Fast IR-Actuated Shape-Memory Polymers Using in Situ Silver Nanoparticle-Grafted Cellulose Nanocrystals.
In recent years, shape-memory polymers (SMPs) have gained a key position in the realm of actuating applications from daily life products to biomedical and aeronautic devices. Most of these SMPs rely mainly on shape changes upon direct heat exposure or after stimulus conversion (e.g., magnetic field and light) to heat, but this concept remains significantly limited when both remote control and fine actuation are demanded. In the present study, we propose to design plasmonic silver nanoparticles (AgNPs) grafted onto cellulose nanocrystals (CNCs) as an efficient plasmonic system for fast and remote actuation. Such CNC- g-AgNPs "nanorod-like" structures thereby allowed for a long-distance and strong coupling plasmonic effect between the AgNPs along the CNC axis, thus ensuring a fast photothermal shape-recovery effect upon IR light illumination. To demonstrate the fast and remote actuation promoted by these structures, we incorporated them at low loading (1 wt %) into poly(ε-caprolactone) (PCL)-based networks with shape-memory properties. These polymer matrix networks were practically designed from biocompatible PCL oligomers end-functionalized with maleimide and furan moieties in the melt on the basis of thermoreversible Diels-Alder reactions. The as-produced materials could find application in the realm of soft robotics for remote object transportation or as smart biomaterials such as self-tightening knots with antibacterial properties related to the presence of the AgNPs.


Control of the Electroporation Efficiency of Nanosecond Pulses by Swinging the Electric Field Vector Direction.
Reversing the pulse polarity, i.e., changing the electric field direction by 180°, inhibits electroporation and electrostimulation by nanosecond electric pulses (nsEPs). This feature, known as "bipolar cancellation," enables selective remote targeting with nsEPs and reduces the neuromuscular side effects of ablation therapies. We analyzed the biophysical mechanisms and measured how cancellation weakens and is replaced by facilitation when nsEPs are applied from different directions at angles from 0 to 180°. Monolayers of endothelial cells were electroporated by a train of five pulses (600 ns) or five paired pulses (600 + 600 ns) applied at 1 Hz or 833 kHz. Reversing the electric field in the pairs (180° direction change) caused 2-fold (1 Hz) or 20-fold (833 kHz) weaker electroporation than the train of single nsEPs. Reducing the angle between pulse directions in the pairs weakened cancellation and replaced it with facilitation at angles <160° (1 Hz) and <130° (833 kHz). Facilitation plateaued at about three-fold stronger electroporation compared to single pulses at 90-100° angle for both nsEP frequencies. The profound dependence of the efficiency on the angle enables novel protocols for highly selective focal electroporation at one electrode in a three-electrode array while avoiding effects at the other electrodes. Nanosecond-resolution imaging of cell membrane potential was used to link the selectivity to charging kinetics by co- and counter-directional nsEPs.


Successful Transfer of a Motor Learning Strategy to a Novel Sport.
This study investigated whether secondary school students who were taught a motor learning strategy could transfer their knowledge of the strategy to learning a novel task. Twenty adolescents were randomly allocated to a strategy or control group. The strategy group was taught Singer's five-step learning strategy, while the control group received information on the evolution and biomechanics of the basketball free throw. Both groups received three 1-hour practice sessions on a modified basketball shooting task. After one month, participants were introduced to the transfer task, golf putting. Performance accuracy was recorded for all tasks, and participants completed questionnaires regarding strategy use during practice. Participants taught the five-step learning strategy successfully recalled and applied it after a 1-month interval, and they demonstrated superior performance on both acquisition and transfer tasks, relative to the control group. Physical education teachers and coaches should consider using this learning strategy to enhance the learning of closed motor skills.


Shorter leucocyte telomere length as a potential biomarker for nonalcoholic fatty liver disease-related advanced fibrosis in T2DM patients.
Telomere length has been linked to hepatic fibrosis. Type 2 diabetes mellitus (T2DM) is considered as a particular risk for the development of hepatic fibrosis. This study is to explore the association of leucocyte telomere length (LTL) and nonalcoholic fatty liver disease (NAFLD)-related advanced fibrosis in T2DM patients. A total of 442 patients with T2DM were enrolled from Tongji Hospital, Wuhan, China. Clinical features were collected and LTL was measured by Southern blot-based terminal restriction fragment length. Hepatic advanced fibrosis was determined by both the NAFLD fibrosis score (NFS) and fibrosis-4 score (FIB-4). Explanatory factors for advanced fibrosis in T2DM patients were identified using multiple logistic regressions. T2DM patients with advanced fibrosis had significant shorter LTL than the no-advanced group. Additionally, LTL, age, male and aminotransferase (ALT) were significantly associated with advanced fibrosis status in T2DM patients. Longer diabetes duration was found to have a strong association with advanced fibrosis in elder T2DM patients. Shorter LTL was significantly associated with advanced fibrosis in T2DM patients. Longer diabetes duration was an independent risk factor for advanced fibrosis in old T2DM patients. Shorter LTL may be used as a biomarker for advanced fibrosis in T2DM patients.


Management of twin-twin transfusion syndrome with an extremely short cervix.
The objective of this study was to describe the management and perinatal outcomes of patients with twin-twin transfusion syndrome (TTTS) and an extremely short cervical length (CL). This retrospective study examined 17 patients with TTTS and a preoperative CL ≤1.0 cm who had undergone laser surgery and perioperative cervical cerclage placement successfully. In this subset of patients, the median interval between surgery and delivery was 9.6 (range 2.1-13.9) weeks and only one patient had PPROM within 3 weeks of surgery. The median gestational age at delivery was 30.9 (range 23.1-37.6) weeks, 30-day survival of at-least-one twin was 88.2% and dual survivorship was 82.4%. Overall, patients with TTTS and a preoperative CL ≤1.0 cm who were able to undergo successful laser surgery and emergent cerclage placement had favourable outcomes. Impact statement The management of patients with twin-twin transfusion syndrome (TTTS) and extremely short cervical length (CL) varies between foetal surgery centres. This study demonstrates that laser surgery and cerclage placement in such patients are not only technically feasible, but also can result in favourable perinatal outcomes. Patients with an extremely short CL should not be uniformly excluded from laser surgery for TTTS.


Acetylcarnitine inhibits alcohol dehydrogenase.
Carnitine and acetylcarnitine are used as dietary supplements and as therapeutic agents. Carnitine attenuates ethanol metabolism in intact animals but the in vitro activities of alcohol dehydrogenase (ADH), microsomal ethanol oxidizing system (MEOS) or catalase are not significantly altered by carnitine. Since acetylcarnitine was a far more potent inhibitor of ethanol oxidation than carnitine in hepatocytes, the activities of rat liver ADH and MEOS were determined with or without acetylcarnitine. The activity of ADH, not MEOS, was significantly inhibited by acetylcarnitine at NAD: acetylcarnitine < or = 1. The inhibition is of a competitive nature where acetylcarnitine competes with NAD+ (Ki = 135 mumol.L-1). This finding is unique in that this is the first report of this function of acetylcarnitine and it is a novel interaction between two important nutrients, niacin and carnitine.


Organ procurement in an urban level I emergency department.
To determine whether an intensive educational campaign of emergency department personnel on the organ donor and procurement process would result in both increased organ donor referrals and organs procured. A retrospective review of the performance of an urban teaching ED in identifying and referring potential organ donor candidates was performed. Subsequently an intensive educational campaign of all ED staff, in conjunction with the Regional Organ Procurement Agency of Southern California (ROPA), was initiated. Physicians and nurses were educated about the procurement process, and a ROPA representative was on call 24 hours a day to assist in this process. The need for aggressive resuscitation and vital sign maintenance in potential donors as a strategy to promote organ recovery was emphasized. Reeducation by ROPA occurred every 2 to 3 months. The identification and referral rates were then retrospectively reviewed to evaluate any improvement. In 1994 the initial referral rate of potential organ donors from the ED was 30% (3 of 10) resulting in no organs procured. After the intervention the referral rate increased to 100% (25 of 25) in 1995 (P < .0001). The number of actual donors procured was 0 in 1994, 5 in 1995, and 9 in 1996. The increased ED referrals resulted in 14 and 32 organs procured in 1995 and 1996, respectively. Emergency physicians are in a unique position as first caregivers to interact with both potential donors and their families. With intensive education of ED staff, proper identification and referral, as well as timely intervention by organ procurement representatives, the consent and donation rate of organs for transplantation can be increased and maintained.


Expert Panel Recommendations on Lower Urinary Tract Health of Women Across Their Life Span.
Urologic and kidney problems are common in women across their life span and affect their daily life, including physical activity, sexual relations, social life, and future health. Urological health in women is still understudied and the underlying mechanisms of female urological dysfunctions are not fully understood. The Society for Women's Health Research (SWHR®) recognized the need to have a roundtable discussion where researchers and clinicians would define the current state of knowledge, gaps, and recommendations for future research directions to transform women's urological health. This report summarizes the discussions, which focused on epidemiology, clinical presentation, basic science, prevention strategies, and efficacy of current therapies. Experts around the table agreed on a set of research, education, and policy recommendations that have the potential to dramatically increase awareness and improve women's urological health at all stages of life.


Discontinuities between maternity and child and family health services: health professional's perceptions.
Continuity in the context of healthcare refers to the perception of the client that care has been connected and coherent over time. For over a decade professionals providing maternity and child and family health (CFH) services in Australia and internationally have emphasised the importance of continuity of care for women, families and children. However, continuity across maternity and CFH services remains elusive. Continuity is defined and implemented in different ways, resulting in fragmentation of care particularly at points of transition from one service or professional to another.This paper examines the concept of continuity across the maternity and CFH service continuum from the perspectives of midwifery, CFH nursing, general practitioner (GP) and practice nurse (PN) professional leaders. Data were collected as part of a three phase mixed methods study investigating the feasibility of implementing a national approach to CFH services in Australia (CHoRUS study). Representatives from the four participating professional groups were consulted via discussion groups, focus groups and e-conversations, which were recorded and transcribed. In total, 132 professionals participated, including 45 midwives, 60 CFH nurses, 15 general practitioners and 12 practice nurses. Transcripts were analysed using a thematic approach. 'Continuity' was used and applied differently within and across groups. Aspects of care most valued by professionals included continuity preferably characterised by the development of a relationship with the family (relational continuity) and good communication (informational continuity). When considering managerial continuity we found professionals' were most concerned with co-ordination of care within their own service, rather than focusing on the co-ordination between services. These findings add new perspectives to understanding continuity within the maternity and CFH services continuum of care. All health professionals consulted were committed to a smooth journey for families along the continuum. Commitment to collaboration is required if service gaps are to be addressed particularly at the point of transition of care between services which was found to be particularly problematic.


