Oleic acid uptake by jejunal and ileal rat brush border membrane vesicles.
In previous works, a membrane fatty acid transport system has been identified in brush border membrane vesicles, but no different intestinal regions were considered in these studies. To test the existence of a proximal-to-distal gradient of fat absorption along the small intestine, transmembrane influx kinetics of a representative long-chain fatty acid, 3H-oleic acid, in both jejunum and ileum of rat has been studied using brush border membrane vesicles (BBMV). With increasing concentration of unbound oleate in the medium, both jejunal and ileal BBMV showed saturable uptake kinetics (Vmax = 0.15 +/- 0.01 nmol.mg protein-1 x 5 min-1 and Km = 136 +/- 29.1 nmol for jejunum, and Vmax = 0.23 +/- 0.03 nmol.mg protein-1 x 5 min1 and Km = 196 +/- 50.3 nmol for ileum). These results support the hypothesis that oleic acid uptake occurs via a carrier-mediated transport mechanism in both jejunum and ileum. Furthermore, the existence of a proximal-to-distal gradient for fat absorption was apparent with a higher density of transport units (Vmax) in ileum compared to jejunum.


Combining Ballast Water Exchange and Treatment To Maximize Prevention of Species Introductions to Freshwater Ecosystems.
The most effective way to manage species transfers is to prevent their introduction via vector regulation. Soon, international ships will be required to meet numeric ballast discharge standards using ballast water treatment (BWT) systems, and ballast water exchange (BWE), currently required by several countries, will be phased out. However, there are concerns that BWT systems may not function reliably in fresh and/or turbid water. A land-based evaluation of simulated "BWE plus BWT" versus "BWT alone" demonstrated potential benefits of combining BWE with BWT for protection of freshwater ecosystems. We conducted ship-based testing to compare the efficacy of "BWE plus BWT" versus "BWT alone" on voyages starting with freshwater ballast. We tested the hypotheses that there is an additional effect of "BWE plus BWT" compared to "BWT alone" on the reduction of plankton, and that taxa remaining after "BWE plus BWT" will be marine (low risk for establishment at freshwater recipient ports). Our study found that BWE has significant additional effect on the reduction of plankton, and this effect increases with initial abundance. As per expectations, "BWT alone" tanks contained higher risk freshwater or euryhaline taxa at discharge, while "BWE plus BWT" tanks contained mostly lower risk marine taxa unlikely to survive in recipient freshwater ecosystems.


Are TrueFISP images T2/T1-weighted?
Images acquired using the TrueFISP technique (true fast imaging with steady-state precession) are generally believed to exhibit T(2)/T(1)-weighting. In this study, it is demonstrated that with the widely used half-flip-angle preparation scheme, approaching the steady state requires a time length comparable to the scan time such that the transient-state response may dominate the TrueFISP image contrast. Two-dimensional images of the human brain were obtained using various phase-encoding matrices to investigate the transient-state signal behavior. Contrast between gray and white matter was found to change significantly from proton-density- to T(2)/T(1)-weighted as the phase-encoding matrix size increased, which was in good agreement with theoretical predictions. It is concluded that TrueFISP images in general exhibit T(2)/T(1)-contrast, but should be more appropriately regarded as exhibiting a transient-state combination of proton-density and T(2)/T(1) contrast under particular imaging conditions. Interpretation of tissue characteristics from TrueFISP images in clinical practice thus needs to be exercised with caution.


Diastereoselective [3 + 1] Cyclization Reaction of Oxindolyl Azaoxyallyl Cations with Sulfur Ylides: Assembly of 3,3'-Spiro[β-lactam]-oxindoles.
Oxindoles and β-lactams are attractive structural motifs because of their unique biological importance. However, the fusion of the two moieties featuring 3,3'-spirocyclic scaffolds is a challenging task in organic synthesis. Herein we designed a novel type of oxindole-based azaoxyallyl cation synthons, which could readily participate in the [3 + 1] cyclization with sulfur ylides. With this protocol, a collection of 3,3-spiro[β-lactam]-oxindoles were facilely produced in up to 94% yield with perfect diastereoselectivity.


Clinical results and survivorship of the Mathys Affinis Short, Short Stem Total Shoulder Prosthesis.
The Mathys Affinis Short is the most frequently used stemless total shoulder prosthesis in the UK. The purpose of this prospective cohort study is to report the survivorship, clinical, and radiological outcomes of the first independent series of the Affinis Short prosthesis. From January 2011 to January 2019, a total of 141 Affinis Short prostheses were implanted in 127 patients by a single surgeon. Mean age at time of surgery was 68 (44 to 89). Minimum one year and maximum eight year follow-up (mean 3.7 years) was analyzed using the Oxford Shoulder Score (OSS) at latest follow-up. Kaplan-Meier survivorship analysis was performed with implant revision as the endpoint. Most recently performed radiographs were reviewed for component radiolucent lines (RLLs) and proximal humeral migration. Five shoulders underwent revision surgery (3.5%); three for rotator cuff failure, one for infection, and one for component malposition. Survivorship of the implant was 95.4% (95% confidence interval 90.1% to 97.9%) at five and nine years. Mean OSS improved significantly compared to preoperative values from 19.0 (1 to 35) to 43.3 (7 to 48) (p < 0.001). Radiological analysis was undertaken for 99 shoulders. This revealed humeral RLLs in one case (1%), glenoid RLLs in 15 cases (15.2%), and radiological rotator cuff failure in 22 cases (22.2%). This prospective cohort study shows encouraging short- to mid-term survivorship and clinical and radiological results for the Mathys Affinis Short, Short Stem Total Shoulder Prosthesis.Level of Evidence: IVCite this article: Bone Jt Open 2021;2(1):58-65.


Identifying RBM47, HCK, CD53, TYROBP, and HAVCR2 as Hub Genes in Advanced Atherosclerotic Plaques by Network-Based Analysis and Validation.
Background: Atherosclerotic cardiovascular diseases accounted for a quarter of global deaths. Most of these fatal diseases like coronary atherosclerotic disease (CAD) and stroke occur in the advanced stage of atherosclerosis, during which candidate therapeutic targets have not been fully established. This study aims to identify hub genes and possible regulatory targets involved in treatment of advanced atherosclerotic plaques. Material/Methods: Microarray dataset GSE43292 and GSE28829, both containing advanced atherosclerotic plaques group and early lesions group, were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was conducted to identify advanced plaque-related modules. Module conservation analysis was applied to assess the similarity of advanced plaque-related modules between GSE43292 and GSE28829. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these modules were performed by Metascape. Differentially expressed genes (DEGs) were mapped into advanced plaque-related modules and module membership values of DEGs in each module were calculated to identify hub genes. Hub genes were further validated for expression in atherosclerotic samples, for distinguishing capacity of CAD and for potential functions in advanced atherosclerosis. Results: The lightgreen module (MElightgreen) in GSE43292 and the brown module (MEbrown) in GSE28829 were identified as advanced plaque-related modules. Conservation analysis of these two modules showed high similarity. GO and KEGG enrichment analysis revealed that genes in both MElightgreen and MEbrown were enriched in immune cell activation, secretory granules, cytokine activity, and immunoinflammatory signaling. RBM47, HCK, CD53, TYROBP, and HAVCR2 were identified as common hub genes, which were validated to be upregulated in advanced atherosclerotic plaques, to well distinguish CAD patients from non-CAD people and to regulate immune cell function-related mechanisms in advanced atherosclerosis. Conclusions: We have identified RBM47, HCK, CD53, TYROBP, and HAVCR2 as immune-responsive hub genes related to advanced plaques, which may provide potential intervention targets to treat advanced atherosclerotic plaques.


Stress-induced p53 drives BAG5 cochaperone expression to control α-synuclein aggregation in Parkinson's disease.
Parkinson's disease (PD) is a common neurodegenerative disorder with the pathological hallmark of α-synuclein aggregation. Dysregulation of α-synuclein homeostasis caused by aging, genetic, and environmental factors underlies the pathogenesis of PD. While chaperones are essential for proteostasis, whether modulation of cochaperones may participate in PD formation has not been fully characterized. Here, we assessed the expression of several HSP70- and HSP90-related factors under various stresses and found that BAG5 expression is distinctively elevated in etoposide- or H2O2-treated SH-SY5Y cells. Stress-induced p53 binds to the BAG5 promoter directly to stimulate BAG5. Induced BAG5 binds α-synuclein and HSP70 in both cell cultures and brain lysates from PD patients. Overexpressed BAG5 may result in the loss of its ability to promote HSP70. Importantly, α-synuclein aggregation in SH-SY5Y cells requires BAG5. BAG5 expression is also detected in transgenic SNCA mutant mice and in PD patients. Together, our data reveal stress-induced p53-BAG5-HSP70 regulation that provides a potential therapeutic angle for PD.


Accelerating newborn survival in Ghana through a low-dose, high-frequency health worker training approach: a cluster randomized trial.
Newborn deaths comprise nearly half of under-5 deaths in Ghana, despite the fact that skilled birth attendants (SBAs) are present at 68% of births, which implies that evidence-based care during labor, birth and the immediate postnatal period may be deficient. We assessed the effect of a low-dose, high-frequency (LDHF) training approach on long-term evidence-based skill retention among SBAs and impact on adverse birth outcomes. From 2014 to 2017, we conducted a cluster-randomized trial in 40 hospitals in Ghana. Eligible hospitals were stratified by region and randomly assigned to one of four implementation waves. We assessed the relative risks (RRs) of institutional intrapartum stillbirths and 24-h newborn mortality in months 1-6 and 7-12 of implementation as compared to the historical control period, and in post-intervention facilities compared to pre-intervention facilities during the same period. All SBAs providing labor and delivery care were invited to enroll; their knowledge and skills were assessed pre- and post-training, and 1 year later. Adjusting for region and health facility type, the RR of 24-h newborn mortality in the 40 enrolled hospitals was 0·41 (95% CI 0·32-0·51; p < 0.001) in months 1-6 and 0·30 (95% CI 0·21-0·43; p < 0·001) in months 7-12 compared to baseline. The adjusted RR of intrapartum stillbirth was 0·64 (95% CI 0·53-0·77; p < 0·001) in months 1-6 and 0·48 (95% CI 0·36-0·63; p < 0·001) in months 7-12 compared to baseline. Four hundred three SBAs consented and enrolled. After 1 year, 200 SBAs assessed had 28% (95% CI 25-32; p < 0·001) and 31% (95% CI 27-36; p < 0·001) higher scores than baseline on low-dose 1 and 2 content skills, respectively. This training approach results in a sustained decrease in facility-based newborn mortality and intrapartum stillbirths, and retained knowledge and skills among SBAs after a year. We recommend use of this approach for future maternal and newborn health in-service training and programs. Retrospectively registered on 25 September 2017 at Clinical Trials, identifier NCT03290924 .


