Tracing the evolution of RNA structure in ribosomes.
The elucidation of ribosomal structure has shown that the function of ribosomes is fundamentally confined to dynamic interactions established between the RNA components of the ribosomal ensemble. These findings now enable a detailed analysis of the evolution of ribosomal RNA (rRNA) structure. The origin and diversification of rRNA was studied here using phylogenetic tools directly at the structural level. A rooted universal tree was reconstructed from the combined secondary structures of large (LSU) and small (SSU) subunit rRNA using cladistic methods and considerations in statistical mechanics. The evolution of the complete repertoire of structural ribosomal characters was formally traced lineage-by-lineage in the tree, showing a tendency towards molecular simplification and a homogeneous reduction of ribosomal structural change with time. Character tracing revealed patterns of evolution in inter-subunit bridge contacts and tRNA-binding sites that were consistent with the proposed coupling of tRNA translocation and subunit movement. These patterns support the concerted evolution of tRNA-binding sites in the two subunits and the ancestral nature and common origin of certain structural ribosomal features, such as the peptidyl (P) site, the functional relay of the penultimate stem helix of SSU rRNA, and other structures participating in ribosomal dynamics. Overall results provide a rare insight into the evolution of ribosomal structure.


Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma.
Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation. Immuno-histochemistry was performed (IGF-IR α and β, GAPDH, HIF-1 alpha, Survivin, GLUT1, CAIX, hTERT and HKII). Response to radiation was assessed through tumour response 3 months after RT completion, through overall survival (OS) and through progression-free survival (PFS). One hundred forty nine patients with a mean age of 46 years were included, with FIGO IIB (n = 53) and FIGO IIIB (n = 96) CCs. 61 patients were treated with exclusive RT + brachytherapy and 88 underwent chemo-radiotherapy + brachytherapy. Our findings suggest an association between hemoglobin level (Hb) (>11 g/dL) and 3 months complete response (p = 0.02). Hb level < 11 g/dL was associated with decreased PFS (p = 0.05) and OS (p = 0.08). Overexpression of IGF-1R β was correlated with a decreased OS (p = 0.007). Overexpression of GLUT1 was marginally correlated with reduced OS (p = 0.05). PFS and OS were significantly improved in patients undergoing chemoradiation versus exclusive radiotherapy (PFS: p = 0.04; OS: p = 0.01). IGF-1R β overexpression and Hb level (≤11 g/dl) were associated with poor prognosis, and thus appear to be possible interesting biomarkers of radiation resistance. Our results corroborate previous pre-clinical studies suggesting IGF-1R and hypoxia to be part of the biological pathways leading to radio-resistance.


OSR1 disruption contributes to uterine factor infertility via impaired Müllerian duct development and endometrial receptivity.
Three sisters, born from consanguineous parents, manifested a unique Müllerian anomaly characterized by uterine hypoplasia with thin estrogen-unresponsive endometrium and primary amenorrhea, but with spontaneous tubal pregnancies. Through whole-exome sequencing followed by comprehensive genetic analysis, a missense variant was identified in the OSR1 gene. We therefore investigated OSR1/OSR1 expression in postpubertal human uteri, and the prenatal and postnatal expression pattern of Osr1/Osr1 in murine developing Müllerian ducts (MDs) and endometrium, respectively. We then investigated whether Osr1 deletion would affect MD development, using WT and genetically engineered mice. Human uterine OSR1/OSR1 expression was found primarily in the endometrium. Mouse Osr1 was expressed prenatally in MDs and Wolffian ducts (WDs), from rostral to caudal segments, in E13.5 embryos. MDs and WDs were absent on the left side and MDs were rostrally truncated on the right side of E13.5 Osr1-/- embryos. Postnatally, Osr1 was expressed in mouse uteri throughout their lifespan, peaking at postnatal days 14 and 28. Osr1 protein was present primarily in uterine luminal and glandular epithelial cells and in the epithelial cells of mouse oviducts. Through this translational approach, we demonstrated that OSR1 in humans and mice is important for MD development and endometrial receptivity and may be implicated in uterine factor infertility.


A molecular recognition strategy towards tetra-chlorinated dibenzo-p-dioxins, TCDDs.
Uniformly sized polymeric separation media were prepared using o- or p-xylene as porogenic template to investigate chromatographic selectivity towards tetra-chlorinated dibenzo-p-dioxins (TCDDs). TCDDs having chlorine atoms at ortho positions of phenyl rings were selectively retained on stationary phase prepared with o-xylene as porogenic template, while TCDDs having chlorine atoms at para positions of phenyl ring were found to be retained selectively on the stationary phase imprinted by the porogenic template, p-xylene. Slightly longer cross-linking agent afforded chromatographically selective retention for larger TCDD isomers. It was also found that positional relationship between substituted chlorine atoms was also important for chromatographic recognition.


Successful rehabilitation of partial edentulous maxilla and mandible with new type of implants: molecular precision implants.
The extraction of teeth results in rapid bone resorption both vertically and horizontally in the first month. The loss of alveolar ridge reduces the chance of implant rehabilitation. Atraumatic extraction, implant placement in extraction socket, and an immediate prosthesis have been proposed as alternative therapies to maintain the volume and contours tissue and reduce time and cost of treatment. The immediate load of implants is a universally practiced procedure; nevertheless a successful procedure requires expertise in both the clinical and the reconstructive stages using a solid implant system. Excellent primary stability and high bone-implant contact are only minimal requirements for any type of implant procedure. In this paper we present a case report using a new type of implants. The new type of implants, due to its sophisticated control system of production, provides to the implantologist a safe and reliable implant, with a macromorphology designed to ensure a close contact with the surrounding bone.


Game theory, conditional preferences, and social influence.
Neoclassical noncooperative game theory is based on a simple, yet powerful synthesis of mathematical and logical concepts: unconditional and immutable preference orderings and individual rationality. Although this structure has proven useful for characterizing competitive multi-player behavior, its applicability to scenarios involving complex social relationships is problematic. In this paper we directly address this limitation by the introduction of a conditional preference structure that permits players to modulate their preference orderings as functions of the preferences of other players. Embedding this expanded preference structure in a formal and graphical framework provides a systematic approach for characterizing a complex society. The result is an influence network that allows conditional preferences to propagate through the community, resulting in an emergent social model which characterizes all of the social relationships that exist and which leads to solution concepts that account for both group and individual interests. The Ultimatum game is presented as an example of how social influence can be modeled with conditional preferences.


[Diagnostic value of interleukin-10 and interleukin-6 in the vitreous of intraocular malignant lymphoma patients].
Recent data suggest that the concentration of interleukin-10 (IL-10) is higher than that of interleukin-6 (IL-6) in the vitreous of eyes of patients with non-Hodgkin's lymphoma. In this study, we evaluated the utility of measuring intravitreal IL-10 and IL-6 concentrations in the diagnosis of intraocular lymphoma. Specimens of undiluted vitreous were collected at the time of pars plana vitrectomy and IL-10 and IL-6 concentrations were determined. Vitreous specimens were obtained from 5 patients with suspected intraocular lymphoma and 10 patients with uveitis presumed to be unrelated to a neoplasm. In all 5 patients eventually diagnosed with intraocular lymphoma, the vitreous IL-10 concentration ranged from 3,040 to 11,200 pg/ml, and was higher than the vitreous IL-6 concentration in all cases. In 9 of the 10 patients with uveitis, the vitreous IL-10 concentrations ranged from less than 2 to 97 pg/ml, with an IL-10/IL-6 ratio of less than 0.11. However, in the remaining case diagnosed as uveitis of unknown etiology, the vitreous IL-10/IL-6 ratio was greater than 1. Our data suggest that the measurement of vitreous IL-10 concentrations would aid in the diagnosis of intraocular lymphoma.


Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia.
Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205.


Writing in a Digital World: Self-Correction While Typing in Younger and Older Adults.
This study examined how younger and older adults approach simple and complex computerized writing tasks. Nineteen younger adults (age range 21-31, mean age 26.1) and 19 older adults (age range 65-83, mean age 72.1) participated in the study. Typing speed, quantitative measures of outcome and process, and self-corrections were recorded. Younger adults spent a lower share of their time on actual typing, and demonstrated more prevalent use of delete keys than did older adults. Within the older group, there was no correlation between the total time spent on the entire task and the number of corrections, but increased typing speed was related to more errors. The results suggest that the approach to the task was different across age groups, either because of age or because of cohort effects. We discuss the interplay of speed and accuracy with regard to digital writing, and its implications for the design of human-computer interactions.


Single-walled carbon nanotube-based near-infrared optical glucose sensors toward in vivo continuous glucose monitoring.
This article reviews research efforts on developing single-walled carbon nanotube (SWNT)-based near-infrared (NIR) optical glucose sensors toward long-term in vivo continuous glucose monitoring (CGM). We first discuss the unique optical properties of SWNTs and compare SWNTs with traditional organic and nanoparticle fluorophores regarding in vivo glucose-sensing applications. We then present our development of SWNT-based glucose sensors that use glucose-binding proteins and boronic acids as a high-affinity molecular receptor for glucose and transduce binding events on the receptors to modulate SWNT fluorescence. Finally, we discuss opportunities and challenges in translating the emerging technology of SWNT-based NIR optical glucose sensors into in vivo CGM for practical clinical use.


Emotion in the criminal psychopath: fear image processing.
We tested the hypothesis that the response mobilization that normally accompanies imagery of emotional situations is deficient in psychopaths. Cardiac, electrodermal, and facial muscle responses of 54 prisoners, assigned to low- and high-psychopathy groups using R. D. Hare's (1991) Psychopathy Checklist--Revised, were recorded while subjects imagined fearful and neutral scenes in a cued sentence-processing task. Groups did not differ on self-ratings of fearfulness, imagery ability, or imagery experience. Low-psychopathy subjects showed larger physiological reactions during fearful imagery than high-psychopathy subjects. Extreme scores on the antisocial behavior factor of psychopathy predicted imagery response deficits. Results are consistent with the idea that semantic and emotional processes are dissociated in psychopaths.


