Geriatric consultation service in emergency department: how does it work?
Hong Kong is having a significant prevalence of geriatric patients who usually require admission after presentation to the hospital through emergency departments. The geriatric consultation programme 'We Care' aims at lowering acute geriatric medical admission. The study aims at analysing the impact of the geriatric consultation service on the acute medical admission, and to study the characteristics and outcome of geriatric patients. Retrospective study. Patients who received geriatric consultations during 1 January 2009 to 1 March 2011 were enrolled. The demographic information, diseases case mix, venue of discharge, clinical severity, community nursing service referrals and adverse outcomes were retrieved and analysed. The incidence of adverse outcomes under the presence of each factor was studied. 2202 geriatric patients were referred. Their age ranged from 45 to 99 (mean 79.91, SD 7.45, median 80). These cases were categorised into: (1) chronic pulmonary disease (n=673; 30.6%), (2) debilitating cardiac disease (n=526; 23.9%), (3) geriatric syndromes (n=147; 6.7%), (4) neurological problems (n=416; 18.9%), (5) diabetes-related problems (n=146; 6.6%), (6) terminal malignancy (n=39; 1.8%), (7) electrolyte or input/output disturbance (n=137; 6.2%), (8) non-respiratory infections (n=36, 1.6%) and (9) others (n=82; 3.7%). Acute medical admission was evaded in 84.7% of all consultations with 1039 (47.2%) patients discharged home and 825 patients (37.5%) admitted to convalescent hospital. The incidence rate of adverse outcomes was 1.6%. Programme 'We Care' provided comprehensive geriatric assessment to suitable geriatric patients, resulting in an effective reduction of acute geriatric hospital admission.


Effect of dosing and dosing frequency on the efficacy of ceftizoxime and the emergence of ceftizoxime resistance during the early development of murine abscesses caused by Bacteroides fragilis and Enterobacter cloacae mixed infection.
The efficacy of beta-lactams is thought to be dependent on the time that the unbound concentrations exceed the MIC (fT>MIC). However, the pharmacokinetic/pharmacodynamic index (PDI) that correlates best to the selection of resistance is not yet clear. The selection of ceftizoxime (CZX)-resistant Enterobacter cloacae mutant strains during the development of murine mixed-infection abscesses was studied to determine the PDI that is important for the emergence of resistance and the PDI value needed for the prevention of resistance. Studies were carried out 24 h after inoculation with Bacteroides fragilis ATCC 23745 and E. cloacae 22491. Six to 1,536 mg of CZX/kg of body weight/day given every 2 h (q2h), q4h, q6h, or q8h was started 30 min before inoculation and continued for 24 h. Resistant mutants were isolated to determine mutant frequencies (MF). The fT>MIC varied from 9 to 98% for E. cloacae, the peak concentration (unbound fraction) was 0.6 to 578 mg/liter, and the area under the concentration-time curve (unbound fraction) (fAUC) was 1.9 to 553 mg.h/liter. The fAUC-to-MIC ratio best explained the in vivo efficacy. CZX-resistant B. fragilis and E. cloacae mutants were isolated from untreated controls at an MF of 10(-5) to 10(-7). The MF of resistant B. fragilis did not increase during therapy. The selection of resistant E. cloacae strains at an MF of 10(-1) to 10(-2) was related to the fT>MIC and the ratio of fAUC to MIC following an inverse U shape. However, the ratio of fAUC to MIC was the stronger driver of resistance. The highest MFs were 0.7 to 0.9 at an fAUC-to-MIC ratio of approximately 250. We conclude that the ratio of fAUC to MIC is the PDI that correlated best to the in vivo efficacy of CZX and probably also to the emergence of resistant E. cloacae mutants. An fAUC-to-MIC ratio of 1,000 was needed to prevent the emergence of this resistance.


Crystal engineering of lattice metrics of perhalometallate salts and MOFs.
The synthesis of the salt 3 and metallo-organic framework (MOF) [{(4,4(')-bipy)CoBr(2)}(n)] 4 by a range of solid state (mechanochemical and thermochemical) and solution methods is reported; they are isostructural with their respective chloride analogues 1 and 2. 3 and 4 can be interconverted by means of HBr elimination and absorption. Single phases of controlled composition and general formula [4,4(')-H(2)bipy][CoBr(4-x)Cl(x)] 5(x) may be prepared from 2 and 4 by solid--gas reactions involving HBr or HCl respectively. Crystalline single phase samples of 5(x) and [{(4,4(')-bipy)CoBr(2-x)Cl(x)}(n)] 6(x) were prepared by solid-state mechanochemical routes, allowing fine control over the composition and unit cell volume of the product. Collectively these methods enable continuous variation of the unit cell dimensions of the salts [4,4(')-H(2)bipy][CoBr(4-x)Cl(x)] (5(x)) and the MOFs [{(4,4(')-bipy)CoBr(2-x)Cl(x)}(n)] (6(x)) by varying the bromide to chloride ratio and establish a means of controlling MOF composition and the lattice metrics, and so the physical and chemical properties that derive from it.


The effect of a polyhexamethylene biguanide mouthrinse compared with a triclosan rinse and a chlorhexidine rinse on bacterial counts and 4-day plaque re-growth.
For various clinical applications, polyhexamethylene biguanide hydrochloride (PHMB) has been used for many years as an antiseptic in medicine. Recently, a 0.04% and a 0.12% PHMB mouthwash were shown to inhibit plaque re-growth and to reduce oral bacterial counts. In this study, a 0.2% PHMB mouthrinse (A) was compared with a positive control 0.12% aqueous chlorhexidine solution (B), a commercially available 0.3% triclosan/2.0% polyvinyl methyl ether maleic acid copolymer mouthrinse (Colgate Total Plax) (C), and a negative control placebo rinse (10% ethanol, flavour) (D). The controlled clinical study was a double blind, randomized, four replicate cross - over design. Plaque re-growth was assessed with the Turesky et al. (1970) modification of the Quigley & Hein (1962) plaque index. The antibacterial effect was assessed by taking bacterial counts on the tooth surface (smears from the buccal surface of 16/26) and mucosa (smears from the buccal mucosa in opposite of area 16/26) after the professional prophylaxis and after the first rinse with the preparations on day 1 and prior to the clinical examination on day 5. Sixteen volunteers participated and, on day 1 of each study period were rendered plaque-free, ceased toothcleaning, and rinsed twice daily with the allocated mouthrinse. On day 5, plaque was scored and smears were collected according to the protocol. A 10-day wash-out period was carried out between each rinse evaluation. Data were analysed using ancova with Bonferroni HSD adjustment for multiple comparisons (colony forming units per sample) with a significance level alpha=0.05. The 0.2% PHMB mouthrinse (A) was significantly better at inhibiting plaque than the placebo (D), but significant less effective than the 0.12% aqueous chlorhexidine solution (B). There is no significant difference between A and the 0.3% triclosan/2.0% copolymer mouthrinse (C). Bacterial count reductions (tooth surface and mucosa) with PHMB (A) were significantly greater compared with the placebo (D) and triclosan (C), but significantly lower compared with chlorhexidine (B) (tooth surface) and equally effective compared with chlorhexidine (B) (mucosa). Consistent with previous studies, a PHMB mouthrinse was shown to inhibit plaque re-growth and to reduce oral bacterial counts, indicating that PHMB could be an alternative to established mouthrinses in preventive applications.


Disentangling the relationship between gender and work-family conflict: An integration of theoretical perspectives using meta-analytic methods.
Implicit in many discussions of work-family issues is the idea that managing the work-family interface is more challenging for women than men. We address whether this intuition is supported by the empirical data via a meta-analysis of gender differences in work-family conflict (WFC) based on more than 350 independent samples (N > 250,000 workers). Challenging lay perceptions, our results demonstrate that men and women generally do not differ on their reports of WFC, though there were some modest moderating effects of dual-earner status, parental status, type of WFC (i.e., time-, strain-, vs. behavior-based), and when limiting samples to men and women who held the same job. To better understand the relationship between gender and WFC, we engaged in theory-testing of mediating mechanisms based on commonly invoked theoretical perspectives. We found evidence in support of the rational view, no support for the sensitization and male segmentation perspectives, and partial support for the asymmetrical domain permeability model. Finally, we build theory by seeking to identify omitted mediators that explain the relationship between gender and work-interference-with-family, given evidence that existing theoretically specified mechanisms are insufficient to explain this relationship. Overall, we find more evidence for similarity rather than difference in the degree of WFC experienced by men and women. (PsycINFO Database Record


Separation of helper T cells from suppressor T cells expressing different Ly components. I. Polyclonal activation: suppressor and helper activities are inherent properties of distinct T-cell subclasses.
Concanavalin A, a nonspecific polyclonal activator of T lymphocytes, activates Lyl and Ly23 subclasses to the same degree. After activation, the Ly23 subclass, but not the Lyl subclass, has the following properties: (a) Suppression of the antibody response to sheep erythrocytes (SRBC) in vitro. (b) Production of a soluble factor that suppresses the anti-SRBC response in vitro. (c) Suppression of the generation of cell-mediated cytotoxicity to H-2 target cells in vitro. Con A-activated cells of the Lyl subclass, but not the Ly23 subclass, express helper function in the anti-SRBC response in vitro. Because the intact Con A-stimulated T-cell population contains both cell types, these cells do not exert detectable helper effects in an anti-SRBC system in vitro, because the helper effect of Lyl cells is masked by the suppressor effect of the Ly23 cells. Each function is revealed by eliminating one or the other population with the relevant Ly antiserum. The resting T-cell population, before activation by Con A, also contains already programmed Lyl and Ly23 cells with similar helper and suppressor potentials, respectively. This is revealed by experiments with Ly subclasses which have been separated from the resting T-cell population and then stimulated by Con A. Thus helper and suppressor functions, as expressed in these systems, are manifestations of separate T-cell-differentiative pathways and do not depend upon stimulation of the cells by antigen.