Low drive voltage optical phase modulator with novel InGaAlAs/InAlAs multiple-quantum-barrier based n-i-n heterostructure.
An optical phase modulator based on novel n-i-n InGaAlAs/InAlAs multiple-quantum-barrier (MQBs) is proposed to reduce the waveguide loss and enhance the modulation efficiency. Efficient bias loading with low leakage current is realized by taking advantages of the large conduction band discontinuity in InGaAlAs/InAlAs heterostructure and high electron reflection by MQBs. Low optical transmission loss of 2.3 dB/cm and improved modulation performance with a voltage length product of 1.06 V⋅cm are demonstrated for TE mode at 1550 nm. The linear and quadratic electro-optic coefficients of the fabricated device are estimated to be 1.0 pm/V and 1.4 × 10⁻¹⁹ m²/V², respectively.


Repeated Impacts Diminish the Impact Performance of Equestrian Helmets.
Context: During thoroughbred races, jockeys are placed in potentially injurious situations, often with inadequate safety equipment. Jockeys frequently sustain head injuries; therefore, it is important that they wear appropriately certified helmets. Objective: The goals of this study are (1) to perform impact attenuation testing according to ASTM F1163-15 on a sample of equestrian helmets commonly used by jockeys in the United States and (2) to quantify headform acceleration and residual crush after repeat impacts at the same location. Participants and Design: Seven helmet models underwent impact attenuation testing according to ASTM F1163-15. A second sample of each helmet model underwent repeat impacts at the crown location for a total of 4 impacts. Setting: Laboratory. Intervention: Each helmet was impacted against a flat and equestrian hazard anvil. Main Outcome Measures: Headform acceleration was recorded during all impact and computed tomography scans were performed preimpact and after impacts 1 and 4 on the crown to quantify liner thickness. Results: Four helmets had 1 impact that exceeded the limit of 300g. During the repeated crown impacts, acceleration remained below 300g for the first and second impacts for all helmets, while only one helmet remained below 300g for all impacts. Foam liner thickness was reduced between 5% and 39% after the first crown impact and between 33% and 70% after the fourth crown impact. Conclusions: All riders should wear a certified helmet and replace it after sustaining a head impact. Following an impact, expanded polystyrene liners compress, and their ability to attenuate head acceleration during subsequent impacts to the same location is reduced. Replacing an impacted helmet may reduce a rider's head injury risk.


[Management of Hepatitis B Virus (HBV) in transplantation].
Clinical manifestations of hepatitis B virus (HBV) infection are ranged from fulminant hepatitis to decompensated cirrhosis or hepatocellular carcinoma. Liver transplantation (LT) is one therapeutic option of these HBV infection complications. Intrahepatic viral persistence and low levels of circulating viral particles despite treatment optimization may lead to HBV recurrence after LT, which jeopardizes graft and patients survival after LT. HBV recurrence prophylactic strategies are based on nucleos(t)ides analogues (NUCs) treatment to block viral replication and anti-HBs immunoglobulin administration to neutralize circulating viral particles. The risk of HBV recurrence is also important in case of transplantation with a graft from a donor with a history of HBV infection (HBc+) to a "HBV naive" recipient or in case of immunosuppressive therapy after solid organ or hematopoietic stem cell transplantation for a HBc+ recipient. Prophylactic strategies are mainly focused on biological monitoring and NUCs therapy for high-risk situations.


Cysteine scanning mutagenesis of the noncatalytic nucleotide binding site of the yeast V-ATPase.
To investigate residues involved in the formation of the noncatalytic nucleotide binding sites of the vacuolar proton-translocating adenosine triphosphatase (V-ATPase), cysteine scanning mutagenesis of the VMA2 gene that encodes the B subunit in yeast was performed. Replacement of the single endogenous cysteine residue at position 188 gave rise to a Cys-less form of the B subunit (Vma2p) which had near wild-type levels of activity and which was used in the construction of 16 single cysteine-containing mutants. The ability of adenine nucleotides to prevent reaction of the introduced cysteine residues with the sulfhydryl reagent 3-(N-maleimidopropionyl)biocytin (biotin-maleimide) was evaluated by Western blot. Biotin-maleimide labeling of the purified V-ATPase from the wild-type and the mutants S152C, L178C, N181C, A184C, and T279C was reduced after reaction with the nucleotide analog 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate (BzATP). These results suggest the proximity of these residues to the nucleotide binding site on the B subunit. In addition, we have examined the level of endogenous nucleotide bound to the wild-type V-ATPase and to a mutant (the A subunit mutant R483Q) which is postulated to be altered at the noncatalytic site and which displays a marked nonlinearity in ATP hydrolysis (MacLeod, K. J., Vasilyeva, E., Baleja, J. D., and Forgac, M. (1998) J. Biol. Chem. 273, 150-156). The R483Q mutant contained 2.6 mol of ATP/mol of V-ATPase compared with the wild-type enzyme, which contained 0.8 mol of ATP/mol of V-ATPase. These results suggest that binding of additional ATP to the noncatalytic sites may modulate the catalytic activity of the enzyme.


Using geo-spatial analysis for assessing the risk of hospital admissions due to community-acquired pneumonia in under-5 children and its association with socially vulnerable areas (Brazil).
The concentration of under-5 child morbidity and mortality due to pneumonia in developing countries reflects the social inequities. This study aimed to map and assess the spatial risk for hospitalization due to Community-Acquired Pneumonia in children under 5 years of age and its association with vulnerable areas. Ecological study in the city of Ribeirão Preto, state of São Paulo, Brazil. The study population consisted of hospitalized under-5 children, diagnosed with community-acquired pneumonia, in Ribeirão Preto-São Paulo-Brazil, from 2012 to 2013. Data were collected in different databases, by a trained team, between March 2012 and August 2013 and from the 2010 Demographic Census of the Brazilian Institute of Geography and Statistics. The 956 urban census tracts were considered as the units of analysis. The incidence of cases per 10,000 inhabitants was calculated by census tracts during the study period. For the identification of the spatial risk clusters, the Kernel density estimator and the Getis-Ord Gi* technique were performed. Generalized additive models were used to verify the association between areas with social vulnerability and the occurrence of childhood pneumonia. The study included 265 children under the age of five, hospitalized due to community-acquired pneumonia. A concentration of cases was identified in the regions with greater social vulnerability (low income, poor housing conditions and homelessness), as well as a lower occurrence of cases in the most developed and economically privileged area of the city. The majority of the children lived in territories served by traditional primary healthcare units, in which the health surveillance and family and community focus are limited. It is important to highlight that the tracts with the highest degrees of vulnerability, such as those identified as high vulnerability (urban) and very high vulnerability (subnormal urban clusters). The results contribute to the comprehension of the social factors involved in child hospitalization due to pneumonia, based on the analysis of the spatial distribution. This approach revealed a strategic tool for diagnosing the disparities as well presenting evidences for the planning in health and strength health care system in achieving equity, welfare and social protection of children.


The Model of PPARγ-Downregulated Signaling in Psoriasis.
Interactions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels of PPARγ expression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model of PPARγ-downregulated signaling in psoriasis. We hypothesize that the expression of IL17, STAT3, FOXP3, and RORC and FOSL1 genes in psoriatic skin is correlated with the level of PPARγ expression, and they belong to the same signaling pathway that regulates the development of psoriasis lesion.


Thalidomide dose proportionality assessment following single doses to healthy subjects.
Thalidomide is approved in the United States for treating erythema nodosum leprosum, a complication of leprosy. The present study determined the single-dose oral pharmacokinetics and dose proportionality from 50 to 400 mg of Celgene's commercial Thalomid thalidomide formulation in an open-label, single-dose, three-way crossover study. Fifteen healthy subjects were given 50, 200, and 400 mg of thalidomide on three occasions, and blood samples were collected over 48 hours. Pharmacokinetic parameters were determined using noncompartmental methods, and dose proportionality was assessed by linear regression of dose-normalized Cmax and AUC0-infinity. No serious or unexpected adverse events occurred. The most common adverse events were dizziness, somnolence, headache, and nausea. One patient was discontinued because of pharyngitis. There was a significant deviation from proportionality for Cmax with increases being less than proportional than changes in dose. AUC0-infinity increased proportionally with dose, suggesting that the overall amount of thalidomide absorbed, as well as its clearance, is independent of dose over the range used. V/F was found to increase with dose. This was most likely due to the terminal rate constant, which is used to calculate V/F, actually representing the absorption process rather than elimination (i.e., flip-flop phenomenon). The terminal rate constant (absorption rate constant) for the highest dose was 50% less than for the other two lower doses. The less than proportional increases in Cmax were most likely due to thalidomide's low aqueous solubility. Thalidomide shows reasonable dose proportionality with respect to AUC from 50 to 400 mg.


