Interrupted Morita-Baylis-Hillman-Type Reaction of α-Substituted Activated Olefins.
It was demonstrated that 3-olefinic oxindoles could generate zwitterionic enolate species with tertiary phosphines and undergo C-C bond formation with various electrophiles in an interrupted Morita-Baylis-Hillman-type reaction manner, followed by a dephosphoration process. Although the in situ formation of phosphorus-ylide intermediates was observed, no Wittig reaction was detected, even in the presence of excess formaldehyde. Moreover, excellent enantioselectivity for the construction of quaternary stereogenic centers was induced with chiral phosphines. Deuterium experiments and density functional theory calculations were conducted to elucidate the reaction mechanism.


Lorentz-like force emerging from kinematic interactions between electrons and nuclei in molecules: A quantum mechanical origin of symmetry breaking that can trigger molecular chirality.
The Longuet-Higgins (Berry) phase arising from nonadiabatic dynamics and the Aharonov-Bohm phase associated with the dynamics of a charged particle in the electromagnetic vector potential are well known to be individually a manifestation of a class of the so-called geometrical phase. We herein discuss another similarity between the force working on a charged particle moving in a magnetic field, the Lorentz force, and a force working on nuclei while passing across a region where they have a strong quantum mechanical kinematic (nonadiabatic) coupling with electrons in a molecule. This kinematic force is indeed akin to the Lorentz force in that its magnitude is proportional to the velocity of the relevant nuclei and works in the direction perpendicular to its translational motion. Therefore this Lorentz-like nonadiabatic force is realized only in space of more or equal to three dimensions, thereby highlighting a truly multi-dimensional effect of nonadiabatic interaction. We investigate its physical significance qualitatively in the context of breaking of molecular spatial symmetry, which is not seen otherwise without this force. This particular symmetry breaking is demonstrated in application to a coplanar collision between a planar molecule and an atom sharing the same plane. We show that the atom is guided by this force to the direction out from the plane, resulting in a configuration that distinguishes one side of the mirror plane from the other. This can serve as a trigger for the dynamics towards molecular chirality.


Ethical decision making in the conduct of research: role of individual, contextual and organizational factors. Commentary on "Science, human nature, and a new paradigm for ethics education".
Despite the importance of scientific integrity to the well-being of society, recent findings suggest that training and mentoring in the responsible conduct of research are not very reliable or effective inhibitors of research misbehavior. Understanding how and why individual scientists decide to behave in ways that conform to or violate norms and standards of research is essential to the development of more effective training programs and the creation of more supportive environments. Scholars in business management, psychology, and other disciplines have identified many important factors that affect ethical behavior, including individual, contextual, and organizational factors. Surprisingly little research has been conducted to examine the role of these factors in either the development of ethical decision-making skills, or their applicability to ethical issues commonly encountered in research and other scholarly and professional activities. Interdisciplinary approaches combined with research and discipline relevant paradigms should greatly enhance understanding of the individual contextual and organizational factors involved in ethical and unethical research conduct. Such studies will inform and facilitate the development of more effective ethics education programs in the sciences and engineering professions.


NCAA strength and conditioning coach demographics, current practice trends and common injuries of athletes during strength and conditioning sessions.
NCAA strength and conditioning coaches are responsible for the day-to-day conditioning and strength training of collegiate athletes. NCAA regulations will likely require all strength and conditioning coaches to have a strength and conditioning certification. NCAA strength and conditioning coaches have varied philosophies on exercise programming based on educational background. The study aims to further evaluate the backgrounds and exercise philosophies of NCAA strength and conditioning coaches. A survey (Survey Monkey®, Palo Alto, CA, USA) was distributed to NCAA strength and conditioning professionals to evaluate their education background, current practice trends, use of specific equipment and footwear, and what injuries occurred during sessions. Of the 208 survey participants, 77.9% were male with an average age of 34.5±9.1 years old. An exercise-related bachelor's degree was held by 80.4% and an exercise-related master's degree by 72.4%. Over 89% had a strength and conditioning certification. Having a master's, bachelor's, or type strength and conditioning certification had no difference in 1-repetition maximal practice with athletes. Lower extremity injuries made up the highest percentage (58.9%) of injuries seen by NCAA Strength and Conditioning Coaches than lumbar spine injuries (16.7%). The five most common injuries reported during workouts were lumbar strain (N.=431, 14.7%), hamstring strain (N.=332, 11.3%), ankle sprain (N.=299, 10.2%), patellar tendonitis (N.=232, 7.9%), and shin splints (N.=226, 7.7%). Collegiate education and certifications have impact on practice patterns of strength and conditioning coaches in the NCAA.


A 3-year magnetic resonance imaging study of cortical lesions in relapse-onset multiple sclerosis.
We assessed the occurrence, extent, and frequency of formation of cortical lesions (CLs) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS), and their relationship with cortical atrophy and disability progression. One-hundred seven MS patients (76 RRMS and 31 SPMS), enrolled in a prospective, longitudinal magnetic resonance imaging (MRI) study, were assessed clinically and by brain MRI (including a double inversion recovery sequence) 3 years after study initiation. CL number and volume, T2 white matter (WM) lesion volume, gray matter fraction, and expanded disability status scale (EDSS) were measured. At baseline, CLs were detected in 64.4% of RRMS and 74.2% of SPMS patients. During follow-up, 132 new CLs were found in 44 RRMS patients (57.9%; 0.8 new CL/patient/yr) and 61 in 15 SPMS patients (48.4%; 1.0 new CL/patient/yr). Among these patients, only 31 also showed at least 1 new WM lesion. CL number and volume increases were higher in the 52 patients with a clinical worsening compared with those without (p < 0.001). Baseline CL volume correlated with baseline EDSS (r = 0.36, p < 0.001) and EDSS changes over time (r = 0.51, p < 0.001). Baseline CL volume was an independent predictor of EDSS accumulation and GM volume change at follow-up in both patient groups. In SPMS patients, baseline T2 WM lesion volume was another independent predictor of EDSS worsening. In relapse-onset MS, CLs accumulate over time and are associated with disability progression. The quantification of CLs might represent an additional useful paraclinical tool to monitor MS evolution.


Technique for sampling subcutaneous fat from the tailhead of sheep.
Previously reported fat biopsy techniques (either omental or subcutaneous) require extensive restraint of the animal, require anesthesia methods, are time-consuming to do, or demand much postoperative care. The biopsy technique reported in the present paper involves the subcutaneous fat located around the tailhead of sheep. With minimal restraint of the sheep and local anesthesia, up to 1 g of subcutaneous fat can be obtained using this surgical procedure. Michel clips facilitate closure of the surgical wound, making this method brief in operative time.


The contribution of smoking to sex differences in mortality.
The contribution of smoking to sex differences in mortality is estimated on the basis of data from 12 studies of the mortality of nonsmoking men and women, together with mortality data for comparable general population samples. Most of the data are for samples drawn from the U.S. population from the late 1950s to 1980. The findings from different studies are generally consistent, once methodological factors are taken into account. The findings indicate that, for total mortality, the proportion of sex differences attributable to smoking decreases from about two-thirds at age 40 to about one-quarter at age 80. Over the adult age span, it appears that about half of the sex difference in total mortality is attributable to smoking. Findings for ischemic heart disease mortality show a similar pattern. For lung cancer, it appears that about 90 percent of the sex difference in mortality is attributable to smoking. The estimated contributions of smoking include both the effects of sex differences in smoking habits and the effects of sex differences in the increase in mortality caused by smoking. The quantitative results should be interpreted with caution, since several lines of argument suggest that multivariate analyses controlling for other relevant factors would produce lower estimates of the contribution of smoking to sex differences in mortality. Despite this limitation, the findings analyzed in this review, together with additional evidence from related research, strongly support the conclusion that cigarette smoking makes a major contribution to men's higher mortality, but other factors also play an important role.


Adaptation and Validation of the Rapid Estimate of Adult Literacy in Dentistry for Chilean Population.
To adapt and validate the Rapid Estimate of Adult Literacy in Dentistry (REALD-30) for the Chilean population. REALD-30 was translated to Spanish, piloted, and revised by experts. Demographics, oral health status, oral health-related quality of life, and health literacy were analyzed. Summary measures, internal consistency, reliability, and convergent and predictive validity were calculated. Cronbach's alpha was 0.876, intra-class correlation coefficient was 0.789 for reliability, Pearson´s and Spearman´s correlations were ≥0.693 for convergent validity, and <= *-0.138 for predictive validity. REALD-30 is a valid and reliable instrument to measure oral health literacy in the Chilean population.


Robust Coatings via Catechol-Amine Codeposition: Mechanism, Kinetics, and Application.
Bioinspired polyphenol/polyamine codeposition has been demonstrated by the competence for surface modification; however, the reaction processes including mechanism and kinetics remain superficially understood. In this work, the catechol (CA)-amine reaction has been thoroughly investigated by using CA and two amines m-phenylenediamine and piperazine. We verify that both primary and secondary amines are prone to link with CA through Michael addition to form polyphenol/polyamine oligomers under aerobic and mild-alkaline conditions. Molecular simulations indicate that the Michael addition products are dominant for both aromatic and aliphatic amines with CA, which supports the durable chem- and phystability of the codeposited coatings. The aggregation kinetics of polyphenol/polyamine is provided for the first time, and the formed aggregates show high-adhesive properties, which can be deposited as the skin layers for high-performance nanofiltration membranes.


Long-term clinical outcome of transurethral microwave thermotherapy (TUMT) 1991-1999 at Karolinska Hospital, Sweden.
Minimal invasive methods, such as transurethral microwave thermotherapy (TUMT), are economical and have modest side effects compared with transurethral electro-resection of the prostate (TUR-P). The treatment results from different TUMT-systems vary. Follow-up studies on each system type are therefore necessary. The objectives of this study are to summon the long-term clinical results of our TUMT-system and search for a pre-treatment parameter that can measure responding patients. Three hundred and seventy-one patients with benign prostate hyperplasia (BPH) were treated with TUMT at Karolinska Hospital, Sweden with the ECP-system (Comair AB, Stockholm), for 30 or 60 min. They were followed up 12 to 72 months after TUMT. At follow up approximately 76% subjectively judged that they had benefited from the treatment and 22% judged that they were fully cured. The over-all IPSS and Quality of Life score decreased approximately 40% and 30% respectively. Forty-one per cent of the patients with CAD (cathéter à demeure) before the treatment became permanently or temporarily catheter-free after the treatment. Q(max) increased 21% and 11% after 1 and 6 months respectively. Q(max) ranging from over 10 ml/s seem to be a selection parameter that increases the number of responding patients. These long-term clinical data show that TUMT treatment with ECP (electro-coagulation, prostate), gives a good success-rate, with reduction of symptoms. Furthermore there is a good chance of becoming catheter-free after TUMT.