Readiness for Discharge After Foot and Ankle Surgery Using Peripheral Nerve Blocks: A Randomized Controlled Trial Comparing Spinal and General Anesthesia as Supplements to Nerve Blocks.
Neuraxial anesthesia is often viewed as superior to general anesthesia but may delay discharge. Comparisons do not typically use multimodal analgesics and nerve blockade. Combining nerve blockade with general anesthesia may reduce pain, opioid consumption, and nausea. We hypothesized that general anesthesia (with nerve blocks) would lead to earlier readiness for discharge, compared to spinal anesthesia (with nerve blocks). All patients underwent ambulatory foot and ankle surgery, with a predicted case duration of 1-3 hours. All patients received popliteal and adductor canal nerve blocks using bupivacaine and dexamethasone. No intraoperative opioids were administered. All patients received ondansetron, dexamethasone, ketamine, and ketorolac. Patients, data collectors, and the data analyst were not informed of group assignment. Patients were randomized to spinal or general anesthesia with concealed allocation. Spinal anesthesia was performed with mepivacaine and accompanied with propofol sedation. After general anesthesia was induced with propofol, a laryngeal mask airway was inserted, followed by sevoflurane and propofol. Time until ready for discharge, the primary outcome, was compared between groups after adjusting for age and surgery time using multivariable unconditional quantile regression. Secondary outcomes compared at multiple timepoints were adjusted for multiple comparisons using the Holm-Bonferroni step-down procedure. General anesthesia patients were ready for discharge at a median of 39 minutes earlier (95% confidence interval, 2-75; P = .038) versus spinal anesthesia patients. Patients in both groups met readiness criteria for discharge substantially before actual discharge. Pain scores at rest were higher among general anesthesia patients 1 hour after leaving the operating room (adjusted difference in means, 2.1 [95% confidence interval, 1.0-3.2]; P < .001). Other secondary outcomes (including opioid use, opioid side effects, nausea, headache, sore throat, and back pain) were not different. General anesthesia was associated with earlier readiness for discharge, but the difference may not be clinically significant and did not lead to earlier actual discharge. Most secondary outcomes were not different between groups. The choice of spinal or general anesthesia as an adjunct to peripheral nerve blockade can reflect patient, clinician, and institutional preferences.


Specific heparan sulfate modifications stabilize the synaptic organizer MADD-4/Punctin at Caenorhabditis elegans neuromuscular junctions.
Heparan sulfate (HS) proteoglycans contribute to the structural organization of various neurochemical synapses. Depending on the system, their role involves either the core protein or the glycosaminoglycan chains. These linear sugar chains are extensively modified by HS modification enzymes, resulting in highly diverse molecules. Specific modifications of glycosaminoglycan chains may thus contribute to a sugar code involved in synapse specificity. Caenorhabditis elegans is particularly useful to address this question because of the low level of genomic redundancy of these enzymes, as opposed to mammals. Here, we systematically mutated the genes encoding HS modification enzymes in C. elegans and analyzed their impact on excitatory and inhibitory neuromuscular junctions (NMJs). Using single chain antibodies that recognize different HS modification patterns, we show in vivo that these two HS epitopes are carried by the SDN-1 core protein, the unique C. elegans syndecan ortholog, at NMJs. Intriguingly, these antibodies differentially bind to excitatory and inhibitory synapses, implying unique HS modification patterns at different NMJs. Moreover, while most enzymes are individually dispensable for proper organization of NMJs, we show that 3-O-sulfation of SDN-1 is required to maintain wild-type levels of the extracellular matrix protein MADD-4/Punctin, a central synaptic organizer that defines the identity of excitatory and inhibitory synaptic domains at the plasma membrane of muscle cells.


Ketogenic Diets and their Therapeutic Potential on Breast Cancer: A Systemic Review.
Breast cancer remains a major cause of morbidity and mortality in women, and there is still a lack of complementary approaches to significantly improve the efficacy of standard therapies. For many kinds of cancers, the usual standard care is the combination of surgery, radiation, and chemotherapy. However, this standard therapy is not effective alone. Therefore, new approaches that increase therapeutic effectiveness are urgently needed. The ketogenic diet is a novel therapeutic approach for certain types of cancers, as indicated by several preclinical and clinical evidences. The ketogenic diet, which consists of a high-fat, low-carbohydrate diet with adequate protein, appears to sensitize most cancers to standard therapy by utilizing the reprogrammed metabolism of cancer cells, making it a promising candidate for adjuvant cancer treatment. The majority of preclinical and clinical studies argue that the use of a ketogenic diet in combination with standard therapies is based on its potential to improve the antitumor effects of conventional chemotherapy, its overall good safety and tolerability, and quality of life improvement. According to new evidence, a ketogenic diet lowers the level of glucose and insulin in the blood, which are necessary for tumor growth. Thus, the ketogenic diet has emerged as a potential treatment option for a variety of cancers, including breast cancer. Besides, implementation of a Ketogenic diet in the clinic could improve progression-free and overall survival for patients with breast cancer. This review summarizes the composition and metabolism of ketogenic diets and their potential mechanisms in breast carcinogenesis in addition to their therapeutic potential on breast cancer.


Effect of nitric oxide donors on oxygen-dependent cytotoxic responses mediated by neutrophils.
We analyzed the effect of nitric oxide (NO) on oxygen-dependent cytotoxic responses mediated by neutrophils against unopsonized erythrocytes using three NO donors: S-nitrosoglutathione (GSNO), S-nitroso-N-acetylpenicillamine (SNAP), and sodium nitroprusside (SNP). Neutrophils were treated with these compounds for 1-2 min at 37 degrees C and cytotoxicity was then triggered in the presence of NO donors by precipitating immune complexes, aggregated IgG, the chemotactic peptide FMLP, or opsonized zymosan. GSNO induced, in all cases, a marked increase in cytotoxic responses, while SNAP moderately increased cytotoxicity triggered by immune complexes, aggregated IgG, or Z, opsonized zymosen, without modifying those responses induced by FMLP. By contrast, SNP dramatically suppressed cytotoxicity triggered by all of the stimuli assessed. The enhancing effects mediated by GSNO and SNAP did not depend on the stimulation of guanylyl cyclase and were prevented by the NO scavengers hemoglobin and PTIO (2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl 3-oxide). The inhibitory activity of SNP, on the other hand, was not prevented by NO scavengers, suggesting that it cannot be ascribed to the release of NO. In another set of experiments, neutrophils were pretreated with GSNO or SNAP for different times. Then cells were washed to remove NO donors from the culture medium, and cytotoxicity was triggered by different stimuli. It was found that neutrophils must be pretreated with NO donors for at least 4 h to increase cytotoxic responses, and pretreatment for longer periods (i.e., 8 or 18 h) further increased cytotoxicity. Not only cytotoxic responses, but also the production of O2- and H2O2, and the release of myeloperoxidase were increased under these conditions.


Response of the Injured Tendon to Growth Factors in the Presence or Absence of the Paratenon.
The paratenon is important for Achilles tendon healing. There is much interest in the use of exogenous growth factors (GFs) as potential agents for accelerating the healing of damaged Achilles tendons. The present study used a rat model to study the responses of the injured Achilles tendon to GFs in the presence or absence of the paratenon. The hypothesis was that responses of the injured tendon to GFs would be lower in the absence of a paratenon. Controlled laboratory study. A 4-mm defect was created in the right Achilles tendon of 60 skeletally mature rats, which were treated with a validated combination of GFs (bFGF, BMP-12, and TGF-β1). Animals were randomly assigned to the intact paratenon (IP) group or resected paratenon (RP) group. Healing was studied anatomically, mechanically, and histologically after 1, 2, and 4 weeks. IP tendons showed improved healing compared with RP tendons. IP tendons were significantly stronger (32.2 N and 48.9 N, respectively) than RP tendons (20.1 N and 31.1 N, respectively) after 1 and 2 weeks. IP tendons did not elongate as much as RP tendons and had greater cross-sectional areas (18.0 mm2, 14.4 mm2, and 16.4 mm2, respectively) after 1, 2, and 4 weeks compared with RP tendons (10.5 mm2, 8.4 mm2, and 11.9 mm2, respectively). On histology, earlier collagen deposition and parallel orientation of fibrils were found for IP tendons. The paratenon is essential for efficient Achilles tendon healing. Healing with GFs in this Achilles tendon defect model was superior in the presence of the paratenon. Biological approaches to tendon engineering using GFs are in vogue and have been shown to improve healing of the rat Achilles tendon, most likely by inducing progenitor cells located within the paratenon. Clinically, resection or incision of the paratenon has been proposed for wound closure. Our data demonstrate the fundamental importance of the paratenon, which therefore should be preserved during Achilles tendon repair, especially if augmented with products such as platelet-rich plasma or autologous conditioned serum that are rich in GFs.


Effects of motilin and ursodeoxycholic acid on gastrointestinal myoelectric activity of different origins in fasted rats.
To investigate gastrointestinal migrating myoelectric complex (MMC) and the effects of porcine motilin and ursodeoxycholic acid (UDCA) on MMC of gastrointestinal tract of different origins in fasted rats. Three bipolar silver electrodes were chronically implanted on the antrum, duodenum and jejunum. Seven days later 24 experimental rats were divided into 2 groups. One group was injected with porcine motilin via sublingual vein at a dose of 20 microg/kg, the other group was perfused into stomach with UDCA. The gastrointestinal myoelectric activity was recorded 1 h before and 2 h after the test substance infusions into the rats. In all fasted rats a typical pattern of MMC was observed. Among the totally 68 activity fronts recorded in fasted rats under control, 67% started in duodenum, and 33% in antrum. MMC cycle duration and duration of phase III of antral origin were longer than those of duodenal origin. Administration of 20 microg/kg porcine motilin induced a premature antral phase III of antral origin. But perfusion into stomach with UDCA resulted in shorter MMC cycle duration, longer duration of phase III of duodenal origin, which were followed with shorter cycle duration and duration of antral phase III. In fasted rats, MMC could originate from antrum and duodenum respectively. The characteristics of MMC of different origins may contribute to the large variations within subjects. The mechanisms of different origins of phase III may be different. Porcine motilin and UDCA could affect MMC of different origins of the gastrointestinal tract in fasted state, respectively.