'Trophic whales' as biotic buffers: weak interactions stabilize ecosystems against nutrient enrichment.
Human activities may compromise biodiversity if external stressors such as nutrient enrichment endanger overall network stability by inducing unstable dynamics. However, some ecosystems maintain relatively high diversity levels despite experiencing continuing disturbances. This indicates that some intrinsic properties prevent unstable dynamics and resulting extinctions. Identifying these 'ecosystem buffers' is crucial for our understanding of the stability of ecosystems and an important tool for environmental and conservation biologists. In this vein, weak interactions have been suggested as stabilizing elements of complex systems, but their relevance has rarely been tested experimentally. Here, using network and allometric theory, we present a novel concept for a priori identification of species that buffer against externally induced instability of increased population oscillations via weak interactions. We tested our model in a microcosm experiment using a soil food-web motif. Our results show that large-bodied species feeding at the food web's base, so called 'trophic whales', can buffer ecosystems against unstable dynamics induced by nutrient enrichment. Similar to the functionality of chemical or mechanical buffers, they serve as 'biotic buffers' that take up stressor effects and thus protect fragile systems from instability. We discuss trophic whales as common functional building blocks across ecosystems. Considering increasing stressor effects under anthropogenic global change, conservation of these network-intrinsic biotic buffers may help maintain the stability and diversity of natural ecosystems.


Ultrasound guided transgluteal sciatic nerve hydrodissection for the treatment of acute sciatica in the emergency department.
Radicular pain due to sciatica is a common occurrence with a lifetime incidence of up to 40%. Typical approaches to treatment vary and may include topical and oral analgesics, such as opioids, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs); however, these medications may be contraindicated in some or result in untoward effects in others. The use of ultrasound-guided regional anesthesia is an important component of multimodal analgesia in the emergency department. Transgluteal sciatic nerve block has been described as an effective method to treat patients with sciatica but carries risk of injury and falls due to its resultant loss of motor function and potential for systemic toxicity when higher volumes are used. Ultrasound-guided peripheral nerve hydrodissection with D5W has been shown to be an effective treatment of various compressive neuropathies in the outpatient setting. Here we present 4 cases of patients who presented to the emergency department with severe acute sciatica and were treated successfully using an ultrasound guided transgluteal sciatic nerve hydrodissection (TSNH). This technique may offer a safe and effective approach to treating patients with sciatica, but more studies are needed to assess its utility on a larger scale.


Non-estrogenic approaches for the treatment of climacteric symptoms.
Non-estrogenic alternatives for the treatment of climacteric symptoms have their origin lost in history. Recent clinical trial data have shown that lifestyle and diet adjustment have some effect in improving both hot flushes and mood. Over-the-counter phytotherapeutic extracts are very popular and women often try a variety of products before resorting to traditional medicine. Preparations containing isoflavones in variable doses, such as soy extract and red clover, or extracts from evening primrose, Cimifuga racemosa, ginseng and black cohosh are often used for treating the climacteric syndrome. The scientific support for their efficacy certainly does not equal their popularity. The most tested pharmacological alternatives to estrogens are serotonin reuptake inhibitors (SSRIs). All available SSRIs have undergone trials for the relief of hot flushes. In spite of the difference between the compounds in both half-life and engagement of serotonin receptors, they appear to have very similar effectiveness in reducing hot flushes. At their best, SSRIs reduce hot flushes by 50-60%, compared with 80% for estrogen, and their effect appears only in the short term. SSRIs have mood-improving effects that appear to be independent of the effect on hot flushes. When used for the treatment of the climacteric syndrome, SSRIs do not adversely affect libido. Dependence is a major concern in women when offered this type of treatment, but does not appear to be a problem with this class of drugs. Withdrawal symptoms have never been reported in trials for hot flushes but are known to occur when SSRIs are used in the long term. In order to avoid these symptoms, the dose should be tapered slowly. Gabapentin, a drug used for the treatment of neuropathic pain and epilepsy, has shown that, in high doses, it has an efficacy similar to that of estrogen; however, this needs further confirmation.


Changes in immunoreactivity of orexin-A-positive neurons after intravenous lipopolysaccharide injection.
Orexins are neuromediators that help regulate many different physiological processes; however, their role in regulating immune system functioning is unclear. This study sought to investigate the distribution of orexin in hypothalamic orexin-containing neurons during the first 6 hours after an intravenous injection of a lipopolysaccharide. Orexin-containing neurons were detected by immunohistochemistry (avidin-biotin) on frontal sections from the brains of intact rats and rats after injections of either saline or lipopolysaccharide. Analysis of immunohistochemically stained sections (levels 26-32 according to Swanson's atlas) revealed that the main pool of orexin-containing neurons was located at brain levels 28 to 30. No changes were shown in the number of orexin-containing neurons in the hypothalamus of intact animals at different times of a day. Visualization of orexin-containing neurons in the lateral hypothalamus decreased only in 6 hours after an injection of lipopolysaccharide (500 microg/kg body weight) at levels 28, 29, and 30 of the rat brain; this might have been the result of changes in the balance of orexin synthesis and utilization. These data suggest that orexin-containing neurons play a role in complex reactions in the brain to lipopolysaccharide application.


[Review on fragmentary volume of original block - printed edition of Nan jing ben yi (Gist of the Classic of Questioning)].
Nan jing ben yi (Gist of the Classic of Questioning) was written by Hua Shou of the Yuan dynasty. The extant first volume of the original block - printed edition, revised by Lü Fu, was collected in the Library of China Academy of Military Medical Science. There is a preface written by Jie Hong, a Director Ministry of Techndogy in 1366 at the front of this volume. The red seal in the first page showed that it had been collected by Yun Xiang, Pan Zuyin et al. It is highly possible that this volume is the only existing copy.


Extracellular matrix and airway smooth muscle interactions: a target for modulating airway wall remodelling and hyperresponsiveness?
The airway smooth muscle from asthmatic airways produces increased amounts and an altered composition of extracellular matrix proteins. The extracellular matrix can in turn influence the phenotype and function of airway smooth muscle cells, affecting the biochemical, geometric, and mechanical properties of the airway wall. This review provides a brief overview of the current understanding of the biology associated with airway smooth muscle interactions with the extracellular matrix. We present future directions needed for the study of cellular and molecular mechanisms that determine the outcomes of extracellular matrix - airway smooth muscle interactions, and discuss their possible importance as determinants of airway function in asthma.


Engineered Zymomonas mobilis for salt tolerance using EZ-Tn5-based transposon insertion mutagenesis system.
The cell growth and ethanol yield of Zymomonas mobilis may be detrimentally affected by salt stress frequently present in some biomass-based fermentation systems, leading to a decrease in the rate of sugar conversion to ethanol or other bioproducts. To address this problem, improving the salt tolerance of Z. mobilis is a desirable way. However, limited progress has been made in development of Z. mobilis with higher salt tolerance for some technical challenges in the past decades. Recently, transposon insertion mutant system has been widely used as a novel genetic tool in many organisms to develop mutant strains. In this study, Tn5-based transposon insertion mutagenesis system firstly used for construction of higher salt tolerance strain in Z. mobilis. Approximately 200 Z. mobilis ZM4 mutants were generated by using Tn5-based transposon mutagenesis system. The mutant strain ZMT2 with improved salt tolerance phenotype was obtained by screening on RM agar plates with additional 1 % NaCl. Strain ZMT2 was confirmed to exhibit better fermentation performance under NaCl stress than wild type of strain ZM4. The transposon insertion was located in ZMO1122 (himA) by genome walking. Discruption of himA gene showed that himA may play an important role in response to salt tolerance in Z. mobils. The mutant strain ZMT2 with a transposon insertion in himA gene of the genome showed obviously higher sugar conversion rate to ethonal under up to 2 % NaCl stress than did the wild ZM4 strain. Besides, ZMT2 exhibited shared fermentative capabilities with wild ZM4 strain under no or low NaCl stress. This report firstly showed that himA played a role in responding to NaCl stress. Furthermore, the result indicated that Tn5-based transposon mutagenesis system was a feasible tool not only for genetic engineering in Z. mobilis strain improvement, but also in tapping resistent genes.


A path model of factors influencing the academic performance of nursing students.
The aim of this study was to build and test a model describing some of the psychological processes underlying nursing students' academic performance. The model hypothesized that age and entry qualifications influence students' academic motivation (locus of control, academic worries, self-efficacy, and expectations), and that this in turn affects their decisions to seek support, which subsequently influences their academic performance. A literature search showed that previous academic motivation research is piecemeal. The present work sought to integrate previous findings into a coherent framework as a way of advancing our understanding of the complex interactive nature of the factors influencing student performance. Path analysis was performed on data obtained from questionnaires and university records for 315 students undertaking a preregistration diploma course in nursing at a university in the Northwest of England. Support-seeking was more predictive of student performance than entry qualifications. Support-seeking also mediated the age-performance relationship: greater willingness to seek support led to the better academic performance of older students. Other features of the accepted model suggested that students who judged their self-efficacy to be higher expected higher grades and that these highly optimistic expectations led to less support-seeking. Academic worries and internal control beliefs were also found to have positive influences on support-seeking. The model developed accounted for 24% of the variance in students' academic performance. Implications for nurse education, and interventions that focus on improving students' academic motivation are discussed in the context of the 'personal teacher' support framework.


[Surveys on the implementation of "rules on stop smoking in the public places in Beijing" from 1997 to 2004].
To find out the situation of the implementation on "rules on stop smoking in the public places in Beijing", a study was carried out to compare the results from 1997 and 2001. Thousands of residents aged above 15 in a family were sampled by stratified sampling, and 4 districts were selected as study locales. (1) About 40% of the department or school leaders considered much about the work on banning of smoking with 70 % of the departments or schools having posters of signs on 'ban on smoking' in the meeting rooms. (2) Some of the departments or schools had inspectors looking after the issue. (3) 60% of the people had never or 10% had seen that the inspectors ever criticizing or punishing the smokers who violating the rules. (4) People still often saw some one would smoke in public (the rates were 19.53% , 37.89% , 6.35% respectively in 1997,2001,2004 ). (5) People received the information of these rules through TV news or newspaper. Although success had been achieved since the implementation of the Rules, it did not seem to have had substantial progress.