Does augmented feedback from pedometers increase adults' walking behavior?
This study investigated whether feedback from pedometers motivated adults to increase their walking behavior. Participants (n =26) were enrolled in one of two 8-wk. "Walking for Fitness" classes. The study used a crossover design, such that Group 1 wore pedometers for the first 3 weeks (Feedback Condition) and sealed "disguised" pedometers for the last 3 weeks (No-feedback Condition). The order of feedback was reversed for Group 2. Analysis indicated that (a) neither group increased their walking behavior significantly over time and, (b) interactions between groups were not significant at Week 3 or 6, indicating that groups did not respond differently to feedback from the pedometers. If a motivational effect from pedometers exists, it may be small, dissipate before 3 wk., only work in combination with goal setting, or only motivate certain types of individuals.


Significant higher-level C-C motif chemokine ligand 2/3 and chemotactic power in cerebral white matter than grey matter in rat and human.
Recent observations indicate that cerebral white matter (WM) exhibits a higher chemoattractant capability for immune cells. The C-C motif chemokine ligands 2 and 3 (CCL2, CCL3) are key chemokines for monocytes and T cells. However, tissue differential of these chemokines is unclear, although the higher CCL2/3 mRNA levels were found in rodent WM. It has been shown that more immune cells infiltrated to WM than to grey matter (GM) in multiple sclerosis (MS) and human/simian immunodeficiency virus (HIV/SIV)-infected brains. More nodular lesions have also been identified in the WM of patients with MS or HIV/SIV encephalitis. We hypothesize that higher levels of CCL2/3 in the WM may associate with neuropathogenesis. To test this hypothesis, we compared CCL2 and CCL3 peptide levels in WM and GM of rat and human, and found both were significantly higher in the WM. Next, we tested the effect of CCL2 on primary rat microglia migration and observed a dose-dependent migratory pattern. Then, we assessed effects of WM and GM homogenates on microglia chemotaxis and observed significant stronger effects of WM than GM in a concentration-dependent manner. The concentration-dependent pattern of tissue homogenates on chemotaxis was similar to the effect of CCL2. Finally, we found the chemoattractant effects of WM on microglia were significantly attenuated by addition of a CCL2 receptor blocker to culture medium and a neutralizing antibody against CCL3 functional motif in the WM homogenate. Taking together, these results suggest that CCL2/3 played significant roles in the microglia chemotaxis toward WM homogenate.


Isolation, Characterization, and Antibacterial Activity of Hard-to-Culture Actinobacteria from Cave Moonmilk Deposits.
Cave moonmilk deposits host an abundant and diverse actinobacterial population that has a great potential for producing novel natural bioactive compounds. In our previous attempt to isolate culturable moonmilk-dwelling Actinobacteria, only Streptomyces species were recovered, whereas a metagenetic study of the same deposits revealed a complex actinobacterial community including 46 actinobacterial genera in addition to streptomycetes. In this work, we applied the rehydration-centrifugation method to lessen the occurrence of filamentous species and tested a series of strategies to achieve the isolation of hard-to-culture and rare Actinobacteria from the moonmilk deposits of the cave "Grotte des Collemboles". From the "tips and tricks" that were tested, separate autoclaving of the components of the International Streptomyces Project (ISP) medium number 5 (ISP5) medium, prolonged incubation time, and dilution of the moonmilk suspension were found to most effectively improve colony forming units. Taxonomic analyses of the 40 isolates revealed new representatives of the Agromyces, Amycolatopsis, Kocuria, Micrococcus, Micromonospora, Nocardia, and Rhodococcus species, as well as additional new streptomycetes. The applied methodologies allowed the isolation of strains associated with both the least and most abundant moonmilk-dwelling actinobacterial operational taxonomic units. Finally, bioactivity screenings revealed that some isolates displayed high antibacterial activities, and genome mining uncovered a strong potential for the production of natural compounds.


Standard and inverse site percolation of straight rigid rods on triangular lattices: Isotropic and perfectly oriented deposition and removal.
Numerical simulations and finite-size scaling analysis have been carried out to study standard and inverse percolation of straight rigid rods on triangular lattices. In the case of standard percolation, the lattice is initially empty. Then, linear k-mers (particles occupying k consecutive sites along one of the lattice directions) are randomly and sequentially deposited on the lattice. In the case of inverse percolation, the process starts with an initial configuration where all lattice sites are occupied by single monomers (each monomer occupies one lattice site) and, consequently, the opposite sides of the lattice are connected by nearest-neighbor occupied sites. Then the system is diluted by randomly removing sets of k consecutive monomers (linear k-mers) from the lattice. Two schemes are used for the depositing/removing process: an isotropic scheme, where the deposition (removal) of the linear objects occurs with the same probability in any lattice direction, and an anisotropic (perfectly oriented) scheme, where one lattice direction is privileged for depositing (removing) the particles. The study is conducted by following the behavior of four critical concentrations with size k: (i) [(ii)] standard isotropic[oriented] percolation threshold θ_{c,k}[ϑ_{c,k}], which represents the minimum concentration of occupied sites at which an infinite cluster of occupied nearest-neighbor sites extends from one side of the system to the other. θ_{c,k}[ϑ_{c,k}] is reached by isotropic[oriented] deposition of straight rigid k-mers on an initially empty lattice; and (iii) [(iv)] inverse isotropic[oriented] percolation threshold θ_{c,k}^{i}[ϑ_{c,k}^{i}], which corresponds to the maximum concentration of occupied sites for which connectivity disappears. θ_{c,k}^{i}[ϑ_{c,k}^{i}] is reached after removing isotropic [completely aligned] straight rigid k-mers from an initially fully occupied lattice. θ_{c,k}, ϑ_{c,k}, θ_{c,k}^{i}, and ϑ_{c,k}^{i} are determined for a wide range of k (2≤k≤512). The obtained results indicate that (1)θ_{c,k}[θ_{c,k}^{i}] exhibits a nonmonotonous dependence on the size k. It decreases[increases] for small particle sizes, goes through a minimum[maximum] at around k=11, and finally increases and asymptotically converges towards a definite value for large segments θ_{c,k→∞}=0.500(2) [θ_{c,k→∞}^{i}=0.500(1)]; (2)ϑ_{c,k}[ϑ_{c,k}^{i}] depicts a monotonous behavior in terms of k. It rapidly increases[decreases] for small particle sizes and asymptotically converges towards a definite value for infinitely long k-mers ϑ_{c,k→∞}=0.5334(6) [ϑ_{c,k→∞}^{i}=0.4666(6)]; (3) for both isotropic and perfectly oriented models, the curves of standard and inverse percolation thresholds are symmetric to each other with respect to the line θ(ϑ)=0.5. Thus a complementary property is found θ_{c,k}+θ_{c,k}^{i}=1 (and ϑ_{c,k}+ϑ_{c,k}^{i}=1) which has not been observed in other regular lattices. This condition is analytically validated by using exact enumeration of configurations for small systems, and (4) in all cases, the critical concentration curves divide the θ space in a percolating region and a nonpercolating region. These phases extend to infinity in the space of the parameter k so that the model presents percolation transition for the whole range of k.


Use of spacers to facilitate inhaled corticosteroid treatment of asthma.
Budesonide, a topically active corticosteroid, was administered in doses of 400 and 1,600 micrograms/day to 35 asthmatic adults, using a standard inhalation device or a tube or cone spacer. The spacers reduced oropharyngeal candidiasis by an amount equivalent to a 90% reduction in drug dose (p = less than 0.005) and doubled the drug's overall antiasthmatic potency (delta FEV1, p = 0.05) without significantly increasing its overall effect on blood eosinophils (p = 0.14) or the A.M. serum cortisol (p = 0.12). Steroid-induced neutrophilia increased by an amount approximating that produced by an extra half tablet of prednisone per day (p = 0.002). Both the airways and systemic effects of the spacers were greater in patients who had small airways dysfunction present prior to the study. The data suggest an increase in intrapulmonary drug deposition during spacer treatment without a material shift in regional delivery within the lung. Spacers should be particularly useful for patients whose response to inhaled steroid is compromised by by dose-limiting oropharyngeal complications. They can also reduce drug costs. They should be used selectively in children until their effect on regional intrapulmonary drug deposition has been more clearly defined.


Harnessing Human N-type Ca(2+) Channel Receptor by Identifying the Atomic Hotspot Regions for Its Structure-Based Blocker Design.
The voltage dependent N-type Ca(2+) channel (NCC) receptor was identified to have therapeutic potential for the treatment of neuropathic pain and stroke disease. The Ca(2+) ion transport through the transmembrane influx is mainly dependent on the closing, opening, or intermediate state gating mechanism of NCC. Harnessing this dynamic gating mechanism at the structural level is an important and challenging physiological phenomenon. The three dimensional (3D) structure of this membrane receptor is not yet experimentally determined to understand its mechanism of action. Based on these observations, we have developed for the first time the structure of the closed state of the NCC receptor at the pore forming domains which mainly involve three transmembrane helices (TMhs) S5, P and S6. Hot-spot binding site residues of this receptor model were identified by molecular docking technique using amlodipine, cilnidipine and nifedipine compounds known to be potent Ca(2+) channel antagonists. Further, the Ca(2+) ion permeability and the hydrophobic gating mechanism provided better structural and functional insights on the NCC receptor. These results are in consonance with other Ca(2+) channel receptors and would provide guidance for further biochemical investigations.


A new micromechanical approach for the preparation of graphene nanoplatelets deposited on polyethylene.
An advantageous micromechanical technique to deposit large area graphene nanoplatelet (GNP) thin films on a low-density polyethylene substrate is proposed. This method is based on the application of shear-stress and friction forces to a graphite platelets/ethanol paste on the surface of a polymeric substrate; it allows us to obtain a continuous film of superimposed nanoplatelets mainly made of 13-30 graphene layers. X-ray diffraction (XRD), atomic force and transmission electron microscopy (TEM) measurements support the occurrence of a partial exfoliation of the graphite platelets due to shear-stress and friction forces applied during film formation. Scanning electron microscopy (SEM) observations point out that the surface of the polymer is uniformly coated by the overlap of GNPs, and TEM analysis reveals the tendency of the nanoplatelets to align parallel to the interface plane. It has been found that the deposited samples, under white light illumination, exhibit a negative photoconductivity and a linear photoresponse as a function of the applied voltage and the optical power density in the -120 ÷ 120 mV and 20.9 ÷ 286.2 mW cm-2 ranges, respectively.


