Pan-genomic analysis to redefine species and subspecies based on quantum discontinuous variation: the Klebsiella paradigm.
Various methods are currently used to define species and are based on the phylogenetic marker 16S ribosomal RNA gene sequence, DNA-DNA hybridization and DNA GC content. However, these are restricted genetic tools and showed significant limitations. In this work, we describe an alternative method to build taxonomy by analyzing the pan-genome composition of different species of the Klebsiella genus. Klebsiella species are Gram-negative bacilli belonging to the large Enterobacteriaceae family. Interestingly, when comparing the core/pan-genome ratio; we found a clear discontinuous variation that can define a new species. Using this pan-genomic approach, we showed that Klebsiella pneumoniae subsp. ozaenae and Klebsiella pneumoniae subsp. rhinoscleromatis are species of the Klebsiella genus, rather than subspecies of Klebsiella pneumoniae. This pan-genomic analysis, helped to develop a new tool for defining species introducing a quantic perspective for taxonomy.


Level of physical activity and aerobic capacity associate with quality of life in patients with temporal lobe epilepsy.
Epilepsy is more than seizures and includes a high risk of comorbidities and psychological disorders, leading to poor quality of life (QOL). Earlier studies have showed a sedentary lifestyle in people with epilepsy (PWE), which could contribute to poorer health and psychological problems. The purpose of the present study was to compare habits of physical activity (PA), aerobic capacity, and QOL between PWE and healthy controls in order to identify the necessity of intervention of habits and information on physical exercise (PE) and to better understand the importance of PE for PWE. The study included 38 patients with temporal lobe epilepsy and 20 normal controls. Both groups answered the WHOQOL-Bref, which assesses the level of QOL, and IPAQ to evaluate the level of PA. In addition, they were submitted to a treadmill maximal cardiopulmonary effort test to identify physical capacity. The continuous variables were compared between groups by t-test and a general linear model, and the frequencies were compared by Chi-Square test through SPSS software. There was no difference in the level of PA between groups by questionnaire evaluation. However, there were significant differences in overall QOL, physical health, and level of PA in relation to work and physical capacity between groups; controls demonstrated better scores than PWE. Controls presented better physical capacity than PWE by cardiopulmonary effort test. According to intra-group analyses, PWE who were physically active had better QOL than inactive PWE. The study concluded that questionnaires about PE may not be the best instrument of evaluation, as demonstrated by the discrepancy of results compared to the validated objective cardiopulmonary evaluation of level of PA and physical capacity in this study.


How important is local food to organic-minded consumers?
The study deals with German consumers' attitudes towards organic food and local food, their food purchase behaviour and their personal characteristics. The purpose is to investigate the differences in attitudes and willingness-to-pay values between consumers who consider the organic production of food (very) important and those who consider it less important. This study combines a consumer survey with an in-store, discrete choice experiment. In the analysis, findings from the consumer survey were related to the choices made by consumers in the experiment. Consumers' preferences and willingness-to-pay values were estimated through random parameter logit modelling. Organic-minded consumers (i.e. those who regarded organic food production as (very) important in the survey) have stronger preferences and estimated willingness-to-pay values for organic as well as local products. Locally produced food, as opposed to food from neighbouring countries or non-EU countries, is preferred over organically produced food by both consumer groups which demonstrates that organic-minded consumers do not only consider organic food production as important, but also value local food production in a purchase situation. Hence, it can be assumed that local food production complements organic food production for the group of organic-minded consumers. This contribution is the first study dealing with local and organic food purchase behaviour in Germany that examines four different products and is carried out in rural as well as urban locations in four different regions. Due to the application of a choice experiment including no-choice options and binding purchase decisions, the results are expected to be closer to real purchase situations than results of direct questioning and choice experiments in online applications.


Feline urine metabolomic signature: characterization of low-molecular-weight substances in urine from domestic cats.
Objectives This aim of this study was to characterize the composition and content of the feline urine metabolome. Methods Eight healthy domestic cats were acclimated at least 10 days before starting the study. Urine samples (~2 ml) were collected by ultrasound-guided cystocentesis. Samples were centrifuged at 1000 × g for 8 mins, and the supernatant was analyzed by gas chromatography/time-of-flight mass spectrometery. The urine metabolome was characterized using an untargeted metabolomics approach. Results Three hundred and eighteen metabolites were detected in the urine of the eight cats. These molecules are key components of at least 100 metabolic pathways. Feline urine appears to be dominated by carbohydrates, carbohydrate conjugates, organic acid and derivatives, and amino acids and analogs. The five most abundant molecules were phenaceturic acid, hippuric acid, pseudouridine phosphate and 3-(4-hydroxyphenyl) propionic acid. Conclusions and relevance This study is the first to characterize the feline urine metabolome. The results of this study revealed the presence of multiple low-molecular-weight substances that were not known to be present in feline urine. As expected, the origin of the metabolites detected in urine was diverse, including endogenous compounds and molecules biosynthesized by microbes. Also, the diet seemed to have had a relevant role on the urine metabolome. Further exploration of the urine metabolic phenotype will open a window for discovering unknown, or poorly understood, metabolic pathways. In turn, this will advance our understanding of feline biology and lead to new insights in feline physiology, nutrition and medicine.


Effect of temperature on the growth and cell wall chemistry of a facultative thermophilic Bacillus.
The morphology and cell wall composition of Bacillus coagulans, a facultative thermophile, were examined as a function of growth temperature. The morphology of the organism varied when it was grown at different temperatures; at 37 C the organism grew as individual cells which increased in length with increasing growth temperature. At 55 C it grew in long chains of cells. Cell wall prepared from cells grown at 37 C contained 44% teichoic acid by weight, whereas cells grown at 55 C contained 29% teichoic acid. Teichoic acid from these cells was a polymer of glycerol phosphate containing galactose and ester alanine. The ratio of ester alanine to phosphate was significantly higher in cell walls and teichoic acid from 37 C-grown cells compared with those from 55 C-grown cells. Other differences observed were that cells grown at 55 C contained a lower level of autolytic ability, produced cell walls which bound more Mg(2+), and contained less peptide cross-bridging in its peptidoglycan layer than cells grown at 37 C.


Predictors of failure in timely tuberculosis treatment completion, United States.
The US tuberculosis (TB) surveillance system. To examine failure in timely TB treatment completion to identify interventions toward achieving the national goal of ≥ 93% treatment completion in ≤ 12 months among patients eligible for 6-9 month regimens. We examined 1993-2006 trends in timely treatment completion; for 2006 cases, we used Poisson regression to assess predictors for failure in timely completion. Timely treatment completion improved from 64% in 1993 to 84% in 2006, with similar trends among foreign- and US-born persons and racial/ethnic subgroups. Annual increases in timely completion were ≤ 1 percentage point during 1998-2006. Subpopulations at highest risk for failure in timely completion were persons with combined pulmonary and extra-pulmonary disease (foreign-born adjusted RR [aRR] 3.25, 95%CI 2.47-4.28; US-born aRR 2.75, 95%CI 1.98-3.83) or incarceration (foreign-born aRR 2.30, 95%CI 1.80-2.93; US-born aRR 1.71, 95%CI 1.36-2.14). Homelessness and human immunodeficiency virus infection were other risk factors. Particular attention to timely completion is needed for subpopulations requiring strong medical expertise in TB management and those at risk for treatment non-adherence, especially if foreign-born. Understanding and addressing causes of delayed completion and improving documentation of treatment completion among all cases will be crucial to achieving the US goal.


[Antistressor effect of delta-sleep-inducing peptide in hypokinetic stress].
The influence of DSIP injection on the levels of neurotransmitters during hypokinetic stress was studied. It was shown that hypokinesia produced considerable changes in the levels of GABA glutamate, aspartate and homocarnosine. The injection of DSIP normalized the level of neurotransmitter amino acids. Administration of DSIP also reduced stress-induced changes in the activity of enzymes of GABA metabolism. Stress protective effect of DSIP was also demonstrated by normalising of the POL of lipids in brain.


Successful transapical implantation of an Edwards Sapien valve within an insufficient aortic CoreValve prosthesis: an initial experience.
Transcatheter aortic valve implantation (TAVI) has become an emerging alternative for high-risk patients with aortic stenosis unsuitable for surgical intervention. We report the case of a 26-mm Edwards Sapien valve (Edwards Lifesciences, Irvine, CA) implanted into an insufficient 29-mm CoreValve prosthesis (Medtronic Inc, Minneapolis, MN) 1 year after implantation using the transapical approach in a 59-year-old man. Transesophageal echocardiography showed severe paravalvular regurgitation and computed tomography revealed the CoreValve to be located slightly below the aortic annulus with evidence of underdeployment. The balloon-expandable Sapien system caused a better expansion of the underdeployed CoreValve and the pericardial skirt adequately covered the leakage. The paravalvular regurgitation disappeared and the patient recovered.


The Association between Food Security and Store-Specific and Overall Food Shopping Behaviors.
Food security is a severe problem in the United States. Few studies have examined its relationship with food shopping behaviors. This study aimed to examine the association between food security and store-specific and overall food shopping among residents of low-income neighborhoods. We conducted a cross-sectional study. Five hundred twenty-seven households were recruited from two counties in South Carolina from November 2013 to May 2014, and 474 households were included in the final analysis. Food security was assessed using the 18-item US-Household Food Security Module questionnaire, and classified into three categories: high or marginal food security (FS), low food security (LFS), and very low food security (VLFS). Store-specific shopping behaviors including frequency, store type, and transportation were queried via in-person interview for the three most-frequented grocery stores. Distance from participants' homes to their reported stores was calculated using Geographic Information Systems. Multivariate linear regression for analyses of distance and frequency and multinomial/ordinary logistic regression for analyses of store type and transportation were used. Compared to FS participants, a significantly higher proportion of VLFS participants reported a convenience/dollar store as their most-frequented store (odds ratio [OR] 2.31, 95% CI 1.08 to 4.95) or a lack of transportation (OR 2.04, 95% CI 1.25 to 3.33). They also shopped less frequently (b=-.31, P=0.03) at their third most-frequented store and traveled fewer total miles for shopping (b=-4.71, P=0.04). In analyses considering all stores jointly, LFS participants had lower odds of shopping at both supermarkets and convenience/dollar stores (OR 0.44, 95% CI 0.21 to 0.91) compared to food-secure residents. The current findings suggest that households with VLFS tend to shop more frequently in stores that have less-healthful options, such as convenience/dollar stores. These findings lend support to ongoing community and policy interventions aimed at improving food access among food-insecure populations.


