Exogenous Autoinducer-2 Rescues Intestinal Dysbiosis and Intestinal Inflammation in a Neonatal Mouse Necrotizing Enterocolitis Model.
Autoinducer-2 (AI-2) is believed to be a bacterial interspecies signaling molecule that plays an important role in the regulation of the physiological behaviors of bacteria. The effect of AI-2 on the process of necrotizing enterocolitis (NEC) is unknown, and the aim of this study was to study the effect of AI-2 in a mouse NEC model. C57BL/6 mouse pups were randomly divided into three groups: the control group, the NEC group, and the NEC+AI-2 (NA) group. Exogenous AI-2 (500 nM) was added to the formula milk of the NA group. The concentrations of fecal AI-2 and flora were tested. The expression of cytokines, TLR4 and NF-κB in intestinal tissue was detected. The AI-2 level was significantly decreased in the NEC group (P<0.05). Compared with the NEC group, the intestinal injury scores, expression of TLR4, NF-kB, and proinflammatory factors (IL-1β, IL-6, IL-8 and TNF-α) were reduced, and expression of anti-inflammatory factor (IL-10) was increased in the NA group mice (P<0.05). At the phylum level, the Proteobacteria abundance in the NA group was significantly increased, while the Bacteroidota abundance in the control group was significantly increased (P<0.05). At the genus level, Helicobacter and Clostridium_sensu_stricto_1 exhibited significantly greater abundance in the NEC group than in the other two groups, while Lactobacillus had the opposite trend (P<0.05). In addition, the abundances of Klebsiella, Rodentibacter and Enterococcus were significantly higher in the NA group than in the NEC and control groups (P < 0.05). Exogenous AI-2 partially reverses flora disorder and decreases inflammation in an NEC mouse model.


The effect of corticosteroids on the disposal of long-acting beta2-agonists by airway smooth muscle cells.
Organic cation transporters (OCTs) have an important role in tissue distribution and elimination of cationic drugs. Carrier-mediated disposal of cationic bronchodilators in the airway tissue, however, is incompletely understood. We sought to assess the uptake of long-acting beta(2)-agonist bronchodilators by bronchial and vascular smooth muscle cells. Human airway cells and tissues obtained from organ donors were evaluated for cationic drug transporter expression by means of quantitative RT-PCR and immunofluorescence. For in vitro functional studies, tritiated formoterol and tritiated salmeterol uptake by bronchial and vascular smooth muscle cells was measured. Quantitative RT-PCR analysis revealed high mRNA levels for the corticosteroid-sensitive OCT3 in bronchial and vascular smooth muscle cells. Immunofluorescence staining of airway sections confirmed OCT3 expression in these cells. In bronchial smooth muscle cells, uptake of the cationic formoterol was inhibited with OCT inhibitors. Corticosteroids also inhibited formoterol uptake through a rapid (within 15 minutes) nongenomic action, with the following rank order for inhibitory potency: corticosterone > budesonide > fluticasone. The corticosteroid-induced inhibition was significantly higher in vascular than bronchial smooth muscle cells. In comparison with formoterol, uptake of the noncharged lipophilic salmeterol was approximately 10-fold higher and insensitive to all OCT inhibitors and corticosteroids. Our findings suggest that corticosteroids, through OCT3 inhibition, rapidly interfere with the disposal of cationic drugs by smooth muscle cells in the airway. This novel immediate interaction between corticosteroids and cationic beta(2)-agonist bronchodilators supports the use of such combinations in the pharmacotherapy of asthma.


Analysis of root surface properties by fluorescence/Raman intensity ratio.
The aim of this study is to evaluate the existence of residual calculus on root surfaces by determining the fluorescence/Raman intensity ratio. Thirty-two extracted human teeth, partially covered with calculus on the root surface, were evaluated by using a portable Raman spectrophotometer, and a 785-nm, 100-mW laser was applied for fluorescence/Raman excitation. The collected spectra were normalized to the hydroxyapatite Raman band intensity at 960 cm-1. Raman spectra were recorded from the same point after changing the focal distance of the laser and the target radiating angle. In seven teeth, the condition of calculus, cementum, and dentin were evaluated. In 25 teeth, we determined the fluorescence/Raman intensity ratio following three strokes of debridement. Raman spectra collected from the dentin, cementum, and calculus were different. After normalization, spectra values were constant. The fluorescence/Raman intensity ratio of calculus region showed significant differences compared to the cementum and dentin (p < 0.05). The fluorescence/Raman intensity ratio decreased with calculus debridement. For this analysis, the delta value was defined as the difference between the values before and after three strokes, with the final 2 delta values close to zero, indicating a gradual asymptotic curve and the change in intensity ratio approximating that of individual constants. Fluorescence/Raman intensity ratio was effectively used to cancel the angle- and distance-dependent fluctuations of fluorescence collection efficiency during measurement. Changes in the fluorescence/Raman intensity ratio near zero suggested that cementum or dentin was exposed, and calculus removed.


Inhibition of interleukin-1beta-induced group IIA secretory phospholipase A2 expression by peroxisome proliferator-activated receptors (PPARs) in rat vascular smooth muscle cells: cooperation between PPARbeta and the proto-oncogene BCL-6.
The inflammation that occurs during atherosclerosis is characterized by the release of large amounts of group IIA secretory phospholipase A2 (sPLA2-IIA). This study was designed to define the function of the three peroxisome proliferator-activated receptors (PPARs) on sPLA2 expression in vascular smooth muscle cells (VSMCs). We found that PPAR ligands decreased sPLA2-IIA activity and inhibited mRNA accumulation under inflammatory conditions. Furthermore, interleukin-1beta-induced sPLA2-IIA promoter activity was inhibited by the three PPAR ligands and in a similar way when cells were cotransfected with PPARalpha, PPARbeta, or PPARgamma, plus retinoid X receptor alpha (RXRalpha). Our study revealed that the regulation of sPLA2-IIA gene transcription by PPARalpha/RXR and PPARgamma/RXR heterodimers requires an interaction with a PPAR response element (PPRE) of the sPLA2-IIA promoter. In contrast, PPARbeta operates through a PPRE-independent mechanism. In addition, we demonstrated that VSMCs expressed the transcriptional repressor BCL-6. Overexpression of BCL-6 markedly reduced sPLA2-IIA promoter activity in VSMCs, while a dominant negative form of BCL-6 abrogated sPLA2 repression by PPARbeta. The PPARbeta agonist induced a BCL-6 binding to the sPLA2 promoter in VSMCs under inflammatory conditions. The knockdown of BCL-6 by short interfering RNA abolished the inhibitory effect of the PPARbeta ligand on sPLA2 activity and prostaglandin E2 release. Thus, the inhibition of sPLA2-IIA activity by PPARbeta agonists may provide a promising approach to impacting the initiation and progression of atherosclerosis.


Cell and neuron densities in the primary motor cortex of primates.
Cell and neuron densities vary across the cortical sheet in a predictable manner across different primate species (Collins et al., 2010b). Primary motor cortex, M1, is characterized by lower neuron densities relative to other cortical areas. M1 contains a motor representation map of contralateral body parts from tail to tongue in a mediolateral sequence. Different functional movement representations within M1 likely require specialized microcircuitry for control of different body parts, and these differences in circuitry may be reflected by variation in cell and neuron densities. Here we determined cell and neuron densities for multiple sub-regions of M1 in six primate species, using the semi-automated flow fractionator method. The results verify previous reports of lower overall neuron densities in M1 compared to other parts of cortex in the six primate species examined. The most lateral regions of M1 that correspond to face and hand movement representations, are more neuron dense relative to medial locations in M1, which suggests differences in cortical circuitry within movement zones.


Thermal fluctuations determine the electron-transfer rates of cytochrome c in electrostatic and covalent complexes.
The heterogeneous electron-transfer (ET) reaction of cytochrome c (Cyt-c) electrostatically or covalently immobilized on electrodes coated with self-assembled monolayers (SAMs) of omega-functionalized alkanethiols is analyzed by surface-enhanced resonance Raman (SERR) spectroscopy and molecular dynamics (MD) simulations. Electrostatically bound Cyt-c on pure carboxyl-terminated and mixed carboxyl/hydroxyl-terminated SAMs reveals the same distance dependence of the rate constants, that is, electron tunneling at long distances and a regime controlled by the protein orientational distribution and dynamics that leads to a nearly distance-independent rate constant at short distances. Qualitatively, the same behavior is found for covalently bound Cyt-c, although the apparent ET rates in the plateau region are lower since protein mobility is restricted due to formation of amide bonds between the protein and the SAM. The experimental findings are consistent with the results of MD simulations indicating that thermal fluctuations of the protein and interfacial solvent molecules can effectively modulate the electron tunneling probability.


beta 2-microglobulin in non-malignant and malignant human breast: a feature of differentiation.
An indirect immunofluorescent method has been used to study the distribution of the membrane protein beta 2-microglobulin in normal, benign and malignant human breast tissue. A uniform staining of epithelial cell membranes has been found in all normal and benign tissues, with only a minor variation in the intensity of reaction between samples. In contrast the carcinomas have shown a variety of reactions, with some behaving in a manner similar to the normal and benign breast tissue, others being heterogeneous with regard to intensity of staining and the remainder having a weak or a negative reaction. The immunohistochemical behaviour of the carcinomas has paralleled the degree of histological differentiation, with poorly differentiated carcinomas showing little reactivity. A comparable relationship with lymph node status has not been found. Although those carcinomas with a staining pattern akin to non-malignant tissue have a lower incidence of lymph node metastasis it has been the heterogeneous reacting group rather than the weak staining and negative tumours which has shown a higher rate of axillary lymph node metastasis. The prognostic significance of this finding is at present uncertain and can probably only be assessed from information about patient survival.