Cross-Kingdom Regulation of Putative miRNAs Derived from Happy Tree in Cancer Pathway: A Systems Biology Approach.
MicroRNAs (miRNAs) are well-known key regulators of gene expression primarily at the post-transcriptional level. Plant-derived miRNAs may pass through the gastrointestinal tract, entering into the body fluid and regulate the expression of endogenous mRNAs. Camptotheca acuminata, a highly important medicinal plant known for its anti-cancer potential was selected to investigate cross-kingdom regulatory mechanism and involvement of miRNAs derived from this plant in cancer-associated pathways through in silico systems biology approach. In this study, total 33 highly stable putative novel miRNAs were predicted from the publically available 53,294 ESTs of C. acuminata, out of which 14 miRNAs were found to be regulating 152 target genes in human. Functional enrichment, gene-disease associations and network analysis of these target genes were carried out and the results revealed their association with prominent types of cancers like breast cancer, leukemia and lung cancer. Pathways like focal adhesion, regulation of lipolysis in adipocytes and mTOR signaling pathways were found significantly associated with the target genes. The regulatory network analysis showed the association of some important hub proteins like GSK3B, NUMB, PEG3, ITGA2 and DLG2 with cancer-associated pathways. Based on the analysis results, it can be suggested that the ingestion of the C. acuminata miRNAs may have a functional impact on tumorigenesis in a cross-kingdom way and may affect the physiological condition at genetic level. Thus, the predicted miRNAs seem to hold potentially significant role in cancer pathway regulation and therefore, may be further validated using in vivo experiments for a better insight into their mechanism of epigenetic action of miRNA.


Temporal Check-All-That-Apply Characterization of Syrah Wine.
Temporal Check-All-That-Apply (TCATA) is a new dynamic sensory method for which analysis techniques are still being developed and optimized. In this study, TCATA methodology was applied for the evaluation of wine finish by trained panelists (n = 13) on Syrah wines with different ethanol concentrations (10.5% v/v and 15.5% v/v). Raw data were time standardized to create a percentage of finish duration, subsequently segmented into thirds (beginning, middle, and end) to capture panel perception. Results indicated the finish of the high ethanol treatments lasted longer (approximately 12 s longer) than the low ethanol treatment (P ≤ 0.05). Within each finish segment, Cochran's Q was conducted on each attribute and differences were detected amongst treatments (P ≤ 0.05). Pairwise tests showed the high ethanol treatments were more described by astringency, heat/ethanol burn, bitterness, dark fruit, and spices, whereas the low ethanol treatment was more characterized by sourness, red fruit, and green flavors (P ≤ 0.05). This study demonstrated techniques for dealing with the data generated by TCATA. Furthermore, this study further characterized the influence of ethanol on wine finish, and by extension wine quality, with implications to winemakers responsible for wine processing decisions involving alcohol management.


Effect of long-term treatment with human leukocyte interferon on various laboratory parameters.
Leukocyte interferon was given by i.m. injection as adjuvant therapy to 9 patients with osteosarcoma. The dose was 3 X 10(6) standard units daily for one month, and then 3 times a week for the next 17 months. Blood samples were drawn at intervals for a number of routine tests during the 18-month course of interferon administration and during the subsequent 18 months. On withdrawal of the interferon treatment, the mean Hb concentration rose significantly and the mean ESR fell significantly. There was no significant change in the leukocyte and platelet counts or in the alkaline phosphatase, alanine and aspartate aminotransferase or plasma protein levels.


Flavan-3-ols, anthocyanins, and inflammation.
The process of inflammation constitutes a reactive response of the organism to tissue damage and is an important factor making part of a number of degenerative pathologies as insulin resistance, dyslipidemia, and hypertension, all of them comprised in the metabolic syndrome. There is an increasing interest in plant products rich in flavan-3-ols and anthocyanins because of their potential beneficial effects observed in epidemiological studies against inflammatory-related diseases. Their anti-inflammatory effects are exerted by modulation of cell redox status and inhibition of signaling pathways as NF-κB activation. The effects depend on their concentrations in target tissues and hence the bioavailability pathways followed by each particular compound. In this sense, in vitro studies performed with parental compounds at doses exceeding to those found in vivo may be drawing erroneous conclusions about their real efficacy. Contradictory results have been observed in human intervention trials, which may be ascribed to the type of population studied, length of study, source of flavan-3-ol/anthocyanin, and dose provided. Human studies are required to confirm the positive effects found in vitro and in animal models. Future research should be focused on the understanding of dose/flavonoid intake-response relationship with pharmacokinetic studies, evaluating proper biomarkers of intake. Long-term dietary interventions are necessary to observe effects on markers of late activation as well as the possible preventive effects of these compounds on long-term inflammation-related diseases.


Time dependence of platelet inhibition after a 600-mg loading dose of clopidogrel in a large, unselected cohort of candidates for percutaneous coronary intervention.
Pretreatment with clopidogrel can reduce the risks associated with percutaneous coronary intervention (PCI). To shorten the time for clopidogrel to become effective, a 600-mg loading dose has been used. We sought to validate this regimen in a large cohort and investigated the time dependence of the antiplatelet effect of 600 mg of clopidogrel. Our study included 1001 patients who were scheduled for cardiac catheterization as potential candidates for PCI. We obtained blood samples before administration of 600 mg of clopidogrel and at the time of catheterization, which varied according to logistic needs. We assessed platelet aggregation by optical aggregometry and surface expression of P-selectin and activated glycoprotein IIb/IIIa by flow cytometry. Platelet aggregation induced by 5 micromol/L ADP was 51+/-14% when catheterization was performed at <1 hour, 41+/-14% at 1 to <2 hours, 37+/-15% at 2 to <4 hours, 36+/-13% at 4 to <6 hours, and 35+/-14% at > or =6 hours after clopidogrel administration. After 2 hours (n=718), the level of platelet aggregation and the surface expression of P-selectin and activated glycoprotein IIb/IIIa did not change significantly with time after clopidogrel (P>0.24 by univariate or multivariate regression). Comedication with CYP3A4 metabolized statins did not significantly affect platelet aggregation after clopidogrel (P=0.62). Among the 428 patients undergoing PCI, the 30-day composite rate of major adverse cardiac events was 1.9%, with no significant difference between patients undergoing PCI within 2 hours after clopidogrel loading and those undergoing PCI at a later time point. After loading with 600 mg of clopidogrel, the full antiplatelet effect of the drug is achieved after 2 hours. Statins do not interfere with the level of platelet inhibition after this dose.


Distinguishing the affective and cognitive bases of implicit attitudes to improve prediction of food choices.
Eating behaviors largely result from automatic processes. Yet, in existing research, automatic or implicit attitudes toward food often fail to predict eating behaviors. Applying findings in cognitive neuroscience research, we propose and find that a central reason why implicit attitudes toward food are not good predictors of eating behaviors is that implicit attitudes are driven by two distinct constructs that often have diverging evaluative consequences: the automatic affective reactions to food (e.g., tastiness; the affective basis of implicit attitudes) and the automatic cognitive reactions to food (e.g., healthiness; the cognitive basis of implicit attitudes). More importantly, we find that the affective and cognitive bases of implicit attitudes directly and uniquely influence actual food choices under different conditions. While the affective basis of implicit attitude is the main driver of food choices, it is the only driver when cognitive resources during choice are limited. The cognitive basis of implicit attitudes uniquely influences food choices when cognitive resources during choice are plentiful but only for participants low in impulsivity. Researchers interested in automatic processes in eating behaviors could thus benefit by distinguishing between the affective and cognitive bases of implicit attitudes.


Effect of endurance exercise training on heart rate onset and heart rate recovery responses to submaximal exercise in animals susceptible to ventricular fibrillation.
Both a large heart rate (HR) increase at exercise onset and a slow heart rate (HR) recovery following the termination of exercise have been linked to an increased risk for ventricular fibrillation (VF) in patients with coronary artery disease. Endurance exercise training can alter cardiac autonomic regulation. Therefore, it is possible that this intervention could restore a more normal HR regulation in high-risk individuals. To test this hypothesis, HR and HR variability (HRV, 0.24- to 1.04-Hz frequency component; an index of cardiac vagal activity) responses to submaximal exercise were measured 30, 60, and 120 s after exercise onset and 30, 60, and 120 s following the termination of exercise in dogs with healed myocardial infarctions known to be susceptible (n = 19) to VF (induced by a 2-min coronary occlusion during the last minute of a submaximal exercise test). These studies were then repeated after either a 10-wk exercise program (treadmill running, n = 10) or an equivalent sedentary period (n = 9). After 10 wk, the response to exercise was not altered in the sedentary animals. In contrast, endurance exercise increased indexes of cardiac vagal activity such that HR at exercise onset was reduced (30 s after exercise onset: HR pretraining 179 +/- 8.4 vs. posttraining 151.4 +/- 6.6 beats/min; HRV pretraining 4.0 +/- 0.4 vs. posttraining 5.8 +/- 0.4 ln ms(2)), whereas HR recovery 30 s after the termination of exercise increased (HR pretraining 186 +/- 7.8 vs. posttraining 159.4 +/- 7.7 beats/min; HRV pretraining 2.4 +/- 0.3 vs. posttraining 4.0 +/- 0.6 ln ms(2)). Thus endurance exercise training restored a more normal HR regulation in dogs susceptible to VF.