Changes in regional cerebral blood flow distribution during postexercise hypotension in humans.
This investigation compared patterns of regional cerebral blood flow (rCBF) during exercise recovery both with and without postexercise hypotension (PEH). Eight subjects were studied on 3 days with randomly assigned conditions: 1) after 30 min of rest; 2) after 30 min of moderate exercise (M-Ex) at 60-70% heart rate (HR) reserve during PEH; and 3) after 30 min of light exercise (L-Ex) at 20% HR reserve with no PEH. Data were collected for HR, mean blood pressure (MBP), and ratings of perceived exertion and relaxation, and rCBF was assessed by use of single-photon-emission computed tomography. With the use of ANOVA across conditions, there were differences (P < 0.05; mean +/- SD) from rest during exercise recovery from M-Ex (HR = +12 +/- 3 beats/min; MBP = -9 +/- 2 mmHg), but not from L-Ex (HR = +2 +/- 2 beats/min; MBP = -2 +/- 2 mmHg). After M-Ex, there were decreases (P < 0.05) for the anterior cingulate (-6.7 +/- 2%), right and left inferior thalamus (-10 +/- 3%), right inferior insula (-13 +/- 3%), and left inferior anterior insula (-8 +/- 3%), not observed after L-Ex. There were rCBF decreases for leg sensorimotor regions after both M-Ex (-15 +/- 4%) and L-Ex (-12 +/- 3%) and for the left superior anterior insula (-7 +/- 3% and -6 +/- 3%), respectively. Data show that there are rCBF reductions within specific regions of the insular cortex and anterior cingulate cortex coupled with a postexercise hypotensive response after M-Ex. Findings suggest that these cerebral cortical regions, previously implicated in cardiovascular regulation during exercise, may also be involved in PEH.


Quantitative analysis of fetal behavioural patterns with real-time sonography and the actocardiograph.
Fetal heart rate patterns, isolated and clustered fetal movements, fetal eye and breathing movements were analysed simultaneously and semiquantitatively in 20 uncomplicated pregnancies in accordance with the classification of fetal behavioural states by Nijhuis and with the aid of two ultrasound scanners and the actocardiograph. According to our own definition state 1 F, 2 F, 3 F and 4 F were observed in 29, 34, 8, and 14% of the registration time. In 15% no state could be identified. Using only the actocardiograph state 1 F, 2 F and 4 F could be identified in around 75%. Periods without a state diagnosis could not be assessed by the actocardiograph alone. The combination of the actocardiograph and one ultrasound scanner for the observation of fetal eye movements reached a similar diagnostic accuracy as the polygraphic monitoring with two ultrasound scanners.


PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer.
Pyruvate kinase M2 (PKM2) is a key kinase of glycolysis and is characteristic of all proliferating cells. The role of PKM2 in gastric cancer (GC) is still ambiguous and yet to be determined. To better understand the role of PKM2 in both the migration and invasion of GC, we measured the expression of PKM2 in GC cell lines using qRT-PCR and western blot. The prognostic value of PKM2 was analyzed by Immunohistochemistry in a cohort containing 88 GC patients. PKM2 was knocked down by the short hairpin RNA plasmid vector in NCI-N87 and BGC-823 cells, and the biological behavior and downstream signaling pathways were also investigated in vitro. Subcutaneous xenografts and pulmonary metastases models were constructed in nude mice to compare the differences in tumorgenesis and metastasis after Knockdown of PKM2. Our results obtained from in vitro cell biological behavior, in vivo tumorigenicity studies, and primary GC samples revealed an oncogenic role for PKM2 in GC. Furthermore, for those GC patients who received radical resection, PKM2 might serve as a novel prognostic biomarker and target which would allow for a brand new treatment strategy for GC in the clinical settings.


Contingent non-invasive prenatal testing: an opportunity to improve non-genetic aspects of fetal aneuploidy screening.
Several countries today struggle with suboptimal performances in many aspects of the fetal aneuploidy screening process and consider introducing non-invasive prenatal screening (NIPT) as a solution. In this study, costs and benefits of different scenarios for contingent NIPT screening in Belgium are evaluated with respect to partial redistribution of the national screening budget into quality improving measures for those screening activities that will be maintained when full NIPT screening is implemented. Data from the Belgian National Institute for Health and Disability Insurance and the Study Centre for Perinatal Epidemiology were used in modeled calculations of medical and economic impact of NIPT after prior conventional screening (1) at thresholds 1:300 and 1:600, and (2) at current and improved screening sensitivity. Contingent NIPT screening under current screening conditions would maintain today's 7.9(0)/000 live birth prevalence of Down syndrome (LBPD) at an 11% reduction of overall short-term costs. Lowering the screening threshold to 1:600 or increasing sensitivity by 10% would reduce LBPD to 7(0)/000 at a maximum 3% increase of overall short-term costs. Today, in Belgium and in many other countries, full NIPT screening is considered too expensive for immediate introduction into the national fetal aneuploidy screening program. Contingent NIPT screening is both clinically and economically beneficial. A temporary contingent NIPT protocol allows for reinvesting economic savings into optimization of those screening aspects, which are to be maintained in parallel to full NIPT screening.


5-Lipoxygenase plays an essential role in 4-HNE-enhanced ROS production in murine macrophages via activation of NADPH oxidase.
4-Hydroxynonenal (HNE) mediates oxidative stress-linked pathological processes; however, its role in the generation of reactive oxygen species (ROS) in macrophages is still unclear. Thus, this study investigated the sources and mechanisms of ROS generation in macrophages stimulated with HNE. Exposure of J774A.1 cells to HNE showed an increased production of ROS, which was attenuated by NADPH oxidase as well as 5-lipoxygenase (5-LO) inhibitors. Linked to these results, HNE increased membrane translocation of p47phox promoting NADPH oxidase activity, which was attenuated in peritoneal macrophages from 5-LO-deficient mice as well as in J774A.1 cells treated with a 5-LO inhibitor, MK886 or 5-LO siRNA. In contrast, HNE-enhanced 5-LO activity was not affected by inhibition of NADPH oxidase. Furthermore, leukotriene B(4), 5-LO metabolite, was found to enhance NADPH oxidase activity in macrophages. Altogether, these results suggest that 5-LO plays a critical role in HNE-induced ROS generation in murine macrophages through activation of NADPH oxidase.


Current smoking improves ulcerative colitis patients' disease behaviour in the northwest of China.
The incidence of ulcerative colitis has increased tremendously over the past few decades, and caused much more attention in China. Several studies have revealed that both environmental and genetic factors play crucial roles in the formation and development of this disease. Among the environmental factors, the smoking condition is highly significant. Although current smoking has been associated with a protective effect on both the development and progression of ulcerative colitis (UC), the clinical characteristics of UC patients with current smoking in China is still unclear. To clarify the relationship between current smoking and the UC in the northwest of China, patients diagnosed with ulcerative colitis in the General Hospital of Ningxia Medical University from 2003.03 to 2012.09 were assessed. Data were collected about clinical features, cigarette smoking conditions, disease location, and therapeutic requirements. A total of 421 patients were included in this study, at diagnosis, 341 (81%) patients were non-smokers, and the current smokers amounted to 80 (19%). As for disease location, there were no differences between the current smokers and non-smokers regarding proctitis and extensive colitis, but the current smokers had less left-sided colitis than non-smokers (p = 0.049). Based on the Modified Mayo score, heavier smokers had lower scores than other smokers and non-smokers. For the therapeutic requirements, current smokers needed fewer corticosteroids than non-smokers (p = 0.048). We found that current smoking is closely associated with a protective factor for UC.


Single-Molecule Observation Reveals Spontaneous Protein Dynamics in the Nucleosome.
Structural dynamics of a protein molecule is often critical to its function. Single-molecule methods provide efficient ways to investigate protein dynamics, although it is very challenging to achieve a millisecond or higher temporal resolution. Here we report spontaneous structural dynamics of the histone protein core in the nucleosome based on a single-molecule method that can reveal submillisecond dynamics by combining maximum likelihood estimation and fluorescence correlation spectroscopy. The nucleosome, comprising ∼147 bp DNA and an octameric histone protein core consisting of H2A, H2B, H3, and H4, is the fundamental packing unit of the eukaryotic genome. The nucleosome imposes a physical barrier that should be overcome during various DNA-templated processes. Structural fluctuation of the nucleosome in the histone core has been hypothesized to be required for nucleosome disassembly but has yet to be directly probed. Our results indicate that at 100 mM NaCl the histone H2A-H2B dimer dissociates from the histone core transiently once every 3.6 ± 0.6 ms and returns to its position within 2.0 ± 0.3 ms. We also found that the motion is facilitated upon H3K56 acetylation and inhibited upon replacing H2A with H2A.Z. These results provide the first direct examples of how a localized post-translational modification or an epigenetic variation affects the kinetic and thermodynamic stabilities of a macromolecular protein complex, which may directly contribute to its functions.


[The expansion characters of a quick-heating gypsum-bonded investment under different heating methods].
To study the effects of different heating timings after mixing the materials and different heating methods on the expansion characters of a quick-heating gypsum-bonded investment. The setting expansion rate of GC Cristoquick II gypsum-bonded investment was measured with a setting expansion tester 30, 60, 120 min after mixing the material respectively. The thermal expansion rates of the material at different setting time (30, 60, 120 min after mixing) and under different heating treatment methods (quick and conventional heating techniques) were also determined using a thermal dilatometer for dental investments, the total linear expansion rate were calculated. The effects of heating time and heating methods on the expansion of the investments were statistically analyzed with SPSS 11.0 software, using ANOVA multiple comparison (alpha=0.05). Statistical differences were found among the setting and thermal expansion rates of the investment at different heating timings after mixing the material (P<0.01). Setting expansion, thermal expansion and total expansion rates increased with the setting time before heat treatment, while thermal expansion rates under different (quick and conventional) heating methods were not statistically significant (P>0.05). The expansion characters of the quick-heating gypsum-bonded investment are influenced by different heating timings after mixing the material. The heat treatment technique of this quick-heating investment recommended needs to be modified to ensure casting precision.


