interferon-gamma-inducible MHC2TA gene as well as the interferon-alpha-inducible G1P3 gene. Further investigation revealed that actin and RNA polymerase II co-localize in vivo and also co-purify. We employed an in vitro system with purified nuclear components to demonstrate that antibodies to beta-actin block the initiation of transcription. This assay also demonstrates that beta-actin stimulates transcription by RNA polymerase II. Finally, DNA-binding experiments established the presence of beta-actin in pre-initiation complexes and also showed that the depletion of actin prevented the formation of pre-initiation complexes. Together, these data suggest a fundamental role for actin in the initiation of transcription by RNA polymerase II.


Method to determine 226Ra in small sediment samples by ultralow background liquid scintillation.
(210)Pb dating of sediment cores is a widely used tool to reconstruct ecosystem evolution and historical pollution during the last century. Although (226)Ra can be determined by gamma spectrometry, this method shows severe limitations which are, among others, sample size requirements and counting times. In this work, we propose a new strategy based on the analysis of (210)Pb through (210)Po in equilibrium by alpha spectrometry, followed by the determination of (226)Ra (base or supported (210)Pb) without any further chemical purification by liquid scintillation and with a higher sample throughput. Although gamma spectrometry might still be required to determine (137)Cs as an independent tracer, the effort can then be focused only on those sections dated around 1963, when maximum activities are expected. In this work, we optimized the counting conditions, calibrated the system for changing quenching, and described the new method to determine (226)Ra in small sediment samples, after (210)Po determination, allowing a more precise determination of excess (210)Pb ((210)Pb(ex)). The method was validated with reference materials IAEA-384, IAEA-385, and IAEA-313.


Transcriptional response of the murine mammary gland to acute progesterone exposure.
Our mechanistic understanding of progesterone's involvement in murine mammary morphogenesis and tumorigenesis is dependent on defining effector pathways responsible for transducing the progesterone signal into a morphogenetic response. Toward this goal, microarray methods were applied to the murine mammary gland to identify novel downstream gene targets of progesterone. Consistent with a tissue undergoing epithelial expansion, mining of the progesterone-responsive transcriptome revealed the up-regulation of functional gene classes involved in epithelial proliferation and survival. Reassuringly, signaling pathways previously reported to be responsive to progesterone were also identified. Mining this informational resource for rapidly induced genes, we identified "inhibitor of differentiation 4" (Id4) as a new molecular target acutely induced by progesterone exposure. Mammary Id4 is transiently induced during early pregnancy and colocalizes with progesterone receptor (PR) expression, suggesting that Id4 mediates the early events of PR-dependent mammary morphogenesis. Chromatin immunoprecipitation assay detecting direct recruitment of ligand occupied PR to the Id4 promoter supports this proposal. Given that Id4 is a member of the Id family of transcriptional regulators that have been linked to the maintenance of proliferative status and tumorigenesis, the establishment of a mechanistic link between PR signaling and Id4 promises to furnish a wider conceptual framework with which to advance our understanding of normal and abnormal mammary epithelial responses to progestins. In sum, the progesterone-responsive transcriptome described herein not only reinforces the importance of progesterone in mammary epithelial expansion but also represents an invaluable information resource with which to identify novel signaling paradigms for mammary PR action.


Factors predicting axial spondyloarthritis among first-degree relatives of probands with ankylosing spondylitis: a family study spanning 35 years.
Factors predicting axial spondyloarthritis (axSpA) among first-degree relatives (FDRs) of ankylosing spondylitis (AS) patients need to be defined. We investigated the predictive value of the probands' HLA-B27 and radiographic sacroiliitis status on disease occurrence among their FDR. We also assessed the predictive value of features of the clinical history, including chronic inflammatory back pain (CIBP) and acute anterior uveitis (AAU), among the FDR and how they can be used to improve classification and diagnosis of axSpA. In 1985, we studied 363 AS probands and 806 FDR who underwent rheumatologic examination, completed questionnaires, provided blood samples for HLA-typing and underwent radiography of sacroiliac joints. At follow-up in 2018-2019, 125 patients and 360 FDR were available for study, and completed a postal questionnaire about axSpA features. FDRs were asked to report whether after 1985 they had been diagnosed by Swiss rheumatologists as having axSpA. Among HLA-B27(+) FDR, axSpA occurred in 25.4%-26.3%, independent of the radiographic sacroiliitis status of the proband. AAU occurred in 13/34 (38.2%) FDR with axSpA vs 29/251 (11.6%) FDR without axSpA (p=0.00004, OR=4.74 95% CI 2.15 to 10.47). The presence of CIBP at baseline did not predict later occurrence of axSpA but combining CIBP and pain/discomfort at the thoracic spine and at anterior (ventral) chest wall ever, assessed at follow-up in 2018-2019, provided 83.1% sensitivity and 87.2% specificity for current axSpA. Occurrence of AAU among FDR of axSpA probands should prompt screening for axSpA. Moreover, co-occurrence of CIBP and pain/discomfort in the thoracic spine and at anterior chest wall as a three-question tool may further enhance clinical suspicion of axSpA among these FDR.