Maximal Sprinting Speed of Elite Soccer Players During Training and Matches.
The aim of the present study was to compare (a) the maximal sprinting speed (MSS) attained by soccer players during matches (MSSmatch) according to their level of play (professional first French division vs. elite amateur fourth French division) and the playing positions and (b) the MSS attained by professional soccer players during 14 different types of small-sided games (SSG, MSSSSG) and match-play. All players monitored through the study performed a 40-m sprint test to assess individual MSS (MSStest) and compare it to the training and match activity, with the calculation of the percentage of MSStest (%MSStest) reached. No differences were found according to the level of play; however, positional wide players achieved a higher MSSmatch, %MSStest, and MSSSSG than central players (both defenders and midfielders) during matches and SSG. MSSmatch were higher than all MSSSSG, and MSSSSG were positively correlated with the area of the pitch (0.45, p < 0.001), its length (0.53, p < 0.001), and the number of players involved (0.38, p < 0.001). The closer SSG was to match situation in terms of rules, the higher the MSSSSG. Wide players reached higher MSS in match and SSG than central players, confirming the relevance of using SSG close to match situation to specifically prepare elite players to the maximal running speed demand of the match.


Process of infection with bacteriophage phiX174. XXXVI. Measurement of virus-specific proteins during a normal cycle of infection.
Double-labeling techniques in which (14)C-labeled, phiX174-infected cells and (3)H-labeled, uninfected cells were used permitted the identification of the virus-specific proteins after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis without prior inhibition of host-cell protein synthesis by ultraviolet irradiation. It was also possible to detect previously undescribed components of high molecular weight which may represent induced host proteins. The gel regions specifically corresponding to cistron II protein and the chloramphenicol-resistant VI protein were identified, and a third new, small peak of unknown origin was detected. Studies of the rate of synthesis of virus-specific proteins at various times after infection indicated that the product of cistron I (lysis) is made only late in infection, but the other proteins seemed to be synthesized at the same relative rates throughout infection (although in different amounts). Studies of the proteins obtained from uniformly labeled phiX virus particles indicated that all of the spikes are identical and allowed a formulation of the structure of the phage capsid.


Optical billiards for atoms.
One of the central paradigms for classical and quantum chaos in conservative systems is the two-dimensional billiard in which particles are confined to a closed region in the plane, undergoing elastic collisions with the walls and free motion in between. We report the first realization of billiards using ultracold atoms bouncing off beams of light. These beams create the desired spatial pattern, forming an "optical billiard." We find excellent agreement between theory and our experimental demonstration of chaotic and stable motion in optical billiards, establishing a new testing ground for classical and quantum chaos.


Upper extremity dyskinesis: a case report.
A case is presented demonstrating upper extremity dyskinesis. Dyskinesia is a kinesiopathology of both hyper and hypomobility. Hyper and hypomobility of the spine are discussed and the theory of this extremity dyskinesia is examined. The necessity for a thorough and complete biomechanical evaluation is emphasized before successful treatment can be initiated.


Melanocytic Nevus on the Rectal Mucosa Removed Using Endoscopic Submucosal Dissection.
Melanocytic nevus is the benign proliferation of melanocytes. The most common location of melanocytic nevus is the skin of the extremities; however, there are few case reports of melanocytic nevus at the rectal mucosa. No prior case of malignant melanoma from melanocytic nevus at the rectal mucosa has been reported; therefore, it is unclear whether resection should be performed or close observation is sufficient. However, the potential malignant transformation of melanocytic nevus should be considered, including melanocytic nevus on the rectum. Melanocytic nevus of the skin can be removed by surgical excision; however, due to rare incidence on the mucosa of the gastrointestinal tract, the optimal treatment for rectal melanocytic nevus remains controversial. Here, we report the first case of melanocytic nevus on the rectal mucosa that was removed by endoscopic submucosal dissection. This case report provides useful information about the optimal management of rectal melanocytic nevus.


Glucose infusion test: a new screening test for vascular access recirculation.
Vascular access recirculation is an important cause of diminished dialysis efficiency. We propose a new screening test based on glucose infusion as a tracer for recirculation. The glucose infusion test (GIT) protocol comprises a basal blood sample (A) from the arterial port, a 5 mL bolus of 20% glucose into the venous chamber (time 0), followed by a second sample (B) in four seconds (from 13 to 17 s with QB 300 mL/min) from the same port. The blood glucose level is determined at the bedside on A and B with a reflectance photometer (CV 1.8%). Interpretation of the test is straightforward: If B = A, there is no recirculation, whereas if B > A, recirculation can be calculated from the regression equation: 0.046 x (B - A) + 0.07, obtained from in vitro tests reproducing artificial recirculation at 0, 5, and 10%. To validate this new method in vivo, we compared GIT and the urea test on 39 hemodialysis patients, obtaining a good correlation (r = 0.93). The two tests were considered positive (recirculation present) when the lower 95% confidence intervals were more than zero. Our patients were divided into two groups: those with (22 out of 39, mean recirculation 11.8%) or without recirculation (17 out of 39, mean 0.06%). The urea test did not recognize 7 out of 22 patients because they had a small recirculation below the urea test limit of detection. GIT was more sensitive (detection limit 0.3%), simpler, and immediate in showing the results than the urea test. It is an accurate and low-cost technique for screening and follow-up of vascular access in a dialysis unit.


User preferences in a carrageenan-based vaginal drug delivery system.
Topical microbicides are a promising solution to address the global threat of HIV and other sexually transmitted infections. To be successful, a microbicide not only needs to be biologically functional but also highly acceptable to users. User acceptability of microbicides can be incorporated early in the product formulation and design process. Previous qualitative research revealed women had strong preferences regarding product shape, while preferences related to size and firmness were less clear. Here, we explored the effect of size and firmness on the acceptability of semisolid ovoid microbicide prototypes intended for vaginal use. Sexually active women (n = 74) were randomized to one of two conditions: with and without applicator. Nine different prototypes were evaluated; they were formulated to low, medium and high firmness using mixtures of kappa and iota carrageenan and potassium chloride. Three sizes were produced at each firmness level. Women manipulated all nine prototypes, rating them for perceived effectiveness, imagined ease-of-insertion and willingness-to-try on visual analog scales. The influence of size and firmness on these three outcome measures were assessed using ANOVA and response surface models. Results indicated size and firmness both influenced the outcome measures, but firmness was more influential than size. Also, the specific effects of size and firmness depended strongly on presence or absence of an applicator. Generally, women in the without applicator condition wanted a larger, firmer product. Collectively, these data suggest efforts to rationally design of microbicides for enhanced user acceptability must consider factors like size and firmness. Also, the decision to include or forego an applicator should be addressed early in the design process, as it strongly influences other design decisions.


Binding of intracellular protein to the erythrocyte membrane during incubation: the production of Heinz bodies.
During sterile incubation of normal human erythrocytes at 37 degrees C., intracellular nonhemoglobin protein is bound to the membrane prior to hemolysis. These studies have characterized this phenomenon further. Protein binding to the membrane began after 12 hours incubation when cellular ATP was depleted and increased to 36 hours incubation. The binding was prevented by adding adenosine or glucose at the start of incubation and was arrested by adding adenosine to regenerate ATP during the course of incubation. However, protein, once bound, was not released by regeneration of ATP. The amount of protein bound was not altered by: (1) addition of Ca++ or EDTA to the medium, (2) blockade of sulfhydryl groups with N-ethylmaleimide, or (3) stabilization of heme-globin bonds by conversion of hemoglobin to cyanmethemoglobin. Conversion of hemoglobin to carboxyhemoglobin by incubations under carbon monoxide inhibited protein binding, but this appeared to be an effect of exclusion of oxygen rather than stabilization of heme-globin bonds since incubation under nitrogen had a similar effect. The morphological counterpart of this chemically-measured membrane-bound protein was visible in red cell ghosts stained with crystal violet as small membrane-associated particles resembling Heinz bodies. Sodium dodecyl sulfate acrylamide gel electrophoresis of membranes of incubated cells revealed a new protein band that was identical to globin monomers. This membrane binding of globin during incubation provides a model for the study of Heinz body formation in clinical disorders.


Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2.
Microsomal cytochrome P450 family 1 enzymes play prominent roles in xenobiotic detoxication and procarcinogen activation. P450 1A2 is the principal cytochrome P450 family 1 enzyme expressed in human liver and participates extensively in drug oxidations. This enzyme is also of great importance in the bioactivation of mutagens, including the N-hydroxylation of arylamines. P450-catalyzed reactions involve a wide range of substrates, and this versatility is reflected in a structural diversity evident in the active sites of available P450 structures. Here, we present the structure of human P450 1A2 in complex with the inhibitor alpha-naphthoflavone, determined to a resolution of 1.95 A. alpha-Naphthoflavone is bound in the active site above the distal surface of the heme prosthetic group. The structure reveals a compact, closed active site cavity that is highly adapted for the positioning and oxidation of relatively large, planar substrates. This unique topology is clearly distinct from known active site architectures of P450 family 2 and 3 enzymes and demonstrates how P450 family 1 enzymes have evolved to catalyze efficiently polycyclic aromatic hydrocarbon oxidation. This report provides the first structure of a microsomal P450 from family 1 and offers a template to study further structure-function relationships of alternative substrates and other cytochrome P450 family 1 members.