Prognostic factors of overall survival and cancer-specific survival in patients with resected early-stage rectal adenocarcinoma: a SEER-based study.
The benefits of radiotherapy for colorectal cancer are well documented, but the impact of adjuvant radiotherapy on early-stage rectal adenocarcinoma remains unclear. This study aimed to identify predictors of overall survival (OS) and cancer-specific survival (CSS) in patients with stage II rectal adenocarcinoma treated with preoperative or postoperative radiation therapy. Patients with early-stage rectal adenocarcinoma in the postoperative state were identified using the Surveillance, Epidemiology, and End Results database. The primary endpoints were OS and overall CSS. Stage IIA patients without radiotherapy had significantly lower OS and CSS compared with those who received radiation before or after surgery. Stage IIB patients with radiotherapy before surgery had significantly higher OS and CSS compared with patients in the postoperative or no radiotherapy groups. Patients with signet ring cell carcinoma had the poorest OS among all the groups. Multivariable analysis showed that ethnicity (HR, 0.388, p=0.006) and radiation before surgery (HR, 0.614, p=0.006) were favorable prognostic factors for OS, while age (HR, 1.064, p<0.001), race (HR, 1.599, p=0.041), stage IIB (HR, 3.011, p=0.011), and more than one tumor deposit (TD) (HR, 2.300, p=0.001) were unfavorable prognostic factors for OS. Old age (HR, 1.047, p<0.00 L), stage IIB (HR, 8.619, p=0.005), circumferential resection margin between 0.1 mm and 10 mm (HR, 1.529, p=0.039), and more than one TD (HR, 2.688, p=0.001) were unfavorable prognostic factors for CSS. This population-based study identified predictors of OS and CSS in patients with early-stage resected rectal adenocarcinoma, which may help to guide future management of this patient population.


The conceptualization and communication of risk among rural appalachian adolescents.
This study uses a meta-theoretical perspective for examining risk perceptions and behavior in the rural Appalachian cultural context, an area that remains largely unexplored. The authors conducted in-depth interviews with 113 rural adolescents to describe how youth conceptualize risk and how risk is communicated in the rural environment. Analyses revealed adolescents viewed behavior as risky when they had personal or vicarious experiences resulting in a loss of control or physical harm. Elements of the rural Appalachian culture including activities, familism, and community ties can prevent and promote adolescent risk taking in various forms. This study demonstrates the conceptualization of risk and messages about risk are culturally situated and communicatively devised and enacted. The implications of these findings for adolescent risk prevention programs are discussed.


Short implants to support mandibular complete dentures - photoelastic analysis.
This study evaluated the stress behavior around short implants in edentulous atrophic mandibles. Six groups included implants with two diameters regular and wide (4 and 5 mm) and three lengths (5, 7 and 9 mm) as follows: Ci9 (9 x 4 mm), Ci7 (7 x 4 mm), Ci5 (5 x 4 mm), Wi9 (9 x 5 mm), Wi7 (7 x 5 mm) and Wi5 (5 x 5 mm). These groups were compared to the control group CG (11 x 4 mm). The analysis was performed with the photoelastic method (n = 6). Each model comprised 4 implants with the same length and diameter connected by a chromium-cobalt bar that simulates a fixed denture. A 0.15 kg force was applied at the end of the cantilever (15 mm), and the maximum shear stress was recorded around the distal and subsequent implants. The stress values were determined, and the quantitative data (Fringes®) were submitted to statistical analysis with one-way ANOVA and the Dunnett test (p < 0.05). It was observed that the reduction in implant length increased stress values with a significant difference (p < 0.05) between CG Ci7 and Ci5, while the increase in implant diameter reduced the stress values without any differences found between short and long implants. Implants with 5 and 7 mm with regular diameter increased stress levels while short implants with larger diameters experienced similar stress to that of longer implants.


Extended Duration Vascular Endothelial Growth Factor Inhibition in the Eye: Failures, Successes, and Future Possibilities.
Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of neovascularization and edema from several common chorioretinal vascular conditions. The intravitreally injected drugs (aflibercept, bevacizumab, conbercept, pegaptanib, and ranibizumab) used to treat these conditions improve the visual acuity and macular morphology in most patients. Monthly or bimonthly injections were administered in the phase III pivotal trials but physicians usually individualize therapy with pro re nata (PRN) or treat and extend regimens. Despite these lower frequency treatment regimens, frequent injections and clinic visits are still needed to produce satisfactory outcomes. Newly developed drugs and refillable reservoirs with favorable pharmacokinetic profiles may extend durations of action and require fewer office visits. However, we have learned from previous experiences that the longer durations of action seen in strategically designed phase III trials often do not translate to less frequent injections in real-life clinical practice. Unfortunately, long-acting therapies that produce soluble VEGF receptors (encapsulated cell technology and adenovirus injected DNA) have failed in phase II trials. The development of longer duration therapies remains a difficult and frustrating process, and frequent drug injections are likely to remain the standard-of-care for years to come.


Genotype-by-Environment-by-Environment Interactions in the Saccharomyces cerevisiae Transcriptomic Response to Alcohols and Anaerobiosis.
Next generation biofuels including longer-chain alcohols such as butanol are attractive as renewable, high-energy fuels. A barrier to microbial production of butanols is the increased toxicity compared to ethanol; however, the cellular targets and microbial defense mechanisms remain poorly understood, especially under anaerobic conditions used frequently in industry. Here we took a comparative approach to understand the response of Saccharomyces cerevisiae to 1-butanol, isobutanol, or ethanol, across three genetic backgrounds of varying tolerance in aerobic and anaerobic conditions. We find that strains have different growth properties and alcohol tolerances with and without oxygen availability, as well as unique and common responses to each of the three alcohols. Our results provide evidence for strain-by-alcohol-by-oxygen interactions that moderate how cells respond to alcohol stress.


Correlation of serum resistin level and other metabolic hormones and immune function in neonatal umbilical cord blood.
The present study was conducted with an attempt to explore the correlation of serum resistin level and other metabolic hormones and immune function in neonatal umbilical cord blood.The levels of umbilical cord blood resistin, adiponectin, insulin, growth hormone, leptin, thyrotropin, thyroid hormone (T3, T4), lgM, lgA, lgG, CD4, and CD8 were measured in 180 full-term newborns delivered in hospital from October 2018 to November 2019. The delivery mode, weight, height, and gender at birth were recorded.The levels of resistin, insulin, and growth hormone in umbilical cord blood of newborns delivered vaginally were significantly higher than those born by cesarean section (P < .05), while the levels of adiponectin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable between the 2 groups (P > .05). The levels of resistin, adiponectin, insulin, growth hormone, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 in cord blood of male and female newborns were comparable (P > .05). The newborns with birth weight ≥ 3501 g reported comparable results in the levels of resistin and growth hormone compared with those with birth weight of 3000 to 3500 g (P > .05), but were significantly higher than those with birth weight ≤ 2999 g (P < 0.05). In addition, the levels of adiponectin, insulin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable among the 3 groups (P > .05). Based on Pearson correlation analysis, neonatal umbilical cord blood resistin was positively correlated with adiponectin, leptin, growth hormone, T3, and T4 (r = 0.281, 0.287, 0.321, 0.276, 0.269, P < .05). However, there was no significant correlation between neonatal umbilical cord blood resistin and insulin, TST, lgM, lgA, lgG, CD4, and CD8.The level of serum resistin in neonatal umbilical cord blood was associated with the delivery mode and birth weight, and positively correlated with adiponectin, leptin, growth hormone, T3, and T4. However, no correlation was observed between serum resistin in neonatal umbilical cord blood and insulin, TST, lgM, lgA, lgG, CD4, and CD8.


[Hypobromite oxidation combined with hydroxylamine hydrochloride reduction method for analyzing ammonium nitrogen isotope in atmospheric samples.]
Ammonium salts, including ammonium nitrate, ammonium sulfate and ammonium hydrogen sulfate, are the main components of secondary inorganic aerosols and play an important role in the formation of haze events. The sources and transformation processes of atmospheric ammonium have received more and more attention. In this study, we modified the previous stable isotope analysis technique by improving the injection volume and adding a pH adjustment step, which gave a rapid and accurate measurement of ammonium nitrogen isotope ratio in atmospheric aerosol samples. Firstly, we added alkaline hypobromite to the extracted solution of the atmospheric aerosol filter samples (0.25 μg·mL-1 ammonium nitrogen in 4 mL) to oxidize ammonium (NH4+) to nitrite (NO2-). Then, after adjusting the pH, nitrite (NO2-) was reduced to nitrous oxide (N2O) by hydroxylamine hydrochloride under pH <0.3. Finally, nitrous oxide (N2O) was analyzed by Precon-GasBench-IRMS system to measure ammonium nitrogen isotope ratio. Our approach required low amount of NH4+ and avoided the use of highly toxic and explosive reagents. Meanwhile, the precision of our method could reach as high as 0.2‰ (n=10). This method could increase the NH4+ reduction efficiency to 100% at a condition of pH <0.3 and satisfy the demands of precision and accuracy for determination of ammonium nitrogen isotope in atmospheric aerosol samples. This method would help us better understand the sources, evolutions, chemical and deposition processes of atmospheric ammonium.


The use of bacterial minicells to transfer plasmid DNA to eukaryotic cells.
The delivery of DNA to mammalian cells is of critical importance to the development of genetic vaccines, gene replacement therapies and gene silencing. For these applications, targeting, effective DNA transfer and vector safety are the major roadblocks in furthering development. In this report, we present a novel DNA delivery vehicle that makes use of protoplasted, achromosomal bacterial minicells. Transfer of plasmid DNA as measured by green fluorescent protein expression was found to occur in as high as 25% of cultured Cos-7 cells when a novel chimeric protein containing the D2-D5 region of invasin was expressed and displayed on the surface of protoplasted minicells. Based on endoplasmic reticulum stress and other responses, protoplasted minicells were non-toxic to recipient eukaryotic cells as a consequence of the transfection process. Taken together, these results suggest that bacterial minicells may represent a novel and promising gene delivery vehicle.


