Effects of a carbohydrate-, protein-, and ribose-containing repletion drink during 8 weeks of endurance training on aerobic capacity, endurance performance, and body composition.
This study compared a carbohydrate-, protein-, and ribose-containing repletion drink vs. carbohydrates alone during 8 weeks of aerobic training. Thirty-two men (age, mean ± SD = 23 ± 3 years) performed tests for aerobic capacity (V(O2)peak), time to exhaustion (TTE) at 90% V(O2)peak, and percent body fat (%fat), and fat-free mass (FFM). Testing was conducted at pre-training (PRE), mid-training at 3 weeks (MID3), mid-training at 6 weeks (MID6), and post-training (POST). Cycle ergometry training was performed at 70% V(O2)peak for 1 hours per day, 5 days per week for 8 weeks. Participants were assigned to a test drink (TEST; 370 kcal, 76 g carbohydrate, 14 g protein, 2.2 g d-ribose; n = 15) or control drink (CON; 370 kcal, 93 g carbohydrate; n = 17) ingested immediately after training. Body weight (BW; 1.8% decrease CON; 1.3% decrease TEST from PRE to POST), %fat (5.5% decrease CON; 3.9% decrease TEST), and FFM (0.1% decrease CON; 0.6% decrease TEST) decreased (p ≤ 0.05), whereas V(O2)peak (19.1% increase CON; 15.8% increase TEST) and TTE (239.1% increase CON; 377.3% increase TEST) increased (p ≤ 0.05) throughout the 8 weeks of training. Percent decreases in %fat from PRE to MID3 and percent increases in FFM from PRE to MID3 and MID6 were greater (p ≤ 0.05) for TEST than CON. Overall, even though the TEST drink did not augment BW, V(O2)peak, or TTE beyond carbohydrates alone, it did improve body composition (%fat and FFM) within the first 3-6 weeks of supplementation, which may be helpful for practitioners to understand how carbohydrate-protein recovery drinks can and cannot improve performance in their athletes.


Circularly Polarized Light Responsive Materials: Design Strategies and Applications.
Circularly polarized light (CPL) with the end of optical vector traveling along circumferential trajectory shows left- and right-handedness, which transmits chiral information to materials via complicated CPL-matter interactions. Materials with circular dichroism respond to CPL illumination selectively with differential outputs that can be used to design novel photodetectors. Racemic or achiral compounds under CPL go through photodestruction, photoresolution, and asymmetric synthesis pathways to generate enantiomeric bias and optical activity. By this strategy, helical polymers and chiral inorganic plasmonic nanostructures are synthesized directly, and their intramolecular folding and subsequent self-assembly are photomodulable as well. In the aggregated state of self-assembly and liquid crystal phase, helical sense of the dynamic molecular packing is sensitive to enantiomeric bias brought by CPL, enabling the chiral amplification to supramolecular scale. In this review, the application-guided design strategies of CPL-responsive materials are aimed to be systematically summarized and discussed. Asymmetric synthesis, resolution, and property-modulation of small organic compounds, polymers, inorganic nanoparticles, supramolecular assemblies and liquid crystals are highlighted based on the important developments during the last decades. Besides, applications of light-matter interactions including CPL detection and biomedical applications are also referred.


Impact of preoperative weight loss and body composition changes on postoperative outcome in surgery for inflammatory bowel disease.
One hundred and twenty seven patients undergoing elective surgery for inflammatory bowel disease were divided into three groups according to their preoperative ideal body weight (less than 80%, 80-90%, and greater than 90%). The groups were well matched in respect of age, sex, corticosteroid therapy, pre-existing sepsis, peroperative antimicrobial chemotherapy, and resection site. None received peroperative nutritional support. The postoperative outcome was similar in each of the three nutritional groups including the incidence of postoperative sepsis, duration of hospital stay, and mortality. Serial peroperative changes in weight, fat, and muscle bulk were assessed by anthropometric measurements in 21 of these patients. The deficits in weight, fat, and muscle bulk were similar at 10 and 21 days postoperatively in the three groups. At 84 days those malnourished preoperatively had recovered their nutritional status faster than the well nourished patients. We conclude that in these patients undergoing elective resection for inflammatory bowel disease preoperative weight loss did not adversely affect the postoperative outcome.


A molecular linear motor consisting of carbon nanotubes.
We experimentally investigated a "molecular-linear-motor" system consisting of a capsule-like carbon nanotube (CNT) in the interior space of a host CNT. Transmission electron microscopy revealed the capsule traveled back and forth between both ends of the hollow space along the axial direction and rotated simultaneously. The mechanism was well explained with molecular dynamics simulation by considering the driving force supplied from thermal energy. The present system operates around room temperature and this opens up the possibility of designing novel nanodevices such as oscillators and switching memory devices.


[Recent data on the cytogenetics of colorectal adenocarcinoma].
A brief description of the results obtained by cytogenetic analyses of cancer cells from colorectal adenocarcinomas is reported. Two distinct patterns of chromosomal anomalies are observed. The major one, called "monosomic type", because many chromosomes losses exist, is characterised by the losses or deletions of the following chromosomes 18, 17 (short arm = p), 1p, 4, 14, 5 (long arm = q) and 21. It frequently evolves towards polyploidy, by duplication of all remaining chromosomes. The minor one, called "trisomic type", is characterised by the gain of several chromosomes: 7, 12, X, 5 and 8. The chromosomal anomalies observed seem to have no topological relationships with oncogenes, and other interpretations for their occurrence were investigated. The numerous and frequent deletions of some chromosomes, like 17p and 18, may indicate the involvement of recessive genes, like in the anti-oncogene system. In addition, it is observed that most deletions involve genes for "de novo" pathways whereas gains involve genes for salvage pathways of the synthesis of nucleotides. A correlated cytogenetic and enzymologic study was thus developed, and the first results show that the chromosomal pattern may well indicate the metabolic deviations. Monosomic type tumors have, on the average, a relatively low "de novo" and a high salvage pathways, and trisomic type tumors a high "de novo" and salvage pathways. Since chemotherapy is principally orientated against "de novo" pathways of the synthesis of nucleotides, these results may help to understand the difficulties of chemotherapy in colorectal cancers and perhaps to adapt it better.


Myofascial Pain: Ultrasound Width of the Masseter Muscle.
To determine whether subjects with temporomandibular disorders (TMD) manifesting as chronic myofascial pain (MFP) involving the masseter muscle present with significantly greater masseter muscle width, as evidenced by ultrasound, compared to individuals without MFP. A case-control study was carried out. A total of 31 subjects presenting with MFP of the masticatory muscles involving the masseter muscle and 35 controls with TMD but no diagnosis of MFP, matched by age and sex, were included. Ultrasound was used to measure the maximum width of both masseter muscles at the intermediate point between the origin and insertion of the muscle in the light occlusal contact (LOC) position and under maximum contraction. Each side was analyzed separately. Means were compared by using single-factor analysis of variance and Mann-Whitney U test; P < .05 was considered to reflect statistical significance. In the study group, the right masseter muscle had a mean ± standard deviation width of 8.6 ± 1.8 mm under LOC (controls: 8.6 ± 1.6 mm; P = .85) and 11.5 ± 2.1 mm under maximum contraction (controls: 11.7 ± 1.9 mm; P = .86). The analagous measures in the left masseter muscle were 8.6 ± 1.6 mm under LOC (controls: 8.2 ± 1.5 mm; P = .42) and 11.3 ± 1.8 mm under maximum contraction (controls: 11.5 ± 1.8 mm) (P = .79), respectively. The increase in width of the right masseter muscle was 2.9 ± 2.1 mm (controls: 3.1 ± 1.2 mm; P = .67) in absolute terms and 1.4 ± 0.3 mm (controls: 1.4 ± 0.2 mm; P = .91) in relative values (width at maximum contraction/LOC width). In the case of the left masseter muscle, the respective values were 2.8 ± 1.7 mm (controls: 3.2 ± 0.9 mm; P = .25) and 1.3 ± 0.2 mm (controls: 1.4 ± 0.1 mm; P = .32). There were no statistically significant differences in masseter muscle width between MFP subjects and control subjects under LOC conditions or maximum contraction. The increase in width under maximum contraction was likewise not significantly different between the groups.


Molecular reorientations in liquid crystals pentyloxybenzylidine hexylanilene (PBHA) and butyloxybenzylidine octylanilene (BBOA).
Molecular reorientational motions in undeuterated pentyloxybenzylidine hexylanilene (PBHA or 5O.6) and butyloxybenzylidine octylanilene (BBOA or 4O.8) as studied by the quasielastic neutron scattering (QENS) technique in their different mesophases are reported. Models are built up in stages to account for the experimental elastic incoherent structure factor (EISF). It is found that there exist simultaneous reorientational motions of the chain group and the reorientational motions of the whole molecule around its molecular axis in the smectic- G, smectic- B, and smectic- C phases. In smectic- A and nematic phases, additional body axis fluctuations are found to exist in both 5O.6 and 4O.8 systems. The average amplitude of body axis fluctuations is found to be approximately 15 degrees and 25 degrees, respectively, in the smectic- A and nematic phases of 5O.6, and approximately 14 degrees and 29 degrees, respectively, in 4O.8.


Influence of creativity on vividness of imagery.
We studied the correlations between creativity and imagery in 1361 university students of Fine Arts, Mathematics, and Geography and History. Significant values were found between certain factors of creativity and imagery, but creativity only accounted for 6% of the total variance in vividness of imagery for the whole sample.


[Study on value of IHA in diagnosis of schistosomiasis japonica].
To evaluate the value of indirect hemagglutination test (IHA) in schistosomiasis diagnosis. The literature concerned schistosomiasis diagnosis with IHA in the databases of Medline, CNKI, VIP and Wanfang Data from 1982 to 2014 was collected and evaluated. Totally 21 articles which were satisfied with the research criteria were analyzed with the Meta-analysis method. The IHA method had high value in schistosomiasis diagnosis, the AUCSROC of IHA in laboratory evaluation was 0.990 6, while in filed evaluation was 0.832 9, and the difference between them was significant (Z = 4.50, P < 0.05). The diagnosis value of IHA in field evaluation is less than that in laboratory. In the process of the elimination of schistosomiasis, developing a new and higher sensitive reagent in schistosomiasis diagnosis is needed.