Synthesis and characterization of an A2BC type phthalocyanine and its visible-light-responsive photocatalytic H2 production performance on graphitic carbon nitride.
A highly asymmetric A2BC type zinc phthalocyanine (Zn-di-PcNcTh) has been designed and synthesized. The Zn-di-PcNcTh used a π electron rich thiophene ring in place of the benzenoid rings of phthalocyanine which acted as an electron donor, diphenylphenoxy substituents to retard aggregation and a carboxyl-naphthalene unit as an electron acceptor. The asymmetric phthalocyanine shows a strongly split Q-band and wide spectral absorption in the visible/near-IR light region, which can extend the spectral response region of graphitic carbon nitride (g-C3N4) from ∼450 nm to more than 800 nm. By using it as a sensitizer of 1.0 wt% Pt-loaded graphitic carbon nitride (g-C3N4), the experimental results indicate that Zn-di-PcNcTh-Pt/g-C3N4 shows a H2 production efficiency of 249 μmol h(-1) with an impressive turnover number (TON) of 9960.8 h(-1) under visible light (λ≥ 420 nm) irradiation, much higher than that of pristine Pt/g-C3N4. Owing to the introduction of a highly bathochromic shift of 3,4-dicyanothiophene and the valuable "push-pull" effect from the thiophene (electron donor) to the carboxyl-naphthalene (electron acceptor) unit, Zn-di-PcNcTh/g-C3N4 gives an extremely high apparent quantum yield (AQY) of 2.44%, 3.05%, and 1.53% under 700, 730, and 800 nm monochromatic light irradiation, respectively, under optimized photocatalytic conditions.


Hybridoma antibodies against protective and nonprotective antigenic determinants of a structurally defined polypeptide fragment of streptococcal M protein.
Hybridoma technology was used to produce a set of monoclonal antibodies against a purified polypeptide fragment of type 24 streptococcal M protein to delineate the protective determinants of M protein exposed on the surface of the virulent streptococci. Several hybridoma antibodies were found to be opsonic against the homologous type streptococci. At least two of these antibodies (IIC3.7 and IIC4.6) protected mice against challenge infections with the homologous, but not a heterologous, serotype of bacteria. One of the hybridoma antibodies that reacted in high dilution (1:204,800) with the isolated M protein failed to react with the M protein on the surface of type 24 streptococci, and thus did not opsonize the homologous organisms or protect mice against challenge infections. Because hybridoma antibodies are directed against a single distinct immunodeterminant, these results indicate that protective immunity may be directed at any one of several distinct antigenic determinants of M protein exposed on the surface of virulent group A streptococci.


Specialization patterns in symbiotic associations: A community perspective over spatial scales.
Specialization, contextualized in a resource axis of an organism niche, is a core concept in ecology. In biotic interactions, specialization can be determined by the range of interacting partners. Evolutionary and ecological factors, in combination with the surveyed scale (spatial, temporal, biological, and/or taxonomic), influence the conception of specialization. This study aimed to assess the specialization patterns and drivers in the lichen symbiosis, considering the interaction between the principal fungus (mycobiont) and the associated Nostoc (cyanobiont), from a community perspective considering different spatial scales. Thus, we determined Nostoc phylogroup richness and composition of lichen communities in 11 Nothofagus pumilio forests across a wide latitudinal gradient in Chile. To measure specialization, cyanobiont richness, Simpson's and d' indices were estimated for 37 mycobiont species in these communities. Potential drivers that might shape Nostoc composition and specialization measures along the environmental gradient were analysed. Limitations in lichen distributional ranges due to the availability of their cyanobionts were studied. Turnover patterns of cyanobionts were identified at multiple spatial scales. The results showed that environmental factors shaped the Nostoc composition of these communities, thus limiting cyanobiont availability to establish the symbiotic association. Besides, specialization changed with the spatial scale and with the metric considered. Cyanolichens were more specialized than cephalolichens when considering partner richness and Simpson's index, whereas the d' index was mostly explained by mycobiont identity. Little evidence of lichen distributional ranges due to the distribution of their cyanobionts was found. Thus, lichens with broad distributional ranges either associated with several cyanobionts or with widely distributed cyanobionts. Comparisons between local and regional scales showed a decreasing degree of specialization at larger scales due to an increase in cyanobiont richness. The results support the context dependency of specialization and how its consideration changes with the metric and the spatial scale considered. Subsequently, we suggest considering the entire community and widening the spatial scale studied as it is crucial to understand factors determining specialization.


Histopathologic study of the so called 'palpation thyroiditis'.
We have reviewed 1066 thyroid lesions and compared the relative incidence of the so called 'palpation thyroiditis' between autoimmune thyroiditis and normal thyroid parenchyme surrounding the nodular thyroid lesion and also discussed the pathogenesis of palpation thyroiditis. The typical histopathologic features of 'palpation thyroiditis' were seen in 275 cases among 467 adenomatous goiters and in none of the autoimmune thyroiditis. We here in this paper suggest that the so called 'palpation thyroiditis' is not merely a secondary phenomenon to mechanical follicular damage by vigorous palpation, but this lesion more likely develops in conditions where certain types of physiologic alteration has occurred in follicular basement membrane, just like a pathogenesis of subacute granulomatous thyroiditis.


[Locomotive syndrome: from paradigms to clinical reality].
Locomotive syndrome is an unsatisfactory condition of patients over 60 years of age who need or may require outside help in the near future due to functional deterioration of the musculoskeletal system, including pathology of bone tissue, joints, muscles and nervous tissue. In real clinical practice, one often has to deal with the following manifestations of locomotive syndrome: osteoarthritis, sarcopenia, balance disorders, chronic musculoskeletal pain. Today, there is a clear understanding that drug therapy should be long-term, include comprehensive support for muscle tissue, balance training, and mandatory cognitive-behavioral therapy. Maximum safety of long-term drug therapy can be ensured by the use of vital micronutrients, which include highly purified forms of chondroitin sulfate and glucosamine sulfate, which have a wide range of anti-inflammatory and regenerative effects.


Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster.
The ratio of noncoding to protein coding DNA rises with the complexity of the organism, culminating in nearly 99% of nonprotein coding DNA in humans. Nevertheless, a large portion of these regions is transcribed, creating the alleged paradox that noncoding RNA (ncRNA) represents the largest output of the human genome. Such a complex scenario may include epigenetic mechanisms where ncRNAs would be involved in chromatin regulation. We have investigated the intergenic, noncoding transcriptomes of mammalian HOX clusters. We show that "opposite strand transcription" from the intergenic spacer regions in the human HOXA cluster correlates with the activity state of adjacent HOXA genes. This noncoding transcription is regulated by the retinoic acid morphogen and follows the colinear activation pattern of the cluster. Opening of the cluster at sites of activation of intergenic transcripts is accompanied by changes in histone modifications and a loss of interaction with Polycomb group (PcG) repressive complexes. We propose that noncoding transcription is of fundamental importance for the opening and maintenance of the active state of HOX clusters.


Swyer-James syndrome--unilateral hyperlucent lung syndrome. A case report and review.
Swyer-James syndrome is a pulmonary condition acquired following bronchiolitis obliterans early in life. Clinically characterized by repeated bouts of pulmonary infections, Swyer-James syndrome is characterized radiographically by a unilateral small, hyperlucent lung that demonstrates diminished arterial supply to the involved lung, air-trapping, and bronchiectasis. Radioimaging procedures may reveal otherwise unsuspected bilateral involvement. A 14-year-old Caucasian female with classic findings of Swyer-James syndrome is presented. The differential diagnosis of conditions that may present with a unilateral hyperlucent lung is discussed. Therapy is aimed primarily at control of the intercurrent episodes of bacterial pneumonia.


[Treatment of the shoulder-hand or algoneurodystrophy syndrome (author's transl)].
The pathogenicity of the shoulder-hand or algoneurodystrophy syndrome of the upper limb remains obscure and treatment in these conditions presents many difficulties. Tiapride was found to reduce pain and allow more effective physiotherapy to be applied with a more rapid return to work.


Myelofibrosis: a concise review of clinical and pathologic features and treatment.
This paper reviews and clarifies the current understanding of the clinical and pathologic features and treatment of MF. Recent investigations indicate that MF may be mediated by platelet- and megakaryocyte-derived growth factors, impaired prostaglandin-mediated stem cell growth inhibition, or excessive endothelial cell and fibroblast proliferation. Immunologic disorders have been associated with MF. MF may be either a primary or a secondary phenomenon. Secondary MF often regresses with appropriate treatment of this underlying disorder. Primary MF may require androgen therapy, splenectomy, splenic irradiation, bone curettage, chemotherapy, or bone marrow transplantation.


Designing Self-Healing Superhydrophobic Surfaces with Exceptional Mechanical Durability.
The past decade saw a drastic increase in the understanding and applications of superhydrophobic surfaces (SHSs). Water beads up and effortlessly rolls off a SHS due to its combination of low surface energy and texture. Whether being used for drag reduction, stain repellency, self-cleaning, fog harvesting, or heat transfer applications (to name a few), the durability of a SHS is critically important. Although a handful of purportedly durable SHSs have been reported, there are still no criteria available for systematically designing a durable SHS. In the first part of this work, we discuss two new design parameters that can be used to develop mechanically durable SHSs via the spray coating of different binders and fillers. These parameters aid in the rational selection of material components and allow one to predict the capillary resistance to wetting of any SHS from a simple topographical analysis. We show that not all combinations of sprayable components generate SHSs, and mechanically durable components do not necessarily generate mechanically durable SHSs. Moreover, even the most durable SHSs can eventually become damaged. In the second part, utilizing our new parameters, we design and fabricate physically and chemically self-healing SHSs. The most promising surface is fabricated from a fluorinated polyurethane elastomer (FPU) and the extremely hydrophobic small molecule 1H,1H,2H,2H-heptadecafluorodecyl polyhedral oligomeric silsesquioxane (F-POSS). A sprayed FPU/F-POSS surface can recover its superhydrophobicity even after being abraded, scratched, burned, plasma-cleaned, flattened, sonicated, and chemically attacked.