Alternative theories of happiness in early adolescents.
The purpose of this study was to examine a set of variables representing enabling mechanisms vis-à-vis a set of variables representing personality characteristics in relation to happiness in early adolescents: these two theoretical perspectives were assessed using hierarchical analyses of sets that determined which of the two has greater explanatory power in relation to happiness. The final sample consisted of 127 early adolescents, ages 12 to 14, who responded to instruments measuring happiness, self-esteem, future time perspective, optimism, vigor, change, and social support in classrooms. Using hierarchical analyses of sets, the results indicated that the enabling mechanisms set explained more variance in happiness when entered first (65%) or second (22%) than did the personality characteristics set when entered first (50%) or second (7%) in the analyses. Implicationsfor nursing are addressed.


Role of oral contraceptive in atherosclerosis.
The possibility that risk of a atherosclerosis complication increases with oral contraceptive use was examined by studying the effect of oral pill containing 0.067 mg menstranol and 0.667 mg ehtynodiol diacetate/kg body weight on the metabolism of lipids in female rats fed a hypercholesterolemic diet for three months. Experimental group clearly exhibited higher levels of triglycerides and cholesterol in plasma and tissues, increase in aorta observed to be two folds. Increased hepatic cholesterogenesis was noted with treatment of oral contraceptive as indicated by higher activity of HMG-CoA reductase. Activity of lipoprotein lipase of extrahepatic tissue was depressed in experimental group. Activity of plasma LCAT, an enzyme involved in the transport of cholesterol from tissues, was also lower with treatment of oral contraceptive. However, activity of malic enzyme and glucose-6-phosphate dehydrogenase enhanced considerably with administration of oral pill. The increase in plasma and aortic cholesterol levels, increase in LDL+VLDL cholesterol and considerable decrease in HDL cholesterol in animals treated with oral contraceptives and fed with atherogenic diet, indicates that prolonged administration of oral pill may predispose towards atherosclerosis.


Emergency Management for Donkeys and Mules.
This article provides an overview of initial assessment and management of common emergency presentations in donkeys and mules. The principles are similar to those in horses (and ponies), but clinicians must be aware of differences in recognition of signs of pain/disease, approach to handling, pharmacology of some drugs, and subtle differences in the physiology and local anatomy in donkeys and mules. The epidemiology of common disease presentations will vary between pet/companion or working/farmed donkeys and mules. Regular dental checks, deworming, vaccination, and monitoring of behavior and quality of life are important aspects of preventive care.


Post-operative consequences of hemodynamic optimization.
Hemodynamic optimization begins with a medical assessment to identify the high-risk patients. This stratification is needed to customize the choice of hemodynamic support that is best adapted to the patient's level of risk, integrating the use of the least invasive procedures. The macro-circulatory hemodynamic approach aims to maintain a balance between oxygen supply (DO2) and oxygen demand (VO2). Volume replacement plays a crucial role based on the titration of fluid boluses according to their effect on measured stroke volume or indices of preload dependency. Good function of the microcirculatory system is the best guarantee to achieve this goal. An assessment of the DO2/VO2 ratio is needed for guidance in critical situations where tissue hypoxia may occur. Overall, all of these strategies are based on objective criteria to guide vascular replacement and/or tissue oxygenation in order to improve the patient's post-operative course by decreasing morbidity and hospital stay.


The antiretroviral-experienced patient.
There are many considerations for stopping and changing antiretroviral (ARV) therapy in the ARV-experienced individual. Given the potential for possible long-term toxicities and the shift to initiating ARV therapy later, it may be reasonable to stop ARV therapy among asymptomatic patients with high CD4 cell counts and low viral loads and carefully monitor them. Ongoing studies are currently evaluating this strategy. Treatment regimen failure may be due to problems with tolerability, adherence, pharmacokinetic issues, or emergence of resistance. Clinicians can utilize two types of resistance testing-genotype and phenotype assays. Generally, continuation of an optimized regimen in the patient with a multidrug resistant (MDR) virus is the best strategy. Structured treatment interruption among patients with an MDR virus is not recommended. New drugs, either recently licensed, such as enfuvirtide, or under investigation, may offer hope to patients with an MDR virus.


A comparison of sufentanil vs. remifentanil in fast-track cardiac surgery patients.
We retrospectively compared patients receiving remifentanil with patients receiving sufentanil undergoing fast-track cardiac surgery. After 1:1 propensity score matching there were 609 patients in each group. The sufentanil group had a significantly longer mean (SD) ventilation time compared with the remifentanil group; 122 (59) vs. 80 (44) min, p < 0.001 and longer mean (SD) length of stay in the recovery area; 277 (77) vs. 263 (78) min, p = 0.002. The sufentanil group had a lower mean (SD) visual analogue pain score than the remifentanil group; 1.5 (1.2) vs. 2.4 (1.5), p < 0.001 and consumed less mean (SD) piritramide (an opioid analgesic used in our hospital); 2.6 (4.7) vs. 18.9 (7.3) mg, p < 0.001. The results of our study show that although remifentanil was more effective in reducing time to tracheal extubation and length of stay in the recovery area, there was an increased requirement for postoperative analgesia when remifentanil was used.


Enhancing crop innate immunity: new promising trends.
Plants are constantly exposed to potentially pathogenic microbes present in their surrounding environment. Due to the activation of the pattern-triggered immunity (PTI) response that largely relies on accurate detection of pathogen- or microbe-associated molecular patterns by pattern-recognition receptors (PRRs), plants are resistant to the majority of potential pathogens. However, adapted pathogens may avoid recognition or repress plant PTI and resulting diseases significantly affect crop yield worldwide. PTI provides protection against a wide range of pathogens. Reinforcement of PTI through genetic engineering may thus generate crops with broad-spectrum field resistance. In this review, new approaches based on fundamental discoveries in PTI to improve crop immunity are discussed. Notably, we highlight recent studies describing the interfamily transfer of PRRs or key regulators of PTI signaling.


An approach to ventilator-dependent neonates with arthrogryposis.
To identify the clinical factors and/or test results necessary to determine the diagnosis and prognosis for a group of neonates who presented with respiratory insufficiency and multiple contractures. We performed a retrospective review of medical records and identified 15 newborns over a 10-year period (1980 through 1990) who had arthrogryposis multiplex congenita and required ventilator support at birth. We designed a 104 item data base to record clinical information; this was subsequently analyzed using the Clinfo data base program for statistical analysis. Fourteen of the 15 patients died. Of the fourteen, 13 were electively extubated after a variable time course (2 hours to 64 days). Autopsies performed on all 14 revealed an approximately equal distribution of central nervous system (CNS) malformations, peripheral neuropathies, and peripheral myopathies as the etiology. The single survivor had myasthenia gravis. In neonates with arthrogryposis, ventilator dependence at birth carries a poor prognosis. Prenatal factors that potentially predict respiratory insufficiency for the fetus with arthrogryposis include decreased fetal movements, polyhydramnios, micrognathia, and thin ribs. The combination of a thorough physical examination and radiographic and neuromuscular studies may not result in a specific diagnosis, but it can indicate whether the abnormality is in the CNS, peripheral nerves or muscles. Before elective withdrawal of ventilatory support, an edrophonium chloride challenge test should be performed to rule out myasthenia gravis.


Reliability of threaded locking screws.
A frequent problem for interlocking nailing that affects the treatment of the fracture is locking screw deformation. The aim of this study is to determine whether bending resistance is different between high, low, and unthreaded locking screws of interlocking femoral nails. Ninety screws were used in this experimental study, with 10 screws used in each of 9 groups. Three-point bending tests were performed on 6 groups of 5 mm screws (titanium, stainless steel, crossed with unthreaded, low threaded, and high threaded) and the same 3 thread types of 5.5 mm stainless steel screws in a 30-mm inner diameter steel tube, imitating the level of the lesser trochanter. An axial compressor was used to determine the yield points for permanent deformation in the locking screws by way of 3-point bending tests. The mean yield point value of the 3-point bending tests of 5-mm low threaded stainless steel locking screws was 2071 N, 53% less than that of unthreaded screws (3169 N). The mean yield point value of 5-mm high threaded stainless steel locking screws was 556 N, 272% less than that of low threaded screws (2071 N). To avoid locking screw deformation, high threaded screws must not be used as locking screws. In cases of unreliable patients, 5-mm low threaded screws should not be used in the nailing of comminuted or oblique femur shaft fractures. All 5-mm unthreaded screws and 5.5-mm low threaded stainless steel screws can be used safely in full weight-bearing conditions of unreliable patients.


Regulation of expression of a family of cross-reactive idiotypes.
It has recently been shown that anti-p-azophenylarsonate antibodies of A/J mice, which share a common idiotype, are not homogeneous but actually comprise a family of idiotypically related molecules. To obtain additional insight into the degree of relatedness of antibodies within this family, we have determined whether inoculation of any idiotype-positive hybridoma product, conjugated to thymocytes, can activate a regulatory mechanism capable of controlling the entire cross-reactive idiotypic response. In addition anti-idiotypic antibodies were prepared against individual hybridoma products, and their suppressive effects on the idiotypic component of the humoral response were determined. Inoculation of each of the idiotype-positive hybridoma products or anti-idiotypic antisera caused virtually complete suppression of the idiotypic component of the immune response. Furthermore, it was shown that the state of suppression induced by the inoculation of a hybridoma products could be adoptively transferred with T cells to mildly irradiated syngeneic recipients. The results indicate that there are sufficient structural similarities among the family of antibodies comprising the major cross-reactive idiotype to permit their recognition by the same set of elements involved in idiotypic regulation.


