Extrauterine Growth Restriction: Definitions and Predictability of Outcomes in a Cohort of Very Low Birth Weight Infants or Preterm Neonates.
Extrauterine Growth Restriction (EUGR) refers to inadequate growth during hospitalization. Current definitions for EUGR are varied and can be classified as cross-sectional (weight at a given t-time <10th centile) or longitudinal (weight loss between birth and a given t-time >1SD). Different t-times are also considered in literature, such as 36 weeks of gestational age (GA) or age at discharge. The aim of this study is to investigate whether EUGR could predict the auxological outcome at 24-30 months, and to evaluate the agreement between cross-sectional and longitudinal definitions. In total, 1589 infants with GA <30 weeks or birthweight ≤ 1500 g and without major congenital anomalies were included in this study. Cross-sectional and longitudinal EUGR were calculated at 36 and 40 weeks of GA, at discharge, and at 28 days. The concordance between the two definitions was estimated by Kappa coefficient. At 24-30 months, 803 infants were measured again. The agreement between the two definitions of EUGR was low. Both EUGR and not-EUGR groups were at lower centiles for weight, but at higher centiles for head circumference at 24-30 months than at birth. Longitudinal EUGR was associated with a poorer growth outcome for weight and height circumference than cross-sectional EUGR. No differences were observed for length. An agreed definition of EUGR is highly desirable in clinical practice to assess medical and nutritional interventions in preterm neonates. Based on the results of this study, we recommend the use of the longitudinal evaluation, that proved to better predict the auxological long-term outcome with respect to the cross-sectional one.


The nature of the chemical bond in BeO0,-, BeOBe+,0,-, and in their hydrogenated products HBeO0,-, BeOH, HBeOH, BeOBeH+,0,-, and HBeOBeH.
The nature of the chemical bond in BeO0,-, BeOBe+,0,-, and in their hydrogenated products HBeO0,-, BeOH, HBeOH, BeOBeH+,0,-, and HBeOBeH has been studied through single and multi reference correlation methods. In all these species, excited and ionized atomic states participate in a resonant way making chemically possible molecules that have been termed hypervalent and explain also the "incompatible" geometrical structure of some species.


Encodable activators of SRC family kinases.
There is considerable current interest in the design of encodable molecules that regulate intracellular protein circuitry and/or activity, ideally with a high level of specificity. Src homology 3 (SH3) domains are ubiquitous components of multidomain signaling proteins, including many kinases, and are attractive drug targets because of the important role their interactions play in diseases as diverse as cancer, osteoporosis, and inflammation. Here we describe a set of miniature proteins that recognize distinct SH3 domains from Src family kinases with high affinity. Three of these molecules discriminate effectively between the SH3 domains of Src and Fyn, which are expressed ubiquitously, and two of these three activate Hck kinase with potencies that rival HIV Nef, one of the most potent kinase activators known. These results suggest that miniature proteins represent a viable, encodable strategy for selective activation of Src family kinases in a variety of cell types.


The classification of depressive disorders. II. A review of historical and physiological classification studies.
A review of recent classification studies of depressive disorders based on historical data and physiological indices was made. It was found that historical variables, such as age of onset and family background, are potentially useful to distinguish depressive subgroups, although these groupings did not differentiate consistently unipolar from bipolar depressives. While the physiological indices do not support the present psychiatric nosology, single physical signs were found to differentiate subgroups within the effective disorders. The implications of these findings for a different research model were discussed.


Risk Factors for Relapse of Childhood B Cell Acute Lymphoblastic Leukemia.
BACKGROUND B cell acute lymphoblastic leukemia (B-ALL) is the most common type of ALL. This study aimed to explore risk factors for relapse of childhood B-ALL. MATERIAL AND METHODS Total of 102 pediatric B-ALL patients were included in this study. B-ALL patients were divided into a relapse group and a non-relapse group. Chemotherapy-induced agranulocytosis time, fusion gene, and minimal residual disease (MRD) were assessed. White blood cell (WBC) count in peripheral blood and risk stratification were evaluated in newly-diagnosed patients. Kaplan-Meier plots were used to evaluate the correlation between risk factors and relapse rates. Multivariate analysis was performed with Cox proportional hazard model to estimate relative risk (RR), 95% confidence interval (95% CI), and hazard ratio (HR). Finally, 99 cases of B-ALL were included in this study. RESULTS There were significant differences between the relapse group and the non-relapse group in age (p=0.004), chemotherapy-induced agranulocytopenia (p=0.001), WBC count in peripheral blood of newly diagnosed patients (p=0.016), risk stratification (p=0.000), and MRD at 12th week (p=0.007). Age over 10 years, high-risk stratification, long period of agranulocytopenia, higher WBC counts, and MRD more than 10⁻⁴ were correlated with higher B-ALL relapse rate (p<0.05). Multivariate analysis showed significantly higher relapse rates for age ≥10 years, high-risk stratification, and MRD at 12th week >10⁻⁴, with RR (95% CI) of 4.001 (1.005-15.930), 4.964 (1.050-23.456), and 4.646 (1.383-15.614), respectively. CONCLUSIONS Agranulocytopenia ≤7 days, peripheral blood WBC >100×10⁹/L, and MRD at 33rd day >10⁻⁴ were associated with B-ALL relapse. Age ≥10 years, high-risk stratification, and MRD at 12th week >10⁻⁴ were independent risk factors for relapse.


Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticity.
The functional significance of cyclooxygenases (COX-1 and -2), the key enzymes that convert arachidonic acid (AA) to prostaglandins (PGs) in brain, is unclear, although they have been implicated in cellular functions and in some neurologic disorders, including stroke, epilepsy, and Alzheimer's disease. Recent evidence that COX-2 is expressed in postsynaptic dendritic spines (which are specialized structures involved in synaptic signaling) and is regulated by synaptic activity implies participation of COX-2 in neuronal plasticity. However, direct evidence is lacking. Here we demonstrate that selective COX-2 inhibitors significantly reduced postsynaptic membrane excitability, back-propagating dendritic action potential-associated Ca2+ influx, and long-term potentiation (LTP) induction in hippocampal dentate granule neurons, while a COX-1 inhibitor is ineffective. All of these actions were effectively reversed by exogenous application of PGE2 but not of PGD2 or PGF(2alpha). Our results indicate that COX-2-generated PGE2 regulates membrane excitability and long-term synaptic plasticity in hippocampal perforant path-dentate gyrus synapses.


Apoptosis in raloxifene-treated postmenopausal women.
As raloxifene is a mixed estrogen receptor agonist and antagonist, it exerts different effects on apoptosis in different tissues. In this study, we aimed to evaluate apoptosis in the peripheral lymphocytes of postmenopausal women treated with raloxifene and compare it with untreated control subjects. In this way, we expected to deduce some results about the effect of raloxifene on the immune system and to serve as a guide for future studies on this newly proposed effect of a well-known agent. Twenty osteoporotic postmenopausal women treated with raloxifene for 12 months were included in this study. Another 20 osteoporotic postmenopausal women matched for age and postmenopausal years, but without any medication, were chosen as the control group. Apoptosis was evaluated using a morphological and DNA fragmentation assay, in the peripheral lymphocytes of these women. Our results revealed a decrease in the apoptosis percentages of the patients treated with raloxifene (14.6%) with respect to the control subjects (15.8%), but the difference was not statistically significant (p=0.467). This study indicated that raloxifene treatment had no apoptotic effect on peripheral human lymphocytes compared to controls.


The renin-angiotensin system.
Unravelling of the molecular mechanisms of the action of RAS has been slow. Nature has been rather stingy in revealing bits and pieces of information. Each step of development has depended on the innovation of an appropriate methodology. The uniqueness of the RAS lies in: The function and regulation of the highly specific enzyme renin which specifically catalyses the conversion of the prohormone angiotensinogen to Ang I by an extracellular mechanism. The production of the agonist Ang II takes place in two steps. Ang II and its metabolites exert exceedingly diverse pathophysiological effects, presumably through the complex and multifunctional receptors. The exquisite mechanisms involved in the regulation of renin release and receptor regulation are fascinating. The intricate mechanisms that nature has devised for the checks and balances to maintain steady blood flow and electrolyte balance present a great challenge to biochemists in their attempts to clarify the mechanisms involved at both molecular and cellular levels. In relation to the pathophysiology of hypertension, particularly essential hypertension, there is no question that the RAS plays a pivotal role. Although numerous mechanisms could explain its hypertensinogenic effects, no single mechanism can be identified as the major determinant at the present stage of our knowledge. However, there is an important consensus that the effect of Ang II is manifested slowly at even subpressor doses of Ang II through long-term effects involving remodelling of the cardiovascular and renal system.


The effects of elevated CO2 concentration on competitive interaction between aceticlastic and syntrophic methanogenesis in a model microbial consortium.
Investigation of microbial interspecies interactions is essential for elucidating the function and stability of microbial ecosystems. However, community-based analyses including molecular-fingerprinting methods have limitations for precise understanding of interspecies interactions. Construction of model microbial consortia consisting of defined mixed cultures of isolated microorganisms is an excellent method for research on interspecies interactions. In this study, a model microbial consortium consisting of microorganisms that convert acetate into methane directly (Methanosaeta thermophila) and syntrophically (Thermacetogenium phaeum and Methanothermobacter thermautotrophicus) was constructed and the effects of elevated CO2 concentrations on intermicrobial competition were investigated. Analyses on the community dynamics by quantitative RT-PCR and fluorescent in situ hybridization targeting their 16S rRNAs revealed that high concentrations of CO2 have suppressive effects on the syntrophic microorganisms, but not on the aceticlastic methanogen. The pathways were further characterized by determining the Gibbs free energy changes (ΔG) of the metabolic reactions conducted by each microorganism under different CO2 concentrations. The ΔG value of the acetate oxidation reaction (T. phaeum) under high CO2 conditions became significantly higher than -20 kJ per mol of acetate, which is the borderline level for sustaining microbial growth. These results suggest that high concentrations of CO2 undermine energy acquisition of T. phaeum, resulting in dominance of the aceticlastic methanogen. This study demonstrates that investigation on model microbial consortia is useful for untangling microbial interspecies interactions, including competition among microorganisms occupying the same trophic niche in complex microbial ecosystems.