A systematic review of general practice-based pharmacists' services to optimize medicines management in older people with multimorbidity and polypharmacy.
Few studies have evaluated roles of general practice-based pharmacists (PBPs), particularly in optimizing medicines management for older people with both multimorbidity and polypharmacy. To explore the types and effectiveness of services provided by PBPs, either alone or in collaboration with other primary health care professionals, that sought to optimize medicines management for older people with multimorbidity and polypharmacy. Eight electronic databases and three trial registries were searched for studies published in English until April 2020. Inclusion criteria were randomized controlled trials, non-randomized controlled trials and controlled before-and-after studies of services delivered by PBPs in primary care/general practice, for patients aged ≥65 years with both multimorbidity and polypharmacy that focused on a number of outcomes. The Cochrane risk of bias tool for randomized trials (RoB 1) and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) assessment tool were used for quality assessment. A narrative synthesis was conducted due to study heterogeneity. Seven studies met inclusion criteria. All included studies employed PBP-led medication review accompanied by recommendations agreed and implemented by general practitioners. Other patient-level and practice-level interventions were described in one study. The limited available evidence suggested that PBPs, in collaboration with other practice team members, had mixed effects on outcomes focused on optimizing medicines management for older people. Most included studies were of poor quality and data to estimate the risk of bias were often missing. Future high-quality studies are needed to test the effects of PBP interventions on a well-defined range of medicines management-related outcomes.


The Specter of Divorce: Views From Working- and Middle-Class Cohabitors.
Young Americans increasingly express apprehension about their ability to successfully manage intimate relationships. Partially in response, cohabitation has become normative over the past few decades. Little research, however, examines social class distinctions in how emerging adults perceive challenges to sustaining intimate unions. We examine cohabitors' views of divorce and how these color their sentiments regarding marriage. Data are from in-depth interviews with 122 working- and middle-class cohabitors. More than two thirds of respondents mentioned concerns with divorce. Working-class women, in particular, view marriage less favorably than do their male and middle-class counterparts, in part because they see marriage as hard to exit and are reluctant to assume restrictive gender roles. Middle-class cohabitors are more likely to have concrete wedding plans and believe that marriage signifies a greater commitment than does cohabitation. These differences in views of marriage and divorce may help explain the bifurcation of cohabitation outcomes among working- and middle-class cohabitors.


Glycosylphosphatidylinositol-anchored proteins in Fusarium graminearum: inventory, variability, and virulence.
The contribution of cell surface proteins to plant pathogenicity of fungi is not well understood. As such, the objective of this study was to investigate the functions and importance of glycosylphosphatidylinositol-anchored proteins (GPI-APs) in the wheat pathogen F. graminearum. GPI-APs are surface proteins that are attached to either the membrane or cell wall. In order to simultaneously disrupt several GPI-APs, a phosphoethanolamine transferase-encoding gene gpi7 was deleted and the resultant mutant characterized in terms of growth, development, and virulence. The Δgpi7 mutants exhibited slower radial growth rates and aberrantly shaped macroconidia. Furthermore, virulence tests and microscopic analyses indicated that Gpi7 is required for ramification of the fungus throughout the rachis of wheat heads. In parallel, bioinformatics tools were utilized to predict and inventory GPI-APs within the proteome of F. graminearum. Two of the genes identified in this screen (FGSG_01588 and FGSG_08844) displayed isolate-specific length variability as observed for other fungal cell wall adhesion genes. Nevertheless, deletion of these genes failed to reveal obvious defects in growth, development, or virulence. This research demonstrates the global importance of GPI-APs to in planta proliferation in F. graminearum, and also highlights the potential of individual GPI-APs as diagnostic markers.


Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study.
WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality. The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all >50 participants) and cardiovascular disease and mortality in 255 communities (all >100 participants), and used individual-level data to adjust for known confounders. 95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p<0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile <4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile >5·08 g/day, mean intake 5·75 g/day, >5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p<0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries. Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate. Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.


Neurosurgical implications of mannitol accumulation within a meningioma and its peritumoral region demonstrated by magnetic resonance spectroscopy: case report.
Mannitol is widely considered the hyperosmolar therapy of choice in routine neurosurgical practice for the reduction of intracranial pressure (ICP). The authors present a unique case of a patient with a large meningioma treated with mannitol, in which mannitol accumulation within the tumor and its surrounding parenchyma was shown using in vivo magnetic resonance spectroscopy (MRS). This rare appearance of mannitol on MRS was characterized by a wide-based peak at 3.8 ppm, which remained detectable several hours after the last dose. These findings provide the first in vivo evidence in support of the prevailing theory that mannitol leakage into the peritumoral edematous region may contribute to rebound increases in ICP and suggest that this phenomenon has the potential to occur in extraaxial tumors. Judicious use of mannitol in the setting of elevated ICP due to tumor may be indicated to avoid potentially deleterious side effects caused by its accumulation.


The oncogene eIF4E: using biochemical insights to target cancer.
The eukaryotic translation initiation factor eIF4E is overexpressed in many human malignancies where it is typically a harbinger of poor prognosis. eIF4E is positioned as a nexus in post-transcriptional gene expression. To carry out these functions, eIF4E needs to bind the m(7)G cap moiety on mRNAs. It plays critical roles in mRNA translation, mRNA export, and most likely in mRNA stability as well. Through these activities, eIF4E coordinately modulates the expression of many transcripts involved in proliferation and survival. eIF4E function is controlled by interactions with protein cofactors in concert with many signaling pathways, including Ras, Mnk, Erk, MAPK, PI3K, mTOR, and Akt. This review describes the eIF4E activity and provides several examples of cellular control mechanisms. Further, we describe some therapeutic strategies in preclinical and clinical development.


In vitro reconstitution of sortase-catalyzed pilus polymerization reveals structural elements involved in pilin cross-linking.
Covalently cross-linked pilus polymers displayed on the cell surface of Gram-positive bacteria are assembled by class C sortase enzymes. These pilus-specific transpeptidases located on the bacterial membrane catalyze a two-step protein ligation reaction, first cleaving the LPXTG motif of one pilin protomer to form an acyl-enzyme intermediate and then joining the terminal Thr to the nucleophilic Lys residue residing within the pilin motif of another pilin protomer. To date, the determinants of class C enzymes that uniquely enable them to construct pili remain unknown. Here, informed by high-resolution crystal structures of corynebacterial pilus-specific sortase (SrtA) and utilizing a structural variant of the enzyme (SrtA2M), whose catalytic pocket has been unmasked by activating mutations, we successfully reconstituted in vitro polymerization of the cognate major pilin (SpaA). Mass spectrometry, electron microscopy, and biochemical experiments authenticated that SrtA2M synthesizes pilus fibers with correct Lys-Thr isopeptide bonds linking individual pilins via a thioacyl intermediate. Structural modeling of the SpaA-SrtA-SpaA polymerization intermediate depicts SrtA2M sandwiched between the N- and C-terminal domains of SpaA harboring the reactive pilin and LPXTG motifs, respectively. Remarkably, the model uncovered a conserved TP(Y/L)XIN(S/T)H signature sequence following the catalytic Cys, in which the alanine substitutions abrogated cross-linking activity but not cleavage of LPXTG. These insights and our evidence that SrtA2M can terminate pilus polymerization by joining the terminal pilin SpaB to SpaA and catalyze ligation of isolated SpaA domains in vitro provide a facile and versatile platform for protein engineering and bio-conjugation that has major implications for biotechnology.


Glyphosate effects on phenolic metabolism of nodulated soybean (Glycine max L. merr.).
Glyphosate is a herbicide that blocks the shikimic acid pathway. Three Bradyrhizobium japonicum strains with different sensitivities to glyphosate were used to test the effect of this herbicide on the phenolic metabolism of nodulated soybeans and on the bacteroid nitrogenase activity. Glyphosate caused an inhibition in the bacteroid nitrogenase activity that was related with the sensitivity of the nodule-forming strains. Both leaves and nodules accumulated huge amounts of shikimate and phenolic acids (mainly protocatechuic acid), indicating that the herbicide was translocated to the nodule and disturbed phenolic metabolism. However, this accumulation was not clearly related to the sensitivity of the different strains. Bacteroids from control plants were incubated with the same concentration of shikimate, and phenolic acid accumulated in glyphosate-treated plants. Despite the high levels found in nodules, they were not responsible for the decrease of the nitrogenase activity. Glyphosate by itself caused a small inhibition of the bacteroid nitrogenase activity.


Glass behaviour: Poisson's ratio and liquid's fragility.
The lack of a reliable theory of glass physics has led to the pursuit of correlations between various glass or viscous liquid parameters, one of which is the slope m of the plot of log(viscosity) against Tg/T, extrapolated at the glass-transition temperature, Tg, also termed 'fragility'. Novikov and Sokolov conclude that the value of m for a liquid varies linearly with the ratio of the instantaneous bulk and shear moduli, K infinity/G infinity, of its glass according to the relation m=29(K infinity/G infinity -0.41). Because of the obvious importance of the elastic properties of a glass, we have investigated the basis for this relation and find that its premise is flawed because of the unjustifiable preference for an empirical variation of m with elastic properties, and because of the selected use of glasses. When more glasses are considered in the same way, m does not seem to be linearly related to K infinity/G infinity.


Antifungal prophylaxis with itraconazole oral solution in neutropenic patients.
The role of itraconazole in anti-fungal prophylaxis has been limited by the low bioavailability of the capsule formulation but the bioavailability of the oral solution is much improved. Three multi-centre studies using itraconazole solution (5 mg/kg/day) have recently been completed. The UK trial compared itraconazole solution with fluconazole suspension (100 mg/day). No invasive aspergillosis occurred in the itraconazole arm and there were more fungal deaths due to proven/suspected infection in the fluconazole group than in the itraconazole group (0 versus 7, p = 0.024). An Italian study compared itraconazole solution with placebo. Proven, suspected and superficial fungal infections were fewer in the itraconazole arm compared with placebo, with significant differences in proven and suspected systemic fungal infections (itraconazole 24% versus placebo 33 %, p = 0.035). The third study compared itraconazole with amphotericin B capsules (2 g/day). There were more invasive fungal infections, Aspergillus infections and fungal deaths in the amphotericin B arm than with itraconazole but none of these differences were statistically significant. Azole prophylaxis in neutropenic patients may reduce the incidence of Candida infections, empirical amphotericin B usage, and the incidence of proven fungal infections. Itraconazole may be more effective than fluconazole in preventing invasive aspergillosis. All of these effects are more pronounced in high risk patients.