[Diab'à'table, a patient education program dedicated to eating behaviors].
A long-lasting change in eating behaviour, essential when treating patients suffering from type 2 diabetes, can be difficult to put in practice. In order to achieve this objective, a therapeutic education programme was used with volunteer patients. Its encouraging results show the benefits it can offer for obese patients suffering from type 2 diabetes.


Catatonia: Clinical Overview of the Diagnosis, Treatment, and Clinical Challenges.
Catatonia is a syndrome that has been associated with several mental illness disorders but that has also presented as a result of other medical conditions. Schizophrenia and other psychiatric disorders such as mania and depression are known to be associated with catatonia; however, several case reports have been published of certain medical conditions inducing catatonia, including hyponatremia, cerebral venous sinus thrombosis, and liver transplantation. Neuroleptic Malignant Syndrome and anti-NMDA receptor encephalitis are also prominent causes of catatonia. Patients taking benzodiazepines or clozapine are also at risk of developing catatonia following the withdrawal of these medications-it is speculated that the prolonged use of these medications increases gamma-aminobutyric acid (GABA) activity and that discontinuation may increase excitatory neurotransmission, leading to catatonia. The treatment of catatonia often involves the use of benzodiazepines, such as lorazepam, that can be used in combination therapy with antipsychotics. Definitive treatment may be found with electroconvulsive therapy (ECT). Aberrant neuronal activity in different motor pathways, defective neurotransmitter regulation, and impaired oligodendrocyte function have all been proposed as the pathophysiology behind catatonia. There are many clinical challenges that come with catatonia and, as early treatment is associated with better outcomes, it becomes imperative to understand these challenges. The purpose of this manuscript is to provide an overview of these challenges and to look at clinical studies regarding the pathophysiology, diagnosis, and treatment of as well as the complications and risk factors associated with catatonia.


A Nutrition Education Intervention to Increase Consumption of Pulses Showed Improved Nutritional Status of Adolescent Girls in Halaba Special District, Southern Ethiopia.
This study aimed to determine the effect of a 6-month in-school nutrition education intervention to improve pulse consumption on weight status of adolescent girls in Ethiopia. At the intervention school, 66 girls received bi-monthly lessons that included recipes and tastings. Girls (n = 66) at the control school had usual in-school activities. With pulse-based nutrition education which included discussions and demonstrations, knowledge, attitude and practice scores improved (p < 0.001) in the intervention group while control scores remained low and unchanged. Prevalence of underweight, measured as Body Mass Index (BMI) for age, decreased with the education intervention, from 13.6% to 3% (p = 0.004), while there was no significant change seen in control girls. In Ethiopia, equipping girls in schools with the knowledge and skills to improve food intake by consuming locally grown pulses may mitigate underweight in Ethiopian female adolescents.


Utilizing Bayesian predictive power in clinical trial design.
The Bayesian paradigm provides an ideal platform to update uncertainties and carry them over into the future in the presence of data. Bayesian predictive power (BPP) reflects our belief in the eventual success of a clinical trial to meet its goals. In this paper we derive mathematical expressions for the most common types of outcomes, to make the BPP accessible to practitioners, facilitate fast computations in adaptive trial design simulations that use interim futility monitoring, and propose an organized BPP-based phase II-to-phase III design framework.


[A new concept of nutrition in treatment of burn injury: from nutrition support to nutrition therapy].
For many years, the major concerns in the treatment of a major burn injury have always been shock resuscitation, infection control, and wound treatment, while nutrition has been considered as a subordinate concern. The concept of nutrition in the treatment of a major burn has been recognized as "nutrition support", only with the purpose of restraining negative nitrogen balance through administration of energy and protein, in order to prevent malnutrition in patients with severe burn. In recent 10 years, however, increasing evidences have showed that optimal nutritional management could improve the outcome of severe burn patients. Now it is recognized that nutrition is not only to provide exogenous nutrients to improve nutritional status of the patients, but also to regulate cell metabolism, enhance cell activity, maintain and uphold the structure and function of the gastrointestinal mucosa, thus to improve patient's outcome. Therefore, the term of "nutrition support"seems to be far from comprehensiveness to reflect the purpose and the aim of this important treatment strategy. Medical literatures especially those in nutritional guidelines have begun to use the term of "nutrition therapy" instead of "nutrition support", which typifies the changes in nutritional concept, aim, means, and clinical evaluation. The aim of nutrition has changed from simply "providing nutritional substrate and improving nutritional status of patients" to "regulating cell metabolism, maintaining organ structure and function, and ultimately improving outcome of patient". Meanwhile, nutritional means has been more consummate, including special nutrients, hormones, and growth factors, in addition to use of conventional nutrients, in order to enhance therapeutic effect of nutrition in treatment of massive burn injury. Burn nutrition is no longer confined to maintenance of positive nitrogen balance, it should also consider the regulation of cell activity, metabolic status, immune and organ function. The purpose of the article is to analyze and discuss the important issues concerning nutrition therapy in treatment of burn injury, including risk screening, optimal energy supply and ratio of different nutritional ingredients, the choice of special nutrient, as well as the determination of optimal time for giving various nutritional supplements.