[Radiological appearance of the cementless ALLOCLASSIC SL-stem implanted in very old patients with primary hip osteoarthritis].
The radiological appearance of the cementless ALLOCLASSIC SL-stem, implanted in patients with primary osteoarthritis of the hip and aged at least 80 years at time of surgery, was investigated. 66 hips in 58 patients were analysed. 17 patients (19 hips) died in the interim, 5 patients (5 hips) were not available for follow-up because of health reasons (4) or lack of co-operation (1). 1 stem had to be explanted after a periprosthetic fracture of the femur. Finally, 41 total hip arthroplasties in 35 patients could be analysed after an average of 67.9 months (39.2-93.4). Bone atrophy - especially in the proximal Gruen zones - was frequently found. In contrast, radiolucent lines and osteolyses were rare occurrences. The Harris Hip score was preoperatively on average 33.0 points, at time of follow-up 81.7 points. The survival rate (endpoint aseptic loosening) was 100 % after a mean follow-up of 5.7 years. Also in very old patients the implantation of a cementless stem is possible and provides very good results.


Losses of nutrients and anti-nutrients in red and white sorghum cultivars after decorticating in optimised conditions.
The aims were to optimise pearling process of red and white sorghum by assessing the effects of pearling time and grain moisture on endosperm yield and flour ash content and to assess nutrient and anti-nutrient losses produced by pearling different cultivars in optimised conditions. Both variables significantly affected both responses. Losses of ashes (58%), proteins (9.5%), lipids (54.5%), Na (37%), Mg (48.5%) and phenolic compounds (43%) were similar among red and white hybrids. However, losses of P (30% vs. 51%), phytic acid (47% vs. 66%), Fe (22% vs. 55%), Zn (32% vs. 62%), Ca (60% vs. 66%), K (46% vs. 61%) and Cu (51% vs. 71%) were lower for red than white sorghum due to different degree of extraction and distribution of components in the grain. Optimised pearling conditions were extrapolated to other hybrids, indicating these criteria could be applied at industrial level to obtain refined flours with proper quality and good endosperm yields.


[Genetic variation of Azov and Black sea herring Alosa pontica (Eihwald, 1838), (Clupeiformes, Alosinae) in Danube river: analysis of biochemical gene markers].
Genetic variation and structure of Danube stock of Aloca pontica pontica were investigated during the spawning moving by means of biochemical genetic marking. The level of heterozygosity was Hobs = 0,009. It is essentially lower than the average level for populations of other Teleostei and Clupeidae representatives. Polymorphism was defined only for Es-D of 20 analyzed loci expressed in muscle tissues. The allele frequencies for this locus were reliably different in the early spawning and later spawning parts of the stock, as well as proportion of heterozygotes and genotype diversity which was higher at the beginning of spawning moving. These results are discussed from two points of view: genetic differences between subpopulations in the course of spawning moving and presence of two close species of herring which come for the spawning together and hybridize to each other.


Shape-controlled synthesis and self-assembly of hexagonal covellite (CuS) nanoplatelets.
Single-crystalline, hexagonal covellite (CuS) nanoplatelets were successfully synthesized through a facile, inexpensive, reproducible, and improved solvothermal process in toluene at 120 degrees C for 24 h with hexadecylamine as a capping agent and copper acetate and carbon disulfide as precursors. These nanoplatelets are about 26+/-1.5 nm in diameter and 8+/-1.2 nm thick, and have a tendency to self-assemble into pillarlike nanostructures with face-to-face stacks, raftlike nanostructures with side-by-side arrays, and stratiform nanostructures with layer-by-layer self-assembly. The crystal shape, morphology, and crystallographic orientation of the covellite obtained were investigated by means of XRD, TEM, and high-resolution TEM, and a potential self-assembly mechanism was proposed.


[Genetic analysis of a fetus with partial 1q monosomy and partial 17q trisomy].
To analyze a fetus with abnormal sonographic features and correlated its genotype with phenotype. G-banding analysis, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed for the fetus. Karyotyping and FISH were also carried out for the parents. SNP array detected a 4.4 Mb deletion at 1q44 and a 10.4 Mb duplication at 17q24.3q25.3 in the fetus. Based on the results of SNP array and FISH analysis, the father was diagnosed with a cryptic t(1;17)(q44;q24.3) translocation. The fetus has inherited a der(1)t(1;17)(q44;q24.3) from its father. The 1q44 deletion and 17q24.3q25.3 duplication may have contributed to the abnormal sonographic features presented by the fetus.


Classification of practitioners by urban Chicano patients: an aspect of the sociology of lay knowledge.
This study in the sociology of lay knowledge seeks to conceptualize the "everyday rules" by which a patient makes choices about which practitioner should be consulted for which episode. A lay person must often choose a practitioner from among competing coteries of specialists, without having recourse to their specialized knowledge in order to classify them. The patient must develop her own typology of specialists, utilizing her own criteria. The patient becomes aware of a number of aspects of an epsiode, each of which requires a response of some sort. In the course of her interaction with a practitioner, the patient discovers that the practitioner is competent, in her perception to handle some aspects and inadequate to handle others, thereby presenting her with a particular constellation of competencies and inadequacies. When seeing different practitioners, the patient encounters vertical and horizontal conflict between the assessments offered her by each. She must decide which offers the competencies most needed and the inadequacies most tolerable. A practitioner's constellation may change over time or by episode. In order to secure the competencies she feels necessary, the patient may utilize a number of practitioners either sequentially or simultaneously, thereby functioning as an assembler of her own health care team.


Recent advances in cluster science.
Small clusters are entities comprised of assemblies of atoms or molecules which often display properties that differ from the individual components and the bulk and, hence, are considered a unique state of matter. Investigating ones of differing sizes provides information that serves to bridge states of matter and, as recently shown, cluster research bridges many disciplines of science. This plenary lecture focused on the varying properties of matter of restricted size, the ability to produce clusters that mimic elements of the periodic table and, hence, behave as super-atoms that can serve as building blocks for new nanoscale matter with designed properties. Mass spectrometry has in the past, and continues in the future, to play a central role in this field.


Toward reliable estimates of seed removal by small mammals and birds in the Neotropics.
Birds are often considered seed predators of less importance when compared to rodents or granivorous ants in studies of seed predation using selective exclosures. However, it is possible that the role of granivorous birds interacting with seeds on the floor of Neotropical forests is being underestimated, if the selective exclosures designed to allow exclusive access to small rodents do not work properly in the Neotropics. We used an experimental approach to evaluate whether birds could remove seeds from selective exclosures designed to allow exclusive access to rodents. We compared seed removal from two paired treatments in the field: an open treatment (control) allowing the access to all vertebrates, and a selective exclosure treatment, where seeds were placed under a cage staked to the ground and covered on top and on the laterals by wire mesh of varying sizes. Treatments were placed in the center of a sand quadrat in order to record the visit of vertebrates from their footprints. Although the selective exclosures are used to tell apart the small mammal seed removal from that of other animals, birds could persistently remove seeds from selective exclosures. Thus, the role of birds interacting with seeds on the floor of tropical forests may be underestimated for some plant species, due to an artifact of the exclosure method employed. Exclosures of 40 x 40 x 40 cm should be efficient to deter the removal of seeds by birds, allowing the consumption of the seeds by small mammals at the same time.


Full sequence analysis and characterization of a human astrovirus type 1 isolate from South Korea.
Human astroviruses are recognized as an important cause of infantile gastroenteritis around the world. In South Korea, sporadic cases of HAstV infection have been reported since 2002. However, hitherto, there have been no studies reporting the whole genome sequence of an HAstV isolate from South Korea. Hence, we sequenced and analyzed the entire genome of an HAstV-1 strain (lhar) that was isolated in Seoul, South Korea. The whole-genome sequence analysis revealed 3 open reading frames comprising the whole genome: ORF1a (2,763 bp), ORF1b (1,548 bp), and ORF2 (2,364 bp). The lhar strain showed amino acid identities with 8 other reference strains of 87.6-98.7%, 94.2-98.8%, and 62.6-99.0% in the ORF1a, ORF1b, and ORF2 regions, respectively. The amino acid sequence of the capsid region encoded by ORF2 was compared with a total of 19 HAstV-1 strains and 8 HAstVs reference strains isolated in various countries. This revealed 1 amino acid substitution, at aa412 (Pro → Arg) in ORF2. This study, the first to report the full-length sequence of an HAstV isolated in South Korea, is meaningful in that it can be used as a full-length HAstV sequence standard for future comparison studies. It may also prove useful to the field of public health field by facilitating the diagnosis and the prediction of new emerging variants.


No. 211-Screening and Management of Bacterial Vaginosis in Pregnancy.
To review the evidence and provide recommendations on screening for and management of bacterial vaginosis in pregnancy. The clinical practice options considered in formulating the guideline. Outcomes evaluated include antibiotic treatment efficacy and cure rates, and the influence of the treatment of bacterial vaginosis on the rates of adverse pregnancy outcomes such as preterm labour and delivery and preterm premature rupture of membranes. Medline, EMBASE, CINAHL, and Cochrane databases were searched for articles, published in English before the end of June 2007 on the topic of bacterial vaginosis in pregnancy. The evidence obtained was rated using the criteria developed by the Canadian Task Force on Preventive Health Care. Guideline implementation will assist the practitioner in developing an approach to the diagnosis and treatment of bacterial vaginosis in pregnant women. Patients will benefit from appropriate management of this condition. These guidelines have been prepared by the Infectious Diseases Committee of the SOGC, and approved by the Executive and Council of the SOGC. The Society of Obstetricians and Gynaecologists of Canada. There is currently no consensus as to whether to screen for or treat bacterial vaginosis in the general pregnant population in order to prevent adverse outcomes, such as preterm birth.