Effect of complexing agent and annealing atmosphere on properties of nanocrystalline ZnS thin films.
The nanocrystalline Zinc Sulfide (ZnS) thin films were prepared on glass substrates by chemical bath deposition (CBD) method using aqueous solutions of zinc acetate, thiourea and tri-sodium citrate in alkaline medium at 80 degrees C. The tri-sodium citrate acts as a complexing agent. The effects of complexing agent and annealing atmosphere (95%N2 + 5%H2S) on structural, morphological and optical properties of ZnS thin films were studied using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and optical absorption. XRD study revealed that single phase ZnS powder was formed in the solution with tri-sodium citrate, however, ZnS and ZnO mixed phase powder was formed in the solution without tri-sodium citrate. The films deposited with trisodium citrate showed ZnS with hexagonal wurtzite phase. However, annealed film in (N2 + H2S) atmosphere showed cubic (zincblende) phase. FE-SEM images show that grain size of as-deposited and annealed ZnS films are about 20 nm and 50 nm, respectively. Optical absorption study showed that the films have moderate optical transmission from 65% to 75% in the visible region and the optical band gap energy of as-deposited ZnS film is 3.91 eV and it decreases to 3.73 eV after annealing.


Remote patient monitoring strategies and wearable technology in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is highly prevalent and is associated with a heavy burden on patients and health systems alike. Exacerbations of COPD (ECOPDs) are a leading cause of acute hospitalization among all adult chronic diseases. There is currently a paradigm shift in the way that ECOPDs are conceptualized. For the first time, objective physiological parameters are being used to define/classify what an ECOPD is (including heart rate, respiratory rate, and oxygen saturation criteria) and therefore a mechanism to monitor and measure their changes, particularly in an outpatient ambulatory setting, are now of great value. In addition to pre-existing challenges on traditional 'in-person' health models such as geography and seasonal (ex. winter) impacts on the ability to deliver in-person visit-based care, the COVID-19 pandemic imposed additional stressors including lockdowns, social distancing, and the closure of pulmonary function labs. These health system stressors, combined with the new conceptualization of ECOPDs, rapid advances in sophistication of hardware and software, and a general openness by stakeholders to embrace this technology, have all influenced the propulsion of remote patient monitoring (RPM) and wearable technology in the modern care of COPD. The present article reviews the use of RPM and wearable technology in COPD. Context on the influences, factors and forces which have helped shape this health system innovation is provided. A focused summary of the literature of RPM in COPD is presented. Finally, the practical and ethical principles which must guide the transition of RPM in COPD into real-world clinical use are reviewed.


Proteins of the Bacillus stearothermophilus ribosome. The amino acid sequences of proteins S5 and L30.
The amino acid sequences of ribosomal proteins S5 and L30 from Bacillus stearothermophilus have been determined. These proteins have recently been crystallized in our institute. Sequence data were obtained by manual sequencing of peptides derived from cyanogen bromide cleavage and digestion with trypsin and chymotrypsin or thermolysin. Proteins S5 and L30 contain 166 and 62 amino acid residues and have calculated Mr values of 17,628 and 7,053, respectively. Comparison of the sequences with those of the homologous proteins from Escherichia coli shows 55% identical residues for S5 and 53% for L30. For both proteins, the distribution of conserved and substituted regions is not uniform throughout the molecule. Secondary structure predictions were carried out for the B. stearothermophilus proteins. Comparison with the results for the homologous E. coli proteins indicated similar secondary structural order for the molecules from the two species.


Multi-drug resistance genes in the management of neoplastic disease.
P-gp can function as an ATP-dependent cytotoxic drug-efflux pump. In normal tissues, protein expression is localized to cell surfaces that face excretory lumina; hence, P-gp may function as a toxic-waste disposal system. Tumors that are derived from these tissues can be high expressors of P-gp, and these tumors tend to display intrinsic chemoresistance. Other non-expressing tumors can become P-gp positive after treatment or at relapse, suggesting that mdr may be involved in acquired resistance. The use of MDR-modifying agents has had some clinical success, and further trials of chemosensitizers are proceeding. P-gp overexpression does not explain how clinical resistance to anthracyclines, alkylating agents, and cis-platinum can arise simultaneously. In these cases, multiple genetic mechanisms of resistance may coexist. Eventually, mdr status can be used to select the most effective chemotherapy protocol for the individual. Currently, conversion of a previously mdr negative tumor to mdr expression, in the face of clinical resistance, justifies changing to a non-MDR drug protocol, or if not feasible, the use of MDR sensitizers.


[Comparative Randomized Study of the Effects of Long-Term Therapy With Rosuvastatin and With Combination of Atorvastatin and Ezetimibe on Carbohydrate Metabolism and Adipokynes Levels in Patients With Coronary Artery Disease and Diabetes Mellitus].
This open randomized study compares the effects of 24-week-long treatment with rosuvastatin and with atorvastatin coadministered with ezetimibe on the parameters of carbohydrate metabolism and the plasma levels of adipokynes in patients with coronary artery disease and type 2 diabetes mellitus or impaired glucose tolerance (IGT). A total of 31 patients with coronary artery disease and type 2 diabetes mellitus or IGT were recruited in the study. Patients were randomized into two groups: group 1 included patients who received rosuvastatin therapy in an average dose of 12.5 mg/day (n=16); group 2 included patients who received combination treatment with atorvastatin in an average dose of 13.3 mg/day and ezetimibe (10 mg) (n=15). Plasma levels of lipids, apoB, apoA1, glucose, insulin, leptin, and adiponectin were evaluated; HOMA-IR index (an empty stomach insulin, mu/l x fasting glucose, mmol/l) / 22.5) was calculated. During the therapy, the LDL-C and apoB levels decreased by 51.7% and 42.3% in group1 and by 51.8% and 44.9% in group 2, respectively. Reduction in the triglyceride levels was significantly more pronounced in group 2 than in group 1: 43.2% vs 17.4% (p<0.02), whereas we did not observed significant changes of HDL-C and apoA1 in either group. The increases in basal glycemia, basal insulinemia, HbA1c levels (from 6.47% [6.10-7.02%] to 6.98% [6.23-8.18%]), and HOMA-IR (from 2.14 [1.68-3.51] to 4.30 [2.31-5.77]) were found only in group 2 (p<0.05 for all). These changes were observed in 75% of patients of group 2 independently of the presence of diabetic state or IGT, but the changes were more pronounced in patients with disturbed carbohydrate metabolism. Changes of leptin levels during the therapy were diverse: 73% patients of group 1 demonstrated decrease in the leptin levels, whereas 67% of patients in group 2 experienced 57%-increase in the leptin concentrations. Degree of increased basal glycemia was associated with increase in the leptin levels (r=0.37, p=0.04) in the entire group of patients (n=31). Furthermore, changes in leptin levels were negatively associated with decreased adiponectin levels (r=-0.57, p=0.034). In case of equivalent degree of the decrease in LDL-C levels, 24-week combination therapy with atorvastatin and ezetimibe, unlike rosuvastatin treatment, induced increases in basal glycemia, insulinemia, HbA1c, and HOMA-IR index irrespective of the presence of carbohydrate metabolism disturbances before treatment. Our data suggest that adiponectin and leptin are involved in the mechanisms of adverse metabolic effects of the combination of atorvastatin and ezetimibe.


[Effect of two-level community-based health education pattern on schistosomiasis control].
To implement a two-level community-based health education pattern of schistosomiasis in residents of endemic areas in marshland and lake regions, so as to explore the suitable pattern of health education under hypo-endemic situation. Two schistosomiasis endemic villages in Jiangling County, Hubei Province were collected as study areas, and among which, one village was treated as an intervention group, where the two-level community-based health education pattern as well as regular control measures was implemented; the other village was a control group, where only regular control measures were implemented. The awareness rates on schistosomiasis control, the rates of correct behavior and the compliance rates of examination, treatment and chemotherapy of the two groups before and after the intervention were compared. According to the results of the baseline survey in 2014, the awareness rates of schistosomiasis control of the intervention and control groups were 84.00% and 77.45%, respectively, the correct rates of behavior of the two groups were 72.00% and 63.73%, respectively, and the compliance rates of the treatment were 80.36% and 82.28%, respectively, there were no statistically significant differences between all the above rates of the two groups (all P > 0.05). After the intervention of the two-level community-based health education, the correct rates of behavior, and the compliance rates of examination and chemotherapy of the two groups were 92.31% and 80.37%, 95.11% and 82.55%, 84.13% and 63.64%, respectively, and the differences between all the rates above of the two groups were statistically significant (all P < 0.05). When compared to those before intervention, the growing rates of the compliance rates of examination, treatment and chemotherapy of the intervention group were 20.97%, 15.33% and 23.29%, respectively, while those of control group were 14.27%, 4.17%, -3.77%, respectively, the growing rates of the intervention groups were higher than those of the control groups. Through the two-level community-based pattern of health education, the compliance rates of examination and treatment of the residents have improved, and therefore, the pattern is suitable for popularization and application in marshland and lake regions.


Fast ion generation in the cathode plasma jet of a multipicosecond laser-triggered vacuum discharge.
Ion generation in the cathode plasma jet of a moderate-current (approximately 2.3 kA), low-energy (< or = 20 J) vacuum spark discharge triggered by approximately 27 ps, 10 mJ laser pulses is studied using time of flight technique. Fastest ion velocity and velocity corresponding to the peak of the time of flight signals for Al cathode were measured to be approximately 5.25x10(8) cm/s (energy of approximately 143 keV/u) and approximately 8.1x10(7) cm/s (energy of approximately 3.4 keV/u), respectively. Corresponding velocities in the case of ions generated from laser-produced Al plasma (energy of approximately 550 mJ, intensity of approximately 10(14) W/cm(2)) were found to be much smaller, viz., approximately 1.05x10(8) cm/s (energy of approximately 5.75 keV/u) and approximately 2.63x10(7) cm/s (energy of approximately 0.36 keV/u), respectively. Study shows efficient acceleration of ions in a current-carrying cathode plasma jet of a small-energy multipicosecond laser-triggered spark discharge as compared with that in a high-energy multipicosecond laser-produced plasma plume.


Re2O7-Catalyzed Approach to Spirocyclic Ether Formation from Acyclic Precursors: Observation of Remote Stereoinduction.
Ketones that are flanked by an allylic alcohol and an alkene isomerize to spirocyclic ethers in the presence of Re2O7 through allylic alcohol transposition, oxocarbenium ion formation, and Prins cyclization. These processes provide significant increases in molecular complexity, with multiple stereocenters being set relative to a stereocenter in the substrate. Stereoselectivity arises from the initial reversible steps being more rapid than the final step, thereby allowing for thermodynamically controlled stereochemical equilibration prior to product formation.