Growth modulation effects of CBM2a under the control of AtEXP4 and CaMV35S promoters in Arabidopsis thaliana, Nicotiana tabacum and Eucalyptus camaldulensis.
The expression of cell-wall-targeted Carbohydrate Binding Modules (CBMs) can alter cell wall properties and modulate growth and development in plants such as tobacco and potato. CBM2a identified in xylanase 10A from Cellulomonas fimi is of particular interest for its ability to bind crystalline cellulose. However, its potential for promoting plant growth has not been explored. In this work, we tested the ability of CBM2a to promote growth when expressed using both CaMV35S and a vascular tissue-specific promoter derived from Arabidopsis expansin4 (AtEXP4) in three plant species: Arabidopsis, Nicotiana tabacum and Eucalyptus camaldulensis. In Arabidopsis, the expression of AtEXP4pro:CBM2a showed trends for growth promoting effects including the increase of root and hypocotyl lengths and the enlargements of the vascular xylem area, fiber cells and vessel cells. However, in N. tabacum, the expression of CBM2a under the control of either CaMV35S or AtEXP4 promoter resulted in subtle changes in the plant growth, and the thickness of secondary xylem and vessel and fiber cell sizes were generally reduced in the transgenic lines with AtEXP4pro:CBM2a. In Eucalyptus, while transgenics expressing CaMV35S:CBM2a showed very subtle changes compared to wild type, those transgenics with AtEXP4pro:CBM2a showed increases in plant height, enlargement of xylem areas and xylem fiber and vessel cells. These data provide comparative effects of expressing CBM2a protein in different plant species, and this finding can be applied for plant biomass improvement.


Picosecond time resolved photoluminescence spectroscopy of a tetracene film on highly oriented pyrolytic graphite: dynamical relaxation, trap emission, and superradiance.
A detailed time resolved investigation of the photoluminescence of a thin tetracene film deposited on highly oriented pyrolytic graphite is presented. In agreement with Lim et al. [Phys. Rev. Lett. 92, 107402 (2004)], we find strong evidence for superradiance: an increase of the relative intensity of the pure electronic transition with respect to the vibronic sideband and a concomitant decrease of the radiative lifetime from 10 to 1.83 ns upon cooling from 300 to 4 K. For lower temperatures, a redshift (approximately 200 cm(-1)) of the free exciton is observed. Previously, this shift was attributed to a structural phase transition. Our time resolved spectra reveal that the spectral shift is related to a dynamical relaxation process which occurs within the first 50 ps.


Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy.
African-American (AA) men have a higher risk of lethal prostate cancer (PCa) compared to European-American (EA) men. However, the molecular basis of this difference, if any, remains unclear. In EA PCa, PTEN loss, but not ERG rearrangement, has been associated with poor outcomes in most studies. Although ERG rearrangement is less common in AA compared to EA PCa, the relative frequency of PTEN loss and the association of PTEN/ERG molecular subtypes with outcomes is unknown for AA PCa. We examined PTEN/ERG status by immunohistochemistry in self-identified AA patients undergoing radical prostatectomy at Johns Hopkins with tumor tissue available on tissue microarray (TMA; n=169) and matched these cases by pathologic parameters to 169 EA patients from the same TMAs. The rate of PTEN loss was significantly lower in AA compared to EA PCa (18% vs 34%; p=0.001), similar to the lower rate of ERG expression (25% vs 51%; p<0.001). To examine the association of PTEN/ERG status with oncologic outcomes, we created an additional TMA of 87 AA tumors with Gleason score > 4 + 3 = 7. Among the total population of AA men with outcome data from all TMAs (n=222), PTEN loss was associated with higher risk of biochemical recurrence (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33-3.82) and metastasis (HR 3.90, 95% CI 1.46-10.4) in multivariable models. PTEN and ERG alterations in prostate cancer are less likely in African-American than in European-American men. However, PTEN loss remains associated with poor prostate cancer outcomes among African-American men.


Multidisciplinary survey of current and future use of emergency laparotomy risk assessment scores in New Zealand.
Risk prediction is an important part of the management of emergency laparotomy (EL) patients. This study aims to investigate the current use of and future directions for EL risk prediction scores. New Zealand members of the Royal Australasian College of Surgery (RACS), Australian and New Zealand College of Anaesthetists (ANZCA) and College of Intensive Care Medicine (CICM) were invited to participate in an anonymous online survey. Responses were received from 316 clinicians (45 RACS, 253 ANZCA and 19 CICM), with 73% of them having >10 years' experience as a consultant. Risk assessment scores were utilised by respondents for approximately 30% of EL cases. The most common EL risk scores used were Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality (P-POSSUM) and American College of Surgeons National Surgical Quality Improvement Programs (ACS-NSQIP). When used, respondents used risk assessment mostly preoperatively (RACS 100%, ANZCA 98% and CICM 78%), although P-POSSUM and ACS-NSQIP scores require intraoperative data (which can only be estimated crudely preoperatively by the clinician). Respondents on average 'somewhat agreed' that risk assessment scores should only include preoperative variables. The most common reasons for using P-POSSUM and ACS-NSQIP scores were familiarity and ease of use and availability of online/app calculators. The most important outcomes that the respondents would like to predict were quality of life and 30-day mortality rather than long-term impact from EL. These findings suggest that developing a new score may be required to improve utilisation and help in decision-making. This may require tailoring risk scores specifically for EL, and designing them to predict what is preferred by the clinicians making the decisions.


Do bronchodilators have an effect on bronchiolitis?
Over the past 12 years there have been 12 randomised control trials, involving 843 infants, evaluating the effect of salbutamol or albuterol on bronchiolitis. Of these, nine (75%) showed that bronchodilators had no effect. In three studies a small transient improvement in the acute clinical score was seen. Ipratropium bromide had no significant effect. There have been five recent randomised trials involving 225 infants, evaluating the effect of nebulised adrenaline (epinephrine) on bronchiolitis. All five (100%) have shown significant clinical improvement, with reductions in oxygen requirement, respiratory rate and wheeze after nebulised adrenaline. Two showed lower hospital admission rates and earlier discharge with adrenaline. A significant improvement in pulmonary resistance was observed after nebulised adrenaline but not after salbutamol or albuterol. Currently there is no compelling evidence that bronchodilators have a role in the routine management of infants with bronchiolitis. There is better evidence for the use of nebulised adrenaline.


Effects of chronic folate deficiency and sex differences on depression-like behavior in mice.
Although previous studies have reported that serum folate levels are negatively associated with depression in women but not men, it remains unclear whether folate deficiency can directly lead to depression and whether sex difference serves a role in this condition, since the potential mechanism remains elusive. Therefore, the present study aimed to investigate whether folate deficiency results in differences in parameters associated with depression between males and females. CD-1 mice received either a standard control diet or a folate-deficient diet from 10 to 38 weeks of age, following which behavioral assays, such as an open field test, sucrose preference test and forced swim test were performed throughout week 38. Serum and cerebral cortex samples were subsequently collected for assessment. Serum folate, homocysteine, estradiol (E2) and testosterone levels were measured using chemiluminescence, enzymatic cycling assay and electrochemiluminescence immunoassays. The cerebral cortex was used for western blot analysis, to detect the expression levels of estrogen receptor β (ERβ), PI3K/AKT pathway and caspase-3. The results revealed that compared with those in female mice that received standard control diet, female mice that received folate-deficient diet exhibited lower E2 concentrations, lower sucrose preferences (as determined through the sucrose preference test), longer durations of immobility (as determined in the forced swim test) and less time spent in the central areas of the open field test. Western blotting demonstrated that the expression levels of ERβ and the phosphorylation levels of PI3K and AKT were decreased, whilst the expression levels of cleaved caspase-3 were increased, in the cerebral cortex of female mice that received folate-deficient diet. However, no differences in E2 concentration, behavioral assay parameters or protein levels of ERβ, phosphorylated (p-)PI3K, p-AKT and cleaved caspase-3 could be observed in male mice regardless of whether they received standard control or folate-deficient diets. Collectively, these results revealed that folate deficiency only led to depression-like behavior in female mice. This may be associated with reduced E2 levels, which may inhibit the PI3K/AKT pathway and upregulate the expression of cleaved caspase-3 to promote neuronal apoptosis.


KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway.
Bladder cancer (BCa) is a common malignancy characterized by high heterogeneity, yet the current treatment modalities are limited. The aim of the present investigation was to unravel the functional role of Karyopherin alpha 2 (KPNA2), a tumor facilitator identified in multiple malignancies, in the progression of BCa. BCa tissues and adjacent normal tissues were surgically resected and analyzed from patients with BCa to determine the expression profile of KPNA2 and Chromobox 8 (CBX8) by RT-qPCR, Western blot analysis and immunohistochemistry. The relationship among KPNA2, CBX8 and PR domain zinc finger protein 1 (PRDM1) was explored by co-immunoprecipitation and chromatin-immunoprecipitation. The functions of KPNA2, CBX8 and PRDM1 on BCa cell proliferation, migration and invasion were evaluated. Next, a nude mouse model of BCa was established for validating the roles of KPNA2, CBX8 and PRDM1 in vivo. KPNA2 and CBX8 were highly expressed in BCa and are in association with dismal oncologic outcomes of patients with BCa. KPNA2 promoted nuclear import of CBX8. CBX8 downregulated PRDM1 by recruiting BCOR in the promoter region of PRDM1. Overexpression of KPNA2 promoted the malignant behaviors of BCa cells, which was counteracted by silencing of CBX8. Overexpressing PRDM1 attenuated the progression of BCa by inhibiting c-FOS expression. The tumor-promoting effects of KPNA2 via the PRDM1/c-FOS pathway were also validated in vivo. Collectively, our findings attached great importance to the interplay between KPNA2 and CBX8 in BCa in mediating the development and progression of BCa, thus offering a promising candidate target for better BCa patient management.


Improved Sepsis Alert With a Telephone Call From the Clinical Microbiology Laboratory: A Clinical Trial.
Early sepsis attention is a standard of care in many institutions and the role of different specialists is well recognized. However, the impact of a telephone call from a specialist in Clinical Microbiology upon blood cultures request has not been assessed to the best of our knowledge. We performed telephone calls followed by an interview with physicians and nurses in charge of adult patients (> 18 years old) whose blood cultures had just been received in the Microbiology Laboratory in a tertiary hospital. Patients were randomly classified in 2 different groups: group A (telephone call performed) and group B (no telephone call). At the end of the telephonic intervention, recommendations on the use of microbiology and biochemical tests as well as on the management and antibiotic therapy of sepsis were made if required. We included 300 patients. Of those fulfilling standard criteria of sepsis, 30.3% of the nurses and 50% of the physicians immediately recognized it. Advice to optimize the use of biochemical and microbiological tests was provided in 36% of the cases and to improve antimicrobial therapy in 57.6%. The median number of days of antibiotic use in groups A and B were, respectively, 6 days (IQR: 2-12) vs 9 days (IQR: 4-16) P = 0.008 and the median number of prescribed daily doses of antimicrobials (6 [IQR: 3-17] vs 10 [IQR: 5-22] P = 0.016) were lower in group A. We estimate a reduction, only in the use of antibiotic, of 1.8 million Euros per year. A telephone call with management advice, immediately after the arrival of blood cultures in the Microbiology Laboratory improves the recognition of sepsis and the use of diagnostic resources and reduces antimicrobial consumption and expenses.