Strain-Driven Formal [1,3]-Aryl Shift within Molecular Bows.
Delving into the influence of strain on organic reactions in small molecules at the molecular level can unveil valuable insight into developing innovative synthetic strategies and structuring molecules with superior properties. Herein, we present a molecular-strain engineering approach to facilitate the consecutive [1,2]-aryl shift (formal [1,3]-aryl shift) in molecular bows (MBs) that integrate 1,4-dimethoxy-2,5-cyclohexadiene moieties. By introducing ring strain into MBs through tethering the bow limb, we can harness the intrinsic mechanical forces to drive multistep aryl shifts from the para- to the meta- to the ortho-position. Through the use of precise intramolecular strain, the seemingly impractical [1,3]-aryl shift was realized, resulting in the formation of ortho-disubstituted products. The solvent and temperature play a crucial role in the occurrence of the [1,3]-aryl shift. The free energy calculations with inclusion of solvation support a feasible mechanism, which entails multistep carbocation rearrangements, for the formal [1,3]-aryl shift. By exploring the application of molecular strain in synthetic chemistry, this research offers a promising direction for developing new tools and strategies towards precision organic synthesis.


A novel derivative of decursin, CSL-32, blocks migration and production of inflammatory mediators and modulates PI3K and NF-κB activities in HT1080 cells.
Decursin and related coumarin compounds in herbal extracts have a number of biological activities against inflammation, angiogenesis and cancer. We have analysed a derivative of decursin (CSL-32) for activity against inflammatory activation of cancer cells, such as migration, invasion and expression of pro-inflammatory mediators. The human fibrosarcoma cell line, HT1080, was treated with TNFα (tumour necrosis factor α) in the presence or absence of CSL-32. The cellular responses and modification of signalling adapters were analysed with respect to the production of pro-inflammatory mediators, as also migration, adhesion and invasion. Treatment of HT1080 cells with CSL-32 inhibited their proliferation, without affecting cell viability, and TNFα-induced expression of pro-inflammatory mediators, such as MMP-9 (matrix metalloproteinase-9) and IL-8 (interleukin-8). CSL-32 also suppressed phosphorylation and degradation of IκB (inhibitory κB), phosphorylation of p65 subunit of NF-κB (nuclear factor-κB) and nuclear translocation of NF-κB, which are required for the expression of pro-inflammatory mediators. In addition, CSL-32 inhibited invasion and migration of HT1080 cells, as also cellular adhesion to fibronectin, an ECM (extracellular matrix) protein. CSL-32 treatment resulted in a dose-dependent inhibition of PI3K (phosphoinositide 3-kinase) activity, required for the cellular migration. The analyses show that CSL-32 inhibits processes associated with inflammation, such as the production of pro-inflammatory mediators, as well as adhesion, migration and invasion in HT1080 cells.


Surface-induced molecular tilt above the smectic-A-smectic-C phase transition in a nonchiral liquid crystal.
A polyimide-coated substrate was rubbed in such a way as to possess two competing easy axes for liquid crystal alignment. On cooling a homeotropically aligned liquid crystal through the smectic-A phase toward the smectic-C phase transition, an increasing tilt of the molecules relative to the layer normal was observed. The tilt was localized to within a smectic-C correlation length of the interface, and was found to increase monotonically with the rubbing strength associated with the preparation of the polyimide surface. The results are discussed in light of the dual easy axis model [T. Shioda et al., Phys. Rev. E 67, 041706 (2003)], and suggest that the two easy axes are not mutually orthogonal.


[The association between the DNA marker rs1842993 and risk for cardioembolic stroke in the Slavic population].
The analysis of association between DNA markers and total stroke risk was performed in 950 Slavonic patients. Patients with cardioembolic stroke were selected for a genome-wide association study. The HUMANCYTOSNP12 v.2 microchip was used to analyze all DNA samples on a panel of 301 000 single nucleotide polymorphisms. SNP rs1842993 on chromosome 7 was found to be associated with cardioembolic stroke risk.


Livestock disease threats associated with intensification of pastoral dairy farming.
This paper provides an overview of the changes in the pasture-based dairy systems of New Zealand and Australia that may influence the health of cattle. There are relatively few available data that can be used to quantify the effects of increased intensification of milk production on the health of cattle. There is evidence that increased production increases the risk of mastitis and culling for udder health. Increased risks of mastitis with treatment with somatotropin support these findings; however, the risk of mastitis may decrease with increased milking frequency. Larger herds with greater stocking density should increase the risk for infectious disease, but evidence to support this contention is sparse. Very intensive grazing patterns associated with higher grass yields achieved using better cultivars and greater use of fertilisers favour nematode parasites. There is some evidence of anthelmintic resistance in both nematodes and liver fluke. Veterinarians will need to be aware of the potential for these to reduce the productivity of cattle. There have been benefits of improved nutrition on the efficiency of energy use for dairy production. Diseases such as bloat and ketosis appear to be of lower prevalence. It also appears that mineral nutrition of pasture-fed cattle is being better addressed, with gains in the control of milk fever, hypomagnesaemia and trace-element deficiencies. However, acidosis is a condition with a high point prevalence in pasture-based dairy systems where cows are fed supplements; one study in Australia found a point prevalence of approximately 11% of cows with acidosis. There is evidence from this study that the neutral detergent fibre (NDF) in pasture-based diets may need to be higher than 30% of the diet to maintain rumen stability. Laminitis and acidosis are different conditions with a similar pathogenesis, specifically highly fermentable diets. The prevalence of lameness was 28% in herds in Australia, suggesting that this condition must be a focus for preventive medical approaches, including the design of laneways, feed pads and dairies.


Evaluation of prenatal care in unit with family health strategy.
We analyzed prenatal care (PN) provided at a unit of the Family Health Strategy Service in São Paulo, according to the indicators of the Program for the Humanization of Prenatal and Birth (PHPB). We compared adequacy of PN in terms of sociodemographic variables, procedures, examinations and maternal and perinatal outcomes. Cross-sectional study with data from records of 308 pregnant women enrolled in 2011. We observed early initiation of PN (82.1%), conducting of a minimum of six consultations (84.1%), puerperal consultation (89.0%); to the extent that there is a sum of the actions, there is a significant drop in the proportion of adequacy. Prenatal care was adequate for 67.9%, with a significant difference between adequacy groups in relation to gestational age and birth weight. Prenatal care deficiencies exist, especially in regards to registration of procedures, exams and immunization. The difference between adequacy groups with respect to perinatal outcomes reinforces the importance of prenatal care that adheres to the parameters of the PHPB.


Pulsed-field gel electrophoresis used to investigate genetic diversity of Haemophilus influenzae type b isolates in Australia shows differences between Aboriginal and non-Aboriginal isolates.
We used pulsed-field gel electrophoresis to study the epidemiology and population structure of Haemophilus influenzae type b. DNAs from 187 isolates recovered between 1985 and 1993 from Aboriginal children (n = 76), non-Aboriginal children (n = 106), and non-Aboriginal adults (n = 5) in urban and rural regions across Australia were digested with the SmaI restriction endonuclease. Patterns of 13 to 17 well-resolved fragments (size range, approximately 8 to 500 kb) defining 67 restriction fragment length polymorphism (RFLP) types were found. Two types predominated. One type (n = 37) accounted for 35 (46%) of the isolates from Aboriginals and 2 (2%) of the isolates from non-Aboriginals, and the other type (n = 41) accounted for 2 (3%) of the isolates from Aboriginals and 39 (35%) of the isolates from non-Aboriginals. Clustering revealed seven groups at a genetic distance of approximately 50% similarity in a tree-like dendrogram. They included two highly divergent groups representing 50 (66%) isolates from Aboriginals and 6 (5%) isolates from non-Aboriginals and another genetically distinct group representing 7 (9%) isolates from Aboriginals and 81 (73%) isolates from non-Aboriginals. The results showed a heterogeneous clonal population structure, with the isolates of two types accounting for 42% of the sample. There was no association between RFLP type and the diagnosis of meningitis or epiglottitis, age, sex, date of collection, or geographic location, but there was a strong association between the origin of isolates from Aboriginal children and RFLP type F2a and the origin of isolates from non-Aboriginal children and RFLP type A8b. The methodology discriminated well among the isolates (D = 0.91) and will be useful for the monitoring of postvaccine isolates of H. influenzae type b.


Nanochemistry and nanomaterials for photovoltaics.
Nanochemistry and nanomaterials provide numerous opportunities for a new generation of photovoltaics with high solar energy conversion efficiencies at low fabrication cost. Quantum-confined nanomaterials and polymer-inorganic nanocomposites can be tailored to harvest sun light over a broad range of the spectrum, while plasmonic structures offer effective ways to reduce the thickness of light-absorbing layers. Multiple exciton generation, singlet exciton fission, photon down-conversion, and photon up-conversion realized in nanostructures, create significant interest for harvesting underutilized ultraviolet and currently unutilized infrared photons. Nanochemical interface engineering of nanoparticle surfaces and junction-interfaces enable enhanced charge separation and collection. In this review, we survey these recent advances employed to introduce new concepts for improving the solar energy conversion efficiency, and reduce the device fabrication cost in photovoltaic technologies. The review concludes with a summary of contributions already made by nanochemistry. It then describes the challenges and opportunities in photovoltaics where the chemical community can play a vital role.


Spherical Image Generation From a Few Normal-Field-of-View Images by Considering Scene Symmetry.
Spherical images taken in all directions (360 degrees by 180 degrees) can represent an entire space including the subject, providing free direction viewing and an immersive experience to viewers. It is convenient and expands the usage scenarios to generate a spherical image from a few normal-field-of-view (NFOV) images, which are partial observations. The primary challenge is generating a plausible image and controlling the high degree of freedom involved in generating a wide area that includes all directions. We focus on scene symmetry, which is a basic property of the global structure of spherical images, such as the rotational and plane symmetries. We propose a method for generating a spherical image from a few NFOV images and controlling the generated regions using scene symmetry. We incorporate the intensity of the symmetry as a latent variable into conditional variational autoencoders to estimate the possible range of symmetry and decode a spherical image whose features are represented through a combination of symmetric transformations of the NFOV image features. Our experiments show that the proposed method can generate various plausible spherical images controlled from asymmetrically to symmetrically, and can reduce the reconstruction errors of the generated images based on the estimated symmetry.