Th1 and type 1 cytotoxic T cells dominate responses in T-bet overexpression transgenic mice that develop contact dermatitis.
Contact dermatitis in humans and contact hypersensitivity (CHS) in animal models are delayed-type hypersensitivity reactions mediated by hapten-specific T cells. Recently, it has become clear that both CD4(+) Th1 and CD8(+) type 1 cytotoxic T (Tc1) cells can act as effectors in CHS reactions. T-bet has been demonstrated to play an important role in Th1 and Tc1 cell differentiation, but little is known about its contribution to CHS. In the present study, we used C57BL/6 mice transgenic (Tg) for T-bet to address this issue. These Tg mice, which overexpressed T-bet in their T lymphocytes, developed dermatitis characterized by swollen, flaky, and scaly skin in regions without body hair. Skin histology showed epidermal hyperkeratosis, neutrophil, and lymphocyte infiltration similar to that seen in contact dermatitis. T-bet overexpression in Tg mice led to elevated Th1 Ig (IgG2a) and decreased Th2 Ig (IgG1) production. Intracellular cytokine analyses demonstrated that IFN-gamma was increased in both Th1 and Tc1 cells. Furthermore, Tg mice had hypersensitive responses to 2,4-dinitrofluorobenzene, which is used for CHS induction. These results suggest that the level of expression of T-bet might play an important role in the development of contact dermatitis and that these Tg mice should be a useful model for contact dermatitis.


Adenoid Cystic Carcinoma of the lacrimal gland metastasising to the liver: report of a case.
Adenoid Cystic Carcinoma of the lacrimal gland is a rare tumour. Their aggressive behaviour, with a high-risk of local recurrence, and late distant spread of the tumour even after aggressive management has been reported. Metastasis to the liver is rare and when it occurs, it is usually part of widespread metastasis, and therefore surgical treatment is seldom considered. We report a rare case of an isolated liver metastasis from a lacrimal gland adenoid cystic carcinoma 20 years after resection of the primary tumour. The patient presented with right upper quadrant pain radiating to the back and shortness of breath of 3 months duration. No local recurrence was detected during a 15 year follow-up with computerized tomography (CT) of the head. Abdominal CT scan demonstrated a solitary liver tumour with no other primary source, and the bone scan was normal. The patient was treated with an extended right hemihepatectomy. The histology revealed a predominantly cribriform tumour with focal areas of basaloid type metastatic lacrimal gland adenoid cystic carcinoma. This case illustrates the unpredictable behaviour of adenoid cystic carcinoma and the need for a life long follow up for these patients after treatment. The possibility of surgical resection for liver metastasis from adenoid cystic carcinoma should always be considered.


Epigenetic regulation of the ras effector/tumour suppressor RASSF2 in breast and lung cancer.
RASSF2 is a recently identified member of a class of novel tumour suppressor genes, all containing a ras-association domain. RASSF2 resides at 20p13, a region frequently lost in human cancers. In this report we investigated methylation status of the RASSF2 promoter CpG island in a series of breast, ovarian and non-small cell lung cancers (NSCLC). RASSF2 was frequently methylated in breast tumour cell lines (65%, 13/20) and in primary breast tumours (38%, 15/40). RASSF2 expression could be switched back on in methylated breast tumour cell lines after treatment with 5'-aza-2'deoxycytidine. RASSF2 was also frequently methylated in NSCLC tumours (44%, (22/50). The small number of corresponding normal breast and lung tissue DNA samples analysed were unmethylated. We also did not detect RASSF2 methylation in ovarian tumours (0/17). Furthermore no mutations were found in the coding region of RASSF2 in these ovarian tumours. We identified a highly conserved putative bipartite nuclear localization signal (NLS) and demonstrated that endogenous RASSF2 localized to the nucleus. Mutation of the putative NLS abolished the nuclear localization. RASSF2 suppressed breast tumour cell growth in vitro and in vivo, while the ability of NLS-mutant RASSF2 to suppress growth was much diminished. Hence we demonstrate that RASSF2 has a functional NLS that is important for its tumour suppressor gene function. Our data from this and a previous report indicate that RASSF2 is frequently methylated in colorectal, breast and NSCLC tumours. We have identified RASSF2 as a novel methylation marker for multiple malignancies and it has the potential to be developed into a valuable marker for screening several cancers in parallel using promoter hypermethylation profiles.


Dataset on exogenous application of salicylic acid and methyljasmonate and the accumulation of caffeine in young leaf tissues and catabolically inactive endosperms.
Exogenous exposure of coffee plants to 50 μM and 500 μM salicylic acid through liquid hydroponic medium or the exposure to volatile fumes of methyljasmonate was carried out to study the role of salicylic acid and methyljasmonate on the accumulation of caffeine and other methylxanthines like 7-methylxanthine, theobromine and theophylline. Transcript levels of the first, second and third N-methyltransferase involved in the core caffeine biosynthetic pathway namely, xanthosine methyltransferase (XMT), methylxanthine methyltransferase (MXMT) and di-methylxanthine methyltransferase (DXMT) was investigated by semi-quantitative RT-PCR for validating the reason behind the changes of caffeine biosynthetic potential under the influence of the two analogues of plant phytohormones. Maturing coffee fruits are known to be biologically inactive with respect to caffeine biosynthetic activity in the endosperms. To understand this, fruits were treated with different doses of salicylic acid in a time-course manner and the de-repression of tissue maturation-mediated knockdown of caffeine biosynthesis by exogenously applied salicylic acid was achieved. In our companion paper [1] it was shown that the repression of NMT genes during the dry weight accumulation phase of maturing endosperm could be relaxed by the exogenous application of salicylic acid and methyljasmonate. A probable model based on the work carried out therein and based on other literature [2], [3], [4] was proposed to describe that the crosstalk between salicylic acid or methyljasmonate and the ABA/ethylene pathway and might involve transcription factors downstream to the signaling cascade.


Raltegravir Pharmacokinetics in Patients on Asunaprevir-Daclatasvir.
Raltegravir pharmacokinetics was studied in 20 patients included in the ANRS HC30 QUADRIH Study before and after addition of anti-hepatitis C virus (anti-HCV) quadritherapy, including pegylated-interferon-ribavirin and asunaprevir plus daclatasvir. Raltegravir pharmacokinetic parameters remained unchanged whether administered on or off anti-HCV therapy. In addition, concentrations of raltegravir, asunaprevir, and daclatasvir were not affected by liver cirrhosis. These data suggest that in human immunodeficiency virus (HIV)-HCV-coinfected patients, whether cirrhotic or not, asunaprevir and daclatasvir could be administered safely with raltegravir.


[Early and late results following simple suturing of the perforated stomach ulcer and duodenal ulcer].
Between 1968 and 1983, 1077 patients with gastric or duodenal ulcer underwent surgery in our department. 207 patients presented with perforation of the ulcer, which in all cases was closed by oversewing . They comprised 137 men and 70 females with a mean age of 55.7 years. 26.1% of the patients were aged over 71 years. Postoperative mortality was 15.9%. The prognosis was mainly influenced by age, time interval between perforation and surgery, and--probably--duration of ulcer disease. Follow-up (at least 3 years after surgery) demonstrated no symptoms of ulcer disease in 58.2%. In 21.9% a second and definitive operation had been performed in patients with persistent symptoms or complications of the ulcer.


Home telehealth: mainstreaming what we do well.
The number of home telehealth programs implemented both domestically and abroad and the number of peer-reviewed publications detailing positive outcomes for chronic disease management, preventive care, and self-management have increased over the past 5 years. The most dramatic growth has been in populations with diabetes, chronic obstructive pulmonary disease, and congestive heart failure. A review of home telehealth developments, current status, opportunities, and challenges provides a foundation for understanding why we need to mainstream what we already know works.


Correction: Synthesis, cytotoxic and hydrolytic studies of titanium complexes anchored by a tripodal diamine bis(phenolate) ligand.
Correction for 'Synthesis, cytotoxic and hydrolytic studies of titanium complexes anchored by a tripodal diamine bis(phenolate) ligand' by Sónia Barroso et al., Dalton Trans., 2014, 43, 17422-17433.


Candida tropicalis fungaemia in adult patients with haematological malignancies: clinical features and risk factors.
Candida tropicalis fungaemia is a serious opportunistic infection. Eighteen consecutive patients with C. tropicalis fungaemia diagnosed within a five-year period were studied retrospectively. All patients had haematological malignancies treated by chemotherapy or bone marrow transplantation (BMT). Antifungal prophylaxis included nystatin (20 mg daily) for patients receiving chemotherapy, and fluconazole (200 mg daily) for patients undergoing BMT. Sixteen patients had refractory and advanced haematological malignancies. All patients were neutropenic, had central venous catheters, and were receiving treatment with broad-spectrum antibiotics at the time of fungaemia. Septic shock with skin emboli were the most common presenting features. In seven cases, fungaemia was preceded by a positive culture of C. tropicalis in the urine. Concomitant bacteraemia was found in 11 cases, of which six cases were due to Staphylococcus aureus. The overall mortality rate was 56%. The predominance of chemotherapy-treated patients developing fungaemia in this series might be attributable to the omission of fluconazole prophylaxis. The clinicopathologic features and risk factors identified in this study may help design better treatment strategies for this often-lethal complication.


In-silico simulations of advanced drug delivery systems: what will the future offer?
This commentary enlarges on some of the topics addressed in the Position Paper "Towards more effective advanced drug delivery systems" by Crommelin and Florence (2013). Inter alia, the role of mathematical modeling and computer-assisted device design is briefly addressed in the Position Paper. This emerging and particularly promising field is considered in more depth in this commentary. In fact, in-silico simulations have become of fundamental importance in numerous scientific and related domains, allowing for a better understanding of various phenomena and for facilitated device design. The development of novel prototypes of space shuttles, nuclear power plants and automobiles are just a few examples. In-silico simulations are nowadays also well established in the field of pharmacokinetics/pharmacodynamics (PK/PD) and have become an integral part of the discovery and development process of novel drug products. Since Takeru Higuchi published his seminal equation in 1961 the use of mathematical models for the analysis and optimization of drug delivery systems in vitro has also become more and more popular. However, applying in-silico simulations for facilitated optimization of advanced drug delivery systems is not yet common practice. One of the reasons is the gap between in vitro and in vivo (PK/PD) simulations. In the future it can be expected that this gap will be closed and that computer assisted device design will play a central role in the research on, and development of advanced drug delivery systems.


