Pulmonary function in patients with multiple trauma and associated severe head injury.
1) Sodium and water balance and pulmonary function studies were obtained in five patients with multiple injuries, including pulmonary contusion, plus severe intracranial trauma. All patients received dexamethasone, 4-6 every 6 hours during the 72-hour study period after injury. 2) Results were compared with those from 14 previously reported patients without head injury; none had received corticosteroids. 3) Study patients with head injury achieved negative water balance and almost-zero sodium balance within 72 hours of injury be excreting a high-volume, low-sodium urine. Despite elevated alveolar-arterial oxygen gradients and low-normal pulmonary compliance initially, there was progressive improvement and no patient developed post-traumatic pulmonary insufficiency. 4) The data suggest that the "negative" effects of major intracranial trauma on the kidney, heart, and lung are cancelled by dexamethasone, or that corticosteroids protect pulmonary function in the patient with multiple injuries and prevent post-traumatic pulmonary insufficiency, perhaps through their effect on the kidney leading to rapid restoration of sodium and water balance.


A New Promising Treatment Strategy for Carbon Monoxide Poisoning: High Flow Nasal Cannula Oxygen Therapy.
BACKGROUND High-flow nasal cannula (HFNC) is an alternative to conventional normobaric oxygen therapy (NBO) for hypoxemic patients. Since nothing is known about its effect on carbon monoxide (CO) poisoning, we hypothesized that HFNC might be a useful device in the treatment of CO poisoning victims. MATERIAL AND METHODS We retrospectively reviewed the medical records of patients who were admitted consecutively to the emergency department with CO intoxication. Patients were divided into 2 groups: patients treated with HFNC and patients treated with conventional face mask (CFM). Demographic data, pretreatment, and control (after 1 hour) arterial blood gas analyses values of the patients were evaluated. RESULTS Sixty-eight patients (mean age 35.8±18.7 years) were included in this study. NBO was given via HFNC to 38 patients (55.9%), and via CFM to 30 patients (44.1%). The demographic characteristics and pretreatment values of carboxy-hemoglobin (COHb) were similar in the 2 groups. The mean COHb value of the HFNC group at the first hour was found significantly lower than the CFM group: 9.5±4.7 and 12.0±5.1, respectively (P=0.041). Improvement of COHb level was significantly higher in the HFNC group compared to the CFM group: 12.5±4.5 versus 6.7±3.7, respectively (P=0.001). CONCLUSIONS HFNC was superior than CFM in alleviating COHb levels in the victims of CO poisoning. We believe that using HFNC will increase patient comfort by shortening the duration of treatment in emergency department settings, especially in patients who have mild clinical findings of CO poisoning.


The role of mechanical loading in the onset and progression of osteoarthritis.
Osteoarthritis is a progressive joint disease characterized by an imbalance of articular cartilage biosynthesis and degradation attributed to both inflammatory and biomechanical factors. Whereas moderate mechanical loading appears necessary for maintaining healthy cartilage, abnormal joint loading increases the risk of osteoarthritis. Obesity-induced osteoarthritis and the benefits of physical activity may be mediated by systemic levels of proinflammatory mediators as well as local biomechanical factors in the joint.


Psychological mindedness, work, and outcome in day treatment.
A recently completed clinical trial that investigated the effectiveness of a group-oriented, day treatment program provided an opportunity to pursue a multidimensional approach to the prediction of treatment outcome. The sample consisted of 99 psychiatric outpatients, most of whom had received diagnoses of affective and personality disorders. The predictor variables included a patient personality characteristic (psychological mindedness), a group process variable (patient work), and their interaction. Univariate analyses revealed significant direct relationships between psychological mindedness and both work and favorable outcome, and between work and favorable outcome. Multivariate analyses indicated that psychological mindedness and work had independent significant relationships (additive or interactive) with several of the outcome variables. In combination they accounted for up to a quarter of the outcome variance. The results demonstrate the benefit of using a theoretically consistent multidimensional approach. The time-efficient nature of the predictor measures used in the study make them particularly amenable for use by clinicians and researchers.


Lateral shearing interferometer for measuring photoinduced refractive index change in As(2)S(3).
We have built and demonstrated a lateral shearing interferometer as a process engineering and control tool for the fabrication and characterization of direct-laser-written waveguide structures in chalcogenide glasses. Photoinduced change in refractive index of 0.154+/-0.002 was measured for as-deposited amorphous As(2)S(3) thin films at 633 nm with an estimated measurement uncertainty of 1.3% for this air-gap interferometer configuration. The simple design of this interferometer can easily be adapted to other wavelengths including mid- and long-wave infrared regions to measure changes in refractive index or material inhomogeneities in transmissive materials.


Diabetes mellitus: Trends in northern India.
Diabetes mellitus is becoming a global health issue with more than 80% diabetics living in developing countries. India accounts for 62.4 million diabetics (2011). Indian Council of Medical Research India Diabetes Study (ICMR-INDIAB) study showed highest weighted prevalence rate in the north India among all studied regions. Diabetes in north India has many peculiarities in all aspects from risk factors to control programmers. North Indians are becoming more prone for diabetes and dyslipidemia because rapid westernization of living style and diet due rapid migration to metropolitan cities for employment. North Indian diabetes is plagued with gender bias against females, poor quality of health services, myths, and lack of disease awareness compounded with small number of prevention and awareness programmers that too are immature to counteract the growing pandemic.


Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus.
In B6AF1 mice, T lymphocytes that use the V beta 11-positive (and not V beta 6-positive or V beta 8-positive) segment in their receptor for antigen are greatly reduced in the thymus and peripheral lymphoid tissues, most likely as a result of clonal deletion. The relative number of V beta 11-positive cells in adult lymph nodes was ten times as high in B6AF1 mice thymectomized 1 to 4 days after birth as in normal mice. Moreover, for the first 10 days of life of B6AF1 mice, mature V beta 11-positive T cells were readily detected in the thymus and spleen. Thus neonatal thymectomy results in the maintenance of the receptor repertoire of early postnatal life, and this correlates with the subsequent development of organ-specific autoimmune diseases.


Severe Tardive Dystonia on Low Dose Short Duration Exposure to Atypical Antipsychotics: Factors Explored.
Tardive dystonia (TD) is a serious side effect of antipsychotic medications, more with typical antipsychotics, that is potentially irreversible in affected patients. Studies show that newer atypical antipsychotics have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report a case of 20-year-old male with hyperthymic temperament and borderline intellectual functioning, who developed severe TD after low dose short duration exposure to atypical antipsychotic risperidone and then olanzapine. The goal of this paper is to alert the reader to be judicious and cautious before using casual low dose second generation antipsychotics in patient with no core psychotic features, hyperthymic temperament, or borderline intellectual functioning suggestive of organic brain damage, who are more prone to develop adverse effects such as TD and monitor the onset of TD in patients taking atypical antipsychotics.