[How can asthma in children be controlled?].
Asthma is a disease manifested by recurrent episodes of shortness of breath, wheezing or cough that often require treatment at the emergency department or even hospitalization. These exacerbations are caused by an increased inflammatory process in the airways. This review focuses on the various daily long term control medications used to prevent exacerbations. The pharmacotherapy used to manage asthma is based mainly on inhaled corticosteroids (ICS and leukotriene receptor antagonists. In more severe cases, other drugs can be added, such as long-acting beta 2 agonists lare used only in conjunction with ICS] as well as additional drugs such as slow release theophylline, anti-lgE monoclonal antibodies, and more. The step-up step-down approach is used to decide on the controller medication needed. If the preventive therapy fails, it is essential to assess the adherence to therapy, the technique used, the existence of aggravating factors and the possibility that the cause of the symptoms is not asthma. For proper disclosure the third author (E.K.) has received payment in the past for lectures from Asthma drug companies.


Impact of Doctor of Nursing Practice education in shaping health care systems for the future.
The approval of the Doctor of Nursing Practice (DNP) by the American Association of Colleges of Nursing in 2004 and publication of The Essentials of Doctoral Education for Advanced Nursing Practice in 2006 promised significant benefit to nursing and to shaping health care systems. Currently, 229 DNP programs exist and more are planned. This article provides an overview of program types, graduates, and postgraduation placement, using Pennsylvania as an exemplar, to describe the potential impact of DNP education in health care systems. Nurse educators need to consider whether our current directions enable us to realize opportunities for shaping health care systems or whether we need to make course corrections. [


Staffing, Financial, and Administrative Oversight Models and Rates of Injury in Collegiate Athletes.
Structural features of health care environments are associated with patient health outcomes, but these relationships are not well understood in sports medicine. To evaluate the association between athlete injury outcomes and structural measures of health care at universities: (1) clinicians per athlete, (2) financial model of the sports medicine department, and (3) administrative reporting structure of the sports medicine department. Descriptive epidemiology study. Collegiate sports medicine programs. Colleges that contribute data to the National Collegiate Athletic Association (NCAA) Injury Surveillance Program. We combined injury data from the NCAA Injury Surveillance Program, sports medicine staffing data from NCAA Research, athletic department characteristics from the United States Department of Education, and financial and administrative oversight model data from a previous survey. Rates of injury, reinjury, concussion, and time loss (days) in NCAA athletes. Compared with schools that had an average number of clinicians per athlete, schools 1 standard deviation above average had a 9.5% lower injury incidence (103.6 versus 93.7 per 10000 athlete-exposures [AEs]; incidence rate ratio [IRR] = 0.905, P < .001), 2.7% lower incidence of reinjury (10.6 versus 10.3 per 10000 AEs; IRR = 0.973, P = .004), and 6.7% lower incidence of concussion (6.1 versus 5.7 per 10000 AEs; IRR = 0.933, P < .001). Compared with the average, schools that had 1 standard deviation more clinicians per athlete had 16% greater injury time loss (5.0 days versus 4.2 days; IRR = 1.16, P < .001). At schools with sports medicine departments financed by or reporting to the athletics department (or both), athletes had higher injury incidences (31% and 9%, respectively). The financial and reporting structures of collegiate sports medicine departments as well as the number of clinicians per athlete were associated with injury risk. Increasing the number of sports medicine clinicians on staff and structuring sports medicine departments such that they are financed by and report to a medical institution may reduce athlete injury incidence.


Near-Infrared Fluorescence Lymphatic Imaging of a Toddler With Congenital Lymphedema.
Primary lymphedema in the pediatric population remains poorly diagnosed and misunderstood due to a lack of information on the causation and underlying anatomy of the lymphatic system. Consequently, therapeutic protocols for pediatric patients remain sparse and with little evidence to support them. In an effort to better understand the causation of primary pediatric lymphedema and to better inform clinical care, we report the use of near-infrared fluorescence lymphatic imaging on the extremities of an alert, 21-month-old boy who presented with unilateral right arm and hand lymphedema at birth. The imaging results indicated an intact, apparently normal lymphatic anatomy with no obvious malformation, but with decreased lymphatic contractile function of the affected upper extremity relative to the contralateral and lower extremities. We hypothesized that the lack of contraction of the lymphatic vessels rather than an anatomic malformation was the source of the unilateral extremity swelling, and that compression and manual lymphatic drainage could be effective treatments.


[Antibiotic resistance : situation in Europe and Switzerland, and impact for the physician].
Antibiotic-resistant bacteria constitute a major public health challenge worldwide. In Europe and Switzerland, the incidence of infections due to methicillin-resistant S. aureus has been decreasing during the recent years. But common Enterobacteriaceae, such as E. coli and K. pneumoniae are more and more resistant, causing therapeutic difficulties, also in the outpatient setting and for benign infections. To fight this increasing problem, any physician has to apply simple preventive measures against the spread of resistant bacteria during care, and to prevent their selection by an appropriate antibiotic use, including the adjustment of the antibacterial spectrum, right dosage and short duration.


MaCDSP32 From Mulberry Enhances Resilience Post-drought by Regulating Antioxidant Activity and the Osmotic Content in Transgenic Tobacco.
Desiccation tolerance is a complex phenomenon that depends on the regulated expression of numerous genes during dehydration and subsequent rehydration. Our previous study identified a chloroplast drought-induced stress protein (MaCDSP32) in mulberry, a thioredoxin (Trx) that is upregulated under drought conditions and is likely to confer drought tolerance to transgenic plants. Mulberry (Morus spp.) is an ecologically and economically important perennial woody plant that is widely used in forest management to combat desertification. However, its stress tolerance physiology is not well understood. In this study, the functions of MaCDSP32 gene were investigated. The expression of MaCDSP32 exhibited a circadian rhythm and was induced by mild and severe water deficits. Under abiotic stress, MaCDSP32-overexpressing plants exhibited increased stress sensitivity with lower water retention capacity and more severe lipid peroxidation than the wild-type (WT) plants. Furthermore, the activity of superoxide dismutase (SOD), the contents of proline and soluble sugars and the expression of stress-related transcription factors were lower in the MaCDSP32-overexpressing plants than in the WT plants. However, the MaCDSP32-overexpressing lines exhibited stronger recovery capability after rewatering post-drought. Moreover, the SOD enzyme activity, proline content, and soluble sugar content were higher in the transgenic plants after rewatering than in the WT plants. The production of the reactive oxygen species (ROS) H2O2 and O2 - was significantly lower in the transgenic plants than in the WT plants. In addition, under abiotic stress, the MaCDSP32-overexpressing lines exhibited improved seed germination and seedling growth, these effects were regulated by a positive redox reaction involving MaCDSP32 and one of its targets. In summary, this study indicated that MaCDSP32 from mulberry regulates plant drought tolerance and ROS homeostasis mainly by controlling SOD enzyme activity and proline and soluble sugar concentrations and that this control might trigger the stress response during seed germination and plant growth. Overall, MaCDSP32 exerts pleiotropic effects on the stress response and stress recovery in plants.


Rap1: a key regulator in cell-cell junction formation.
Rap1 is a Ras-like small GTPase that is activated by many extracellular stimuli and strongly implicated in the control of integrin-mediated cell adhesion. Recent evidence indicates that Rap1 also plays a key role in formation of cadherin-based cell-cell junctions. Indeed, inhibition of Rap1 generates immature adherens junctions, whereas activation of Rap1 tightens cell-cell junctions. Interestingly, Rap1 guanine nucleotide exchange factors, such as C3G and PDZ-GEF, are directly linked to E-cadherin or to other junction proteins. Furthermore, several junction proteins, such as afadin/AF6 and proteins controlling the actin cytoskeleton, function as effectors of Rap1. These findings point to a role of Rap1 in spatial and temporal control of cell-cell junction formation.


Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials.
Analogues of the natural product gallinamide A were prepared to elucidate novel inhibitors of the falcipain cysteine proteases. Analogues exhibited potent inhibition of falcipain-2 (FP-2) and falcipain-3 (FP-3) and of the development of Plasmodium falciparum in vitro. Several compounds were equipotent to chloroquine as inhibitors of the 3D7 strain of P. falciparum and maintained potent activity against the chloroquine-resistant Dd2 parasite. These compounds serve as promising leads for the development of novel antimalarial agents.


Longitudinal Rates, Patient Risk Factors, and Economic Impact of Superficial and Deep Incisional Surgical Site Infection After Primary and Revision Total Hip Arthroplasty: A U.S. Retrospective Commercial Claims Database Analysis.
Background: Longitudinal rates, risk factors, and costs of superficial and deep incisional surgical site infection (SSI) were evaluated six months after primary total hip arthroplasty (pTHA) and revision total hip replacement (rTHA). Patients and Methods: Patients who had pTHA or rTHA between January 1, 2016 and March 31, 2018 were identified using the IBM® MarketScan® administrative claims databases. Kaplan-Meier survival curves evaluated time to SSI over six months. Cox proportional hazard models evaluated SSI risk factors. Generalized linear models estimated SSI costs up to 12 months. Results: The total cohort included 17,514 pTHA patients (mean [standard deviation] age 59.6 [10.1] years, 50.2% female; 66.4% commercial insurance), and 2,954 rTHA patients (61.2 [12.0] years, 52.0% female; 48.6% commercial insurance). Deep and superficial post-operative SSI at six months affected 0.30% (95% confidence interval [CI], 0.22%-0.39%) and 0.67% (95% CI, 0.55%-0.79% of patients in the pTHA, and 8.9% (95%CI: 7.8%-10.0%) and 4.8% (95% CI, 4.0%-5.6%) of patients in the rTHA cohorts. Hazards for SSI were related to patient comorbidities that included diabetes mellitus, obesity, renal failure, pulmonary or circulatory disorders, and depression. The adjusted average all-cause incremental commercial costs associated with post-operative infection ranged from $21,434 to $42,879 for superficial incisional SSI and $53,884 to $76,472 for deep incisional SSI, over a 12-month post-operative assessment period. Conclusions: The SSI rate after revision total hip arthroplasty (rTHA) was nearly 9% compared with 1.0% after pTHA. The risk of infection was influenced by several comorbid risk factors. The incremental cost associated with SSIs was substantial.