Complications of distraction lengthening in the hand.
This study examined the features of 16 complications from 51 distraction lengthenings in the hands of 43 patients. From 1996 to 2006, 24 metacarpals and 27 phalanges were lengthened at a rate of 0.5 and 0.25 mm/day, respectively, using a callus distraction technique. The indications were congenital (33 cases in 27 patients) and traumatic (18 cases in 16 patients) deformities. The average percentage lengthening in the phalanges and metacarpals was 62% (16 mm) and 63% (34 mm), respectively. The distraction rates in the phalanges and metacarpals were 69 and 52 days/cm, respectively. The overall complication rate was 31%. Major complications requiring secondary procedures were non-union (one case), fracture (one case), premature union (one case), angulations (two cases) and dislodgment of pins (two cases). The minor complications encountered were delayed callus formation (four cases), joint stiffness (four cases) and soft tissue thinning (one case). Traumatic deformities had more complications than the congenital ones (nine of 18 cases and seven of 33 cases, respectively). The phalanges had a higher rate of complication than the metacarpals (11 of 27 cases and four of 24 cases, respectively). Most patients with complications except for two children with dislodgment were as satisfied with the final results as those without complications. Although callus distraction in the hand requires a long treatment period and has a relatively high rate of complication, it appears to be effective in achieving adequate bone length. A high level of patient compliance and prompt management of complications by an experienced surgeon are essential for achieving good results.


High temperature acclimation of C4 photosynthesis is linked to changes in photosynthetic biochemistry.
With average global temperatures predicted to increase over the next century, it is important to understand the extent and mechanisms of C4 photosynthetic acclimation to modest increases in growth temperature. To this end, we compared the photosynthetic responses of two C4 grasses (Panicum coloratum and Cenchrus ciliaris) and one C4 dicot (Flaveria bidentis) to growth at moderate (25/20 degrees C, day/night) or high (35/30 degrees C, day/night) temperatures. In all three C4 species, CO2 assimilation rates (A) underwent significant thermal acclimation, such that when compared at growth temperatures, A increased less than what would be expected given the strong response of A to short-term changes in leaf temperature. Thermal photosynthetic acclimation was further manifested by an increase in the temperature optima of A, and a decrease in leaf nitrogen content and leaf mass per area in the high- relative to the moderate-temperature-grown plants. Reduced photosynthetic capacity at the higher growth temperature was underpinned by selective changes in photosynthetic components. Plants grown at the higher temperature had lower amounts of ribulose-1,5-bisphosphate carboxylase/oxygenase and cytochrome f and activity of carbonic anhydrase. The activities of photosystem II (PSII) and phosphoenolpyruvate carboxylase were not affected by growth temperature. Chlorophyll fluorescence measurements of F. bidentis showed a corresponding decrease in the quantum yield of PSII (phi(PSII)) and an increase in non-photochemical quenching (phi(NPQ)). It is concluded that through these biochemical changes, C4 plants maintain the balance between the various photosynthetic components at each growth temperature, despite the differing temperature dependence of each process. As such, at higher temperatures photosynthetic nitrogen use efficiency increases more than A. Our results suggest C4 plants will show only modest changes in photosynthetic rates in response to changes in growth temperature, such as those expected within or between seasons, or the warming anticipated as a result of global climate change.


Effects of native diversity, soil nutrients, and natural enemies on exotic invasion in experimental plant communities.
Many factors can promote exotic plant success. Three of these factors-greater pressure from natural enemies on natives, increased soil nutrient supply, and low native species richness-may interact during invasions. To test for independent and interactive effects of these drivers, we planted herbaceous perennial communities at two levels of native richness (monocultures and five-species polycultures). We then factorially manipulated soil nutrient supply and access to these communities by aboveground foliar enemies (fungal pathogens and insect herbivores), and allowed natural colonization to proceed for four years. We predicted that nutrient addition would increase exotic success, while enemy exclusion and increasing native richness would reduce exotic success. Additionally, we expected that enemy exclusion would reduce the benefits of nutrient addition to exotic species most in species-poor communities, and that this effect would be weaker in species-rich communities. In total, we found no evidence that nutrient supply, enemy access, and native richness interacted to influence exotic success. Furthermore, native richness had no effect on exotic success. Instead, nutrient addition increased, and enemy exclusion decreased, exotic success independently. As predicted, enemy exclusion reduced exotic success, primarily by slowing the decline in abundance of planted native species. Together, these results demonstrate that multiple drivers of exotic success can act independently within a single system.


Characterisation of dic(9;20)(p11-13;q11) in childhood B-cell precursor acute lymphoblastic leukaemia by tiling resolution array-based comparative genomic hybridisation reveals clustered breakpoints at 9p13.2 and 20q11.2.
Although the dic(9;20)(p11-13;q11) is a recurrent chromosomal abnormality in paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL), occurring in approximately 2% of the cases, its molecular genetic consequences have not been elucidated. In the present study, high-resolution genome-wide array-based comparative genomic hybridisation (array-CGH) and fluorescence in situ hybridisation (FISH) were used to characterise the 9p and 20q breakpoints (BPs) in seven childhood BCP ALLs with dic(9;20), which was shown to be unbalanced in all of them, resulting in loss of 9p13.2-pter. Five of the cases had loss of 20q11.2-qter, whereas two displayed gain of 20cen-pter. All BPs on 9p clustered in a 1.5 Mb segment of the sub-band 9p13.2; in three of the cases, the 20q BPs mapped to three adjacent clones covering a distance of 350 kb at 20q11.2. Thus, the aberration should be designated dic(9;20)(p13.2;q11.2). One of the ALLs, shown to have a complex dic(9;20), was further investigated by FISH, revealing a rearrangement of the haemapoietic cell kinase isoform p61 (HCK) gene at 20q11. The disruption of HCK may result in a fusion gene or in loss of function. Unfortunately, lack of material precluded further analyses of HCK. Thus, it remains to be elucidated whether dic(9;20)(p13.2;q11.2) leads to a chimaeric gene or whether the functionally important outcome is loss of 9p and 20q material.


Cotranscriptional RNA processing and modification in plants.
The activities of RNA polymerases shape the epigenetic landscape of genomes with profound consequences for genome integrity and gene expression. A fundamental event during the regulation of eukaryotic gene expression is the coordination between transcription and RNA processing. Most primary RNAs mature through various RNA processing and modification events to become fully functional. While pioneering results positioned RNA maturation steps after transcription ends, the coupling between the maturation of diverse RNA species and their transcription is becoming increasingly evident in plants. In this review, we discuss recent advances in our understanding of the crosstalk between RNA Polymerase II, IV, and V transcription and nascent RNA processing of both coding and noncoding RNAs.


Requirements for growth of Epstein-Barr virus-transformed cells at low cell densities.
We investigated the requirements for growth of Epstein-Barr virus-transformed cells at low cell densities in a homotypic system: only Epstein-Barr virus-transformed cells or their products were used to supply feeder activity. The cloning efficiency was increased markedly under conditions favouring close cell-to-cell contact: culture in round-bottomed rather than in flat-bottomed wells or the addition of irradiated Epstein-Barr virus-transformed cells. Further enhancement was obtained by the addition of the tumour promoter phorbol-myristate acetate. Part of this effect was also induced by supernatants of Epstein-Barr virus-transformed cells, in particular when the latter had been stimulated with phorbol ester. Thus, under limiting dilution conditions, Epstein-Barr virus-transformed cells were found to be dependent upon autologous cell-mediated and soluble proliferation-stimulating signals. In such a homotypic feeder system, the cloning efficiency could be enhanced up to eight-fold; a 100% cloning efficiency could not be achieved. Evidence is presented that the residual deficit in cloning efficiency is inherent to these cell lines.


Direct activation by dopamine of recombinant human 5-HT1A receptors: comparison with human 5-HT2C and 5-HT3 receptors.
The effects of dopamine (DA) on the function of human 5-HT1A receptors expressed in Xenopus oocytes and CHO-K1 cells were investigated. In addition, the effect of DA on the activation of three different types of human 5-HT receptors (5-HT1A, 5-HT2C, and 5-HT3) were studied comparatively in Xenopus oocyte expression system. Application of 5-HT or DA in oocytes coexpressing 5-HT1A receptors and G-protein-activated inwardly rectifying potassium channels (GIRK1) induced inward currents with respective EC50 values of 4.2 nM and 11.2 microM. Maximal responses induced by DA were 85 +/- 4% of maximal 5-HT currents and DA responses were blocked by the specific 5-HT1A antagonist, WAY-100635 (50 nM). In CHO-K1 cells expressing 5-HT1A receptors, 5-HT and DA inhibited the specific binding of selective antagonist [3H]-8-OH-DPAT with IC50 values of 10.2 nM and 1.4 microM, and both 5-HT and DA inhibited the forskolin-induced accumulation of cAMP. In oocytes expressing 5-HT2C receptors, 5-HT and DA induced inward currents with respective EC50 values of 6.2 nM and 67.7 microM. Magnitudes of maximal DA induced currents were 42 +/- 3% of maximal 5-HT responses and blocked by the 5-HT2 antagonist, piperazine (1 microM). In oocytes expressing 5-HT3 receptors, 5-HT and DA induced fast inward currents with respective EC50 values of 2.1 microM and 266.3 microM. Maximal DA induced currents were 37 +/- 3% of maximal 5-HT responses and blocked the specific 5-HT3 antagonist LY-278584 (0.1 microM). Comparison of the potencies and efficacies of 5-HT and DA indicated that the relative potency of DA increased in the order of 5-HT3 > 5-HT1A > 5-HT2C, and relative efficacy increased in the order of 5-HT1A > 5-HT2C > 5-HT3. These results suggest that although DA activates different subtypes of human 5-HT receptors directly, the potency and efficacy of the binding site varies significantly among different receptors.


The morphological and ecological variation of Arctostaphylos (Ericaceae) fruit: A link between plant ecology and animal foraging behavior.
Persistent soil seed banks are characteristic of Arctostaphylos (Ericaceae) species in the Mediterranean-climate California Floristic Province. While most species are obligate seeders, regeneration of stands of all Arctostaphylos species ultimately depends on post-fire seedling recruitment. Arctostaphylos seed banks are created, in large part, by scatter-hoarding rodents. Variation in fruit morphology, therefore, is expected to impact the Arctostaphylos-rodent interaction. Seeds produce sufficient rewards (nutritious mature embryo) to entice rodents to disperse and ultimately bury seeds in the soil. Hard seed coats increase the time required to extract the embryo, encouraging rodents to choose storage over immediate predation, and nutlets are frequently empty. We assessed the variation of fruit nutlet fusion and seed viability among 38 Arctostaphylos taxa. Factors such as latitude, elevation, life history, ploidy, and phylogenetic position were also analyzed. Generalized mixed-effects models were used to determine the factors contributing to variation in fruit nutlet fusion and seed viability. Our results indicate that fruit volume and shape are the most important variables affecting nutlet fusion and seed viability. Additionally, other potential influences only show a weak correlation and are not predicted to significantly impact nutlet fusion or seed viability. These findings provide insights into evolved strategies used by plants to increase reproductive success via scatter-hoarding rodents. Our study benefits the conservation and restoration of Arctostaphylos stands by emphasizing the importance of animal-mediated dispersal and providing estimates of seed viability for different species. With the anticipated effects of climate change, such as departures from historic fire regimes, the preservation of the relationship between plants and animal foragers is crucial for the continued survival of Arctostaphylos and California's evergreen chaparral.