Congenital Cytomegalovirus Prevention, Awareness and Policy Recommendations - A Scoping Study.
Congenital cytomegalovirus (cCMV) is known to cause childhood deafness, neurodevelopmental disability and death. Simple hygiene precautions are effective in reducing maternal risk of CMV infection. To review i) awareness of CMV infection and available primary prevention strategies both in the community and amongst health professionals ii) available cCMV information sources in the literature, grey literature and published professional guidelines. Scoping study to i) identify literature pertaining to cCMV awareness amongst parents and health professionals using MedLine and CINAHL databases via EBSCO ii) review one high income country's guidelines and recommendations regarding cCMV infection and pregnancy (example country Australia) iii) grey literature for parental information. Worldwide awareness of cCMV and of available prevention strategies amongst women and health professionals are poor. Findings internationally suggest at least half of maternity care health professionals do not routinely provide advice to women regarding simple hygiene precautions that can reduce their risk of infection during pregnancy. Though information resources regarding cCMV are available, they are frequently not included within general healthy pregnancy advice and require individuals to search for 'congenital cytomegalovirus'. cCMV is a preventable cause of serious congenital disability and death. Prevention opportunities are being missed because most women are not aware of cCMV or how to reduce their risk of infection in pregnancy, in part due to poor health professional awareness. New strategies to disseminate cCMV information to the community and to support health professionals to embed cCMV advice within routine pregnancy counselling is required.


Cellular proteins reactive with monoclonal antibodies directed against simian virus 40 T-antigen.
Several recently isolated monoclonal antibodies which reacted with simian virus 40 T antigens also reacted with proteins found in uninfected and untransformed cells. The proteins were different from each other, PAb419 reacting with a 35,000-molecular-weight protein, PAb427 reacting with a 75,000-molecular-weight phosphoprotein, PAb405 reacting with a 150,000-molecular-weight phosphoprotein, and PAb204 reacting with a 68,000-molecular-weight protein. It is suggested that although some of these cross-reactions may be fortuitous, they may, as an alternative, reflect similarities of shape and perhaps function between domains of the viral T antigen and the relevant host proteins.


Nutritional quality and price of plant-based dairy and meat analogs in the Canadian food supply system.
There has been an increased consumer interest and public health emphasis on plant-based protein foods, resulting in a rise in the availability of highly processed plant-based analogs. The objectives of this study were to assess the nutritional quality and the price of plant-based dairy and meat analogs compared to their respective animal-derived products and to examine the association between processing levels and the nutritional quality among these products. Using a branded food composition database, products in cheese, yogurt, milk, and meat categories were examined (n = 3231). Products were categorized as plant-based analogs versus animal-derived products using the ingredient list. Products were examined for their nutrient content, overall nutritional quality using the Food Standards Australia New Zealand nutrient profiling model, price, and processing levels using the NOVA classification. All plant-based analogs had lower protein and higher total carbohydrate, sugar, and fiber content compared to their respective animal-derived products. Compared to their respective animal-derived products, plant-based milk and meat analogs had lower energy, total fat, and saturated fat content; plant-based yogurt and meat analogs had lower sodium content; and all plant-based dairy analogs had lower calcium content. Plant-based cheese and yogurt analogs were more expensive than animal-based products; however, there was no significant difference among milk and meat products. There was no association between processing levels and overall nutritional quality among dairy and meat products. Plant-based analogs may be part of a healthy and affordable diet to reduce the intakes of nutrients of concern; however, additional compositional guidelines and/or labeling may be needed to highlight the differences in the levels of nutrients to encourage.


Silver staining of 2D electrophoresis gels.
Silver staining is used to detect proteins after electrophoretic separation on polyacrylamide gels. It -combines excellent sensitivity (in the low nanogram range) with the use of very simple and cheap equipment and chemicals. For its use in proteomics, two important additional features must be considered, compatibility with mass spectrometry and quantitative response. Both features are discussed in this chapter, and optimized silver staining protocols are proposed.


Two-year outcomes after sacrocolpopexy with and without burch to prevent stress urinary incontinence.
To report anatomic and functional outcomes 2 years after sacrocolpopexy in stress-continent women with or without prophylactic Burch colposuspension. In the Colpopexy and Urinary Reduction Efforts (CARE) trial, stress-continent women undergoing sacrocolpopexy were randomized to receive or not receive a Burch colposuspension. Outcomes included urinary symptoms, other pelvic symptoms, and pelvic support. Standardized pelvic organ prolapse quantification examinations and validated outcome measures including the Pelvic Floor Distress Inventory and the Pelvic Floor Impact Questionnaire were completed before surgery and at several postoperative intervals, including at 2 years. This analysis is based on 322 randomized participants; certain analyses were done with a subset based on data availability. Most were Caucasian (94%), with a mean age of 62±10 years (mean±standard deviation). Two years after surgery, 41.8% and 57.9% of women in the Burch and control groups, respectively, met the stress incontinence endpoint (presence of symptoms or positive cough stress test or interval treatment for stress incontinence, P=.020). The apex was well supported (point C within 2 cm of total vaginal length) in 95% of women, and this was not affected by concomitant Burch (P=.18). There was a trend toward fewer urgency symptoms in the Burch group (32.0% versus 44.5% no Burch, P=.085). Twenty participants experienced mesh or suture erosions. The early advantage of prophylactic Burch colposuspension for stress incontinence that was seen at 3 months remains at 2 years. Apical anatomic success rates are high and not affected by concomitant Burch. (www.clinicaltrials.gov), ClinicalTrials.gov, NCT00065845. I.


Electrochemiluminescence of dipicolinic acid (DPA) and (bpy)(2)Ru(DPA)(+) (bpy = 2,2'-bipyridine).
The spectroscopic and electrochemiluminescence (ECL) properties of dipicolinic acid (DPA), (bpy)(2)Ru(2+) (bpy = 2,2'-bipyridine) and the species formed when DPA and (bpy)(2)Ru(2+) [abbreviated to (bpy)(2)Ru(DPA)(+)] are allowed to react are reported. The UV-Vis absorption maxima for (bpy)(2)Ru(2+) and (bpy)(2)Ru(DPA)(+) are 493 and 475 nm, respectively, indicating the in situ formation of a complex between DPA and (bpy)(2)Ru(2+). DPA, (bpy)(2)Ru(2+) and (bpy)(2)Ru(DPA)(+) display ECL upon oxidation in the presence of the oxidative-reductive co-reactant tri-n-propylamine (TPrA). The ECL of (bpy)(2)Ru(DPA)(+) is at least two-fold higher than either of the parent species. An ECL spectrum of (bpy)(2)Ru(DPA)(+) displays a peak maximum 40 nm red-shifted from the photoluminescence peak maximum, suggesting that the excited state formed electrochemically is different from that formed spectroscopically.


Association between breast cancer chemotherapy, oral health and chronic dental infections: a pilot study.
Breast cancer has developed to become the leading type of cancer in females. For this study, 80 women were examined after chemotherapy for breast cancer and compared to 80 healthy age-matched women. This cross-sectional study comprised a dental examination with number of teeth, caries frequency (DMFT) and the presence of periodontal diseases (PSI). With the help of X-rays (OPG), the number of root canal fillings and apical lesions (LEO/LPO) were recorded. Furthermore, the education level, body mass index (BMI), smoking habits and general health conditions were recorded. All women completed questionnaires on oral health-related quality of life (OHIP-G14) and general well-being (HADS-D). To assess the influence of cancer therapy on oral health parameters, appropriate generalized linear models were fitted with disease status as main explanatory variable, adjusting for age and education. For OHIP and HADS, we additionally adjusted for number of missing teeth. The examined 160 women showed a comparable mean age (60.4 years) and an average BMI of 24.6. Cancer patients showed a higher risk for missing teeth (p < 0.001) and more apical lesions (p < 0.0041), particularly those of endodontic origin without root canal fillings (p = 0.0046), than the control women. The general well-being of cancer patients was significantly reduced with a HADS score of 9.4 for women with breast cancer compared to 5.3 for the healthy control. This study suggests that women after breast cancer chemotherapy are inclined to have a poorer oral health status with more missing teeth and apical lesions. Therefore, tightly scheduled dental recall visits should be recommended.


Sensor-Aided EMF Exposure Assessments in an Urban Environment Using Artificial Neural Networks.
This paper studies the time and space mapping of the electromagnetic field (EMF) exposure induced by cellular base station antennas (BSA) using artificial neural networks (ANN). The reconstructed EMF exposure map (EEM) in urban environment is obtained by using data from EMF sensor networks, drive testing and information accessible in a public database, e.g., locations and orientations of BSA. The performance of EEM is compared with Exposure Reference Map (ERM) based on simulations, in which parametric path loss models are used to reflect the complexity of urban cities. Then, a new hybrid ANN, which has the advantage of sorting and utilizing inputs from simulations efficiently, is proposed. Using both hybrid ANN and conventional regression ANN, the EEM is reconstructed and compared to the ERM first by the reconstruction approach considering only EMF exposure assessed from sensor networks, where the required number of sensors towards good reconstruction is explored; then, a new reconstruction approach using the sensors information combined with EMF along few streets from drive testing. Both reconstruction approaches use simulations to mimic measurements. The influence of city architecture on EMF exposure reconstruction is analyzed and the addition of noise is considered to test the robustness of ANN as well.