Bio-inspired liposomal thrombomodulin conjugate through bio-orthogonal chemistry.
We report the synthesis of bioinspired liposomal thrombomodulin (TM) conjugates by chemoselective and site-specific liposomal conjugation of recombinant TM at C-terminus. TM is an endothelial cell membrane protein that acts as a major cofactor in the protein C anticoagulant pathway. To closely mimic membrane protein structural features of TM, we proposed membrane-mimetic re-expression of recombinant TM onto liposome. A recombinant TM containing the EGF-like 456 domains and an azidohomoalanine at C-terminus was expressed in E. coli. Conjugation of the recombinant TM onto liposome via Staudinger ligation and copper-free click chemistry were investigated as an optimal platform for exploring membrane protein TM's activity, respectively. The bioinspired liposomal TM conjugates were confirmed with Western blotting and protein C activation activity. The recombinant TM-liposome conjugates showed a 2-fold higher k(cat)/K(m) value for protein C activation than that of the recombinant TM alone, which indicated that the lipid membrane has a beneficiary effect on the recombinant TM's activity. The reported liposomal protein conjugate approach provides a rational design strategy for both studying membrane protein TM's functions and generating a membrane protein TM-based anticoagulant agent.


[Effects of guifu dihuang pills extract on rabbit IgG accelerated mouse nephritis induced by nephrotoxic serum].
The effects of Guifu Dihuang Pills extract were observed in rabbit IgG accelerated mouse nephritis model induced by nephrotoxic serum. The results showed that this preparation could increase serum albumin, reduce urine protein, serum urea nitrogen and total cholesterol in serum, and improve the histological lesions in kidneys. The effects of Guifu Dihuang Pills extract in dosages of 0.3g/kg and 1.2g/kg were similar to those of cyclophosphamide 0.015g/kg.


[Analysis and research of brain-computer interface experiments for imaging left-right hands movement].
This is a research carried out to explore a pragmatic way of BCI based imaging movement, i. e. to extract the feature of EEG for reflecting different thinking by searching suitable methods of signal extraction and recognition algorithm processing, to boost the recognition rate of communication for BCI system, and finally to establish a substantial theory and experimental support for BCI application. In this paper, different mental tasks for imaging left-right hands movement from 6 subjects were studied in three different time sections (hint keying at 2s, 1s and 0s after appearance of arrow). Then we used wavelet analysis and Feed-forward Back-propagation Neural Network (BP-NN) method for processing and analyzing the experimental data of off-line. Delay time delta t2, delta t1 and delta t0 for all subjects in the three different time sections were analyzed. There was significant difference between delta to and delta t2 or delta t1 (P<0.05), but no significant difference was noted between delta t2 and delta t1 (P>0.05). The average results of recognition rate were 65%, 86.67% and 72%, respectively. There were obviously different features for imaging left-right hands movement about 0.5-1s before actual movement; these features displayed significant difference. We got higher recognition rate of communication under the hint keying at about 1s after the appearance of arrow. These showed the feasibility of using the feature signals extracted from the project as the external control signals for BCI system, and demon strated that the project provided new ideas and methods for feature extraction and classification of mental tasks for BCI.


Computer-Based Training Programs for Older People with Mild Cognitive Impairment and/or Dementia.
Currently, due to the demographic trends, the number of aging population groups is dramatically rising, especially in developed countries. This trend causes serious economic and social issues, but also an increase of aging disorders such as mild cognitive impairment (MCI) or dementia in older population groups. MCI and dementia are connected with deterioration of cognitive functions. The aim of this mini review article is therefore to explore whether computer-based training programs might be an effective intervention tool for older people with MCI and/or dementia or not. The methods include a literature search in the world's acknowledged databases: Web of Science, Scopus, Science Direct, MEDLINE and Springer, and consequently, evaluation of the findings of the relevant studies. The findings from the selected studies are quite neutral with respect to the efficacy of the computer assisted intervention programs on the improvement of basic cognitive functions. On the one hand, they suggest that the computer-based training interventions might generate some positive effects on patients with MCI and/or dementia, such as the improvement of learning and short-term memory, as well as behavioral symptoms. On the other hand, these training interventions seem to be short-term, with small sample sizes and their efficacy was proved only in the half of the detected studies. Therefore more longitudinal randomized controlled trials (RCTs) are needed to prove the efficacy of the computer-based training programs among older individuals with MCI and/or dementia.


Mycelial compatibility groups and pathogenic diversity in Sclerotium rolfsii populations from sugar beet crops in Mediterranean-type climate regions.
The population structure of Sclerotium rolfsii from autumn-sown sugar beet crops in Mediterranean-type climate regions of Chile, Italy, Portugal and Spain was determined by analyses of mycelial compatibility groups (MCGs) and pathogenicity to 11 economically important plant species. Twelve MCGs (i-xii) were identified among 459 S. rolfsii isolates. MCG iii was the most prevalent group in all countries except Italy. MCG i, the most abundant group (64·7% of isolates) was identified in Portugal and Spain. The remaining MCGs were restricted to various regions within one country (ii, vi, ix) or different countries (v), or to specific localities (iv, vii, viii, x, xi, xii). MCGs iv, vii and x each comprised one isolate. Fields extensively sampled in southern Spain were infected with one to three MCGs. Plant species differed in susceptibility to MCG tester isolates with a MCG by species interaction. Cluster analyses allowed selection into five MCG groupings and grouped plant species into species-groups 1 (broccoli, chickpea, sunflower, tomato) and 2 (cotton, pepper, sugar beet, watermelon). MCG groupings 1 (i, ix), 2 (ii, iii, vi, viii) and 5 (x, xii) were moderately virulent to species-group 1 and mildly virulent to species-group 2. MCG groupings 3 (iv, v, xi) and 4 (vii) were mildly virulent to both species-groups. Across MCG groups, species were rated highly susceptible (chickpea, sunflower), susceptible (cotton, pepper, tomato, watermelon), moderately resistant (broccoli, melon, sugar beet) and resistant (corn, wheat). Establishing the MCG population structure and virulence variability among S. rolfsii isolates should help in the management of sclerotium root rot diseases.


Pyrethroid epidemiology: a quality-based review.
Pyrethroids are commonly used around the home and in agricultural production to control insects. Human contact to one or more pyrethroid insecticides is likely. Numerous epidemiology studies have evaluated the association between health outcomes in humans and pyrethroid exposure. The purpose of this review was to identify and evaluate the quality of pyrethroid-related epidemiology studies that addressed chronic health effects, and compare findings with animal toxicology studies. We evaluated the quality of 61 studies published between 2000 and 2016 by using elements of outcome, exposure metric, exposure level, and study design. None of the 61 publications demonstrated strong quality for all elements. A few of the outcome measures were strong, particularly those relying upon medical diagnoses. Most of the pyrethroid epidemiology studies used a poor exposure metric, relying upon a single sample of pyrethroid urinary metabolites, which is subject to misclassification of past exposures. In addition, many studies were a cross-sectional design, preventing an evaluation of the temporality of the exposure-disease association. Furthermore, none of the effects observed in the epidemiological literature was concordant with toxicological effects noted in extensive testing of pyrethroids in animals. In order to provide more robust data on potential health outcomes from low dose exposure to pyrethroid insecticides, future epidemiological studies should fully characterize an adverse outcome, include exposure validation components, and quantify exposure over time.


Modulating effect of the A-278C promoter polymorphism in the cholesterol 7alpha-hydroxylase gene on serum lipid levels in normolipidaemic and hypertriglyceridaemic individuals.
The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7alpha-hydroxylase (CYP7A1). An A to C substitution 278 bp upstream in the promoter of the CYP7A1 gene was found to be associated with variations in serum lipid levels in normolipidaemic populations. In the present study, we investigated the involvement of this polymorphism in four different lipid disorders: hypertriglyceridaemia (HTG), combined hyperlipidaemia (CH), familial dysbetalipoproteinaemia (FD) and familial hypercholesterolaemia (FH). In a normolipidaemic male population, homozygous for the apoE3 isoform, an association was found between the AA genotype and higher levels of serum triglycerides (AA: +34%, P = 0.036). In HTG patients, the AA genotype was associated with significantly higher concentrations of total cholesterol (+23%, P = 0.005). There was a tendency towards increased levels of serum triglycerides (+39%, P = 0.06), VLDL-triglycerides (+48%, P = 0.053) and VLDL-cholesterol (+35%, P = 0.059). No significant associations were found between serum lipid levels and the CYP7A1 polymorphism in patients with CH, FD and FH. Our results show that the A-278C polymorphism in the CYP7A1 gene has an effect on triglyceride levels in normolipidaemic males and on cholesterol levels in patients with hypertriglyceridaemia..


Baseline Susceptibility and Cross-Resistance in Adult and Larval Alphitobius diaperinus (Coleoptera: Tenebrionidae) Collected from Poultry Farms in Arkansas.
Insecticide resistance in the lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), can pose a serious threat to their successful management in broiler chicken farms in Arkansas. Resistance and cross-resistance were determined in lesser mealworm populations collected from two broiler farms in Arkansas, with different insecticide application histories. Farm M was treated with insecticides over the past 10 yr, whereas Farm S had no insecticidal usage history. Concentration-mortality bioassays using selected insecticides were conducted on adults and seventh-instar larval beetles. A probit analysis suggested the M population to be resistant to cyfluthrin and tetrachlorvinphos, while the S population was susceptible to both compounds. The M population showed no cross-resistance to imidacloprid, spinosad, or chlorfenapyr. The M and S populations were similar in their susceptibility to imidacloprid, spinosad, and chlorfenapyr. The suitability of imidacloprid and spinosad, and further testing of chlorfenapyr as a potential candidate for lesser mealworm control is discussed.


DNA-binding chromosomal non-histone proteins. Isolation, characterization, and tissue specifity.
A fractionation schedule is described which allows the isolation of a group of chromosomal non-histone proteins (NP) with affinity for DNA. In polyacrylamide gel electrophoresis these proteins isolated from rat liver are represented principally by a group of low molecular weight polypeptides. The NP fraction comprises about 2-4% of the total chromatin protein content in rat liver or Novikoff hepatoma. Experiments in vivo and in vitro revealed that the NP proteins do not incorporate significant amounts of 32P. Complexes of the chromosomal proteins NP with homologous DNA are immunologically tissue specific and the specificity can be transferred by reconstituting the NP proteins from one tissue to the residual chromatin from another.