[Blood pressure responses in children of normotensive and of hypertensive parents treated with pressor stimulus].
To compare cardiovascular reactivity in adolescents with and without family history of hypertension. Thirty two subjects, males, students, aging between 13 to 18 years old were examined. One half of them had no family history of hypertension and the other half had at least one hypertensive parent. Basal blood pressure level was obtained before the application of the following selected tests: isometric handgrip exercise test, cold pressor test and arithmetic mental stress test. The blood pressure values were obtained by a digital, oscilometric device, previously calibrated. The subjects with family history of hypertension exhibited higher basal levels of both systolic and diastolic blood pressure (p < 0.10). Concerning the tests applied, the subjects with family history of hypertension also exhibited higher responses, but only the responses of the diastolic blood pressure to the mental stress test was statistically significant (p < 0.10). Our findings point to the need of a special follow-up of children with a family history of hypertension.


Reactions of [PhI(pyridine)2]2+ with model Pd and Pt II/IV redox couples.
The results of the reactions of the dicationic iodine(III) family of oxidants [PhI(pyridine)2](2+) with model Pd(II) and Pt(II) complexes are described. Depending on the specific reaction pairs, a variety of outcomes are observed. For palladium, Pd(IV) complexes cannot be observed but are implicated in C-C and C-N bond formation for Pd(II) starting materials based on phenylpyridine and 2,2-bipyridine, respectively. Theoretical comparisons with similar processes for -Cl and -OAc rather than pyridine indicate that these provide greater thermodynamic stability, and our results here show that they also give greater kinetic stability (the failure of MP2 methods for these systems is quite dramatic). In contrast, oxidation and delivery of the pyridine ligands gives dicationic Pt(IV) complexes that may be isolated and structurally characterized.


Realizing the promise of cancer predisposition genes.
Genes in which germline mutations confer highly or moderately increased risks of cancer are called cancer predisposition genes. More than 100 of these genes have been identified, providing important scientific insights in many areas, particularly the mechanisms of cancer causation. Moreover, clinical utilization of cancer predisposition genes has had a substantial impact on diagnosis, optimized management and prevention of cancer. The recent transformative advances in DNA sequencing hold the promise of many more cancer predisposition gene discoveries, and greater and broader clinical applications. However, there is also considerable potential for incorrect inferences and inappropriate clinical applications. Realizing the promise of cancer predisposition genes for science and medicine will thus require careful navigation.


Overcoming families' fears and concerns in the donation discussion.
Research into the fears and concerns families have about donation and other issues at the time of the donation discussion substantiates that many fears and concerns act as impediments to consent. Twenty fears and concerns voiced by families at the time of the donation discussion have been identified. Specific strategies have been developed to deal with 19 of those concerns. Using gentle probing questions and targeted strategies, trained requestors may successfully address many fears and concerns, thus increasing the likelihood of the family consenting to donation.


Postsecretory hydrolysis of nectar sucrose and specialization in ant/plant mutualism.
Obligate Acacia ant plants house mutualistic ants as a defense mechanism and provide them with extrafloral nectar (EFN). Ant/plant mutualisms are widespread, but little is known about the biochemical basis of their species specificity. Despite its importance in these and other plant/animal interactions, little attention has been paid to the control of the chemical composition of nectar. We found high invertase (sucrose-cleaving) activity in Acacia EFN, which thus contained no sucrose. Sucrose, a disaccharide common in other EFNs, usually attracts nonsymbiotic ants. The EFN of the ant acacias was therefore unattractive to such ants. The Pseudomyrmex ants that are specialized to live on Acacia had almost no invertase activity in their digestive tracts and preferred sucrose-free EFN. Our results demonstrate postsecretory regulation of the carbohydrate composition of nectar.


Validation of the Dutch version of the Hip disability and Osteoarthritis Outcome Score.
The Hip disability and Osteoarthritis Outcome Score (HOOS) was constructed in Sweden; this questionnaire has proved to be valid for persons with hip disability with or without hip osteoarthritis (OA) and with high demands of physical function. The objective of this study was to evaluate the internal consistency, reliability, construct validity, and floor and ceiling effects of the Dutch version of the HOOS questionnaire. After translation with a forward/backward protocol, 74 hip arthroplasty patients and 88 hip OA patients filled in the Dutch HOOS, as well as a Short Form-36 (SF-36), an Oxford Hip Score (OHS) and a VAS-pain questionnaire. The Dutch version of the HOOS questionnaire achieved excellent scores in all of the clinimetric properties. The Dutch HOOS questionnaire has a good internal consistency and reliability. Moreover, the construct validity is good and no floor and ceiling effects were found. The HOOS is a good instrument for patients with different stadia of hip OA.


TNF pretreatment interferes with mitochondrial apoptosis in the mouse liver by A20-mediated down-regulation of Bax.
Pretreatment with low doses of the proinflammatory cytokine TNF has been shown to prevent hepatocellular apoptosis and liver damage in inflammatory as well as in ischemia/reperfusion-induced liver injury. The underlying mechanisms of protection have not been elucidated so far. In this study, these mechanisms were investigated in murine hepatocyte cultures as well as in a mouse model of TNF-dependent apoptotic liver damage (galactosamine/TNF model). Our results show that pretreatment with TNF, or application of small-interfering RNA directed against the proapoptotic Bcl2 family member Bax, interfered with the onset of mitochondrial apoptosis in vivo. Knockdown of TNF-alpha-induced-protein 3 (A20) restored mitochondrial apoptosis, Bax expression, and liver damage. The underlying mechanism of protection seems to involve a cascade of events, where TNF induces the expression of A20 in hepatocytes, A20 down-modulates Bax expression by interference with transcriptional activation, and the reduced availability of Bax interferes with the onset of mitochondrial apoptosis and the ensuing apoptotic liver damage. In conclusion, we identified Bax and A20 as key players in TNF-induced protection from apoptotic liver damage. Because treatment with TNF itself might be a risk factor for patients, we propose that overexpression of A20 might represent an alternative approach for protection from inflammation related apoptotic liver damage, as well as for TNF preconditioning during transplantation.


In vitro replication of Nosema algerae (Microsporidia), a parasite of anopheline mosquitoes, in human cells above 36 degrees C.
Microsporidia form a large and ubiquitous group of obligately intracellular parasitic eukaryotes, increasingly recognized as pathogens in humans. Transmission of invertebrate microsporidia to mammals has been considered impossible because temperature seemed to be a limiting factor for development. Nosema algerae, a microsporidian of anopheline mosquitoes, was cultured in human muscle fibroblasts at temperatures of 31 degrees C and 38 degrees C. This is the first record of an invertebrate microsporidian developing in human cells at a temperature above 36 degrees C. The ultrastructure of N. algerae growing in human muscle fibroblasts is similar to that of Brachiola vesicularum, a microsporidian species previously described in the muscle of an AIDS patient.


Antimicrobial compounds from Pimpinella species growing in Turkey.
A new, 4-(2-propenyl)-phenyl angelate ( 1) and four known phenylpropanoids ( 2 - 5), were isolated from Pimpinella isaurica, a species endemic in Turkey. One new sesquiterpene, 1-methyl-4-(5-methyl-1-methylenehex-4-enyl)-7-oxabicyclo[4.1.0]heptane ( 6) was obtained from P. aurea and two known phenylpropanoids were isolated ( 7, 8), from P. corymbosa. The structure elucidation of the new compounds 1 and 6 was achieved by a combination of one- ( (1)H, and (13)C) and two-dimensional NMR techniques (G-DQF-COSY, G-HMQC, and G-HMBC) and LC-ESI-FTMS. Compounds 1, 2, 4, 6, 7, 8 have been evaluated for their antimalarial and antimicrobial activities. Compound 1, 2, 4, 6, 8 had antimicrobial activity against Mycobacterium intracellulare with IC (50) values of 7.0, 15.0, 2.5, 10.0 and 1.5 microg/mL, respectively.


The influence on cell cycle and cell division by various cadmium-containing quantum dots.
Quantum dots (QDs) have attracted great attention because of their favorable optical properties and have been widely applied in biomedical fields. However, in recent years, there have been an increasing number of reports about the cytotoxicity of QDs, especially cadmium-containing QDs, which may release cadmium ions to induce cytotoxicity. Importantly, the chemical composition and surface modifications of cadmium-based QDs determine the amount of Cd(2+) released inside the cell. Thus, there is an urgent need for more systematic work to study the relationship between cytotoxicity and the surface properties of QDs. In this article, the cytotoxicity of seven cadmium-containing QDs with different constituent elements and surface chemistries are compared. The results show that the cytotoxicity of QDs is closely related to their constituent elements and surface properties: First, CdTe@ZnS core-shell QDs show much lower cytotoxicity than naked ones when they have similar surface modifications; second, the positively charged QDs are more toxic than the negatively charged ones. Moreover, both positively and negatively charged QDs without ZnS coatings lead to multipolar spindles, misaligned chromosomes, and G2/M checkpoint failures. Interestingly, although CdSe QDs with a PEG coating cause no apparent cytotoxicity in any of the cell lines studied, they can localize near the contractile ring during cytokinesis and then block contractile ring disassembly. The cellular effect of CdTe QDs comes not only from the release of cadmium ions but also the intracellular distribution of QD nanoparticles in cells and the associated nanoscale effects. It is also found that QD-caused cytokinesis failure is closely related to the decreased expression of Cyclin A and Cyclin B. Taken together, the above findings provide new insight into the dynamic fate of QDs during cell mitosis, and are important for understanding the intracellular effects of QDs on the mitotic spindle and chromosomes during cell division. Furthermore, this kind of cytotoxicity evaluation method should be applicable to studies of the biological effects and health impacts of other nanomaterials.