Chemical Differentiation of Plant Latexes and Their Anti-herbivory Activity against Thrips Frankliniella occidentalis.
Despite the extensive studies on latex, some fundamental questions on their chemical specialization and the factors influencing this specialization have yet to be investigated. To address this issue, latexes and their bearing tissues from diverse species were profiled by 1HNMR and GC-MS. Additionally, the antiherbivory activity of these materials was tested against thrips (Frankliniella occidentalis Pergande, 1895). The multivariate data analysis showed a clear separation between latexes and leaves from the same species. Conversely, the chemical profiles of latexes from different species were highly similar, that is, they displayed much less metabolic species-specificity. These shared chemical profiles of latexes were reflected in their overall higher mortality index (80.4% ± 7.5) against thrips compared with their bearing tissues (55.5% ± 14.9). The metabolites correlated to the antiherbivory activity of latexes were triterpenoids and steroids. However, the activity could not be attributed to any single terpenoid. This discrepancy and the reduction of the latex activity after fractionation suggested a complementary effect of the compounds when in a mixture as represented by the latex. Additionally, aqueous fractions of several latexes were found to possess simple spectra, even with only 1 metabolite. These metabolites were determined to be organic acids that might be involved in the modulation of the rate of latex coagulation, potentially increasing the sealing and trapping effects of the latex.


Overexpression of high mobility group box 1 with poor prognosis in patients after radical prostatectomy.
What's known on the subject? and What does the study add? Recent studies have indicated that high mobility group box 1 (HMGB1) is related to the development and progression of human carcinomas. However, further studies were required to confirm the roles played by HMGB1 in clinical prostate cancer treatment. We investigated the relationship between HMGB1 expression and the characteristics of prostate cancer, and also evaluated the significance of HMGB1 as a prognostic factor for biochemical recurrence-free survival after radical prostatectomy. • To investigate high mobility group box 1 (HMGB1) expression in human prostate cancer (PC) cell lines and its prognostic significance after radical prostatectomy (RP). • Quantitative reverse-transcription polymerase chain reaction and western blotting were used to detect HMGB1 mRNA and protein expression in PC cell lines. • Immunohistochemistry coupled with the tissue microarray technique was performed to evaluate HMGB1 protein expression in 168 primary prostatectomy tissue samples. • Clinicopathological features were compared between positive and negative HMGB1 protein expression groups. • Kaplan-Meier and multivariate Cox analyses were applied to determine the prognostic value of HMGB1 protein expression on biochemical recurrence (BCR) for patients with PC who were undergoing RP. • There were three PC cells (DU145, PC-3 and LNCaP) with overexpression of HMGB1 mRNA and protein compared to the non-transformed immortalized prostate cell RWPE-1. • A total of 60.1% (101/168) of the PC samples appeared to have positive protein expression of HMGB1. • HMGB1 protein expression was correlated with some clinicopathological parameters, such as pathological stage (pT) (P= 0.011), Gleason score, preoperative prostate-specific antigen concentration and BCR (P < 0.001, respectively). • Positive HMGB1 immunostaining in patients with PC who were undergoing RP was significantly associated with poor median BCR-free survival (23.1 months vs 15.6 months) (P < 0.001). • Multivariate analysis indicated that HMGB1 protein expression was an independent prognostic factor for BCR-free survival after RP (hazard ratio = 2.348, 95% confidence interval = 1.373-6.361, P= 0.001). • Up-regulation of HMGB1 mRNA and protein concentrations was confirmed in PC cells. • HMGB1 expression may contribute to the malignant progression of PC. • HMGB1 presents as a novel prognostic factor for BCR after RP.


Workplace violence: are some nurses more vulnerable?
Workplace violence pervades the healthcare setting. This study describes workplace violence events (WPVE) by type, frequency, perpetrator, and contributing factors and explores the relationship between WPVE and a history of childhood/adult abuse. Sixty-seven randomly selected registered nurses responded to the study. Both closed and open-ended responses were obtained. The majority of nurses experienced WPVE, typically emotional and verbal events. Physicians were commonly the perpetrators. Contributing factors included drugs, poor staffing, hospital location, gangs, easy access to triage, long hours worked, no training, power/control, stress, and negative characteristics of perpetrators. Over half of the nurses reported being victims of childhood or adult abuse; this abuse history was found to influence type (sexual and physical), frequency, and timing of WPVE. In an effort to prevent and reduce the frequency of WPVE, risk assessments of all health care environments should be made, followed with education discussing prevalency, type of WPVE, perpetrators, and contributing factors, including past victimization.


Keeping up with COVID-19 information: Capacity issues and knowledge uncertainty early in the pandemic.
This article examines the relationship between information consumption and mental health during the early stages of the COVID-19 pandemic. Adopting a qualitative approach, we interviewed 39 people in British Columbia, Canada between October and December 2020. Interestingly, half of the participants did not want to seek out new information on COVID-19, making their early insights and initial confusion salient. While some individuals did desire up-to-date information on outbreaks and new risks, many expressed confusion over what was perceived to be an evolving landscape of public health policy and practice. Overall, our research found that capacity issues, information overload/fatigue, politics, distrust, and competing sources of news all contributed to a culture of confusion towards public health information. As a consequence, this confusion resulted in knowledge uncertainty about the virus, vaccinations, and the pandemic itself. Our findings highlight the need for a host of future projects that examine how citizens experience disempowerment and limited agency towards compliance with health and safety initiatives.


Female healthcare workers and the Covid-19 pandemic in Brazil: a sociological analysis of healthcare work.
The article aims to discuss the care provided by female healthcare workers in Brazil during the Covid-19 pandemic, based on a sociological analysis by authors who discuss such care as devalued and poorly paid work performed to a large extent by low-income women. The work involves social constructions of emotions and has used the body as a work instrument in care for others. In addition, the increasingly precarious nature of health work in Brazilian society, aggravated in recent decades, with an increase in temporary contracts, loss of labor rights, overload of tasks, and adverse work conditions, among others, adds to the increase in medical and hospital care in the Covid-19 pandemic. In this context, female healthcare workers experience lack of personal protective equipment, fear of coronavirus infection, concerns with their children and other family members, and illness and death of coworkers and themselves. The article highlights the need for government attention and management of healthcare work and professional societies, analyzing the work conditions female healthcare workers are experiencing in confronting the pandemic.


Spatiotemporal dynamics of the Landolt reaction in an open spatial reactor with conical geometry.
In a previous study, the iodate-sulfite proton autoactivated reaction (Landolt reaction) was shown to exhibit spatial bistability and spatiotemporal oscillations when operated in an open spatial reactor with fixed "thickness", i.e., feed boundary to core distance. Here, we show that the spatial reactors with conical geometry enable one to rapidly probe the sensitivity of the above phenomena over a large range of the "thickness" parameter. This often-neglected parameter in chemical pattern studies plays an important role on the selection and stability of states. We reveal that the quenching capacity of slow diffusing polyacrylate ions on the spatiotemporal oscillations depends on this "thickness". The presented results should be useful for further research on reaction diffusion patterns and chemomechanical structures.


Imprinting and anticipation. Are they relevant to genetic studies of schizophrenia?
Among 29 multiply affected pedigrees, age of onset among parents and offspring was examined for evidence of both anticipation and genomic imprinting. The results do not suggest that either mechanism is operating in schizophrenia, but only very large effects can be confidently excluded.


Angular Dependence of Strong Field Ionization of CH3X (X = F, Cl, Br, or I) Using Time-Dependent Configuration Interaction with an Absorbing Potential.
Methyl halides have been used to test basis set effects on simulations of strong field ionization using time dependent configuration interaction with an absorbing potential. Standard atom centered basis sets need to be augmented by several sets of diffuse functions on each atom so that the wave function in the strong field can interact with the absorbing potential used to model ionization. An absorbing basis of 3 s functions, 2 p functions, 3 d functions, and 1 f function is sufficient for CH3F. Large absorbing basis sets with 4 s functions, 3 or 4 p functions, 4 or 5 d functions, and 2 f functions are recommended for the heavier halogens. The simulations used static fields in the 0.035-0.07 au range to explore the angular dependence of ionization of methyl halides. CH3F ionizes mainly from the methyl group; CH3Cl and CH3Br show ionization from both the methyl group and the halogen, and CH3I ionizes almost exclusively from the pπ orbitals of the iodine.


Simultaneous quantification of protein-DNA interactions and transcriptomes in single cells with scDam&T-seq.
Protein-DNA interactions are essential for establishing cell type-specific chromatin architecture and gene expression. We recently developed scDam&T-seq, a multi-omics method that can simultaneously quantify protein-DNA interactions and the transcriptome in single cells. The method effectively combines two existing methods: DNA adenine methyltransferase identification (DamID) and CEL-Seq2. DamID works through the tethering of a protein of interest (POI) to the Escherichia coli DNA adenine methyltransferase (Dam). Upon expression of this fusion protein, DNA in proximity to the POI is methylated by Dam and can be selectively digested and amplified. CEL-Seq2, in contrast, makes use of poly-dT primers to reverse transcribe mRNA, followed by linear amplification through in vitro transcription. scDam&T-seq is the first technique capable of providing a combined readout of protein-DNA contact and transcription from single-cell samples. Once suitable cell lines have been established, the protocol can be completed in 5 d, with a throughput of hundreds to thousands of cells. The processing of raw sequencing data takes an additional 1-2 d. Our method can be used to understand the transcriptional changes a cell undergoes upon the DNA binding of a POI. It can be performed in any laboratory with access to FACS, robotic and high-throughput-sequencing facilities.


Pre-heating effect on the catalytic growth of partially filled carbon nanotubes by chemical vapor deposition.
The surface reconstruction of the Fe catalyst films due to high temperature processing in hydrogen prior to nanotube nucleation and its effect on the growth morphologies of partially filled carbon nanotubes (CNTs) synthesized using atmospheric pressure chemical vapor deposition (APCVD) of propane was investigated. Results show that pre-heating of the catalyst film deeply influences the particle size distribution, which governs the growth morphologies of the corresponding CNTs. The distribution of the catalyst particles over the Si substrate was analyzed before and after the heat treatment by atomic force microscopy (AFM) which reveals that heat treatment causes clusters of catalyst to coalesce and form macroscopic islands. The X-ray diffraction (XRD) pattern of the grown material indicates that they are graphitic in nature. Scanning electron microscopy (SEM) analysis suggested that the growth density strongly depends on the pre heat treatment of the Fe catalyst film. Multiwalled CNTs with partial catalyst filling were observed via high-resolution transmission electron microscopy (HRTEM) measurements. The degree of graphitization of the CNTs also depends on the pre heating as demonstrated by Raman analysis. A simple model for the growth of partially catalyst filled nanotubes is proposed.