The HSV-1 2-kb latency-associated transcript is found in the cytoplasm comigrating with ribosomal subunits during productive infection.
We have examined the nuclear and cytoplasmic distribution of the latency-associated transcripts (LATs) of HSV-1. During latency these transcripts accumulate in the nuclei of neurons in the peripheral and central nervous system of infected animals. However, our Northern blot analyses demonstrate that the 2-kb LAT is found in the cytoplasm of HSV-1-infected CV-1 cells, and brainstems of HSV-1 productively infected mice. Like the nuclear LAT from latently infected tissue, most of the cytoplasmic 2-kb LAT from lytically infected CV-1 cells is unpolyadenylated. In order to determine if cytoplasmic LAT could be translated, we compared its distribution with that of glycoprotein C mRNA in polysome profiles from HSV-1-infected tissue culture cells. Specific association of RNAs to polysomes was verified by disruption of polysomes with EDTA or puromycin. Analyses of numerous experiments indicate that most of the cytoplasmic 2-kb LAT migrates at the position of ribosomal subunits in polysome profiles. Thus, the 2-kb LAT may not be efficiently translated during productive infection. This suggests that if the 2-kb LAT is indeed translated, its translation may be tightly regulated during HSV-1 infection, possibly in a cell type- or cell cycle-specific manner. Another possibility is that the 2-kb LAT is not a translated RNA but may have another function, possibly related to translation as indicated by its apparent association to ribosomal complexes.


Airways inflammation and glucan exposure among household waste collectors.
A field study was made on 17 workers collecting unsorted household waste, eight workers collecting organic/nonorganic separated waste, and 24 controls. Measurements of airborne endotoxin and (1-->3)-beta-D-glucan were made in their working environments. Examinations consisted of a questionnaire for symptoms, spirometry, airway responsiveness, and blood and sputum sampling for determination of cell counts, eosinophilic cationic protein (ECP), and myeoloperoxidase (MPO). A higher proportion of waste collectors reported diarrhea, congested nose, and unusual tiredness as compared to controls. The number of blood lymphocytes was higher among waste collectors and were dose-related to the amount of airborne (1-->3)-beta-D-glucan at the workplaces. The amount of ECP and the number of macrophages were lower in sputum among waste collectors as compared with controls. The results suggest that certain dusts from household waste may cause airway inflammation as well as general symptoms, and the effects were associated with higher (1-->3)-beta-D-glucan levels.


An analysis of 7836 successive new outpatient referrals.
An analysis has been performed of 7836 successive new outpatient referrals seen by one consultant neurologist. In approximately a quarter of the patients, a specific diagnosis was not possible. A further 30% of the total was accounted for by epilepsy, tension headache, cerebrovascular disease and migraine.


Detecting hepatic lesions: the added utility of CT liver window settings.
To prospectively evaluate the utility of adding computed tomographic (CT) liver windows to conventional soft-tissue windows for the detection of hepatic disease. One of four radiologists experienced in abdominal imaging interpreted 1,175 consecutive abdominal CT scans from one institution. Hepatic images were first interpreted by using standard soft-tissue windows. The number of lesions and confidence in lesion detection were recorded. The liver-window images were then interpreted in conjunction with the soft-tissue-window images, and the number of lesions and confidence in detection were recorded again. The proportion of patients in whom additional lesions were found by using liver windows was determined. On soft-tissue-window and liver-window scans interpreted together, 869 (74%) patients had no hepatic lesions. Thirty-six (3.1%) patients had new lesions seen with the addition of liver windows. Twelve of these 36 patients had no lesions seen on soft-tissue-window scans. Twenty-six of the 36 patients with additional lesions seen had a history of neoplasm. There was a change in diagnosis in 1.7% of the patients with the addition of liver windows and a change in recommendation for follow-up in 0.85%. Routine interpretation of liver-window scans for all abdominal CT scans has limited added utility in detecting hepatic disease.


[The actual issues of development of manpower potential in health care].
The analysis was implemented concerning main directions of development of health care manpower policy in Moscow. The activities are established related to improvement of actual situation with development of potential of medical personnel, increasing of motivation ofphysicians and paramedical personnel, improvement of conditions of development of manpower resources.


Adsorbate-enhanced field-emission from single-walled carbon nanotubes: a comparative first-principles study.
We report a comparative ab initio study of different types of adsorbates and their adsorption mechanism on the field-emission performance of single-walled carbon nanotubes by analyzing electrical properties and transport characteristics and considering the thermal stability of the adsorbed structure. Adsorbates were found to reduce the work function by up to 1.3 eV, enhance tunneling near the carbon nanotube tip, and increase the field-emission current by as much as two orders of magnitude. A significant localization of the electron cloud was also observed near the adsorbates under a high applied electric field.


Reducing the risk of transmitting genital herpes: advances in understanding and therapy.
This review considers the epidemiology and impact of genital herpes, discusses how herpes simplex virus-2 (HSV-2) is transmitted, and reviews data on methods of reducing the risk of HSV transmission. Information for the paper was identified through multiple PubMed searches. Information in the section on interventions was identified through PubMed searches using several pairs of key words (herpes and transmission, herpes and treatment, herpes and antiviral, herpes and valacyclovir, herpes and famciclovir, herpes and acyclovir, herpes and condom, herpes and clinical trial). The searches, conducted in January 2005, did not have date limits. Papers were selected for inclusion based on the author's judgment of their relevance to the topic of the review. An estimated 45 million persons in the United States have genital herpes infection, and new infections occur at a rate of approximately one million per year. Approximately 85% to 90% of infections are unrecognized and therefore undiagnosed. Individuals with genital HSV-2 infection shed virus during asymptomatic periods as well as symptomatic periods. In fact, transmission frequently occurs during periods of asymptomatic viral shedding. Asymptomatic viral shedding (1) occurs in the majority of patients with genital HSV-2 infection; (2) accounts for approximately one third of the days of viral shedding; (3) occurs regardless of duration of infection but is most frequent during the first year after infection; (4) occurs more than 7 days before or after a symptomatic recurrence 50% of the time; and (5) does not differ significantly when comparing patients with 1 to 12 annual recurrences to those with no recurrences. A recently published study of discordant couples counseled on safe sex practices found that once daily suppressive therapy with valacyclovir reduced the risk of transmission of HSV-2 in heterosexual immunocompetent adult couples discordant for HSV-2 infection. In an 8-month study, daily valacyclovir compared with placebo reduced the risk of acquisition of symptomatic genital HSV-2 infection by 75% (2.2% placebo vs. 0.5% valacyclovir; hazard ratio = 0.25; p = 0.008). The overall risk of acquisition of HSV-2 infection (defined via laboratory-confirmed symptoms or seroconversion) was reduced by 48% (3.6% placebo vs. 1.9% valacyclovir hazard ratio = 0.52; p = 0.04). The most common adverse events in the study were headache, nasopharyngitis, and upper respiratory infection. Daily suppressive therapy is recommended as a therapeutic option for HSV-2 seropositive individuals at risk of transmitting HSV-2. Because no intervention completely protects against transmission of HSV, infected individuals and their partners should be counseled to use safer sex practices, including the use of condoms.


Hepatitis C virus NS3-4A protease inhibitors: countering viral subversion in vitro and showing promise in the clinic.
Hepatitis C virus (HCV) NS3.4A protease inhibitors have potential for treating chronic HCV disease. Robust antiviral effects have been reported for the three HCV NS3.4A inhibitors (BILN-2061 (ciluprevir), telaprevir (VX-950; Vertex Pharmaceuticals Inc./Janssen Pharnmaceutica NV/Mitsubishi Pharma Corp.) and SCH-503034; Schering-Plough Research Institute) that have been studied in clinical trials to date in HCV-infected patients, and new inhibitor molecules continue to appear on the horizon. Herein, toe relate the remarkable progress of these drug candidates to recent evidence that suggests HCV might depend on NS3.4A protease to subvert multiple innate cellular defense mechanisms.


Sexual dysfunction and sex therapy: an historical perspective.
Summary Sexual dysfunction has been reported across cultures and across time. The Hindu literature and the Ayurvedic system offer insights into assessment and management of various kinds of sexual dysfunction. Behavioural regimes were fairly well known in the traditional Ayurvedic texts. Religious writings have often proved to be the richest source of information about sexual behaviour. The relationship between the nature of creation, the need for reproduction and the importance of sex in life has often been discussed in religions. Artificial sexual aids were well known in both ancient China and India. This paper attempts to draw an historical analysis of varieties of sexual dysfunction across various societies. It also comments on the historical development of sex therapy.


Palladium-Catalyzed Alkoxycarbonylation of Unactivated Secondary Alkyl Bromides at Low Pressure.
Catalytic carbonylations of organohalides are important C-C bond formations in chemical synthesis. Carbonylations of unactivated alkyl halides remain a challenge and currently require the use of alkyl iodides under harsh conditions and high pressures of CO. Herein we report a palladium-catalyzed alkoxycarbonylation of secondary alkyl bromides that proceeds at low pressure (2 atm CO) under mild conditions. Preliminary mechanistic studies are consistent with a hybrid organometallic-radical process. These reactions efficiently deliver esters from unactivated alkyl bromides across a diverse range of substrates and represent the first catalytic carbonylations of alkyl bromides with carbon monoxide.


Safety and efficacy of bipolar energy for transurethral resection of bladder tumours: a prospective quasi-randomized study.
The primary aim of the study was to evaluate the safety and efficacy of bipolar energy in resecting bladder tumors. The study was done between March 2012 and February 2013. This is a prospective quasi-randomized study evaluating the safety and efficacy of bipolar energy in transurethral resection of bladder tumours (TURBT). Institutional Ethics Committee approval was obtained. Informed consent was taken from all patients. Patients were randomized into two groups of 50 each to undergo either monopolar TURBT or bipolar TURBT using glycine and saline irrigation solutions, respectively. Most important of all, the means of variables were compared between the two energy sources to know the difference between them and its significance. Hematocrit level, resection time and obturator jerks had significant values. The results of this study indicated that bipolar resection of bladder tumours have lower incidence of complications especially bleeding, TUR syndrome, obturator jerks and bladder perforation. Bipolar TURBT is safe and efficacious in managing bladder tumours.