The roles of Australian chairs in clinical nursing.
Australian chairs in clinical nursing have been established in order to achieve more effective partnerships between academia and the health care sector in education, research and quality of nursing care. The aim of this study was to describe the goals, obstacles, supports and outcomes of such appointments. The study explored the perceptions of a purposive sample of Australian professors holding clinical chairs, stratified to ensure representation of both the geographical and clinical specialty diversity of the population. Eight professors were interviewed using semi-structured telephone interviews. The interviews covered three phases: role establishment, current foci and future developments. Qualitative analysis for common themes and areas of divergence was conducted with concurrent analysis providing the opportunity to seek confirmation for emerging themes. The participants highlighted the diversity of arrangements between university and health sector partners in establishing their respective roles. Clear communication was crucial to successful partnership arrangements. All roles included components of education, research and politics but the relative contribution of each of these areas depended to a large extent on the priorities of the employing partners. The participants felt the need to secure sustainable income sources and consolidate outcomes to ensure the continued viability of their positions. Clinical professorial nursing appointments provide one means of addressing perceived gaps in the links between the university and health care sectors, academia and clinicians, thus enhancing nursing education, research and politics. Through emphasizing common purpose and mutual respect, these positions can illuminate the crucial role nursing plays in Australian health care delivery.


Global Fund collusion with liquor giant is a clear conflict of interest.
Alcohol is the third leading contributor to death and disability in South Africa, where SABMiller is the major supplier of malt beer, the most popular beverage consumed. The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) has recently included SABMiller as a recipient of funding for an education intervention aimed at minimizing alcohol-related harm, including HIV prevention, among men in drinking establishments. Global Fund support for this initiative is cause for concern. It is debatable whether these men are the best target group for the intervention, whether a drinking establishment is the best location, and whether the educational intervention itself is effective. Our experience is that the liquor industry is inclined to support alcohol interventions that will not affect drinking rates at a population level. These interventions allow the industry to simultaneously fulfil social and legal obligations to address the harmful use of alcohol while ensuring that sales and profits are maintained. Providing funding for a highly profitable industry that could afford to fund its own interventions also reduces the funds available for less well-resourced organizations. Do we take it that the problem of "corporate capture" has now spread to one of the largest health funders in the world?


The times they are a-changin'.
Change is the one constant in a constantly changing world, including the world of dietetic practice. Over a 40-year career, I have witnessed and participated in many such changes. Key lessons from my early career with Manitoba Agriculture and Manitoba Health include an understanding of the power of teamwork, of the importance of communication skills, of the need for shared knowledge and expertise, and of ways to connect nutrition messages with food and eating. Later, my work as director of education in a family medicine residency program taught me the value of building a portfolio of knowledge and skills and of working with families. Similarly, my work with the Organization for Cooperation in Overseas Development led me to appreciate the need for cultural sensitivity in our work. Opportunities with Dietitians of Canada have shown me that future directions must include continued interdisciplinary development of policy and position papers. Other important challenges include determining issues relevant to various areas of dietetic practice, working to achieve Vision 2020 goals, and inspiring and nurturing new leadership among younger Dietitians of Canada members.


Multiprotein microcontact printing with micrometer resolution.
Depositing multiple proteins on the same substrate in positions similar to the natural cellular environment is essential to tissue engineering and regenerative medicine. In this study, the development and verification of a multiprotein microcontact printing (μCP) technique is described. It is shown that patterns of multiple proteins can be created by the sequential printing of proteins with micrometer precision in registration using an inverted microscope. Soft polymeric stamps were fabricated and mounted on a microscope stage while the substrate to be stamped was placed on a microscope objective and kept at its focal distance. This geometry allowed for visualization of patterns during the multiple stamping events and facilitated the alignment of multiple stamped patterns. Astrocytes were cultured over stamped lane patterns and were seen to interact and align with the underlying protein patterns.


The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein.
MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.


Evaluating quality in clinical cancer research: the M.D. Anderson Cancer Center experience.
Despite the unquestionable importance of clinically oriented research designed to test the safety and efficacy of new therapies in patients with malignant disease, there is limited information regarding strategies to evaluate the quality of such efforts at academic institutions. To address this issue, a committee of senior faculty at the University of Texas M.D. Anderson Cancer Center established specific criteria by which investigators from all departments engaged in clinical research could be formally evaluated. Scoring criteria were established and revised based on the results of a pilot study. Beginning in January 2004, the committee evaluated all faculty involved in clinical research within 35 departments. Scores for individual faculty members were assigned on a scale of 1 (outstanding) to 5; a score of 3 was set as the standard for the institution. Each department also received a score. The results of the evaluation were shared with departmental chairs and the Chief Academic Officer. 392 faculty were evaluated. The median score was 3. Full professors more frequently received a score of 1, but all faculty ranks received scores of 4 and 5. As a group, tenure/tenure track faculty achieved superior scores compared to nontenure track faculty. Based on our experience, we believe it is possible to conduct a rigorous consensus-based evaluation of the quality of clinical cancer research being conducted at an academic medical center. It is reasonable to suggest such evaluations can be used as a management tool and may lead to higher-quality clinical research.