[Emergency obstetrical hysterectomy].
Hysterectomy on pregnant uterus is a mutilating procedure used by obstetrician only when he haven't choice in case of major complications of pregnancy or delivery. This retrospective study worked on 35 cases of obstetrical hysterectomy performed on 22 months period (January 94-October 95). The frequency of the procedure among all the in hospital deliveries was 0.45%. The mean age of the patients was 31 years, and the mean parity was 7. 77.5% of the women were referred from over surrounding hospitals where natural deliveries had failed. We performed the hysterectomy because of uncontrolled haemorrhage in 71.7%, and infection in 25.8%. Sub-total hysterectomy was performed in 82.8%. Maternal mortality was 20%. Hysterectomy is very mutilating, but is a life rescueing procedure behind a lifethreatening complication of pregnancy or delivery. The best strategy to prevent the necessity of hysterectomy, is to develop the early obstetrical reference program that unfortunately is not yet in practice in our health care system.


Distributed Generalized Nash Equilibrium Seeking for Monotone Generalized Noncooperative Games by a Regularized Penalized Dynamical System.
In this work, we study the generalized Nash equilibrium (GNE, see Definition 1) seeking problem for monotone generalized noncooperative games with set constraints and shared affine inequality constraints. A novel projected gradient-based regularized penalized dynamical system is proposed to solve this issue. The idea is to use a differentiable penalty function with a time-varying penalty parameter to deal with the inequality constraints. A time-varying regularization term is used to deal with the ill-poseness caused by the monotonicity assumption and the time-varying penalty term. The proposed dynamical system extends the regularized dynamical system in the literature to the projected gradient-based regularized penalized dynamical system, which can be used to solve generalized noncooperative games with set constraints and coupled constraints. Furthermore, we propose a distributed algorithm by using leader-following consensus, where the players have access to neighboring information only. For both cases, the asymptotic convergence to the least-norm variational equilibrium of the game is proven. Numerical examples show the effectiveness and efficiency of the proposed algorithms.


Insight to Biofabrication of Liver Microtissues for Disease Modeling: Challenges and Opportunities.
In the last decade, liver diseases with high mortality rates have become one of the most important health problems in the world. Organ transplantation is currently considered the most effective treatment for compensatory liver failure. An increasing number of patients and shortage of donors has led to the attention of reconstructive medicine methods researchers. The biggest challenge in the development of drugs effective in chronic liver disease is the lack of a suitable preclinical model that can mimic the microenvironment of liver problems. Organoid technology is a rapidly evolving field that enables researchers to reconstruct, evaluate, and manipulate intricate biological processes in vitro. These systems provide a biomimetic model for studying the intercellular interactions necessary for proper organ function and architecture in vivo. Liver organoids, formed by the self-assembly of hepatocytes, are microtissues and can exhibit specific liver characteristics for a long time in vitro. Hepatic organoids are identified as an impressive tool for evaluating potential cures and modeling liver diseases. Modeling various liver diseases, including tumors, fibrosis, non-alcoholic fatty liver, etc., allows the study of the effects of various drugs on these diseases in personalized medicine. Here, we summarize the literature relating to the hepatic stem cell microenvironment and the formation of liver Organoids.


Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother.
A child with X-linked osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency (OL-EDA-ID) was recently reported. We report the clinical features of a second boy with this novel syndrome and his mother, who presented with signs of incontinentia pigmenti (IP). The child had mild osteopetrosis without neurosensory complications, unilateral lymphedema of the left leg, and characteristic features of anhidrotic ectodermal dysplasia with sparse hair, facial dysmorphy, delayed eruption of teeth, and sweat gland abnormalities. He died at 18 months of severe immunodeficiency with multiple infections caused by Gram-negative (Salmonella enteritidis) and Gram-positive (Streptococcus pneumoniae) bacteria, nontuberculous mycobacteria (Mycobacterium kansasii), and fungi (Pneumocystis carinii). His 30-year-old mother's medical history, together with residual cutaneous lesions, was highly suggestive of IP without neurologic impairment. In this patient with OL-EDA-ID, we detected the same NF-kappaB essential modulator stop codon hypomorphic mutation identified in the previous patient. The occurrence of the same clinical features in 2 unrelated patients with the same genotype demonstrates that OL-EDA-ID is a genuine clinical syndrome. The clinical and biological descriptions of the proband and his mother further corroborate the relationship between IP and EDA. Both syndromes are allelic and are associated with mutations in NF-kappaB essential modulator, with a genotype-phenotype correlation in hemizygous males. In contrast, loss-of-function mutations and hypomorphic mutations may cause IP in females.


Indications for penetrating keratoplasty in north China.
To analyze leading indications for penetrating keratoplasty (PKP) in north China and changing trends in them. We retrospectively reviewed the records of patients who underwent PKP at Shandong Eye Institute from January 1997 to December 2002. Infectious keratitis (fungal, bacterial, and acanthamoeba), herpes simplex keratitis (HSK), corneal scarring, keratoconus, bullous keratopathy, regrafting, corneal dystrophy and degeneration, and others were included in the indications for PKP. Initial diagnoses and causes of regrafting were recorded, as well as the related intraocular surgeries for bullous keratopathy. A total of 1702 patients (1702 eyes) were included in this study. The leading indications for PKP were infectious keratitis (31%), followed by HSK (18%), corneal scarring (16%), keratoconus (13%), bullous keratopathy (7%), regrafting (5%), and corneal dystrophy and degeneration (4%). Percentage of PKP for keratoconus and bullous keratopathy increased significantly during the 6 years, contrary to HSK and corneal scarring. Fungal infections accounted for 66% of infectious keratitis. Of 118 bullous keratopathy cases, 90 (76%) were associated with cataract surgery. The leading initial diagnoses of regrafting were corneal burns (25%), HSK (23%), and infectious keratitis (14%); the major causes included immune rejection (61%), graft infection (14%), and recurrence of HSK (10%). Infectious keratitis remains the most common indication for PKP in north China. Moreover, there is an increasing trend in the percentage of PKP for keratoconus and bullous keratopathy.


Successful treatment of pachydermoperiostosis patients with etoricoxib, aescin, and arthroscopic synovectomy: Two case reports.
Pachydermoperiostosis (PDP) is a rare hereditary disorder that affects the skin and bones. PDP is characterized by periostosis, digital clubbing, and pachydermia. Previous studies demonstrated that increased prostaglandin E2 (PGE2) levels resulting from defective protein degradation pathways play a crucial role in PDP pathogenesis, and males were more commonly and severely affected than females. Moreover, nearly all PDP patients suffer from refractory arthralgia. Although several different treatment modalities are used for PDP, therapy for this disease remains challenging. Two cases of PDP showing symptoms consistent with polyarthritis and arthralgia that mainly affected the knees and ankles. The diagnostic criteria for PDP include digital clubbing, periostosis, and pachydermia. The 2 patients were diagnosed as PDP based on the finger clubbing, facial cutis furrowing, knee and ankle arthritis, and radiographic evidence of periosteal proliferation. Patient 1 had massive joint effusion that was treated by oral administration of etoricoxib and aescin combined with arthroscopic synovectomy, whereas Patient 2 had mild joint swelling and accepted only oral medication. Clinical symptoms of the 2 patients greatly improved after the treatment. During the 1-year follow-up, the patient experienced no adverse effects or recurrence. The therapeutic results showed that oral etoricoxib could reduce inflammation and retard progression of pachydermia, or even relieve facial skin furrowing, but had limited efficacy for arthralgia. However, oral aescin had satisfactory efficacy for arthralgia. Thus, etoricoxib combined with aescin is a safe and effective treatment for PDP. Meanwhile, arthroscopic synovectomy can be used to treat joint effusion, but had no therapeutic effect on arthralgia. Therefore, postoperative oral medications would be needed as subsequent therapy for joint problems. In conclusion, this study proposes an effective and safe treatment plan to address symptoms experienced by PDP patients.


Effects of rapamycin on apoptosis of rheumatoid synovial cells.
In the present study, we investigated the effects of an immunosuppressant, rapamycin, on bcl-2 expression and the susceptibility of human rheumatoid synovial fibroblasts to Fas-mediated apoptosis. Rapamycin treatment down-regulated bcl-2 expression on rheumatoid synovial cells in a dose-dependent manner. In contrast, Fas antigen expression was not influenced by rapamycin treatment. Rapamycin treatment also enhanced the susceptibility of rheumatoid synovial cells to anti-Fas monoclonal antibody-mediated apoptosis. Our results suggest that rapamycin augments the sensitivity of rheumatoid synovial fibroblasts to apoptosis by down-regulating bcl-2 expression. This pharmacological alteration of sensitivity to apoptosis in the rheumatoid synovium may represent a new therapeutic approach for rheumatoid arthritis.


Plasma amino acids of the mid-trimester human fetus.
The amino acid concentrations in umbilical cord plasma taken at fetoscopy were measured from 12 fetuses between 18 and 29 weeks gestation. Concurrent maternal plasma levels were measured. Fetal plasma showed consistently higher concentrations of plasma amino acids with the ratios varying between 1.1:1 and 3:1 and the difference always reached statistical significance. It is suggested that these results reflect the in vivo situation of the mid-trimester human fetus.


Cardiac dysfunction during liver transplantation: incidence and preoperative predictors.
The aim was to investigate the cardiac response during liver transplantation (LT) and analyze its relationship with clinical factors, echocardiographic, and hemodynamic findings. All patients undergoing LT for cirrhosis from 1998 to 2004 were included. Clinical data, comprehensive echocardiography, hepatic, and right heart hemodynamic measurements were analyzed. During LT patients underwent continuous right-heart pressure monitorization. Measurements 10 min after reperfusion were compared with baseline values. Abnormal cardiac response was defined as a decrease in left ventricular stroke work index despite a rise in pulmonary wedge capillary pressure. Predictors of abnormal cardiac response were investigated using logistic regression. Data were available from 209 patients (mean age 52 (9) yrs; Child A 27; B 93; C 89) with a mean model for end-stage liver disease score 16.3 (4.7). Abnormal cardiac response was observed in 47 (22.5%) patients after reperfusion. Patients who developed this response had hyponatremia, lower central venous pressure, lower pulmonary artery pressure, and lower pulmonary wedged capillary pressure. Abnormal cardiac response was related to a longer postoperative intubation time. Abnormal cardiac response is observed during LT and may be a manifestation of occult cirrhotic cardiomyopathy. This finding is underestimated with usual diagnostic tools and could be related to indirect signs of circulatory dysfunction of advanced liver disease.


Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells.
Although nicotinic acetylcholine receptors in both the central and peripheral nervous systems play a prominent role in the control of urinary bladder function, little is known regarding expression or function of nicotinic receptors in the bladder epithelium, or urothelium. Nicotinic receptors have been described in epithelial cells lining the upper gastrointestinal tract, respiratory tract, and the skin. Thus the present study examined the expression and functionality of nicotinic receptors in the urothelium, as well as the effects of stimulation of nicotinic receptors on the micturition reflex. mRNA for the alpha3, alpha5, alpha7, beta3, and beta4 nicotinic subunits was identified in rat urothelial cells using RT-PCR. Western blotting also confirmed urothelial expression of the alpha3- and alpha7-subunits. Application of nicotine (50 nM) to cultured rat urothelial cells elicited an increase in intracellular Ca2+ concentration, indicating that at least some of the subunits form functional channels. These effects were blocked by the application of the nicotinic antagonist hexamethonium. During in vivo bladder cystometrograms in urethane-anesthetized rats, intravesical administration of nicotine, choline, or the antagonists methyllycaconitine citrate and hexamethonium elicited changes in voiding parameters. Intravesical nicotine (50 nM, 1 microM) increased the intercontraction interval. Intravesical choline (1-100 microM) also affected bladder reflexes similarly, suggesting that alpha7 nicotinic receptors mediate this effect. Intravesical administration of hexamethonium (1-100 microM) potentiated the nicotine-induced changes in bladder reflexes. Methyllycaconitine citrate, a specific alpha7-receptor antagonist, prevented nicotine-, choline-, and hexamethonium-induced bladder inhibition. These results are the first indication that stimulation of nonneuronal nicotinic receptors in the bladder can affect micturition.


Antibacterial diterpenoids from Fabiana densa var. ramulosa.
A biologically monitored fractionation of the resinous exudate of Fabiana densa Remy var. ramulosa Wedd. led to the isolation of the two new diterpenes: ent-beyer-15-en-18-O-succinate and ent-beyer-15-en-18-O-oxalate as the unique compounds responsible for the observed antibacterial activity of this extract. Their structures were determined by 1D and 2D NMR spectroscopy.


Change in physiological variables in the last 2 weeks of life: an observational study of hospital in-patients with cancer.
Recognising dying remains a difficult clinical skill which has gained increasing importance in the United Kingdom since the Neuberger review. Clinical and research methods exist to aid recognition of dying but do not exhibit the level of accuracy required for such an important decision. To explore change in key clinical parameters as cancer patients near the end of life. This is a retrospective cohort study of terminally ill patients. Data were collected from hospital case-notes. Case-note data were analysed using multilevel modelling to explore absolute values and rates of change of given variables. Hospital in-patients who died from solid-tumour malignancies within a 3-month period in 2009 formed the cohort. The setting was an acute hospital trust in the North of England. A total of 15,337 data points from the case-notes of 102 patients were analysed. There was a clinically and statistically significant deterioration in respiratory function and renal function over the last 2 weeks of life. Heart rate and serum sodium also changed but did not vary greatly from normal limits. White cell parameters, haemoglobin and albumin showed evidence for change over longer periods. Results demonstrate statistically and clinically significant change in routinely measured respiratory and renal function variables during the final 2 weeks of life in people dying with cancer. Although useful in acute early warning scores, in a terminally ill patient, relative haemodynamic stability should not be interpreted as reassuring. Further work is needed to understand how these findings apply to the individual or inform other prognostic work.


Theorizing healthy settings: a critical discussion with reference to Healthy Universities.
The settings approach appreciates that health determinants operate in settings of everyday life. Whilst subject to conceptual development, we argue that the approach lacks a clear and coherent theoretical framework to steer policy, practice and research. To identify what theories and conceptual models have been used in relation to the implementation and evaluation of Healthy Universities. A scoping literature review was undertaken between 2010 and 2013, identifying 26 papers that met inclusion criteria. Seven theoretical perspectives or conceptual frameworks were identified: the Ottawa Charter; a socio-ecological approach (which implicitly drew on sociological theories concerning structure and agency); salutogenesis; systems thinking; whole system change; organizational development; and a framework proposed by Dooris. These were used to address interrelated questions on the nature of a setting, how health is created in a setting, why the settings approach is a useful means of promoting health, and how health promotion can be introduced into and embedded within a setting. Although distinctive, the example of healthy universities drew on common theoretical perspectives that have infused the settings discourse more generally this engagement with theory was at times well-developed and at other times a passing reference the paper concludes by pointing to other theories that offer value to healthy settings practice and research and by arguing that theorization has a key role to play in understanding the complexity of settings and guiding the planning, implementation and evaluation of programmes.


A liquid metal dropper for experiments on the wettability of liquid metals on plasma facing components.
A liquid metal dropper has been developed as a part of the Ion-Gas-Neutral Interactions with Surfaces 2 (IGNIS-2) facility at The Pennsylvania State University. The dropper has the capability of directly applying drops to candidate plasma facing materials for nuclear fusion reactors to enable measurements of their liquid metal wetting properties. The results presented here are specific to the use of lithium in the dropper. This paper discusses the design choices of the liquid metal dropper and its chamber, including the heating and temperature control and the dropper's motorized operation. Lithium drops of masses ranging from 0.05 g up to 0.13 g, equivalent to drop diameters between 5.6 mm to 1 cm, have been consistently dispensed by the dropper. A new algorithm is developed and used to automate the analysis of the contact angle between the liquid drops and substrate material for efficient analysis of video data recorded to study the wetting properties of candidate plasma-facing components.


A survey of starch particle counts in the hospital environment in relation to the use of powdered latex gloves.
As latex proteins, which cause latex hypersensitivity, can be found on starch particles and inhalation may be a route for sensitization, the presence of starch particles in hospital air was examined. The starch particles were demonstrated by immobilization onto cellulose acetate filters and staining with iodine. Rooms in which powdered latex gloves were used gave counts of up to > 3,667 particles per cubic meter of air. Starch particles were not found in the air in rooms where latex gloves were not used, and were highest in rooms with a high glove usage but no ventilation. A change to powder-free gloves significantly reduced the count of starch particles in the unventilated Accident/Emergency Department air. Use of powder-free gloves should be considered especially in unventilated areas in healthcare premises.


Intraspecific Variation in Functional Traits of Medicago sativa Determine the Effect of Plant Diversity and Nitrogen Addition on Flowering Phenology in a One-Year Common Garden Experiment.
Nitrogen deposition and biodiversity alter plant flowering phenology through abiotic factors and functional traits. However, few studies have considered their combined effects on flowering phenology. A common garden experiment with two nitrogen addition levels (0 and 6 g N m-2 year-1) and five species richness levels (1, 2, 4, 6, and 8) was established. We assessed the effects of nitrogen addition and plant species richness on three flowering phenological events of Medicago sativa L. via changes in functional traits, soil nutrients, and soil moisture and temperature. The first flowering day was delayed, the last flowering day advanced, and the flowering duration shortened after nitrogen addition. Meanwhile, the last flowering day advanced, and flowering duration shortened along plant species richness gradients, with an average of 0.64 and 0.95 days change per plant species increase, respectively. Importantly, it was observed that plant species richness affected flowering phenology mainly through changes in plant nutrient acquisition traits (i.e., leaf nitrogen and carbon/nitrogen ratio). Our findings illustrate the non-negligible effects of intraspecific variation in functional traits on flowering phenology and highlight the importance of including functional traits in phenological models to improve predictions of plant phenology in response to nitrogen deposition and biodiversity loss.


Avoiding adverse drug reactions by pharmacogenetic testing: a systematic review of the economic evidence in the case of TPMT and AZA-induced side effects.
The study aims at evaluating the economic evidence related to testing for genetic variants of the drug-metabolizing enzyme, TPMT. Detecting TPMT genetic variants before the administration of azathioprine (AZA) has the potential to prevent serious and costly adverse drug reactions (ADRs), such as neutropenia. In particular, our analysis concentrated on assessing the reliability of data on costs of neutropenia and performing the tests, the two main cost categories that could inform an economic evaluation of TPMT pharmacogenetic testing. A systematic literature review was performed to gather evidence on the costs of testing and neutropenia. Articles were critically appraised for their comprehensiveness and quality. To better estimate costs of TPMT tests, a small-scale survey of European diagnostic laboratories was conducted. Only seven articles were retrieved specifying the costs associated with the management and treatment of AZA-induced neutropenia. Most of these studies are based on theoretical modeling reconstructed with key-informants or on very few cases of ADRs, and either the methodology for cost calculation is not specified or costs are based on national cost databases and tariffs. After critical appraisal of these studies, we considered 2,116 euros as the most reliable estimate for the cost of a case of neutropenia. Literature review accompanied by the survey of several diagnostic laboratories also provided an estimate (68 euros) for TPMT testing. Based on these values, the net cost per prevented case of neutropenia equals to 5,300 euros. Solid economic considerations related to TPMT pharmacogenetic testing are still limited by underreporting of ADRs and high level of approximation related to cost data. Ad hoc observational studies and the ADR recording process embedded in pharmacovigilance systems, established across Europe, should represent more reliable sources of cost data in the future.


Homeostatic interplay between FoxO proteins and ER proteostasis in cancer and other diseases.
Cancer cells are exposed to adverse conditions within the tumor microenvironment that challenge cells to adapt and survive. Several of these homeostatic perturbations insults alter the normal function of the endoplasmic reticulum (ER), resulting in the accumulation of misfolded proteins. ER stress triggers a conserved signaling pathway known as the unfolded protein response (UPR) to cope with the stress or trigger apoptosis of damaged cells. The UPR has been described as a major driver in the acquisition of malignant characteristics that ultimately lead to cancer progression. Although, several reports describe the relevance of the UPR in tumor growth, the possible crosstalk with other cancer-related pathways is starting to be elucidated. The Forkhead Box O (FoxO) subfamily of proteins has a major role in cancer progression, where chromosomal translocations and deregulated signaling lead to loss-of-function of FoxO proteins, contributing to tumor progression. Here we discuss the homeostatic connection between the UPR and FoxO proteins and its possible implications to tumor progression and the acquisition of several hallmarks of cancer. In addition, studies linking a crosstalk between the UPR and FoxO proteins in other diseases, including neurodegeneration and metabolic disorders is provided.