Contributions of EEG-fMRI to Assessing the Epileptogenicity of Focal Cortical Dysplasia.
Purpose: To examine the ability of the BOLD response to EEG spikes to assess the epileptogenicity of the lesion in patients with focal cortical dysplasia (FCD). Method: Patients with focal epilepsy and FCD who underwent 3T EEG-fMRI from 2006 to 2010 were included. Diagnosis of FCD was based on neuroradiology (MRI+), or histopathology in MRI-negative cases (MRI-). Patients underwent 120 min EEG-fMRI recording session. Spikes similar to those recorded outside the scanner were marked in the filtered EEG. The lesion (in MRI+) or the removed cortex (in MRI-) was marked on the anatomical T1 sequence, blindly to the BOLD response, after reviewing the FLAIR images. For each BOLD response we assessed the concordance with the spike field and with the lesion in MRI+ or the removed cortex in MRI-. BOLD responses were considered "concordant" if the maximal t-value was inside the marking. Follow-up after resection was used as gold-standard. Results: Twenty patients were included (13 MRI+, 7 MRI-), but in seven the EEG was not active or there were artifacts during acquisition. In all 13 studied patients, at least one BOLD response was concordant with the spike field; in 9/13 (69%) at least one BOLD response was concordant with the lesion: in 6/7 (86%) MRI+ and in 3/6 (50%) MRI- patients. Conclusions: Our study shows a high level of concordance between FCD and BOLD response. This data could provide useful information especially for MRI negative patients. Moreover, it shows in almost all FCD patients, a metabolic involvement of remote cortical or subcortical structures, corroborating the concept of epileptic network.


Relationships among self-esteem, stress, and physical activity in college students.
The purpose of this study was to identify population and sex-specific relationships between perceived stress, self-esteem, and physical activity in college students. 90 students, ages 18 and older and enrolled in five sections of a health and human behavior class during the spring 2010 semester, were contacted for this study with 74 consenting to serve as study participants. Each participant completed three surveys: the Rosenberg Self-Esteem Scale, the Perceived Stress Scale, and the International Physical Activity Questionnaire. Significant correlations were observed between perceived stress and self-esteem in men, and in women. Physical activity was not significantly correlated with perceived stress or self-esteem.


Chronic inflammation of the placenta: definition, classification, pathogenesis, and clinical significance.
Chronic inflammatory lesions of the placenta are characterized by the infiltration of the organ by lymphocytes, plasma cells, and/or macrophages and may result from infections (viral, bacterial, parasitic) or be of immune origin (maternal anti-fetal rejection). The 3 major lesions are villitis (when the inflammatory process affects the villous tree), chronic chorioamnionitis (which affects the chorioamniotic membranes), and chronic deciduitis (which involves the decidua basalis). Maternal cellular infiltration is a common feature of the lesions. Villitis of unknown etiology (VUE) is a destructive villous inflammatory lesion that is characterized by the infiltration of maternal T cells (CD8+ cytotoxic T cells) into chorionic villi. Migration of maternal T cells into the villi is driven by the production of T-cell chemokines in the affected villi. Activation of macrophages in the villi has been implicated in the destruction of the villous architecture. VUE has been reported in association with preterm and term fetal growth restriction, preeclampsia, fetal death, and preterm labor. Infants whose placentas have VUE are at risk for death and abnormal neurodevelopmental outcome at the age of 2 years. Chronic chorioamnionitis is the most common lesion in late spontaneous preterm birth and is characterized by the infiltration of maternal CD8+ T cells into the chorioamniotic membranes. These cytotoxic T cells can induce trophoblast apoptosis and damage the fetal membranes. The lesion frequently is accompanied by VUE. Chronic deciduitis consists of the presence of lymphocytes or plasma cells in the basal plate of the placenta. This lesion is more common in pregnancies that result from egg donation and has been reported in a subset of patients with premature labor. Chronic placental inflammatory lesions can be due to maternal anti-fetal rejection, a process associated with the development of a novel form of fetal systemic inflammatory response. The syndrome is characterized by an elevation of the fetal plasma T-cell chemokine. The evidence that maternal anti-fetal rejection underlies the pathogenesis of many chronic inflammatory lesions of the placenta is reviewed. This article includes figures and histologic examples of all chronic inflammatory lesions of the placenta.


Few-Layered Mo(1-x)WxS2 Hollow Nanospheres on Ni3S2 Nanorod Heterostructure as Robust Electrocatalysts for Overall Water Splitting.
Owing to unique optical, electronic, and catalytic properties, MoS2 have received increasing interest in electrochemical water splitting. Herein, few-layered Mo(1-x)WxS2 hollow nanospheres-modified Ni3S2 heterostructures are prepared through a facile hydrothermal method to further enhance the electrocatalytic performance of MoS2. The doping of W element optimizes the electronic structure of MoS2@Ni3S2 thus improving the conductivity and charge-transfer ability of MoS2@Ni3S2. In addition, benefitting from the few-layered hollow structure of Mo(1-x)WxS2, the strong electronic interactions between Mo(1-x)WxS2 and Ni3S2 and the hierarchical structure of one-dimensional nanorods and three-dimensional Ni foam, massive active sites and fast ion and charge transportation are obtained. As a result, the optimized Mo(1-x)WxS2@Ni3S2 heterostructure (Mo-W-S-2@Ni3S2) achieves an extremely low overpotential of 98 mV for hydrogen evolution reaction and 285 mV for oxygen evolution reaction at 10 mA cm-2 in alkaline electrolyte. Particularly, using Mo-W-S-2@Ni3S2 heterostructure as a bifunctional electrocatalyst, a cell voltage of 1.62 V is required to deliver a 10 mA cm-2 water splitting current density. In addition, the electrode can be maintained at 10 mA cm-2 for at least 50 h, indicating the excellent stability of Mo-W-S-2@Ni3S2 heterostructure. Therefore, this development demonstrates an effective and feasible strategy to prepare highly efficient bifunctional electrocatalysts for overall water splitting.


A new RAS mutation that suppresses the CDC25 gene requirement for growth of Saccharomyces cerevisiae.
In the yeast Saccharomyces cerevisiae, the activation of adenylate cyclase requires the products of the RAS genes and of CDC25. We isolated several dominant extragenic suppressors of the yeast cdc25 mutation. They did not suppress a thermosensitive allele of the adenylate cyclase gene (CDC35). One of these suppressors was a mutated RAS2 gene in which the transition C/G----T/A at position 455 resulted in replacement of threonine 152 by isoleucine in the protein. The same mutation in a v-Ha-ras gene reduces the affinity of p21 for guanine nucleotides (L.A. Feig, B. Pan, T.M. Roberts, and G.M. Cooper, Proc. Natl. Acad. Sci. USA 83:4607-4611, 1986). These results support a model in which the CDC25 gene product is the GDP-GTP exchange factor regulating the activity of the RAS gene product.