Macrophage migration inhibitory factor and hypothalamo-pituitary-adrenal function during critical illness.
In patients with septic shock (n = 32), multitrauma (n = 8), and hospitalized matched controls (n = 41), we serially measured serum macrophage inhibitory factor (MIF), cortisol, plasma ACTH, tumor necrosis factor-alpha, and interleukin-6 (IL-6) immunoreactivity during 14 days or until discharge/death. MIF levels were significantly elevated on day 1 in septic shock (14.3 +/- 4.5 microg/L), as opposed to trauma (3.1 +/- 1.7 microg/L) and control patients (2.5 +/- 2.1 microg/L). The time course of MIF, parallel to cortisol, but in contrast to ACTH, showed persistently elevated levels in septic patients. On admission, nonsurvivors of septic shock (n = 11) showed significantly higher MIF levels than survivors (18.4 +/- 4.8 and 10.2 +/- 4.2 microg/L, respectively). Patients with septic adult respiratory distress syndrome (ARDS; n = 8) showed higher MIF levels than those who did not develop ARDS (19.4 +/- 4.7 vs. 9.2 +/- 4.3 microg/L, respectively). Multiple logistic regression analysis demonstrated that both MIF and ARDS were independent predictors of adverse outcome. On admission, tumor necrosis factor-alpha, IL-6, procalcitonin, and lipopolysaccharide-binding protein levels were higher in patients with septic shock than in patients with multitrauma. In septic patients, regression analysis showed significant correlations between MIF and cortisol as well as between MIF and IL-6 levels and disease severity scores. No relation was found between MIF and markers of the acute phase response (procalcitonin, C- reactive protein, and lipopolysaccharide-binding protein). In multitrauma patients, MIF levels were not elevated at any time point and were not related to other variables. Our data suggest that during immune-mediated inflammation (such as septic shock) MIF is an important neuroendocrine mediator: a contraregulator of the immunosuppressive effects of glucocorticoids.


Development of novel major histocompatibility complex class I and class II-deficient NOD-SCID IL2R gamma chain knockout mice for modeling human xenogeneic graft-versus-host disease.
Immunodeficient mice have been used as recipients of human peripheral blood mononuclear cells (PBMC) for in vivo analyses of human xeno-graft-versus-host disease (GVHD). This xeno-GVHD model system in many ways mimics the human disease. The model system is established by intravenous or intraperitoneal injection of human PBMC or spleen cells into unconditioned or irradiated immunodeficient recipient mice. Recently, the development of several stocks of immunodeficient Prkdc ( scid ) (scid) and recombination activating 1 or 2 gene (Rag1 or Rag2) knockout mice bearing a targeted mutation in the gene encoding the IL2 receptor gamma chain (IL2rgamma) have been reported. The addition of the mutated IL2rgamma gene onto an immunodeficient mouse stock facilitates heightened engraftment with human PBMC. Stocks of mice with mutations in the IL2rgamma gene have been studied in several laboratories on NOD-scid, NOD-Rag1 ( null ), BALB/c-Rag1 ( null ), BALB/c-Rag2 ( null ), and Stock-H2(d)-Rag2 ( null ) strain backgrounds. Parameters to induce human xeno-GVHD in H2(d)-Rag2 ( null ) IL2rgamma ( null ) mice have been published, but variability in the frequency of disease and kinetics of GVHD were observed. The availability of the NOD-scid IL2rgamma ( null ) stock that engrafts more readily with human PBMC than does the Stock-H2(d)-Rag2 ( null ) IL2rgamma ( null ) stock should lead to a more reproducible humanized mouse model of GVHD and for the use in drug evaluation and validation. Furthermore, GVHD in human PBMC-engrafted scid mice has been postulated to result predominately from a human anti-mouse major histocompatibility complex (MHC) class II reactivity. Our recent development of NOD-scid IL2rgamma ( null ) beta2m ( null ) and NOD-scid IL2rgamma ( null ) Ab ( null ) stocks of mice now make it possible to investigate directly the role of host MHC class I and class II in the pathogenesis of GVHD in humanized mice using NOD-scid IL2rgamma ( null ) stocks that engraft at high levels with human PBMC and are deficient in murine MHC class I, class II, or both classes of MHC molecules.


Photocontrol of Anthocyanin Synthesis: VII. Factors Affecting the Spectral Sensitivity of Anthocyanin Synthesis in Young Seedlings.
Light-dependent anthocyanin synthesis is a typical high irradiance response (HIR) of plant photomorphogenesis. The spectral sensitivity of this response in young seedlings of cabbage and tomato is strongly affected by the length and mode of application of the light treatments. This observation suggests that the different experimental conditions, used in different action spectroscopy studies, might have been responsible, at least in part, for some of the reported differences in the characteristics of the HIR action spectra of different response-system combinations. In both cabbage and tomato, the values of the far red/blue, far red/red, and blue/red action ratios increase with increasing durations of the light treatments; this finding is in agreement with hypotheses of K. M. Hartmann (1966, 1967) and E. Schäfer (1975) for phytochrome action in the HIR. The similarity in the trend of change of the values of the action ratios suggests the possibility that the photomorphogenic pigment system, involved in the photoregulation of anthocyanin synthesis, may be the same in cabbage and tomato, even though there are some differences in the spectral sensitivity of the response between the two species.


Total endoscopic and video-assisted thyroidectomy: cervical approach.
Several procedures have been proposed for surgical treatment of the thyroid nodule; they have not gained wide acceptance, however, because of the expertise required, the relatively long operation times, the wide dissection needed to create a working space, and the extra cost of specialized instruments, especially when port sites are created in the remote area. These barriers have led some surgeons to perform video-assisted thyroidectomy via the neck. We describe the indications for, procedures related to, and results of both total endoscopic thyroidectomy and video-assisted thyroidectomy via the neck. Excellent cosmetic results were obtained by both procedures; however, video-assisted procedures required less time and a smaller dissection area.


Dupuytren's disease in children-differential diagnosis.
Dupuytren's disease in children is uncommon; only a few histologically confirmed diagnoses are found in literature. In its early, proliferative phase with many fibroblasts, it can resemble the early stadium of an epitheloid sarcoma, which also is a rare tumor. The purpose of this report is to show pediatric surgeons and pathologists the importance of differential diagnosis of nodules and fibrotic bands in children's hands, especially to exclude a malignancy. Between 1998 and 2000, 3 children at ages of 2(1/2) years, 9 years, and 10 years, respectively, presented with the clinical signs of Dupuytren's disease of the hand. Each of them had fibrous bands with a flexion contracture of the fingers. All of them underwent fasciectomy. In patient 1, a 10 degrees extension lag of the index finger resulted after 3 operations. Histology findings showed the typical features of Dupuytren's disease. In patient 2, histology findings showed a recurring digital fibroma of childhood. After consultation with the pathologist and reevaluation of the slides, the histologic diagnosis was corrected to Dupuytren's disease. Full extension and thumb abduction has been achieved. In patient 3, histology of the first and second operation was misdiagnosed as Dupuytren's disease. In the third operation 2(1/2) years later, the histologic diagnosis of epitheloid sarcoma was made. Amputation of the forearm was necessary. Exact anamnesis, location of the lesion, and suspicious diagnosis must be mentioned to the pathologist in the case of biopsy or excision of Dupuytrenlike lesions in children's hands. Awareness of the possibility of the epitheloid sarcoma may help prevent misdiagnosis.


DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis.
Mutations in the DAX-1 gene are responsible for congenital X-linked adrenal hypoplasia, a disease that is associated with hypogonadotropic hypogonadism. DAX-1 expression is tissue-specific and is finely regulated throughout development, suggesting that it has a role in both adrenal and gonadal function. DAX-1 is an unusual member of the nuclear-receptor superfamily of transcription factors which contains no canonical zinc-finger or any other known DNA-binding motif. Binding sites for DAX-1 are found in the promoters of the dax-1 and StAR (for steroidogenic acute regulatory protein) genes. Here we show that DAX-1 binds DNA and acts as a powerful transcriptional repressor of StAR gene expression, leading to a drastic decrease in steroid production. We provide in vitro and in vivo evidence that DAX-1 binds to DNA hairpin structures. Our results establish DAX-1 as the first member of the nuclear receptor superfamily with novel DNA-binding features and reveal that it has regulatory properties critical to the understanding of its physiological functions.


Continuous pneumothorax monitoring by remittance measurement.
The feasibility of a noninvasive method, based on a remittance measurement, to monitor continuously for the occurrence of pneumothorax in neonates under ventilation, was investigated through animal experiments. Light from a He-Ne laser (632.8 nm) or a semiconductor laser (790 nm) was incident on the chest wall of rabbits and piglets. The remittance was measured as a function of distance from the source. Remittances under physiological conditions were compared with remittances during the introduction of an artificial pneumothorax and with remittances during inflation of the pleural space. The remittance varied with a frequency similar to the respiratory frequency. The amplitude of these variations changed as a function of the volume of air that was introduced into the pleural space (rabbits/He-Ne laser, p < 0.025; piglets/semiconductor laser, p < 0.01). We conclude that optical measurements are potentially usable for monitoring continuously for the occurrence of a pneumothorax in neoatology.


Effectiveness of home-based and remotely supervised aerobic exercise in Parkinson's disease: a double-blind, randomised controlled trial.
High-intensity aerobic exercise might attenuate the symptoms of Parkinson's disease, but high-quality evidence is scarce. Moreover, long-term adherence remains challenging. We aimed to evaluate the effectiveness of aerobic exercise-gamified and delivered at home, to promote adherence-on relieving motor symptoms in patients with Parkinson's disease with mild disease severity who were on common treatment regimes. In this single-centre, double-blind, randomised controlled trial (Park-in-Shape), we recruited sedentary patients with Parkinson's disease from the outpatient clinic at Radboudumc, Nijmegen, Netherlands. Patients were made aware of the study either by their treating neurologist or via information in the waiting room. Patients could also contact the study team via social media. We included patients aged 30-75 years with a Hoehn and Yahr stage of 2 or lower, who were on stable dopaminergic medication. Patients were randomly assigned (in a 1:1 ratio) to either aerobic exercise done on a stationary home-trainer (aerobic intervention group) or stretching (active control group) by means of a web-based system with minimisation for sex and medication status (treated or untreated) and permuted blocks of varying sizes of more than two (unknown to study personnel). Patients were only aware of the content of their assigned programme. Assessors were unaware of group assignments. Both interventions were home based, requiring 30-45 min training three times per week for 6 months. Both groups received a motivational app and remote supervision. Home trainers were enhanced with virtual reality software and real-life videos providing a so-called exergaming experience (ie, exercise enhanced by gamified elements). The primary outcome was the between-group difference in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor section at 6 months, tested during the off state (≥12 h after last dopaminergic medication). The analysis was done on an intention-to-treat basis in patients who completed the follow-up assessment, regardless of whether they completed the assigned intervention. Patients reported adverse events directly to their coach and also after the 6-month visit retrospectively. A between-group difference of 3·5 points or more was deemed a-priori clinically relevant. The study is concluded and registered with the Dutch Trial Registry, NTR4743. Between Feb 2, 2015, and Oct 27, 2017, 139 patients were assessed for eligibility in person, of whom 130 were randomly assigned to either the aerobic intervention group (n=65) or the active control group (n=65). Data from 125 (96%) patients were available for the primary analysis; five patients were lost to follow-up (four in the intervention group; one in the control group). 20 patients (ten in each group) did not complete their assigned programme. The off-state MDS-UPDRS motor score revealed a between-group difference of 4·2 points (95% CI 1·6-6·9, p=0·0020) in favour of aerobic exercise (mean 1·3 points [SE 1·8] in the intervention group and 5·6 points [SE 1·9] for the control group). 11 patients had potentially related adverse events (seven [11%] in the intervention group, four [6%] in the control group) and seven had unrelated serious adverse events (three in the intervention group [vestibilar disorder, vasovagal collapse, knee injury during gardening that required surgery; 6%], four in the control group [supraventricular tachycardia, hip fracture, fall related injury, severe dyskinesias after suprathreshold dose levodopa in a patient with deep brain stimulation; 7%]). Aerobic exercise can be done at home by patients with Parkinson's disease with mild disease severity and it attenuates off-state motor signs. Future studies should establish long-term effectiveness and possible disease-modifying effects. Netherlands Organization for Health Research and Development.