Carbonic anhydrase 8 (CAR8) negatively regulates GLP-1 secretion from enteroendocrine cells in response to long-chain fatty acids.
Glucagon-like peptide-1 (GLP-1) is an incretin secreted from enteroendocrine preproglucagon (PPG)-expressing cells (traditionally known as L cells) in response to luminal nutrients that potentiates insulin secretion. Augmentation of endogenous GLP-1 secretion might well represent a novel therapeutic target for diabetes treatment in addition to the incretin-associated drugs currently in use. In this study, we found that PPG cells substantially express carbonic anhydrase 8 (CAR8), which has been reported to inhibit inositol 1,4,5-trisphosphate (IP3) binding to the IP3 receptor and subsequent Ca2+ efflux from the endoplasmic reticulum in neuronal cells. In vitro experiments using STC-1 cells demonstrated that Car8 knockdown increases long-chain fatty acid (LCFA)-stimulated GLP-1 secretion. This effect was reduced in the presence of phospholipase C (PLC) inhibitor; in addition, Car8 knockdown increased the intracellular Ca2+ elevation caused by α-linolenic acid, indicating that CAR8 exerts its effect on GLP-1 secretion via the PLC/IP3/Ca2+ pathway. Car8wdl null mutant mice showed significant increase in GLP-1 response to oral corn oil administration compared with that in wild-type littermates, with no significant change in intestinal GLP-1 content. These results demonstrate that CAR8 negatively regulates GLP-1 secretion from PPG cells in response to LCFAs, suggesting the possibility of augmentation of postprandial GLP-1 secretion by CAR8 inhibition.NEW & NOTEWORTHY This study focused on the physiological significance of carbonic anhydrase 8 (CAR8) in GLP-1 secretion from enteroendocrine preproglucagon (PPG)-expressing cells. We found an inhibitory role of CAR8 in LCFA-induced GLP-1 secretion in vitro and in vivo, suggesting a novel therapeutic approach to diabetes and obesity through augmentation of postprandial GLP-1 secretion by CAR8 inhibition.


Effect of conalbumin on the activity of Syn 2190, a 1,5 dihydroxy-4-pyridon monobactam inhibitor of AmpC beta-lactamases.
Syn 2190, a 1,5 dihydroxy-4-pyridon monobactam inhibitor of AmpC enzymes, was tested against beta-lactamase-producing bacteria with piperacillin, piperacillin-tazobactam and ceftazidime as partner drugs. In the presence of conalbumin as an iron chelator, Syn 2190 potentiated these drugs against most AmpC producers, although Klebsiella spp. with plasmidic AmpC enzymes were an exception. Potentiation was much weaker without conalbumin, suggesting that Syn 2190 exploits a ferric uptake pathway, as do catecholic cephalosporins. Syn 2190 had little ability to potentiate partner drugs against strains with other beta-lactamase types but, with conalbumin, increased the activity of piperacillin-tazobactam against Escherichia coli transconjugants producing various class A or D enzymes.


Fatigue in progressive multiple sclerosis is associated with low levels of dehydroepiandrosterone.
Fatigue is one of the most limiting symptoms in multiple sclerosis (MS) and the mechanisms underlying its origin are poorly understood. Our aim was to test whether fatigue in MS is associated with endocrine markers. We longitudinally studied 73 progressive MS patients. Fatigue was assessed at baseline and at 3, 6, 12 and 24 months using the Fatigue Severity Scale (FSS). Given the longitudinal design of our study, patients were labelled as sustained fatigued when FSS scores were >5.0 at all time points, and as non-fatigued when FSS scores were < or = 5.0 at all time points. Serum levels of dehydroepiandrosterone (DHEA), its sulphated conjugate (DHEAS) and cortisol were measured at each time point. Twenty-nine patients scored >5.0 in the FSS at all time points, and 9 patients (12.3%) scored 5.0 at all time points. Mean baseline levels of DHEAS and DHEA were lower in MS patients with sustained fatigue when compared to patients without fatigue (P = 0.01 and P = 0.03 respectively). Analysis of DHEAS and DHEA over time showed significantly lower hormone levels in patients with fatigue [F(1,31) = 6.14, P=0.019 for DHEAS; F(1,32) = 6.63, P=0.015 for DHEA]. Fatigue in progressive MS could be related to low serum levels of DHEA and DHEAS. Our results suggest that these hormones should be considered as biological markers of fatigue in MS patients and that hormone replacement may thus be tested as an option to treat fatigue in MS patients.