Loss of vinculin and membrane-bound β-catenin promotes metastasis and predicts poor prognosis in colorectal cancer.
Loss of cell-cell adhesion is important for the development of cancer invasion and metastasis. Vinculin, a key adhesion-related protein, can affect metastasis and prognosis in several tumours. Here, we determined the biological roles of vinculin in the metastasis of colorectal cancer (CRC) and evaluated its clinical significance as a potential disease biomarker. The expression level of vinculin in CRC cell lines and tissues was measured using Real-Time PCR and western blotting. Moreover, vinculin function was analysed using Transwell assays and in vivo metastasis assays in gain- and loss-of-function experiments. Furthermore, the impact of vinculin together with membrane-bound β-catenin on the prognosis of 228 CRC patients was investigated by immunohistochemistry. Additionally, the expression of epithelial-mesenchymal transition (EMT) indicators was verified by immunohistochemistry in CRC tissues obtained from these patients. Vinculin expression was found to be significantly downregulated in highly metastatic CRC cell lines and metastatic tissues. Both in vitro and in vivo experiments showed that vinculin suppressed invasion, migration and metastasis in CRC cells and that this suppression could be attenuated by silencing β-catenin. Moreover, the expression of vinculin and membrane-bound β-catenin were positively correlated in CRC tissues, and lack of vinculin expression emerged as an independent prognostic factor in patients with CRC. Finally, the loss of vinculin and membrane-bound β-catenin was associated with node metastasis, organ metastasis and expression of EMT indicators. Our results suggest that vinculin may play specific roles in the EMT and metastasis of CRC and that loss of vinculin could be used as a prognostic factor for CRC.


Linker-Assisted CdS-TiO2 Nanohybrids as Reusable Visible Light Photocatalysts for the Oxidative Hydroxylation of Arylboronic Acids.
A variety of phenols have been obtained in aqueous media with moderate to excellent chemical yields (≤100%) by using arylboronic acids and esters as substrates, a robust CdS-TiO2 nanohybrid as a heterogeneous photocatalyst, visible light irradiation (467 nm), and an O2-saturated atmosphere. The nanohybrid was prepared through a linker-assisted methodology that uses mercapto alkanoic acids as the organic linkers. The nanohybrid showed improved photocatalytic activity in the hydroxylation of substituted arylboronic acids and phenyl boronic esters compared with that of pristine CdS quantum dots. The nanohybrid can be reused in up to five photocatalytic cycles with ∼90% of its outstanding activity preserved.


Learning and memory of factual content from narrative and expository text.
Research on the presentation of information in narrative versus expository text genres is inconclusive with respect to the question of which is more beneficial for student learning. We examine the effect of presenting factual content in either narrative or expository genres on student learning. We also consider relevant prior knowledge and working memory capacity (WMC) as potential mediating variables. Ninety university undergraduate students. Subjects studied circulatory system content embedded in either narrative or expository texts. Prior circulatory system knowledge, knowledge improvement (learning) and free recall were assessed. Learning and recall did not differ as a function of text genre overall, but did interact with prior knowledge. Learning from the narrative and one expository text was optimal at intermediate levels of prior knowledge, with higher knowledge readers benefiting more from the expository text compared with the narrative text. Prior knowledge was positively related to recall for the expository texts, but unrelated for the narrative text. Subjects' WMC did not predict learning or recall. Results suggest that narrative and expository processing differ with respect to integration of text content with prior knowledge.


Antireflux Metal Stent as a First-Line Metal Stent for Distal Malignant Biliary Obstruction: A Pilot Study.
In distal malignant biliary obstruction, an antireflux metal stent (ARMS) with a funnel-shaped valve is effective as a reintervention for metal stent occlusion caused by reflux. This study sought to evaluate the feasibility of this ARMS as a first-line metal stent. Patients with nonresectable distal malignant biliary obstruction were identified between April and December 2014 at three Japanese tertiary centers. We retrospectively evaluated recurrent biliary obstruction and adverse events after ARMS placement. In total, 20 consecutive patients were included. The most common cause of biliary obstruction was pancreatic cancer (75%). Overall, recurrent biliary obstruction was observed in seven patients (35%), with a median time to recurrent biliary obstruction of 246 days (range, 11 to 246 days). Stent occlusion occurred in five patients (25%), the causes of which were sludge and food impaction in three and two patients, respectively. Stent migration occurred in two patients (10%). The rate of adverse events associated with ARMS was 25%: pancreatitis occurred in three patients, cholecystitis in one and liver abscess in one. No patients experienced nonocclusion cholangitis. The ARMS as a first-line biliary drainage procedure was feasible. Because the ARMS did not fully prevent stent dysfunction due to reflux, further investigation is warranted.


Thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in hepatocellular carcinoma and metastatic liver cancer.
Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are considered to be key enzymes affecting the prognosis for patients with various cancers. We tried to prove the correlation of TP and DPD expression in hepatocellular carcinoma (HCC) and liver metastasis. We quantified TP and DPD levels by an enzyme-linked immunosorbent assay (ELISA) in the tumor (T) and adjacent normal tissue (N) obtained from 8 HCC patients, and 11 liver metastasis patients together with 9 of their primary cancers. TP levels were higher in the primary cancer, liver metastasis, and HCC compared with each adjacent tissue. TP levels were higher in HCC than in liver metastasis, and TP levels in the adjacent tissues of HCC were also higher than those in adjacent tissues of liver metastasis. TP levels were higher in liver metastasis than in primary cancer, and TP levels in adjacent tissues of liver metastasis were also higher than those in adjacent tissues of primary cancer. However, there were no differences in TP T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. DPD levels were lower in the liver metastasis compared with the adjacent liver tissues, and DPD levels in liver metastasis or its adjacent liver tissues were higher than those in primary cancer or its adjacent tissues. There were no differences in DPD T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. Thus, we demonstrated that TP was highly expressed in liver malignancy. We may be able to increase the success of anticancer chemotherapy for liver malignancy while decreasing the side effects by analysis of T/N ratios in TP, DPD, and TP/DPD in addition to TP expression.


Tissue Biomarkers in Hepatocellular Tumors: Which, When, and How.
Few tissue markers are currently available to pathologists in the study of hepatocellular tumors. These markers should be used carefully taking into consideration not only morphology but also, and sometimes even more important, the clinical setting where the lesion to be diagnosed had developed. Glypican-3, heat shock protein 70, and glutamine synthetase (GS) are markers currently used, as a single panel, to discriminate the nature of a <2 cm hepatocellular lesion lacking radiological features of hepatocellular carcinoma (HCC) detected in a cirrhotic patient under surveillance. Their use, which can be improved by clathrin heavy chain, is mostly requested on liver biopsy. Hepatocyte paraffin 1, arginase-1, polyclonal carcinoembryonic antigen, CD10, and bile salt export pump are tissue markers used to confirm, at histology, the diagnosis of HCC made by imaging before enrollment for phase III studies on novel anti-HCC drugs. In this setting, pathologists are usually requested a conclusive diagnosis on a liver biopsy of a poorly differentiated, necrotic, enriched in stem-phenotype, carcinoma. Liver fatty acid-binding protein, serum amyloid A, C-reactive protein, prostaglandin D2 synthetase, GS, and β-catenin can be used either on biopsy or surgical specimen to classify hepatocellular adenoma into hepatocyte nuclear factor (HNF-1α) inactivated (steatotic), inflammatory, with dysregulation of sonic hedgehog and prostaglandin pathways, β-catenin mutated, and unclassified.


Effects of Mannitol 20% on Outcomes in Nontraumatic Intracerebral Hemorrhage.
A large number of stroke patients are not the perfect candidate for craniotomy and invasive procedures, so providing an alternative and noninvasive method, which is applicable in terms of costs and facilities, is necessary. Thus, the present study aimed to determine the effects of mannitol 20% on outcome of the patients with nontraumatic intracerebral hemorrhage (ICH) in patients admitted to Isfahan's Al-Zahra Hospital during 2012 and 2013. This is a clinical trial study which is conducted during 2012-2013 in Isfahan's Al-Zahra Hospital. In this study, 41 patients suffering from ICH received mannitol 20% for 3 days, and volume of hemorrhage and Glasgow Coma Scale (GCS) of patients were controlled every 12 h. The collected data were analyzed via SPSS software. The mean ICH volume was 22.1 ± 6.3 ml in pre intervention and 38.4 ± 19.3 ml in post intervention, and according to the t-paired test, before and after treatment the difference was significant (P < 0.001). Hemorrhage volume was stable in nine patients (22%), it increased in 25 patients (61%), and decreased in seven patients (17.1%). The mean index of GCS before and after treatment was 11.85 ± 1.6 and 9.37 ± 2.65, respectively. Moreover according to t-paired test, the difference was significant before and after treatment (P < 0.001). During using mannitol, the GCS index was stable in eight patients (19.5%), it increased in eight patients (19.5%) and decreased in 25 patients (61%). Mannitol injection was not effective in reducing hemorrhage size, and its use is not recommended, also, further studies in this field have been proposed.


Effect of cost-effective substrates on growth cycle and yield of lingzhi or reishi medicinal mushroom, Ganoderma lucidum (higher Basidiomycetes) from Northwestern Himalaya (India).
To find a cost-effective alternative substrate, the medicinal mushroom Ganoderma lucidum was grown on sawdusts of sheesham, mango, and poplar. Optimum spawn level was determined by spawning in substrates at various levels (1, 2, 3, and 4%). To determine the effect of supplementation, substrates were supplemented with wheat bran, rice bran and corn flour at different concentrations (10, 20, and 30%). Duration of growth cycle, mushroom yield, and biological efficiency data were recorded. Among substrates, mango sawdust was superior, with 1.5-fold higher yields than poplar sawdust, which was the least suitable. However with respect to fructification, mango sawdust produced the first primordia earlier (21±1 days) compared with the other investigated substrates. 3% spawn level was found to be optimal irrespective of the substrate. Yield and biological efficiency (BE) were maximally enhanced by supplementation with wheat bran, whereas rice bran was the least suitable supplement among those tested. Growth cycle shortened and mushroom yield increased to a maximum at the 20% level of supplements. Mango sawdust in combination with 20% wheat bran, if spawned at the 3% level, resulted in a high yield (BE = 58.57%).


Imaging of multistep human hepatocarcinogenesis.
In Japan, there are approximately 32 000 deaths ( approximately 30 deaths per 100 000) per year due to hepatocellular carcinoma (HCC), and it is the third most common cancer in men and fifth in women. Approximately 90% of them are associated with chronic liver diseases due to hepatitis C or B virus infection. Therefore, it has become possible to detect small early stage HCC by the periodic screening in these high-risk patients group. During the screening imaging diagnosis of HCC, various kinds of hepatocellular nodules are also frequentlydetected. To characterize them is very important for the early diagnosis and treatment of HCC. For this purpose, it is necessary to understand the concept of multistep hepatocarcinogenesis and the sequential changes of imaging findings.