Probing Long Non-coding RNA-Protein Interactions.
Non-coding RNA sequences outnumber the protein-coding genes in the human genome, however our knowledge of their functions is still limited. RNA-binding proteins follow the transcripts, including non-coding RNAs, throughout their life, regulating not only maturation, nuclear export, stability and eventually translation, but also RNA functions. Therefore, development of sophisticated methods to study RNA-protein interactions are key to the systematic characterization of lncRNAs. Although mostly applicable to RNA-protein interactions in general, many approaches, especially the computational ones, need adjustment to be adapted to the length and complexity of lncRNA transcripts. Here we critically review all the wet lab and computational methods to study lncRNA-protein interactions and their potential to clarify the dark side of the genome.


A machine learning model for prediction of 30-day primary graft failure after heart transplantation.
Primary graft failure (PGF) remains the most common cause of short-term mortality after heart transplantation. The main objective was to develop and validate a risk model for prediction of short-term mortality due to PGF after heart transplantation using the ISHLT Heart Transplant Registry. We developed a non-linear artificial neural networks (ANN) model to evaluate the association between recipient-donor variables and post-transplant PGF. Patients in the ISHLT registry were randomly divided into derivation and an independent internal validation cohort. The primary endpoint was PGF defined as death within 30 days due to Graft failure or Cardiovascular causes or retransplant within 30 days for causes other than rejection. Among 64,964 adult recipients transplanted between 1994 and 2013, mean age was 51 years and 22% were female. The incidence of PGF up to 30 days was 3.7%. The ANN model selected 33 of 77 risk variables as relevant for PGF prediction. The C-index in the test cohort was 0.70 (95% CI: 0.68-0.71). The risk variables which most influenced the PGF were underlying HF diagnosis, ischemia time and sex, while renal function had a lower influence. An ANN model to predict primary graft dysfunction was derived and independently validated. The good discrimination of the ANN model likely results from its flexibility to model potentially non-linear relationships and interactions. Whether this model with improved discrimination can assist in clinical decisions at the time of transplant should be tested.


The "Pelvic Harness": a skeletonized mesh implant for safe pelvic floor reconstruction.
To evaluate the feasibility, safety and surgical results of skeletonized mesh implants to form a pelvic harness for pelvic floor reconstruction surgery. Patients with advanced pelvic floor prolapse were enrolled to this study. Study model was a kit mesh, reduced to 75% of the original surface area by cutting out mesh material from the central mesh body. Patients were evaluated at the end of the 1st and 6th post-operative months and interviewed at the study conclusion. Ninety-five women with advanced pelvic floor prolapse had this implant. Mean follow-up duration was 9 months (6-12 months). The POP-Q point's measurements showed marked and statistically significant improvements. Bladder over-activity symptoms, fecal incontinence, pelvic pain and constipation rates were all reduced as well. No adverse effects related to the dissection or mesh implantation were marked. The first and sixth post-operative month follow-up records as well as the study conclusion interview findings were satisfactory in terms of subjective and objective cure and adverse effects occurrence. This study data proposes that skeletonizing meshes might be safely and successfully implanted for potentially improved pelvic floor reconstruction.


Central nervous systen alpha-adrenergic mechanisms and cardiovascular regulation in rats.
Noradrenaline (NA) induced a decrease in blood pressure and heart rate when injected into specific areas in either the medulla oblongata or the hypothalamus. In the medulla the area of the nucleus tractus solitarius was specifically sensitive to NA; in the hypothalamus depressor effects were obtained only after NA injections into the anterior hypothalamic/preoptic region. The cardiovascular effects induced by NA (3-40 nmol) in these areas consisted of an immediate decrease in both arterial pressure and heart rate. Size and duration of these effects depended upon the dose of NA injected. Alpha-methylNA (5-15 nmol) induced a long lasting decrease in blood pressure and heart rate when injected into the anterior hypothalamic/preoptic region. These data are discussed in view of the existence of at least two sites within the central nervous system (CNS) from which interference with noradrenergic mechanisms can cause changes in the cardiovascular system.


Wafer-Scale Nanopillars Derived from Block Copolymer Lithography for Surface-Enhanced Raman Spectroscopy.
We report a novel nanofabrication process via block copolymer lithography using solvent vapor annealing. The nanolithography process is facile and scalable, enabling fabrication of highly ordered periodic patterns over entire wafers as substrates for surface-enhanced Raman spectroscopy (SERS). Direct silicon etching with high aspect ratio templated by the block copolymer mask is realized without any intermediate layer or external precursors. Uniquely, an atomic layer deposition (ALD)-assisted method is introduced to allow reversing of the morphology relative to the initial pattern. As a result, highly ordered silicon nanopillar arrays are fabricated with controlled aspect ratios. After metallization, the resulting nanopillar arrays are suitable for SERS applications. These structures readily exhibit an average SERS enhancement factor of above 10(8), SERS uniformities of 8.5% relative standard deviation across 4 cm, and 6.5% relative standard deviation over 5 × 5 mm(2) surface area, as well as a very low SERS background. The as-prepared SERS substrate, with a good enhancement and large-area uniformity, is promising for practical SERS sensing applications.


[New methodological approaches to the hygienic standards of clothes for children and adults].
The hygienic assessment is presently a research issue related mainly with commissioning new materials into production; the above issue is equally related with materials' diversity, with expanding the choice of commodities and with the multi-functionality of the latter as well as with modern technologies and with the forthcoming admittance of our country to the WTO, which necessitates a harmonization of regulating requirements in various countries. The old approaches towards regulations of cloths are outdated and are no longer in line with the requirements of today. The chemical stability of contemporary synthetic fibers and the narrowing-of-gap between their physical-and-hygienic indices and those of natural fibers ensures unified approaches towards the hygienic evaluation of both. A real load that is conceptually found as a product of the impact intensity on the impact duration time is a hygienically valuable criterion ensuring a universal approach towards regulating the cloths hygienic safety. A hygienic classification provides, in case of each item, for defining the index of its hygienic safety (HIS), which is a basis for designing the differential requirements towards cloths of various functional purposes and for various age groups. The area of contact with the skin during wear and the age of consumer are the key components of system (The Hygienic Classification of Cloths". The article is supplemented by 1 drawing, 2 tables and a list of literature (8 entries; article's volume is 5 pages).


Meta-analysis of human connection to nature and proenvironmental behavior.
Understanding what drives environmentally protective or destructive behavior is important to the design and implementation of effective public policies to encourage people's engagement in proenvironmental behavior (PEB). Research shows that a connection to nature is associated with greater engagement in PEB. However, the variety of instruments and methods used in these studies poses a major barrier to integrating research findings. We conducted a meta-analysis of the relationship between connection to nature and PEB. We identified studies through a systematic review of the literature and used Comprehensive Meta-Analysis software to analyze the results from 37 samples (n = 13,237) and to test for moderators. A random-effects model demonstrated a positive and significant association between connection to nature and PEB (r = 0.42, 95% CI 0.36, 0.47, p < 0.001). People who are more connected to nature reported greater engagement in PEB. Standard tests indicated little effect of publication bias in the sample. There was significant heterogeneity among the samples. Univariate categorical analyses showed that the scales used to measure connection to nature and PEB were significant moderators and explained the majority of the between-study variance. The geographic location of a study, age of participants, and the percentage of females in a study were not significant moderators. We found that a deeper connection to nature may partially explain why some people behave more proenvironmentally than others and that the relationship is ubiquitous. Facilitating a stronger connection to nature may result in greater engagement in PEB and conservation, although more longitudinal studies with randomized experiments are required to demonstrate causation.


Threshold improvement and acoustic gain with hearing aids.
Aided speech reception thresholds were obtained from 20 hearing-impaired listeners with three hearing aids adjusted to confort settings, and with the aids adjusted to deliver 40 dB of acoustic gain. The aided speech reception threshold under each condition was substracted from the unaided speech reception threshold to yield a measure of threshold improvement. Threshold improvement and acoustic gain comparisons revealed that, at comfort setting, these two measures were quite similar. However, at the 40-dB gain setting, acoustic gain exceeded threshold improvement by an average of 5.6 dB. For the high-gain condition, it appeared that the threshold improvement obtained by subjects with relatively good unaided sensitivity was limited by the ambient noise in the test chamber.


Cetuximab or nimotuzumab plus intensity-modulated radiotherapy versus cisplatin plus intensity-modulated radiotherapy for stage II-IVb nasopharyngeal carcinoma.
To compare intensity-modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II-IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with stage II-IVb NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4). Efficacy and safety were compared between the CTX/NTZ and CDDP groups of this well-balanced cohort. Furthermore, we conducted multivariate analysis and subgroup analysis based on all the 1,837 eligible cases. There was no significant difference between CTX/NTZ group and CDDP group in terms of DFS (3-year, 86.7% vs. 86.2%, p > 0.05), LRRFS (96.2% vs. 96.3%, p > 0.05), DMFS (91.1% vs. 92.3%, p > 0.05) and OS (91.7% vs. 91.9%, p > 0.05). Subgroup analysis demonstrated a significant interaction effect between patients with IMRT plus CTX/NTZ and N3 node stage on LRRFS with the highest risk of loco-regional relapse (HR 8.85, p = 0.001). Significantly increased hematologic toxicities, gastrointestinal reactions were observed in the CDDP group (p < 0.05). Patients of 3.4-4.7% experienced severe hematologic toxicities during the treatment with concomitant CTX and NTZ. Increased rate of CTX related-skin reaction and mucositis was observed in the CTX group. CTX/NTZ used concurrently with IMRT may be comparable to those of the standard CDDP-IMRT combination for maximizing survival for patients with stage II-IVb NPC.


First description of buccopharyngeal anatomy in Pelodryadinae larvae: Morphological comparison and systematic implications (Anura: Hylidae: Pelodryadinae: Litoria rubella and Ranoidea caerulea).
Pelodryadinae, the Australian tree frogs, is a monophyletic group endemic to the Australo-Papuan region. Although we have a relatively good knowledge about tadpoles' phenotypic diversity in terms of external morphology, information about internal anatomy is rare for the subfamily; for instance, their buccopharyngeal cavity is completely unknown. Herein I describe for the first time the buccopharyngeal anatomy of two pelodryadins: Litoria rubella and Ranoidea caerulea. I compare my results with available evidence from Phyllomedusidae, that is, the sister clade to Pelodryadinae, and briefly comment on buccopharyngeal cavity within Hylidae. Both species can be readily distinguished based on lateral ridge, postnarial, buccal roof arena, infralabial papillae, and lingual papillae. Variation between the two species may suggest a large diversity within Pelodryadinae. Pelodryadinae and Phyllomedusinae present similar buccopharyngeal morphologies, although Agalychnis callidryas has a unique morphology and putative apomorphic transformations can be observed in Pithecopus + Phyllomedusa, Ranoidea, and Phasmahyla.