The mitochondrion as a primary site of action of regulatory agents involved in neuroimmunomodulation.
A major system of neuroimmunomodulation is the hypothalamic-pituitary-adrenocortical (HPA) axis, acting through glucocorticoids and their intracellular signaling components, exerting both stimulatory and inhibitory effects on the immune reaction. Glucocorticoids inhibit the production of proinflammatory cytokines by interacting with nuclear transcription factors (nuclear factor [NF]-kappaB, activated protein [AP]-1) and induce the production of several anti-inflammatory cytokines by gene activation. In some cells and/or in extreme stress conditions, apoptosis is evoked. In most processes related to neuroimmunomodulation a prominent role is emerging for mitochondria. These organelles generate more than 90% of the cell's energy requirements through oxidative phosphorylation (OXPHOS), which is regulated by several agents, including steroid and thyroid hormones. These hormones are inducers of nuclear and mitochondrial OXPHOS gene transcription and they exert a primary action not only on nuclear but also on mitochondrial genes by way of cognate receptors. Recently, additional nuclear transcription factors involved in neuroimmunomodulation have been detected in mitochondria (NF-kappaB, AP-1, p53, calcium/cAMP response element binding protein [CREB]), and binding sites of these and putative binding sites of other nuclear transcription factors have been identified in the mitochondrial genome. The interaction of these factors with mitochondrial regulatory proteins, with receptors and with the genome has been shown and, in some cases, modulation of mitochondrial transcription was observed with possible effects on energy yield. The mitochondria store a host of critical apoptotic activators and inhibitors in their intermembrane space and the release of these factors could be another possible mode of action of the mitochondrially translocated regulatory agents and receptors.


Role of Ligand Shell Density in the Diffusive Behavior of Nanoparticles in Hydrogels.
The diffusion coefficients of poly(ethylene glycol) methyl ether thiol (PEGSH)-functionalized gold nanoparticles (NPs) with different effective grafting densities were measured in polyacrylamide hydrogels. The NP core size was held constant, and the NPs were functionalized with mixtures of short oligomeric ligands (254 Da PEGSH) and longer (either 1 or 2 kDa PEGSH) ligands. The ratio of short and long ligands was varied such that the grafting density of the high-molecular-weight (MW) ligand ranged from approximately 1 to 100 high-MW ligands/NP. The diffusion coefficients of the NPs were then measured in gels with varying average mesh sizes. The measured diffusion coefficients decreased with higher MW ligand density. Interestingly, the diffusion coefficients for NPs with high effective grafting densities were well-predicted by their hydrodynamic diameters, but the diffusion coefficients for NPs with low effective grafting densities were higher than expected from their hydrodynamic diameters. These results suggest that crowding in the NP ligand shell influences the mechanism of diffusion, with lower grafting densities allowing ligand chain relaxations that facilitate movement through the gel. This work brings new insights into the factors that dictate how NPs move through hydrogels and will inform the development of models for applications such as drug delivery in complex viscoelastic biological materials.


Past caring? The influence of technology.
The increase in technology in 'general' clinical areas as well as specialized units such as intensive care units and theatres influences the delivery of nursing care. This paper reports findings from a longitudinal study exploring the changes in self-est eem of two cohorts of pre-registration nursing students. The study involved the measurement of the global and professional self-esteem, but its main focus was a qualitative grounded theory approach to identify changes in the self-esteem. The findings det ailed here emphasize the importance of practical nursing skills and the use of technology to student nurses. Results showed that students' self-esteem was effected and constructed by practical and technological competence. The emphasis on both of these a ctivities changed through students' 3-year training course in that although initially students derived their professional self-esteem from being practically capable, this was subjugated to a lower place in gaining their professional self-worth by the end of the course. Instead, the use of technology had ahigh status throughout the course and had associations with scientific and medical power.


Core and peripheral organisations in prevention: Insights from social network analysis.
Formal (eg funded) community-level organisational collaborations are becoming more common in prevention. Rapid methods to assess organisational relationships could allow us to consider the significance of any pre-existing relationship patterns in communities that might impact on collaboration effectiveness. Insights may identify new options for practice. We used social network analysis to study organisations engaged in prevention but not (yet) part of a formal purposive collaboration. Within a single community, we identified organisations providing programs in chronic disease prevention. We used whole network analysis methods to describe the extent to which organisations were aware, had contact, coordinated activity and/or collaborated more intensively. We also identified the contribution made to prevention locally. Results were compared with key informant interviews. There was an identifiable network structure, with more relationships across the network than one would expect by chance. The network had a core-periphery structure, meaning that, in terms of the relationships we measured, there were highly connected organisations who were strongly interlinked with each other (the core), alongside less connected organisations that were linked to the core but not to each other (the periphery). Core organisations were significantly more likely to have expertise in prevention and to have prevention staff. To our knowledge, it is new to identify inherent or "pre-existing" core-periphery structures in interorganisational health promotion. Yet, core-periphery structures are common in many social settings. They advantage entities in the core and are prone to further entrenchment. SO WHAT?: Our results map and quantify intuitive understandings about organisational "key players", thus enabling practitioners/organisations to critically reflect on what their role should be when it comes to activating communities ie to embed, or attempt to counterbalance, pre-existing power structures.


Lightweight and Durable PVDF-SSPF Composites for Photovoltaics Backsheet Applications: Thermal, Optical and Technical Properties.
Photovoltaic module backsheets are characterized according to their thermal, optical, mechanical, and technical properties. This work introduces new fabricated backsheets for PV modules using polyvinylidene fluoride (PVDF) reinforced with short sugar palm fiber (SSPF) composites. The preparation of composites undergoes multiple phases of fabrication. Thermal, optical, and technical investigations of their properties were conducted. Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, in-situ scanning probe microscopy (SPM), dynamic mechanical analysis (DMA), thermal mechanical analysis (TMA), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and prolonged technical testing were accomplished to expansively understand the complex behavior of composites under various conditions. The optical properties of PV backsheets are critical components in determining the reflectance, absorbance, and transmittance of light. The PVDF-SSPF composites exhibited exceptional compatibility and thermal stability, further revealing a homogenous composite structure with enhanced interfacial bonding between the short fiber and polymer matrix.


The genes for interleukins 3 and 5 map to the same locus on mouse chromosome 11.
The cytokines, IL-3, IL-4, IL-5, and GM-CSF (encoded by murine genes Il-3, Il-4, Il-5, and Csfgm) belong to a family of secreted glycoprotein hormones that regulate the haemopoietic and immune systems. We demonstrate here using in situ hybridization that Il-3 and Il-5 are both probably located in the segment comprising band A5 and the proximal half of band B1 on mouse chromosome 11 with a possible location point in band B1 near its proximal interface with band A5. In studies reported elsewhere we have shown close physical linkage between Il-3 and Csfgm and also between Il-4 and Il-5. The in situ hybridization results therefore indicate that all four cytokine genes are clustered on chromosome 11 raising the possibility that they arose by ancient gene duplication.


Sodium intake, health implications, and the role of population-level strategies.
Evidence to date suggests that high sodium intake affects health adversely, yet the role of a population-level strategy to reduce sodium intake is often contested. This review focuses on current available evidence on regional sodium intake levels, health implications of sodium intake, and population-level strategies implemented worldwide. The limitations in evidence, the difficulties in implementing population-wide strategies to reduce sodium intake, and the need for such strategies are critically reviewed. Evidence clearly shows that sodium has an adverse effect on blood pressure, cardiovascular disease, and mortality. However, whether reduced sodium intake benefits all individuals or only hypertensive individuals is still unclear. Methodological issues and publication bias in current evidence are other matters of concern in sodium-related research. While it is essential to continue working toward the World Health Organization's target of 30% reduction in sodium intake, due consideration should be given to improving the quality of research, reducing bias in publications, and reviewing evidence more critically.


Neuropathological features of genetically confirmed DYT1 dystonia: investigating disease-specific inclusions.
Early onset isolated dystonia (DYT1) is linked to a three base pair deletion (ΔGAG) mutation in the TOR1A gene. Clinical manifestation includes intermittent muscle contraction leading to twisting movements or abnormal postures. Neuropathological studies on DYT1 cases are limited, most showing no significant abnormalities. In one study, brainstem intraneuronal inclusions immunoreactive for ubiquitin, torsinA and lamin A/C were described. Using the largest series reported to date comprising 7 DYT1 cases, we aimed to identify consistent neuropathological features in the disease and determine whether we would find the same intraneuronal inclusions as previously reported. The pathological changes of brainstem inclusions reported in DYT1 dystonia were not replicated in our case series. Other anatomical regions implicated in dystonia showed no disease-specific pathological intracellular inclusions or evidence of more than mild neuronal loss. Our findings suggest that the intracellular inclusions described previously in DYT1 dystonia may not be a hallmark feature of the disorder. In isolated dystonia, DYT1 in particular, biochemical changes may be more relevant than the morphological changes.


Research Progress of the Types and Preparation Techniques of Scaffold Materials in Cartilage Tissue Engineering.
The management of chondral defects has been a challenge for a long time because of the poor self-healing capacity of articular cartilage. Many approaches ranging from symptomatic treatment to structural cartilage regeneration are not that successful with very limited satisfactory results. Chondral defects caused by tumor, trauma, infection, congenital malformations are very common in clinical trials. It seriously affects the patient's physical function and quality of life. The appearance of cartilage tissue engineering has brought good news for cartilage defect repair. Through this review, we are aimed at reviewing the progress of the types and preparation techniques of scaffold materials in cartilage tissue engineering.


Bilateral hematosalpinx in a case of ectopic pregnancy: a clinical dilemma.
A 31-year-old woman with a positive pregnancy test and a transvaginal ultrasound scan result that was suggestive of a right tubal ectopic pregnancy underwent a laparoscopy, which showed bilateral hematosalpinx. In the presence of active bleeding and deteriorating hemodynamic status of the patient, a minilaparotomy was performed that revealed a right-sided hematosalpinx and a left-sided ectopic gestation.


Early expression of requisite developmental growth hormone imprinted cytochromes P450 and dependent transcription factors.
The sexually dimorphic expression of cytochromes P450 (CYP) drug metabolizing enzymes has been reported in all species examined. These sex differences are initially expressed during puberty and are solely regulated by sex differences in the circulating growth hormone (GH) profiles. Once established, however, the different male- and female-dependent CYP isoforms are permanent and immutable, suggesting that adult CYP expression requires imprinting. Since the hormone that regulates an adult function is likely the same hormone that imprints the function, we selectively blocked GH secretion in some newborn male rats while others also received a concurrent physiologic replacement of rat GH. Rats were subsequently challenged, peripubertally, with either a masculine-like episodic GH regimen or the GH vehicle alone. The results demonstrate that episodic GH regulation of male-specific CYP2C11 and CYP3A2, as well as female-predominant CYP2C6, are dependent on developmental GH imprinting. Moreover, the induction and/or activation of major components in the signal transduction pathway regulating the expression of the principal CYP2C11 isoform is obligatorily dependent on perinatal GH imprinting without which CYP2C11 and drug metabolism would be permanently and profoundly suppressed. Since there are additional adult metabolic functions also regulated by GH, pediatric drug therapy that is known to disrupt GH secretion could unintentionally impair adult health.