Radial intercalation is regulated by the Par complex and the microtubule-stabilizing protein CLAMP/Spef1.
The directed movement of cells is critical for numerous developmental and disease processes. A developmentally reiterated form of migration is radial intercalation; the process by which cells move in a direction orthogonal to the plane of the tissue from an inner layer to an outer layer. We use the radial intercalation of cells into the skin of Xenopus laevis embryos as a model to study directed cell migration within an epithelial tissue. We identify a novel function for both the microtubule-binding protein CLAMP and members of the microtubule-regulating Par complex during intercalation. Specifically, we show that Par3 and aPKC promote the apical positioning of centrioles, whereas CLAMP stabilizes microtubules along the axis of migration. We propose a model in which the Par complex defines the orientation of apical migration during intercalation and in which subcellular localization of CLAMP promotes the establishment of an axis of microtubule stability required for the active migration of cells into the outer epithelium.


Contactless Monitoring of Respiratory Rate and Breathing Absence from Head Movements Using an RGB Camera.
Contactless vital sign monitoring is more demanding for long-term, continuous, and unobtrusive measurements. Camera-based respiratory monitoring is receiving growing interest with advanced video technologies and computational power. The volume variations of the lungs for airflow changes create a periodic movement of the torso, but identifying the torso is more challenging than face detection in a video. In this paper, we present a unique approach to monitoring respiratory rate (RR) and breathing absence by leveraging head movements alone from an RGB video because respiratory motion also influences the head. Besides our novel RR estimation, an independent algorithm for breathing absence detection using signal feature extraction and machine learning techniques identifies an apnea event and improves overall RR estimation accuracy. The proposed approach was evaluated using videos from 30 healthy subjects who performed various breathing tasks. The breathing absence detector had 0.87 F1 score, 0.9 sensitivity, and 0.85 specificity. The accuracy of spontaneous breathing rate estimation increased from 2.46 to 1.91 bpm MAE and 3.54 to 2.7 bpm RMSE when combining the breathing absence result with the estimated RR.Clinical relevance- Our contactless respiratory monitoring can utilize a consumer RGB camera to offer a significant benefit in continuous monitoring of neonatal monitoring, sleep monitoring, telemedicine or telehealth, home fitness with mild physical movement, and emotion detection in the clinic and remote locations.


A monoclonal antibody directed against a serotype-specific, outer-membrane protein of Haemophilus influenzae type b.
Monoclonal antibodies (Mabs) were produced against outer-membrane proteins (OMPs) of Haemophilus influenzae type b. The clones were screened by ELISA with outer-membrane preparations of H. influenzae type b and untypable strains as coating antigens. Antibodies directed against the proteins of mol. wt (10(3)) 43, 37 and 13 were identified by immunoblotting of SDS-PAGE patterns of OMPs. Proteolytic enzyme treatments of the OMPs resulted in reduction of Mab reactivity as measured by ELISA. Furthermore, the absence of reactivity of Mab Hb-2 with a preparation of lipopolysaccharide confirmed the protein nature of its corresponding epitope. Binding assays with live bacteria showed that Hb-2 reacted with a cell surface-exposed antigenic determinant. Mab Hb-2 was bactericidal in vitro in the presence of complement. The characterisation of Hb-2 (IgG2a) by Western immunoblotting analysis revealed that it was directed against the 37 X 10(3)-mol. wt OMP. In a dot-enzyme immunoassay, Hb-2 reacted specifically with 326 strains of H. influenzae type b. It did not cross-react with the other serotypes or untypable strains of H. influenzae or with other bacterial species. This is the first report of a monoclonal antibody identifying a serotype-specific surface-exposed OMP of H. influenzae type b.


Apparent digestibility of protein and amino acids in broiler chickens fed a corn-soybean diet supplemented with microbial phytase.
The effect of microbial phytase supplementation on CP and amino acid (AA) digestibility was investigated in a 28-d trial using 360 sexed, day-old broiler chickens fed corn-soybean meal diets. The experimental design was a completely randomized one with a 3 x 2 factorial arrangement of treatments. The variables included P and Ca levels and phytase: P and Ca levels were: normal P-normal Ca [0.45% available P (Pa), 1.0% Ca], low P-normal Ca (0.35% Pa, 1.0% Ca), and low P-low Ca (0.35 Pa and 0.6% Ca); and phytase at 0 and 600 U/kg diet. Phytase supplementation increased body weight gain (P < 0.014) and feed intake (P < 0.004) at 19 d in male chickens; in females, phytase increased (P < 0.012) only body weight gain at 19 d. The low P-normal Ca diet reduced (P < 0.05) feed intake and body weight gain in both sexes at 7, 14, and 19 d, compared to the normal P-normal Ca diet; the reduction of Ca in the low P diet prevented the above depression, resulting in body weight gain and feed intake to a level comparable to that of the normal P-normal Ca diet. Microbial phytase supplementation had no effect (P < 0.065) on the apparent ileal digestibility (AID) of CP or any AA except Met and Phe in male broiler chickens. In females, adding phytase increased the AID of all AA except Lys, Met, Phe, and Pro. The low P-normal Ca diet reduced (P < 0.05) the AID of Phe, Asp, and Ser in male chickens and reduced the AID of all the AA except Met and Pro in females compared to the normal P-normal Ca diet. The reduction of Ca in the low P diet prevented the depression of the AID of the AA caused by the low P-normal Ca diet, resulting in AID of AA having a level comparable to that of the normal P-normal Ca diet in both sexes. Phytase supplementation did not have any effect (P > 0.05) on apparent "fecal" digestibility (AFD) of CP or any of the AA in male chickens; however, in female chickens it increased the AFD of Thr, Asp, Glu, and Ser. In summary, phytase supplementation increased growth performance in both sexes; increased AID and AFD of most of the AA, particularly in female chickens. The optimum growth performance and AA digestibilities were obtained with the lowest input of resources, in the low P-low Ca diet supplemented with microbial phytase.


Application of coloring theory to reduce intensity modulated radiotherapy dose calculations.
Coloring theory is applied to reduce the dose calculations under intensity modulated radiotherapy. Intensity modulated radiotherapy varies the intensity profile across the beam. The beam face is divided into a panel of small squares or "bixels." Each square may be opened or closed for different lengths of time by moving collimator leaves in and out of the beam. It has been shown that the distribution of dose from radiation directed through any open square depends on whether the adjacent squares are opened or closed. Taking the states of neighboring bixels into account greatly increases the required dose calculations. There are 2(8) possible ways to select open or closed states for the eight neighbors of a given bixel. Each combination represents one coloring of a 3 x 3 panel, and each coloring demands a separate dose calculation. The number of calculations is reduced by considering the symmetries of a square. The 256 possible colorings can be divided into 51 distinct patterns through application of Burnside's theorem. Each pattern consists of selections of closed bixels that are the same except for a symmetric transformation of coordinates. If the symmetry between x and y coordinates is broken by collimator leaves whose ends and sides have different effects on bordering bixels, the number of patterns increases to 84. The theoretic gain in the number of calculations through the application of Burnside's theorem is fivefold if bixel borders are symmetric, and threefold if the borders are asymmetric. The results are applied to examples of generated intensity maps. The symmetry rules divide the bixel arrangements into proportionately fewer patterns as the intensity maps become larger, allowing computational gains to be achieved.


First Report of Fusarium Wilt of Industrial Hemp (Cannabis sativa L.) Caused by Fusarium oxysporum in the Northeast China.
Industrial hemp (Cannabis sativa L.) is an ancient and economically important crop used in food, medicine, textile, and paper industries (Chandra et al. 2017). In July 2021, an estimated 30% of the industrial hemp plants showed wilted leaves and root rot in the greenhouse at the Modern Agriculture Demonstration Area Management Center, Harbin City, Heilongjiang Province, China. Initially, the diseased plants exhibited green and reversible wilting of lower canopy leaves. Upon progression the plants showed irreversible wilting. The epidermal tissue of root and rhizome showed slight cracks and the vascular bundle exhibited light brown discoloration, and then died. Six randomly selected disease plants were collected. Small fragments (5 mm) were cut from the infected roots, surface-sterilized with 70% ethanol for 30s and 1% sodium hypochlorite for 5 min and rinsed three times in sterile H2O. Then the small pieces were embedded on potato dextrose agar at 25℃ for 4 days and sub-cultured by hyphal tipping to isolate the fungus. A single-spore culture was obtained by monosporic isolation. The colonies were characterized by an abundant white cottony mycelium, which became gray or purple with age. The macroconidia were transparent, short to medium in length, straight to slightly curved, septate 0 to 4, 16.8 to 26.6 µm long × 3.5 to 4.1 µm wide. The apical cells were long and tapering to a point and the basal cells were notched. Microconidia were elliptic or kidney-shaped, and septate 0 to 4. The conidia were 4.2 to 11.3 µm long × 3.5 to 5.5 µm wide (n = 50). The morphological characteristics were very similar to those of Fusarium oxysporum (Leslie and Summerell 2006). For molecular identification, the internal transcribed spacer (ITS), translation elongation factor 1-α (TEF1) and RNA polymerase II beta subunit (RPB2) genes were amplified and sequenced with the primers ITS1/ITS4, EF-1/EF-2 (Uwaremwe et al. 2020), and 5f2/7c (O'Donnell et al. 2010). The 520 bp (ITS), 948 bp (TEF1), and 861 bp (RPB2) sequences were deposited in GenBank with acce. nos. MZ722998, OK180473 and OK180474, respectively. NCBI BLAST analysis showed 98 to 100% similarity with the sequences of F. oxysporum. Moreover, the sequences alignment similarity for the six isolates were 100%. Based on the morphological and molecular characteristics, the isolates were identified as F. oxysporum. For the pathogenicity test, 20 seedlings were inoculated 30 ml of a conidial suspension (106 conidia/ml) using the root dip method. Another set of 20 seedlings were inoculated with the same quantity of sterile distilled water as the controls. After inoculation, all seedlings were maintained in a greenhouse at 25°C ± 2, with a relative humidity of 60 to 70% and a 16 h light/8 h dark cycle. This test was repeated twice. The leaves of the inoculated seedlings gradually became yellow and exhibited wilting within 15 to 20 days, the epidermal tissue of root showed light brown discoloration. Eventually the plants were dead within 40 to 50 days after inoculation. The control seedlings did not show any wilt symptoms. F. oxysporum was re-isolated from the infected root tissues to fulfill the Koch's postulates. In addition to F. oxysporum, F. brachygibbosum, Pythium aphanidermatum, F. solani, and F. equiseti have also been reported to cause wilt symptoms of industrial hemp (Zamir et al. 2018). To our knowledge, this is the first report of Fusarium wilt on C. sativa caused by F. oxysporum in the Northeast China.