Validation of a simplified sham acupuncture technique for its use in clinical research: a randomised, single blind, crossover study.
The validity of a new sham acupuncture technique was tested on acupuncture naïve healthy subjects. The procedure was tested in accupoints LI4 and ST6 in a randomised, single blind and crossover study. The participants were blind to which technique they received. 32 healthy volunteers (15 men, 17 women, aged between 20 and 62 years, mean age 34 years) were recruited at the Universidad de la República, Uruguay. Interventions Participants were randomly assigned to one of two groups: (1) real acupuncture or (2) sham acupuncture. After 30 min, the patients were 'needled' again in a crossover design. Main outcome measures A yes/no questionnaire was used to assess the credibility and characteristics of the procedure. For the credibility question (do you think you received real acupuncture?) no statistically significant group differences were evident before or after the crossover. Subjects who answered yes to this question ranged from 14/16 (87.5%) before crossover to 10/16 (62.5%) after crossover for the sham and 12/16 (75%) before crossover to 15/16 (93.8%) after crossover for the real acupuncture. The question that showed a significant difference (only after crossover) was the question, "did you feel the needle penetrating the skin?"; after crossover 12/16 (75%) subjects in the real acupuncture group said yes and 2/16 (12%) subjects in the sham group said yes to this question (p<0.01). These data suggests that this method is credible and constitutes a simple and inexpensive technique for use as a control in clinical research in acupuncture naïve subjects.


Electronic structure of the glyoxalbis(2-hydroxyanil) (gha) ligand in [Co(III)(gha)(PPh3)2]+: radical vs. non-radical states.
The synthesis, structure and spectroscopic properties of a complex salt [Co(III)(gha)(PPh3)2][Co(II)Cl3(PPh3)] x C2H5OH (1) are reported; gha = glyoxalbis(2-hydroxyanil). This is the first single crystal X-ray structure of a (gha)2- complex with a transition element. Though the determined bond parameters and UV-Vis spectroscopic data correlate well with a diradical description for the cation in 1, detailed electronic structure calculations using density functional theory confirm that [Co(gha)(PPh3)2]+ can be described as a closed shell singlet species which nevertheless displays an interesting electronic structure with significant electron transfer to the formally unoccupied LUMO of the square planar [Co(gha)]+ fragment. It was found that without the phosphine coligands, the [Co(gha)]+ unit has a triplet ground state with the lowest energy singlet diradical state lying only 1 kcal mol(-1) higher in energy. The chemistry of the gha ligand is of interest as a spin diverse redox active system.


[Characteristics of antiviral drugs].
This article summarizes the principal characteristics of the drugs used to treat viral infections, with the exception of human immunodeficiency virus infection. It includes antiviral agents active against herpes virus, cytomegalovirus, hepatitis B and C virus, and respiratory viruses, such as influenza and respiratory syncytial virus. Dosage according to the indication, dose adjustment in the case of renal or hepatic insufficiency, significant pharmacokinetic characteristics, and the main adverse effects and interactions are described.


Effects of flower thrips (Thysanoptera: Thripidae) on nutritional quality of banana (Zingiberales: Musaceae) buds.
The abundance of banana flower thrips (Thrips hawaiiensis Morgan) in a banana (Musa acuminata Colla "Williams" cultivar) plantation was investigated using yellow sticky traps (29.70 cm × 21.00 cm) in 2015. Banana flower thrips occurred throughout the year with monthly variation, and the maximum occurrence was observed in October and November during the bud burst (73.80 ± 6.32 adults/trap) and young fruit (70.06 ± 5.69 adults/trap) periods. The damage rates were as follows: interior flowers >3rd-layer flowers > 2nd-layer flowers > 1st-layer flowers > young fruits. This result indicates that thrips migrated to lower bracts, young fruits, and other flower buds as bracts gradually opened. Results also showed that the reducing sugar, vitamin C, protein and ash contents in thrips-damaged flowers were all significantly lower than those in undamaged flowers, while there was no significant difference between damaged and undamaged young banana fruit. Our results indicated that the abundances of banana flower thrips were closely associated with the growing stage of banana. Thrips mainly infested flower buds and caused a reduction in nutrients for the host plant, especially the reducing sugar and vitamin C contents, which reduced the nutritional quality of banana fruits and the quality of flower bud by-products of banana.


Clinical and hemodynamic improvement of congestive heart failure by long-term vasodilator therapy with postjunctional alpha 1-adrenoceptor blockade.
Eleven of 12 patients with severe congestive heart failure who were pretreated with diuretics and digitalis benefited from long-term therapy with prazosin which was titrated to the individual's maximally tolerated dose. Nine of the 11 patients improved their functional state by one (n = 4) or two (n = 5) New York Heart Association (NYHA) classes. Within 4 weeks the stroke volume index increased from 23 +/- 10 to 29 +/- 9 SD (ml/beat/m2) while pulmonary capillary pressure decreased from 29 +/- 8 +/- 9 mm Hg (p less than 0.05 for both) and peripheral vascular resistance fell from 2,245 +/- 792 to 1,603 +/- 355 dyn/s cm-5 (p less than 0.01). Hemodynamics results were similar on the same regimen in eight patients assessed for 6 months. Death of three patients (week 5 and week 17) was unrelated to prazosin therapy. Prazosin resulted in improved cardiac performance during leg-up-tilt or supine ergometry. Increase in stroke volume index was related to the fall in peripheral vascular resistance (r = -0.79, p less than 0.01). Plasma adrenaline (301 +/- 480 pg/Ml), noradrenaline (1,312 +/- 1,382 pg/ml), and renin activity (22 +/- 30 ng/ml/h) were in the range observed with pheochromocytoma; variables did not change on prazosin. This reflects an important role of alpha-adrenoceptor-mediated vascular regulation in patients with heart failure in whom long-term treatment with prazosin produces a sustained and well-tolerated vasodilator effect without further rise in catecholamines and renin.


[Mesenchymal stem cells derived apoptotic extracellular vesicles attenuate pro-inflammatory macrophages induced by Porphyromonas gingivalis lipopolysaccharide].
Objective: To investigate whether bone marrow mesenchymal stem cells (BMMSCs) derived apoptotic extracellular vesicles (ApoEVs) could regulate the polarization of mouse macrophage cell line RAW264.7 and whether BMMSCs derived ApoEVs could attenuate pro-inflammatory condition of RAW264.7 induced by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS), so as to provide experimental evidence and theoretical basis for using BMMSCs derived ApoEVs as a method to treat periodontitis. Methods: The Operetta CLS high-content analysis system was used to observe the time-dependent apoptosis process of BMMSCs. Besides, field emission scanning electron microscopy (FESEM), dynamic light scattering technology and streaming potential method were used to measure the surface characteristics of BMMSCs derived ApoEVs. The Operetta CLS high-content analysis system was used to observe the process of RAW264.7 phagocyting 5-carboxy-tetramethylrhodamine, succinimidyl ester (5-TAMRA-SE) labeled ApoEVs. Real-time quantitative PCR was used to detect the mRNA expression of arginase-1 (Arg-1). Cell immunofluorescence and Western blotting were used to detect the number of inducible nitric oxide synthase (iNOS)(+) macrophages and iNOS protein expression level in each experiment group. Enzyme linked immunosorbent assay was used to detect tumor necrosis factro-α (TNF-α) level in the Pg-LPS induced pro-inflammatory macrophage culture supernatant in each experiment group. Results: After treating with 0.5 μmol/L staurosporine for 12 hours, mouse BMMSCs underwent shrinking with obvious vesicles structure around. The FESEM showed the ApoEVs were in spherical shapes. The size range of ApoEVs was about 100-1 000 nm and the average Zeta potential was -16.6 mV. The Operetta CLS high-content analysis system showed RAW264.7 could phagocytose 5-TAMRA-SE labeled ApoEVs by pseudopodia. The relative mRNA expression of Arg-1 was significantly increased in RAW 264.7 after being treated with interleukin 4 (IL-4) and ApoEVs (261.97±15.91) compared to that with IL-4 alone (115.29±15.42) (P<0.01). Cell immunofluorescence showed that ApoEVs could reduce the number of iNOS(+) macrophages induced by Pg-LPS (39.33±4.70) comparing to those without ApoEVs (95.33±4.70) (P=0.007). In the meanwhile, ApoEVs could also down-regulate the iNOS protein level of macrophages induced by Pg-LPS (5.84±1.05) comparing to those without ApoEVs (14.91±3.87) (P<0.01). Besides, ApoEVs could also reduce the TNF-α secretion in the culture supernatant of pro-inflammatory macrophages induced by Pg-LPS [(21 899.71±409.73) ng/L] comparing to those without ApoEVs [(71 296.50±2 344.22) ng/L] (P=0.003). Conclusions: BMMSCs derived ApoEVs could regulate the polarization of macrophages and could also attenuate the pro-inflammatory condition of macrophages induced by Pg-LPS.


Rab6a/a' are important Golgi regulators of pro-inflammatory TNF secretion in macrophages.
Lipopolysaccharide (LPS)-activated macrophages secrete pro-inflammatory cytokines, including tumor necrosis factor (TNF) to elicit innate immune responses. Secretion of these cytokines is also a major contributing factor in chronic inflammatory disease. In previous studies we have begun to elucidate the pathways and molecules that mediate the intracellular trafficking and secretion of TNF. Rab6a and Rab6a' (collectively Rab6) are trans-Golgi-localized GTPases known for roles in maintaining Golgi structure and Golgi-associated trafficking. We found that induction of TNF secretion by LPS promoted the selective increase of Rab6 expression. Depletion of Rab6 (via siRNA and shRNA) resulted in reorganization of the Golgi ribbon into more compact structures that at the resolution of electron microcopy consisted of elongated Golgi stacks that likely arose from fusion of smaller Golgi elements. Concomitantly, the delivery of TNF to the cell surface and subsequent release into the media was reduced. Dominant negative mutants of Rab6 had similar effects in disrupting TNF secretion. In live cells, Rab6-GFP were localized on trans-Golgi network (TGN)-derived tubular carriers demarked by the golgin p230. Rab6 depletion and inactive mutants altered carrier egress and partially reduced p230 membrane association. Our results show that Rab6 acts on TNF trafficking at the level of TGN exit in tubular carriers and our findings suggest Rab6 may stabilize p230 on the tubules to facilitate TNF transport. Both Rab6 isoforms are needed in macrophages for Golgi stack organization and for the efficient post-Golgi transport of TNF. This work provides new insights into Rab6 function and into the role of the Golgi complex in cytokine secretion in inflammatory macrophages.