Interleukin-3, -5, and granulocyte macrophage colony-stimulating factor induce adhesion and chemotaxis of human eosinophils via p38 mitogen-activated protein kinase and nuclear factor kappaB.
Hematopoietic cytokines such as interleukin (IL)-3, IL-5, and granulocyte macrophage colony-stimulating factor (GM-CSF) play a fundamental role in eosinophil functions in allergic asthma. The intracellular signal transduction mechanisms of these cytokines regulating the activation of eosinophils have been potential therapeutic targets. We investigated the roles of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-kappaB) in IL-3, IL-5, and GM-CSF-induced adhesion, morphological changes, and subsequence transmigration of human eosinophils. IL-3, IL-5, and GM-CSF could augment the phosphorylation of p38 MAPK and nucleus translocation of NF-kappaB in eosinophils. cDNA expression arrays demonstrated that the gene expression levels of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), alpha6, beta2 integrin (CD18), and CD44 were upregulated by these cytokines. Results from functional assays showed that adhesion of eosinophils onto airway epithelial cells was enhanced after IL-3 and IL-5 but not GM-CSF stimulation. These cytokines could markedly induce shape change and augment the transmigration of eosinophils. Moreover, administration of either p38 MAPK inhibitor, SB 203580, or proteasome inhibitor, N-cbz-Leu-Leu-leucinal (MG-132), could inhibit the cytokine-induced adhesion, shape change, and transmigration of eosinophils. Together, our findings suggest that IL-3, IL-5, and GM-CSF regulated the adhesion and chemotaxis of human eosinophils through shared signaling pathways involving both p38 MAPK and NF-kappaB. Our results therefore shed light on the further development of more effective agents for allergic and inflammatory diseases.


C-Glycoside analogues of beta-galactosylceramide with a simple ceramide substitute: synthesis and binding to HIV-1 gp120.
The synthesis and HIV-1 gp120 binding of C- and aza-C-glycoside analogues of beta-galactosylceramide (GalCer) that contain a simple C-17 hydrocarbon chain as a ceramide substitute are described. Both compounds originate from stearic acid, and a carbohydrate-derived thioacetal-alcohol, and their syntheses are potentially general for beta-C-galactosides and their aza-C-partners. They showed potent and specific affinity for gp120 in an assay based on the change of surface pressure when the glycolipid monolayers were exposed to solutions of gp120. Interestingly, the aza-C-glycoside exhibited a significantly higher affinity than GalCer, whereas the C-glycoside was as active as GalCer.


Optimal Treatment Strategies in Patients with Chronic Kidney Disease and Coronary Artery Disease.
Chronic kidney disease is an independent risk factor for coronary artery disease and is associated with an increase in adverse outcomes. However, the optimal treatment strategies for patients with chronic kidney disease and coronary artery disease are yet to be defined. MEDLINE, EMBASE, and CENTRAL were searched for studies including at least 100 patients with chronic kidney disease (defined as estimated glomerular filtration rate ≤60 mL/min/1.73 m2 or on dialysis) and coronary artery disease treated with medical therapy, percutaneous coronary intervention, or coronary artery bypass surgery and followed for at least 1 month and reporting outcomes. The outcome evaluated was all-cause mortality. Meta-analysis was performed to evaluate the outcomes with revascularization (percutaneous coronary intervention or coronary artery bypass surgery) when compared with medical therapy alone. In addition, outcomes with percutaneous coronary intervention vs coronary artery bypass surgery were evaluated. The search yielded 38 nonrandomized studies that enrolled 85,731 patients. Revascularization (percutaneous coronary intervention or coronary artery bypass surgery) was associated with lower long-term mortality (mean 4.0 years) when compared with medical therapy alone (relative risk [RR] 0.73; 95% confidence interval [CI], 0.62-0.87), driven by lower mortality with percutaneous coronary intervention vs medical therapy and coronary artery bypass surgery vs medical therapy. Coronary artery bypass surgery was associated with a higher upfront risk of death (RR 1.81; 95% CI, 1.47-2.24) but a lower long-term risk of death (RR 0.94; 95% CI, 0.89-0.98) when compared with percutaneous coronary intervention. In chronic kidney disease patients with coronary artery disease, the current data from nonrandomized studies indicate lower mortality with revascularization, via either coronary artery bypass surgery or percutaneous coronary intervention, when compared with medical therapy. These associations should be tested in future randomized trials.


Assessment of neuropsychiatric manifestations in a cohort of intensive care unit survivors: A proof of concept study.
The aim of this study was to assess the feasibility and outcome of a neuropsychiatric evaluation protocol intended for adult intensive care unit survivors in a Danish regional hospital, in which a follow-up consultation was conducted 2 months after hospital discharge. Twenty-three participants were able to finalize the neuropsychiatric evaluation, and 20 (87%) among those were detected with neuropsychiatric manifestations, including cognitive impairment (n = 17; 74%) and fatigue (n = 17, 74%). This study finds a high prevalence of neuropsychiatric manifestations and fatigue, and evaluates a follow-up protocol for the ICU patient population.


Spatial confinement governs orientational order in patchy particles.
Orientational order in condensed matter plays a key role in determining material properties such as ferromagnetism, viscoelasticity or birefringence. We studied purely orientational ordering in closely-packed one-patch colloidal particles confined between flat substrates, where the particles can only rotate and are ordered via the sticky interaction between the patches. For the first time, we experimentally realized a rich variety of mesoscopic patterns through orientational ordering of colloids by controlling patch size and confinement thickness. The combination of experiment and numerical simulation reveals the decisive role of confinement: An ordered state(s) is selected from the (meta)stable options in bulk when it is commensurate with the system geometry and boundary conditions; otherwise, frustration induces a unique order. Our study offers a new means of systematic control over mesoscopic structures via orientational ordering in patchy particles. The system would also possess unique functionalities through the rotational response of the particles to external stimuli.


Computerized tomography of cranial sutures. Part 2: Abnormalities of sutures and skull deformity in craniosynostosis.
Preoperative computerized tomographic (CT) scans of 24 children who had surgery for either single or multiple craniosynostoses were compared with skull radiographs and operative and pathological findings. In addition to providing accurate imaging of calvarial and skull base deformities secondary to premature suture closure, high-resolution CT with bone definition algorithms supplied valuable detail of anatomical changes at the abnormally developed suture. The CT findings varied with the location of the suture. Thickened bony ridges predominated at the sagittal suture, focal bone thickening and erosions were more likely to be found at the metopic suture, and parasutural sclerosis was the prevalent finding on one side of the lambdoid suture. No evidence of the suture could be detected in the majority of patients with complete coronal craniosynostosis. Radiographs of the skull were shown to be a relatively insensitive means of imaging the zone of limited fusion, especially the lambdoid suture. An excellent correlation was found between the CT scan and the operative and pathological findings. There was histological evidence of progressive suture fusion in virtually all patients. An asymmetrically narrowed lucent zone with parasutural sclerosis or bony ridges seen on CT scans correlated well with fibrous union of the suture found on histological examination. The authors conclude that high-definition CT used in conjunction with bone windows and thin and coronal slices for the evaluation of sagittal sutures is a useful imaging method for the evaluation of craniosynostosis.


Effect and Safety Analysis of PRP and Yifu Combined with Ultrapulsed CO2 Lattice Laser in Patients with Sunken Acne Scar.
To investigate the effect and safety of PRP and Yifu combined with ultrapulsed CO2 lattice laser in patients with sunken acne scar. 700 subjects were selected from the group of patients with sunken acne scar treated in our hospital from November 2010 to December 2020. They were divided into control group (n = 350) and study group (n = 350). The grouping was mainly based on the random number table method. Patients in the control group were treated with ultrapulse CO2 lattice laser, while those in the study group were treated with ultrapulse CO2 lattice laser combined with PRP and Yifu. The clinical effect, scar improvement and quality of life before and after treatment, and adverse events during treatment were compared between the two groups. The clinical effect was categorized into cure after treatment, significant effect, effective, and ineffective. The total effective rate = 1 - ineffective rate. After treatment, the total effective rate of the study group (81.43%) was higher than that of the control group (70.00%). After treatment, ECCA, VSS scores, daily activities, symptoms and feelings, work and study, leisure and entertainment, interpersonal relationship, treatment status, and total scores were all lower in both groups than before treatment, and the study group was lower than the control group. During the treatment, the incidence of adverse events in the study group (17.33%) was lower than that in the control group (28.57%), P < 0.05. PRP and Yifu combined with ultrapulse CO2 lattice laser in the treatment of sunken acne scar can effectively improve the scar, reduce the incidence of adverse events, and the treatment effect is obvious, which can improve the quality of life of the patients.


Gender Differences in Heart Rate Variability Among Individuals Undergoing Regular Resistance Training Preliminary observations.
Frequency-domain analysis of heart rate variability (HRV) is an effective tool to evaluate autonomic balance. This study aimed to investigate gender differences in HRV among individuals undergoing regular resistance training. This preliminary cross-sectional study was conducted from April to September 2016 in João Pessoa, Paraíba, Brazil. The low-frequency (LF), high-frequency (HF) and LF/HF ratio components of HRV spectral analysis were analysed among 22 men and 27 women undergoing regular resistance training. Among the male participants, the LF component was significantly increased compared to females in both the supine (1,171 ± 192 versus 545 ± 74 ms2; P = 0.0067) and upright (1,824 ± 260 versus 738 ± 133; P = 0.0011) positions. The LF/HF ratio was also significantly increased in both positions among male participants (P <0.0500 each). These preliminary data suggest a possible gender difference in the HRV of individuals undergoing resistance training.