Deciphering the cross talk between hnRNP K and c-Src: the c-Src activation domain in hnRNP K is distinct from a second interaction site.
The protein tyrosine kinase c-Src is regulated by two intramolecular interactions. The repressed state is achieved through the interaction of the Src homology 2 (SH2) domain with the phosphorylated C-terminal tail and the association of the SH3 domain with a polyproline type II helix formed by the linker region between SH2 and the kinase domain. hnRNP K, the founding member of the KH domain protein family, is involved in chromatin remodeling, regulation of transcription, and translation of specific mRNAs and is a target in different signal transduction pathways. In particular, it functions as a specific activator and a substrate of the tyrosine kinase c-Src. Here we address the question how hnRNP K interacts with and activates c-Src. We define the proline residues in hnRNP K in the proline-rich motifs P2 (amino acids [aa] 285 to 297) and P3 (aa 303 to 318), which are necessary and sufficient for the specific activation of c-Src, and we dissect the amino acid sequence (aa 216 to 226) of hnRNP K that mediates a second interaction with c-Src. Our findings indicate that the interaction with c-Src and the activation of the kinase are separable functions of hnRNP K. hnRNP K acts as a scaffold protein that integrates signaling cascades by facilitating the cross talk between kinases and factors that mediate nucleic acid-directed processes.


Layered hybrid PAM-DMT for IM/DD OWC systems.
Traditional pulse-amplitude-modulated discrete multitone modulation (PAM-DMT) suffers from poor overall performance of spectral and power efficiencies in optical wireless communication (OWC) systems. We propose layered hybrid PAM-DMT (LHPAM-DMT) to utilize more subcarriers to improve the performance. The real part of frequency domain signal is divided into several layers and symmetry biases are added in time domain to generate real-valued and nonnegative signals for intensity modulation with direct detection (IM/DD) OWC systems. By appropriately designing the orthogonality between the signals in lower layers and signals & added biases in higher layers, we further propose an iterative receiver to recover the transmitted information. Theoretical derivation proves that LHPAM-DMT has higher spectral efficiency than PAM-DMT and lower complexity than layered PAM-DMT. Numerical results suggest that LHPAM-DMT is more power efficient than PAM-DMT as well as direct-current (DC) biased optical OFDM (DCO-OFDM), one of the most popular schemes.


Mathematical filtering minimizes metallic halation of titanium implants in MicroCT images.
Microcomputed tomography (MicroCT) images containing titanium implant suffer from x-rays scattering, artifact and the implant surface is critically affected by metallic halation. To improve the metallic halation artifact, a nonlinear Total Variation denoising algorithm such as Split Bregman algorithm was applied to the digital data set of MicroCT images. This study demonstrated that the use of a mathematical filter could successfully reduce metallic halation, facilitating the osseointegration evaluation at the bone implant interface in the reconstructed images.


[Clinical and haemodynamic results after repeat valvotomy of the mitral valve using the Inoue balloon. A comparison with the results after primary valvotomy].
Percutaneous mitral valvotomy (MVT) with the Inoue balloon is the most frequently performed therapeutic alternative to surgical commissurotomy in patients with symptomatic mitral valve stenosis. Few data are available on the results of repeat MVT. We compared the immediate and 3-month results of all patients who had a repeat MVT (n = 39) with those who had a primary intervention (n = 1,117) in our institution between February 1989 and January 2001. Mean age of the 31 women and 8 men with repeat MVT was 53 +/- 14 years at the first and 57 +/- 14 years at the second intervention performed 3 - 10 years later. Following primary intervention the invasively assessed mitral valve are (MVA) had increased from an average of 1.0 +/- 0.2 cm(2) to 1.7 +/- 0.4 cm(2). Echocardiography three months after the intervention revealed a MVA of 1.7 +/- 0.3 cm(2). Repeat MVT resulted in an immediate increase of MVA from 1.0 +/- 0.2 cm(2) to 1.6 +/- 0.4 cm(2), after 3 months the average MVA was 1.6 +/- 0.3 cm(2). According to the NYHA classification clinical symptoms had improved on average from 2.6 to 1.6 three months after primay intervention and from 2.8 to 2.1 three months following the repeat procedure. The incidence of significant procedure-related complications was less than 3 % for both primary and repeat MVT. The clinical and hemodynamic results demonstrated in our patients suggests repeat MVT as the treatment option of choice in mitral restenosis after previous balloon intervention, if mitral valve morphology is still suitable.


The pleiotropic effects of ARB in vascular endothelial progenitor cells.
Angiotensin II regulates blood pressure and contributes to endothelial dysfunction and the progression of atherosclerosis. Bone marrow-derived endothelial progenitor cells (EPCs) in peripheral blood contribute to postnatal vessel repair and neovascularization. Impaired EPC function in patients with hypertension and diabetes inhibits the endogenous repair of vascular lesions and leads to the progression of atherosclerosis. The number of EPCs in peripheral blood is inversely correlated with mortality and the occurrence of cardiovascular events. Angiotensin II-mediated signaling is implicated in oxidative stress, inflammation and insulin resistance, factors that cause EPC dysfunction. Blockade of the angiotensin II type 1 receptor may therefore present a new therapeutic target for enhancing EPC function.


Chloroplast protein import. Chloroplast envelopes and thylakoids have different abilities to unfold proteins.
Proteins have to be at least partially unfolded upon passage through the biological membranes. Previous studies with a dihydrofolate reductase fusion protein containing a chloroplast transit peptide showed that stabilization of the tertiary structure of the fusion protein by binding of a ligand, methotrexate, failed to block its translocation across the envelopes, suggesting that chloroplast envelopes have strong activity to unfold proteins [America, T., Hageman, J., Guéra, A., Rook, F., Archer, K., Keegstra, K. & Weisbeek, P. (1994) Plant Mol. Biol. 24, 283-294]. In the present study, we have analyzed in vitro translocation of a fusion protein consisting of the entire plastocyanin precursor and dihydrofolate reductase across the chloroplast envelope membranes and the thylakoid membrane. In the presence of methotrexate, the fusion protein was imported into the stroma but its translocation across the thylakoid membrane was blocked. The fusion protein that bound to the envelope became susceptible to digestion by thermolysin. These results suggest that, while the envelope membranes can unfold the methotrexate-bound fusion protein to allow its passage, the thylakoid membrane cannot unfold the fusion protein that has re-bound to methotrexate in the stroma.


The risk of viral transmission in feed: What do we know, what do we do?
The role of animal feed as a vehicle for the transport and transmission of viral diseases was first identified in 2014 during the porcine epidemic diarrhoea virus epidemic in North America. Since the identification of this novel risk factor, scientists have conducted numerous studies to understand its relevance. Over the past few years, the body of scientific evidence supporting the reality of this risk has grown substantially. In addition, numerous papers describing actions and interventions designed to mitigate this risk have been published. Therefore, the purpose of this paper is to review the literature on the risk of feed (what do we know) and the protocols developed to reduce this risk (what do we do) in an effort to develop a comprehensive document to raise awareness, facilitate learning, improve the accuracy of risk assessments and to identify knowledge gaps for future studies.


Maternal steroid levels and the autistic traits of the mother and infant.
Prenatal sex steroids have been associated with autism in several clinical and epidemiological studies. It is unclear how this relates to the autistic traits of the mother and how early this can be detected during pregnancy and postnatal development. Maternal serum was collected from pregnant women (n = 122) before or during their first ultrasound appointment [mean = 12.7 (SD = 0.7) weeks]. Concentrations of the following were measured via immunoassays: testosterone, estradiol, dehydroepiandrosterone sulphate, progesterone; and sex hormone-binding globulin which was used to compute the free fractions of estradiol (FEI) and testosterone (FTI). Standardised human choriogonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) values were obtained from clinical records corresponding to the same serum samples. Mothers completed the Autism Spectrum Quotient (AQ) and for their infants, the Quantitative Checklist for Autism in Toddlers (Q-CHAT) when the infants were between 18 and 20 months old. FEI was positively associated with maternal autistic traits in univariate (n = 108, Pearson's r = 0.22, p = 0.019) and multiple regression models (semipartial r = 0.19, p = 0.048) controlling for maternal age and a diagnosis of PCOS. Maternal estradiol levels significantly interacted with fetal sex in predicting infant Q-CHAT scores, with a positive relationship in males but not females (n = 100, interaction term: semipartial r = 0.23, p = 0.036) after controlling for maternal AQ and other covariates. The opposite was found for standardised hCG values and Q-CHAT scores, with a positive association in females but not in males (n = 151, interaction term: r = -0.25, p = 0.005). Sample size of this cohort was small, with potential ascertainment bias given elective recruitment. Clinical covariates were controlled in multiple regression models, but additional research is needed to confirm the statistically significant findings in larger cohorts. Maternal steroid factors during pregnancy are associated with autistic traits in mothers and their infants.


Damage-Associated Molecular Patterns and Systemic Signaling.
Cellular damage inflicted by wounding, pathogen infection, and herbivory releases a variety of host-derived metabolites, degraded structural components, and peptides into the extracellular space that act as alarm signals when perceived by adjacent cells. These so-called damage-associated molecular patterns (DAMPs) function through plasma membrane localized pattern recognition receptors to regulate wound and immune responses. In plants, DAMPs act as elicitors themselves, often inducing immune outputs such as calcium influx, reactive oxygen species generation, defense gene expression, and phytohormone signaling. Consequently, DAMP perception results in a priming effect that enhances resistance against subsequent pathogen infections. Alongside their established function in local tissues, recent evidence supports a critical role for DAMP signaling in generation and/or amplification of mobile signals that induce systemic immune priming. Here we summarize the identity, signaling, and synergy of proposed and established plant DAMPs, with a focus on those with published roles in systemic signaling.


Ovarian Sertoli-Leydig cell tumor with heterologous gastrointestinal epithelium as a source of alpha-fetoprotein: a case report.
Ovarian Sertoli-Leydig cell tumors (SLCT) are rare sex cord stromal neoplasms. To date there have been approximately 25 case reports of ovarian SLCT expressing alpha-fetoprotein (AFP). In such cases, AFP was immunohistochemically detected in the Sertoli cells, Leydig cells, or hepatocytes. This case report confirms heterologous gastrointestinal epithelium expression of AFP. A 20-year-old woman presented with complaints of abdominal enlargement and irregular menstrual cycles over one year. A right ovarian tumor was detected and the patient's serum AFP was elevated. A right salpingo-oophorectomy was performed. On microscopic examination, the tumor was composed of a fibrosarcoma-like area and a poorly differentiated SLCT area with heterologous gastrointestinal epithelium. Immunohistochemical analysis detected AFP in the gastrointestinal epithelium only. Postoperatively, serum AFP levels fell to normal. A recurrent tumor was discovered in the omentum after adjuvant chemotherapy, but serum AFP remained normal. A second laparotomy was performed and the recurrent tumor showed only fibrosarcoma-like features. The patient received second line chemotherapy and is currently in remission. This is the first case of AFP production by heterologous gastrointestinal epithelium in SLCT.