[Dependence of peripheral blood lymphocyte subpopulations on causative microorganisms able to produce superantigens].
A retrospective study of 176 immunologically tested patients admitted to Kaunas Medical University Hospital during 1997-2000 was performed. All patients had positive bacteriological culture test result confirming an infectious etiology of the disease. Our results showed that majority of immunological parameters were dependent on such non-specific factors as intensity and localization of the inflammatory process, an overall functional status of the patient, and the number of the disease exacerbation episodes during the last year before admission. In contrast to this, the absolute number of CD4 lymphocytes, the relative amount of HLA-DR positive lymphocytes and the index of neutrophil latex phagocytosis were exceptionally dependent on the species of the causative microorganism, in particular on superantigen producing cocci. In this case, the HLA-DR positive lymphocyte amount and the neutrophil phagocytosis index were significantly higher. In addition, the CD4/CD8 lymphocyte ratio (the immunoregulatory index) was significantly lower in this group. As much as those findings are concordant with the signs of excessive immune activation, we conclude that they reflect a possible superantigenic action of the disease causing bacteria. Therefore, a need for immunomodulating therapy during the infections caused by species able to produce superantigens is confirmed.


CT Measures of Bone Mineral Density and Muscle Mass Can Be Used to Predict Noncancer Death in Men with Prostate Cancer.
Purpose To determine if computed tomographic (CT) metrics of bone mineral density and muscle mass can improve the prediction of noncancer death in men with localized prostate cancer. Materials and Methods Institutional review board approval was obtained, with waiver of informed consent. All patients who underwent radiation therapy for localized prostate cancer between 2001 and 2012 with height, weight, and past medical history documented and who underwent CT that included the L4-5 vertebral interspace were included. On a single axial CT section obtained at the mid-L5 level, the mean CT attenuation of the trabecular bone of the L5 vertebral body (L5HU) was measured. The height-normalized psoas cross-sectional area (PsoasL4-5) was measured on a single CT section obtained at the L4-5 vertebral interface. Multivariable Cox proportional hazards models were used to assess effects on noncancer death. By using parameter estimates from an adjusted model, a prognostic index for prediction of noncancer death was generated and compared with age-adjusted Charlson Comorbidity Index (CCI) by using the Harrell c statistic. Results Six hundred fifty-three men met the inclusion criteria. Prostate cancer risk grouping, androgen deprivation, race, age-adjusted CCI, L5HU, and PsoasL4-5 were included in a multivariable model. Age-adjusted CCI (hazard ratio [HR] = 1.36, P < .001), L5HU (HR = 2.88 for L5HU < 105 HU, HR = 1.42 for 105 HU ≤ L5HU ≤ 150 HU, P < .001), PsoasL4-5 (HR = 1.95 for PsoasL4-5 < 7.5 cm2/m2, P = .003), and race (HR = 1.68 for African American race, HR = 1.77 for other nonwhite race, P = .019) were independent predictors of noncancer death. The prognostic index yielded a c value of 0.747 for the prediction of noncancer death versus 0.718 for age-adjusted CCI alone. Conclusion L5HU and PsoasL4-5, which are surrogates for bone mineral density and muscle mass, respectively, were independent predictors of noncancer death. The prognostic index that incorporated these measures with the CCI was associated with improved accuracy for prediction of noncancer death. © RSNA, 2016 Online supplemental material is available for this article.


Primary Structure of Cytochrome b(5) from Cauliflower (Brassica oleracea L.) Deduced from Peptide and cDNA Sequences.
Cytochrome b(5) is a microsomal protein that functions as an intermediate electron donor in fatty acid desaturation and other oxidation/reduction reactions. cDNA clones were isolated from cauliflower (Brassica oleracea L.) by using oligonucleotides based on the partial amino acid sequence of the protein. The deduced amino acid sequence of the polypeptide exhibited approximately 30% sequence identity with the homologous protein from vertebrates.


Detection of single nucleotide polymorphisms using a DNA Holliday junction nanoswitch--a high-throughput fluorescence lifetime assay.
We report a simple DNA sensor device, using a combination of binding and conformational switching, capable of rapid detection of specific single nucleotide polymorphisms in an unlabelled nucleic acid target sequence. The detection is demonstrated using fluorescence lifetime measurements in a high-throughput micro plate reader instrument based on the time-correlated single-photon counting technique. The sensor design and instrumental architecture are capable of detecting perturbations in the molecular structure of the probe-target complex (which is similar to that of a Holliday junction), due to a single base pair mismatch in a synthetic target. Structural information, including fluorophore separations, is obtained using time-resolved Förster resonance energy transfer between two fluorophores covalently bound to the probe molecule. The two probes required are designed to detect a single nucleotide polymorphism from a sequence present on each of the two copies of human chromosome 11.


Activation of Nod1 and Nod2 induces innate immune responses of prostate epithelial cells.
Nod1 and Nod2 are cytosolic receptors which are responsible for sensing bacterial peptidoglycan derivatives. In this study, we determined whether Nod1 and Nod2 are involved in the innate immune responses of prostate epithelial cells. The expression of Nod1 and Nod2 was examined by RT-PCR and immunohistochemistry. ELISA was performed to determine the production of cytokines/chemokines. Activation of NF-κB and MAPK was examined using western blot analysis. The Nod1 gene was distinctly expressed in all tested cells including DU145, PC3, and TRAMP-C2 cells, whereas Nod2 expression was weak. Both Nod1 and Nod2 proteins were expressed in normal mouse prostate epithelia with difference of expression levels. Tri-DAP (Nod1 agonist), but not MDP (Nod2), increased the production of IL-8 (or KC) and IL-6 in prostate epithelial cells. Tri-DAP and MDP could upregulate the gene expression of COX-2 and activate NF-κB and MAPK. In addition, Tri-DAP and MDP synergized with TLR agonists to induce the production of IL-8/KC or IL-6 in PC3 and TRAMP-C2 cells. We finally showed that Nod1 and Nod2 were also expressed in a wide range of prostate lesions including prostate intraepithelial neoplasm (PIN), phyllodes-like tumor, and adenocarcinoma in TRAMP (transgenic adenocarcinoma of the mouse prostate) mice, even though the expression level of Nod1 and Nod2 was different. These results indicate that Nod1 and Nod2 may play important roles in the innate immune response of prostate epithelial cells and the development and progression of prostate cancer.