Deletion of the N- or C-Terminal Helix of Apolipophorin III To Create a Four-Helix Bundle Protein.
Apolipophorin III (apoLp-III) is an exchangeable apolipoprotein found in insects and plays an important function in lipid transport. The protein has an unusual five-helix bundle architecture, deviating from the common four-helix bundle motif. To understand the role of the additional helix in apoLp-III, the N-terminal or C-terminal helix was deleted to create a putative four-helix bundle protein. While the protein lacking helix-1 could be expressed in bacteria albeit at reduced yields, apoLp-III lacking helix-5 could not be produced. Mutational analysis by truncating helix-5 showed that a minimum segment of approximately one-third of the C-terminal helix is required for protein expression. The variant lacking helix-5 was produced by inserting a methionine residue between helix-4 and -5; subsequent cyanogenbromide cleavage generated the four-helix variant. Both N- and C-terminal helix deletion variants displayed significantly reduced helical content, protein stability, and tertiary structure. Despite the significantly altered structure, the variants were still fully functional. The rate of dimyristoylphosphatidylcholine vesicle solubilization was enhanced 4-5-fold compared to the wild-type protein, and the deletion variants were effective in binding to lipolyzed low density lipoprotein thereby preventing lipoprotein aggregation. These results show that the additional helix of apoLp-III is not essential for lipid binding but is required for proper folding to keep the protein into a stable conformation.


[Preparation of ethanol-diesel fuel blends and exhausts emission characteristics in diesel engine].
The technology that diesel oil is partly substituted by ethanol can reduce diesel engine exhausts emission, especially fuel soot. This research is concentrated on preparation of ethanol-diesel blend fuel and exhausts emission characteristics using diesel engine bench. Absolute ethanol can dissolve into diesel fuel at an arbitrary ratio. However, a trace of water (0.2%) addition can lead to the phase separation of blends. Organic additive synthesized during this research can develop the ability of resistance to water and maintain the stability of ethanol-diesel-trace amounts of water system. The effects of 10%, 20%, and 30% ethanol-diesel fuel blends on exhausts emission, were compared with that of diesel fuel in direct injection (DI) diesel engine. The optimum ethanol percentage for ethanol-diesel fuel blends was 20%. Using 20% ethanol-diesel fuel blend with 2% additive of the total volume, bench diesel engine showed a large amount decrease of exhaust gas, e.g. 55% of Bosch smoke number, 70% of HC emission, and 45% of CO emission at 13 kW and 1540 r/min. Without the addition of additive, the blend of ethanol produced new organic compounds such as ethanol and acetaldehyde in tail gas. However, the addition of additive obviously reduced the emission of ethanol and acetaldehyde.


Effects of smoking on uteroplacental blood flow.
The effects of nicotine consumption on uteroplacental blood flow were studied in 20 pregnant women by means of placental blood flow measurements using indium-113m-transferrin. Smokers were found to have a higher rate of poor perfusion patterns than subjects of a control group. In addition, the number of cigarettes smoked daily was significantly correlated with the placental perfusion type. The mean birth weight of infants born by smokers was 250 g lower than in the control group. The results suggest that smoking during pregnancy may compromise uteroplacental blood flow and thus result in poor fetal development.


Contribution of MATE1 to Renal Secretion of the NMDA Receptor Antagonist Memantine.
The weak base memantine is actively secreted into urine, however the underlying mechanisms are insufficiently understood. Potential candidates involved in memantine renal secretion are organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATE1, MATE2-K). The aim of this in vitro study was the examination of the interaction of memantine with OCT2 and MATEs. Memantine transporter inhibition and transport were examined in HEK cells expressing human OCT2, MATE1, or MATE2-K. Monolayers of single- (MDCK-OCT2, MDCK-MATE1) and double-transfected MDCK cells (MDCK-OCT2-MATE1) were used for studies on vectorial, basal to apical memantine transport. Memantine inhibited OCT2-, MATE1-, and MATE2-K-mediated metformin transport with IC50 values of 3.2, 40.9, and 315.3 μM, respectively. In HEK cells, no relevant memantine uptake by OCT2, MATE1, or MATE2-K was detected. Vectorial transport experiments, however, indicated a role of MATE1 for memantine export: After memantine administration to the basal side of the monolayers, memantine cellular accumulation was considerably lower (MDCK-MATE1 vs MDCK control cells, P < 0.01) and memantine transcellular, basal to apical transport was higher in MATE1 expressing cells (MDCK-MATE1 vs MDCK control cells, P < 0.001 at 60 and 180 min). Both effects were abolished upon addition of the MATE inhibitor cimetidine. These experiments suggest a relevant role of MATE1 for renal secretion of memantine. In the clinical setting, renal elimination of memantine could be impaired by coadministration of MATE inhibitors.


Precancerous and cancerous breast lesions during lifetime and at autopsy. A study of 83 women.
Among 83 consecutive, unselected female autopsy cases, 6 had been treated for invasive breast carcinoma (IBC) during lifetime. At autopsy, of these six women, two had IBC in the contralateral breast, and another two had in situ carcinoma. Among the 77 women without previous clinical breast cancer, one case of IBC and 14 cases of in situ carcinoma were found at autopsy. Thus, the total occurrence of primary malignant breast lesion was as high as 25.4%. Assuming that all IBCs evolve from in situ forms and that in situ carcinomas do not undergo total regression, our results seem to indicate that about one third of all in situ carcinomas develop into IBC.


Cation transport of red blood cells from hypertensive patients in Japan.
This study was performed to determine whether there is any difference in cation transport of red blood cells from normotensive subjects and hypertensive patients in Japan. Net Na+ efflux and net K+ influx rates were measured in sodium-loaded red cells from 19 normotensive subjects, 22 essential hypertensive patients, and 8 secondary hypertensive patients. The ratio of Na+/K+ net fluxes and the net cation flux rate were compared between these groups. The ratio of Na+/K+ net fluxes was significantly lower in essential hypertensive patients than in normotensive subjects. Parameters such as age, sex, blood pressure, plasma renin activity, and plasma aldosterone concentration were also examined in 2 groups of essential hypertensive patients, divided on the basis of their Na+/K+ net fluxes. However, there is no significant difference between the groups. These results suggest that the ratio of cation flux is related to hypertension independently of these parameters.


Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway.
This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.


Gender-specific research on mental illness in the emergency department: current knowledge and future directions.
Mental illness is a growing, and largely unaddressed, problem for the population and for emergency department (ED) patients in particular. Extensive literature outlines sex and gender differences in mental illness' epidemiology and risk and protective factors. Few studies, however, examined sex and gender differences in screening, diagnosis, and management of mental illness in the ED setting. Our consensus group used the nominal group technique to outline major gaps in knowledge and research priorities for these areas, including the influence of violence and other risk factors on the course of mental illness for ED patients. Our consensus group urges the pursuit of this research in general and conscious use of a gender lens when conducting, analyzing, and authoring future ED-based investigations of mental illness.


Correlation between sport and depression.
Does sport really produce positive effects in mental illness? The author discusses this question, through a survey of the literature. There is evidence that exercise increases endorphine levels. In order to support the prevention and treatment of depression through sport, it seems particularly useful, to encourage the practice of moderate, diversified physical activity.


Fixation systems of greater trochanteric osteotomies: biomechanical and clinical outcomes.
The development of cerclage systems for fixation of greater trochanteric osteotomies has progressed from monofilament wires to multifilament cables to cable grip and cable plate systems. Cerclage wires and cables have various clinical indications, including fixation for fractures and for trochanteric osteotomy in hip arthroplasty. To achieve stable fixation and eventual union of the trochanteric osteotomy, the implant must counteract the destabilizing forces associated with pull of the peritrochanteric musculature. The material properties of cables and cable grip systems are superior to those of monofilament wires; however, potential complications with the use of cables include debris generation and third-body polyethylene wear. Nevertheless, the cable grip system provides the strongest fixation and results in lower rates of nonunion and trochanteric migration. Cable plate constructs show promise but require further clinical studies to validate their efficacy and safety.


Antipsychotic polypharmacy in patients with schizophrenia in a brief hospitalization unit.
Antipsychotic monotherapy is considered the gold standard in pharmacological treatment of schizophrenia and other psychotic disorders. Only 2 of the main clinical guides recommend the use of antipsychotic polypharmacy (AP) for those patients refractory to monotherapy. Nonetheless, there is a large rate of studies, conducted in many different settings, showing that AP is more frequent as would be expected attending experts' recommendations. In this retrospective study, we review all the psychotropic drugs dispensed to inpatients of a brief hospitalization psychiatric unit diagnosed as having schizophrenia or schizoaffective disorder (International Statistical Classification of Diseases, 10th Revision) at time of discharge in the year 2005. These included a total of 209 patients older than 18 years. Of the 209 studied patients, 55.5% were discharged under AP treatment. Inpatients were given a mean of 3.06 psychotropic drugs and a mean of 1.61 antipsychotics at the time of hospital discharge. A total of 33.2% of the studied patients got anticholinergic drugs, and 66.2% were given benzodiazepines. The most prevalent combination of drugs was intramuscular long-acting risperidone plus an atypical antipsychotic. Amisulpride was the most used antipsychotic as adjuvant treatment. Despite different clinical guidelines, AP is a common pharmacological strategy as it is shown in our study and in the reviewed literature. Data in our study indicate that the observed rates of AP cannot exclusively be attributed to the treatment of patients with clozapine-resistant schizophrenia.