[Unusual subclavian steal syndrome].
A case of unusual subclavian steal syndrome in a 50-years-old man without vertebro-basilar deficiency symptoms is reported. The lack of typical symptoms was caused by an uncommon collateral between the left vertebral and the left external carotid artery. The subclavian steal syndrome was revealed while diagnosing right hemiparesis which was the main cause of hospitalization.


[Historical review of insulin and its preparations in pharmacopoeia (3). Fish insulins].
Existence of encapsulated glands situated in the mesentery of certain teleosti was reported by Brockmann (1846) and Stannius (1848), respectively. Thus the gland was named stannius corpuscle or Brockmann body. Later, as results of histological study, cells of stannius corpuscle tissues were constituted with Langerhans islet cells observed in mammalian pancreas by Diammare (1899) and Laguesse (1906). Thus, before the days of discovery of insulin by Banting and Best in 1921, stannius corpuscle has been interesting from the aspects of comparative anatomy and physiology. Rennie (1906) examined a large number of specimens in various species of teleosti and gave the term "principal islet" to easily recognizable stannius corpuscle. Osawa studied comparative anatomy in Freiburg and returned to Tokyo. He continued the study of comparative anatomy of Langerhans islet aand published a report on observation of "principal islet" of flatfish, limanda yokohamae Gth. in 1912 in Japanese. His report seemed to be a milestone of studies of fish insulin in Japan. Macleod attempted to demonstrate direct evidence on secretion of insulin from Langerhans islet cells. Experiments were made on extraction of "principal islet" of teleosti, angler Lophius) and sculpin (Myoxocephalus) to obtain insulin and demonstrated activity. No insulin activity was obtained from pancreatic tissues constituted with acinar cells of these fishes. In the case of elasmobranch, Langerhans islets are not separated, but potent insulin could be extracted from the pancreas. His report published in 1922 was the first report on fish insulin. Succeeding to Macleod's report, several reports on fish insulin were contnributed from Canada, England and U.S.A. until 1929. Dr. Kkumagai, Professor of Internal Medicine, Tohoku Imperial University (Sendai) also conducted the studies on extraction of active principle of pancreas since 1920, independently. But, a Toronto group reached the goal on discovery of insulin earlier than the Sendai group. The Sendai group also described extraction of active principle from the "principal islet" of teleosti. Especially, Ukai (1926) described morphological study on pancreas and stannius corpuscle for more than twenty species of fish. His report played an important role as the next milestone on the road of fish insulin development studies in Japan. In 1926, Dr. Sakaguchi who was a leading clinical diabetologist in Japan published a monograph entitled "Insulin" written in Japanese. He referred the report on fish insulins of McCormick and Noble and Dr. Kumagai's report, however, he commented that production of insulin from fish seemed to be less worthy due to requirements of laborious work to collect small stannius corpuscle from fish. Professor A. Ogata described a textbook entitled "Zoki-Yakuhin-Kagaku (chemistry of organotherapeutics): in 1931. In the first edition, papers of Macleod, McCormick, Dudley and Osawa were referred. In the revised fifth edition (1940) contained description of unpublished data of insulin content of various kinds of fish caught in Japan and supplied from his student Nagasawa. Under the circumstance of expanding tendency of the China Incident to World War II, shortage of importation and production of insulin preparations manufactured from domestic animals was anticipated. Development on manufacture of fish insulin became urgent. [Truncated]


Plasma glutamine decreases immediately after surgery and is related to incisiveness.
Glutamine (gln) is the most abundant free amino acid in the blood. It is involved in important metabolic and biochemical processes, like cell proliferation and oxidative stress. Previous studies have demonstrated that gln concentration in human plasma decreases in several conditions such as sepsis, ischemia-reperfusion, trauma, major surgery and burn. The aim of the present work was to compare the acute effects of different types of surgical interventions and of anesthetization on blood gln concentration. Plasma samples from 88 subjects (30 males and 58 females) were collected before and after major or minor surgery and the gln concentration was analyzed with high-performance liquid chromatography. The results showed that plasma gln concentration after surgery was lower than pre-surgery values and that in major surgery the decrease of gln was higher than in minor surgery. No significant effect was shown for sex or type of anesthesia. These results demonstrate the importance of a gln supplementation before a surgical intervention and show that the amount of gln supplementation should also be adjusted based on the type of surgery.


Influence of blue light spectrum filter on short-wavelength and standard automated perimetries.
To evaluate the influence of a blue light spectrum filter (BLSF), similar in light spectrum transmittance to the intraocular lens Acrysof Natural, on standard automated perimetry (SAP) and short-wavelength automated perimetry (SWAP). Twenty young individuals (< 30 y.o.), without any systemic or ocular alterations (twenty eyes) underwent a random sequence of four Humphrey visual field tests: standard automated perimetry (SAP) and short-wavelength automated perimetry (SWAP) with and without a blue light spectrum filter. All patients had intraocular pressure lower than 21 mmHg, normal fundus biomicroscopy, and no crystalline lens opacity. Foveal threshold (FT), mean deviation (MD), and pattern standard deviation (PSD) indexes obtained from the visual field tests and the difference caused by eccentricity in short-wavelength automated perimetry examinations were analyzed using paired t test. Interindividual variability (standard deviation) was calculated using Pitman's test for correlated samples. Statistically significant reductions in the mean deviation (p < 0.001) and in the foveal threshold (p < 0.001) measured by short-wavelength automated perimetry with the use of the blue light spectrum filter in comparison to short-wavelength automated perimetry without the use of the blue light spectrum filter were observed, but not in standard automated perimetry exams. No other parameters showed statistically significant differences in the short-wavelength automated perimetry and standard automated perimetry tests. Interindividual standard deviation of the test points in the short-wavelength automated perimetry exams increased with eccentricity both with and without the use of the blue light spectrum filter, as sensitivity for inferior and superior hemifields (inferior hemifield minus superior hemifield), but no statistically significant difference in the variability when comparing the use or not of the blue light spectrum filter was noted. When comparing only the four most inferior points and the four most superior points, the inferior-superior difference increases in both situations - without and with the use of the blue light spectrum filter. The difference between without and with the use of the blue light spectrum filter was not statistically significant. Statistically significant reductions in mean deviation and foveal threshold in the short-wavelength automated perimetry with the use of the blue light spectrum filter were observed, but not in standard automated perimetry examinations. Additional studies are necessary to determine the influence of intraocular lenses with short-wavelength light filter after cataract extraction on short-wavelength automated perimetry.


Multiple cutaneous lipomatous neurofibromas.
Cutaneous lipomatous neurofibroma is a rare variant of neurofibroma with a little known pathogenesis; its presence has never been described in Brazil. A 61- year-old woman complaining scalp papules for one year, presented with skin colored to yellowish papules on the scalp. She noted that they were sometimes itchy and occasionally bled. Dermoscopy showed amorphous material, milky white, with a small poorly delimited yellowish area. Histopathological examination revealed spindle cell proliferation associated with mature adipocytes. Cutaneous lipomatous neurofibroma appears to be an underdiagnosed condition owing to the low index of suspicion and lack of knowledge of its existence. Few cases have been reported in the literature.


PDE3 inhibition by C-type natriuretic peptide-induced cGMP enhances cAMP-mediated signaling in both non-failing and failing hearts.
We have previously shown that the natriuretic peptide receptor B (NPR-B) agonist C-type natriuretic peptide (CNP) enhances cyclic adenosine 3´,5´-monophosphate (cAMP)-mediated signaling in failing hearts, through cyclic guanosine 3´,5´-monophosphate (cGMP)-mediated phosphodiesterase (PDE) 3 inhibition. As several signaling pathways are importantly changed in failing hearts, it could not be taken for granted that this crosstalk would be the same in non-failing hearts. Thus, we wanted to clarify to which extent this effect of CNP occurred also in non-failing hearts. Inotropic and lusitropic responses were measured in muscle strips and cGMP levels, localized cAMP levels, cAMP-PDE activity and mRNA levels were analyzed in isolated cardiomyocytes from left ventricles of non-failing and failing rat hearts. CNP increased cGMP and enhanced β1- and β2-adrenoceptor-mediated inotropic and β1-adrenoceptor-mediated lusitropic responses, in non-failing and failing hearts. The NPR-A agonist brain natriuretic peptide (BNP) increased cGMP, but did not affect inotropic or lusitropic responses, indicating different compartmentation of cGMP from the two natriuretic peptide receptors. cAMP-PDE activity of PDE3 was concentration-dependently inhibited by cGMP with the same potency and to the same extent in non-failing and failing cardiomyocytes. CNP enhanced β1-adrenoceptor-induced cAMP increase in living cardiomyocytes in the absence, but not in the presence of a PDE3 inhibitor indicating involvement of PDE3. In summary, CNP sensitizes cAMP-mediated signaling in non-failing as in failing hearts, via NPR-B-mediated increase of cGMP that inhibits the cAMP-PDE activity of PDE3.


Viral Anterior Uveitis: A Practical and Comprehensive Review of Diagnosis and Treatment.
Anterior uveitis is the most common type of uveitis worldwide. The etiologies of anterior uveitis can be divided into infectious and non-infectious (idiopathic, autoimmune, autoinflammatory, trauma, and others). The viral pathogens most commonly associated with infectious anterior uveitis include Herpes Simplex Virus, Varicella-Zoster Virus, Cytomegalovirus, and Rubella Virus. Other emerging causes of viral anterior uveitis are West Nile Virus, Human-Immunodeficiency Virus, Epstein-Barr Virus, Parechovirus, Dengue Virus, Chikungunya Virus, and Human Herpesvirus type 6,7, and 8. Early recognition allows prompt management and mitigates its potential ocular complications. This article provides an updated literature review of the epidemiology, clinical manifestations, diagnostic tools, and treatment options for viral anterior uveitis.