[Current views on brain concussion].
Modern views on brain concussion are reviewed by the authors who present also the evolution of the views on this problem in the last five decades. Owing to devising of an experimental model of light craniocerebral injuries the presence of structural changes in the central nervous system developing after concussion has been demonstrated. Using the modern diagnostic imaging techniques (SPECT) in clinical practice persistent disturbances of regional cerebral blood flow were found following such head injuries. The mechanism, which could explain the development of cerebral perfusion changes, could produce also axonal disorders, breakdown of the blood-brain barrier, atrophy of hippocampal neurons which lesions had been noted previously in experiments. The results of SPECT investigations put in doubt the presence of a "pure" functional brain damage following slight craniocerebral injury and provide evidence for the existence will aim at correlating of electrophysiological phenomena, vascular changes and biochemical disturbances with lesions leading to disorders of behaviour observed in the so called postconcussion syndromes.


Accidental out-of-hospital births in Finland: incidence and geographical distribution 1963-1995.
The study aims to describe the incidence and geographical distribution of accidental out-of-hospital births (accidental births) in Finland in relation to the changes in the hospital network, and to compare the perinatal outcomes of accidental births and all hospital births. Data for the incidence and distribution analyses of accidental births were obtained from the official statistics between 1962 and 1973 and from the national Medical Birth Registry (MBR) in 1992-1993. The infant outcomes were analyzed for the MBR data in 1991-1995. Between 1963 and 1975 the central hospital network expanded and by 1975 they covered 72% of births. The number of small maternity units has decreased since 1963. The incidence of accidental births decreased between 1963 and 1973, from 1.3 to 0.4 per 1000 births, and rose by the 1990s to 1/1000. In the 1990s the parity adjusted risk of an accidental birth was higher for residents of northern than of southern Finland, OR 2.51 (CI 1.75-3.60), and for residents of rural compared to urban municipalities, OR 3.26 (CI 2.48-4.27). The birthweight adjusted risk for a perinatal death was higher in accidental births than in hospital births, OR 3.11 (CI 1.42-6.84). A temporal correlation between closing of small hospitals and an increase in accidental birth rates was detected. Due to the poor infant outcomes of accidental births, centralization policies should include measures to their prevention.


Finding meaning in the hidden curriculum - the use of the hermeneutic window in medical education.
We have published a model of the GP consultation where biomedical and humanistic elements of the consultation are seen as complementary and where hermeneutics, the discovery and creation of meaning, plays an integral role in enriching the conversation between clinicians and patients. The relationship between teachers and learners shows strong parallels with the relationship between practitioners and patients. We therefore explore how a similar analysis can enhance the relationship between teachers and learners and propose that hermeneutics can be particularly powerful in exploring and making explicit elements of the hidden curriculum.


Kinetic mechanism of quinol oxidation by cytochrome bd studied with ubiquinone-2 analogs.
Cytochrome bd is a heterodimeric terminal ubiquinol oxidase of Escherichia coli under microaerophilic growth conditions. The oxidase activity shows sigmoidal concentration-dependence with low concentrations of ubiquinols, and a marked substrate inhibition with high concentrations of ubiquinol-2 analogs [Sakamoto, K., Miyoshi, H., Takegami, K., Mogi, T., Anraku, Y., and Iwamura H. (1996) J. Biol. Chem. 271, 29897-29902]. Kinetic analysis of the oxidation of the ubiquinol-2 analogs, where the 2- or 3-methoxy group has been substituted with an azido or ethoxy group, suggested that its peculiar enzyme kinetics can be explained by a modified ping-pong bi-bi mechanism with the formation of inactive binary complex FS in the one-electron reduced oxygenated state and inactive ternary complex (E2S)S(n) on the oxidation of the second quinol molecule. Structure-function studies on the ubiquinol-2 analogs suggested that the 6-diprenyl group and the 3-methoxy group on the quinone ring are involved in the substrate inhibition. We also found that oxidized forms of ubiquinone-2 analogs served as weak noncompetitive inhibitors. These results indicate that the mechanism for the substrate oxidation by cytochrome bd is different from that of the heme-copper terminal quinol oxidase and is tightly coupled to dioxygen reduction chemistry.