Role of the Paraspinal Muscles in the Sagittal Imbalance Cascade: The Effects of Their Endurance and of Their Morphology on Sagittal Spinopelvic Alignment.
The role of paraspinal muscle degeneration in the cascade of sagittal imbalance is still unclear. This study aimed to compare paraspinal muscle degeneration in the 4 stages of sagittal imbalance: sagittal balance (SB), compensated sagittal balance (CSB), decompensated sagittal imbalance (DSI), and sagittal imbalance with failure of pelvic compensation (SI-FPC). In addition, it aimed to compare the effects paraspinal muscle endurance and morphology on sagittal spinopelvic alignment in patients with lumbar spinal stenosis. A cross-sectional study of 219 patients hospitalized with lumbar spinal stenosis was performed. The isometric paraspinal extensor endurance test and evaluation of atrophy and fat infiltration of the paraspinal extensor muscles and psoas major on magnetic resonance imaging were performed at baseline. Spinopelvic parameters including lumbar lordosis, pelvic tilt, sacral slope, pelvic incidence, and the sagittal vertical axis were measured. The patients with lumbar spinal stenosis were divided into 67 with SB, 85 with CSB, 49 with DSI, and 17 with SI-FPC. There were significant differences in paraspinal muscle endurance and morphology among the 4 groups. Furthermore, the SI-FPC group had poorer paraspinal muscle endurance than either the SB or the CSB group. In multiple linear regression analysis, paraspinal muscle endurance and the relative functional cross-sectional area of the paraspinal extensor muscles were the independent predictors of the sagittal vertical axis, and the relative functional cross-sectional area of the psoas major was the independent predictor of relative pelvic version. This study indicated that paraspinal muscle degeneration is not only an initiating factor in pelvic retroversion but also a risk factor for progression from a compensated to a decompensated stage. Specifically, the impairment of muscle endurance in the CSB stage may be the reason why patients experience failure of pelvic compensation. In addition, paraspinal muscle endurance and muscle morphology (relative functional cross-sectional area of the paraspinal extensor muscles and psoas major) had different clinical consequences. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.


Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial.
The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported. In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial. Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer. Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.


Does training method matter? Evidence for the negative impact of aversive-based methods on companion dog welfare.
Dog training methods range broadly from those using mostly positive punishment and negative reinforcement (aversive-based) to those using primarily positive reinforcement (reward-based). Although aversive-based training has been strongly criticized for negatively affecting dog welfare, there is no comprehensive research focusing on companion dogs and mainstream techniques, and most studies rely on owner-reported assessment of training methods and dog behavior. The aim of the present study was to evaluate the effects of aversive- and reward-based training methods on companion dog welfare within and outside the training context. Ninety-two companion dogs were recruited from three reward-based schools (Group Reward, n = 42), and from four aversive-based schools, two using low proportions of aversive-based methods (Group Mixed, n = 22) and two using high proportions of aversive-based methods (Group Aversive, n = 28). For evaluating welfare during training, dogs were video recorded for three sessions and six saliva samples were collected, three at home (baseline levels) and three after training (post-training levels). Video recordings were used to examine the frequency of stress-related behaviors (e.g., lip lick, yawn) and the overall behavioral state of the dog (e.g., tense, relaxed), and saliva samples were analyzed for cortisol concentration. For evaluating welfare outside the training context, dogs participated in a cognitive bias task. Results showed that dogs from Group Aversive displayed more stress-related behaviors, were more frequently in tense and low behavioral states and panted more during training, and exhibited higher post-training increases in cortisol levels than dogs from Group Reward. Additionally, dogs from Group Aversive were more 'pessimistic' in the cognitive bias task than dogs from Group Reward. Dogs from Group Mixed displayed more stress-related behaviors, were more frequently in tense states and panted more during training than dogs from Group Reward. Finally, although Groups Mixed and Aversive did not differ in their performance in the cognitive bias task nor in cortisol levels, the former displayed more stress-related behaviors and was more frequently in tense and low behavioral states. These findings indicate that aversive-based training methods, especially if used in high proportions, compromise the welfare of companion dogs both within and outside the training context.


Measurement of macular structure-function relationships using spectral domain-optical coherence tomography (SD-OCT) and pattern electroretinograms (PERG).
Retinal ganglion cell (RGC) death is a common cause of loss of vision during glaucoma. Pattern electroretinogram (PERG) is an objective measure of the central retinal function that correlates with macular GCL thickness. The aim of this study is to determine possible relationships between the N95 amplitude of pattern electroretinogram (PERGamp) and macular ganglion cell/inner plexiform layer thickness (GCIPLT). This was a retrospective and comparative study including 74 glaucoma patients (44 early stage and 30 advanced stage cases) and 66 normal control subjects. Macular GCIPLT was measured using Cirrus spectral domain-optical coherence tomography. Standard automated perimetry and pattern ERGs were used in all patient examinations. Three types of regression analysis (broken stick, linear regression, and quadratic regression) were used to evaluate possible relationships between PERGamp and GCIPLT. Correlations between visual field parameters and GCIPLT were evaluated according to glaucoma severity. The best fit model for the relationship between PERGamp and GCIPLT was the linear regression model (r2 = 0.22; P < 0.001). The best-fit model for the relationship between visual field parameters and GCIPLT was the broken stick model. During early glaucoma, macular GCIPLT was positively correlated with PERGamp, but not with visual field loss. In advanced glaucoma, macular GCIPLT was positively correlated with both PERGamp and visual field loss. PERGamp was significantly correlated with macular GCIPT in early glaucoma patients, while visual field performance showed no correlation with GCIPLT. PERGamp can therefore assist clinicians in making an early decision regarding the most suitable treatment plan, especially when GCIPLT is thinning with no change in visual field performance.


The mouse pale ear pigment mutant as a possible animal model for human platelet storage pool deficiency.
The mouse pigment mutant pale ear, ep/ep, which has a defect in kidney lysosomal enzyme secretion, had prolonged bleeding on experimental injury. Platelet counts and platelet protein did not differ from normal. There was, however, a deficiency in the platelet dense granule contents, serotonin, ATP, and ADP. Furthermore, a marked reduction of platelet dense granules was observed by electron microscopy. The results suggest that pale ear is a useful animal model in the study of platelet storage pool disease. Studies on this mutant and other pigment mutants have established that one gene can regulate at least three subcellular organelles, including the melanosome, the lysosome, and the platelet dense granule.


Leucine partially protects muscle mass and function during bed rest in middle-aged adults.
Physical inactivity triggers a rapid loss of muscle mass and function in older adults. Middle-aged adults show few phenotypic signs of aging yet may be more susceptible to inactivity than younger adults. The aim was to determine whether leucine, a stimulator of translation initiation and skeletal muscle protein synthesis (MPS), can protect skeletal muscle health during bed rest. We used a randomized, double-blind, placebo-controlled trial to assess changes in skeletal MPS, cellular signaling, body composition, and skeletal muscle function in middle-aged adults (n = 19; age ± SEM: 52 ± 1 y) in response to leucine supplementation (LEU group: 0.06 g ∙ kg(-1) ∙ meal(-1)) or an alanine control (CON group) during 14 d of bed rest. Bed rest decreased postabsorptive MPS by 30% ± 9% (CON group) and by 10% ± 10% (LEU group) (main effect for time, P < 0.05), but no differences between groups with respect to pre-post changes (group × time interactions) were detected for MPS or cell signaling. Leucine protected knee extensor peak torque (CON compared with LEU group: -15% ± 2% and -7% ± 3%; group × time interaction, P < 0.05) and endurance (CON compared with LEU: -14% ± 3% and -2% ± 4%; group × time interaction, P < 0.05), prevented an increase in body fat percentage (group × time interaction, P < 0.05), and reduced whole-body lean mass loss after 7 d (CON compared with LEU: -1.5 ± 0.3 and -0.8 ± 0.3 kg; group × time interaction, P < 0.05) but not 14 d (CON compared with LEU: -1.5 ± 0.3 and -1.0 ± 0.3 kg) of bed rest. Leucine also maintained muscle quality (peak torque/kg leg lean mass) after 14 d of bed-rest inactivity (CON compared with LEU: -9% ± 2% and +1% ± 3%; group × time interaction, P < 0.05). Bed rest has a profoundly negative effect on muscle metabolism, mass, and function in middle-aged adults. Leucine supplementation may partially protect muscle health during relatively brief periods of physical inactivity. This trial was registered at clinicaltrials.gov as NCT00968344.


Condensin in Chromatid Cohesion and Segregation.
After replication of genomic DNA during the S phase, 2 chromatids hold together longitudinally. When cells enter mitosis, the paired sister chromatids start to condense and then segregate into individual chromatids except for the centromeric region. Upon attachment of microtubules to the kinetochore, subsequent pulling of the 2 sister chromatids by the spindles towards opposite poles results in 2 completely separated chromatids. Besides more than 100 kinds of kinetochore proteins, several key proteins such as cohesin, separase, shugoshin, and condensin contribute to chromatid cohesion and segregation. Among these proteins, condensin, a protein complex composed of 5 subunits discovered 2 decades ago, has been extensively studied in terms of the maintenance of chromosome morphology as its major function. Recent studies on condensin uncovered its role in chromatid cohesion and segregation, which will be reviewed in this article.