Genetic variation and population structure among larval Lethenteron spp. within the Yukon River drainage, Alaska.
The absence of information on genetic variation and population structure of lampreys Lethenteron spp. in the eastern part of their distribution limits our understanding of the migration ecology and spatial population genetic structure of the species. We examined genetic variation within and among three aggregations of Lethenteron spp. larvae in the Yukon River drainage, Alaska, using microsatellite genotypes. A total of 120 larval lampreys were genotyped at eight microsatellite loci. Global FST was 0.053 (95% CI 0.021-0.086), while pairwise FST values ranged from 0.048-0.057. Model-based Bayesian clustering analyses with sample locality priors (LOCPRIOR) identified three distinct, but admixed, genetic clusters that corresponded with the three aggregations. Estimates of contemporary gene flow indicate substantial reciprocal migration among sites consistent with no or low-fidelity natal homing. These results are largely in agreement with previous reports of historic and contemporary gene flow among Lethenteron spp. in other parts of their geographic distribution.


Multicenter Comparison of Seven 25OH Vitamin D Automated Immunoassays.
The measurement of 25OH vitamin D continues to grow in clinical laboratories. The aim of this multi-center study was to compare the results of seven automated commercial immunoassays with a reference HPLC technique. One hundred and twenty consecutive outpatient serum samples were centrifuged, divided in aliquots, frozen and shipped to the participating laboratories. 25OH Vitamin D was measured with a reference HPLC system and with seven automated commercial immunoassays (Roche Cobas E601, Beckman Coulter Unicel DXI 800, Ortho Vitros ES, DiaSorin Liaison, Siemens Advia Centaur, Abbott Architect i System and IDS iSYS). Compared to the reference method, the regression coefficients ranged from 0.923 to 0.961 (all p<0.001). The slope of Deming fit ranged from 0.95 to 1.06, whereas the intercept was comprised between -15.2 and 9.2 nmol/L. The bias from the reference HPLC technique varied from -14.5 to 8.7 nmol/L. The minimum performance goal for bias was slightly exceeded by only one immunoassay. The agreement between HPLC and the different immunoassays at 50 nmol/L 25OH Vitamin D varied between 0.61 and 0.85 (all p<0.001). The percentage of samples below this cut-off was significantly different with only one immunoassay. The excellent correlation with the reference HPLC technique attests that all seven automated immunoassays may be reliably used for routine assessment of 25OH-D in clinical laboratories. The significant bias among the different methods seems mostly attributable to the lack of standardization and calls for additional efforts for improving harmonization of 25OH-D immunoassays.


The roof step cut: A novel technique for bony reconstruction of acetabular roof deficiency during total hip replacement.
This study aims to present a new technique, the roof step cut (RSC), for acetabular augmentation of hip dysplasia. Between December 2008 and March 2020, we applied the RSC technique in a total of 48 hips of 41 patients (2 males, 39 females; mean age: 50.1±9.5 years; range, 30 to 75 years) with Hartofilakidis type A, B, C hip dysplasia. The RSC technique uses a L-shaped graft cut from the femoral head. The graft is partially inside the acetabulum and partially on the lateral aspect of the ilium. It is fixed with two screws at a 45° angle allowing simultaneous distalization and lateral covering of the cementless cup. Follow-up was done at six weeks, three months, and annually thereafter using standard pelvis anteroposterior X-ray and function scores. The 99mTc bone scintigraphy examination was also performed at around two weeks, six months, and 12 months postoperatively to evaluate the healing process of the graft. The mean follow-up time was 59.6±25.6 (range, 12 to 109) months. No significant center-edge angle changes and no contiguous radiolucent zones at the bone prosthesis interface were observed at the final follow-up. The single-photon emission tomography (SPECT) showed the activity of the bone graft gradually increased after surgery and became almost the same as the reference area after 12 months. Functional evaluation showed a significant improvement after the operation. No complication directly related to the technique was observed. In the short-term follow-up, the RSC technique is a reliable procedure for acetabular augmentation of hip dysplasia, providing enough coverage for the cementless cup and assuring proper stability.


High osmolality: a potent parathyroid hormone secretogogue in dispersed parathyroid cells.
We have examined possible mechanisms by which osmolality might modulate PTH secretion in dispersed bovine parathyroid cells. Increasing medium osmolality by adding sodium chloride causes a marked, dose-dependent increase in PTH release. The maximum effect (4-fold increase) is observed when osmolality is around 650 mosM, with half-maximal stimulation at about 400 mosM. When osmolality is increased to a similar extent with either sucrose or sodium chloride, PTH secretion is enhanced to a comparable degree, suggesting that osmolality itself, rather than ionic strength, is responsible for the increase in PTH secretion. Time course experiments show that the increased secretion of PTH with high osmolality occurs very rapidly (in less than 5 min). In contrast to the suppressive effects of high Ca2+ on PTH release, increasing calcium concentration in the incubation media does not inhibit the stimulation of PTH secretion by high osmolality. Moreover, the effects of dopamine (10(-5) M) and high osmolality on PTH release are additive, further suggesting that high osmolality and cAMP modulate PTH release by different mechanisms. In fact, direct measurement of cellular cAMP in cells exposed to high osmolality shows no change relative to control cells incubated with normal osmolality, 127 +/- 20 vs. 146 +/- 21 fmol/10(5) cells, respectively. Cytosolic Ca2+ increases from 257 +/- 29 nM to 703 +/- 50 nM after 200 mM NaCl is added to the incubation medium at low Ca2+ (0.5mM). Prior removal of extracellular calcium abolished this effect. Increasing the osmolality to a similar level by adding sucrose to the medium does not demonstrate any increase in cytosolic calcium. We conclude that high osmolality is a potent secretogogue in dispersed bovine parathyroid cells. Unlike dopamine and isoproterenol, high osmolality does not act through changes in intracellular cAMP. It also prevents the normal inhibitory effect of high Ca2+ on PTH release. Change of cytosolic Ca2+ is variable and suggests that the effect of high osmolality on PTH release cannot be explained by cytosolic Ca2+ alone. Further understanding of the mechanisms by which osmolality affects PTH release, therefore, may provide clues to the unusual inverse relationship between extracellular and cytosolic calcium and PTH release.


Translocation of Photosynthetic Carbon From Two Algal Symbionts to the Sea Anemone Anthopleura elegantissima.
The intertidal sea anemone Anthopleura elegantissima contains two symbiotic algae, zoochlorellae and zooxanthellae, in the Northern Puget Sound region. Possible nutritional advantages to hosting one algal symbiont over the other were explored by comparing the photosynthetic and carbon translocation rates of both symbionts under different environmental conditions. Each alga translocated 30% of photosynthetically fixed carbon in freshly collected anemones, although zoochlorellae fixed and translocated less carbon than zooxanthellae. The total amount of carbon translocated to the host was equivalent because densities of zoochlorellae were two to three times greater than were densities of zooxanthellae. In A. elegantissima maintained under high and low irradiance (100 and 10 {mu}mol photons/m2/s) at 20{deg}C and 13{deg}C for 21 days, both algae fixed and translocated carbon at greater rates at 20{deg}C (translocation rates: 0.38 pg C /zoochlorella/h; 1.12 pg C /zooxanthella/h) than at 13{deg}C (translocation rates: 0.06 pg C /zoochlorella/h; 0.37 pg C /zooxanthella/h). However, zoochlorellate anemones received 3.5 times less carbon at 20{deg}C than at 13{deg}C because the higher temperature caused a significant reduction in the density of zoochlorellae. Environmental variables, like temperature, that influence the densities of the two symbionts will affect their relative nutritional contribution to the host. Whether these differences in carbon translocation rates of the two algal symbionts affect the ecology of their anemone host awaits further investigation.


Synthesis and Isomerization Behavior of a Macrocycle with Four Photoresponsive Moieties.
The macrocycle 1 containing four photoresponsive fluorenylidene moieties was designed. The EZEZ form of 1, 1 EZEZ, was selectively produced. Reversible photochemical isomerization between 1 EZEZ and 1 ZZZZ was achieved, the extent of which was dependent on the light source used. Furthermore, the intermediate 1 EZZZ was selectively isomerized to 1 ZZZZ thermally and photochemically.


Combined Effect of Genetic Variants on Long-Term Weight Response after Bariatric Surgery.
The pathophysiology of body weight control involves complex interactions between hormonal, environmental, behavioral and genetic factors. The purpose of this study was to analyze the association between single nucleotide polymorphisms (SNPs) of 13 genes encoding gastrointestinal peptides, their receptors or the proteins involved in their expression, with long-term weight response in a cohort of 375 patients undergoing bariatric surgery (BS). To evaluate weight response, we combined several variables to define specific response phenotypes six years after surgery. The study protocol was registered in ISRCTN (ID80961259). The analysis of the selected SNPs was performed via allelic discrimination using Taqman® probes (Applied Biosystems, Foster City, CA, USA). The genotype association study was performed using the SNPstat program, with comparisons adjusted for sex, age, initial body mass index, type 2 diabetes, hypertension diagnosis and the type of surgery. We identified eight genetic variants associated with the weight response to BS, independently of the presurgery patient profile and the type of surgical technique, from which we calculated the unweighted risk score (RS) for each phenotype. The highest scoring category in each RS was significantly associated with lower weight loss (p = 0.0001) and greater weight regain (p = 0.0012) at the end of the follow-up.


[A case of epidermoid cyst in an intrapancreatic accessory spleen showing cyst-in-cyst-like structure mimicking mucinous cystic neoplasm].
In 2010, a 39-year-old woman presented with a cystic lesion, 16 mm in diameter, in the tail of the pancreas. Regular follow-ups were conducted to monitor this lesion; its diameter was found to increase to 45 mm in 2013. Thus, the patient was admitted to our hospital for further examination and treatment. Abdominal US, abdominal contrast-enhanced CT, and MRI showed a cystic lesion of 45 mm in diameter in the tail of the pancreas, which had internal septae and mural nodules inside. EUS revealed a cyst-in-cyst-like structure, with a thickened cystic wall along the entire circumference. Thus, distal pancreatectomy and splenectomy were performed on the basis of a diagnosis of mucinous cystic neoplasm. Histopathological examination of a resected specimen showed that the lesion comprised a substantial component of red-brown tone, with adjacent cystic components. The final diagnosis was an epidermoid cyst in an intrapancreatic accessory spleen.