Bone formation in rabbit cancellous bone defects filled with bioactive glass granules.
We examined new bone formation after filling cancellous bone defects with bioactive glass (BG) in granular form. Cylindrical defects in the trochanter area of 18 rabbit femora were filled with BG granules (diameter 600-830 microns) and compared with similar defects filled with morcellized autogenous bone. New bone formation and surface reaction of BG particles were evaluated by light microscopy, histomorphometry, and scanning electron microscopy. The chemical profile at the bone- material interface was studied by energy dispersive x-ray analysis (EDXA). In the BG group, 41, 32, and 38 percent of the defects were filled with new bone after 3, 6, and 12 weeks, respectively. The corresponding figures for the autogenous bone group were 36, 29, and 34 percent. The thickness of the reaction layer on the glass surface increased from 82 to 163 microns during the observation periods. An intimate contact without intervening soft tissue between new bone lamellae and BG granules was a constant finding. EDXA showed a chemical continuum between the granules and the new bone. No adverse reactions related to BG were observed. BG is a promising material for filling cancellous bone defects.


Molecular dynamics study on Au/Fe3O4 nanocomposites and their surface function toward amino acids.
The deposition of gold nanoparticles on the magnetite (Fe(3)O(4)) surface is demonstrated through a molecular dynamics method. The simulated results show that an intermediate layer composed by such as a surfactant, polymer, or silica plays a key role in the formation of core/shell Fe(3)O(4)/Au nanostructures. The functional groups of the intermediate layer are crucial factors in depositing gold onto the Fe(3)O(4) surface via nonbonding interactions, in which the van der Waals and columbic forces will determine the strength of interaction toward the gold and iron oxide. Such interactions can affect the stability of the metal-coated nanocomposites and hence the functional properties. The nanocomposite is further investigated on the surface adsorption of amino acids (e.g., cysteine), which may be useful for functional exploration in biomedical applications.


Copper-zinc superoxide dismutase (CuZnSOD) in antioxidant deficient pigs.
Six piglets, aged 4 weeks (weaning) at the beginning of the experiment, were fed a diet lacking antioxidants (vitamin E and selenium) and enriched with oxidated cod liver oil (the peroxide value of which was 112.54 meqv/kg). Four of the experimental pigs were killed for necropsy at the age of 2 months and the remaining two pigs at the age of 3 months. Two piglets from the same litter served as controls. Myodegeneration of the skeletal muscles was induced in the experimental group. Macroscopically, the condition of nutritional myodegeneration ('white muscle disease') was characterized by a pale, yellowish colour and translucence of the skeletal muscles. The livers were pale and mottled. Light microscopy revealed degenerative alterations in the heart and skeletal muscle and infiltrations by lipidic substances. The ultrastructure of some lipidic droplets was analogous to those of ceroid and lipofuscin. Peroxisomes were frequent in degenerating hepatocytes. In order to elucidate the lysosomal involvement in the residual formation, light and electron microscopical immunocytochemistry using copper-zinc superoxide dismutase (CuZnSOD) was applied. Degradation of mitochondria in the skeletal muscles appeared to be due to the direct coalescence of mitochondria with primary lysosomes. Probably zinc was recruited into the antioxidant protection upon conclusion of the increased erythrocyte superoxide dismutase (E-SOD) activity.


Documenting participation in an employer-sponsored disease management program: selection, exclusion, attrition, and active engagement as possible metrics.
The objective of this study was to document participation in a large employer-sponsored disease management program. This retrospective study tracked participation and attrition rates for asthma, diabetes, coronary heart disease, and congestive heart failure programs over a 4-year period. Across all four illnesses, only 25% of those identified had any participation. Over 12 months, only 7% continued participating. Of the 93% who were lost, 35% were excluded, 15% could not be contacted, 25% declined to participate, and 17% dropped out over time. All groups improved their adherence to recommended treatment guidelines. Nonparticipants showed the greatest absolute improvement in receiving recommended medical services; however, they also had the lowest rate of service use at baseline and remained lowest at follow up. Documenting active engagement and attrition rates may provide useful information for decision-makers.


Siegesbeckia glabrescens induces apoptosis with different pathways in human MCF-7 and MDA-MB-231 breast carcinoma cells.
Breast cancer is one of the most common malignancies diagnosed in women and it is increasing in incidence. Siegesbeckia glabrescens (SG) has been used in traditional oriental medicine to treat cardiovascular diseases such as hypertension and angina pectoris. This study examined whether or not SG could induce apoptosis in human breast carcinoma cells. The treatment of estrogen-receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cells with a variety of SG concentrations (0-1.0 mg/ml) resulted in a dose-dependent sequence of events that were marked by apoptosis. Furthermore, this apoptosis was accompanied by the cleavage of procaspase-9 and -3, and poly(ADP-ribose) polymerase (PARP) in the MCF-7 cells, and procaspase-8 and -3 and PARP in the MDA-MB-231 cells. Although, the SG-induced apoptosis was associated with a decrease in the level of Bcl-2 mRNA expression and an increase in the level of Bax mRNA expression in MCF-7 cells, there was no detectable change in the MDA-MB-231 cells. This suggests that SG might exert anti-proliferative action in human breast carcinoma cells via two different apoptotic pathways, namely an intrinsic signal in MCF-7 cells and an extrinsic signal in MDA-MB-231 cells. Therefore, regardless of the ER status, SG might be a promising pro-apoptotic agent for treating breast cancer.