Effects of succinylcholine on the recovery of block produced by mivacurium in rats.
This study investigates the effects of succinylcholine on the recovery of neuromuscular blockade produced by mivacurium in rats. In 48 anesthetized animals, the sciatic nerve was prepared and stimulated, and twitches of the flexor digitorum longus muscle were recorded. Animals were randomly divided into four groups (n = 12 each): bolus dose of succinylcholine 0.1 mg/kg (GroupSch), bolus dose of mivacurium 0.15 mg/kg (GroupMiv), bolus dose of mivacurium 0.15 mg/kg, followed by succinylcholine 0.1 mg/kg at 25% neuromuscular recovery from mivacurium (Group-MivSch(25)), or bolus dose of mivacurium 0.15 mg/kg, followed by succinylcholine 0.1 mg/kg at 75% neuromuscular recovery from mivacurium (GroupMivSch(75)). Onset times of neuromuscular block following succinylcholine in mivacurium-treated groups were comparable and significantly shorter than in GroupSch (p < 0.001). Duration of action of succinylcholine was more prolonged when it was given in the presence of deeper neuromuscular block induced by mivacurium (p < 0.001 in GroupMivSch(25) and p < 0.01 in GroupMivSch(75)). Our results suggest that, in rats, mivacurium administration has a significant potentiating effect on a subsequent succinylcholine-induced neuromuscular block.


Intramolecular structural heterogeneity altered by long-range contacts in an intrinsically disordered protein.
Short-range interactions and long-range contacts drive the 3D folding of structured proteins. The proteins' structure has a direct impact on their biological function. However, nearly 40% of the eukaryotes proteome is composed of intrinsically disordered proteins (IDPs) and protein regions that fluctuate between ensembles of numerous conformations. Therefore, to understand their biological function, it is critical to depict how the structural ensemble statistics correlate to the IDPs' amino acid sequence. Here, using small-angle X-ray scattering and time-resolved Förster resonance energy transfer (trFRET), we study the intramolecular structural heterogeneity of the neurofilament low intrinsically disordered tail domain (NFLt). Using theoretical results of polymer physics, we find that the Flory scaling exponent of NFLt subsegments correlates linearly with their net charge, ranging from statistics of ideal to self-avoiding chains. Surprisingly, measuring the same segments in the context of the whole NFLt protein, we find that regardless of the peptide sequence, the segments' structural statistics are more expanded than when measured independently. Our findings show that while polymer physics can, to some level, relate the IDP's sequence to its ensemble conformations, long-range contacts between distant amino acids play a crucial role in determining intramolecular structures. This emphasizes the necessity of advanced polymer theories to fully describe IDPs ensembles with the hope that it will allow us to model their biological function.


#influenced! The impact of social media influencing on self-esteem and the role of social comparison and resilience.
Social media influencers (SMIs) are online personas that acquire significant audiences on social networking sites (SNS) and have become a prevalent part of social media. Previous research indicates potentially detrimental effects of social media use on mental well-being, however, little is known about whether, how, and for whom online comparisons with SMIs lead to adverse psychological effects. In this study, we investigate the impact of positivity-biased images of female SMIs on the state self-esteem of female participants while considering social comparison processes as mediating and individual resilience as moderating factors. Regression analyses showed that acute exposure to positivity-biased SMI images led to upward social comparisons, which in turn predicted lower state self-esteem. Thus, results revealed a significant mediating effect of social comparisons on the association between image type and state self-esteem. However, when observing the direct effect of image type on state self-esteem, we found that the exposure to positivity-biased SMI images unexpectedly led to higher overall levels of state self-esteem relative to the control group. In light of contemporary social comparison literature, subsequent post-hoc analyses suggest that exposure to SMI images in this study may have prompted both contrastive and assimilative upwards comparisons, leading to varying consequences for distinct self-esteem dimensions, ultimately manifesting in the observed suppression effect. Resilience was not found to moderate the proposed associations. Thus, the findings of this study offer new insights into the impact of SMIs on individuals' self-evaluations online, challenging previous assumptions, and suggest a need for further examination.


Theory and measurement of the soliton self-frequency shift and efficiency in optical microcavities.
Dissipative Kerr cavity solitons experience a so-called self-frequency shift (SFS) as a result of Raman interactions. The frequency shift has been observed in several microcavity systems. The Raman process has also been shown numerically to influence the soliton pumping efficiency. Here, a perturbed Lagrangian approach is used to derive simple analytical expressions for the SFS and the soliton efficiency. The predicted dependences of these quantities on soliton pulse width are compared with measurements in a high-Q silica microcavity. The Raman time constant in silica is also inferred. Analytical expressions for the Raman SFS and soliton efficiency greatly simplify the prediction of soliton behavior over a wide range of microcavity platforms.


The first example of molecularly imprinted nanogels with aldolase type I activity.
The molecular-imprinting approach was used to obtain a nanogel preparation capable of catalysing the cross-aldol reaction between 4-nitrobenzaldehyde and acetone. A polymerisable proline derivative was used as the functional monomer to mimic the enamine-based mechanism of aldolase type I enzymes. The diketone template used to create the cavity was designed to imitate the intermediate of the aldol reaction and was bound to the functional monomer using a reversible covalent interaction prior to polymerisation. By using a high-dilution polymerisation method, soluble imprinted nanogels were prepared with dimensions similar to those of an enzyme and with the advantage of solubility and flexibility previously unattainable with monolithic polymers. Following template removal and estimation of active-site concentrations, the kinetic characterisation of both imprinted and non-imprinted nanogels was carried out with catalyst concentrations between 0.7 and 3.5 mol %. Imprinted nanogel AS147 was found to have a k(cat) value of 0.25 x 10(-2) min(-1), the highest value ever achieved with imprinted polymers catalysing C--C bond formation. Comparison of the catalytic constants for both imprinted nanogel AS147 and non-imprinted nanogel AS133 gave a ratio of k(cat 147)/k(cat 133)=18.8, which is indicative of good imprinting efficiency and highlights the significance of the template during the imprinting process. This work represents a significant demonstration of the superiority of nanogels, when the molecular-imprinting approach is used, over "bulk" polymers for the generation of catalysts.


Grouped beating: to couple into trouble.
We discuss the 12-lead electrocardiogram and differential diagnosis of a regularly irregular narrow QRS-complex rhythm obtained from a patient with a history of atrial fibrillation who was admitted because of bradycardia-associated symptoms.


The role of cGMP as a mediator of lipolysis in bovine oocytes and its effects on embryo development and cryopreservation.
This study aimed to determine the influence of cyclic guanosine 3'5'-monophosphate (cGMP) and cGMP-dependent kinase (PKG) during in vitro maturation (IVM) on lipolysis-related parameters in bovine cumulus-oocyte complexes (COCs), and on embryo development and cryosurvival. COCs were matured with cGMP/PKG modulators and assessed for metaphase II rates (MII), cGMP levels, lipid content in oocytes (OO), transcript abundance for genes involved in lipolysis (ATGL) and lipid droplets (PLIN2) in cumulus cells (CC) and OO, and presence of phosphorylated (active) hormone sensitive lipase (HSLser563) in OO. Embryo development, lipid contents and survival to vitrification were also assessed. Phosphodiesterase 5 inhibition (PDE5; cGMP-hydrolyzing enzyme) with 10-5M sildenafil (SDF) during 24 h IVM increased cGMP in COCs (56.9 vs 9.5 fMol/COC in untreated controls, p<0.05) and did not affect on maturation rate (84.3±6.4% MII). Fetal calf serum (FCS) in IVM medium decreased cGMP in COCs compared to bovine serum albumin (BSA) + SDF (19.6 vs 66.5 fMol/COC, respectively, p<0.05). FCS increased lipid content in OO (40.1 FI, p<0.05) compared to BSA (34.6 FI), while SDF decreased (29.8 and 29.6 FI, with BSA or FCS, respectively p<0.05). PKG inhibitor (KT5823) reversed this effect (38.9 FI, p<0.05). ATGL and PLIN2 transcripts were detected in CC and OO, but were affected by cGMP and PKG only in CC. HSLser563 was detected in OO matured with or without modulators. Reduced lipid content in embryos were observed only when SDF was added during IVM and IVC (27.6 FI) compared to its use in either or none of the culture periods (34.2 FI, p<0.05). Survival to vitrification was unaffected by SDF. In conclusion, cGMP and PKG are involved in lipolysis in OO and possibly in CC and embryos; serum negatively affects this pathway, contributing to lipid accumulation, and cGMP modulation may reduce lipid contents in oocytes and embryos, but without improving embryo cryotolerance.


Chemicals eluting from disposable plastic syringes and syringe filters alter neurite growth, axogenesis and the microtubule cytoskeleton in cultured hippocampal neurons.
Cultures of dissociated hippocampal neurons are often used to study neuronal cell biology. We report that the development of these neurons is strongly affected by chemicals leaching from commonly used disposable medical-grade syringes and syringe filters. Contamination of culture medium by bioactive substance(s) from syringes and filters occurred with multiple manufacturing lots and filter types under normal use conditions and resulted in changes to neurite growth, axon formation and the neuronal microtubule cytoskeleton. The effects on neuronal morphology were concentration dependent and significant effects were detected even after substantial dilution of the contaminated medium. Gas chromatography-mass spectrometry analyses revealed many chemicals eluting from the syringes and filters. Three of these chemicals (stearic acid, palmitic acid and 1,2-ethanediol monoacetate) were tested but showed no effects on neurite growth. Similar changes in neuronal morphology were seen with high concentrations of bisphenol A and dibutyl phthalate, two hormonally active plasticisers. Although no such compounds were detected by gas chromatography–mass spectrometry, unknown plasticisers in leachates may affect neurites. This is the first study to show that leachates from laboratory consumables can alter the growth of cultured hippocampal neurons. We highlight important considerations to ensure leachate contamination does not compromise cell biology experiments.


Direct zincation of functionalized aromatics and heterocycles by using a magnesium base in the presence of ZnCl2.
A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF by using (TMP)(2)Mg2 LiCl (TMP=2,2,6,6-tetramethylpiperamidyl) in the presence of ZnCl(2). The possible pathways of this metalation procedure as well as possible reactive intermediates are discussed. This experimental protocol expands the tolerance of functional groups and allows an efficient zincation of sensitive heterocycles such as quinoxaline or pyrazine. The zincated arenes and heteroarenes react with various electrophiles providing the expected products in 60-95 % yield.


Structure of the O-chain of the lipopolysaccharide of Haemophilus pleuropneumoniae serotype 1.
By phenol-water extraction an aqueous-phase soluble cellular lipopolysaccharide was isolated from Haemophilus pleuro-pneumoniae serotype 1. It was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, hydrolysis, methylation, and both one- and two-dimensional 1H and 13C nuclear magnetic resonance studies to be an S-type lipopolysaccharide, which could be cleaved to yield a lipid A and an O-chain polysaccharide identified as a high molecular weight branched polymer of a tetrasaccharide repeating unit having the structure: (Formula: see text).