Measurement of platelet aggregation functions using whole blood migration ratio in a microfluidic chip.
Platelets play a major role in maintaining endothelial integrity and hemostasis. Of the various soluble agonists, ADP is an important in vivo stimulus for inducing platelet aggregation. In this study, a simple, rapid, and affordable method was designed for testing bleeding time (BT) and platelet aggregation with a two-channel microfluidic chip. Whole blood migration ratio (MR) from a microchip system was evaluated in comparison to the closure time (CT) from PFA-100 assays (Siemens, Germany) and CD62P expression on platelets. To induce platelet aggregation, a combination of collagen (1.84 mg/ml) and ADP (37.5 mg/ml) were used as agonists. After adding the agonists to samples, whole blood MR from the microchip system was measured. The outcome of the assessment depended on reaction time and agonist concentration. MR of whole blood from the microchip system was significantly correlated with CT from PFA-100 (r = 0.61, p < 0.05, n = 60). In addition, MR was negatively correlated with CD62P expression (r =-0.95, p < 0.05, n = 60). These results suggest that the measurement of MR using agonists is an easy, simple and efficient method for monitoring platelet aggregation in normal and ADP-receptors defective samples, along with the BT test. Thus, usage of the current microfluidic method could expand to diverse applications, including efficacy assessments in platelet therapy.


[Surgical treatment of pulmonary metastases of colorectal tumors].
In 22 cases of the 510 patients underwent surgery and followed up because of colorectal cancer, only pulmonary metastases were found. General problems in the surgery of pulmonary metastases are discussed and the possibilities and the expected results of the surgical therapy of pulmonary metastases in colorectal patients are analysed in details on the base of the data of their 8 patients underwent surgery and according to the literature. In carefully selected cases the surgical therapy of the metastases can be recommended.


Further studies of a simian virus 40-like virus isolated from human brain.
A virus similar to simian virus 40 was reisolated from brain homogenates of a patient with progressive multifocal leukoencephalopathy onto cultures of human fetal brain cells.


A pilot study on transplant eligibility criteria: valuing the stories in numbers.
The medical and nursing literature often seem divided between numerical, qualitative studies, and quantitative, narrative-based case histories. Rarely are the numbers generated by the first informed by the experiences and insights offered by the second type of study. This paper reports on a pilot study carried out at the Hospital for Sick Children, Toronto, on a methodology combining qualitative and quantitative data. Using the Analytic Hierarchy Process (AHP), a type of multicriterion decision making, focus groups were used to analyze survey-based organ transplant eligibility criteria. Through this process, a portrait of the limits of that data was generated by staff members. Organ transplant eligibility was chosen because of its importance, and very public discussions arising from high profile cases in Canada and the United States.


Role of Interleukin-17A in the Pathomechanisms of Periodontitis and Related Systemic Chronic Inflammatory Diseases.
Periodontitis is a chronic inflammatory and destructive disease caused by periodontal microbial infection and mediated by host immune response. As the main cause of loosening and loss of teeth in adults, it is considered to be one of the most common and serious oral diseases in the world. The co-existence of periodontitis and systemic chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, diabetes and so on is very common. It has been found that interleukin-17A (IL-17A) secreted by various innate and adaptive immune cells can activate a series of inflammatory cascade reactions, which mediates the occurrence and development of periodontitis and related systemic chronic inflammatory diseases. In this work, we review the role of IL-17A in the pathomechanisms of periodontitis and related systemic chronic inflammatory diseases, and briefly discuss the therapeutic potential of cytokine targeted agents that modulate the IL-17A signaling. A deep understanding of the possible molecular mechanisms in the relationship between periodontitis and systemic diseases will help dentists and physicians update their clinical diagnosis and treatment ideas.


DNA haplotypes in the G6PD gene cluster studied in the Chinese Li population and their relationship to G6PDCanton.
In an effort to investigate the subtelomeric region of the X chromosome among Orientals, five DNA sites in the F8C and G6PD genes were analyzed in a sample of 46 chromosomes belonging to the Chinese Li population, an ethnic group characterized by a high prevalence of G6PD deficiency. The DNA sites analyzed, which are highly polymorphic in other populations, have a low degree of heterozygosity in the Li sample and, furthermore, the distribution of the corresponding haplotypes is very different from that previously observed in Italian populations. Interestingly, three unrelated Li G6PD-deficient variants analyzed at the DNA level have the 1376G-->T mutation characteristic of G6PDCanton and they share the same haplotype, including the sites mentioned above, as well as eight DNA polymorphisms in the red/green color vision pigment genes located proximal to G6PD on chromosome X.


Relative importance of aneurysm diameter and body size for predicting abdominal aortic aneurysm rupture in men and women.
Women have been shown to have up to a fourfold higher risk of abdominal aortic aneurysm (AAA) rupture at any given aneurysm diameter compared with men, leading to recommendations to offer repair to women at lower diameter thresholds. Although this higher risk of rupture may simply reflect greater relative aortic dilatation in women who have smaller aortas to begin with, this has never been quantified. Our objective was therefore to quantify the relationship between rupture and aneurysm diameter relative to body size and determine whether a differential association between aneurysm diameter, body size, and rupture risk exists for men and women. We performed a retrospective review of all patients in the Vascular Study Group of New England (VSGNE) database who underwent endovascular or open AAA repair. Height and weight were used to calculate each patient's body mass index and body surface area (BSA). Next, indices of each measure of body size (height, weight, body mass index, BSA) relative to aneurysm diameter were calculated for each patient. To generate these indices, we divided aneurysm diameter (in cm) by the measure of body size; for example, aortic size index (ASI) = aneurysm diameter (cm)/BSA (m(2)). Along with other relevant clinical variables, we used these indices to construct different age-adjusted and multivariable-adjusted logistic regression models to determine predictors of ruptured repair vs elective repair. Models for men and women were developed separately, and different models were compared using the area under the curve. We identified 4045 patients (78% male) who underwent AAA repair (53% endovascular aortic aneurysm repairs). Women had significantly smaller diameter aneurysms, lower BSA, and higher BSA indices than men. For men, the variable that increased the odds of rupture the most was aneurysm diameter (area under the curve = 0.82). Men exhibited an increased rupture risk with increasing aneurysm diameter (<5.5 cm: odds ratio [OR], 1.0; 5.5-6.4 cm: OR, 0.9; 95% confidence interval [CI], 0.5-1.7; P = .771; 6.5-7.4 cm: OR, 3.9; 95% CI, 1.9-1.0; P < .001; ≥ 7.5 cm: OR, 11.3; 95% CI, 4.9-25.8; P < .001). In contrast, the variable most predictive of rupture in women was ASI (area under the curve = 0.81), with higher odds of rupture at a higher ASI (ASI >3.5-3.9: OR, 6.4; 95% CI, 1.7-24.1; P = .006; ASI ≥ 4.0: OR, 9.5; 95% CI, 2.3-39.4; P = .002). For women, aneurysm diameter was not a significant predictor of rupture after adjusting for ASI. Aneurysm diameter indexed to body size is the most important determinant of rupture for women, whereas aneurysm diameter alone is most predictive of rupture for men. Women with the largest diameter aneurysms and the smallest body sizes are at the greatest risk of rupture.


A novel gene's role in an ancient mechanism: secreted Frizzled-related protein 1 is a critical component in the anterior-posterior Wnt signaling network that governs the establishment of the anterior neuroectoderm in sea urchin embryos.
The anterior neuroectoderm (ANE) in many deuterostome embryos (echinoderms, hemichordates, urochordates, cephalochordates, and vertebrates) is progressively restricted along the anterior-posterior axis to a domain around the anterior pole. In the sea urchin embryo, three integrated Wnt signaling branches (Wnt/β-catenin, Wnt/JNK, and Wnt/PKC) govern this progressive restriction process, which begins around the 32- to 60-cell stage and terminates by the early gastrula stage. We previously have established that several secreted Wnt modulators of the Dickkopf and secreted Frizzled-related protein families (Dkk1, Dkk3, and sFRP-1/5) are expressed within the ANE and play important roles in modulating the Wnt signaling network during this process. In this study, we use morpholino and dominant-negative interference approaches to characterize the function of a novel Frizzled-related protein, secreted Frizzled-related protein 1 (sFRP-1), during ANE restriction. sFRP-1 appears to be related to a secreted Wnt modulator, sFRP3/4, that is essential to block Wnt signaling and establish the ANE in vertebrates. Here, we show that the sea urchin sFRP3/4 orthologue is not expressed during ANE restriction in the sea urchin embryo. Instead, our results indicate that ubiquitously expressed maternal sFRP-1 and Fzl1/2/7 signaling act together as early as the 32- to 60-cell stage to antagonize the ANE restriction mechanism mediated by Wnt/β-catenin and Wnt/JNK signaling. Then, starting from the blastula stage, Fzl5/8 signaling activates zygotic sFRP-1 within the ANE territory, where it works with the secreted Wnt antagonist Dkk1 (also activated by Fzl5/8 signaling) to antagonize Wnt1/Wnt8-Fzl5/8-JNK signaling in a negative feedback mechanism that defines the outer ANE territory boundary. Together, these data indicate that maternal and zygotic sFRP-1 protects the ANE territory by antagonizing the Wnt1/Wnt8-Fzl5/8-JNK signaling pathway throughout ANE restriction, providing precise spatiotemporal control of the mechanism responsible for the establishment of the ANE territory around the anterior pole of the sea urchin embryo.


Behavior of Listeria monocytogenes and Staphylococcus aureus in yogurt fermented with a bacteriocin-producing thermophilic starter.
Streptococcus salivarius subsp. thermophilus B producing a bacteriocin active against Listeria monocytogenes ATCC 7644 and Staphylococcus aureus SAD 30 was isolated from bakery yeast. The bacteriocin was partially purified by an adsorption/desorption technique, and its spectrum of action was compared to that of a neutralized cell-free supernatant (CFS). Although the CFS inhibited a number of gram-positive and -negative bacteria of health and spoilage significance, the spectrum of action of the partially purified bacteriocin was limited to gram-positive bacteria. L. monocytogenes was the most sensitive to both preparations. The bacteriocin-producing streptococcal strain was used in combination with a Bac- Lactobacillus delbrueckii subsp. bulgaricus CY strain isolated from commercial yogurt to assess the effectiveness of the resulting thermophilic starter in controlling L. monocytogenes and S. aureus in yogurt during fermentation and storage at refrigeration (ca. 7 degrees C) or abuse (ca. 22 degrees C) temperature. Yogurt samples were contaminated with L. monocytogenes or S. aureus to the approximate levels of 10(3) and 10(6) CFU/ml of milk, respectively. The results showed that in situ bacteriocin production was more active against L. monocytogenes than against S. aureus in vitro and in contaminated samples. While L. monocytogenes leveled off below the detectable limit in a 1-ml sample of yogurt within 24 h of processing, S. aureus survived in Bac+ and Bac- samples during 10 days of storage at room temperature (ca. 22 degrees C). Use of a Bac+ starter resulted in a 5-day extension of the shelf life.