Analysis for the convergence problem of the plane-wave expansion method for photonic crystals.
The convergence feature of two types of plane-wave expansion methods commonly used for photonic crystals is analyzed. It is shown that the reason for the slow convergence of these plane-wave expansion methods is not the slow convergence of the Fourier series for the permittivity profile of the photonic crystal but the inappropriate formulation of the eigenproblem. A new formulation of the eigenproblem is presented to improve the convergence in the one-dimensional case.


[Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State].
Diabetic ketoacidosis and the hyperosmolar hyperglycemic state are the most serious diabetic emergencies. Before the discovery of insulin in 1921 by Banting and Best the diagnosis of type 1 diabetes was fatal ending in diabetic ketoacidosis equivalent to a torturous death. Today, mortality from diabetic ketoacidosis is low at approximately 2 %. But each death from these two acute metabolic complications of diabetes is potentially avoidable by improved patient and healthcare professional education. Therefore, there is a need to raise awareness of hyperglycemic crisis and its management amongst physicians. Insulin deficiency or resistence and increased concentrations of counterreulatory hormones (glucagon, catecholamines, cortisol and growth hormone) are responsible for the development of diabetic ketoacidosis and the hyperosmolar hyperglycemic state. Hyperglycemia develops as a result of increased gluconeogenesis and accelerated glyconeogenesis. In DKA, the absolute insulin deficiency additionally leads to increased lipolysis and production of ketone bodies and resulting metabolic acidosis. Both DKA and HHS require prompt recognition and management. The diagnosis can be suspected by clinical features and confirmed by laboratory findings. The treatment of DKA and HHS is similar, including correction of fluid and electrolyte abnormalities and the administration of insulin.


Three-Dimensional (3D) Analysis of Orbital Morphometry in Healthy Anatolian Adults: Sex, Side Discrepancies, and Clinical Relevance.
Background and objective The complex structural integrity of the orbit is crucial for visual functions. Three-dimensional (3D) reconstructions from radiological images have revolutionized anatomical understanding, eliminating the limitations of two-dimensional (2D) imaging and offering intricate spatial details for complex structures. The aim of this study was to analyze the detailed morphometry of the orbit in healthy Anatolian adults, considering sex, side discrepancies, and clinical relevance using 3D models reconstructed from multidetector computed tomography (MDCT) images. Materials and methods Fifty-six (44.44%) males and 70 (55.56%) females (total: 126, mean age: 48.62) MDCT images were randomly selected and 3D skull models were reconstructed using 3D Slicer software. Measurements were conducted in millimeters (mm) for transverse and vertical diameters, circumference of the orbital opening, orbital wall lengths, as well as intraorbital and extraorbital distances. Results The method of measurements showed high reproducibility of results. The mean values for transverse and vertical diameters, circumference of the orbital opening, medial and lateral wall lengths, roof and floor lengths, and intraorbital and extraorbital distances were 40.23±2.12 mm (p<0.001), 34.94±2.16 mm (p=0.365), 44.74 ±3.02 mm (p<0.001), 46.30±2.69 mm (p<0.001), 51.26±2.91 mm (p<0.001), 49.01±3.22 mm (p<0.001), 126.10±5.71 mm (p<0.001), 19.63±2.35 mm (p=0.026), and 94.09±4.84 mm (p<0.001), respectively. Conclusion The study's high measurement reproducibility contributes significantly to the existing literature and clinical practice. These findings offer specific insights into Anatolian orbital morphometry, aiding in surgical planning, implant placement, and diagnostic assessments. The precise measurement values serve as a reliable reference for clinicians, facilitating the identification of normal and abnormal orbital anatomy and enhancing patient care. We believe this study provides valuable data for craniofacial and ophthalmological research, benefiting both clinical practice and future research endeavors in these fields.


Milk-alkali-induced pancreatitis in a chronically hypocalcemic patient with DiGeorge syndrome.
Pancreatitis is a common diagnosis in the emergency department (ED), and milk-alkali syndrome (MAS) is an uncommon etiology for pancreatitis. MAS is caused by increased calcium and alkali ingestion, causing hypercalcemia accompanied by metabolic alkalosis and renal failure. Once considered rare, MAS is an increasingly common cause of hypercalcemia. Awareness of the resurgence of this syndrome is important for emergency physicians when recalling the causes of renal failure and pancreatitis. We present a case of pancreatitis and acute renal failure (ARF) in a chronically hypocalcemic DiGeorge syndrome patient, resulting from hypercalcemia secondary to excessive ingestion of calcium carbonate tablets. A patient with DiGeorge syndrome and chronic abdominal pain due to gastroesophageal reflux disease (GERD) presented to our ED for severe abdominal pain. He reported nausea and vomiting, as well as epigastric pain that seemed worse than his typical pain. Laboratory evaluation revealed pancreatitis and ARF, although the patient had no prior history of these conditions. Upon further questioning, his mother divulged that the patient had been taking large quantities of calcium carbonate tablets for his worsening GERD symptoms. The patient was admitted to the intensive care unit where his pancreatitis and ARF eventually resolved as his calcium levels returned to his baseline. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: MAS is a relatively uncommon diagnosis, but can lead to serious sequelae such as pancreatitis and ARF. Questioning the patient about calcium ingestion is an important facet to the diagnosis and work-up of pancreatitis and ARF. Recognition of this etiology can improve patient outcomes and prevent recurrences.


Characterization of acetic acid bacteria in "traditional balsamic vinegar".
This study evaluated the glucose tolerance of acetic acid bacteria strains isolated from Traditional Balsamic Vinegar. The results showed that the greatest hurdle to acetic acid bacteria growth is the high sugar concentration, since the majority of the isolated strains are inhibited by 25% of glucose. Sugar tolerance is an important technological trait because Traditional Balsamic Vinegar is made with concentrated cooked must. On the contrary, ethanol concentration of the cooked and fermented must is less significant for acetic acid bacteria growth. A tentative identification of the isolated strains was done by 16S-23S-5S rDNA PCR/RFLP technique and the isolated strains were clustered: 32 strains belong to Gluconacetobacter xylinus group, two strains to Acetobacter pasteurianus group and one to Acetobacter aceti.


[Immune modulating effect of isoprinosine in patients with post-alcoholic liver cirrhosis].
Immunomodulating effect of isoprinosine was estimated in group of 10 patients with postalcoholic liver cirrhosis and compared with another group of 10 patients with postinflammatory liver cirrhosis with infection of hepatitis B virus. Disturbances of immunologic reactivity in the patients with postalcoholic liver cirrhosis mainly concerned increased immunoglobulin G, A concentrations in the blood serum, decreased percentage values of lymphocytes T and their subpopulations (lymphocytes T4 and T8) and increased percentage of lymphocytes B. Disturbances of the examined indices of the immunologic reactivity in the group of patient with postinflammatory liver cirrhosis concerned increased concentrations of circulating immunologic complexes, immunoglobulins A and M in the blood serum and decreased percentage of lymphocytes T and their subpopulation. Treatment with isoprinosine resulted in different immunologic effect in the examined patients concerning mainly increased concentrations of circulating immunologic complexes in the blood serum and increased percentage values of lymphocytes T, T4, T8, B in the course of postalcoholic liver cirrhosis. Patients with postinflammatory liver cirrhosis treated with isoprinosine mainly showed decreased concentrations of circulating immunologic complexes, immunoglobulins A, M the blood serum, increased percentage values of lymphocytes T4 and T8.


Lessons learned from dinuclear lanthanide nano-magnets.
The quest for higher density information storage has led to the investigation of Single-Molecule Magnets (SMMs) as potential molecules to be applied in materials such as hard discs. In order for this to occur, one must first design metal complexes which can retain magnetic information at temperatures where these applications become possible. This can only be achieved through answering and understanding fundamental questions regarding the observed physical properties of SMMs. While mononuclear lanthanide complexes have shown promise in obtaining high energy barriers for the reversal of the magnetisation they are limited to Single-Ion Magnet behaviour intrinsic to one metal centre with a limited number of unpaired electrons. As a way of increasing the effective anisotropic barrier, systems with higher nuclearity have been sought to increase the spin ground state of the molecule. Dinuclear complexes are presented as key compounds in studying and understanding the nature of magnetic interactions between metal ions. This tutorial review will span a number of dinuclear 4f complexes which have been critical in our understanding of the way in which lanthanide centres in a complex interact magnetically. It will examine key bridging moieties from the more common oxygen-based groups to newly discovered radical-based bridges and draw conclusions regarding the most effective superexchange pathways allowing the most efficient intracomplex interactions.


Encouraging top-down attention in visual search:A developmental perspective.
Four experiments are reported in which 60 younger children (7-8 years old), 60 older children (10-11 years old), and 60 young adults (18-25 years old) performed a conjunctive visual search task (15 per group in each experiment). The number of distractors of each feature type was unbalanced across displays to evaluate participants' ability to restrict search to the smaller subset of features. The use of top-down attention processes to restrict search was encouraged by providing external aids for identifying and maintaining attention on the smaller set. In Experiment 1, no external assistance was provided. In Experiment 2, precues and instructions were provided to focus attention on that subset. In Experiment 3, trials in which the smaller subset was represented by the same feature were presented in alternating blocks to eliminate the need to switch attention between features from trial to trial. In Experiment 4, consecutive blocks of the same subset features were presented in the first or second half of the experiment, providing additional consistency. All groups benefited from external support of top-down attention, although the pattern of improvement varied across experiments. The younger children benefited most from precues and instruction, using the subset search strategy when instructed. Furthermore, younger children benefited from blocking trials only when blocks of the same features did not alternate. Older participants benefited from the blocking of trials in both Experiments 3 and 4, but not from precues and instructions. Hence, our results revealed both malleability and limits of children's top-down control of attention.


Little tips with big rewards.
We all would like to reduce the pain of injecting a local anesthetic, to simplify the treatment of xanthelasma palpebrarum and chondrodermatitis nodularis; and to improve methods of shave excision of nevi and cosmetic extirpation of large seborrheic keratoses. Here are some tips that might help.