Functions of IQD proteins as hubs in cellular calcium and auxin signaling: A toolbox for shape formation and tissue-specification in plants?
Calcium (Ca2+) ions play pivotal roles as second messengers in intracellular signal transduction, and coordinate many biological processes. Changes in intracellular Ca2+ levels are perceived by Ca2+ sensors such as calmodulin (CaM) and CaM-like (CML) proteins, which transduce Ca2+ signals into cellular responses by regulation of diverse target proteins. Insights into molecular functions of CaM targets are thus essential to understand the molecular and cellular basis of Ca2+ signaling. During the last decade, IQ67-domain (IQD) proteins emerged as the largest class of CaM targets in plants with mostly unknown functions. In the March issue of Plant Physiology, we presented the first comprehensive characterization of the 33-membered IQD family in Arabidopsis thaliana. We showed, by analysis of the subcellular localization of translational green fluorescent protein (GFP) fusion proteins, that most IQD members label microtubules (MTs), and additionally often localize to the cell nucleus or to membranes, where they recruit CaM Ca2+ sensors. Important functions at MTs are supported by altered MT organization and plant growth in IQD gain-of-function lines. Because IQD proteins share structural hallmarks of scaffold proteins, we propose roles of IQDs in the assembly of macromolecular complexes to orchestrate Ca2+ CaM signaling from membranes to the nucleus. Interestingly, expression of several IQDs is regulated by auxin, which suggests functions of IQDs as hubs in cellular auxin and calcium signaling to regulate plant growth and development.


High risk and low prevalence diseases: Hemophilia emergencies.
Hemophilia is a bleeding disorder due to coagulation pathway factor deficiency that is associated with significant morbidity and mortality. This review highlights the pearls and pitfalls of the emergency department (ED) evaluation of hemophilia, including diagnostic procedures, imaging, and management based on current evidence. Hemophilia is marked by deficiency in factor VIII (in hemophilia A) or IX (in hemophilia B), which may result in severe bleeding. The severity of the disease depends upon factor levels. Patients with severe deficiency most commonly present in the first two years of life. Severe bleeding may include intracranial hemorrhage, retroperitoneal bleeding, large hematomas, bleeding within the chest or abdomen/pelvis, and subacute or delayed postpartum bleeding. ED management is the immediate replacement of clotting factors based on the suspicion of bleed rather than the confirmation of one. The doses for factor concentrate replacement to achieve factor levels of 100% are 50 U/kg for FVIII and 100 U/kg for FIX. The development of inhibitors can complicate the clinical picture and treatment possibilities. Consultation with the hematology specialist is recommended to assist with evaluation and management. Emergency physician knowledge of hemophilia, including the presentation, evaluation, and management, can improve the care of these patients.


Initial mercury evaporation from amalgams made with in-containing commercial alloys.
This study examined the Hg evaporation behavior during the early setting of amalgams that contain In in the alloy powders. Two different types of commercially available In-containing alloys were tested: an In-particle admixed powder (Indisperse, D) and an In-containing single-composition powder (Indiloy, S). Mercury evaporation from specimens (4 mm in dia, 8 mm tall) was monitored 10 min after trituration to 180 min using a mercury vapor analyzer according to the methods used in a previous study. The amounts released from 10 min to 180 min were compared with the results of our previous study on a single-composition amalgam (Tytin, T) with pure Hg and with Hg-In liquids (5 or 10%). Amalgam S and In-containing T terminated Hg evaporation within 180 min. There was no significant (p > 0.05) difference in the amount released between T amalgam made using pure mercury and D, and between T amalgam made with 5% In-containing mercury and S amalgam. Mercury release from amalgam D was significantly (p < 0.05) higher than from S or both types of In-containing T amalgam. Adding In to mercury or alloying In into the alloy particles appeared to be more effective in reducing the mercury vapor than admixing pure In particles into the amalgam.


Increased incidence of liver cancer after successful DAA treatment of chronic hepatitis C: Fact or fiction?
Therapy of hepatitis C has been revolutionized by Direct Antiviral Agents. These drugs are safe and efficacious in all infected patients, including those with advanced, or decompensated cirrhosis, and are currently largely used in such cases in clinical practice worldwide. It was therefore cause of great concern the publication of two reports suggesting that treatment with DAAs could increase the risk of hepatocellular carcinoma in cirrhotic patients, particularly in those receiving antiviral therapy after having been cured for an HCC. These reports have generated a great and controversial debate and have been followed by a series of other publications not confirming such increased risk. This article summarizes published studies assessing the relation between DAA therapy and HCC in two different clinical setting: HCC recurrence in patients with an history of cured HCC and "de novo" HCC occurrence in patients without previous HCC. Rates of HCC recurrence after DAAs were extremely variable in different studies, reflecting great heterogeneity of this clinical setting. Data on "de novo" HCC incidence were more homogeneous and suggest that treatment with DAAs is not modifying the risk of developing HCC in the first 6-12 months. The possibility that treatment with DAAs may favour tumour growth and spread in individual patients with active HCC foci is suggested by some observations but remains unproven. There is clearly a need for prospective studies designed to better define these issues.


Oral Manifestation as the Main Sign of an Advanced Stage Acute Promyelocytic Leukemia.
Acute myeloid leukemia is an aggressive malignant neoplasm occurring mainly in elderly, with the median age of 65 years. Oral manifestations, mainly spontaneous bleeding, are a common finding in acute myelocytic leukemia and may represent the initial evidence of the disease. This report describes a case of a 47-year-old man with a one-month history of spontaneous oral bleeding. The patient had already been consulted by two professionals but he remained undiagnosed. The physical examination revealed paleness, fever, epistaxis and ecchymoses in the oral mucosa. The complete blood count revealed anemia, severe thrombocytopenia and leukocytosis with blasts predominance, reinforcing the diagnosis hypothesis of an acute leukemia. The patient was immediately referred to the Hospital and despite having received a quick intervention, he died 3 days after the admission due to diffuse pulmonary alveolar hemorrhage. According to the peripheral blood immunophenotyping the diagnosis of hypogranular variant of acute promyelocytic leukemia was established. The delay in the diagnosis may have influenced the unfavorable outcome. Early diagnosis and management are indispensable for survival of leukemia patients. In this way, dentists may be responsible for an early detection of oral manifestations of leukemia and for a fast referral to an adequate professional.