Op Patwin Part 2: HMS illustrious' medical response to typhoon Haiyan.
Operation PATWIN was the United Kingdom's (UK) response to the disaster caused by Typhoon Haiyan. The UK deployed a force including HMS DARING and HMS ILLUSTRIOUS and this article describes the medical response including the deployment of a Role 2 medical team and the hosting of a UK civilian medical team UK Med. The deployment followed humanitarian guidelines in UK doctrine and contained in the Oslo guidelines, but demonstrated a unique example of a civilian team supported by the military.


Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation.
Interleukin-23 (IL-23) and CD4(+) T helper 17 (Th17) cells are thought to be critical in psoriasis pathogenesis. Here, we report that IL-23 predominantly stimulated dermal γδ T cells to produce IL-17 that led to disease progression. Dermal γδ T cells constitutively expressed the IL-23 receptor (IL-23R) and transcriptional factor RORγt. IL-17 production from dermal γδ T cells was independent of αβ T cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell receptor δ-deficient (Tcrd(-/-)) and IL-17 receptor-deficient (Il17ra(-/-)) mice but occurred normally in Tcra(-/-) mice. Imiquimod-induced skin pathology was also significantly decreased in Tcrd(-/-) mice. Perhaps further promoting disease progression, IL-23 stimulated dermal γδ T cell expansion. In psoriasis patients, γδ T cells were greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal γδ T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.


The co-occurrence of common mental and physical disorders within Australian families: a national population-based study.
Because comorbidity between mental and physical disorders is commonly found in patients, it would be expected that this pattern would also be reflected at the family level. During a recent population-based survey of common mental disorders, respondents were asked about the presence of selected mental and physical disorders in their relatives. The aim of this research was to describe the within-family co-occurrence of selected common physical and mental disorders in a population-based sample. Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. A modified version of the World Mental Health Survey Initiative of the Composite International Diagnostic Interview (WMH-CIDI 3.0, henceforth CIDI) was used to identify lifetime-ever common psychiatric disorders (anxiety disorders, depression, drug or alcohol disorders). The respondents were asked if any of their relatives had one of a list of psychiatric (anxiety, bipolar disorder, depression, drug or alcohol problem, schizophrenia) or general physical disorders (cancer, heart problems, intellectual disability, memory problems). We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors. Compared to otherwise-well respondents, those who had a CIDI diagnosis of major depressive disorders, anxiety disorders, or drug or alcohol abuse/dependence were significantly more likely to have first-degree relatives with (a) the same diagnosis as the respondent, (b) other mental disorders not identified in the respondent, and (c) a broad range of general physical conditions. Individuals with common mental disorders report greater familial co-occurrence for a range of mental and physical disorders. When eliciting family histories, clinicians should remain mindful that both mental and physical disorders can co-occur within families.


Neuroanatomical basis in the temporal lobes for processing living things.
Category-specific impairment in living things was examined in patients with temporal lobe damage to investigate whether specific neuroanatomical regions could be identified in processing the knowledge of specific categories. Tasks involving more effortful retrieval naming and less effortful attribute judgment were administered to 3 groups of patients with either bilateral, unilateral left, or unilateral right temporal lobe damage. Category-specific impairment in living things was observed for patients with unilateral or bilateral damage, results that are consistent with previous findings. Depending on its site and extent, the damage in the temporal lobe might lead to deficits in processing or loss of semantic knowledge for living things. Therefore, intact category-specific semantic processes may involve associations among different neural substrates in the temporal lobe.


Ligand-binding modes in cationic biogenic amine receptors.
The binding site in G protein-coupled cationic biogenic amine receptors is formed in the cleft of the seven transmembrane segments. Upon binding the ligand, the receptors are activated or inactivated through the conformational changes of the transmembrane segments. G protein-coupled receptors bind four functionally distinct ligands; inverse agonists, antagonists, partial agonists, and full agonists. Hence, putative structural models for biogenic amine receptors corresponding to the ligand function (inverse agonist-, antagonist-, partial agonist-, and full agonist-bound receptor models) were built by using photointermediate models in the rhodopsin photocascade (M. Ishiguro et al. ChemBioChem. 2004, 5, 298-310). The ligand-receptor recognition of each was examined by modeling receptor-ligand complexes with functional ligands. The complex models suggested that each functional ligand binds the corresponding receptor structure and that ligand-specific interactions contribute to stabilization of the corresponding receptor structure.


Achieving High Breast Cancer Survival for Women in Rural and Remote Areas.
Significant improvements in breast cancer survival have been made in the past few decades in many developed countries including Australia with a five-year relative survival of 90%. The aim of the present study is to obtain a brief estimate of the relative importance of demographic factors such as rurality, socio-economic standard and ethnicity versus traditional risk factors for women diagnosed with breast cancer in Far North Queensland, Australia. This was a retrospective longitudinal study of all women diagnosed with their first episode of breast cancer in 1999-2013 in Far North Queensland, Australia. Cox proportional hazards regression analysis was used to identify factors independently associated with mortality for women with any type of breast cancer (in situ or invasive) and for women with invasive cancer. Life tables were used to assess five and ten-year absolute survival. Standard linear regression and binary logistic regression were used to identify any association between demographic factors and late presentation. Five and ten-year absolute survival was 0.90 and 0.86 respectively. Aboriginal and Torres Strait Islander status, remoteness of area of residence, and socioeconomic status were not associated with more advanced disease at presentation or increased risk of breast cancer death. Only traditional risk factors such as increased tumour size, absence of progesterone receptor, high tumour grade and presence of metastasis in axillary lymph nodes were associated with increased risk of breast cancer death. The effect of the classical risk factors on breast cancer mortality outweighs the effects of demographic factors. The fact that ethnicity, remoteness and socioeconomic status is not associated with late presentation or breast cancer death suggests that given appropriate resources it may be possible to close the gap of inequalities in breast cancer.


Regional block anesthesia for mastectomy: a community hospital experience.
This report describes a community hospital experience with regional anesthesia for mastectomy. The authors believe this is a modality deserving of wider application. This report is intended to illuminate the benefits of the approach.


Chemokine receptor CCR5 expression in conjunctival epithelium of patients with dry eye syndrome.
To characterize chemokine receptor CCR5 expression on the conjunctival epithelium in dry eye syndromes. Conjunctival impression cytology samples were obtained from normal subjects (n = 15) and patients with dry eye syndrome (n = 45). Cells were harvested from impression cytology samples, and flow cytometry was performed to quantitatively analyze the cell surface expression of chemokine receptor CCR5. Characterization of CCR5-positive cells was done by 2-color flow cytometry using fluorescein-conjugated anti-CCR5 and phycoerythrin-conjugated anti-CD45 antibodies (where CD45 is a marker for bone marrow-derived cells). To study CCR5 messenger RNA transcripts, real-time polymerase chain reaction was done on RNA isolated from the impression cytology samples of normal subjects (n = 5) and patients with dry eye syndrome (n = 14). We found significant up-regulation in cell surface expression of CCR5 in patients with both aqueous tear-deficient and evaporative forms of dry eye syndrome (P<.001). The real-time polymerase chain reaction results (for messenger RNA) corroborated the flow cytometry data (for protein). The majority of the cells expressing CCR5 were non-bone marrow-derived resident epithelial cells of the conjunctiva. Our findings suggest that CCR5 up-regulation is significantly associated with dry eye syndrome-associated ocular surface disease. Clinical Relevance Chemokine receptor CCR5 or its ligands may serve as useful targets for modulation of tissue immunoinflammatory responses in dry eye syndromes.


The Potential Use of the CRISPR-Cas System for HIV-1 Gene Therapy.
The HIV-1 virus (human immunodeficiency virus) affects 36.9 million people worldwide, with approximately 900000 deaths in 2017. The virus carrier can develop severe immunodeficiency since CD4+ T lymphocytes are the main target, leading to acquired immunodeficiency syndrome (AIDS). Despite advances in pharmacological treatment, it is still difficult to eliminate latent reservoirs, becoming one of the main obstacles for viral eradication. The CRISPR- (clustered regularly interspaced short palindromic repeat-) Cas system is a genome-editing method which uses a guide RNA, a complementary sequence to the interested site, recruiting a nuclease that can break the viral or the host cell genetic material. From this double-stranded break, cellular repair mechanisms are activated being able to generate deletions, insertions, or substitutions, in order to inactivate specific gene loci, leading to loss of function. The objective of this minireview is to synthesize the current knowledge on the application of CRISPR-Cas-based gene therapy for HIV-1. The strategies encompass all steps of the viral infection cycle, from inhibition of cell invasion, through viral replication and integration inhibition, to excision of the latent provirus. Off-target effects and ethical implications were also discussed to evaluate the safety of the approach and viability of its application in humans, respectively. Although preclinical and clinical tests are still needed, the recent results establish an exciting possibility of applying this technology for prophylaxis and treatment of HIV-1.