Development of a stereo-symmetrical nanosecond pulsed power generator composed of modularized avalanche transistor Marx circuits.
Avalanche transistors have been widely studied and used in nanosecond high voltage pulse generations. However, output power improvement is always limited by the low thermal capacities of avalanche transistors, especially under high repetitive working frequency. Parallel stacked transistors can effectively improve the output current but the controlling of trigger and output synchronism has always been a hard and complex work. In this paper, a novel stereo-symmetrical nanosecond pulsed power generator with high reliability was developed. By analyzing and testing the special performances of the combined Marx circuits, numbers of meaningful conclusions on the pulse amplitude, pulse back edge, and output impedance were drawn. The combining synchronism of the generator was confirmed excellent and lower conducting current through the transistors was realized. Experimental results showed that, on a 50 Ω resistive load, pulses with 1.5-5.2 kV amplitude and 5.3-14.0 ns width could be flexibly generated by adjusting the number of combined modules, the supply voltage, and the module type.


Pulmonary edema associated with ritodrine and dexamethasone treatment of threatened premature labor. A case report.
Pulmonary edema occurred in association with the use of ritodrine and steroids to treat threatened premature labor. Twin gestation, intravenous ritodrine infusion longer than 24 hours and excessive fluid administration appear to be risk factors for the development of pulmonary edema. Careful case selection, scrupulous attention to the principles of fluid and electrolyte management and central venous pressure monitoring may help to diminish the incidence and severity of this complication of pregnancy.


Comparison of a long-acting LHRH agonist and polyoestradiol phosphate in the treatment of advanced prostatic carcinoma. An open prospective, randomized multicentre study.
In a prospective, randomized open study, a long-acting LHRH agonist (Zoladex) was compared with polyoestradiol phosphate (Estradurin), both widely used in Finland for palliative treatment of prostatic carcinoma, as regards efficacy and side effects. Of the 236 enrolled patients, 129 were randomized to receive LHRH agonist and 107 to oestrogen treatment. The median follow-up was 25 months. Reduction of prostatic volume was quicker and more effective in the LHRH than in the oestrogen group, and serum testosterone concentrations fell to castration level after 1 month and 1 year, respectively. In locally advanced (M0) and histologically well or moderately differentiated tumours, LHRH agonist therapy was considerably more effective than oestrogen as regards time to progression of the carcinoma, but in metastatic (M1) and histologically poorly differentiated tumours both methods gave similar results. Cardiovascular complications showed equal incidence in both groups. LHRH agonist therapy thus seemed to be more effective than polyoestradiol phosphate against locally advanced prostatic cancer in the doses used.


The distribution of effector cells for antibody-dependent cytotoxicity is species dependent.
Murine lymphoma cells were lysed by using either an allogeneic or a xenogeneic (rat) antiserum and antibody-dependent effectors from mice and rats. It was found that murine spleens were poorly antibody-dependent effectors against this target. The peritoneal cavities of mice were a good source of effectors. In rats, the spleen contained effectors, whereas adherent cells from the peritoneal cavity were comparatively ineffective. Cells from both rat and murine spleens lysed sheep erythrocytes in conjunction with an appropriate antiserum. The data emphasize that there is a difference in the antibody-dependent lysis of erythrocytes compared to nucleated mammalian cells. They also demonstrate that the distribution of antibody-dependent effectors is species dependent.


Hypoxemia in patients with idiopathic or heritable pulmonary arterial hypertension.
The prevalence and prognostic implications of hypoxemia either at rest or during six-minute walk test (6MWT) in patients with idiopathic or heritable pulmonary arterial hypertension (IPAH or HPAH) have not been systemically studied. We sought to determine the prevalence, phenotypic and prognostic implications of hypoxemia in patients with IPAH and HPAH. Patients with IPAH or HPAH were identified from the Cleveland Clinic Pulmonary Hypertension Registry. Pulse oximetry (SpO2) at rest and during 6MWT was used to define hypoxemia at rest or during activities when measurements were lower than 90%, respectively. A total of 292 patients (age 50.6 ± 18.0 years, 73% females) with IPAH (88%) and HPAH (12%) were included. Of them, 143 (49%) had SpO2 >90% at rest and during 6MWT, 89 (31%) subjects had hypoxemia during 6MWT and 60 (20%) had hypoxemia at rest. Patients with hypoxemia had older age, greater body mass index, higher prevalence of cardiovascular risk factors, worse functional capacity and pulmonary function tests but less severe pre-capillary pulmonary hypertension. Individuals with hypoxemia either at rest or during the initial 6MWT had worse long-term survival when compared to subjects without hypoxemia, even when adjusting for a great number of potential confounders. (HR: 2.5 (95% CI: 1.54-3.98)). Hypoxemia in patients with IPAH and HPAH is associated with more comorbidities, less severe pre-capillary pulmonary hypertension and worse survival.


Hoffa's fat pad tumours like: results of the arthroscopic resection.
We performed a retrospective cohort study to increase awareness in orthopaedic community of this rare but interesting disease which is often misdiagnosed as meniscal pathology and to analyze present results of arthroscopic resection in seven patients. we retrospectively reviewed records from 2008-2012 and identified 7 patients with symptomatic Hoffa's fat pad impingement. The diagnosis was made by clinical exam, MRI imaging and verified arthroscopically. Of the 7 patients 2 were excluded due to receiving open resection. The remaining five underwent arthroscopic resection. Lysholm and American knee society scores were obtained pre and post operative and at final follow up. There was a significant improvement in their symptoms and function after the surgery at an average follow-up of 14 months. The one poor result was because of paresthesia over the distribution of the infrapatellar branch of the saphenous nerve after open resection. tumours like of the fat pad should be treated by arthroscopic resection because of less residual pain and less complication was found using arthroscopy. In case of high volume of tumours only open excision can provide complete excision.


CCL9 Induced by TGFβ Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Organ.
Tumor cell survival in the hostile distant organ is a rate-limiting step in cancer metastasis. Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor-promoting microenvironment. However, it is unclear whether these myeloid cells in the premetastatic site have any direct effect on tumor cell survival. Here, we report that chemokine CCL9 was highly induced in Gr-1(+)CD11b(+) immature myeloid cells and in premetastatic lung in tumor-bearing mice. Knockdown of CCL9 in myeloid cells decreased tumor cell survival and metastasis. Importantly, CCL9 overexpression in myeloid cells lacking TGFβ signaling rescued the tumor metastasis defect observed in mice with myeloid-specific Tgfbr2 deletion. The expression level of CCL23, the human orthologue for CCL9, in peripheral blood mononuclear cells correlated with progression and survival of cancer patients. Our study demonstrates that CCL9 could serve as a good candidate for anti-metastasis treatment by targeting the rate-limiting step of cancer cell survival. In addition, targeting CCL9 may avoid the adverse effects of TGFβ-targeted therapy.


Evaluation of slower-growing broiler genotypes grown with and without outdoor access: growth performance and carcass yield.
Consumer interest in organic and free-range poultry production is growing. An experiment was conducted to assess the impact of genotype and outdoor access on growth rate and carcass yield. One slow-growing genotype (S), 2 medium-growing genotypes (M1 and M2), and a commercial fast-growing genotype (F) were raised (straight-run) for 81, 67, and 53 d, respectively. The placement date was staggered in order to achieve a similar final body weight and each genotype was processed on the same day. Each genotype was assigned to 3 pens of 24 birds each and raised in indoor floor pens in a curtain-sided house with ventilation fans; the S and F genotypes were also assigned to 2 floor pens with outdoor access (during daylight hours) containing 36 birds each. All birds were provided with the same starter, grower, and finisher feeds, and birds were commercially processed. Weight gain was similar (P > 0.05) among genotypes, but males gained more weight (P < 0.05) than females. The S and F genotypes had the highest and lowest (P < 0.05) feed intakes and, consequently, the lowest and highest (P < 0.05) feed efficiencies, respectively. The F genotype had the greatest (P < 0.05) breast yield (%) and the lowest (P < 0.05) wing yield (%). The S genotype exhibited the lowest (P < 0.05) breast yield (%) and the greatest leg quarter yield (%). Birds given outdoor access had greater (P < 0.05) bone strength in the tibia, and the F genotype had highest (P < 0.05) bone strength. These data indicate that substantial growth performance and yield differences exist among genotypes in alternative poultry systems.


Cerebral blood flow velocity in handicapped children.
Using a transcranial Doppler blood flowmeter, the blood flow velocity (BFV) ratio of the middle cerebral artery (MCA) to the basilar artery (BA) was investigated in 12 patients with severe motor and intellectual disability syndrome. The BFV of the MCA was also investigated in 58 handicapped children, classified according to the severity of their motor and intellectual disability. The ratio of the MCA to the BA was lower by 2 SD from the mean of our previously reported standard value in 8 out of the 12 cases with severe motor and intellectual disability syndrome, suggesting a more profound decrease in the level of brain activity in the MCA area than that of the BA area. The BFV of the MCA mainly decreased in cases belonging to the category of the most severe motor disability (bed-ridden). Hence, it is suggested that motor disability is the main factor related to the decrease in the BFV of the MCA.


Characterization of IGF-II isoforms in binge eating disorder and its group psychological treatment.
Binge eating disorder (BED) affects 3.5% of the population and is characterized by binge eating for at least 2 days a week for 6 months. Treatment options include cognitive behavioral therapy, interpersonal psychotherapy, and pharmacotherapy which are associated with varied success. Little is known about the biology of BED. Since there is evidence that the insulin like growth factor system is implicated in regulation of body weight, insulin sensitivity and feeding behavior, we speculated it may be involved in BED. A cross-sectional comparison was made between three groups of women: overweight with BED, overweight without BED and normal weight without BED. Women were assigned to Group Psychodynamic Interpersonal Psychotherapy. Blood was collected before therapy, at completion and at 6 months follow up for evaluation of IGF-II using Western blot. 97 overweight women with BED contributed to the cross-sectional comparison. The two control groups comprised 53 overweight women without BED, and 50 age matched normal weight women without BED. Obese women had significantly lower Big IGF-II than normal weight women, p = .028; Overweight women with BED had higher Mature IGF-II than normal weight women, p<.05. Big IGF-II showed a significant decreasing slope from pre- to post- to six months post-group psychological treatment, unrelated to changes in BMI (p = .008). Levels of IGF-II isoforms differed significantly between overweight and normal weight women. Overweight women with BED display abnormal levels of circulating IGF-II isoforms. BED is characterized by elevated mature IGF-II, an isoform shown to carry significant bioactivity. This finding is not related to BMI or to changes in body weight. The results also provide preliminary evidence that BIG IGF-II is sensitive to change due to group psychological treatment. We suggest that abnormalities in IGF-II processing may be involved in the neurobiology of BED.