High-frequency ventilation in lung edema: effects on gas exchange and perfusion.
In six open-chest dogs, unilobar pulmonary edema was induced by injection of oleic acid into a lower lobe pulmonary arterial branch. Two hours later, intermittent positive-pressure ventilation (IPPV) and high-frequency oscillatory ventilation (HFOV) at matched mean alveolar pressures (MAP) were compared at 30-min intervals. The edematous lobar venous admixture (Qva/QT) increased by 0.14 (P less than 0.1) and its relative perfusion (QL/QT) decreased by 0.03. (P less than 0.1) during HFOV compared with IPPV. In another six dogs the MAP was increased by 1.5 cmH2O during HFOV; now the edematous lobar Qva/QT decreased by 0.15 (P less than 0.03) and QL/QT increased by 0.03 (P less than 0.03) during HFOV compared with IPPV. Greater MAP during HFOV also improved the edematous lobar ventilation (lobar venous PCO2) during HFOV compared with IPPV. Conceivably, the increase in MAP inflated collapsed, flooded regions, and thereby increased their O2 transfer, perfusion, and ventilation. Whole-lung Qva/QT was similar during IPPV and HFOV in both groups because of the opposing effects of lobar Qva/QT and QL/QT. We conclude that HFOV supports cardiovascular-respiratory function in open-chest unilobar pulmonary edema compared with IPPV at similar MAP; gas exchange and perfusion of edematous units may be sensitive to small changes in MAP, and we detected no intrinsic effects of HFOV on these variables. We speculate that similar beneficial effects in diffuse pulmonary edema may be effected by small variations in MAP during HFOV without the barotrauma side effects sometimes observed when MAP is increased during IPPV.


Intracerebral Bleeding and Massive Pericardial Effusion as Presenting Symptoms of Myxedema Crisis.
The endocrinological emergency of a fully blown myxedema crisis can present as a multicolored clinical picture. This can obscure the underlying pathology and easily lead to mistakes in clinical diagnosis, work-up, and treatment. We present a case of an unconscious 39-year-old patient with a medical history of weakness, lethargy, and findings of hyponatremia, intracerebral bleeding, and massive pericardial effusion. Finally, myxedema crisis was diagnosed as underlying cause. Replacement therapy of thyroid hormone and conservative management of the intracerebral bleeding resulted in patient's survival without significant neurological impairment. However, diagnostic pericardiocentesis resulted in life-threatening pericardial tamponade. It is of tremendous importance to diagnose myxoedema crisis early to avoid adverse health outcomes.


Cancer mortality 1981-2016 and contribution of specific cancers to current socioeconomic inequalities in all cancer mortality: A population-based study.
In many high-income countries cancer mortality rates have declined, however, socioeconomic inequalities in cancer mortality have widened over time with those in the most deprived areas bearing the greatest burden. Less is known about the contribution of specific cancers to inequalities in total cancer mortality. Using high-quality routinely collected population and mortality records we examine long-term trends in cancer mortality rates in Scotland by age group, sex, and area deprivation. We use the decomposed slope and relative indices of inequality to identify the specific cancers that contribute most to absolute and relative inequalities, respectively, in total cancer mortality. Cancer mortality rates fell by 24 % for males and 10 % for females over the last 35 years; declining across all age groups except females aged 75+ where rates rose by 14 %. Lung cancer remains the most common cause of cancer death. Mortality rates of lung cancer have more than halved for males since 1981, while rates among females have almost doubled over the same period. Current relative inequalities in total cancer mortality are dominated by inequalities in lung cancer mortality, but with contributions from other cancer sites including liver, and head and neck (males); and breast (females), stomach and cervical (younger females). An understanding of which cancer sites contribute most to inequalities in total cancer mortality is crucial for improving cancer health and care, and for reducing preventable cancer deaths.


[Medicine in Taiwan, during the period of Dutch occupation].
During the 38 years of Dutch occupation, by dispatching doctors from the East Indie Company to Taiwan, working at the trading institution for clinical purpose, the Dutchman achieved its missionary and ruling aims. This paper analyses the causes of the Dutch not being able to root on Taiwan. Comparison is made on the medicines between the periods of Dutch occupation and the period of Japanese closed-door policy.


3,5-Nonadiyne isolated from the rhizome of Cachrys ferulacea inhibits endogenous nitric oxide release by rat peritoneal macrophages.
3,5-Nonadiyne, in vitro, selectively inhibits endogenous nitric oxide release (IC(50)=6.7+/-0.8 microM) by rat peritoneal macrophages at doses that do not inhibit T cell proliferation. 3,5-Nonadiyne was isolated from root essential oil of Cachrys ferulacea (L.) CALESTANI, synonym Prangos ferulacea (L.) LINDLEY, obtained by hydrodistillation and spectrometricaly identified unambiguously.


Mori-Zwanzig memory analysis in single-molecule spectroscopy.
We study the dynamical behavior of the Rhodospirillum molischianum LH2 complex based on intensity time series obtained from single-molecule spectroscopy experiments. This is achieved by reconstructing the memory function describing the time-dependent fluctuations of the excited states. We conclude that the apparent stochastic evolution of the dynamics is controlled by at least two different non-Markovian main processes.


A new small molecule for treating inflammation and chorioretinal neovascularization in relapsing-remitting and chronic experimental autoimmune uveitis.
We investigated the effect of PP-001, a new small molecule inhibitor of dihydro-orotate dehydrogenase in two experimental rat experimental autoimmune uveitis (EAU) models: a spontaneously relapsing-remitting model and a monophasic/chronic disease model that results in late chorioretinal neovascularization. Both of the diseases are induced by immunization with autoantigen peptides. Prevention was tested using daily oral applications of PP-001 after immunization with the retinal S-antigen peptide PDSAg (for induction of monophasic uveitis and neovascularization) or the interphotoreceptor retinoid-binding protein peptide R14 (for induction of spontaneously relapsing-remitting EAU). Treatment to inhibit relapses and neovascularization was tested using PP-001 daily after the first attack of R14-induced or after onset of PDSAg-induced EAU. Uveitis was graded clinically and histologically. The effect of PP-001 on cytokine secretion and proliferation was evaluated using rat T-cell lines. Preventive feeding of PP-001 abrogated both types of EAU. Starting treatment after the resolution of the first attack led to a significant reduction of the number and intensity of relapses in R14-induced EAU. PP-001-treatment initiated after onset or after peak of PDSAg-induced EAU significantly reduced neovascularization (as determined by histology). Proliferation of antigen-specific T-cell lines and secretion of IFN-γ, IL-17, IL-10, IP-10, and VEGF were efficiently suppressed by PP-001. We investigated a new dihydroorotate dehydrogenase inhibitor as treatment for primary and recurrent disease in relapsing-remitting and chronic rat models of experimental autoimmune uveitis. The small molecule compound PP-001 suppressed proliferation and cytokine secretion of autoreactive T cells (i.e., IFN-g, IL-17, and VEGF) and chorioretinal neovascularization in chronic EAU.


The association between discharge status, mental health, and substance misuse among young adult veterans.
Although 85% of military service members are discharged honorably, veterans who engage in misconduct during military service may receive other types of administrative or punitive discharges. The discharge type not only affects eligibility for benefits, but is associated with negative downstream consequences (e.g., homelessness, criminal justice involvement). However, limited empirical research has examined the mental health and substance use-related needs of veterans who were not Honorably discharged, and the few that have only focus on veterans who received punitive discharges. This study addressed gaps in the research literature on discharge status by examining differences in mental health, substance use, and attitudes toward psychological treatment among veterans who received Honorable, General Under Honorable Conditions, and Other Than Honorable (OTH) discharges. Young adult veterans (N = 734) were recruited online and completed a battery of self-report measures. Results indicated that veterans who received General and OTH discharges endorsed significantly greater rates of mental health conditions and substance misuse. They also reported more negative perceptions of mental health care. Because these veterans may also experience more barriers to accessing mental health services, it is critical to consider ways to connect these veterans with needed services.


Live Cells versus Fixated Cells: Kinetic Measurements of Biomolecular Interactions with the LigandTracer Method and Surface Plasmon Resonance Microscopy.
Cell-based kinetic studies of ligand or candidate drug binding to membrane proteins have produced affinity and kinetic values that are different from measurements using purified proteins. However, ligand binding to fixated cells whose membrane constituents (e.g., proteins and their glycosylated forms) are partially connected by a cross-linking reagent has not been compared to that to live cells. Under the same experimental conditions for the LigandTracer method, we measured the interactions of fluorophore-labeled lectins and antibody molecules with glycans at HFF cells and the human epithelial growth receptor 2 at SKBR3 cells, respectively. In conjunction with surface plasmon resonance microscopy, the effects of labels and cell/sub-cell heterogeneity on binding kinetics were investigated. Our results revealed that, for cell constituents whose structures and functions are not closely dependent on cell viability, the ligand binding kinetics at fixated cells is only slightly different from that at live cells. The altered kinetics is explained on the basis of a less mobile receptor confined in a local environment created by partially interconnected protein molecules. We show that cell/sub-cell heterogeneity and labels on the ligands can alter the binding reaction more significantly. Thus, fixating cells not only simplifies experimental procedures for drug screening and renders assays more robust but also provides reliable kinetic information about drug binding to cell constituents whose structures are not changed by chemical fixation.


Intrauterine restriction (IUGR).
Perinatal mortality and morbidity is markedly increased in intrauterine growth restricted (IUGR) fetuses. Prenatal identification of IUGR is the first step in clinical management. For that purpose a uniform definition and criteria are required. The etiology of IUGR is multifactorial and whenever possible it should be assessed. When the cause is of placental origin, it is possible to identify the affected fetuses. The major complication is chronic fetal hypoxemia. By monitoring the changes of fetal vital functions it is thus possible to improve both management and outcome. The timing of delivery is crucial but the optimal management scheme has not yet been identified. When IUGR is identified at very early gestational ages, serial assessments of the risk of continuing the in utero fetal life under adverse conditions versus the risks of the prematurity should be performed. Delivery of IUGR fetuses should take place in centers where appropriate neonatal assistance can be provided. Careful monitoring of the IUGR fetus during labor is crucial as the IUGR fetus can quickly decompensate once uterine contractions have started.


Liver transplantation for benign hepatic tumors: a systematic review.
Orthotopic liver transplantation (OLT) has been performed for several benign hepatic tumors. Most of these diseases are usually managed conservatively, or treated by liver resection. OLT might be required when the lesions are symptomatic, diffuse in hepatic parenchyma, causing life-threatening complications or malignant transformation cannot be ruled out. Polycystic liver disease is the most common indication for OLT. We present a review of transplantable benign hepatic lesions to evaluate the need of OLT for these diseases, to summarize in which OLT is a good therapeutic option, and to show the early and long-term survival which might be expected.