Quantitative thyroid scintigraphy in greyhounds suspected of primary hypothyroidism.
The existence of hypothyroidism in greyhounds remains controversial and its investigation is complicated by the low circulating thyroid hormone concentrations typically found in healthy dogs of this breed. Quantitative measurement of thyroidal technetium-99m pertechnetate ((99m)TcO4-) uptake is known to be useful in assessing thyroid function in other breeds. The aim of this study was to evaluate thyroid scintigraphy as a method of assessing thyroid function in greyhounds suspected of primary hypothyroidism. Twenty greyhounds (eight females, 12 males) were studied. Thirteen had bald thigh syndrome and seven poor performance and low total T4. Total T4 concentrations were decreased in 18 (90%), and free T4 in two (10%) dogs. All canine thyroid stimulating hormone concentrations were within the reference interval. Thyroidal (99m)TcO4- uptake values (mean +/- SD, 0.76 +/- 0.26%) were within the reference limits published for euthyroid dogs (0.39-1.86%) making hypothyroidism highly unlikely. There were no significant differences (P < 0.05) when comparing data between dogs with bald thigh syndrome (13 dogs) and the remaining dogs (seven dogs). Seventeen (85%) dogs had higher uptake in the left thyroid gland than in the right that might reflect an anatomic feature of the greyhound breed. Calculation of percent thyroidal uptake of (99m)TcO4- is more accurate than thyroid: salivary gland ratios because of high variability in salivary gland uptake. Percent thyroidal uptake of (99m)TcO4- should be used when assessing thyroid function scintigraphically in the greyhound breed.


Non-linear relationships between nurse staffing and patients' length of stay in acute care units: Bayesian dependence modelling.
This study sought to analyse relationships between nurse staffing and patients' length of stay in acute care units and to determine whether non-linear relationships exist between variables. Healthcare systems are complex and it could be assumed that they comprise non-linear associations. However, current planning and evaluation of nurse staffing are based primary on linear reasoning. This quantitative study adopted a retrospective longitudinal design. Retrospective register data, consisting of information relating to 35,306 patient episodes and administrative information concerning 381 nurses, were used. Data were collected in 2009 from 20 somatic inpatient units at a university hospital in Finland as a monthly time series of 2008 data and analysed using Bayesian dependency modelling. Patients' acuity was the most important agent that connected all eleven variables in the dependency network of nurse staffing and short length of stay. Non-linear associations were found between short length of stay and the proportion of Registered Nurses. Skill mix consisting of an average proportion of Registered Nurses (65-80%) was conducive to a short length of stay and predicted a 66% likelihood of short length of stay. Higher and lower percentages of Registered Nurses predicted lower likelihood of short length of stay. Flexible nurse staffing is preferable to fixed staffing to provide patients with shorter length of stay in acute care units. In the present research, the Bayesian method revealed non-linear relationships between nurse staffing and patient and care outcomes.


Immune mechanisms involved in cardiovascular complications of chronic kidney disease.
A sustained status of chronic inflammation is closely linked to several complications of chronic kidney disease (CKD), such as vascular degeneration, myocardial fibrosis, loss of appetite, insulin resistance, increased muscle catabolism and anemia. These consequences of a chronically activated immune system impact on the acceleration of atherosclerosis, vascular calcification and development of heart dysfunction. Recent evidence suggests that these immune-mediated consequences of uremic toxicity are not only important to stratify the risk and understand the mechanisms of disease, but also represent an important area for intervention. Thus, the aim of this brief review is to discuss the immune mechanisms behind atherosclerosis and myocardiopathy in CKD. We also display the emerging evidence that strategies focusing on modulating the immune response or reducing the generation of triggers of inflammation may represent an important tool to reduce mortality in this group of patients. Ongoing studies may generate the evidence that will translate these strategies to definitive changes in clinical practice.


Bilateral Hemorrhages in a Premature Infant With Subarachnoid Hemorrhage: An Underrecognized Etiology.
The authors describe an 8-day-old male infant born premature at 31 weeks and 6 days (corrected gestational age: 33 weeks) with cholestatic jaundice and cytomegalovirus (CMV) viremia found to have bilateral multilaminar hemorrhages that represented a diagnostic challenge. Fluorescein angiography (FA) ruled out vasculitis, retinitis, and neovascular process. An extensive laboratory work-up for infectious and coagulopathic etiologies was negative other than a positive systemic viral titer for CMV, but there was no retinitis based on serial exams and FA. Magnetic resonance imaging showed a right-sided subarachnoid hemorrhage, which was felt to be parturitional and confirmed the unifying diagnosis of delivery-associated retinopathy and intracranial hemorrhages in a preterm infant, a term that has been previously described. Simultaneous subarachnoid hemorrhage and vitreoretinal hemorrhage may represent an underrecognized cause of neonatal hemorrhage in preterm infants. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:596-600.].