Progressive Increases in Dietary Iron Are Associated with the Emergence of Pathologic Disturbances of Copper Homeostasis in Growing Rats.
Consumption of a high-iron diet causes copper deficiency in weanling rodents; however, the minimum amount of dietary iron that disrupts copper homeostasis has not been established. We tested the hypothesis that dietary iron at only several-fold above physiologic requirements would cause copper depletion. Weanling male Sprague-Dawley rats (n = 6/group) were fed AIN-93G-based diets with adequate (88 µg Fe/g = 1×), or excessive (4×, 9.5×, 18.5×, 38×, or 110×) iron content for 7 wk (110× group, due to notable morbidity) or 8 wk (all other groups). Copper-related physiologic parameters were then assessed. A hierarchy of copper-related, pathologic symptoms was noted as dietary iron concentrations increased. All statistical comparisons reported here refer to differences from the 1× (i.e., control) group. The highest iron concentration (110×) impaired growth (final body weights decreased ∼40%; P < 0.0001), and caused anemia (blood hemoglobin and hematocrit decreased ∼65%; P < 0.0001) and hepatic copper depletion (>85% reduction; P < 0.01). Cardiac hypertrophy occurred in the 110× (∼130% increase in mass; P < 0.0001) and 38× (∼25% increase; P < 0.05) groups, whereas cardiac copper content was lower in the 110× (P < 0.01), 38× (P < 0.01), and 18.5× (P < 0.05) groups (∼70% reductions). Splenic copper was also depleted in the 110× (>90% reduction; P < 0.0001), and in the 38× (P < 0.001) and 18.5× (P < 0.01) groups (∼70% reductions). Moreover, serum ceruloplasmin activity was decreased in the 110× and 38× (>90% reductions; P < 0.0001), and 18.5× (P < 0.001) and 9.5× (P < 0.05) (∼50% reductions) groups, typifying moderate to severe copper deficiency. Increasing dietary iron intakes to ∼9.5-fold above dietary recommendations caused copper deficiency. Importantly, human iron supplementation is common, and recommended intakes for at-risk individuals may be ≤10-fold above the RDA. Whether these iron intakes perturb copper metabolism is worth considering, especially since copper defi-ciency can impair iron utilization (e.g., by decreasing the ferroxidase activity of ceruloplasmin).


Folate metabolism and the risk of Down syndrome.
Folate is an important vitamin that contributes to cell division and growth and is therefore of particular importance during infancy and pregnancy. Folate deficiency has been associated with slowed growth, anaemia, weight loss, digestive disorders and some behavioural issues. Adequate folate intake around the time of conception and early pregnancy can reduce the risk of certain problems including neural tube defects. It has been suggested that certain versions (polymorphisms) of some genes can increase the risk of conceiving a baby with Down syndrome. If this is the case, then people with Down syndrome may be more likely to carry these forms of these genes and to experience associated problems in folate metabolism. Studies to date have found conflicting results, suggesting that these gene variants may be part of a more complex picture. In this issue, a further study reports no association between the presence of a common polymorphism of one of these genes and the risk of having a child with Down syndrome among mothers of Northern Indian origin. This article reviews these challenging findings and looks at where investigations can now go to resolve these issues.


Structural properties of Kudzu protein enzymatic hydrolysate and its repair effect on HepG2 cells damaged by H2O2 oxidation.
We investigated the structural properties, foaming capacity and foaming stability, antioxidant activity, and amino acid composition of Kudzu protein (KP) and Kudzu protein hydrolysate (KPH). The peptide sequence of KPH was analyzed using ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), and the binding ability of the peptide sequence to Keap1 was predicted through molecular docking simulations. The electrophoresis and molecular weight distribution analysis results showed that the molecular weight of KPH was significantly lower than that of KP, with a mean molecular weight of approximately 2000-5000 Da. The structures and properties were characterized using Fourier transform infrared spectroscopy, relative fluorescence, and circular dichroism. The results showed that KP exposed a large number of hydrophobic groups after enzymatic hydrolysis, and its structure changed from α-helical to random coils. KPH has a higher foaming capacity (200%) and foaming stability (97.5%) than KP, which may be related to the change in structure. These results indicate that moderate hydrolysis can improve the functional properties of KP, providing a new opportunity for its application as a food ingredient. The antioxidant assay results showed that KP and KPH had a good hydroxyl radical, superoxide anion, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging capacity and a high reducing capacity. KPH exerted better antioxidant effects than KP. The scavenging rates for DPPH, ABTS, hydroxyl radicals, and superoxide anions were 89.31%, 93.14%, 85.74%, and 58.29%, respectively, and its reducing capacity was 2.191, which may be related to the increase in amino acids with antioxidant activity after enzymolysis. In vitro, KP and KPH could significantly repair H2O2-induced oxidative damage in HepG2 cells, reduce the apoptosis rate, activate the Nrf2-Keap1 signaling pathway, reduce the accumulation of reactive oxygen species and malondialdehyde after oxidative damage, increase the activities of superoxide dismutase and glutathione (GSH) peroxidase, and increase the content of GSH and the total antioxidant capacity. Twenty-one peptide components were identified in KPH using UPLC-MS/MS, and the binding ability of 21 peptide components to Keap1 was analyzed through molecular docking technology. The results showed that all 21 peptides in KPH had good antioxidant activity, and real-time quantitative PCR (qRT-PCR) analysis was conducted to further explain the high antioxidant activity of KPH at the genetic level. These results show that KP and KPH are suitable for preparing antioxidant foods and related health foods to prevent oxidation-related diseases. KPH has more beneficial effects than KP.


Novel stroke risk reduction in atrial fibrillation: left atrial appendage occlusion with a focus on the Watchman closure device.
Atrial fibrillation (AF) remains an important clinical problem with severe complications such as stroke, which especially harms those with risk factors as calculated by the CHADS2 or CHA2DS2-VASc. Until now, no therapy has proven 100% effective against AF. Since the left atrial appendage (LAA) is the most prominent nonvalvular AF-related thromboembolic source and (novel) oral anticoagulant [(N)OAC] carries the hazard of bleeding, LAA occlusion may be an alternative, especially in patients who are ineligible for (N)OAC therapy. In this review, we discuss several LAA occlusion techniques with a focus on the Watchman device since this device is the most thoroughly studied device of all.


[On the operative treatment of tear opening atresia (author's transl)].
The authors describe a method of identifying and opening tear canaliculi when the openings are closed. For this purpose the common canaliculus under the medial palpebral ligament by the lateral wall of the tear sac is exposed by lamellar dissection under the microscope and opened. The roof of the tear point (where the tear opening should be) is excised over conical sounds laid retrogradely. Finally a vein catheter is placed from the upper and lower tear duct openings through the tear sac into the nasal cavity and left in situ for 12 weeks.


Inactivation of phosphodiesterase-4B gene in rat nucleus accumbens shell by CRISPR/Cas9 modulates the motivation to chronically self-administer nicotine.
Large scale human genome wide association studies (GWAS) have identified a growing pool of genes associated with cigarette smoking. One of the most prominent, phosphodiesterase-4B (PDE4B), has been associated with multiple smoking phenotypes. Although PDE4B modulates the half-life of neuronal cAMP, its precise role in smoking behaviors is unknown. To address this knowledge gap, we used a reverse translational approach. We inactivated PDE4B in bilateral medial nucleus accumbens shell (NAcs) neurons by injecting AAV containing a specific gRNA in female transgenic Cas9+ Long Evans rats. These rats then were given 23-hour chronic access to nicotine intravenous self-administration (IVSA) under a schedule of increasing fixed ratios (FR). With the increased effort required at FR7, nicotine SA (i.e. active presses and drug infusions) declined significantly in controls, whereas it was maintained in the mutagenized group. A progressive ratio (PR) study also showed significantly greater cumulative nicotine infusions in the mutant group. Hence, we hypothesized that enhanced PDE4B protein activity would reduce nicotine IVSA. A positive allosteric modulator,2-(3-(4-chloro-3-fluorophenyl)-5-ethyl-1H-1,2,4-triazol-1-yl)-N-(3,5-dichlorobenzyl)acetamide (MR-L2), was microinfused into NAcs bilaterally at FR3 or FR5; in both cohorts, MR-L2 acutely reduced nicotine IVSA. In summary, these studies show that the activity of PDE4B regulates the capacity of NAcs to maintain nicotine IVSA in face of the cost of increasing work. This finding and the results of the PR study indicate that PDE4B affects the motivation to obtain nicotine. These reverse translational studies in rats provide insight into the motivational effects of NAcs PDE4B that advance our understanding of the smoking behaviors mapped in human GWAS.


Alpha-AP-2 directs myosin VI-dependent endocytosis of cystic fibrosis transmembrane conductance regulator chloride channels in the intestine.
The actin motor myosin VI regulates endocytosis of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestine, but the endocytic adaptor linking CFTR to myosin VI is unknown. Dab2 (Disabled 2) is the binding partner for myosin VI, clathrin, and alpha-AP-2 and directs endocytosis of low density lipoprotein receptor family members by recognizing a phosphotyrosine-binding domain. However, CFTR does not possess a phosphotyrosine-binding domain. We examined whether alpha-AP-2 and/or Dab2 were binding partners for CFTR and the role of myosin VI in localizing endocytic adaptors in the intestine. CFTR co-localized with alpha-AP-2, Dab2, and myosin VI and was identified in a complex with all three endocytic proteins in the intestine. Apical CFTR was increased in the intestines of Dab-2 KO mice, suggesting its involvement in regulating surface CFTR. Glutathione S-transferase pulldown assays revealed binding of CFTR to alpha-AP-2 (but not Dab2) in the intestine, whereas Dab-2 interacted with alpha-AP-2. siRNA silencing of alpha-AP-2 in cells significantly reduced CFTR endocytosis, further supporting alpha-AP-2 as the direct binding partner for CFTR. alpha-AP-2 and Dab2 localized to the terminal web regions of enterocytes, but Dab2 accumulated in this location in Snell's Waltzer myosin VI((sv/sv)) intestine. Ultrastructural examination revealed that the accumulation of Dab2 correlated with prominent involution and the loss of normal positioning of the intermicrovillar membranes that resulted in expansion of the terminal web region in myosin VI((sv/sv)) enterocytes. The findings support alpha-AP-2 in directing myosin VI-dependent endocytosis of CFTR and a requirement for myosin VI in membrane invagination and coated pit formation in enterocytes.