Adaptation and Psychometric Evaluation of the Chinese Counseling Competencies Scale-Revised.
Objectives: This study conducted a linguistic and psychometric evaluation of the Chinese Counseling Competencies Scale-Revised (CCS-R). Methods: The Chinese CCS-R was created from the original English version using a standard forward-backward translation process. The psychometric properties of the Chinese CCS-R were examined in a cohort of 208 counselors-in-training by two independent raters. Fifty-three counselors-in-training were asked to undergo another counseling performance evaluation for the test-retest. The confirmatory factor analysis (CFA) was conducted for the Chinese CCS-R, followed by internal consistency, test-retest reliability, inter-rater reliability, convergent validity, and concurrent validity. Results: The results of the CFA supported the factorial validity of the Chinese CCS-R, with adequate construct replicability. The scale had a McDonald's omega of 0.876, and intraclass correlation coefficients of 0.63 and 0.90 for test-retest reliability and inter-rater reliability, respectively. Significantly positive correlations were observed between the Chinese CCS-R score and scores of performance checklist (Pearson's γ = 0.781), indicating a large convergent validity, and knowledge on drug abuse (Pearson's γ = 0.833), indicating a moderate concurrent validity. Conclusion: The results support that the Chinese CCS-R is a valid and reliable measure of the counseling competencies. Practice implication: The CCS-R provides trainers with a reliable tool to evaluate counseling students' competencies and to facilitate discussions with trainees about their areas for growth.


Replication of mini-P1 plasmid DNA in vitro requires two initiation proteins, encoded by the repA gene of phage P1 and the dnaA gene of Escherichia coli.
We have developed an in vitro DNA-replication system that replicates exogenously added mini-P1 plasmid DNA. The system consists of purified P1 RepA protein and a partially purified mixture of Escherichia coli replication proteins. It is essentially the same as that described for the replication of oriC plasmid DNA [Fuller, R.S., Kaguni, J.M. & Kornberg, A. (1981) Proc. Natl. Acad. Sci. USA 78, 7370-7374]. Mini-P1 DNA replication requires the E. coli DnaA initiation protein in addition to the P1 RepA initiation protein. The reaction is inhibited by rifampicin, novobiocin, and antibody to DnaB, suggesting the involvement of RNA polymerase, DNA gyrase, and DnaB protein. Replication is initiated in the region of the P1 origin of replication and proceeds unidirectionally as determined by electron microscopy. Thus, the in vitro system mimics the essential features of mini-P1 replication as suggested by genetic studies.


Structure and functional analysis of the RNA- and viral phosphoprotein-binding domain of respiratory syncytial virus M2-1 protein.
Respiratory syncytial virus (RSV) protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp) complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties are related to the core region of M2-1 encompassing residues S58 to K177. Here we report the NMR structure of the RSV M2-1(58-177) core domain, which is structurally homologous to the C-terminal domain of Ebola virus VP30, a transcription co-factor sharing functional similarity with M2-1. The partial overlap of RNA and P interaction surfaces on M2-1(58-177), as determined by NMR, rationalizes the previously observed competitive behavior of RNA versus P. Using site-directed mutagenesis, we identified eight residues located on these surfaces that are critical for an efficient transcription activity of the RdRp complex. Single mutations of these residues disrupted specifically either P or RNA binding to M2-1 in vitro. M2-1 recruitment to cytoplasmic inclusion bodies, which are regarded as sites of viral RNA synthesis, was impaired by mutations affecting only binding to P, but not to RNA, suggesting that M2-1 is associated to the holonucleocapsid by interacting with P. These results reveal that RNA and P binding to M2-1 can be uncoupled and that both are critical for the transcriptional antitermination function of M2-1.


Tubulin glycylation controls primary cilia length.
As essential components of the eukaryotic cytoskeleton, microtubules fulfill a variety of functions that can be temporally and spatially controlled by tubulin posttranslational modifications. Tubulin glycylation has so far been mostly found on motile cilia and flagella, where it is involved in the stabilization of the axoneme. In contrast, barely anything is known about the role of glycylation in primary cilia because of limitations in detecting this modification in these organelles. We thus developed novel glycylation-specific antibodies with which we detected glycylation in many primary cilia. Glycylation accumulates in primary cilia in a length-dependent manner, and depletion or overexpression of glycylating enzymes modulates the length of primary cilia in cultured cells. This strongly suggests that glycylation is essential for the homeostasis of primary cilia, which has important implications for human disorders related to primary cilia dysfunctions, such as ciliopathies and certain types of cancer.


CT Angiography in the Diagnosis of Brain Death.
Summary Brain death is defined as the irreversible cessation of functioning of the entire brain, including the brainstem. Brain death is principally established using clinical criteria including coma, absence of brainstem reflexes and loss of central drive to breathe assessed with apnea test. In situations in which clinical testing cannot be performed or when uncertainty exists about the reliability of its parts due to confounding conditions ancillary tests (i.a. imaging studies) may be useful. The objective of ancillary tests in the diagnosis of brain death is to demonstrate the absence of cerebral electrical activity (EEG and evoked potentials) or cerebral circulatory arrest. In clinical practice catheter cerebral angiography, perfusion scintigraphy, transcranial Doppler sonography, CT angiography and MR angiography are used. Other methods, like perfusion CT, xenon CT, MR spectroscopy, diffusion weighted MRI and functional MRI are being studied as potentially useful in the diagnosis of brain death. CT angiography has recently attracted attention as a promising alternative to catheter angiography - a reference test in the diagnosis of brain death. Since 1998 several major studies were published and national guidelines were introduced in several countries (e.g. in France, Austria, Switzerland, the Netherlands and Canada). This paper reviews technique, characteristic findings and criteria for the diagnosis of cerebral circulatory arrest in CT angiography.


Using clinical questions to structure the content of a web-based information resource for primary care physicians.
The Medical Home Portal is a web site aimed at supporting physicians and families in improving the care and outcomes for children with special health care needs (CSHCN) in the Medical Home model. To optimize access to its information and resources, the content has been structured using XML schemas that incorporate relevant clinical questions. This approach guides authors as they develop content and informs the organization of the site, aimed at assuring that users can readily locate needed information and resources. It will also enable direct access to relevant content via "infobuttons" or a questions-based interface, and extraction of content for use in electronic health records or other electronic media.


[Fibronectin in the sputum in malignant and inflammatory diseases of the respiratory tract].
Fibronectin , a glycoprotein, which is detectable in the pericellular space, can not be found on the surface of malignant transformed cells, but in the surrounding medium in a higher concentration. Which this finding, it was possible to differentiate between inflammatory and malignant genesis of pleural fluid and ascites. In the sputum and in the bronchial lavage different concentrations can be found too: In carcinomas the concentration on the average is much higher but not constant. This glycoprotein can therefore be used as a further tool in the search for neoplasms in the bronchial tree.