Inflammasome Inhibitors.
In recent years, the interplay between the activation of the immune system, the development of chronic inflammation and the onset and progression of many different diseases has been studied extensively [...].


[The aged: medical and social aspects].
Physical health is affected by physiological aging that impacts on all tissues and organs, notably sensorial systems (hearing, sight), the locomotory and the immunological systems (lowering of resistance to infections). There is an increase with age in the incidence of many cancers (particularly breast, prostate, and colon cancers) and cardiovascular diseases. Regular check-ups are useful in order to take appropriate measures in time. It is important that people maintain regular physical activity and a balanced diet even up to an advanced age and the elderly must learn to adapt themselves to the ever-changing abilities of their organism. It is possible to slow down the aging process through good hygiene and often to maintain autonomy until the end of life. Mental health is threatened by impairment of mental functions, depressive tendencies, and the risk of senile dementia that cannot be foreseen or avoided. It appears that keeping intellectually active and having a good level of education impact favorably on mental aging. Social health depends, for a large part, on the way society accepts and treats the elderly. They must be kept integrated into society and allowed to live at home for as long as possible. Any measures of rejection, discrimination, and exclusion should be opposed. The dignity of the elderly must be respected and activities giving them a feeling of usefulness should be encouraged. It is important to help families who care for their parents at home, to develop and evaluate healthcare networks, and encourage medical professionals and social services to work together. The change in the demographic structure of France is a considerable phenomenon requiring a long-term strategy and not only superficial and cosmetic measures.


Insect vector interactions with persistently transmitted viruses.
The majority of described plant viruses are transmitted by insects of the Hemipteroid assemblage that includes aphids, whiteflies, leafhoppers, planthoppers, and thrips. In this review we highlight progress made in research on vector interactions of the more than 200 plant viruses that are transmitted by hemipteroid insects beginning a few hours or days after acquisition and for up to the life of the insect, i.e., in a persistent-circulative or persistent-propagative mode. These plant viruses move through the insect vector, from the gut lumen into the hemolymph or other tissues and finally into the salivary glands, from which these viruses are introduced back into the plant host during insect feeding. The movement and/or replication of the viruses in the insect vectors require specific interactions between virus and vector components. Recent investigations have resulted in a better understanding of the replication sites and tissue tropism of several plant viruses that propagate in insect vectors. Furthermore, virus and insect proteins involved in overcoming transmission barriers in the vector have been identified for some virus-vector combinations.


[Dorsal root identification using spinal endoscopy and electro-physiology].
We aimed to develop a method of accurately identifying the dorsal root for the corresponding peripheral afferent nerve under endoscopic observation. We developed an endoscope with an external diameter of 1.8 mm. After small laminectomy on the lower thoracic vertebrae, we inserted this endoscope carefully into the epidural and then subarachnoid spaces. We observed structures in these spaces with the endoscope. We tried to determine the spatial relationship between these electrodes and dorsal root. After identifying each space, we inserted two electrodes into the visualized space to record evoked potentials; a bipolar electrode (protocol 1) and a catheter-type eight polar electrode (protocol 2). Each pole could be distinguished by marks. To stimulate peripheral nerves, we inserted needle-type electrodes into Th 10, 11 and 12 intercostal nerves. We attempted to record potentials from dorsal surface of the cord generated by intercostal nerve stimulus. Protocol 1: We moved the position of the bipolar recording electrodes between Th 9 and L 1 by 1 cm increment, and obtained evoked potentials correspondingly. Protocol 2: We chose the neighboring pairs of poles sequentially from the tip of the catheter for bipolar recording. At the end of each experiment, we dissected the animal and checked the intercostal nerve originating from the root. With the endoscope, we could clearly observe structures in the epidural and subarachnoid spaces. We could record evoked potentials from the dorsal spinal cord with the electrodes located either in epidural or in subarachnoid spaces. Shapes of evoked potentials changed characteristically according to the relative position between the root and the electrode. The largest potentials were obtained when the electrode was nearest to the dorsal root, of which the peripheral nerve was being stimulated. By combining endoscopy with the electrophysiological technique, we could accurately identify the dorsal roots for the corresponding peripheral afferent nerves. This method may be used for the selective dorsal root blockade under the visual field.


Flight control in the hawkmoth Manduca sexta: the inverse problem of hovering.
The inverse problem of hovering flight, that is, the range of wing movements appropriate for sustained flight at a fixed position and orientation, was examined by developing a simulation of the hawkmoth Manduca sexta. Inverse problems arise when one is seeking the parameters that are required to achieve a specified model outcome. In contrast, forward problems explore the outcomes given a specified set of input parameters. The simulation was coupled to a microgenetic algorithm that found specific sequences of wing and body motions, encoded by ten independent kinematic parameters, capable of generating the fixed body position and orientation characteristic of hovering flight. Additionally, we explored the consequences of restricting the number of free kinematic parameters and used this information to assess the importance to flight control of individual parameters and various combinations of them. Output from the simulated moth was compared to kinematic recordings of hovering flight in real hawkmoths; the real and simulated moths performed similarly with respect to their range of variation in position and orientation. The simulated moth also used average wingbeat kinematics (amplitude, stroke plane orientation, etc) similar to those of the real moths. However, many different subsets of the available kinematic were sufficient for hovering flight and available kinematic data from real moths does not include sufficient detail to assess which, if any, of these was consistent with the real moth. This general result, the multiplicity of possible hovering kinematics, shows that the means by which Manduca sexta actually maintains position and orientation may have considerable freedom and therefore may be influenced by many other factors beyond the physical and aerodynamic requirements of hovering flight.


Influence of heterogeneity of infection thresholds on epidemic spreading with neighbor resource supporting.
The spread of disease on complex networks has attracted wide attention in physics, mathematics, and epidemiology. Recent works have demonstrated that individuals always exhibit different criteria for disease infection in a network that significantly influences the epidemic dynamics. In this paper, considering the heterogeneity of node susceptibility, we proposed an infection threshold model with neighbor resource support. The infection threshold of an individual is associated with the degree, and a parameter follows the normal distribution. Based on improved heterogeneous mean-field theory and extensive numerical simulations, we find that the mean and standard deviation of the infection threshold model can affect the phase transition and epidemic outbreak size. As the mean of the normal distribution parameter increases from a small value to a large value, the system shows a change from a continuous phase transition to a discontinuous phase transition, and the disease even stops spreading. The disease spreads from a discontinuous phase transition to continuous for the sizeable mean value as the standard deviation increases. Furthermore, the standard deviation also varies in the outbreak size.


NIST High Accuracy Reference Reflectometer-Spectrophotometer.
A new reflectometer-spectrophotometer has been designed and constructed using state-of-the-art technology to enhance optical properties of materials measurements over the ultraviolet, visible, and near-infrared (UV-Vis-NIR) wavelength range (200 nm to 2500 nm). The instrument, Spectral Tri-function Automated Reference Reflectometer (STARR), is capable of measuring specular and diffuse reflectance, bidirectional reflectance distribution function (BRDF) of diffuse samples, and both diffuse and non-diffuse transmittance. Samples up to 30 cm by 30 cm can be measured. The instrument and its characterization are described.


What is the true evidence for gender-related differences during plant and cut maneuvers? A systematic review.
Female athletes have a significantly higher risk of sustaining an anterior cruciate ligament (ACL) injury than male athletes. Biomechanical and neuromuscular factors have been reported as the main cause. The purpose of this review was to critically review results of the published literature on gender differences regarding biomechanical and neuromuscular movement patterns during plant and cutting maneuvers. MEDLINE (1966 to December 2008), EMBASE (1947 to December 2008) and CINAHL (1981 to December 2008) searches were performed. The seven studies meeting the inclusion criteria were analyzed. Biomechanical gender differences were of questionable clinical relevance. Quadriceps dominance was not found in women. The question raises whether ACL injuries during plant and cutting maneuvers are purely gender related and whether women do have to move like men in order to reduce injury risk? Caution is warranted in making inferences as studies were heterogeneous in terms of subject and study characteristics and had low statistical power as a result of insufficient number of subjects. It is advised that future research moves beyond the isolated gender comparison and that larger sample sizes will be included. This review may aid in improving experiments to draw valid conclusions, in order to direct future ACL injury prevention programs, which might need to be more individualized.


Molecular/genetic determinants of repolarization and their modification by environmental stress.
Although a variety of factors, inherited or environmental, can influence expression of ion channel proteins to impact on repolarization, that environment can affect genetic determinants of repolarization for intervals of varying duration is a concept that is not as generally appreciated as it should be. In the following pages we review the molecular/genetic determinants of cardiac repolarization and summarize how pathologic events and environmental intrusions can affect these determinants. Understanding the chains of events involved should yield insights into both the causes and potential avenues of treatment for abnormalities of repolarization.


Selective internal carotid artery cross-clamping increases the specificity of cerebral oximetry for indication of shunting during carotid endarterectomy.
An indication for selective shunting during carotid endarterectomy (CEA) is based on monitoring during a procedure. Cerebral oximetry (CO) using near-infrared spectroscopy (NIRS) may be a simple technique, but its relevance during CEA, especially with respect to cutoff values indicating shunt implantation, still needs to be elucidated. One hundred twenty five patients underwent CEA under local anesthesia (LA) and were monitored clinically throughout the whole procedure. The patients were also monitored using bilateral NIRS probes during surgery. The NIRS values were recorded and evaluated before and after selective cross-clamping, firstly by the external carotid artery (ECA), followed by the internal carotid artery (ICA). The decrease in the ipsilateral CO values, with respect to the indication of shunting, was only analyzed after selective cross-clamping of the ICA. The decision to use an intraluminal shunt was solely based on the neurological status evaluation after ICA cross-clamping. One hundred five patients (85%) were stable throughout the CEA, while 20 patients (15%) clinically deteriorated during surgery. The mean drop in the CO after selective ICA clamping in clinically stable patients was 6%, while in patients with clinical deterioration, the NIRS decreased by 14.5% (p < 0.05). When the cutoff value for selective shunting was set as a 10% decrease of the ipsilateral CO after selective ICA clamping, the sensitivity of the technique was 100% and the specificity 83.0%. Our study showed that a 10% decrease in the ipsilateral brain tissue oximetry after selective cross-clamping the ICA provides a reliable cutoff value for selective shunting during CEA. Despite the availability of a variety of monitoring tools, the NIRS may be an easy, reliable option, especially in the scenario of acute CEA in general anesthesia.