Untargeted metagenomics shows a reliable performance for synchronous detection of parasites.
Shotgun metagenomics with high-throughput sequencing (HTS) techniques is increasingly used for pathogen identification and characterization. While many studies apply targeted amplicon sequencing, here we used untargeted metagenomics to simultaneously identify protists and helminths in pre-diagnosed faecal and tissue samples. The approach starts from RNA and operates without an amplification step, therefore allowing the detection of all eukaryotes, including pathogens, since it circumvents the bias typically observed in amplicon-based HTS approaches. The generated metagenomics datasets were analysed using the RIEMS tool for initial taxonomic read assignment. Mapping analyses against ribosomal reference sequences were subsequently applied to extract 18S rRNA sequences abundantly present in the sequence datasets. The original diagnosis, which was based on microscopy and/or PCR, could be confirmed in nearly all cases using ribosomal RNA metagenomics. In addition to the pre-diagnosed taxa, we detected other intestinal eukaryotic parasites of uncertain pathogenicity (of the genera Dientamoeba, Entamoeba, Endolimax, Hymenolepis) that are often excluded from routine diagnostic protocols. The study clearly demonstrates the applicability of untargeted RNA metagenomics for the parallel detection of parasites.


In situ hybridization in human and rodent tissue by the use of a new and simplified method.
In situ hybridization (ISH) is a method that detects and localizes DNA or RNA in morphologically preserved tissue and cell preparations. The method is based on the principle that DNA or RNA will undergo hydrogen binding to complimentary sequences. Selective probes are labeled and used in order to detect specific sequences in tissues or cell preparations. Even though the method has improved over the past decades, there are still issues with sensitivity and specificity. The protocols are nonstandardized, and often time consuming due to multiple steps. In this paper, we have used a new and commercially available ISH kit for the detection of mRNA in formalin-fixed paraffin-embedded tissue. We have used both human and Mongolian gerbil tissue, and we evaluated mRNA expression of the neuroendocrine markers chromogranin A and histidine decarboxylase in both normal tissue and poorly differentiated tumor. In our experience, this method offers excellent sensitivity and specificity. The protocol is more standardized, and our results have been consistent. It is also less time consuming than conventional ISH protocols.


Phorbol 12-myristate 13-acetate induced cell death of porcine peripheral blood polymorphonuclear leucocytes.
Polymorphonuclear leucocytes (PMNs) circulating in mammalian peripheral blood are terminally differentiated cells, and once isolated in serum-free medium, they undergo apoptosis within 1 or 2 days. In this study, we studied the effects of phorbol myristate acetate (PMA) on the viability of porcine PMNs in vitro. PMA is known to suppress apoptosis in many cell types. PMA but not dioctanoyl glycerol (DOG) induced morphological degeneration and cell death within 3 to 5 hours as assessed by light microscopy observation and the MTT viability assay. This occurred despite the fact that DNA fragmentation associated with "spontaneous apoptosis" was not observed. Morphological degeneration and death were not due to the oxidative damage from superoxides or its metabolites produced by polymorphonuclear leucocytes, because PMA and DOG similarly stimulated superoxide production. Several other inactive phorbol derivatives tested did not cause cell death, suggesting that the toxicity of PMA did not result from non-specific effect of the reagent.


Escherichia coli translocation in experimental short bowel syndrome: probiotic supplementation and detection by polymerase chain reaction.
After massive bowel resection, bacterial overgrowth is frequent and favors the occurrence of Gram-negative intestinal bacterial translocation (BT). Probiotics have been recommended in several diseases and may also have beneficial effects on BT. Conversely, polymerase chain reaction (PCR) technique has shown better sensitivity than conventional methods in bacterial detection and has not been investigated in experimental models of short bowel syndrome and BT. To test the hypothesis that Bifidobacterium lactis (BL) administration decreases Escherichia coli bacterial translocation (ECBT) in experimental short bowel syndrome and to confirm the better sensitivity of PCR technique to detect ECBT. Forty-eight adult Wistar rats, orally fed with standard rat chow and tap water ad libitum, were maintained in individual metabolic cages for 10 days and divided into three groups: Control group (n = 15): non-manipulated animals. RES group (n = 15): 80% gut resection. 1 ml of sterile water was administered daily after orogastric intubation. RES-PRO group (n = 18): same resection as RES group and daily administration of 7.8 × 10(9) BL (CFU). At the end of the study, portal blood, peripheral blood and mesenteric lymph node (MLN) samples were recovered and cultured. Also, genomic DNA from E. coli was detected by PCR technique. In conventional culture there was no ECBT in control animals whereas 73% of RES and 33% of RES-PRO animals showed it. PCR detected ECBT in 47, 87 and 33%, respectively, showing higher sensitivity.


The antiangiogenic properties of bactericidal/permeability-increasing protein (BPI).
Inhibition of angiogenesis is regarded as a promising tool in the treatment of diseases such as cancer, arthritis and atherosclerosis. This fact has led to the search for novel endogenous or synthetic angiogenesis inhibitors. Recently, antiangiogenic properties were ascribed to an endogenous molecule that until only recently was known for its antibacterial effects. This molecule, bactericidal/permeability-increasing protein (BPI), that was discovered as a bacterial permeabilizing and lipopolysaccharide-neutralizing protein, was found to inhibit angiogenesis by specific induction of apoptosis in endothelial cells. This paper gives a short introduction on angiogenesis and reviews the current knowledge on BPI as an angiogenesis inhibitor. In addition, the issue of commonality between antibacterial and antiangiogenic functions will be addressed.


Statistical learning facilitates the strategic use of attentional control.
A growing body of research suggests that observers rely on a variety of suboptimal strategies when searching for objects. However, real-world environments contain a variety of statistical regularities that enable more efficient processing of information. In the present study, we examined whether statistical learning can influence the strategic use of attentional control using a modified version of the adaptive choice visual search task. Participants searched through an array of colored squares and identified a digit located within a red or blue target square. Each trial contained both a red and a blue target, and participants were free to choose which color to search for. On each trial, more squares were presented in one color than the other color. Thus, the optimal strategy was to search for the color with the fewest squares. Critically, one color was the optimal color on 75% of trials, while the other color was the optimal color on the remaining 25% of trials. Participants were faster to identify targets and made a larger proportion of optimal choices when the high-probability optimal color was optimal. Thus, statistical learning facilitated both search for the targets and the optimal choice of attentional control settings. These effects persisted when the color contingencies were equated, suggesting that these findings were not simply due to intertrial priming. Moreover, participants were not slower to identify targets when the high-probability optimal color appeared as a distractor, suggesting that these findings were not due to attentional capture by this color. Together, these findings suggest that statistical learning can facilitate the strategic use of attentional control by biasing which features observers choose to search for.


[Aneurysm of the left sinus of Valsalva producing obstruction of the left main coronary artery and aortic regurgitation].
A 50-year-old male was admitted with dyspnea on exertion and palpitation. On physical examination, a grade 2/6 aortic regurgitant murmur was heard at the left sternal border. A chest roentogenogram showed an oval shadow on the left cardiac border. Digital subtraction angiogram, aortogram and coronary arteriogram revealed an unruptured-large aneurysm of the left sinus of Valsalva, which compressed the left main coronary artery and produced aortic regurgitation. Surgical correction consisted of obliteration of the orifice of the aneursym with woven Dacron graft patch, aortic valve replacement using SJM23A, and a saphenous vein bypass from the ascending aorta to the left anterior descending coronary artery. Postoperative studies showed complete obliteration of the orifice of the aneurysm, a patent aorto-coronary bypass graft and no perivalvular leakage. This aneurysm was considered congenital in origin, because of no inflammatory and infectious evidence, negative serologic test for syphilis and no aneurysmal dilatation of the ascending aorta.


Long term telemedicine study of compliance in paranoid schizophrenia.
Low compliance is one of the crucial problems of contemporary psychiatry. Relapses, deterioration of cognitive functioning, negative symptoms, neuroleptic resistance are the examples of many consequences of noncompliance in schizophrenia The study was designed to assess the compliance in the 200 patients diagnosed with paranoid schizophrenia, all in the state of symptomatic remission and on the stable neuroleptic treatment. The compliance was assessed using a telepsychiatric system, sending reminders: 1 hour before the planned dose to remind them that drug intake is approaching, and at the moment of intake to check if they took the drug. The confirmed drug intakes were counted by the telepsychiatric system. 158 patients completed the study period. The compliance in the first month of the treatment was 44.6% and decreased over the rest of the period to the level of 33.4%. 50% of the schizophrenic patients were compliant at a level lower than 37%. This group was considered the low compliance group, and in this group the compliance increased after 6 months from 9.3% to 10.3% (p<0.0001). The compliance in the group of schizophrenic patients in remission is very low. The telemedicine system improves the compliance in the patients with the worst compliance.


Coupling of plasmon and photon modes in a graphene-based multilayer structure.
We propose a graphene-based plasmonic heterostructure in which a new class of plasmon polariton modes can be realized via fundamental coupling of conventional graphene plasmons (GPs) and spoof surface plasmons or radiation modes. We name these electromagnetic modes coupled graphene plasmon polaritons (CGPPs). It is found that the properties of the CGPPs can be tuned by the geometry of the heterostructure, the material used to fill the holes, and the electron density in graphene. Most interestingly, we show that it is possible to achieve CGPPs with about 10 times enhancement of wave localization or about 300 times enhancement of propagation length, compared to usual GPs through varying device parameters. These features can be applied to tunable terahertz and infrared plasmonic devices.