[Liver transplantation. Selection criteria and risk evaluation].
The significant advances achieved in the last years in the field of liver transplantation have led to an almost routinely performance of this therapeutic approach throughout North America and Western Europe. This has led to an increased demand so that today the real problem is the organ availability and the need to use those supplied only for patients with best chances of success. For this reason timing of the operation and patient selection are of critical importance. The ultimate success depends on better surgical procedures and advances in immunosuppressive therapy, but perhaps even more on an accurate patient evaluation. The patient selection is based on standardized medical criteria which constitute the indication in patients with end-stage liver disease and on a careful search for risk factors. To this purpose the evaluation of the tolerance of the hemodinamic stress during clamping of the inferior vena cava is of critical importance and must be carefully evaluated both in patients with known and unknown coronary disease. Another condition to be considered is lung hypertension which is frequently associated with portal hypertension. Finally, important conditions for a good evaluation are the epatopulmonary syndrome and diabetes. The last condition is not a contraindication unless associated with severe vascular, cardiac or renal complications.


[Pulmonary involvement in tuberous sclerosis].
The authors present a case of tuberous sclerosis with marked pulmonary involvement, confirmed by both radiological and pathological studies. The radiological manifestations and basic pathology of this rare condition are reviewed with emphasis on differential diagnosis.


Congenital hybrid basal cell adenoma--adenoid cystic carcinoma of the salivary gland.
A congenital parotid gland tumor involving the facial nerve was excised, revealing histologic and ultrastructural features of a basal cell adenoma and adenoid cystic carcinoma. An asynchronous regional metastasis was successfully eradicated with adriamycin. Seven other similar appearing tumors occurring in neonates are documented in the literature and serve to establish this tumor as a clinicopathologic entity. The surrounding parotid gland had "dysplastic" changes attributed to obstruction during morphogenesis.


Effects of pretreatment during drying on the antioxidant properties and color of selected tomato varieties.
Drying is essential in lowering the water activity and increasing the shelf stability of perishables. Thus, this study investigated the effect of pretreatment on the retention of the antioxidant properties and color of four tomato varieties; that is, Anna F1, Kilele, Prostar F1, and Riogrande during drying. Prepared quarters were treated by spraying with 0.5% sodium metabisulfate, 0.5% calcium chloride, and distilled water. The quarters were oven dried at 50°C, 60°C, and 70°C to 13% moisture content. Lycopene, β carotene, total phenolics, color, and moisture content were determined in both the fresh and dried samples. Initial moisture content among the four varieties did not differ significantly and ranged between 94.2 and 94.6%. Results showed that the main effects were significant (p < .05) on all measurable variables. Significantly (p < .05) higher retention levels in lycopene, β carotene, total phenolics, and lightness was observed in chemically pretreated samples compared to the control during drying.


[Effect of reactive oxygen species during the leukemogenic process associated with exposure to benzene].
To study the effect of reactive oxygen species (ROS) during the leukemogenic process associated with exposure to benzene. HL-60 was treated with 3 micromol/L benzoquinone (BQ). Generation of ROS in cells was measured by DCFH-DA method. For proliferation assays,cells were stained with alamar blue dye and counted. ROS production and the proliferation of cell were all increased in BQ-treated cells (13.10 +/- 0.15, 185% +/- 30.00%) as compared with control cells (11.32 +/- 0.09, 100% +/- 0.00%) (P < 0.05); The addition of catalase just before BQ addition reduced ROS generation to basal levels and decreased the growth of cell (P < 0.05). ROS may play an important role in the process of proliferation of HL-60 cells induced by BQ.


Ceftriaxone reverses deficits of behavior and neurogenesis in an MPTP-induced rat model of Parkinson's disease dementia.
Hyperactivity of the glutamatergic system is involved in excitotoxicity and neurodegeneration in Parkinson's disease (PD) so that glutamatergic modulation maybe a potential therapeutic target for PD. Ceftriaxone (CEF) has been reported to increase glutamate uptake by increasing glutamate transporter expression and has been demonstrated neuroprotective effects in animal study. The aim of this study was to determine the effects of CEF on behavior and neurogenesis in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. MPTP was stereotaxically injected into the substantia nigra pars compacta (SNc) of male Wistar rats. Starting on the same day after MPTP lesioning (day 0), the rats were injected daily with either CEF or saline for 14days and underwent a T-maze test on days 8-10 and an object recognition test on days 12-14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased motor function, working memory, and object recognition and reduced neurogenesis in the substantial nigra and dentate gyrus of the hippocampus. These behavioral and neuronal changes were prevented by CEF treatment. To our knowledge, this is the first study showing that CEF prevents loss of neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD.


The Role of Endovascular In Situ Revascularization in the Treatment of Arterial and Graft Infections.
Mycotic aneurysms and prosthetic graft infections are traditionally treated with excision of the infected tissue or graft, often requiring anatomical or extraanatomical bypass, carrying significant morbidity and mortality. Currently, the role of endovascular repair without excision in this setting has yet to be defined. We present 2 case scenarios, whereby mycotic pseudoaneurysms were successfully treated with endovascular stent-graft coverage and to present an in-depth review of endovascular in situ revascularization in the treatment of arterial and graft infections. There are data to support the use of stent grafting in mycotic aortic and iliac aneurysms, lower and upper extremity native arterial infections, lower extremity prosthetic bypass infections, and infections of carotid artery aneurysms. It is our belief that this technique may be utilized as primary therapy if there is no significant contamination and certainly serves an essential role in acute rupture or hemorrhage. In situations where there is significant tissue infection, stent grafting should be considered as a bridge if traditional excision is warranted.


Expanding the role of striatal cholinergic interneurons and the midbrain dopamine system in appetitive instrumental conditioning.
The basal ganglia are a collection of subcortical nuclei thought to underlie a wide variety of vertebrate behavior. Although a great deal is known about the functional and physiological properties of the basal ganglia, relatively few models have been formally developed that have been tested against both behavioral and physiological data. Our previous work (Ashby FG, Crossley MJ. J Cogn Neurosci 23: 1549-1566, 2011) showed that a model grounded in the neurobiology of the basal ganglia could account for basic single-neuron recording data, as well as behavioral phenomena such as fast reacquisition that constrain models of conditioning. In this article we show that this same model accounts for a variety of appetitive instrumental conditioning phenomena, including the partial reinforcement extinction (PRE) effect, rapid and slowed reacquisition following extinction, and renewal of previously extinguished instrumental responses by environmental context cues.


Does optimal partitioning of color space account for universal color categorization?
A 2007 study by Regier, Kay, and Khetarpal purports to show that universal categories emerge as a result of optimal partitioning of color space. Regier, Kay, and Khetarpal only consider color categorizations of up to six categories. However, in most industrialized societies eleven color categories are observed. This paper shows that when applied to the case of eleven categories, Regier, Kay, and Khetarpal's optimality criterion yields unsatisfactory results. Applications of the criterion to the intermediate cases of seven, eight, nine, and ten color categories are also briefly considered and are shown to yield mixed results. We consider a number of possible explanations of the failure of the criterion in the case of eleven categories, and suggest that, as color categorizations get more complex, further criteria come to play a role, alongside Regier, Kay, and Khetarpal's optimality criterion.


Measurement of 100 nm and 60 nm Particle Standards by Differential Mobility Analysis.
The peak particle size and expanded uncertainties (95 % confidence interval) for two new particle calibration standards are measured as 101.8 nm ± 1.1 nm and 60.39 nm ± 0.63 nm. The particle samples are polystyrene spheres suspended in filtered, deionized water at a mass fraction of about 0.5 %. The size distribution measurements of aerosolized particles are made using a differential mobility analyzer (DMA) system calibrated using SRM(®) 1963 (100.7 nm polystyrene spheres). An electrospray aerosol generator was used for generating the 60 nm aerosol to almost eliminate the generation of multiply charged dimers and trimers and to minimize the effect of non-volatile contaminants increasing the particle size. The testing for the homogeneity of the samples and for the presence of multimers using dynamic light scattering is described. The use of the transfer function integral in the calibration of the DMA is shown to reduce the uncertainty in the measurement of the peak particle size compared to the approach based on the peak in the concentration vs. voltage distribution. A modified aerosol/sheath inlet, recirculating sheath flow, a high ratio of sheath flow to the aerosol flow, and accurate pressure, temperature, and voltage measurements have increased the resolution and accuracy of the measurements. A significant consideration in the uncertainty analysis was the correlation between the slip correction of the calibration particle and the measured particle. Including the correlation reduced the expanded uncertainty from approximately 1.8 % of the particle size to about 1.0 %. The effect of non-volatile contaminants in the polystyrene suspensions on the peak particle size and the uncertainty in the size is determined. The full size distributions for both the 60 nm and 100 nm spheres are tabulated and selected mean sizes including the number mean diameter and the dynamic light scattering mean diameter are computed. The use of these particles for calibrating DMAs and for making deposition standards to be used with surface scanning inspection systems is discussed.


Temperature-programmed Deoxygenation of Acetic Acid on Molybdenum Carbide Catalysts.
Temperature programmed reaction (TPRxn) is a simple yet powerful tool for screening solid catalyst performance at a variety of conditions. A TPRxn system includes a reactor, furnace, gas and vapor sources, flow control, instrumentation to quantify reaction products (e.g., gas chromatograph), and instrumentation to monitor the reaction in real time (e.g., mass spectrometer). Here, we apply the TPRxn methodology to study molybdenum carbide catalysts for the deoxygenation of acetic acid, an important reaction among many in the upgrading/stabilization of biomass pyrolysis vapors. TPRxn is used to evaluate catalyst activity and selectivity and to test hypothetical reaction pathways (e.g., decarbonylation, ketonization, and hydrogenation). The results of the TPRxn study of acetic acid deoxygenation show that molybdenum carbide is an active catalyst for this reaction at temperatures above ca. 300 °C and that the reaction favors deoxygenation (i.e., C-O bond-breaking) products at temperatures below ca. 400 °C and decarbonylation (i.e., C-C bond-breaking) products at temperatures above ca. 400 °C.