Clinical and hematological correlates of aberrant immunophenotypic profiles in adult and pediatric acute myeloid leukemia at presentation.
Aberrant phenotypes in acute leukemia have been reported with varying frequencies in independent studies and their association with prognostic factors is still a matter of debate. This study aims to identify the frequency of aberrant immunophenotypes in de novo acute myeloid leukemia (AML) and to evaluate their association with initial clinical and hematological features. A total of 181 patients of de novo AML were included during the time (July 2010-June 2012). The immunophenotype of all cases of AML was studied by using flow cytometry. Aberrant lymphoid antigen expression was seen in 43.1% cases. Most frequent aberrant lymphoid antigen was CD7, seen in 26.5% cases. All French-American-British (FAB) subtypes except AML-M3 expressed aberrant lymphoid antigens. The expression was most common in AML-M4 in the current study. CD34 expression in AMLs was significantly associated with the expression of aberrant lymphoid antigens. Lymphoid antigen expression in adult AML was significantly associated with higher white blood cell (WBC) count (>50,000/mm3) and higher number of peripheral blasts (>70%). In summary, CD7 is the most common aberrant lymphoid antigen expressed in AML. FAB subtype AML-M3 is usually not associated with aberrant lymphoid antigen expression. AML cases with CD34 positivity are more likely to express aberrant lymphoid markers. The current study also supports that aberrant lymphoid antigen expression in adult AML is associated with adverse presenting hematological features (WBC count >50,000/mm3, peripheral blasts >70%). Pediatric Ly + AML cases are not associated with adverse presenting clinical and biological features.


Investigation of betaine as a novel psychotherapeutic for schizophrenia.
Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic. Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with "betaine deficit-oxidative stress pathology". We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. The present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. FUND: This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018-2809 (YK) and RIKEN Epigenetics Presidential Fund (100214-201801063606-340120) (TY).


MicroRNA profiles in B-cell non-Hodgkin lymphoma.
B-cell non-Hodgkin's lymphomas are tumors of B-cells that arise following clonal expansion and consequent invasion of immune organs by B-cells blocked at a certain step of the differentiation process. Genetic abnormalities with altered gene expression are common in the transformed state of B-cells at any stage of B-cell development. These stages are regulated by a combination of transcription factors, epigenetic modifications, microRNAs, and extrinsic signals. MicroRNAs are a class of short non-coding single-stranded RNAs implicated in the regulation of mRNA function and translation. Each microRNA can regulate multiple transcripts; and a transcript is under potential control by multiple microRNAs. Their dysregulation can contribute to the pathogenesis of B-cell non-Hodgkin lymphomas, and they could be used as a potential target for diagnosis, evaluation of prognosis and therapy monitoring. The mechanisms of microRNA dysregulation range from dysregulation of the DNA sequences encoding the microRNAs to transcriptional regulation of microRNA loci. In this review, we summarized the microRNA profiles of the most common B-cell Non-Hodgkin Lymphomas for the pathogenesis, diagnosis and their potential therapeutic implications.


Incorporating concepts of end-of-life care into a psychiatric nursing course.
Providing quality care to patients who are at the end of life is recognized as an important aspect of health care. Nurse educators are in a unique position to influence future care by imparting essential information on this topic to students during their basic nursing education. The author offers support for the suggestion that select end-of-life concepts be included in psychiatric-mental health nursing courses and presents suggestions for incorporating such concepts into psychiatric nursing clinical learning experiences.


Utilization of both benthic macroinvertebrates and physicochemical parameters for evaluating water quality of the stream Cekerek (Tokat, Turkey).
This study examines the applicability of five European biotic indices and the Gammarus:Asellus ratio (G:A), compared with the measurement of physicochemical parameters, in order to determine the water quality at ten sites along the Tokat part of Cekerek stream, in Anatolia, Turkey, during the period February 2002 to January 2003. The biological and chemical results are in good agreement with respect to the water quality. In particular, the G:A ratio was calculated to be high at the first three stations and this result was correlated with the ETBI and the Chandler scores. Consequently, the water quality of Cekerek stream was classified as class I for biological and physicochemical data, except for phosphate, ammonia nitrogen, nitrate and nitrite at the last seven stations. The high concentrations of these chemicals probably result from agricultural runoff and urban sewage. In total, 55 taxa of benthic macroinvertebrates were identified from the Cekerek stream during this study period.


A glimpse of nursing student life in China.
When Toni Bewley first arrived at Harbin University in Daqing, north-eastern China, she was intrigued to discover that students do not undertake any clinical placements during their three-year degree courses.


Effects of the UV filter benzophenone-2 on reproduction in fish.
The UV filter benzophenone-2 (BP-2) is largely used in personal care products such as cosmetics and in numerous other materials for UV protection. Like other UV filters, BP-2 has been found to be estrogenic in vitro and in vivo, but potential effects on reproduction of fish are unknown. In this study, we evaluate whether BP-2 affects important reproductive parameters such as fecundity, gametogenesis and secondary sex characteristics. After a pre-exposure period of 19 days, reproductively mature fathead minnows (Pimephales promelas) were exposed to 0.002, 0.1, 1.2, 5.0 and 9.7 mg/L BP-2 for 15 days. BP-2 was accumulated in fish up to 3.1 microg/g body weight. In males, a dose-dependent vitellogenin induction and decrease in the number of nuptial tubercles occurred. Moreover, significant dose-related effects on gonads of male and female fish were observed. At concentrations of 1.2 mg/L and higher, spermatocyte and oocyte development was significantly inhibited in male and female fish, respectively. Testes of exposed males had much fewer spermatocytes and ovaries of exposed females had much fewer mature and more atretic follicles. Reproduction was negatively affected in a dose-dependent manner with a decrease in egg production at 5.0 mg/L and a complete cessation of spawning activity at 9.7 mg/L BP-2. Our findings show significant estrogenic effects of the common UV filter BP-2 on vitellogenin induction, secondary sex characteristics, gonadal development, and reproduction in fish.


A new water-cooled and doubly bent crystal monochromator for Compton scattering experiments.
The design and performance of a new water-cooled and doubly bent crystal monochromator for Compton scattering experiments are described. Its mechanical system is similar to that of a usual bent cylindrical X-ray mirror. A monolithic Si (111) crystal is mounted on a water-cooled and cylindrically polished copper crystal holder with liquid Ga-In alloy between them in order to obtain good thermal and mechanical contact. The sagittal bending radius of the holder, R(s), is 508 mm. The holder is mounted on a mechanical bender making a meridian radius, R(m), of 596 m. The performance of the monochromator, which has been installed at the Photon Factory Accumulator Ring beamline NE1, is as follows. The focused beam size, flux and energy resolution for 60 keV X-rays are 0.5 mm in height and 2.0 mm in width, 5 x 10(12) photons s(-1) and about 60 eV, respectively. The new monochromator gives one order higher brightness at the sample position and also better energy resolution than the previous monochromator. The overall momentum resolution for high-resolution Compton scattering experiments becomes 0.08 atomic units, and the background can be reduced by a third, because it is possible to insert a fine slit after the analyser crystal without losing any Compton scattering signal.


Ramping Up Antimicrobial Peptides Against Severe Acute Respiratory Syndrome Coronavirus-2.
Human-derived antimicrobial peptides (AMPs), such as defensins and cathelicidin LL-37, are members of the innate immune system and play a crucial role in early pulmonary defense against viruses. These AMPs achieve viral inhibition through a variety of mechanisms including, but not limited to, direct binding to virions, binding to and modulating host cell-surface receptors, blocking viral replication, and aggregation of viral particles and indirectly by functioning as chemokines to enhance or curb adaptive immune responses. Given the fact that we are in a pandemic of unprecedented severity and the urgent need for therapeutic options to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), naturally expressed AMPs and their derivatives have the potential to combat coronavirus disease 2019 (COVID-19) and impede viral infectivity in various ways. Provided the fact that development of effective treatments is an urgent public health priority, AMPs and their derivatives are being explored as potential prophylactic and therapeutic candidates. Additionally, cell-based platforms such as human mesenchymal stem cell (hMSC) therapy are showing success in saving the lives of severely ill patients infected with SARS-CoV-2. This could be partially due to AMPs released from hMSCs that also act as immunological rheostats to modulate the host inflammatory response. This review highlights the utilization of AMPs in strategies that could be implemented as novel therapeutics, either alone or in combination with other platforms, to treat CoV-2-infected individuals.


A theoretical study of the UV absorption of 4-methylbenzylidene camphor: from the UVB to the UVA region.
In this study, a theoretical approach was used to study the UV absorption of the UVB filter, 4-methylbenzylidene camphor. The main objective of this work was to design new UVA filters based on this rather photo-stable compound, so that photo-degradation in this UV region can be avoided without the use of other molecules. This objective was achieved by the simultaneous addition of two appropriate substituents, which led to red-shifts of up to 0.69 eV while maintaining appreciable oscillator strength. Also, useful structure-energy relationships were derived, which allow for the development of more UVA filters based on 4-methylbenzylidene camphor.


Matrix-producing Carcinoma as an Aggressive Triple-negative Breast Cancer: Clinicopathological Features and Response to Neoadjuvant Chemotherapy.
Breast matrix-producing carcinomas (MPCs) are rare, and usually triple-negative (TNBC; i.e. oestrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor 2-negative). This study evaluated the clinical features, immunohistochemical profiles, and pathological response to neoadjuvant chemotherapy (NAC) of patients with MPCs. Five MPCs were identified among 247 patients with TNBC receiving anthracycline- and taxane-based NAC. Pathological response was assessed using surgical specimens. All tumours were histological grade 3 according to pre-treatment core biopsies. Mean Ki-67 and p53 positivity were 65% and 90%, respectively. All tumours were TNBC, and epidermal growth factor receptor-, cytokeratin 5/6-, and vimentin-positive. Grade 3 (pathological complete response) was achieved in 0% (0/5) and 32% (77/242) of those with MPCs and with TNBCs of no specific histological type, respectively, and grade 1a (poor response) in 80% (4/5) and 13% (31/242), respectively. MPCs are basal-type TNBCs expressing epithelial-mesenchymal transition markers, with a poor response to standard NAC. Further studies are needed to improve the treatment of this rare but aggressive tumour.