Altered secretion of Sertoli cells hormones in 2-year-old prepubertal cryptorchid boys: a cross-sectional study.
In cryptorchid boys, failures in germ cell development have been clearly established. Some studies reported some abnormalities in Sertoli cells morphology but the results regarding their endocrine secretion remain controversial. To compare testicular hormone levels in young boys with and without cryptorchidism, we performed a cross-sectional hospital-based study. From surgery appointment records, we identified a case group of boys with unilateral or bilateral cryptorchidism and a control group undergoing dental care, minor osteoarticular or dermal surgery. Blood samples were withdrawn during the surgical procedure to perform testosterone, inhibin B and anti-müllerian hormone (AMH) immunoassays. We included 27 cryptorchid boys and 27 controls aged of 26.6 vs. 24.2 months, respectively (p = 0.172) far from the post-natal mini-puberty and the corresponding hormonal surges. Age-adjusted AMH and inhibin B levels were significantly lower in cryptorchid than in control boys (AMH: 87 ng/mL vs. 135 ng/mL; p = 0.009, inhibin B: 97 pg/mL vs. 133 pg/mL; p = 0.019, respectively). Moreover, AMH and inhibin B levels were significantly lower in the bilateral cryptorchid subgroup, being 50% lower than in the controls (p = 0.011 and 0.019, respectively) and while both hormones levels were independent in controls, they became strongly correlated in bilateral cryptorchid boys (R² = 0.75, p = 0.001). In addition, testosterone levels were still detectable in some boys, with significantly lower levels in cryptorchid group than in controls. Overall, 2-year-old cryptorchid patients presented a simultaneous and significant drop in AMH and inhibin B levels, suggesting a functional defect of Sertoli cells. This deficiency appeared more pronounced in bilateral cryptorchidism and thus, regarding the pivotal role of Sertoli cells in germ cell development, it may explain the compromised fertility found later in men born with such a malformation.


A comparison of inflammatory mediators released by basophils of asthmatic and control subjects in response to high-affinity IgE receptor aggregation.
In human blood basophils, cross-linking the high-affinity IgE receptor Fc epsilonRI with multivalent antigen activates a signaling pathway leading to secretion of inflammatory mediators and cytokine production. Basophils are known to play an important role in the pathogenesis of asthma but there has been no comprehensive examination of the effectors these cells produce. Here a study of the transcription and release of a selection of chemokines and cytokines from basophils was undertaken. A Cartesian antibody array provided an effective method of assaying for multiple cytokines and chemokines simultaneously. Results were verified by RT-PCR and ELISA assays. This allowed the comparison of freshly prepared peripheral blood basophil responses to cross-linking of the high-affinity IgE receptor, with and without preincubation with IL-3. Evidence that human blood basophils produce the chemokines MIP-5, eotaxin and GM-CSF was provided by antibody array and RT-PCR analyses. Preincubation with IL-3 enhanced the expression and release of IL-13, IL-8 and mRNA transcripts encoding MIP-5 and GATA2 in basophils from both asthmatic and control subjects. Leptin mRNA transcription, storage and release in basophils are described for the first time. Surveying cytokine and chemokines stored and released by peripheral blood basophils shows that asthmatic and control subjects share similar profiles even when their degranulation responses are distinct. Evidence is provided for the production of leptin, GM-CSF, eotaxin and MIP-5 by peripheral blood basophils. IL-3 preincubation enhances the production and release of IL-8 upon IgE receptor cross-linking.


Perineural invasion as a prognostic risk factor in patients with early cervical cancer.
The aim of the present study was to investigate the influence of perineural invasion (PNI) on the prognosis of patients with early cervical cancer (stages IA2-IIA2). A retrospective analysis was conducted on 406 patients with early cervical cancer who underwent a radical hysterectomy and pelvic lymphadenectomy between January 2007 and December 2014 at the Affiliated Hospital of Jiangnan University (Wuxi, China). The clinicopathological data of the patients were obtained and follow-up assessments were performed. A statistical analysis of the association between PNI and each index was performed, and the effect of PNI and the clinicopathological parameters on the prognosis of the patients was evaluated. Among the 406 cases with early cervical cancer, 41 cases were lost, with a follow-up rate of 89.90%. Overall, 43 PNI-positive patients were observed, with an occurrence rate of 10.59%. PNI-positivity was associated with hypertension, lymph node metastasis, depth of cervical invasion, surgical margin and vascular invasion (P<0.05), but it was not associated with age, diabetes, clinical stage, histological type or tumor size (P>0.05). The overall survival (OS) and disease-free survival (DFS) times of PNI-positive patients were significantly lower compared with those of PNI-negative patients. A multivariate regression analysis revealed that age, tumor size, clinical stage and PNI were independent risk factors for OS and DFS times. PNI is a poor prognostic factor for patients with early cervical cancer.


The physiatrist as primary physician for patients on an inpatient rehabilitation unit.
Eighty-two patients admitted to a predominantly geriatric inpatient rehabilitation unit were followed throughout their stay in order to document their need for medical management. Their average age was 74.1 years and mean length of stay was 27.9 days. A total of 302 indications for medical intervention (3.7/patient) were found. In addition there were 2.8 medication changes/patient found when comparing admission to discharge medications, and 0.7 medications/patient prescribed for intercurrent illnesses. Actual documented loss of planned therapy time was found 21 times, involving 19 patients but exceeded 1 day in only six patients. Fifty-eight patients were ultimately discharged home, 14 were discharged to nursing homes (7 for social reasons), and 10 were transferred to an acute general hospital. Adverse drug reactions occurred in 27% of the patients and incidence rate paralleled the number of medications prescribed for the patient. This study indicates that the physiatrist on an inpatient rehabilitation unit must function as team manager or program director, and as the patient's primary physician. By managing medical problems effectively, the physician limits the loss of therapy time, thus shortening the length of stay and enabling the patient to continue to participate in his rehabilitation program.


Structures of dimeric human NPC1L1 provide insight into mechanisms for cholesterol absorption.
Polytopic Niemann-Pick C1-like 1 (NPC1L1) plays a major role in intestinal absorption of biliary cholesterol, vitamin E (VE), and vitamin K (VK). The drug ezetimibe inhibits NPC1L1-mediated absorption of cholesterol, lowering of circulating levels of low-density lipoprotein cholesterol. Here, we report cryo-electron microscopy structures of human NPC1L1 (hNPC1L1) bound to either cholesterol or a lipid resembling VE. These findings, together with functional assays, reveal that the same intramolecular channel in hNPC1L1 mediates transport of VE and cholesterol. hNPC1L1 exists primarily as a homodimer; dimerization is mediated by aromatic residues within a region of transmembrane helix 2 that exhibits a horizonal orientation in the membrane. Mutation of tryptophan-347 lies in this region disrupts dimerization and the resultant monomeric NPC1L1 exhibits reduced efficiency of cholesterol uptake. These findings identify the oligomeric state of hNPC1L1 as a target for therapies that inhibit uptake of dietary cholesterol and reduce the incidence of cardiovascular disease.


Afferents to the abducens nucleus in the monkey and cat.
The abducens nucleus is a central coordinating element in the generation of conjugate horizontal eye movements. As such, it should receive and combine information relevant to visual fixation, saccadic eye movements, and smooth eye movements evoked by vestibular and visual stimuli. To reveal possible sources of these signals, we retrogradely labeled the afferents to the abducens nucleus by electrophoretically injecting horseradish peroxidase into an abducens nucleus in four monkeys and two cats. The histologic material was processed by the tetramethyl benzidine (TMB) method of Mesulam. In both species the largest source of afferents to the abducens nucleus was bilateral projections from the ventrolateral vestibular nucleus and the rostral pole of the medial vestibular nucleus. Scattered neurons were also labeled in the middle and caudal levels of the medial vestibular nucleus. Large numbers of neurons were labeled in the ventral margin of the nucleus prepositus hypoglossi in the cat and in the common margin of the nucleus prepositus and the medial vestibular nucleus in the monkey, a region we call the marginal zone. Substantial numbers of retrogradely labeled neurons were found in the dorsomedial pontine reticular formation both caudal and rostral to the abducens nuclei. In the monkey, large numbers of labeled neurons were present in the contralateral medial rectus subdivision of the oculomotor complex, while smaller numbers occurred in the ipsilateral medial rectus subdivision and elsewhere in the oculomotor complex. In the cat, large numbers of retrogradely labeled cells were present in a small periaqueductal gray nucleus immediately dorsal to the caudal pole of the oculomotor complex, and a few labeled neurons were also dispersed through the caudal part of the oculomotor complex. Occasional labeled neurons were present in the contralateral superior colliculus in both species. The size and distribution of the labeled neurons within the intermediate gray differed dramatically in the two species. In the cat, the retrogradely labeled neurons were very large and occurred predominantly in the central region of the colliculus, while in the monkey, they were small to intermediate in size and were distributed more uniformly within the middle gray. Among the afferent populations present in the monkey, but not in the cat, was a group of scattered neurons in the ipsilateral rostral interstitial nucleus of the medial longitudinal fasciculus and a denser, bilateral population in the interstitial nucleus of Cajal.(ABSTRACT TRUNCATED AT 400 WORDS)


Mapping fermion and boson systems onto the Fock space of harmonic oscillators.
The fluctuation-dissipation theorem (FDT) is very general and applies to a broad variety of different physical phenomena in condensed matter physics. With the help of the FDT and following the famous work of Caldeira and Leggett, we show that, whenever linear response theory applies, any generic bosonic or fermionic system at finite temperature T can be mapped onto a fictitious system of free-harmonic oscillators. To the best of our knowledge, this is the first time that such a mapping is explicitly worked out. This finding provides further theoretical support to the phenomenological harmonic oscillator models commonly used in condensed matter. Moreover, our result helps in clarifying an interpretation issue related to the presence and physical origin of the Bose-Einstein factor in the FDT.


The evidence for a narrower thyrotropin reference range is compelling.
Debate and controversy currently surround the recommendations of a recent consensus conference that considered issues related to the management of early, mild, or so-called subclinical hypothyroidism and hyperthyroidism. Intimately related to the controversy is the definition of the normal reference range for TSH. It has become clear that previously accepted reference ranges are no longer valid as a result of both the development of more highly sensitive TSH assays and the appreciation that reference populations previously considered normal were contaminated with individuals with various degrees of thyroid dysfunction that served to increase mean TSH levels for the group. Recent laboratory guidelines from the National Academy of Clinical Biochemistry indicate that more than 95% of normal individuals have TSH levels below 2.5 mU/liter. The remainder with higher values are outliers, most of whom are likely to have underlying Hashimoto thyroiditis or other causes of elevated TSH. Importantly, data indicating that African-Americans with very low incidence of Hashimoto thyroiditis have a mean TSH level of 1.18 mU/liter strongly suggest that this value is the true normal mean for a normal population. Recognition and establishment of a more precise and true normal range for TSH have important implications for both screening and treatment of thyroid disease in general and subclinical thyroid disease in particular.