Shuttlecock-Shaped Molecular Rectifier: Asymmetric Electron Transport Coupled with Controlled Molecular Motion.
A fullerene derivative with five hydroxyphenyl groups attached around a pentagon, (4-HOC6H4)5HC60 (1), has shown an asymmetric current-voltage (I-V) curve in a conducting atomic force microscopy experiment on gold. Such molecular rectification has been ascribed to the asymmetric distribution of frontier molecular orbitals over its shuttlecock-shaped structure. Our nonequilibrium Green's function (NEGF) calculations based on density functional theory (DFT) indeed exhibit an asymmetric I-V curve for 1 standing up between two Au(111) electrodes, but the resulting rectification ratio (RR ∼ 3) is insufficient to explain the wide range of RR observed in experiments performed under a high bias voltage. Therefore, we formulate a hypothesis that high RR (>10) may come from molecular orientation switching induced by a strong electric field applied between two electrodes. Indeed, molecular dynamics simulations of a self-assembled monolayer of 1 on Au(111) show that the orientation of 1 can be switched between standing-up and lying-on-the-side configurations in a manner to align its molecular dipole moment with the direction of the applied electric field. The DFT-NEGF calculations taking into account such field-induced reorientation between up and side configurations indeed yield RR of ∼13, which agrees well with the experimental value obtained under a high bias voltage.


Sarcoidosis and pregnancy: obstetrical and neonatal outcomes in a population-based cohort of 7 million births.
Data on sarcoidosis in pregnancy is sparse and limited to a few case reports and series. Our aim is to determine the prevalence of sarcoidosis at delivery, and related maternal and newborn outcomes. Using the United States Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) from 2003 to 2010, we conducted a population-based retrospective cohort study to compare women with and without sarcoidosis at delivery. We calculated the prevalence of sarcoidosis in pregnancy and used logistic regression analyses to estimate the associated risks of maternal and neonatal outcomes. There were 678 cases of sarcoidosis in 7,094,400 births over an 8-year period for an overall prevalence of nine and six-tenths cases per 100,000 births. Compared with controls, women with sarcoidosis were older, more likely to be African American and to report being smokers. Women with sarcoidosis were more likely to have preeclampsia odds ratio (OR) 1.62 (95% CI 1.18-2.22), eclampsia OR 5.27 (95% CI 1.69-16.40), deep vein thrombosis OR 4.92 (95% CI 1.58-15.33), pulmonary embolism OR 6.68 (95% CI 3.99-11.21), and premature delivery OR 1.73 (95% CI 1.40-2.15). There was also an increased risk of cesarean deliveries and postpartum hemorrhages. There were no cases of maternal death reported. Sarcoidosis in pregnancy is a rare disease associated with an increased risk of adverse obstetrical outcomes. Women with sarcoidosis can carry out successful pregnancies, however should be made aware of the higher risk of adverse events. Given the higher risk of venous thromboembolic events, consideration should be given to thromboprophylaxis in pregnancy.


Social influence on selection behaviour: Distinguishing local- and global-driven preferential attachment.
Social influence drives human selection behaviours when numerous objects competing for limited attentions, which leads to the 'rich get richer' dynamics where popular objects tend to get more attentions. However, evidences have been found that, both the global information of the whole system and the local information among one's friends have significant influence over the one's selection. Consequently, a key question raises that, it is the local information or the global information more determinative for one's selection? Here we compare the local-based influence and global-based influence. We show that, the selection behaviour is mainly driven by the local popularity of the objects while the global popularity plays a supplementary role driving the behaviour only when there is little local information for the user to refer to. Thereby, we propose a network model to describe the mechanism of user-object interaction evolution with social influence, where the users perform either local-driven or global-driven preferential attachments to the objects, i.e., the probability of an objects to be selected by a target user is proportional to either its local popularity or global popularity. The simulation suggests that, about 75% of the attachments should be driven by the local popularity to reproduce the empirical observations. It means that, at least in the studied context where users chose businesses on Yelp, there is a probability of 75% for a user to make a selection according to the local popularity. The proposed model and the numerical findings may shed some light on the study of social influence and evolving social systems.


Can evolutionary design of social networks make it easier to be 'green'?
The social Web is swiftly becoming a living laboratory for understanding human cooperation on massive scales. It has changed how we organize, socialize, and tackle problems that benefit from the efforts of a large crowd. A new, applied, behavioral ecology has begun to build on theoretical and empirical studies of cooperation, integrating research in the fields of evolutionary biology, social psychology, social networking, and citizen science. Here, we review the ways in which these disciplines inform the design of Internet environments to support collective pro-environmental behavior, tapping into proximate prosocial mechanisms and models of social evolution, as well as generating opportunities for 'field studies' to discover how we can support massive collective action and shift environmental social norms.


Intimate Partner Violence, Economic Insecurity, and Health Outcomes Among American Indian and Alaska Native Men and Women: Findings From a National Sample.
Limited data are available on experiences of intimate partner violence (IPV) and sexual violence (SV) and health outcomes among American Indian and Alaska Native (AIAN) populations. This study explores the relationship between IPV and SV, food insecurity, housing insecurity, healthcare access, and self-reported physical and mental health status in a nationally representative sample of AIAN adults (N = 3,634). IPV and SV were associated with poorer physical and mental health at the bivariate level, but not in multivariate analyses. Economic inequalities are a salient predictor of health and may be compounded by demographic and geographic contexts.


DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway.
With increasing incidence, pancreatic cancer (PC) is one of the most common digestive tract tumors. However, the prognosis of PC is particularly dismal due to the highly invasive and metastatic behavior of this deadly disease. DEP domain-containing protein 1B (DEPDC1B), which is overexpressed in multiple tumors, such as breast cancer, oral cancer and non-small cell lung cancer, plays a significant role in cell movement, cell cycle and cytoskeleton reorganization. However, the function of DEPDC1B in PC remains poorly understood. The function of DEPDC1B in the migration and invasion of PC was evaluated by wound healing and Transwell assays in vitro and PC-derived liver metastasis models in vivo. The molecular mechanisms of DEPDC1B were investigated through cell line establishment, Western blotting, qRT-PCR, immunoprecipitation, histological examination and immunohistochemistry analysis. DEPDC1B was overexpressed in PC cell lines. DEPDC1B regulated cell migration and invasion. DEPDC1B regulated the Rac1/PAK1-LIMK1-cofilin1 signaling pathway by interacting with Rac1. Rac1 inhibition suppressed DEPDC1B-induced migration and invasion in PC in vitro and DEPDC1B-induced liver metastasis in vivo. DEPDC1B promoted cell migration and invasion by activating the Rac1/PAK1-LIMK1-cofilin1 signaling pathway, thus providing a potential therapeutic target against PC.


Identification of a response element in a herpesvirus saimiri mRNA recognized by the ORF57 protein.
The herpesvirus saimiri (HVS) ORF57 protein binds viral RNA, enabling the efficient nuclear export of intronless viral mRNAs. However, it is not known how ORF57 recognizes these viral mRNAs. In this study, a systematic evolution of ligands by exponential enrichment (SELEX) approach was used to select RNA sequences that are preferentially bound by the ORF57 protein. Results identified a recurring motif, GAAGRG, within the majority of selected RNAs, which is also present in many late HVS mRNAs. RNA immunopreciptations demonstrated that disruption of this motif within a viral intronless RNA ablates ORF57 binding. These data suggest that the GAAGRG motif may be required within a HVS intronless mRNA for recognition by the ORF57 protein.


The Association of Sleep Duration, Mental Health, and Health Risk Behaviors among U.S. Afghanistan/Iraq Era Veterans.
Short and long sleep duration have been linked with higher rates of comorbid medical and mental health issues, as well as increased mortality. The current study examined the association between sleep duration, mental health problems, and health risk behaviors in a large sample of U.S. Afghanistan/Iraq era veterans. NA. Mid-Atlantic VA Medical Center(s). The sample (N = 1,640) included 20% women (n = 333) and had an average age of 37 years (SD = 10.0). NA. Results from logistic regression analyses that included age, minority status, gender, military rank, number of deployments, combat exposure, and health risk behaviors as covariates indicated that very short sleep duration (≤ 5 h of sleep) and long sleep duration (≥ 9 h) were each associated with increased odds of current post traumatic stress disorder (PTSD), major depressive disorder (MDD), and smoking; while poor sleep quality was associated with PTSD, panic disorder (PD), MDD, suicidal ideation (SI), and risky drinking. Sleep duration may be an important marker for psychiatric and health risk behavior problems, and our results suggest that clinical assessment of sleep disturbance in this veteran group is warranted to assess for both short and long sleep. Swinkels CM; Ulmer CS; Beckam JC; Buse N; the VA Mid-Atlantic MIRECC Registry Workgroup; Calhoun PS. The association of sleep duration, mental health, and health risk behaviors among U.S. Afghanistan/Iraq era veterans. SLEEP 2013;36(7):1019-1025.


Hippocampal system and declarative (relational) memory: summarizing the data from functional neuroimaging studies.
In the last several years there have been impressive strides in the ability to explore the nature of hippocampal system functioning in humans by employing functional neuroimaging methods, permitting such methods to be used in conjunction with neuropsychological methods to better understand the role of the hippocampal system in memory. In this paper, we review the literature on functional imaging studies of the hippocampal system, summarizing the data and testing these data against a number of theories or explanatory accounts of hippocampal function. We consider five alternative explanatory accounts of, or ideas about, hippocampal function- some from already existing work, for which the functional imaging data can provide a new test, and others that have emerged directly from the functional imaging work, and that have yet to be tested for their fit of data from neuropsychological methods. We conclude that the relational (declarative) memory account, in which it is proposed that the hippocampal system plays a critical role in binding together multiple inputs to permit representations of the relations among the constituent elements of scenes or events, can better accommodate the full range of imaging (and other existing) data than any other explanatory account of hippocampal function.