Big data in mental health research - do the ns justify the means? Using large data-sets of electronic health records for mental health research.
Advances in information technology and data storage, so-called 'big data', have the potential to dramatically change the way we do research. We are presented with the possibility of whole-population data, collected over multiple time points and including detailed demographic information usually only available in expensive and labour-intensive surveys, but at a fraction of the cost and effort. Typically, accounts highlight the sheer volume of data available in terms of terabytes (1012) and petabytes (1015) of data while charting the exponential growth in computing power we can use to make sense of this. Presented with resources of such dizzying magnitude it is easy to lose sight of the potential limitations when the amount of data itself appears unlimited. In this short account I look at some recent advances in electronic health data that are relevant for mental health research while highlighting some of the potential pitfalls.


Chaotic region of elastically restrained single-walled carbon nanotube.
The occurrence of chaos in the transverse oscillation of the carbon nanotube in all of the precise micro-nano mechanical systems has a strong impact on the stability and the precision of the micro-nano systems, the conditions of which are related with the boundary restraints of the carbon nanotube. To generalize some transverse oscillation problems of the carbon nanotube studied in current references, the elastic restraints at both ends of the single-walled carbon nanotube are considered by means of rotational and translational springs to investigate the effects of the boundary restraints on the chaotic properties of the carbon nanotube in this paper. Based on the generalized multi-symplectic theory, both the generalized multi-symplectic formulations for the governing equation describing the transverse oscillation of the single-walled carbon nanotube subjected to the transverse load and the constraint equations resulting from the elastic restraints are presented firstly. Then, the structure-preserving scheme with discrete constraint equations is constructed to simulate the transverse oscillation process of the carbon nanotube. Finally, the chaotic region of the carbon nanotube is captured, and the oscillations of the two extreme cases (including simply supported and cantilever) are investigated in the numerical investigations. From the numerical results, it can be concluded that the relative bending stiffness coefficient and the absolute bending stiffness coefficients at both ends of the carbon nanotube are two important factors that affect the chaotic region of the carbon nanotube, which provides guidance on the design and manufacture of precise micro-nano mechanical systems. In addition, the different routes to the chaos of the carbon nanotube in two extreme cases are revealed.


Effects of the Degree of Phenol Substitution on Molecular Structures and Properties of Chitosan-Phenol-Based Self-Healing Hydrogels.
Click chemistry is commonly used to prepare hydrogels, and chitosan-phenol prepared by using a Schiff base has been widely employed in the field of biomaterials. Chitosan-phenol is a derivative of chitosan; the phenol groups can disrupt both the inter- and intramolecular hydrogen bonds in chitosan, thereby reducing its crystallinity and improving its water solubility. In addition, chitosan-phenol exhibits various beneficial physiological functions. However, it is still unclear whether the degree of phenol substitution in the chitosan main chain affects the molecular interactions and structural properties of the self-healing hydrogels. To explore this issue, we investigated the molecular structure and network of self-healing hydrogels composed of chitosan-phenol with varying degrees of phenol substitution and dibenzaldehyde poly(ethylene oxide) (DB-PEO) using molecular dynamics simulations. We observed that when the degree of phenol substitution in the self-healing hydrogel was less than 15%, an increase in the degree of phenol substitution led to an increase in the interactions between chitosan-phenol and DB-PEO, and it enhanced the dynamic covalent bond cross-linking generated through the Schiff base reaction. However, when the degree of phenol substitution exceeded 15%, excessive phenol groups caused excessive intramolecular interactions within chitosan-phenol molecules, which reduced the binding between chitosan-phenol and DB-PEO. Our results revealed the influence of the degree of phenol substitution on the molecular structure of the self-healing hydrogels and showed an optimal degree of phenol substitution. These findings provide important insights for the future design of self-healing hydrogels based on chitosan and should help in enhancing the applicability of hydrogels in the field of biomedicine.


Clinical characteristics and indications for blood transfusion in patients with SARS-CoV-2 infection.
There are few data on the clinical characteristics of COVID-19 patients who require blood transfusion. We aimed to investigate the clinical characteristics and indication for transfusion in COVID-19 patients seen during the epidemic's first wave. Cross-sectional study that included all consecutive COVID-19 patients admitted to the Hospital Clínic of Barcelona, Spain, from mid-March to mid-May 2020. A total of 80 patients received 354 RBC units, 116 plasma units, and 48 platelet units. Median age was 71 years (IQR: 62-76), and 59 (74%) were males. In total, 138 of the 261 transfusion episodes that involved RBCs (59%) were related to spontaneous (n=94) or procedure-related (n=44) bleeding. Spontaneous bleeding was more frequent in the retroperitoneal space and the gastrointestinal apparatus. Tracheostomy with endotracheal intubation, surgical interventions, and cannulation of femoral vessels were the main procedures behind non-spontaneous bleeding. Most patients (91%) were on anticoagulants, mostly intermediate- or full-dose heparin. Anticoagulation-related bleeding was a leading cause of blood transfusion in COVID-19 patients during the epidemic's first-wave.


Systematic data in biodiversity studies: use it or lose it.
Systematic data in the form of collections data are useful in biodiversity studies in many ways, most importantly because they serve as the only direct evidence of species distributions. However, collecting bias has been demonstrated for most areas of the world and has led some to propose methods that circumvent the need for collections data. New methods that model collections data in combination with abiotic data and predict potential total species distribution are examined using 25,111 records representing 5,123 species of plants and animals from Guyana; some methods use the reduced number of 320 species. These modeled species distributions are evaluated and potential high-priority biodiversity sites are selected based on the concept of irreplaceability, a measure of uniqueness. The major impediments to using collections data are the lack of data that are available in a useful format and the reluctance of most systematists to become involved in biodiversity and conservation research.


Bacteriorhodopsin conjugates as anchors for supported membranes.
The sophistication of supported lipid bilayer membranes has increased steadily as new applications are being explored. In general, tethered lipids are used to anchor the lipid bilayer to the substrate. Here we describe a new type of anchoring system for supported lipid bilayers that is based on biotin-PEG3400-bacteriorhodopsin conjugates. Amine-based coupling was used to construct the polymer conjugates, followed by fluorophore labeling to enable confocal imaging. The bacteriorhodopsin-based anchoring system was used to construct solid-supported vesicles from streptavidin-coated microspheres. This method could provide a new route for the stability enhancement of supported lipid bilayer membrane assemblies.


Pancreatic cancer and oligonucleotide therapy: Exploring novel therapeutic options and targeting chemoresistance.
Pancreatic cancer (PC) represents a malignancy with increased mortality rate, as less than 10% of patients survive for 5 years after diagnosis. Current evolution in basic sciences has revealed promising results by decrypting genetic loci vulnerable to mutations, as potential targets of novel treatment choices. In this regard, the "Oligonucleotide therapeutics", based on synthetic nucleotides, modify the function and expression of their targets. Antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNAs (miRNAs), aptamers, CpG oligodeoxynucleotides and decoys comprise the main representatives of this emerging technology, by regulating oncogenes' expression, restoring DNA repairment mechanisms, sensitizing cancer cells in chemotherapy, and inhibiting PC progress. A plethora of genetic treatment molecules and respective targets have been described and are currently studied, thus providing a broad range of probable pharmaceutical options. This narrative review illuminates the main parameters of genetic treatment molecules for PC and underlines their deficiencies, to clarify the upcoming future and trigger further investigation in PC management.


An analysis of the therapeutic elements in a black church service.
Twenty members of an independent urban black church who frequently attended a midweek service were interviewed to determine the nature of their experiences during the service and to assess its psychological impact. The majority were relatively young, married, and from a Northern urban or Southern rural background. Their responses differed for each of four selected aspects of the service. Testimony was an ineffable and explicitly religious experience. Holy Ghost possession provided an emotionally ecstatic feeling that also produced a sense of relief. Dancing and speaking in tongues were intense individualistic experiences; speaking in tongues was a more explicitly religious phenomenon. The service as a whole imparted feelings of group closeness and strength. The authors note that participants' responses correspond to several curative factors associated with group psychotherapy and suggest that the black church service is a functional community mental health resource for its participants.


Association between Helicobacter pylori infection and angiographically demonstrated coronary artery disease: A meta-analysis.
Coronary artery disease (CAD) is a leading cause of mortality globally. However, the etiology and pathogenesis of CAD are not fully understood. The aim of the present meta-analysis was to estimate the association between the risk of CAD and Helicobacter pylori (H. pylori) infection. A literature search was performed to identify eligible studies published prior to August 14, 2014. Fixed or random effect meta-analytical methods were used to pool the data and perform the subgroup analyses. The effect measures estimated were the odds ratios (OR) for dichotomous data reported with 95% confidence intervals (95% CI). Of the 109 studies identified using the search parameters, 26 cross-sectional studies were eligible involving 3,901 CAD patients and 2,751 controls. H. pylori infection was associated with an increased risk of CAD (OR: 1.96, 95% CI: 1.47-2.63, P<0.00001). When the adjusted ORs were used to conduct another meta-analysis, the OR value decreased, but the association remained significant (OR: 1.42, 95% CI: 1.09-1.86, P=0.008). The association between H. pylori infection and CAD risk was stronger in younger individuals than in older individuals (OR: 2.36, 95% CI 1.50-3.73 vs. OR: 1.59, 95% CI: 1.19-2.11). A significant association was observed in studies from Europe (OR: 2.11, 95% CI: 1.54-2.88, P=0.01) and the USA (OR: 1.43, 95% CI: 1.08-1.91, P=0.36). There is a potential association between H. pylori infection and the risk of CAD. The association may be influenced by age and ethnicity.


Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy.
Clinical benefit early in urate-lowering treatment of gout is difficult to document. We examined data from 1,832 gouty subjects treated with either urate-lowering agents or placebo to identify determinants of gout flare incidence and tophus size during year 1 of treatment. Reductions from pretreatment serum urate levels influenced flare frequency and tophus size, but the effect of urate level on flare incidence was biphasic. Lower urate levels were associated with higher flare incidence early in treatment but lower incidence by one year. The complex relationship between urate-lowering and clinical outcome early in treatment has implications for both clinical and investigative approaches to urate-lowering management.