Cadaveric study of division of the median nerve by the persistent median artery.
The purpose of this study is to characterize the division of the median nerve by the persistent median artery (PMA) and highlight the associated clinical implications. Penetration of the median nerve by the PMA is believed to cause compression of the median nerve and affect nerve conduction velocity. This paper explored whether the origin and the pattern of PMA dictate its ability to divide the median nerve. Origin, and relationship of the PMA to the median nerve were documented in 60 cadavers donated to the Human Anatomy Program at UT Health San Antonio. Entire path of this artery was followed in the forearm and the hand. Twenty-five cases of a persistent median artery (PMA) were found in the upper limbs (20.83%; 25/120) of these donated cadavers. Most of the persistent median arteries originated from the ulnar artery (48%; 12/25) and the others originated either from the anterior interosseous artery (36%; 9/25) or from the common interosseous artery (16%; 4/25). Sixty percent (15/25) of the persistent median arteries penetrated and divided the median nerve in the forearm. Interestingly, all the persistent median arteries that originated from the ulnar artery (100%; 12/12) divided the median nerve in the forearm and a palmar type of PMA was found to be more likely to divide the median nerve. Clinicians performing surgeries in the forearm and hand need to be aware of this anomaly and should screen patients for the presence of this artery prior to surgical intervention.


Hydrodynamics govern the pre-fusion docking time of synaptic vesicles.
Synaptic vesicle fusion is a crucial step in the neurotransmission process. Neurotransmitter-filled vesicles are pre-docked at the synapse by the mediation of ribbon structures and SNARE proteins at the ribbon synapses. An electrical impulse triggers the fusion process of pre-docked vesicles, leading to the formation of a fusion pore and subsequently resulting in the release of neurotransmitter into the synaptic cleft. In this study, a continuum model of lipid membrane along with lubrication theory is used to determine the traverse time of the synaptic vesicle under the influence of hydrodynamic forces. We find that the traverse time is strongly dependent on how fast the driving force decays or grows with closure of the gap between the vesicle and the plasma membrane. If the correct behaviour is chosen, the traverse time obtained is of the order of a few hundred milliseconds and lies within the experimentally obtained value of approximately 250 ms (Zenisek D, Steyer JA, Almers W. 2000 Nature406, 849-854 (doi:10.1038/35022500)). We hypothesize that there are two different force behaviours, which complies with the experimental findings of pre-fusion docking of synaptic vesicles at the ribbon synapses. The common theme in the proposed force models is that the driving force has to very rapidly increase or decrease with the amount of clamping.


Professional identity development: Learning and journeying together.
Pharmacy students start to develop their professional values through engagement with the course, practice exposure, staff and fellow students. Group working is an element of pedagogy which draws on the social aspects of learning to facilitate knowledge and skills development, but its potential role in facilitating professional identity formation has as yet been under researched. This study aimed to explore the potential of mutual learning through group work to contribute not only to academic knowledge and understanding, but also to the development of students' professional values and selves. Semi-structured interviews were conducted with 17 home and international first year undergraduate pharmacy students in a UK School of Pharmacy, to explore their experiences of interacting for learning with other students on the course. Thematic analysis of the interview data highlighted four main benefits of mutual learning, which are that it: promotes friendly interactions; aids learning about the subject and the profession; opens the mind through different opinions and ways of thinking; and enables learning about other people. Through working together students developed their communication skills and confidence; reflectively considered their own stance in the light of others' experiences and healthcare perspectives; and started to gain a wider worldview, potentially informing their future interactions with patients and colleagues. Some difficulties arose when group interactions functioned less well. Opportunity for collaboration and exchange can positively influence development of students' professional outlook and values. However, careful management of group working is required, in order to create a mutually supportive environment wherein students feel able to interact, share and develop together.


Electroencephalography Amplitude Modulation Analysis for Automated Affective Tagging of Music Video Clips.
The quantity of music content is rapidly increasing and automated affective tagging of music video clips can enable the development of intelligent retrieval, music recommendation, automatic playlist generators, and music browsing interfaces tuned to the users' current desires, preferences, or affective states. To achieve this goal, the field of affective computing has emerged, in particular the development of so-called affective brain-computer interfaces, which measure the user's affective state directly from measured brain waves using non-invasive tools, such as electroencephalography (EEG). Typically, conventional features extracted from the EEG signal have been used, such as frequency subband powers and/or inter-hemispheric power asymmetry indices. More recently, the coupling between EEG and peripheral physiological signals, such as the galvanic skin response (GSR), have also been proposed. Here, we show the importance of EEG amplitude modulations and propose several new features that measure the amplitude-amplitude cross-frequency coupling per EEG electrode, as well as linear and non-linear connections between multiple electrode pairs. When tested on a publicly available dataset of music video clips tagged with subjective affective ratings, support vector classifiers trained on the proposed features were shown to outperform those trained on conventional benchmark EEG features by as much as 6, 20, 8, and 7% for arousal, valence, dominance and liking, respectively. Moreover, fusion of the proposed features with EEG-GSR coupling features showed to be particularly useful for arousal (feature-level fusion) and liking (decision-level fusion) prediction. Together, these findings show the importance of the proposed features to characterize human affective states during music clip watching.


Visceral myopathy: Clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes.
Visceral motility dysfunction is a key feature of genetic disorders such as megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS, MIM moved from 249210 to 155310), chronic intestinal pseudo-obstruction (CIPO, MIM609629), and multisystemic smooth muscle dysfunction syndrome (MSMDS, MIM613834). The genetic bases of these conditions recently begun to be clarified with the identification of pathogenic variants in ACTG2, ACTA2, and MYH11 in individuals with visceral motility dysfunction. The MMIHS was associated with the heterozygous variant in ACTG2 and homozygous variant in MYH11, while the heterozygous variant in ACTA2 was observed in patients with MSMDS. In this study, we describe the clinical data as well as the molecular investigation of seven individuals with visceral myopathy phenotypes. Five patients presented with MMIHS, including two siblings from consanguineous parents, one had CIPO, and the other had MSMDS. In three individuals with MMIHS and in one with CIPO we identified heterozygous variant in ACTG2, one being a novel variant (c.584C>T-p.Thr195Ile). In the individual with MSMDS we identified a heterozygous variant in ACTA2. We performed the whole-exome sequencing in one sibling with MMIHS and her parents; however, the pathogenic variant responsible for her phenotype could not be identified. These results reinforce the clinical and genetic heterogeneity of the visceral myopathies. Although many cases of MMIHS are associated with ACTG2 variants, we suggest that other genes, besides MYH11, could cause the MMIHS with autosomal recessive pattern. © 2016 Wiley Periodicals, Inc.


Antisense Oligonucleotide Therapy for Neurodevelopmental Disorders.
Antisense oligonucleotides (ASOs) are short oligonucleotides that can modify gene expression and mRNA splicing in the nervous system. The FDA has approved ASOs for treatment of ten genetic disorders, with many applications currently in the pipeline. We describe the molecular mechanisms of ASO treatment for four neurodevelopmental and neuromuscular disorders. The ASO nusinersen is a general treatment for mutations of SMN1 in spinal muscular atrophy that corrects the splicing defect in the SMN2 gene. Milasen is a patient-specific ASO that rescues splicing of CNL7 in Batten's disease. STK-001 is an ASO that increases expression of the sodium channel gene SCN1A by exclusion of a poison exon. An ASO that reduces the abundance of the SCN8A mRNA is therapeutic in mouse models of developmental and epileptic encephalopathy. These examples demonstrate the variety of mechanisms and range of applications of ASOs for treatment of neurodevelopmental disorders.


Plant immunity suppressor SKRP encodes a novel RNA-binding protein that targets exon 3' end of unspliced RNA.
The regulatory roles of RNA splicing in plant immunity are emerging but still largely obscure. We reported previously that Phytophthora pathogen effector Avr3c targets a soybean protein SKRP (serine/lysine/arginine-rich protein) to impair soybean basal immunity by regulating host pre-mRNA alternative splicing, while the biochemical nature of SKRP remains unknown. Here, by using Arabidopsis as a model, we studied the mechanism of SKRP in regulating pre-mRNA splicing and plant immunity. AtSKRP confers impaired plant immunity against Phytophthora capsici and associates with spliceosome component PRP8 and splicing factor SR45, which positively and negatively regulate plant immunity, respectively. Enhanced crosslinking and immunoprecipitation followed by high-throughput sequencing (eCLIP-seq) showed AtSKRP is a novel RNA-binding protein that targets exon 3' end of unspliced RNA. Such position-specific binding of SKRP is associated with its activity in suppressing intron retention, including at positive immune regulatory genes UBP25 and RAR1. In addition, we found AtSKRP self-interact and forms oligomer, and these properties are associated with its function in plant immunity. Overall, our findings reveal that the immune repressor SKRP is a spliceosome-associated protein that targets exon 3' end to regulate pre-mRNA splicing in Arabidopsis.


Colony-Stimulating Factor 1 Receptor Blockade Inhibits Tumor Growth by Altering the Polarization of Tumor-Associated Macrophages in Hepatocellular Carcinoma.
Colony-stimulating factor-1 (CSF-1) and its receptor, CSF-1R, regulate the differentiation and function of macrophages and play an important role in macrophage infiltration in the context of hepatocellular carcinoma. The therapeutic effects of CSF-1R blockade in hepatocellular carcinoma remain unclear. In this study, we found that CSF-1R blockade by PLX3397, a competitive inhibitor with high specificity for CSF-1R tyrosine kinase, significantly delayed tumor growth in mouse models. PLX3397 inhibited the proliferation of macrophages in vitro, but intratumoral macrophage infiltration was not decreased by PLX3397 in vivo Gene expression profiling of tumor-associated macrophages (TAM) showed that TAMs from the PLX3397-treated tumors were polarized toward an M1-like phenotype compared with those from vehicle-treated tumors. In addition, PLX3397 treatment increased CD8+ T-cell infiltration, whereas CD4+ T-cell infiltration was decreased. Further study revealed that tumor cell-derived CSF-2 protected TAMs from being depleted by PLX3397. In conclusion, CSF-1R blockade delayed tumor growth by shifting the polarization rather than the depletion of TAMs. CSF-1R blockade warrants further investigation in the treatment of hepatocellular carcinoma. Mol Cancer Ther; 16(8); 1544-54. ©2017 AACR.