Inappropriate use of oxygen: loss of a valuable healthcare resource.
Oxygen (O2) use is well established in hospitalized patients with hypoxemia. However, its value in patients without hypoxemia is not well documented. The authors conducted a retrospective study to evaluate the excess use of O2 and the resulting loss of resources. They established criteria for O2 use by faculty consensus. Ninety-six patients (102 admissions) receiving O2 between August and October 1991 were identified. Principal discharge diagnoses included cardiac diseases (37%), pulmonary diseases (26.5%), and miscellaneous (36.5%). Cumulative oxygen use was 9,742 hours. Appropriate O2 amounted to 3,272 hours (34%), and inappropriate O2 use was 6,470 hours (66%). The billing for O2 use was $38,468, of which $25,880 constituted inappropriate use. In 1991, there were 7,743 admissions, with oxygen charges of $1.06 million. Extrapolation of the data shows billing for inappropriate oxygen was $697,000. The authors conclude that inappropriate use of oxygen results in significant loss of resources. Educational efforts to decrease this loss and evaluate its impact on patient outcome is needed.


Tetracyclines: what a rheumatologist needs to know?
Tetracyclines are broad-spectrum antibiotics that act at the ribosomal level. They were first introduced in 1948 and were widely prescribed by dermatologists in the early 1950s for treatment of acne. More recently, biologic actions of tetracyclines affecting inflammation, angiogenesis, and bone metabolism have been researched. The therapeutic effects of tetracycline and its analogues in rheumatic diseases have also been investigated. This article will review the rheumatological use of tetracycline and its analogues.


Association of matrix metalloproteinase-9 and decorin expression with the infiltration of cervical cancer.
Matrix metalloproteinase-9 (MMP9) has been recognized to be an important factor in cancer invasion and metastasis. In contrast, decorin has been revealed to inhibit primary tumor development. The aim of the present study was to investigate the function of MMP9 and decorin in cervical cancer. Three experiments were performed to analyze the function of MMP9 and decorin in the invasion of cervical cancer by: i) Analyzing the expression of MMP9 and decorin by immunohistochemistry in 100 cervical specimens; ii) determining the concentration of decorin by an enzyme-linked immunosorbent assay (ELISA) using the human squamous cervical cancer cell line CaSki and human endometrial stromal cell line CRL4003 and iii) evaluating the invasion ability of CaSki cells in a cervical invasion model by an invasion assay. Immunohistochemistry revealed that MMP9 was overexpressed in microinvasive carcinoma (100.0%) but was less strongly expressed in normal or pre-malignant squamous epithelium (0-41.9%). In contrast, the activity of decorin in stroma adjacent to neoplastic cells was lower in microinvasive carcinoma (9.1%) compared with in normal or pre-malignant lesions (74.2-100.0%). An ELISA revealed that MMP9 released from CaSki cells resolved the decorin released from CRL4003 cells. An invasion assay demonstrated that the invasive ability of CaSki cells was suppressed by an MMP inhibitor, and decorin was released from CRL4003 cells. These data suggested that decorin prevented the invasion of malignant cells in uterine cervical cancer; however, MMP9 promotes cell invasion by destroying decorin.


How is membrane phospholipid biosynthesis controlled in neural tissues?
Phospholipids are the major constituents of cell membranes, and have numerous structural and functional roles in the nervous system. Although the metabolic pathways responsible for the syntheses of the phosphatides phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), and phosphatidylserine (PtdSer) are well understood, the mechanisms controlling these pathways in neural tissue have not been fully characterized. Recent studies have suggested that the main factors controlling PtdCho and PtdEtn synthesis by the Kennedy cycle tend to be the intracellular levels of key substrates for the biosynthetic enzymes, or changes in the activities of the rate-limiting enzymes. Moreover, different control mechanisms may operate, depending upon the functional state of the tissue.


Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin.
In this study we examined the interaction of the anti-nerve agent drug pyridostigmine bromide (PB, 3,3-dimethylaminocarbonyloxy- N-methylpyridiniyum bromide), the insect repellent DEET ( N, N-diethyl- m-toluamide), and the insecticide permethrin [3-(2,2-dichloroethyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester] in binding to human serum albumin (HSA). Concentrations between 500 ng/ml and 10 microg/ml PB, DEET and permethrin, alone or in combination, were incubated with HSA at 37 degrees C for 60 min. Concentrations of PB, DEET and permethrin were determined using high performance liquid chromatography (HPLC). The results showed that 81.2+/-4.2%, and 84.6+/-2.5% of the initial concentration of PB was bound to HSA when incubated alone or in combination with DEET or permethrin, respectively. DEET and permethrin did not significantly interact with HSA after 1 h of incubation. Incubation of combinations of two or three compounds did not significantly alter the binding pattern of any of the compounds with HSA. These results showed that PB is highly bound to albumin protein, while the competition between PB, DEET and permethrin on binding sites of HSA as a possible site of interaction following combined administration in vivo is not likely.


Sleep deprivation increases cortical excitability in epilepsy: syndrome-specific effects.
To use transcranial magnetic stimulation (TMS) to investigate the hypothesis that sleep deprivation increases cortical excitability in people with epilepsy. We performed paired pulse TMS stimulation, using a number of interstimulus intervals (ISIs) on each hemisphere of 30 patients with untreated newly diagnosed epilepsy (15 idiopathic generalized epilepsy [IGE] and 15 focal epilepsy) and on the dominant hemisphere of 13 healthy control subjects, before and after sleep deprivation. Both hemispheres in patients with IGE and the hemisphere ipsilateral to the EEG seizure focus in those with focal epilepsy showed an increase in cortical excitability following sleep deprivation at a number of ISIs. This change in excitability was most prominent in the patients with IGE. Although there were minor changes after sleep deprivation in control subjects and the contralateral hemisphere in the focal epilepsy group seen at the 250-millisecond ISI, it was less than in the other groups. Sleep deprivation increases cortical excitability in epilepsy; the pattern of change is syndrome dependent.


Sodium hydrosulfide relieves neuropathic pain in chronic constriction injured rats.
Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP). Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS) could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI) were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S). The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL), mechanical withdrawal threshold (MWT), and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group (P < 0.05). NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats.