The endocytic catalysts, Rab5a and Rab7, are tandem regulators of thyroid hormone production.
Rab proteins are small GTPases that control distinct vesicular transport steps. Along the endocytic pathway, Rab5a is a rate-limiting catalyst of internalization, and Rab7 controls trafficking through late endosomes to lysosomes. The dependence of thyroid hormone production by thyrocytes on thyroglobulin endocytosis and intracellular processing in late endosomes/lysosomes suggests that its rate can be regulated by the expression or function of these endocytic catalysts. We compared the expression level and membrane recruitment of Rab5a and Rab7 in autonomous thyroid adenomas (where the cAMP cascade is constitutively activated) and surrounding quiescent tissues. The concentrations of Rab5a and Rab7, but not of Rab8, were coordinately increased up to 6-fold in adenomas, and correlated with a proportionate decrease in soluble thyroglobulin content (reflecting colloid depletion by accelerated endocytic uptake in hyperactive tissue). In adenomas, a higher proportion of Rab5a and Rab7 was membrane associated, and the equilibrium density of particulate Rab7 and iodine shifted toward lysosomal fractions, indicating that progression along the degradation pathway also was promoted. In cultures of polarized human thyrocytes from normal patients, thyroid-stimulating hormone or forskolin increased, to a similar extent, Rab5a and Rab7 but not Rab8 expression, apical endocytosis of thyroglobulin and lucifer yellow, and basolateral secretion of T(3) and T(4). Taken together, these in vivo and in vitro observations demonstrate that thyroid-stimulating hormone, via cAMP, coordinately enhances the expression of Rab5a and Rab7, which promote Tg endocytosis and transfer to lysosomes, respectively, resulting in accelerated thyroid hormone production.


Fibrinogen receptors do not undergo spontaneous redistribution on surface-activated platelets.
Studies with fibrinogen coupled to colloidal fibrinogen-gold (Fgn/Au) have suggested that fibrinogen receptors glycoprotein IIb-IIIa (GPIIb-IIIa) on human platelets may undergo spontaneous reorganization and centralization during surface activation. The present study has examined that hypothesis. Platelets were allowed to spread on grids for 20 minutes, just as in previous studies, but they were fixed before, rather than after, exposure to Fgn/Au or latex spherules. A monoclonal antibody to GPIIb-IIIa was also employed. Control experiments demonstrated that Fgn/Au and latex move toward the central zones and into channels of the open canalicular system on surface-activated platelets treated in the usual manner. However, when surface-activated platelets were fixed after spreading and before exposure to ligand, Fgn/Au particles and latex sperules were evenly dispersed over the entire cell membrane. Immunogold staining of GPIIb-IIIa also revealed edge-to-edge localization of the GPIIb-IIIa receptors on surface-activated cells. The findings are consistent with the concept that fibrinogen receptors do not undergo spontaneous reorganization on surface-activated platelets.


Echocardiography in pediatric pulmonary hypertension.
Pulmonary hypertension (PH) can be a rapidly progressive and fatal disease. Although right heart catheterization remains the gold standard in evaluation of PH, echocardiography remains an important tool in screening, diagnosing, evaluating, and following these patients. In this article, we will review the important echocardiographic parameters of the right heart in evaluating its anatomy, hemodynamic assessment, systolic, and diastolic function in children with PH.


"Clockness" in the detection of dementia: a semantic-conceptual effect.
We studied aspects of clock cognition that might underlie the sensitivity of the CDT in screening for dementia of the Alzheimer type (DAT). Two groups, 15 patients with mild-moderate DAT and 15 controls, were assessed with the CDT and specially designed tests of clock-related cognition. Patients were impaired on the CDT, but they did not differ from controls in copying a clock face or selecting the correct representation of a given time. Patients were worse than controls at distinguishing between clock and nonclock objects, detecting anomalies in clocks, and in setting time irrespective of response format. These findings suggest that semantic-conceptual aspects of clock-related cognition are important in discriminating between patients with DAT and controls.


Passenger flow anomaly detection in urban rail transit networks with graph convolution network-informer and Gaussian Bayes models.
Passenger flow anomaly detection in urban rail transit networks (URTNs) is critical in managing surging demand and informing effective operations planning and controls in the network. Existing studies have primarily focused on identifying the source of anomalies at a single station by analysing the time-series characteristics of passenger flow. However, they ignored the high-dimensional and complex spatial features of passenger flow and the dynamic behaviours of passengers in URTNs during anomaly detection. This article proposes a novel anomaly detection methodology based on a deep learning framework consisting of a graph convolution network (GCN)-informer model and a Gaussian naive Bayes model. The GCN-informer model is used to capture the spatial and temporal features of inbound and outbound passenger flows, and it is trained on normal datasets. The Gaussian naive Bayes model is used to construct a binary classifier for anomaly detection, and its parameters are estimated by feeding the normal and abnormal test data into the trained GCN-informer model. Experiments are conducted on a real-world URTN passenger flow dataset from Beijing. The results show that the proposed framework has superior performance compared to existing anomaly detection algorithms in detecting network-level passenger flow anomalies. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.


Apolipoproteins A-1 and B and the likelihood of non-fatal stroke and myocardial infarction -- data from The Third National Health and Nutrition Examination Survey.
The measurement of plasma apolipoproteins (APO) has been proposed for predicting the risk of cardiovascular diseases. However, the association between APOs and stroke is not well defined. We evaluated the association between plasma concentrations of APO A-1 and APO B with a physician diagnosis of stroke (n=153), and electrocardiogram evidence or physician diagnosis of myocardial infarction (n=379), in a nationally representative sample of 3,696 US adults aged >40 years who participated in the Third National Health and Nutrition Examination Survey. Multivariate logistic regression analyses were used to investigate these relationships. After adjusting for differences in age, gender, race/ethnicity, education, hypertension, cholesterol, body mass index, and cigarette smoking, the upper quartile of APO A-1 (> or = 161 mg/dl) when compared with the lowest quartile (<126 mg/dL) was inversely associated with the likelihood of myocardial infarction (Odds Ratio [OR], 0.6; 95% Confidence Interval [CI] 0.4-0.9) but not stroke. APO B concentrations were not associated with either myocardial infarction or stroke. However, an APO A-1 to B ratio > or = 1.59 when compared with a ratio < or = 1.04 was associated with a decreased likelihood of myocardial infarction (OR, 0.3; 95% CI, 0.2-0.6); and stroke (OR 0.4, 95% CI, 0.2-1.0). Higher APO A-1 concentrations were associated with a decreased likelihood for myocardial infarction but not for stroke. The APO A-1 to B ratio was inversely associated with both myocardial infarction and stroke and may be an important protective clinical marker for atherosclerosis.


Metabolic, renal, and hematological changes in chronic hepatitis C patients achieving rapid virologic response after 12 weeks of direct-acting antiviral treatment: A prospective cohort study.
The impact of direct-acting antivirals (DAA) therapy on lipid and glucose metabolism and kidney function in patients with hepatitis C virus (HCV) infection, along with its side effects on blood cells, remains controversial. Therefore, we conducted a study that enrolled 280 patients with HCV infection who achieved sustained virologic response after treatment with DAA therapy without ribavirin to evaluate the metabolic changes, renal function, and anemia risk based on real-world data. This study was an observational prospective study with a follow-up period of 12 weeks after the initiation of DAA therapy. Data on biochemical tests, renal function, blood counts, viral load, and host genomics were recorded before treatment and after 12 weeks of treatment with DAAs. DAA therapy reduced fibrosis-4 scores and improved liver function, with significant reductions in aspartate transaminase, alanine aminotransferase, and total bilirubin levels. However, DAA therapy slightly increased uric acid, cholesterol, and low-density lipoprotein cholesterol levels. It significantly reduced fasting blood glucose levels and hemoglobin A1C index (HbA1C) in the study group, while hemoglobin (Hb) and hematocrit (HCT) concentrations decreased significantly (4.78 ± 21.79 g/L and 0.09% ± 0.11%, respectively). The estimated glomerular filtration rate (eGFR) decreased by 12.89 ± 39.04 mL/min/1.73m2. Most variations were not related to the genotype, except for Hb, HCT, and HbA1C. Anemia incidence increased from 23.58% before treatment to 30.72% after treatment. Patients with HCV-1 genotype had a higher rate of anemia than did patients with genotype 6 (36.23% vs. 24.62%). Multivariate analysis showed that the risk of anemia was related to female sex, cirrhosis status, fibrosis-4 score, pretreatment eGFR, and pretreatment Hb level. The results of our study can provide helpful information to clinicians for the prognosis and treatment of HCV infection.


Bacterial phosphoenolpyruvate-dependent phosphotransferase system. Mechanism of the transmembrane sugar translocation and phosphorylation.
The phosphoryl-group transfer from PHPr to glucose or alpha-methylglucose and from glucose 6-phosphate to these same sugars catalyzed by membrane-bound EIIBGlc of the bacterial phosphoenolpyruvate-dependent phosphotransferase system has been studied in vitro. Kinetic measurements revealed that both the phosphorylation reaction and the exchange reaction proceed according to a ping-pong mechanism in which a phosphorylated membrane-bound enzyme II acts as an obligatory intermediate. The occurrence of a phospho-IIBGlc/IIIGlc has been physically demonstrated by the production of a glucose 6-phosphate burst from membranes phosphorylated by phosphoenolpyruvate, HPr, and EI. The observation of similar second-order rate constants for the production of sugar phosphate starting with different phosphoryl-group donors confirms the catalytic relevance of the phosphoenzyme IIBGlc intermediate. The in vitro results, together with data published by other investigators, have led to a model describing sugar phosphorylation and transport in vivo.


Effect of single amino acid changes in the region of the adenylylation site of T4 RNA ligase.
Preparation and analysis of a series of mutants of bacteriophage T4 RNA ligase that carry single amino acid changes at or near the site of covalent reaction with ATP (adenylylation) are described. The mutant proteins were constructed by site-directed mutagenesis of the gene for T4 RNA ligase (g63) cloned in M13 vectors, transfer of the mutant genes into a lambda pL-containing expression plasmid, and subsequent expression in Escherichia coli. The results give further evidence that Lys-99 is the adenylylation site and that the residue is also important to step 3 in the RNA ligase mechanism (ligation between acceptor and adenylylated donor). Mutations at Glu-100 or Asp-101 have no effect on adenylylation, but Asp-101 is shown to be crucial to both step 2 (transfer of adenylyl to donor) and step 3.