Colonic exclusion bypass principle: its use in the palliative treatment of malignant duodenocolic and gastrocolic fistulas.
Two patients with malignant upper gastrointestinal-to-colon fistulas had palliative operations utilizing the exclusion bypass principle. This principle entails isolating the affected portions of the colon from the remaining large intestine and anastomosing it to itself. Exclusion bypass reduces bacterial contamination of the upper tract (which is the important mechanism for the unrelenting diarrhea and malnutrition), eliminates prograde shunting, which can contribute to symptoms in malignant fistulas, and avoids the potential for closed-loop obstruction.


Psychiatric judgments across cultural contexts: relativist, clinical-ethnographic, and universalist-scientific perspectives.
Psychiatrists encounter persons from diverse cultures who profess experiences (e.g., communicating with spirits) that evoke intuitions of abnormality. This view might not be shared with the person or her/his cultural peers, raising questions concerning the justification of such intuitions. This article explores three positions relevant to the process of justification. The relativist position transfers powers of judgment to the subject's peers yet neglects individual values and operates with a discredited holistic view of culture. The clinical-ethnographic position remedies this by suspending judgment subject to understanding the individual in a sociocultural context yet finds objections with the universalist-scientific position: objective standards exist and could justify intuitions of abnormality cross-culturally. This article argues that the claim to objectivity is value-laden, reflecting instead a brand of normality and relationship to reality further upheld through epistemological utility and valued technological progress. In conclusion, it is suggested that the clinical-ethnographic position takes personal values and context seriously, both of which are crucial for responsible clinical practice.


Surgical treatment of kyphosis in children in healed stages of spinal tuberculosis.
Very less literature focuses on the treatment of kyphosis in healed stages of spinal tuberculosis (TB), especially in children. The purpose of this study was to evaluate the outcomes of anterior release, decompression, deformity correction, and instrumented fusion, followed by posterior osteotomy, deformity correction, and pedicle screw instrumented fusion, which is used to treat kyphosis in children in healed stages of spinal TB. Sixteen children with kyphotic deformity of the spine in healed stages of TB underwent anterior release, decompression, deformity correction, and instrumented fusion, followed by posterior osteotomy, deformity correction, and pedicle screw instrumented fusion between 2003 and 2007 with at least 2 years of follow-up. Radiologic assessment including the angle of kyphosis and scoliosis, and neurologic status using the modified Frankel grade were analyzed before surgery, after surgery, and at the last follow-up. Fusion was evaluated on flexion-extension lateral radiographs. Good cosmetic results were achieved in all patients. Neurologic improvement was shown in all 4 patients with paraplegia. The mean preoperative angle of kyphosis was 55.8 degrees that reduced to 21.7 degrees, postoperatively. The difference in the mean angle of kyphosis was statistically significant (P<0.05). The mean angle of kyphosis at the last follow-up was 23.2 degrees. The mean correction loss was 1.5 degree, and there was no statistically significant difference in the mean angles of kyphosis between the postoperative and last follow-up measurements. The mean preoperative angle of scoliosis was 6.9 degrees that reduced to 0.8 degree postoperatively. The difference in the mean angle of scoliosis was statistically significant (P<0.05). The mean angle of scoliosis at the last follow-up was 0.9 degree. The mean correction loss was 0.2 degree and there was no statistically significant difference in the mean angles of scoliosis between the postoperative and last follow-up measurements. All patients returning for follow-up had bony fusion. There were no cases of failure of fixation. Combined anterior and posterior osteotomy, deformity correction, and instrumented fusion halted progression of kyphosis and improved neurologic symptoms. Therapeutic-level IV, retrospective study.


Actinomyces europaeus Brain Abscess in a 69-Year-Old Female Causing Irreversible Neurologic Complications.
Actinomycosis is a chronic, indolent, granulomatous disease process caused by the Actinomyces genus of bacteria. More severe forms of actinomycosis include disseminated or central nervous system (CNS) infections. Actinomyces meyeri is the most common species of Actinomyces isolated from brain abscesses. A. europaeus species is commonly associated with skin and soft tissue abscesses. However, it rarely causes brain abscesses. We present an unusual case of A. europaeus brain abscess in a 69-year-old female who presented with acute encephalopathy and bilateral lower extremity weakness. She was diagnosed with left-sided mastoiditis with intracranial extension, left posterior fossa epidural abscess, and transverse sinus thrombosis. The patient's hospital course was complicated by hydrocephalus and declining neurological status. Empiric antimicrobial therapy was initiated, and the patient underwent mastoidectomy and external ventricular drain placement followed by decompression craniotomy and subarachnoid abscess aspiration. Given her poor and unchanged neurologic status, the patient was transitioned to comfort-oriented measures after shared decision-making with the family. It is crucial to identify Actinomyces as a causal agent of severe CNS infections like brain abscesses, meningoencephalitis, or subdural empyema, as untreated infections can lead to irreversible neurologic complications.


Effects of age, ethnicity and health behaviours on the prevalence of adverse birth outcomes in Taiwan.
This study sampled 8432 singleton first live births from Taiwan's 2005 Birth Registration Database to determine if there were more pre-term or low birth weight deliveries among aboriginal women than there were among Han Chinese women, and if the 'weathering' hypothesis applied to aboriginal women in Taiwan. Although the aboriginal women were socially disadvantaged and engaged in more unhealthy behaviours, including smoking, drinking, chewing betel quid and exposure to second-hand smoke, the evidence did not support the hypothesis that these teenaged minority women would have better birth outcomes, as has been demonstrated among teenage African-American women in the United States. Behaviours and not ethnicity were risk factors for teenage aboriginal mothers, who started deleterious health behaviours earlier than did their older counterparts. Teenage mothers had more adverse outcomes regardless of ethnicity and aboriginal mothers had more risky behaviours in all age groups. The prevalence of detrimental health behaviour among teenage mothers in Taiwan is of concern, particularly for aboriginal teenage mothers.


Detecting SARS-CoV-2 BA.2, BA.4, and BA.5 Variants Utilizing a Robust RT-RPA-CRISPR/Cas12a-Based Method - China, 2023.
Since 2019, numerous variants of concern for severe acute respiratory syndrome virus 2 (SARS-CoV-2) have emerged, leading to significant outbreaks. The development of novel, highly accurate, and rapid detection techniques for these new SARS-CoV-2 variants remains a primary focus in the ongoing efforts to control and prevent the coronavirus disease 2019 (COVID-19) pandemic. Reverse transcription-recombinase polymerase amplification combined with the clustered regularly interspaced short palindromic repeats-associated protein 12a (CRISPR/Cas12a) system was used to validate the detection of the Omicron BA.2, BA.4, and BA.5 variants of SARS-CoV-2. Our results demonstrate that the CRISPR/Cas12a assay is capable of effectively detecting the SARS-CoV-2 BA.2, BA.4, and BA.5 variants with a limit of detection of 10, 1, and 10 copies/μL, respectively. Importantly, our assay successfully differentiated the three SARS-CoV-2 Omicron strains from one another. Additionally, we evaluated 46 SARS-CoV-2 positive clinical samples consisting of BA.2 (n=20), BA.4 (n=6), and BA.5 (n=20) variants, and the sensitivity of our assay ranged from 90% to 100%, while the specificity was 100%. This research presents a swift and reliable CRISPR-based method that may be employed to track the emergence of novel SARS-CoV-2 variants.


Predicting embryonic aneuploidy rate in IVF patients using whole-exome sequencing.
Infertility is a major reproductive health issue that affects about 12% of women of reproductive age in the United States. Aneuploidy in eggs accounts for a significant proportion of early miscarriage and in vitro fertilization failure. Recent studies have shown that genetic variants in several genes affect chromosome segregation fidelity and predispose women to a higher incidence of egg aneuploidy. However, the exact genetic causes of aneuploid egg production remain unclear, making it difficult to diagnose infertility based on individual genetic variants in mother's genome. In this study, we evaluated machine learning-based classifiers for predicting the embryonic aneuploidy risk in female IVF patients using whole-exome sequencing data. Using two exome datasets, we obtained an area under the receiver operating curve of 0.77 and 0.68, respectively. High precision could be traded off for high specificity in classifying patients by selecting different prediction score cutoffs. For example, a strict prediction score cutoff of 0.7 identified 29% of patients as high-risk with 94% precision. In addition, we identified MCM5, FGGY, and DDX60L as potential aneuploidy risk genes that contribute the most to the predictive power of the model. These candidate genes and their molecular interaction partners are enriched for meiotic-related gene ontology categories and pathways, such as microtubule organizing center and DNA recombination. In summary, we demonstrate that sequencing data can be mined to predict patients' aneuploidy risk thus improving clinical diagnosis. The candidate genes and pathways we identified are promising targets for future aneuploidy studies.


Efficacy and safety of octreotide for the treatment of congenital hyperinsulinism: a prospective, open-label clinical trial and an observational study in Japan using a nationwide registry.
Octreotide, a long-acting somatostatin analog, has been used for treating hypoglycemia caused by congenital hyperinsulinism (CHI). However, octreotide has not been evaluated in clinical trials and has not been approved in any developed country. We aimed to test the efficacy and safety of octreotide for diazoxide-unresponsive CHI through a combination of a single-arm, open-label clinical trial (SCORCH study) and an observational study to collect data on the clinical course of patients treated off-label in Japan (SCORCH registry). In the SCORCH study, 5 patients were stabilized (blood glucose > 45 mg/dL) by hypertonic glucose infusion, and treated by continuous subcutaneous octreotide infusion at a dose of 5-25 μg/kg/day. Continuous blood glucose monitoring was performed between -24 and +48 hours. In 3 patients, a clinically meaningful rise in blood glucose was achieved and therapy was continued. The glucose infusion was gradually decreased and stopped after 5, 11, and 174 days, respectively. In one case, remission of CHI was reached after 606 days and octreotide was discontinued. The SCORCH registry included 19 diazoxide-unresponsive patients treated by subcutaneous octreotide, by continuous infusion or multiple daily injections. Of the 17 patients treated with hypertonic glucose infusion, the infusion rate was reduced after 4 weeks to less than 50% in 11 patients (64.7%) and stopped in 9 (52.9%). During the combined observation period of 695.4 patient-months in both studies, no severe adverse events related to octreotide were observed. In conclusion, subcutaneous octreotide injection was effective and well tolerated in the majority of patients with diazoxide-unresponsive CHI.