A new firing paradigm for integrate and fire stochastic neuronal models.
A new definition of firing time is given in the framework of Integrate and Fire neuronal models. The classical absorption condition at the threshold is relaxed and the firing time is defined as the first time the membrane potential process lies above a fixed depolarisation level for a sufficiently long time. The mathematical properties of the new firing time are investigated both for the Perfect Integrator and the Leaky Integrator. In the latter case, a simulation study is presented to complete the analysis where analytical results are not yet achieved.


Application of the protection motivation theory in predicting cigarette smoking among adolescents in China.
Reducing tobacco use among adolescents in China represents a significant challenge for global tobacco control. Existing behavioral theories developed in the West - such as the Protection Motivation Theory (PMT) - may be useful tools to help tackle this challenge. We examined the relationships between PMT factors and self-reported cigarette smoking behavior and intention among a random sample of vocational high school students (N=553) in Wuhan, China. Tobacco-related perceptions were assessed using the PMT Scale for Adolescent Smoking. Among the total sample, 45% had initiated cigarette smoking, and 25% smoked in the past month. Among those who never smoked, 15% indicated being likely or very likely to smoke in a year. Multiple regression modeling analysis indicated the significance of the seven PMT constructs, the four PMT perceptions and the two PMT pathways in predicting intention to smoke and actual smoking behavior. Overall, perceived rewards of smoking, especially intrinsic rewards, were consistently positively related to smoking intentions and behavior, and self-efficacy to avoid smoking was negatively related to smoking. The current study suggests the utility of PMT for further research examining adolescent smoking. PMT-based smoking prevention and clinical smoking cessation intervention programs should focus more on adolescents' perceived rewards from smoking and perceived efficacy of not smoking to reduce their intention to and actual use of tobacco.


LncRNA SAMD12-AS1 Suppresses Proliferation and Migration of Hepatocellular Carcinoma via p53 Signaling Pathway.
Assessment of lncRNA SAMD12-AS1 expression in liver cancer tissues and cell lines to investigate the underlying molecular mechanisms that regulate liver cancer cell growth, development, invasion, and migration. The lncRNA SAMD12-AS1 expression in tumor tissues of 32 liver cancer patients was measured by real-time PCR, and its effect on the clinicopathological manifestations and liver cancer patients' prognosis was determined. LncRNA SAMD12-AS1 overexpression and knockdown in liver cancer cell lines were established by cell transfection. The effects of lncRNA SAMD12-AS1 knockdown and overexpression on liver cancer cell growth, development, invasion, and migration were determined by MTT, Transwell, and clonogenic assays. Furthermore, its effects on the expression of E-cadherin, vimentin, p53, and p21 in hepatocellular carcinoma cells were determined by Western blot assay. The level of lncRNA SAMD12-AS1 expression in tumor tissues was remarkably higher than that in paracancerous liver tissues (p < 0.01). It was found that the lncRNA SAMD12-AS1 expression was largely correlated with TNM stage of tumor, vascular invasion, and hepatitis B surface (HBs) antigen in liver cancer patients (p < 0.05). Cell function experiments showed that lncRNA SAMD12-AS1 overexpression promoted liver cancer development, migration, and invasion (p < 0.05), while lncRNA SAMD12-AS1 knockdown inhibited the activity of liver cancer cells to invade and migrate (p < 0.05). Western blot analysis showed that overexpression of lncRNA SAMD12-AS1 markedly inhibited p21, p53, and E-cadherin expression and promoted vimentin expression. Conversely, knockdown of lncRNA SAMD12-AS1 significantly promoted p21, p53, and E-cadherin expression and inhibited vimentin expression (p < 0.05). LncRNA SAMD12-AS1 is associated with the TNM stage and vascular invasion of liver cancer. It promotes liver cancer cell development, invasion, and migration by regulating p53 expression. Thus, lncRNA SAMD12-AS1 could be a novel biological target for the treatment of liver cancer.


Prophylactic ephedrine prevents hypotension during spinal anesthesia for Cesarean delivery but does not improve neonatal outcome: a quantitative systematic review.
The objective of this systematic review was to assess the effectiveness and safety of ephedrine compared with control when given prophylactically to prevent hypotension during spinal anesthesia for Cesarean delivery. Randomized, controlled trials obtained through MEDLINE, EMBASE, the Cochrane Controlled Trials Registry, contact with leading experts, and a reference list of published articles were analyzed. The following keywords were utilized: spinal anesthesia, hypotension, Cesarean section, pregnancy complications, pregnancy outcome, fetal outcome, neonatal outcome, umbilical blood cord gases, vasopressor and ephedrine. Clinical trials were considered if they compared prophylactic ephedrine, given by any dose or route, vs control. The 14 clinical trials identified included data from a total of 641 patients. Ephedrine was more effective than control for preventing hypotension (relative risk [RR], 0.73; 95% confidence interval [CI], 0.63 to 0.86). Most importantly, there was no difference in the risk of fetal acidosis, defined as umbilical arterial pH < 7.2 (RR, 1.36; 95% CI, 0.55 to 3.35) or the incidence of low Apgar scores (< 7 or < 8) at one minute (RR, 0.77; 95% CI, 0.29 to 2.06) and five minutes (RR, 0.72; 95% CI, 0.24 to 2.19). Prophylactic ephedrine is more effective than control for preventing hypotension during spinal anesthesia for elective Cesarean delivery but a clinically relevant positive effect on neonatal outcome was not observed. Therefore, the routine use of prophylactic ephedrine to prevent any adverse effects of maternal hypotension following spinal anesthesia for Cesarean delivery is not supported by the current systematic review.


Structures of high and low density amorphous ice by neutron diffraction.
Neutron diffraction with isotope substitution is used to determine the structures of high (HDA) and low (LDA) density amorphous ice. Both "phases" are fully hydrogen bonded, tetrahedral networks, with local order similarities between LDA and ice Ih, and HDA and liquid water. Moving from HDA, through liquid water and LDA to ice Ih, the second shell radial order increases at the expense of spatial order. This is linked to a fifth first neighbor "interstitial" that restricts the orientations of first shell waters. This "lynch pin" molecule which keeps the HDA structure intact has implications for the nature of the HDA-LDA transition that bear on the current metastable water debate.


Drug-Integrating Amphiphilic Nanomaterial Assemblies: 1. Spatiotemporal control of cyclosporine delivery and activity using nanomicelles and nanofibrils.
Immunomodulatory therapies are limited by unavoidable side effects as well as poor solubility, stability, and pharmacokinetic properties. Nanomaterial-based drug delivery may overcome these limitations by increasing drug solubility, site-targeting, and duration of action. Here, we prepared innovative drug-integrating amphiphilic nanomaterial assemblies (DIANA) with tunable hydrophobicity, size, and morphology, and we evaluated their ability to deliver cyclosporine A (CsA) for immunomodulatory applications. We synthesized amphiphilic block copolymers made of poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) and poly(ethylene glycol)-oligo(ethylene sulfide) (PEG-OES) that can self-assemble into solid core nanomicelles (nMIC, with ≈20 nm diameter) and nanofibrils (nFIB, with ≈5 nm diameter and > 500 nm length), respectively. nMIC and nFIB displayed good CsA encapsulation efficiency (up to 4.5 and 2 mg/mL, respectively in aqueous solution), superior to many other solubilization methods, and provided sustained release (>14 and > 7 days for the nMIC and nFIB) without compromising CsA's pharmacological activity. Treatment of insulin-secreting cells with unloaded DIANAs did not impair cell viability and functionality. Both CsA-loaded DIANAs inhibited the proliferation and activation of insulin-reactive cytotoxic T cells in vitro. Subcutaneous injections of CsA-loaded DIANAs in mice provided CsA sustained release, decreasing alloantigen-induced immune responses in the draining lymph node at lower doses and reduced administration frequency than unformulated CsA. While nMIC solubilized higher amounts and provided more sustained release of CsA in vitro, nFIB enhanced cellular uptake and promoted local retention due to slower trafficking in vivo. DIANAs provide a versatile platform for a local immune suppression regimen that can be applied to allogeneic cell transplantation.


Determinants of respirable quartz exposure in farming.
The objectives of this article are to quantify personal respirable quartz exposure on sandy, sandy loam, and clay soil farms and to identify exposure determinants. The methods applied included observing and examining the variables soil type, commodity farmed, activity, process, quartz % in respirable dust, and weather variables. Multiple linear regression was used to identify determinants of respirable quartz concentration and logistic regression was applied to identify determinants of respirable quartz concentration > 50 µg.m-3 (a commonly used reference value of over-exposure). The highest quartz concentration was 626 µg.m-3 and 30%, 22%, and 31% of measurements were > 50 µg.m-3 for sandy, sandy loam, and clay soil farms, respectively. In general, the commodities livestock farming and cereal grains as well as the activity cereal planter operator, decreased humidity on the day of measurement, the mechanical processes, and quartz % in respirable dust (in a confounding way) were associated with higher respirable quartz concentrations (p ≤ 0.10) as well as season (p = 0.14). Variables associated with quartz levels above 50 µg.m-3 were cereal planter operator, increased quartz % in respirable dust, decreased humidity on day of measurement, and increased respirable dust concentration. Cereal planter operator (Multivariate Odds Ratio (OR) 4.56, 95% CI: 1.79-8.89) and levels of quartz % > 10 µg.m-3 (Multivariate OR 6.01, 95% CI: 3.52-9.71 if quartz % > 10 but ≤ 20 µg.m-3, and Multivariate OR 5.32, 95% CI: 2.56-8.34 if quartz % > 20 µg.m-3) were clear determinants of quartz over-exposure. It can therefore be concluded that over-exposure to quartz in farming is possible. Joint influences of more farming characteristics and weather variables should be included, together with soil type in future farming exposure assessments.