A Rare Cause of Pulmonary Edema in the Postoperative Period.
With the increasing longevity of the population, the annual rates of hip arthroplasties performed have been steadily increasing over the past decade. Given the presence of medical comorbidities in the older patients, the peri-operative care of these individuals requires multi-specialty care, now more than ever. Hip arthroplasty is generally well tolerated, with early mortality after the procedure being <1%. Bone cement implantation syndrome (BCIS) is an entity that is occasionally encountered during or after the surgery. It is characterized by hypoxemia, hypotension, cardiac arrhythmias, and cardiac arrest leading to death, in severe cases. We report a case of a middle-aged female who developed refractory hypotension and pulmonary edema while undergoing hemiarthroplasty for a pathological femoral neck fracture and experienced cardiac arrest in the immediate postoperative period. Critical care physicians must familiarize themselves with promptly diagnosing and managing BCIS.


Adult and two children with fetal methotrexate syndrome.
The folic acid antagonists, methotrexate and aminopterin, are known to be teratogenic in humans. The critical period for their teratogenecity is suspected to be between 6 to 8 weeks post-conception. Fetal exposure from 10 to 32 weeks weeks post-conception to methotrexate alone or in combination with other anti-cancer drugs has not resulted in obvious teratogenic effects. Methotrexate is often used to treat cancers but is occasionally used as an abortifacient. The long-term outcome of the fetal aminopterin syndrome has been published in only four adults. We report on a 28-year-old man with fetal methotrexate syndrome and two children with mild manifestations of the syndrome. One child was inadvertently exposed to methotrexate from 7 1/2 through 30 weeks post-conception because his mother was receiving it for treatment of breast cancer. The other was exposed from 11 weeks and 5 days through 25 weeks in an attempt to induce abortion. The 28-year-old man has craniofacial and digital anomalies, growth retardation but normal intelligence as noted in the previously reported cases. These cases remind us of the teratogenicity of methotrexate and should serve as a warning that if methotrexate is used as an abortifaciant and an abortion does not ensue, there is a teratogenic risk.


Long non-coding RNA MALAT1 interacts with miR-124 and modulates tongue cancer growth by targeting JAG1.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), was the earliest discovered to be correlated with cancer and contributes to the initiation and development of several types of tumors. Dysregulation of MALAT1 expression is frequently observed in many types of cancer such as gastric cancer, esophageal squamous cell carcinoma and glioma. To date, the role of MALAT1 and the underlying mechanisms in tongue cancer development remain unclear. In the present study, we studied the influence of MALAT1 on tongue cancer cell lines and clinical tongue cancer samples so as to detect its function and the underlying mechanism. In the present study, lncRNA-MALAT1 was specifically upregulated in tongue cancer cell lines and overexpression promoted tongue cancer cell growth by targeting miR-124. Knockdown of MALAT1 suppressed the growth and invasion of human tongue cancer cells and inhibited metastasis in vitro and in vivo. In addition, miR-124-dependent jagged1 (JAG1) regulation was required for MALAT1-induced tongue cancer cell growth. Our data revealed that MALAT1 inhibited tongue cancer cell growth and metastasis through miR-124-dependent JAG1 regulation. In conclusion, we revealed that MALAT1 may play an oncogenic role by increasing proliferation and metastasis of tongue cancer and is a potential therapeutic target in human tongue cancer.


Solvent Stokes' shifts revisited: application and comparison of Thompson-Schweizer-Chandler-Song-Marcus theories with Ooshika-Bakshiev-Lippert theories.
The "classical" treatment of solvent Stokes' shifts has been with us for 50 years or more. Twenty-five years ago, aided by new statistical mechanical underpinnings of liquid-state theory, Chandler and others [Thompson, M.; Schweizer, K.; Chandler, D. J. Chem. Phys. 1982, 76, 1128-1135. Schweizer, K.; Chandler, D. J. Chem. Phys. 1983, 78, 4118-4125. Song, X.; Chandler, D.; Marcus, R. J. Phys. Chem. 1996, 100, 11954-959.] developed newer approaches to predicting solvent shifts. I employ these here in a direct comparison with the older methods for three molecules of general interest in four different solvents. I also suggest new routes to future methods that may retain the advantages of both methods.


Astellas' lawsuit against Prescrire: French court rules that prescrire did not "denigrate" protopic (tacrolimus).
A Paris court handed down its ruling on 2 March, rejecting a suit brought by pharmaceutical company Astellas against the French journal Prescrire. At a time when French society is reeling in the wake of the scandal caused by weight-loss drug Mediator (benfluorex), the 2 March ruling comes as very good news for healthcare professionals and for patients.


Crystal structure of the archaeal ammonium transporter Amt-1 from Archaeoglobus fulgidus.
Ammonium transporters (Amts) are integral membrane proteins found in all kingdoms of life that fulfill an essential function in the uptake of reduced nitrogen for biosynthetic purposes. Amt-1 is one of three Amts encoded in the genome of the hyperthermophilic archaeon Archaeoglobus fulgidus. The crystal structure of Amt-1 shows a compact trimer with 11 transmembrane helices per monomer and a central channel for substrate conduction in each monomer, similar to the known crystal structure of AmtB from Escherichia coli. Xenon derivatization has been used to identify apolar regions of Amt-1, emphasizing not only the hydrophobicity of the substrate channel but also the unexpected presence of extensive internal cavities that should be detrimental for protein stability. The substrates ammonium and methylammonium have been used for cocrystallization experiments with Amt-1, but the identification of binding sites that are distinct from water positions is not unambiguous. The well ordered cytoplasmic C terminus of the protein in the Amt-1 structure has allowed for the construction of a docking model between Amt-1 and a homology model for its physiological interaction partner, the P(II) protein GlnB-1. In this model, GlnB-1 binds tightly to the cytoplasmic face of the transporter, effectively blocking conduction through the three individual substrate channels.


Heterodyned fifth-order two-dimensional IR spectroscopy: third-quantum states and polarization selectivity.
A heterodyned fifth-order two-dimensional (2D) IR spectrum of a model coupled oscillator system, Ir(CO)(2)(C(5)H(7)O(2)), is reported. The spectrum is generated by a pulse sequence that probes the eigenstate energies up to the second overtone and combination bands, providing a more rigorous potential-energy surface of the coupled carbonyl local modes than can be obtained with third-order spectroscopy. Furthermore, the pulse sequence is designed to generate and then rephase a two-quantum coherence so that the spectrum is line narrowed and the resolution improved for inhomogeneously broadened systems. Features arising from coherence transfer processes are identified, which are more pronounced than in third-order 2D IR spectroscopy because the transition dipoles of the second overtone and combination states are not rigorously orthogonal, relaxing the polarization constraints on the signal intensity for these features. The spectrum provides a stringent test of cascading signals caused by third-order emitted fields and no cascading is observed. In the Appendix, formulas for calculating the signal intensities for resonant fifth-order spectroscopies with arbitrarily polarized pulses and transition dipoles are reported. These relationships are useful for interpreting and designing polarization conditions to enhance specific spectral features.


Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine.
Immunohistochemistry and an immunofluorescence technique was used to detect folate receptor expression in tissue samples and cell lines of head and neck squamous carcinoma, including 20 tissue samples of nasopharyngeal carcinoma, 16 tissue samples of laryngeal carcinoma, and HNE-1, HNE-2, CNE-1, CNE-2, SUNE-1, 5-8F, and Hep-2 cell lines. Iron staining, electron microscopy, and magnetic resonance imaging were used to observe endocytosis of folate-conjugated cisplatin-loaded magnetic nanoparticles (CDDP-FA-ASA-MNP) in cultured cells and transplanted tumors. As shown by immunohistochemistry, 83.3% (30/36) of the head and neck squamous carcinomas expressed the folate receptor versus none in the control group (0/24). Only the HNE-1 and Hep-2 cell lines expressed the folate receptor, and the other five cell lines did not. Endocytosis of CDDP-FA-ASA-MNP was seen in HNE-1 and Hep-2 cells by iron staining and electron microscopy. A similar result was seen in transplanted tumors in nude mice. Magnetic resonance imaging showed low signal intensity of HNE-1 cells and HNE-1 transplanted tumors on T2-weighted images after uptake of CDDP-FA-ASA-MNP, and this was not seen in CNE-2 transplanted tumors. In conclusion, head and neck squamous carcinoma cell strongly expressed the folate receptor, while normal tissue did not. The folate receptor can mediate endocytosis of folate-conjugated anticancer nanomedicines, and lays the foundation for molecular targeted treatment of cancer.


Efficacy and durability of nevirapine in antiretroviral drug näive patients.
Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was first reported in the scientific literature in 1990. Varying doses of nevirapine (NVP) and a number of regimens containing this NNRTI have been studied in antiretroviral (ARV) näive patients. Four key studies have compared the efficacy and safety of triple drug regimens containing NVP in ARV näive, HIV-1 infected patients. The INCAS study was the first demonstration of how to use NVP in an effective and durable manner: as a component of a triple drug regimen. The COMBINE Study was a comparison of protease inhibitor (PI)-based and NVP-based triple regimens. The Atlantic Study is comparing the safety and efficacy of three triple drug regimens in ARV näive patients. In this study, treatment consists of a divergent drug regimen (PI and nucleoside reverse transcriptase inhibitors, NRTIs) targeting both HIV-1 protease and reverse transcriptase or a convergent regimen targeting reverse transcriptase alone (three NRTIs or two NRTIs plus a NNRTI). A clinical endpoint study (BI 1090) compared the efficacy and durability of multi-drug regimens in ARV näive patients with high baseline plasma HIV-1 RNA levels (pVLs) and low peripheral blood CD4+ lymphocyte counts. Data from these studies confirm that triple regimens containing NVP suppressed viral replication for up to one year, even when the ARV näive patients had low CD4+ cell counts at baseline. Nevirapine-containing regimens suppressed pVLs to < 50 copies/ mL in approximately 50% of patients in the studies discussed (Intent to Treat analyses). Data from 96 weeks of follow up in the Atlantic Study demonstrates that the regimens containing didanosine and stavudine plus indinavir or NVP were significantly more successful in suppressing pVLs to < 50 copies/mL during this period than a regimen composed of these NRTIs and lamivudine (p < or = 0.001). As with other ARV drugs, NVP should always be used as part of a fully suppressive ARV regimen. When used in this way, it is an effective ARV drug, which contributes to durable virological and immunological responses in approximately half of all treated patients. Nevirapine-containing regimens are effective in patients with advanced HIV-1 infection, i.e., low CD4+ cell counts. Data will soon be available from the 2NN Study that compares the efficacy and safety of four different regimens using NVP once daily, NVP twice daily, efavirenz once daily or a combination of NVP and efavirenz. All four arms of the study include a backbone of stavudine and lamivudine.


Parenting experiences during cancer.
This paper reports a study to increase our understanding of how cancer affects childcare through assessing the parenting experiences of cancer patients and their spouses with young children. A parent's cancer brings insecurity into the life of a child. It affects their well-being and increases their needs for comfort and care. However, little research has been conducted to understand how a parent's illness affects parenting and the care of the child. The study was carried out in 2001-2002. An explorative design was chosen and data were collected through in-depth interviews with a convenience sample of 18 parents of 23 children (aged 0-18 years) in 10 families. Parents described living in a state of emergency. Cancer was consuming their energy, physically and emotionally. In spite of their difficulties, they were striving to be good parents. Positive aspects of illness reported were a shift of priorities and change of values that often brought family members closer together. The parents would face the challenges of illness by making the best of it, putting the needs of the children in focus and trying to maintain normal family life. The overall aim of parenting would be to protect the children and make the illness situation as secure and normal as possible for them. Cancer is a challenge and often necessitates changes in parenting roles, responsibilities and goals. In the future, nurses need to approach parents with young children more directly about these extra challenges, and offer them further assistance in dealing with them.


Electroporation of suspension cell lines - A proposed assay set for optimizations.
To make in vitro single cell electroporation protocols more comparable between various cancer types and groups, we propose a set of assays to test a range of electric field strengths at the start of any new project to determine the optimal electric field strength for a given cell line. While testing a range of electric field strengths, we kept the other ESOPE parameters constant (8 pulses, 100 µs pulse duration, 1 Hz pulse frequency). Basic assays were employed to measure short-term viability, effectiveness of treatment, metabolic activity, and recovery potential post-treatment to determine the optimal field strength for a particular cell line. Six cancer cell lines were tested, three of human (A549, A375 and Pan02) and three murine (LLC, B16F10 and MIA-PACA2). Our findings demonstrate that the optimal electroporation setting while keeping with all other ESOPE parameters are 800 V/cm for A549 and Pan02, 700 V/cm for A375, Mia-PACA2, and B16F10, and 1300 V/cm for LLC. Having an agreed upon set of assays to determine each cell lines optimal electric field strength should allow an improve translation of findings between cell lines for in vitro work from various groups and potentially improve translation into the clinic.