Myxoid hepatocellular adenoma, a rare variant of hepatocellular adenoma with distinct imaging features: A case report with immunohistochemical and molecular analysis and literature review.
Preoperative imaging and histopathology, immunohistochemistry and molecular analysis after resection of 2 hepatocellular adenomas (HCAs) (20 and 2cm) in a 53-year-old female patient were performed. On imaging, the large lesion resembled a myxoid HCA, while the small lesion resembled a more conventional HCA with a small myxoid/fluid area. On microscopy, the large lesion showed cords and nests of hepatocytes embedded in abundant myxoid matrix, while the small lesion resembled a conventional HCA with small foci of myxoid change and serosities; both consistent with a myxoid HCA. Immunophenotyping and molecular subtyping excluded inflammatory HCA, CTNNB1 mutated HCA and sonic hedgehog HCA, and was consistent with HNF1A mutated HCA. The myxoid change as well as the serosities may allow imaging diagnosis of myxoid HCA. As fluid vacuoles can also be present in ASS1+HCA, sonic hedgehog HCA has to be considered in the differential diagnosis.


Renal dysfunction induced by long-term exposure to depleted uranium in rats.
Depleted uranium (DU) is a kind of radioactive heavy metal which can enter into the body via inhalation (aerosols), ingestion (drinking and eating) and wounds (embedded), and causes chemical and/or radiation-induced toxicities. In this study, male Sprague Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at three dose levels (low-dose, medium-dose and high-dose), with biologically inert tantalum (Ta) fragments served as controls. At 1 day, 7 days, and 3, 6, and 12 months after implantation, the rats were euthanized and tissue samples were collected, and uranium levels were measured in a variety of tissues by inductively coupled plasma-mass spectrometry (ICP-MS) to analyze the dynamic changes and distribution of uranium in rats. Thereafter, at 3, 6 and 12 months after implantation, the rats were euthanized after the collection of 24 h urine, blood and kidney samples were collected for analysis of DU-induced renal histopathologic changes and renal dysfunction. It was observed that DU concentrations in all the DU implanted groups were higher than that in Ta control group, and DU concentrations in the kidney increased with the implanted times, peaked at the 90 days after implantation, with a high correlation to the implanted DU doses, and then began to decrease gradually and slowly, and the DU concentrations in kidney still maintained at a relatively high level even at the 360 days after implantation. Otherwise, chronic DU contamination could induce the pathological changes of renal glomeruli, tubules and mesenchyme, such as interstitial fibrosis, enlarged interstice of renal tubular epithelial cells, tumefactions and necrosis of epithelial cells, shrinkage and disappearance of cavity of Bowman's capsule. By TEM, it was shown that the basement membrane of glomerulus was incrassated, mitochondrial of kidney proximal tubule had visible tumefaction and became bigger, and the mitochondrial cristae became shorter and disorderly in alignment. Compared to the control group, it was found that there was significant increase in the DU implantation group in terms of their blood urea nitrogen (BUN) and serum creatinine, urinary beta2-microglobulin (beta2-MG) and albumin, with a high correlation to the implanted DU dosage and periods. It was concluded that DU could accumulate in kidneys for a long period, and causes kidney injury by the toxic chemical/radioactive action such as renal dysfunction and structural damage.


Impact of Feed Delivery Pattern on Aerial Particulate Matter and Behavior of Feedlot Cattle.
Fine particulate matter with less than 2.5 microns diameter (PM2.5) generated by cattle in feedlots is an environmental pollutant and a potential human and animal health issue. The objective of this study was to determine if a feeding schedule affects cattle behaviors that promote PM2.5 in a commercial feedlot. The study used 2813 crossbred steers housed in 14 adjacent pens at a large-scale commercial West Texas feedlot. Treatments were conventional feeding at 0700, 1000, and 1200 (CON) or feeding at 0700, 1000, and 1830 (ALT), the latter feeding time coincided with dusk. A mobile behavior lab was used to quantify behaviors of steers that were associated with generation of PM2.5 (e.g., fighting, mounting of peers, and increased locomotion). PM2.5 samplers measured respirable particles with a mass median diameter ≤2.5 μm (PM2.5) every 15 min over a period of 7 d in April and May. Simultaneously, the ambient temperature, humidity, wind speed and direction, precipitation, air pressure, and solar radiation were measured with a weather station. Elevated downwind PM2.5 concentrations were measured at dusk, when cattle that were fed according to the ALT vs. the CON feeding schedule, demonstrated less PM2.5-generating behaviors (p < 0.05). At dusk, steers on ALT vs. CON feeding schedules ate or were waiting to eat (standing in second row behind feeding cattle) at much greater rates (p < 0.05). Upwind PM2.5 concentrations were similar between the treatments. Downwind PM2.5 concentrations averaged over 24 h were lower from ALT compared with CON pens (0.072 vs. 0.115 mg/m³, p < 0.01). However, dry matter intake (DMI) was less (p < 0.05), and average daily gain (ADG) tended to be less (p < 0.1) in cattle that were fed according to the ALT vs. the CON feeding schedules, whereas feed efficiency (aka gain to feed, G:F) was not affected. Although ALT feeding may pose a challenge in feed delivery and labor scheduling, cattle exhibited fewer PM2.5-generating behaviors and reduced generation of PM2.5 when feed delivery times matched the natural desires of cattle to eat in a crepuscular pattern.


Accuracy of hepatitis C virus core antigen testing in pools among seroconverters.
Screening blood units for hepatitis C virus (HCV) with nucleic acid testing (NAT) reduces the risk associated with the long "window period" (8-9 weeks) after HCV infection. The feasibility of adding the HCV core antigen assay in pools to the existing anti-HCV individual screening was examined as an alternative of NAT, for early detection of HCV. Eighteen HCV seroconversion panels were tested for HCV antibodies, HCV antigen, and HCV RNA. Each sample was tested for HCV antigen individually and in pools of 3, 6, and 12. Statistical analyses included estimation of time until detection of the first positive HCV antigen bleed in each pool size, with a locally weighted regression (LOWESS) model. Sensitivity was calculated compared to NAT. Detection of HCV antigen in individual samples and in pools of 3 and 6 significantly preceded the detection of antibodies by 63, 53, and 46 days, respectively. Although the sensitivity of the HCV antigen test decreased with the increase in pool size, the estimated overall sensitivity of the "two-stage" antigen and antibody screening (where NAT of individual samples was the gold standard) was not significantly different between individual and the different pool sizes. Screening for HCV antigen in pools of 6 can be considered an efficient and easier-to-implement alternative to the costly NAT for identifying blood donors in the seroconversion period. It may offer a cost-effective approach in resource utilization in poor countries, that, after the implementation of HCV antibody testing, want to further improve blood safety.


[Loco typico radius fractures--personal experience].
Fractura radii loco typico (FRLT) is the fracture of the distal radius. That is the one of the most frequent fractures of locomotor system with the widest range of treatment in traumatology. Therapy depends on the stability of the fracture: nonoperative or operative. We analysed the five-year experience of our Department of Traumatology where more than 1500 patients with FRLT have been treated in the urgent surgery clinic and 126 of them were hospitalized. In our study we evaluated the results of the operative treatment and postoperative functional status of a treated wrist. According to the A-O classification, we hospitalized 36 patients with A type, 28 patients with B type, and 62 patients with C type of FRLT. We operated 80 patients. The postoperative functional status of a treated wrist was excellent or good in 64 patients and good in 16 patients. The treatment of FRLT depends on the type and the complications of the fracture and the age of the patients. Operative therapy is indicated in the unstable FRLT or after an inadequate nonoperative treatment.


Oxidative stress, plant-derived antioxidants and liver fibrosis.
There is accumulating evidence that oxidative stress plays a considerable role in the development of liver fibrosis by acting in different cell types and in different signaling pathways. Consequently, antioxidants, particularly those of plant origin, have emerged as potent antifibrotic agents. This review briefly summarizes current views of the mechanisms of fibrogenesis and recent findings on the antifibrotic potential of plant-derived antioxidants.


Anaesthetic mortality rates in Western Australia 1980-2002.
The Western Australian Anaesthetic Mortality Committee has collected data since 1980. During this time, reporting of anaesthesia mortality has been mandatory in Western Australia, confidentiality and legal protection have been ensured, consistent definitions and classifications have been used, and reasonable estimates have been available for the number of surgical procedures performed. The data indicate that there was a decrease in anaesthesia-related mortality in the mid 1980s. Since then the rates have been relatively stable, in relation to both population and number of surgical procedures performed. At present, the rates are extremely low (< 1:50, 000 surgical procedures per annum), and similar to rates reported from other Australian states. While these figures are encouraging, their main function is to serve as the baseline for further improvements.


Design and Fabrication of Integrated Fabry-Perot Type Color Reflector for Reflective Displays.
A Fabry-Perot type integrated color reflector, with red/blue/green colors as subpixels, was designed and fabricated with Si substrate. Ag films were used as reflective mirror layers, SiO2 films were used as Fabry-Perot cavity layers and W films were used as partially reflective layers for the cavity. To minimize the effects of the thickness variation of the oxide cavity layers, the structure of the color reflector was optimized, and the differential deposition scheme was devised and applied in the fabrication process. The integrated color reflector was successfully fabricated with the proposed fabrication scheme. The measured white reflectance was > 45% in the visible spectrum range and -49% at 550 nm wavelength. The fabricated reflector had moderate color gamut of 17% of the National Television System Committee (NTSC) standard and it showed very high white reflectivity. The fabricated color reflector is expected to be applicable to reflective displays.


Discussions and implications of the recent enactment & revision of the healthcare law.
Recently, there have been many changes in the area of healthcare. There is no certainty how these changes will affect the healthcare system and public health. However, to at least have these changes positively implemented, it is clear that evaluation through continuous monitoring is necessary. The enforcement of the Medical Institution Accreditation and Medical Dispute Mediation Law as well as legal revisions regarding the public healthcare system are changes to improve the quality of healthcare, while at the same time, provide penalties for infractions of the new law such as medicine/medical device rebates; moreover, legal revisions regarding telemedicine are anticipated to impartially vitalize technical development as well as the pharmaceutical industry. For these changes to have a positive effect on the medical field and people's lives, an accurate comprehension of the system and understanding of the details is necessary to be able to respond sensitively to any changes in the future. Therefore, this paper examined the background information on the current discussion on the changes in the healthcare system, examined the detailed content of the system, and reviewed the areas that were in dispute as well as the main issues to contemplate the expected effects of the changes and future tasks that may be generated as a result. These considerations will act as foundation for an in depth understanding of recent trends in the healthcare system.