[Family participation in the decision making process for life support limitation: paternalism, beneficence and omission].
To analyze and discuss the medical aspects related to the family involvement in the decision making process regarding end of life care to children admitted to the pediatric intensive care unit (PICU). The authors selected articles on end-of-life care published during the last years searching the PubMed, MedLine and LILACS database, with special interest on studies of death conducted in pediatric intensive care units in Brazil, Latin America, Europe and North America, using the following keywords: death, bioethics, PICU, decision-making, terminal care, parents interview and life support limitation (LSL). Several studies have demonstrated the relevance of the family participation in the decision making process regarding LSL. In our region the family participation in this process is not stimulated and valued, ranging from 20%-55%. The authors present a practical sequence for discussing and defining LSL with the families. Despite of the family participation in the decision making process for LSL be legally, morally and ethically accepted in developed countries, this approach is adopted in a very few cases in our region. To explain this difficulty observed among the Brazilian pediatric intensivist, some studies should be conducted in our region.


Structural changes on a molecular basis of canola meal by conditioning temperature and time during pelleting process in relation to physiochemical (energy and protein) properties relevant to ruminants.
The objectives of this study were: (1) To investigate the effects of conditioning temperature (70, 80, 90°C), time (30, 60 sec), and interaction (temperature × time) during the pelleting process on internal protein molecular structure changes of the co-products; (2) To identify differences in protein molecular structures among pellets that were processed under different conditions, and between unprocessed mash and pellets; 3) To quantify protein molecular structure changes in relation to predicted energy and protein utilization in dairy cows. The final goal of this program was to show how processing conditions changed internal feed structure on a molecular basis and how molecular structure changes induced by feed processing affected feed milk value in dairy cows. The hypothesis in this study was that processing-induced protein inherent structure changes affected energy and protein availability in dairy cattle and the sensitivity and response of protein internal structure to the different pelleting process conditions could be detected by advanced molecular spectroscopy. The protein molecular structures, amides I and II, amide I to II ratios, α-helix structure, β-sheet structure, and α to β structure ratios, were determined using the advanced vibrational molecular spectroscopy (ATR-FT/IR). The energy values were determined using NRC2001 summary approach in terms of total digestible nutrients, metabolizable and net energy for lactation. The protein and carbohydrate subfactions that are related to rumen degradation characteristics and rumen undegraded protein supply were determined using updated CNCPS system. The experiment design was a RCBD and the treatment design was a 3x2 factorial design. The results showed that pelleting induced changes in protein molecular structure. The sensitivity and response of protein inherent structure to the pelleting depended on the conditioning temperature and time. The protein molecular structure changes were correlated (P < 0.05) with energy values and protein subfractions of the pelleted co-product. The results indicated that the protein internal molecular structure had significant roles in determining energy and protein nutritive values in dairy cows. Multi-regression study with model variables selection showed that the energy and protein profiles in pelleted co-products could be predicted with the protein molecular structure profiles. This approach provides us a relatively new way to estimate protein value in dairy cows based on internal protein molecular structure profile.


Posterior mediastinal arteriovenous malformation with atypical color Doppler sonographic findings.
An arteriovenous malformation (AVM) is an anomaly of capillary development that results in a direct connection between branches of an artery and veins, with no intervening capillary network. A definite diagnosis of AVM is usually made with angiography. We report the case of a posterior mediastinal AVM found on routine sonography in a 64-year-old woman with neglected hypertension and severe back pain. Color Doppler imaging showed 2 adjoined vascular structures without a typical mosaic-like flow pattern, and spectral Doppler analysis showed low-resistance flow and arteriovenous shunting in 2 adjoined vascular structures. The diagnosis was subsequently confirmed by angiography. Because disastrous bleeding could result if needle biopsy were performed inadvertently in the case of a suspected mediastinal AVM, we suggest that color Doppler sonography be attempted if there is an adequate acoustic window.


Supramolecular cancer photoimmunotherapy based on precise peptide self-assembly design.
Combinational photoimmunotherapy (PIT) is considered to be an ideal strategy for the treatment of highly recurrent and metastatic cancer, because it can ablate the primary tumor and provide in situ an autologous tumor vaccine to induce the host immune response, ultimately achieving the goal of controlling tumor growth and distal metastasis. Significant efforts have been devoted to enhancing the immune response caused by phototherapy-eliminated tumors. Recently, supramolecular PIT nanoagents based on precise peptide self-assembly design have been employed to improve the efficacy of photoimmunotherapy by utilizing the stability, targeting capability and flexibility of drugs, increasing tumor immunogenicity and realizing the synergistic amplification of immune effects through multiple pathways and collaborative strategy. This review summarizes peptide-based supramolecular PIT nanoagents for phototherapy-synergized cancer immunotherapy and its progress in enhancing the effect of photoimmunotherapy, especially focusing on the design of peptide-based PIT nanoagents, the progress of bioactive peptides combined photoimmunotherapy, and the synergistic immune-response mechanism.


Topographic EEG mapping of the relaxation response.
The purpose of this study was to assess the central nervous system effects of the relaxation response (RR) in novice subjects using a controlled, within- subjects design and topographic EEG mapping as the dependent measure. Twenty subjects listened to a RR and control audiotape presented in a counterbalanced order while EEG was recorded from 14 scalp locations. The RR condition produced greater (p < .0164) reductions in frontal EEG beta activity relative to the control condition. No significant differences were observed for any other frequency band or scalp region. These findings suggest that elicitation of the RR produces significant reductions in cortical activation in anterior brain regions in novice subjects.


Urea cycle disorders.
Most patients with urea cycle disorders who present as neonates, do so with deteriorating feeding, drowsiness and tachypnoea, following a short initial period when they appear well. The plasma ammonia should be measured at the same time as the septic screen in such patients. Ammonia levels above 200 micromol/l are usually caused by inherited metabolic diseases and it is essential to make a diagnosis for genetic counselling, even if the patients die. The aim of treatment is to lower the ammonia concentrations as fast as possible. Sodium benzoate, sodium phenylbutyrate and arginine can exploit alternative pathways for the elimination of nitrogen but haemodialysis or haemofiltration should be instituted if ammonia concentrations are >500 micromol/l or if they do not fall promptly. Long-term management involves drugs, dietary protein restriction and use of an emergency regimen during illness. Severe hyperammonaemia is usually associated with irreversible neurological damage, particularly if levels have been above 800 micromol/l for >24 hours, and the option of withdrawing treatment should be discussed with the family.


[Cross-sectional visualization of regurgitant jet by color flow mapping to evaluate aortic regurgitation].
In the noninvasive evaluation of aortic regurgitation by Doppler echocardiography, flow mapping of the aortic regurgitant jet using the long-axis approach is of limited value in cases of combined mitral stenotic lesions. This is because the transmitral flow yields flow disturbances in the left ventricle, making it difficult to identify the extent of the aortic regurgitant jet. To overcome these limitations, the severity of aortic regurgitation was evaluated using the cross-sectional area of the aortic regurgitant jet at the level of the aortic valve as visualized by color flow imaging technique. The study population consisted of 16 patients with aortic regurgitation (10 with pure aortic regurgitation, five with superimposed mitral stenosis, and one with mitral valve replacement). Three normal subjects served as controls. The cross-section of the aortic regurgitant jet was visualized as a mosaic of yellow and blue in all patients with aortic regurgitation, but not in any of the controls. Planimetric measurements of the cross-sectional area of the regurgitant jet (J) and the aortic annulus area (Ao) were performed, and the Doppler parameter, J/Ao, was calculated. As a reference, the aortic regurgitant fraction (RF) was calculated from Doppler measurements of systolic aortic and pulmonary flows (AF and PF); RF (%) = (AF - RF)/AF x 100. The Doppler parameter, J/Ao, correlated well with the Doppler measurement of RF (r = 0.82, p less than 0.005), irrespective of the presence of associated mitral lesions. Thus, the cross-sectional area of the aortic regurgitant jet determined by color flow imaging technique would be a useful estimate of the severity of aortic regurgitation, even in the presence of associated mitral stenotic changes.


Significance of broad-spectrum racemases for the viability and pathogenicity of Aeromonas hydrophila.
Aim: To investigate the function of broad-spectrum racemases in Aeromonas hydrophila (BsrA). Results: The A. hydrophila gene encoding BsrA (bsr) mutants (AHΔbsr) exhibited a significant decrease in growth, motility, extracellular protease production and biofilm formation compared with the wild-type. Furthermore, bsr gene knockout instigated cell wall damage compared with the wild-type strains. The survival rate and replication capability in the blood and organs of the AHΔbsr-infected mice were significantly decreased. The degree of tissue injury in the AHΔbsr-infected group was lower than that of the wild-type-infected group. Moreover, there was a significant decrease in the expression of 12 AHΔbsr virulence genes. Conclusion: The bsr gene is essential for the viability and virulence of A. hydrophila.


MicroRNA regulation of melanoma progression.
The aetiology of melanoma, the most lethal form of skin cancer, is complex, involving both genetic and environmental components. Over the past decade, many genetic alterations affecting melanoma development have been identified and more recently a new epigenetic level of regulation has increasingly been explored. MicroRNA (miRNA)-mediated epigenetic regulation of tumour suppressor genes and oncogenes has been shown to play a central role in melanomagenesis. Over the past few years, many studies combining miRNA expression arrays and quantitative reverse transcriptase-PCR assays have identified different miRNAs deregulated during melanoma progression. Several groups have focused their efforts on understanding the functional role of these different miRNAs in melanoma, identifying their direct targets and elucidating their mechanisms of regulation. This review summarizes the present knowledge of miRNA dysregulation in melanoma. On the basis of the current literature, we present a network of miRNA interactions involved in melanoma progression. Some of these key miRNAs may have utility as diagnostic markers or in targeted treatments.