5-HT modulation of pain in SI and SII revealed by fMRI.
To observe the different cerebral activations between pre-administration and post-administration of tryptophan-depleted amino acid mixture (TRP-)/balanced amino acid mixture (BAL) in healthy volunteers through functional magnetic resonance imaging (fMRI) when they received electrical stimulation at the same time. Furthermore, the effects of 5-hydroxytryptamine (5-HT) were explored in pain modulation network. Two-phase crossover design was adopted. Six right-handed healthy volunteers participated in the experiment. TRP- and BAL were administered to each participant according to the Young's method. Volunteers were scanned under fMRI with or without administration of TRP- or BAL when receiving electrical stimulation simultaneously. Analysis of functional neuroimages (AFNI) software was used to show the different activations in the human brain between pre- and post-administration of TRP-/BAL. Then all the results were analyzed by SPSS 14.0. (1) Bilateral primary somatosensory cortex (SI) and secondary somatosensory cortex (SII) were activated during pre-administration and post-administration of TRP-, but the activated volumes of bilateral SI and SII during post-administration of TRP- were found significantly larger than that during pre-administration of TRP (P<0.05). (2) All the activated regions showed no difference between pre- and post-administration of BAL. (3) There were significant differences of pain threshold between pre- and post-administration of TRP- (P<0.01), which meant that pain threshold reduced remarkably after TRP- administration, while it showed no difference between pre- and post-administration of BAL (P>0.05). 5-HT plays an important role in pain modulation in the central nervous system, TRP- causes acute tryptophan depletion (ATD) through reducing the level of 5-HT in the human brain, which can induce the decrease of volunteers' pain threshold. The activated volumes of bilateral SI and SII display significant difference between pre- and post-administration of TRP-, suggesting these brain areas may not only involve in the 5-HT related activities but in pain modulation network as well.


Wavefront-correction for nearly diffraction-limited focusing of dual-color laser beams to high intensities.
We demonstrate wavefront correction of terawatt-peak-power laser beams at two distinct and well-separated wavelengths. Simultaneous near diffraction-limited focusability is achieved for both the fundamental (800 nm) and second harmonic (400 nm) of Ti:sapphire-amplified laser light. By comparing the relative effectiveness of various correction loops, the optimal ones are found. Simultaneous correction of both beams of different color relies on the linear proportionality between their wavefront aberrations. This method can enable two-color experiments at relativistic intensities.


Strategies for identifying modifier genes in cystic fibrosis.
Even in patients with cystic fibrosis (CF) with identical CFTR genotypes, there is a wide range in the severity of lung disease, with some individuals facing death or lung transplantation early in life and others demonstrating mild lung disease well into adulthood. Although numerous environmental factors have been identified that influence CF pulmonary phenotype, there is now growing evidence that polymorphic variants in genes besides CFTR play an important role in determining severity of CF lung disease. This article reviews the most recent findings regarding genetic modifiers in CF and also discusses in detail the strategies currently being used to identify novel modifiers of CF pulmonary phenotype. These include single- and multicenter studies, twin and sib studies, microarray approaches, and whole genome association studies.


Cellular distribution of transforming growth factor-beta 1 and procollagen types I, III, and IV transcripts in carbon tetrachloride-induced rat liver fibrosis.
The cellular distribution and temporal expression of transcripts from transforming growth factor-beta 1 (TGF-beta 1) and procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) genes were studied in carbon tetrachloride (CCl4)-induced rat liver fibrosis by using in situ hybridization technique. During the fibrotic process, TGF-beta 1 and procollagen genes were similarly and predominantly expressed in Desmin-positive perisinusoidal cells (e.g., fat-storing cells and myofibroblasts) and fibroblasts and their expression continued to be higher than those observed in control rats. These transcripts were also observed in inflammatory cells mainly granulocytes and macrophage-like cells at the early stages of liver fibrosis. The production of extracellular matrix along small blood vessels and fibrous septa coincided with the expression of these genes. Expression of TGF-beta 1 and procollagen genes were not detected in hepatocytes throughout the experiment. No significant differences in cellular distribution or time course of gene expression among procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) were observed. Desmin-positive perisinusoidal cells and fibroblasts appeared to play the principal role in synthesis of collagens in CCl4-induced hepatic fibrosis. The simultaneous expression of TGF-beta 1 and procollagen genes in mesenchymal cells, including Desmin-positive perisinusoidal cells, during hepatic fibrosis suggests the possibility that TGF-beta 1 may have an important role in the production of fibrosis.


Use of Unannounced Telephone Pill Counts to Measure Medication Adherence Among Adolescents and Young Adults Living With Perinatal HIV Infection.
To examine unannounced telephone pill counts as a measure of adherence to antiretroviral therapy among adolescents and young adults living with perinatal HIV infection. Participants were recruited from an ongoing longitudinal study to complete four monthly, unannounced telephone pill counts. Detailed notes concerning participants' medication habits surrounding adherence were recorded. Two-thirds of 102 eligible participants aged 18-27 years participated; 57% were female, 69% were Black. Blacks and participants with viral loads >40 and >1,000 copies/ml were less likely to participate. Average adherence across calls was 77%. Those who completed all calls averaged significantly higher adherence scores than those who did not. Calls revealed adherence barriers at individual (e.g., medication disorganization), social (e.g., limited support), and system (e.g., pharmacy problems) levels. Despite challenges, this procedure can be implemented with this population and can help identify adherence barriers important for interventions that address medication-taking behaviors.


Laparoscopic Resection of a Jejunal Inflammatory Fibroid Polyp that Caused Occult Gastrointestinal Bleeding, Diagnosed via Capsule Endoscopy and Double-Balloon Enteroscopy: A Case Report.
An inflammatory fibroid polyp (IFP) is a mesenchymal tumor of the gastrointestinal tract. IFPs in the small intestine are the most frequently detected with symptoms, such as abdominal pain and tarry stool due to intussusception. Accordingly, few studies have reported jejunal IFP as a cause of occult gastrointestinal bleeding (OGIB) diagnosed via both of capsule endoscopy (CE) and double-balloon enteroscopy (DBE). A 68-year-old woman presented with a progression of anemia and a positive fecal occult blood test result. Esophagogastroduodenoscopy and total colonoscopy findings were unremarkable. CE revealed a tumor with bleeding in the jejunum. DBE also revealed a jejunal polypoid tumor. Bleeding from the tumor seemed to have caused anemia. The patient underwent partial laparoscopic resection of the jejunum, including resection of the tumor. The tumor was histopathologically diagnosed as IFP. To our knowledge, this is the first reported case of laparoscopic resection of jejunal IFP with OGIB diagnosed via CE and DBE preoperatively.


[Chronic hepatitis C presenting with a diagnosis of hepatocellular carcinoma].
Chronic hepatitis C (CHC) affects around 16,000 individuals in Denmark of whom about 50% are diagnosed. In the presence of CHC and cirrhosis the annual risk of hepatocellular carcinoma (HCC) is 1-5%. We report on two patients who presented with disseminated HCC at the time of CHC diagnosis. At the time of diagnosis only non-curative treatment was available. An earlier diagnosis of CHC could potentially have led to a cure and prevention of HCC.


Lck is required for stromal cell-derived factor 1 alpha (CXCL12)-induced lymphoid cell chemotaxis.
Stromal cell-derived factor 1alpha (CXCL12) induces chemotaxis of lymphocytes through its receptor CXCR4. We examined the role of nonreceptor tyrosine kinases in CXCL12-induced chemotaxis of T cells and natural killer (NK) cells. Damnacanthal, a specific Lck inhibitor, but not the Syk inhibitor piceatannol, inhibited CXCL12-induced chemotaxis of both lymphocyte subsets. Similarly, damnacanthal was shown to inhibit CXCL12-induced chemotaxis of the Jurkat T-cell line. Stimulating T and NK cells with CXCL12 increased both the tyrosine phosphorylation and the kinase activity of Lck. A direct involvement of Lck in CXCL12-induced chemotaxis was demonstrated in the Lck-deficient Jurkat-derived cell line JCaM1.6. Although JCaM1.6 cells express CXCR4, no significant migration was detected after CXCL12 stimulation. Reconstitution with wild-type Lck restored both CXCL12-induced chemotaxis and Lck activation. Furthermore, cotransfection of wild-type Lck with C-terminal Src kinase (Csk) into JCaM1.6 failed to restore the chemotactic response induced by CXCL12. Finally, by targeting critical residues in the Src homology-2 (SH2) or SH3 domains of Lck, we observed that the SH3 domain is important for the function of Lck in CXCL12-mediated chemotaxis. Together, these results suggest a role for Lck in CXCL12-induced signaling pathways leading to lymphocyte chemotaxis.