[RESEARCH OF ACETABULAR ORIENTATION DETERMINATION AND ACCURACY IN TOTAL HIP ARTHROPLASTY FOR BONY ANKYLOSED HIP].
To explore the method of acetabular orientation determination in total hip arthroplasty (THA) for bony ankylosed hip and the accuracy of the postoperative evaluation. Between January 2009 and March 2013, 33 consecutive patients (49 hips) underwent THA. There were 25 males and 8 females with a mean age of 35.8 years (range, 18-69 years). The left hip was involved in 10 cases, the right hip in 7 cases, and bilateral hips in 16 cases. The causes were ankylosing spondylitis in 18 patients, tuberculosis in 6 patients, traumatic arthritis in 6 patients, osteoarthritis in 2 patients, and suppurative infection in 1 patient. The disease duration was 7-15 years with an average of 10.8 years. The acetabular orientation was determined with periacetabular bone marks (the upper margin of the obturator foramen, acetabular notch etc.) and soft tissue signs (acetabulum transverse ligament etc.). The hip or pelvic radiograph was taken to measure the acetabular prosthesis anteversion and abduction angle, and upward or downward, inward or outward acetabular migration degree. The acetabular anteversion angle of 15 degrees, the abduction angle of 45 degrees, and upward or downward, inward or outward acetabular migration degree of 0 served as a reference value to evaluate the accuracy of acetabular position. There was no complications of neurovascular injury, fracture, joint dislocation, and infection. All of patients were followed up 13-63 months (mean, 30.3 months). The anteversion angle and abduction angle were (13.904 +/- 4.034) degrees and (42.898 +/- 7.474) degrees at last follow-up, showing no significant difference when compared with reference value (t=1.386, P=0.178; t=1.969, P=0.055). The inward or outward and upward or downward acetabulum migration degree were (2.530 +/- 2.261) mm and (3.886 +/- 3.334) mm respectively, showing significant differences when compared with reference value (t=7.830, P=0.000; t=8.159, P=0.000); it was less than 5 mm in 29 hips, 5-10 mm in 18 hips, and more than 10 mm in 2 hips; the acetabulum center coincidence rate was 59.2%. For bony ankylosed hip having loss of normal anatomy structure, intraoperative residues and permanent anatomical structure should be used for acetabular positioning.


A Video Recall Study of In-session Changes in Sentiment Override.
This study examines in-session changes in sentiment override over the first three sessions of couple therapy. Couples viewed a video recording of therapy sessions immediately after each of the first three sessions and continuously rated their level of sentiment override. Ninety-eight changes were randomly chosen for analysis. Three talk turns prior to each change was coded using the Family Relational Communication Control Coding System. Results show that changes in sentiment override occur frequently. Repeated incidents of communication control were related to negative change in sentiment override for females. Repeated incidents of being left out of the conversation were related to negative changes in sentiment override for females and positive changes for males.


Comparative Analysis of Stylet Penetration Behaviors of Eriosoma lanigerum (Hemiptera: Aphididae) on Main Apple Cultivars in China.
The preference and behavioral mechanism of the feeding behavior of the woolly apple aphid, Eriosoma lanigerum (Hausmann), on Chinese apple cultivars was investigated using the electrical penetration graph (EPG) technique. Feeding of adult aphids was assessed for the four main cultivars of apple in China (Red Fuji, Ralls Genet, Starkrimson, and Jonagold) over an 8-h monitoring period, what that of fourth-instar nymphs was assessed for 8 h on Jonagold only. EPG waveforms representing the details of probing behaviors, parameters were measured for analysis. We found that at the nonphloem phase, the total duration of the nonpenetration (np) waveform and the total duration of the stylet pathway phase (the 'C wave') on Ralls Genet and Starkrimson were significantly longer than on Red Fuji. In addition, the phloem-feeding phase, the total duration of 'release of saliva into the phloem', (the E1 waveform) was significantly longer on Ralls Genet and Jonagold than on Red Fuji. The total duration of the 'ingestion from sieve cells' phase (the E2 waveform) on Red Fuji, meanwhile, was significantly longer than on Ralls Genet or Starkrimson. At the same time, when combined with EPG parameters, Red Fuji was found to have no obvious resistance to woolly apple aphid and to be a susceptible cultivar. This experiment also recorded the feeding waveform of fourth-instar aphid nymphs. Based on the phloem and nonphloem parameters recorded in this study, it was inferred that adult aphids are more likely than nymphs to feed on apple trees.


Glucose determination in human aqueous humor with Raman spectroscopy.
It has been suggested that spectroscopic analysis of the aqueous humor of the eye could be used to indirectly predict blood glucose levels in diabetics noninvasively. We have been investigating this potential using Raman spectroscopy in combination with partial least squares (PLS) analysis. We have determined that glucose at clinically relevant concentrations can be accurately predicted in human aqueous humor in vitro using a PLS model based on artificial aqueous humor. We have further determined that with proper instrument design, the light energy necessary to achieve clinically acceptable prediction of glucose does not damage the retinas of rabbits and can be delivered at powers below internationally acceptable safety limits. Herein we summarize our current results and address our strategies to improve instrument design.


Myocardial ischemia is more important than the effects of cardiopulmonary bypass on myocardial water handling and postoperative dysfunction: a pediatric animal model.
Low cardiac output state is the principal cause of morbidity after surgical intervention for congenital heart disease. Myocardial ischemia-reperfusion injury, apoptosis, capillary leak syndrome, and myocardial edema are associated factors. We established a clinically relevant model to examine relationships between myocardial ischemia, edema, and cardiac dysfunction and to assess the role of the water transport proteins aquaporins. Sixteen lambs were studied. Seven were control animals not undergoing cardiopulmonary bypass, and 9 underwent bypass. Six had 90 minutes of aortic crossclamping with blood cardioplegia and moderate hypothermia. The remaining 3 underwent cardiopulmonary bypass without aortic crossclamping. Hemodynamic and biochemical data were recorded, and myocardial edema, apoptotic markers, and aquaporin expression were determined after death. The group undergoing cardiopulmonary bypass with aortic crossclamping had a low cardiac output state, with early postoperative tachycardia, hypotension, increased serum lactate levels, and impaired tissue oxygen delivery (P < .05) compared with the group undergoing cardiopulmonary bypass without aortic crossclamping. The lambs undergoing cardiopulmonary bypass with aortic crossclamping had increased myocardial water (P < .05) compared with those not undergoing cardiopulmonary bypass and a 2-fold increase in aquaporin 1 mRNA expression (P < .05) compared with those not undergoing cardiopulmonary bypass and those undergoing cardiopulmonary bypass without aortic crossclamping. A temporal association between hemodynamic dysfunction, myocardial edema, and increased aquaporin 1 expression was demonstrated. Cardiopulmonary bypass without ischemia was associated with minimal edema, negligible myocardial dysfunction, and static aquaporin expression. Ischemic reperfusion injury is the main cause of myocardial edema and myocardial dysfunction, but a causal relationship between edema and dysfunction remains to be proved.


Mycobacterium bovis infection in Holstein Friesian cattle, Iran.
To identify strains of Mycobacterium bovis circulating in Iran, we used region of difference, spoligotypes, and variable number tandem repeats to genotype 132 M. bovis isolates from Holstein Friesian cattle. Despite wide geographic origins, the strains were genetically homogeneous. Increased distribution of cattle herds and inadequate control measures may have contributed to strain dispersion.


A novel MGP mutation in a consanguineous family: review of the clinical and molecular characteristics of Keutel syndrome.
Keutel syndrome (KS) [OMIM 245150] is a rare autosomal recessive condition, characterized by abnormal cartilage calcification. Mutations in the matrix Gla protein gene (MGP) have been previously reported in three unrelated KS families. MGP is an extracellular matrix protein that acts as a calcification inhibitor by repressing bone morphogenetic protein 2 (BMP2). Loss-of-function mutations of MGP result in abnormal calcification of the soft tissues, a cardinal feature of KS. We report the fourth MGP mutation (IVS2 + 1G > A) in a consanguineous Arab family, which results in the loss of the consensus donor splice site at the exon 2-intron 2 junction. In addition to the typical manifestations, we observed abnormalities in the white matter of the brain, optic nerve atrophy, and mid-dermal elastolysis in the affected individuals of this family. This report broadens the clinical phenotype observed in patients with KS. The effect of the IVS2 + 1G > A mutation is consistent with the previously reported loss-of-function mutations of MGP.


Combining 1D and 2D waveguiding in an ultrathin GaAs NW/Si tandem solar cell.
As an effective means to surpass the Shockley-Queisser efficiency limit, tandem solar cells have been successfully designed and used for years. However, there are still economical and design set-backs hampering the terrestrial implementation of tandem solar cells. Introducing high efficiency, thin Si-based tandem cells that are flexible in design (shape and curvature) will be the next major step towards integrating highly efficient solar cells into fashionable designs of today's buildings and technologies. In this work we present an optically coupled tandem cell that consists of a GaAs nanowire array on a 2μm-thick Si film as the top and bottom cells, respectively. By performing FDTD simulations, we show that coupling the incident light to guided modes of the 1D wires not only boosts the absorption in the wires, but also efficiently transfers the below bandgap photons to the Si bottom cell. Due to diffraction by the nanowire array the momentum of the transmitted light is matched to that of guided modes of the 2D Si thin film. Consequently, infrared light is up to four times more efficiently trapped in the Si bottom cell compared to when the film is not covered by the nanowires.


Incidental finding at methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA): how to proceed?
Introduction: Since the advent of new generation sequencing, professionals are aware of the possibility of obtaining findings unrelated to the pathology under study. However, this possibility is usually forgotten in the case of studies aimed at a single gene or region. We report a case of a 16-month-old girl with clinical suspicion of Silver-Russell syndrome (SRS). Methods: Following the international SRS consensus, methylation alterations and copy number variations (CNVs) at 11p15 region and maternal uniparental disomy of chromosome 7 were analysed and discarded by MS-MLPA. Results: Unexpectedly, the 11p15 region MS-MLPA showed a decrease in the signal of a copy number reference probe. Deletions affecting a single probe are inconclusive. So, we faced the ethical dilemma of whether it was appropriate to confirm this alteration with independent techniques and to offer a diagnostic possibility that was in no way related to clinical suspicion. Fortunately, in this particular case, the informed consent had not been specific to a particular pathology but to any disorder associated with growth failure. Performed alternative studies allowed the final diagnosis of 22q deletion syndrome. Conclusion: We demonstrate the importance of informing patients about the possibility of obtaining incidental findings in genetic techniques (not only in next generation sequencing) during pre-test genetic counselling consultations. In addition, we highlight the relevance of including in the informed consent the option of knowing these unexpected incidental findings as in some cases, this will help to elucidate the definitive diagnosis and provide the correct follow-up and treatment.