Characterization of genomic regions directing the cell-specific expression of the mouse aldose reductase gene.
Aldose reductase (AR), an enzyme implicated in the pathogenesis of diabetic complications, is highly expressed in such target organs of complications as the lens and peripheral nerve of experimental animals. In mouse, however, a very low level of the transcript was expressed in these tissues. To explore the unique expression pattern of AR in mice, genomic structure and upstream regions regulating the basal expression of the enzyme were determined. In NIH3T3 cells, a -1.1-kb upstream portion demonstrated the highest promoter activity. The ability to drive the luciferase reporter gene was reduced by 56% when the -1.1/-0.86-kb region was deleted. In Chinese hamster ovary (CHO) cells, deletion up to -0.67 kb did not affect basal promoter activity. The activity in CHO cells was reduced by 73% when the -0. 67/-0.24-kb region was deleted. These findings indicate that a genomic region directing the cell-specific transcription of the mouse AR gene exists.


Nociceptin/orphanin FQ modulates the cardiovascular, but not renal, responses to stress in spontaneously hypertensive rats.
1. The central administration of the endogenous opioid-like peptide nociceptin/orphanin FQ (N/OFQ) produces marked cardiovascular depressor and renal sympathoinhibitory responses in conscious animals. These findings are evidence that central N/OFQ may modulate the cardiovascular and renal responses to acute environmental stress. 2. The changes in cardiovascular and renal function produced by intracerebroventricular (i.c.v.) N/OFQ were measured in conscious spontaneously hypertensive rats (SHR) under basal conditions and during the acute environmental stimulus of air jet stress. 3. In SHR, central N/OFQ produced profound hypotensive, bradycardic, renal sympathoinhibitory (delayed) and water-diuretic effects by a pathway that does not involve activation of central alpha2-adrenoceptors or classical opioid receptors. 4. Intracerebroventricular injection of N/OFQ prevented the pressor response and blunted the tachycardia to air jet stress. A similar renal sympathoexcitatory and antinatriuretic response was observed in conscious SHR during air stress, before and after i.c.v. N/OFQ. 5. These findings are evidence that, in conscious SHR, i.c.v. N/OFQ selectively inhibited the neural responses to air jet stress by attenuating sympathetic outflow to the heart and, potentially, vasculature, but not to the kidneys. Central endogenous N/OFQ systems may be activated and contribute to regional changes in sympathetic outflow during acute stress.


Controlling the kinetics of viscoelastic phase separation through self-assembly of spherical nanoparticles or block copolymers.
Viscoelastic phase separation (VPS) can produce a network structure of the minor phase, which needs to be stabilized for designing a heterogeneous structure with desired mechanical and electrical functions. In this work, we investigate the stabilization of the VPS-induced network structure in a dynamically asymmetric PS/PVME blend by incorporation of a SEBS-g-MA block copolymer or dimethyldichlorosilane modified nanosilica. The addition of SEBS-g-MA retards the volume shrinking process and slows down the kinetics of phase separation due to its localization at the PS/PVME interfaces. Consequently, in the later stage of VPS, phase inversion occurs at longer times with respect to the neat blend due to the decreased interfacial tension. In contrast, hydrophobic nanoparticles self-assemble in the bulk of PS-rich phase and restrain the dynamics of polymer chains enhancing the dynamic asymmetry of the system. The efficiency of nanoparticles in controlling the kinetics of phase separation is found to be superior compared to block copolymer-based compatibilizers indicating the significance of chain dynamics. Moreover, beyond a critical nanoparticle volume fraction, phase separation is pinned due to particle percolation within the PS-rich phase, yielding a kinetically trapped VPS-induced network structure.


Multiple imputation to estimate the association between eyes in disease progression with interval-censored data.
In many ophthalmologic studies, progression of diseases such as diabetic retinopathy, age-related maculopathy, cataract, and glaucoma is only noted when each eye is examined at intervals that commonly vary between subjects. Such data are often analysed using continuous time survival methods with observed progression assumed to occur at the end of the interval. Tied times of progression can lead to substantial bias in estimation of the association between progression in right and left eyes. We describe a multiple imputation strategy to create multiple data sets without ties, based on drawing interval-censored progression times from a parametric gamma frailty model that accounts for continuous and discrete covariates. We illustrate the method with data from 478 patients with insulin-dependent diabetes mellitus who were followed for progression of diabetic retinopathy in the Sorbinil Retinopathy Trial. Resolution of tied failure times allows for valid estimation of the hazard of progression in one eye given the progression status of the other eye. A simulation study suggests that the method performs well. Results highlight the advantage of multiple imputation that data imputed under one model can be analysed under several alternative models.


Development of an isotopic stream index connecting physiographic characteristics of montane catchments.
This study is to develop an isotopic catchment-effect index (CEI) connecting the physiographic characteristics of stream catchments. A CEI, describing the extent of difference in stable water isotopic compositions (δ values) between stream water and local precipitation at any given sampling site, can help in judging whether water resource management should be focused on upstream regions of streams or local hydrology issues. To establish the isotopic CEI, this study measured δ values of stream water and derived δ18 O of local precipitation based on regional isotopic altitude gradient at montane catchments of various sizes. Results indicate that the CEI is strongly related to catchment physiographic characteristics, such as length of main stream, mean area, mean elevation, perimeter, and slope. These characteristics are considered important indices of streamflow. Based on mathematical regression modeling describing the relationships between CEI and respective physiographic factors, CEI values can predict respective physiographic factors and vice versa. Moreover, according to the multiple equations derived in this study, catchments of larger size and steeper slope give elevated CEI values while greater stream length reduces the CEI's value. A greater CEI value indicates that local stream water is principally sourced from upstream reaches rather than contributions from local precipitation. In addition, CEI values are greater in winter than in summer resulting from monsoon effect. Consequently, this study establishes CEI as a useful descriptor of the physiographic characteristics of catchments.


The health-care practices of Vietnamese-Canadian women: cultural influences on breast and cervical cancer screening.
Breast and cervical cancer are major contributors to morbidity and mortality among Vietnamese-Canadian women. Vietnamese women are at risk due to their low participation rate in screening programs for these cancers. The purpose of this exploratory qualitative study, informed by Kleinman's Exploratory Model of Health and Illness, was to explore the participation of Vietnamese-Canadian women in screening for breast and cervical cancer; the appropriateness of current cancer-prevention services for Vietnamese women; and the influence of social, cultural, political, historical, and economic factors, shaped by race, gender, and class, on the screening practices of Vietnamese-Canadian women. Fifteen Vietnamese-Canadian women and 6 health-care providers were interviewed. Analysis revealed that several factors influenced the women's participation in cancer screening. This paper reports on the process by which cultural knowledge and beliefs contributed to the women's health-care practices. The study revealed that the following cultural factors influenced the women's level of participation in screening programs for breast and cervical cancer: cultural knowledge and values with regard to women's bodies, conceptualization of health and illness, and beliefs and values concerning the patient/health-care provider relationship. The author offers recommendations on the promotion of screening for breast and cervical cancer among Vietnamese-Canadian women.


Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague-Dawley Rat.
There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs, and other researchers in understanding and interpreting chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically stained tissues for estrogen, progesterone, and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically induced mammary gland anomalies that may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylstilbestrol, or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated, and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies.


Humidity-Controlled Dynamic Engineering of Buckling Dimensionality in MoS2 Thin Films.
Dynamic engineering of buckling deformation is of vital importance as it provides multiphase modulation of thin film devices. In particular, dynamic switch of buckles between one-dimensional (1D) and two-dimensional (2D) configurations in a single film system on rigid substrates is intriguing but very challenging. The current approach to changing buckling configuration is mainly achieved by varying the built-in stress at the film-substrate interface, but it is difficult to realize dynamic engineering on rigid substrates. Herein, we report a dynamic engineering of buckling deformation in MoS2 thin films by humidity-tuned interfacial adhesion. With the change of humidity, the MoS2 thin films deform from 1D telephone-cord buckles to 2D web-like buckles due to the hydrophilic nature of both MoS2 and substrate. Such 1D-to-2D evolution of buckles is attributed to the weakened interfacial adhesion of mixed deformation modes induced by humidity, which is verified by finite-element modeling. These buckled films further find potential applications as patterned templates for liquid condensation and sensing units for tactile sensors. Our work not only demonstrates the humidity-controlled dimensionality engineering of buckles in MoS2 thin films but also sheds light on the functional applications of buckled films based on their profile features.


Eleven trinucleotide repeat loci that map to chromosome 12 excluded from involvement in the pathogenesis of bipolar disorder.
The hypothesis that one or more genes containing expanded trinucleotide repeats contribute to the pathogenesis of bipolar disorder has received support from three independent studies demonstrating that bipolar patients tend to have larger CAG/CTG repeat expansion detection products than controls. In an attempt to identify the specific expanded CAG/CTG locus or loci which are associated with bipolar disorder, we determined repeat size at CAG/CTG loci mapping to candidate regions for bipolar disorder. Recent linkage studies suggest the existence of a bipolar susceptibility gene on chromosome 12q23-q24.1 in the region of the Darier's disease (DAR) gene. In this study we report our findings from 11 loci which map to chromosome 12, including CAG repeat polymorphisms within the genes SCA2 and ASH1. We conclude that all of these loci are excluded as candidates for CAG/CTG repeat expansion in bipolar disorder.


The resuscitation status of a patient: a constant dilemma.
Since the first description of closed chest cardiac massage in 1960, healthcare has evolved considerably. The modern-day skill and expertise of both doctors and nurses in cardiopulmonary resuscitation (CPR) techniques are now supported by an advanced medical technology. Indeed, CPR is now perceived as the definitive life-saving procedure. However, paradoxically, it has also prolonged the process of dying and denied many patients a dignified and peaceful death. It has also denied the patient's loved ones the opportunity to be present at the time of death. The main focus of this article is to explore the current ethical issues in clinical practice relating to determining the resuscitation status of patients. Attention will also be given to patient advocacy, and the nurse's role in supporting this concept.


Low-grade clear cell eccrine carcinoma.
Two patients had facial tumors that had a distinctive microscopic appearance. Each consisted of multiple nests of glycogen-filled clear cells dispersed in the dermis and associated with a hyalinized, collagenous stroma. There were also ductular features suggestive of eccrine differentiation. The lesions had a locally infiltrative microscopic appearance, and one involved the subcutaneous fat and skeletal muscle. Although neither tumor has recurred following excision, we believe that they are low-grade eccrine carcinomas and that they may represent a distinctive, albeit rare, subtype of adnexal neoplasm.