Validation of the eighth edition of the AJCC staging system for patients with pancreatic adenocarcinoma initially receiving chemoradiotherapy and proposal of modifications.
Objective: To validate the eighth edition of the AJCC staging system in patients with pancreatic adenocarcinoma receiving only stereotactic body radiation therapy and chemotherapy, and to propose modifications to improve prognostic accuracy. Methods: Patients with pathologically confirmed pancreatic adenocarcinoma without metastasis who were undergoing only chemoradiotherapy were included and staged according to the seventh and eighth editions of the AJCC staging system. Meanwhile, another group of stage T4 patients from the above enrollment with only portal vein involvement with or without tumor thrombi (PV ± PVTT) were retrieved for survival comparisons. Modifications were proposed according to the survival comparisons. A cohort from the SEER database was used for external validation of the modified staging system. Results: A total of 683 patients were included. Patients with N2 or N1 but different T stages had significantly different survival outcomes according to the eighth edition. The survival of patients with PV ± PVTT was comparable to that of patients with T4 tumors. The concordance index of the seventh and eighth editions, and the modified staging system was 0.744 (95%CI: 0.718-0.769), 0.750 (95%CI: 0.725-0.775), and 0.788 (95%CI: 0.762-0.813), respectively. For external validation, the concordance index was 0.744 (95%CI: 0.718-0.770), 0.750 (95%CI: 0.724-0.776), and 0.788 (95%CI: 0.762-0.814), respectively. Conclusions: The modified staging system is suggested to have the most accurate prognostic value. Hence, PV ± PVTT should be added to the definition of T4 tumors regardless of tumor size. Patients with N2 or N1 in different T stages could be regrouped into different substages. Additionally, stage III should be subclassified into IIIA (T3N2 and T4N0) and IIIB (T4N1-2).


[The role of melatonin in lipid peroxidation in healthy subjects].
Melatonin is naturally occurring hormone, synthesized in the pineal gland of the vertebrates. There were reports that it has an antioxidative properties connected with scavenging of reactive oxygen species. The aim of the study is to investigate the changes in the blood antioxidative activity and in lipid peroxidation after oral administration of small doses of melatonin. Melatonin was given for 2 weeks and the estimation of lenght of hormone therapy effect was carried out. Venous blood was obtained from healthy volunteers (n = 20; 12 women and 8 men, aged 42 +/- 2), who were treated with 3 mg melatonin per day. Blood was obtained before melatonin adminstration, on 7 and on 14th day of melatonin treatment, and on 10th day after last melatonin administration. The antioxidative properties were examined by FRAP method (ferric reducing ability of plasma) and concentration of lipids' peroxidation products were examined by reaction with thiobarbituric acid (TBARS). The higest plasma antioxidant activity was observed after 14 days of melatonin treatment and that increased level was maintained for the next 10 days after last dose of melatonin. The TBARS plasma concentrations reached the lowest level after 14 days of melatonin treatment and stayed the low level for 10 days after last dose of melatonin. It was estimated that oral administration of melatonin increases the plasma antioxidative properties and parallely decreases the process of lipids peroxidation. The biochemical changes were still observed on the 10th day of the end of melatonin treatment.


Diagnosis of sepsis with inflammatory biomarkers, cytokines, endothelial functional markers from SIRS patients.
Sepsis is a life-threatening illness with a challenging diagnosis. Rapid detection is the key to successful treatment of sepsis. To investigate diagnostic value, the plasma protein profiles of inflammatory biomarkers, cytokines, and endothelial functional markers were compared between healthy controls, SIRS, and septic patients. The plasma protein profiles were performed by Luminex Assay in a cohort of 50 SIRS patients, 82 septic patients and 25 healthy controls. Fourteen plasma proteins were analyzed in the same cohort: IL-1β, IL-6, IL-8, IL-10, CCL-2, VEGF, VEGF-C, VEGFR2, CD62E, CD62P, MFG-E8, ICAM-1, TFPI, Urokinase. IL-2R, IL-6, IL-8, IL-10, CCL-2, ICAM-1, and Urokinase were significantly higher in sepsis patients than SIRS patients. VEGF, IL-1β, CD62E, CD62P, MFG-E8, and TFPI have no statistical difference. VEGF-C, VEGFR2 were significantly different in SIRS patients than sepsis patients. Urokinase, ICAM-1, and VEGFR2 were significantly different between sepsis group and SIRS group. The AUCs of Urokinase, ICAM-1, and VEGFR2 and the combination for the diagnosis of sepsis were 0.650, 0.688, 0.643, and 0.741, respectively. Most patients have the higher level of several cytokines and developed endothelial cell injury in the initial phase of sepsis, Urokinase, ICAM-1, and VEGFR2 may be useful to evaluate severity and prognosis of sepsis patients.


Low Prevalence of Salmonella Enterica in Cull Dairy Cattle at Slaughter in Northern Italy.
In order to evaluate Salmonella carrier status of cull dairy cattle at slaughter, 125 animals were randomly selected during the period February-May 2016. Dairy cows were reared in 89 farms located in two regions of Northern Italy (Lombardy and Emilia-Romagna regions), where bovine milk is primarily used for Parmigiano-Reggiano cheese and Grana Padano cheese production. Samples were collected by swabbing a 400-cm2 area of the brisket hide and by rectoanal mucosal swabs. They were tested following the reference ISO 6579 method and the isolates were serotyped following the Kauffmann-White-Le Minor scheme and genotyped by XbaI PFGE. Salmonella was detected in 1.6% of the brisket hide samples (2/125) (95% CI: 0.4-5.6) and never found in faecal samples (95% CI: 0-3%). The positive cattle were reared in two farms located only in Emilia-Romagna region. The isolates were typed as S. Derby and S. Seftenberg. The comparison of the pulsed-field gel electrophoresis (PFGE) patterns of the bovine strains with all the PFGE patterns of the same serotypes responsible for human salmonellosis cases notified in Emilia-Romagna region in the years 2013-2015 did not find any correspondence. Therefore, the role of cull dairy cattle in transmitting Salmonella to humans seems to be less important than those of pigs and poultry in EU, but more data are needed for completing attribution source studies.


Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids.
Diverse classes of phytochemicals initiate biological responses that effectively lower cancer risk. One class of phytochemicals, broadly defined as pure and mixed isoprenoids, encompasses an estimated 22,000 individual components. A representative mixed isoprenoid, gamma-tocotrienol, suppresses the growth of murine B16(F10) melanoma cells, and with greater potency, the growth of human breast adenocarcinoma (MCF-7) and human leukemic (HL-60) cells. beta-Ionone, a pure isoprenoid, suppresses the growth of B16 cells and with greater potency, the growth of MCF-7, HL-60 and human colon adenocarcinoma (Caco-2) cells. Results obtained with diverse cell lines differing in ras and p53 status showed that the isoprenoid-mediated suppression of growth is independent of mutated ras and p53 functions. beta-Ionone suppressed the growth of human colon fibroblasts (CCD-18Co) but only when present at three-fold the concentration required to suppress the growth of Caco-2 cells. The isoprenoids initiated apoptosis and, concomitantly arrested cells in the G1 phase of the cell cycle. Both suppress 3-hydroxy-3-methylglutaryl CoA reductase activity. beta-Ionone and lovastatin interfered with the posttranslational processing of lamin B, an activity essential to assembly of daughter nuclei. This interference, we postulate, renders neosynthesized DNA available to the endonuclease activities leading to apoptotic cell death. Lovastatin-imposed mevalonate starvation suppressed the glycosylation and translocation of growth factor receptors to the cell surface. As a consequence, cells were arrested in the G1 phase of the cell cycle. This rationale may apply to the isoprenoid-mediated G1-phase arrest of tumor cells. The additive and potentially synergistic actions of these isoprenoids in the suppression of tumor cell proliferation and initiation of apoptosis coupled with the mass action of the diverse isoprenoid constituents of plant products may explain, in part, the impact of fruit, vegetable and grain consumption on cancer risk.


Cystic fibrosis newborn screening: impact of early screening results on parenting stress.
Newborn screening for cystic fibrosis (CF) is currently available through dried blood analysis for immunoreactive trypsinogen (IRT). The possible parenting stress associated with false-positive results or the early diagnosis of an asymptomatic infant has yet to be systematically addressed. This exploratory study examined levels of parenting stress among mothers of these infants. Results indicated significantly less total parenting stress but greater defensiveness in responding among families of false-positive screened children relative to their healthy comparison families. Parents of children diagnosed with CF through newborn screening did not show significantly higher stress scores than their healthy or "traditionally-diagnosed" CF comparison families. They did however have high frequencies of "at-risk scores" warranting referral based on clinical cut-off levels for Total Parenting Stress scores (45%) and Child Demandingness subscale score (50%). As the possibility for expanding CF neonatal screening to other states is considered, the need for further exploration of psychosocial sequelae affecting parenting will be increasingly important.


Increased tissue factor pathway inhibitor and homocysteine in Alzheimer's disease.
We investigated the possible involvement of vascular damage in the pathogenesis of Alzheimer's disease (AD), by assessment of plasma levels of tissue factor pathway inhibitor (TFPI), a serine protease inhibitor induced by endothelial injury, and homocysteine (Hcy), a known risk factor for cerebrovascular disorders, folate levels were also measured. 110 probable AD, 38 mild cognitive impairment, 31 patients affected by idiopathic Parkinson's disease (without dementia) and 100 healthy controls, who displayed no vascular disorders were enrolled. TFPI and Hcy were significantly higher in AD patients with respect to other groups. The levels of TFPI and Hcy were positively correlated in hyperhomocysteinemic AD and mild cognitive impairment subjects, and were negatively correlated with folate levels. Our findings suggest that an impairment of endothelial function associated with high Hcy levels may occur in AD patients, despite the absence of manifest cerebrovascular lesions. Therefore, TFPI may represent a candidate marker of endothelial damage in AD and might be used for the identification and monitoring of patients that would benefit from folate supplementation treatment.


Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions--parallels and contrasts.
The emergence of diuretic drugs and angiotensin converting enzyme (ACE) inhibitors ranks amongst the major therapeutic advances of modern medicine. The discovery of these drug groups arose largely by chance, yet each has dramatically influenced the treatment of congestive cardiac failure and arterial hypertension. The central role which diuretics have had in the management of both oedema and hypertension hinges on their ability to induce a net renal excretion of solute and water by selective interference with either active or passive ion transport processes in different segments of the nephron. Irrespective of sites of action, the continued antihypertensive action of diuretics is characterized by a reduction in plasma volume and extracellular fluid (ECF) volume that lasts for as long as the diuretic is given. The mechanism of this effect remains unclear but may involve autoregulatory reactions that leave cardiac output unaltered but maintain a sustained reduction in total peripheral resistance. ACE inhibitors also lower blood pressure by decreasing total peripheral resistance, leaving cardiac output, plasma volume and ECF volume unchanged. The detailed way these haemodynamic changes are achieved remains unknown but inhibition of converting enzyme present not only in the kidney but also in many extrarenal tissue sites, appears important. In both hypertension and cardiac failure, however, the kidney acts as a key target organ for ACE inhibitors. The increased renal vascular resistance and inappropriate renal salt excretion are reversed with enhanced renal blood flow and saluresis. Both angiotensin II (AII) and vasopressin-mediated contraction of glomerular mesangial cells is inhibited, making glomerular filtration more efficient. Reduced aldosterone secondary to blockade of AII formation contributes to saluresis whilst encouraging positive potassium balance. ACE inhibition also impairs breakdown of kinins which may contribute to intrarenal and peripheral vasodilation either on their own or via release of prostaglandins and other vasoactive substances. The hypotensive actions of diuretics are potentiated by ACE inhibition primarily through blockade of AII formation and prevention of secondary aldosteronism. In combination, these drugs permit low doses to be used because of their synergistic effects. Caution has to be exercised whenever ACE inhibition is used, without and especially with diuretics, in the management of renovascular hypertension and other low-perfusion states. In these circumstances, AII plays an important autoregulatory role in preserving glomerular filtration through an increase in post-glomerular resistance.(ABSTRACT TRUNCATED AT 400 WORDS)


Quantitative evaluation of the murine B16 melanoma tumor model after gene marking with an EGFP/Neo expressing retroviral vector.
Reliable evaluation of tumor growth in animal models depends upon accurate identification of all malignant cells in affected organs. An ideal tumor cell label is non-toxic, labels the cells in a population uniformly and does not affect their biological behavior. A good candidate for such a cell label is enhanced green fluorescence protein (EGFP). However, the stability of EGFP expression and the characteristics of EGFP-marked tumors cells in vivo have not yet been elucidated in detail. We here report that a B16 murine melanoma subline stably transduced with an EGFP/Neo encoding retroviral vector display the same growth patterns in vitro and in vivo as the parental cell line. Furthermore, the transduced cells were found to maintain the level of EGFP expression in vivo for at least 15 days. Thus, B16 malignant melanoma cells stably transduced with the gene for EGFP seem well suited for studies on tumor growth in mouse models.


Resuscitation after uncontrolled venous hemorrhage: Does increased resuscitation volume improve regional perfusion?
Recent studies have questioned the use of aggressive fluid resuscitation after uncontrolled arterial hemorrhage until the bleeding is controlled. However, it remains unknown whether resuscitation after hemorrhage from a venous origin (usually nonaccessible to surgical intervention) has any beneficial or deleterious effects on regional perfusion. The aim of this study, therefore, was to determine whether increased volume of fluid resuscitation after uncontrolled venous hemorrhage improves hemodynamic profile and regional perfusion in various tissues. After methoxyflurane anesthesia and midline laparotomy, both lumbar veins in the rat were severed, which resulted in lowering the mean arterial blood pressure to approximately 40 mm Hg. This pressure was maintained for 45 minutes by allowing further bleeding from the lumbar veins. The abdominal incision was then closed in layers and the animals received either 0, 10, or 30 mL of lactated Ringer's solution intravenously over a period of 60 minutes. Cardiac output and regional blood flow were determined by radioactive microspheres immediately or at 1.5 hours after the completion of resuscitation. Fluid resuscitation with 10 or 30 mL lactated Ringer's solution increased mean arterial blood pressure and cardiac output immediately after resuscitation compared with the nonresuscitated animals. At both time points, regional perfusion in the heart, kidney and intestines remained significantly decreased compared with the sham values, irrespective of the volume of fluid resuscitation. Moreover, no further improvements in hemodynamics or regional perfusion occurred when volume resuscitation was increased from 10 mL to 30 mL. Total hepatic blood flow, however, increased with 10 mL lactated Ringer's solution compared with the other hemorrhage groups and the increase was evident even at 1.5 hours after resuscitation. Fluid resuscitation after uncontrolled venous bleeding transiently increased cardiac output and mean arterial blood pressure compared with nonresuscitated animals. Moderate fluid administration, i.e., 10 mL, however, did increase total hepatic blood flow. In contrast, increasing the resuscitation volume to 30 mL did not improve hemodynamic parameters or regional perfusion. Thus moderate instead of no resuscitation or larger volume of resuscitation is recommended in an uncontrolled model of venous hemorrhage.


Alternative to the gold standard for alveolar ridge augmentation: tenting screw technology.
Studies have discussed the potential issues associated with the placement of implants in unfavorable locations. Today, it is possible to optimize implant placement despite the significant ridge resorption that often occurs after tooth extraction. This objective is achievable because techniques exist to augment resorbed alveolar ridges to prerequisite widths and heights for proper implant position. A group of surgical procedures have evolved that are considered to be the gold standard for achieving alveolar ridge width and height augmentation. This article discusses the purported gold standard procedure of onlay block grafts for ridge augmentation and contrasts those grafts with the equally successful, more time- and cost-effective tenting screw technology, in conjunction with guided bone regeneration, which has less morbidity and involves only one surgical site. Three cases are presented to illustrate the utilization and effectiveness of tenting screw technology.


Work performance of high-altitude Aymara males.
The sample for this study consisted of 28 Aymara males between the ages of 15 and 43 years. The subjects were rural high-altitude natives who were temporarily working as porters in La Paz, Bolivia (3700 m). Mean VO2max was 46 X 5 ml/kg/min. There was a significant negative relationship between VO2max and age in adult porters . However, there was also a significant positive relationship between maximal work output and age and a significant negative relationship between VO2 during submaximal exercise and age. Relative work intensity (VO2/VO2max) during submaximal exercise did not change significantly with age. Thus, even though VO2max decreased significantly with age, these data suggest that there may not be a substantial decrease with age in the adaptive status of these men. Minimal support was found for the hypothesis that chest size in Andean highlanders influences the effectiveness of the oxygen transport system.


The European Brain Injury Questionnaire (EBIQ) as a reliable outcome measure for use with people with brain injury.
There is a need to develop reliable outcome measures to determine well-being after brain injury. In 1997, Teasdale et al. published the European Brain Injury Questionnaire (EBIQ), a self-report and relative-report measure of the subjective experience of cognitive, emotional and social difficulties experienced by people with brain injury. It is now used in several rehabilitation centres as an outcome measure, but its test-re-test reliability has yet not been determined. The primary purpose of the present study is to establish this degree of reliability. The EBIQ was administered twice within an approximately 1-month period to 50 people with brain injury, to 20 relatives of people with brain injury and to 51 normal controls. The results showed significant and satisfactory test-re-test reliabilities for all three groups across all nine EBIQ scales (r = 0.55-0.90). It is concluded that the EBIQ is a clinically reliable measure to determine the subjective well-being of people with brain injury and to assess change of subjective concerns over time.


Serum cytocines values in patients after endoscopic surgery for ureteral lithiasis.
Obstructive uropathy due to ureteral stones can cause renal infection and, if left untreated, can cause impairment of renal function. Endoscopic surgery such as ureteroscopy (URS) and laser lithotripsy are the primary therapeutic approach. Cytokines as non invasive markers may have a role to diagnose ureteral damage and infection. We aimed to evaluate serum cytokine levels of tumor necrosis factor-a (TNFa) and interleukin-6 (IL6) in patients undergoing URS and holmium laser lithotripsy. The study included 40 patients (male 25 and 15 female) with a mean age of 47 years and 10 healthy blood donors serving as the control group. None of them had any additional systemic diseases, previous insertion of a ureteral double "j" stent or of a nephrostomy tube, neoplasmatic disease ot renal insufficiency. Routine urine examination and urine culture were obtained to exclude urinary infection. Preoperatively and 1h, 2h, 24h and 48h postoperatively serum samples of TNF-a and IL-6 were collected and measured. Serum TNFa and IL-6 values were correlated with the other variables measured from blood samples after the URS using paired samples Students t-test with confidence interval 95%. A P value of less than 0.01 was considered statistically significant. Correlation between serum TNF-a and IL6 levels with healthy donors were statistically significant in 1h (0.004), 2h (0.001), 24h (0.001) and 48h (0.001 and 0.001) postoperatively, respectively. In conclusion, our study shows that cytokines could be helpful as markers of renal tissue damage. However, further studies are needed to get more accurate results.


Lessons from ximelagatran: issues for future studies evaluating new oral direct thrombin inhibitors for venous thromboembolism prophylaxis in orthopedic surgery.
Venous thromboembolism is a frequent complication of total hip and knee replacement requiring prophylaxis with anticoagulants. A direct thrombin inhibitor-ximelagatran-did not show advantages over other anticoagulants and it was withdrawn from the market; however, new drugs are being developed. We conducted a systematic review and meta-analysis to identify conditions under which ximelagatran might potentially be superior to current standards. Medline, EMBASE, the Cochrane Library, and grey literature were screened for randomized trials comparing ximelagatran with warfarin or low-molecular-weight heparin for thromboprophylaxis in total hip or knee replacement. Two reviewers independently assessed and extracted data. A meta-analysis with especial attention to statistical heterogeneity was conducted. This study suggested that the risk-benefit profile of ximelagatran-and probably other similar agents-depends on the type of surgery, the initial timing of administration, and probably the dose. These issues should be explicitly explored in future trials evaluating new direct thrombin inhibitors.


Muckle-Wells syndrome in the setting of basal cell nevus syndrome.
Muckle-Wells syndrome (MWS) is a rare disorder inherited in an autosomal-dominant fashion that belongs to a group of hereditary periodic fever syndromes. It specifically belongs to the cryopyrin-associated periodic syndromes (CAPSs) in which there is a mutation in the NLRP3 (NLR family pyrin domain containing 3) gene that leads to overproduction of IL-1β, the source of the multisystem inflammatory symptoms. Muckle-Wells syndrome is characterized by a recurrent urticarial eruption that is associated with episodic fever, myalgia, arthralgia, malaise, progressive sensorineural hearing loss, and amyloid nephropathy (the most severe complication). Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare, autosomal-dominant inherited genodermatosis linked to a mutation in the PTCH1 (patched 1) gene and is characterized by a broad range of anomalies. We report the case of a patient with MWS and BCNS in whom basal cell carcinoma (BCC) treatment was complicated by symptoms of MWS.