[Multi-occupational description of medical cooperation during a disaster].
On April 10, 2011, the author was sent to Yugakukan, a general shelter in Ishinomaki, as member of the first Primary Care for All Team (PCAT) mission, which was composed of medical and welfare service-specialists. Although various volunteers, government officials, and local organizations were gathered there, the situation was under control, and individuals cooperated under common goals. In order for all the organizations to cooperate and unify their purpose, PCAT identified all the key individuals and established the importance of conducting advanced meetings. The target of PCAT was to provide continued support until the shelter regained its capabilities as a local medical, welfare, and healthcare facility. We helped convert Yugakukan into a welfare shelter from a general one, with consideration for the needs of the entire disaster-stricken area. Likewise, we planned for the reduction of incidence by the local staff. As a team of pharmacists, we cooperated with the local key pharmacist, Mr. Yoshirou Tanno, to plan how the local pharmacy could be made more useful for revival. I concentrated on the production of a system for three weeks. During this period, I probed into the importance of the connection among people. Sharing information, building cooperation, and organization collaboration facilitated the smooth operations and development of the shelter. The experience of serving at Yugakukan can be used as indicator of pharmacists' role in the comprehensive care system, including supporting the elderly, whose population is currently rising.


Association of tau haplotype-tagging polymorphisms with Parkinson's disease in diverse ethnic Parkinson's disease cohorts.
The overlap in the clinical and pathological features of tauopathies and synucleinopathies raises the possibility that the tau protein may be important in Parkinson's disease (PD) pathogenesis. Several MAPT polymorphisms that define the tau H1 haplotype have been investigated for an association with PD with conflicting results; however, two meta-analyses support an association between haplotype H1 and PD. In this study, we recruited 508 patients and 611 healthy controls from Greek, Finnish and Taiwanese populations. We examined the possible genetic role of variation within MAPT in PD using haplotype-tagging single polymorphisms (SNPs) in these ethnically different PD populations. We identified a moderate association at SNP rs3785883 in the Greek cohort for both allele and genotype frequency (p = 0.01, p = 0.05, respectively) as well as for SNP rs7521 (genotype p = 0.02) and rs242557 (p = 0.01 genotypic, p = 0.04 allelic) in the Finnish population. There were no significant differences in genotype or allele distribution between cases and controls in the Taiwanese cohort. We failed to demonstrate a consistent association between the MAPT H1 haplotype (delineated by intron 9 ins/del) and PD in three ethnically diverse populations. However, the data presented here suggest that subhaplotypes of haplotype H1 may confer susceptibility to PD, and that either allelic heterogeneity or different haplotype composition explain the divergent haplotype results.


SMAD3 pathogenic variants: risk for thoracic aortic disease and associated complications from the Montalcino Aortic Consortium.
Pathogenic variants in SMAD3 cause thoracic aortic aneurysms and dissections, along with aneurysms and rupture of other arteries. Here, we examined differences in clinical presentation of aortic events (dissection or surgical repair of an aneurysm) with respect to age and variant type in an international cohort of individuals with SMAD3 variants. Aortic status and events, vital status and clinical features were abstracted through retrospective review of medical records of 212 individuals with 51 unique SMAD3 variants, including haploinsufficiency (HI) and missense substitutions in the MH2 domain, as well as novel in-frame deletions and missense variants in the MH1 domain. Aortic events were documented in 37% of cases, with dissections accounting for 70% of events. The median age at first aortic event was significantly lower in individuals with SMAD3 MH2 missense variants than those with HI variants (42years vs 49 years; p=0.003), but there was no difference in frequency of aortic events by variant type. The cumulative risk of an aortic event was 50% at 54 years of age. No aortic events in childhood were observed. SMAD3 pathogenic variants cause thoracic aortic aneurysms and dissections in the majority of individuals with variable age of onset and reduced penetrance. Of the covariates examined, the type of underlying SMAD3 variant was responsible for some of this variation. Later onset of aortic events and the absence of aortic events in children associated with SMAD3 variants support gene-specific management of this disorder.


CD8(+) T-cell attenuation of cutaneous herpes simplex virus infection reduces the average viral copy number of the ensuing latent infection.
During an initial encounter with herpes simplex virus type 1 (HSV-1) it takes several days for an adaptive immune response to develop and for herpes-specific CD8(+) T cells to infiltrate sites of infection. By this time the virus has firmly established itself within the innervating sensory nervous system where it then persists indefinitely. Preventing the establishment of viral latency would require blocking the skin to nervous system transmission of the virus. We wished to examine if CD8(+) T cells present early during acute HSV-1 infection could block this transmission. We show that effector CD8(+) T cells failed to prevent the establishment of HSV latency even when present prior to infection. This lack of blocking likely reflects the delayed infiltration of the CD8(+) T cells into the infected skin. Examination of the kinetics of HSV-1 infection highlighted the rapidity at which the virus infects the sensory ganglia and singled out early viral replication within the skin as an important factor in determining the magnitude of the ensuing latent infection. Though unable to prevent the establishment of latency, CD8(+) T cells could reduce the average viral copy number of the residual latent infection by dampening the skin infection and thus limiting the skin-to-nerve transmission of virus.


Transition From Parenteral to Enteral Nutrition and Postnatal Growth in Very Preterm Infants During Their First 28 Days of Life.
Nutrition practices for preterm infants during the first few weeks of life can be divided into three phases: the parenteral nutrition (PN), enteral nutrition (EN), and transition (TN) phases; the TN phase includes both PN and EN. Our purpose was to analyze nutrition practices for very preterm infants during the TN phase and their association with the infants' growth during the first 28 days of life. Data from 268 very preterm infants <32 weeks old from six neonatal intensive care units were analyzed retrospectively. The TN phase was defined as enteral feedings of 30-120 ml/kg/d. Postnatal growth failure (PGF) was defined as a 28-day growth velocity <15 g/kg/d. Differences in protein and energy intake between the PGF and non-PGF groups during the TN phase were calculated, and risk factors for PGF were identified using multivariate regression analysis. The total protein (parenteral + enteral) intake during the TN was 3.16 (2.89, 3.47) g/kg/d, which gradually decreased as the enteral feeding volume increased in the TN phase. The total energy (parenteral + enteral) intake during the TN phase was 115.72 (106.98, 122.60) kcal/kg/d. The PGF group had a lower total protein intake (parenteral + enteral) than the non-PGF group had [3.09 (2.85, 3.38) g/kg/d vs. 3.27 (3.06, 3.57) g/kg/d, P = 0.007, respectively]. No significant difference was found in energy intake during the TN phase. The variables associated with PGF included a lower total protein (parenteral + enteral) intake, a smaller day of age at the end of the TN phase, and a higher birth weight z-score. Increasing the total protein intake (parenteral + enteral) during the TN could reduce the incidence of PGF.


Novel self-nanomicellizing solid dispersion based on rebaudioside A: a potential nanoplatform for oral delivery of curcumin.
Rebaudioside A (RA) has nanocarrier characteristics that allow it to self-assemble into micelles in aqueous solutions. The purpose of this study was to determine if a self-nanomicellizing solid dispersion based on RA could be utilized as an oral nano-drug delivery system. Curcumin (Cur) served as a model hydrophobic drug, and a Cur-loaded self-nanomicellizing solid dispersion based on RA (RA-Cur) was formulated. The properties of RA-Cur in the solid state and in aqueous solution were characterized. The antioxidant activity and mechanism of RA-Cur endocytosis were also investigated. The pharmacokinetics, biodistribution in the intestinal tract, and anti-inflammation properties were also evaluated in vivo. RA-Cur could be easily fabricated, and it self-assembled into ultrasmall micelles (particle size ~4 nm) in a homogeneous distribution state (polydispersity index <0.2) when dissolved in water. Cur was readily encapsulated into RA micelles and this improved its water solubility (to 14.34±1.66 mg/mL), as well as its in vitro release and membrane permeability. The antioxidant activities of Cur in RA-Cur were also significantly improved. Biodistribution in the intestinal tract confirmed a significant enhancement of Cur absorption in the duodenum, jejunum, and ileum by encapsulation in RA-Cur, and the absorption of RA-Cur was governed by mixed transcytosis mechanisms. Pharmacokinetic tests of RA-Cur in rats revealed a dramatic 19.06-fold enhancement of oral bioavailability when compared to free Cur. More importantly, oral administration of RA-Cur could efficiently ameliorate ulcerative colitis in a mouse model induced by dextran sodium sulfate. Self-nanomicellizing solid dispersions based on RA have great potential as novel oral nano-drug delivery systems for hydrophobic drugs such as Cur.


T lymphocytes orient against the direction of fluid flow during LFA-1-mediated migration.
As they leave the blood stream and travel to lymph nodes or sites of inflammation, T lymphocytes are captured by the endothelium and migrate along the vascular wall to permissive sites of transmigration. These processes take place under the influence of hemodynamic shear stress; therefore, we investigated how migrational speed and directionality are influenced by variations in shear stress. We examined human effector T lymphocytes on intercellular adhesion molecule 1 (ICAM-1)-coated surfaces under the influence of shear stresses from 2 to 60 dyn.cm(-2). T lymphocytes were shown to respond to shear stress application by a rapid (30 s) and fully reversible orientation of their migration against the fluid flow without a change in migration speed. Primary T lymphocytes migrating on ICAM-1 in the presence of uniformly applied SDF-1α were also found to migrate against the direction of shear flow. In sharp contrast, neutrophils migrating in the presence of uniformly applied fMLP and leukemic HSB2 T lymphocytes migrating on ICAM-1 alone oriented their migration downstream, with the direction of fluid flow. Our findings suggest that, in addition to biochemical cues, shear stress is a contributing factor to leukocyte migration directionality.