Prompting and stimulus shaping procedures for teaching visual-motor skills to retarded children.
Stimulus shaping appears to be a highly successful way to teach discrimination skills. In stimulus shaping, the topographical configuration of the stimuli is gradually changed over trials so that discrimination is at first easy, and then gradually more difficult. Stimulus shaping procedures might also be effective for training visual-motor tasks. Two experiments were conducted to assess the relative effectiveness of stimulus shaping and "traditional" prompting procedures. Pegboard skills were trained in Experiment 1. In Experiment 2 a self-care skill was trained, in which children learned to hang a toothbrush or a washcloth on a specific hook. Six low-functioning retarded children were studied in each experiment, using a within-subject alternating treatments design. Each participant received concurrent training on two related tasks, using stimulus shaping for one and a standard prompting procedure for the other. Training with the stimulus shaping procedure required less training time to criterion, always resulted in fewer errors, always required fewer and less intrusive therapist's prompts, and always resulted in greater density of reinforcement. These results demonstrate the value of stimulus shaping strategies for training visual-motor skills.


Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis.
Hunner-type interstitial cystitis (HIC) is a rare, chronic inflammatory disease of the urinary bladder with unknown etiology and genetic background. Here, we conduct a genome-wide association study of 144 patients with HIC and 41,516 controls of Japanese ancestry. The genetic variant, rs1794275, in the major histocompatibility complex (MHC) region (chromosome 6p21.3) is associated with HIC risk (odds ratio [OR] = 2.32; p = 3.4 × 10-9). The association is confirmed in a replication set of 26 cases and 1,026 controls (p = 0.014). Fine mapping demonstrates the contribution to the disease risk of a completely linked haplotype of three human leukocyte antigen HLA-DQβ1 amino acid positions, 71, 74, and 75 (OR = 1.94; p = 5 × 10-8) and of HLA-DPβ1 amino acid position 178, which tags HLA-DPB1∗04:02 (OR = 2.35; p = 7.5 × 10-8). The three HLA-DQβ1 amino acid positions are located together at the peptide binding groove, suggesting their functional importance in antigen presentation. Our study reveals genetic contributions to HIC risk that may be associated with class II MHC molecule antigen presentation.


Fine tuning the specificity of the periplasmic phosphate transport receptor. Site-directed mutagenesis, ligand binding, and crystallographic studies.
Phosphorous, primarily in the form of phosphate, is a critical nutrient for the life of a cell. We have previously determined the 1.7-A resolution structure of the phosphate-binding protein, an initial receptor for the high-affinity phosphate active transport system or permease in Escherichia coli (Luecke, H., and Quiocho, F.A. (1990) Nature 347, 402-406). This structure is the first to reveal the key role of hydrogen bonding interactions in conferring the high specificity of the permease, a specificity also shared by other phosphate transport systems. Both monobasic and dibasic phosphates are recognized by the phosphate-binding protein with Asp56 playing a key role. Here we report site-directed mutagenesis, ligand binding, and crystallographic studies of the binding protein which show that introduction of one additional Asp by mutagenesis of the Thr141 in the ligand-binding site restricts binding to only the monobasic phosphate.


Nosocomial bacteremia: clinical significance of a single blood culture positive for coagulase-negative staphylococci.
To describe the epidemiology of nosocomial coagulase-negative staphylococci (CoNS) bacteremia and to evaluate the clinical significance of a single blood culture positive for CoNS. A 3-year retrospective cohort study based on data prospectively collected through hospital-wide surveillance. Bacteremia was defined according to CDC criteria, except that a single blood culture growing CoNS was not systematically considered as a contaminant. All clinically significant blood cultures positive for CoNS nosocomial bacteremia were considered for analysis. A large university teaching hospital in Geneva, Switzerland. A total of 2,660 positive blood cultures were identified. Of these, 1,108 (41.7%) were nosocomial; CoNS were recovered from 411 nosocomial episodes (37.1%). Two hundred thirty-four episodes of CoNS bacteremia in the presence of signs of sepsis were considered clinically relevant and analyzed. Crude mortality and associated mortality were 24.4% and 12.8%, respectively. Associated mortality was similar among patients with one positive blood culture and those with two or more (16.2% vs 10.8%, respectively; P = .3). Mortality rates after bacteremia for patients with a single positive blood culture and for those with two or more were 15.3% and 7.0%, respectively, at day 14 (RR, 2.2; CI95, 0.87-5.46) and 20.8% and 11.3%, respectively, at day 28 (RR, 1.9; CI95, 0.9-3.8). On multivariate analysis, only age and a rapidly fatal disease were independently associated with death. CoNS bacteremia harbor a significant mortality and a single positive blood culture in the presence of signs of sepsis should be considered as clinically relevant.


Inspiring the next generation of Cardiothoracic Surgeons: an easily reproducible, sustainable event increases UK undergraduate interest in the specialty.
There is believed to be declining interest in cardiothoracic surgical careers among UK medical students. Relative lack of undergraduate exposure to the specialty compared with other surgical specialties may be partly responsible. Using pre- and postintervention analysis, we assessed the ability of a student-led extracurricular engagement event to increase undergraduate interest in the specialty. Fifty-four students attended and 50 (93%) participated in the study. Of the total, 32% of delegates had identified a cardiothoracic mentor, with only 8 and 4% exposed to cardiac and thoracic surgery, respectively, compared with 50% exposed to other surgical specialties. Self-reported understanding of cardiothoracic training increased from 20 to 80% (P < 0.001) after the 1-day event; 77% of delegates reported increased interest in the specialty. We demonstrate that it is possible to provide a free-to-user event that increases engagement using a student-led design. Similar events could increase interest in the specialty and may improve recruitment rates. Current levels of cardiothoracic exposure are very low among UK students.


Knockout of RAGE ameliorates mainstream cigarette smoke-induced airway inflammation in mice.
The receptor for advanced glycation end products (RAGE), a multiligand receptor, has been proved to be implicated in inflammatory responses in chronic obstructive pulmonary disease (COPD). In this study, we investigated the role of RAGE in cigarette smoke (CS)-induced airway inflammation in COPD. Wild-type (WT) and RAGE gene knockout (KO) mice were exposed to mainstream CS or room air for 2h twice daily, 6days per week for consecutive 4weeks. Cell counts and proinflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF). Lung tissues were collected for histological examination and gene expression profiling by cDNA microarray. CS exposure induced significant airway inflammation in WT mice evidenced by histological inflammatory changes in HE stain with increased neutrophils and proinflammatory cytokines in the BALF, which were all attenuated by RAGE KO. cDNA microarray indicated a total of 179 upregulated genes and 351 downregulated genes in mouse lungs. Among these genes, S100 proteins (S100A8 and S100A9), the RAGE common ligands, were significantly downregulated, which were validated by real-time qPCR. Further analyses by Gene Ontology, KEGG and Disease Ontology suggested these differentiated expressed genes significantly related to the immune-inflammatory responses in lungs via crosstalking with a complicated network of signaling pathways. Knockout of RAGE significantly ameliorates mainstream CS-induced airway inflammation in mice possibly via downregulating S100A8/A9 expression and its related immune-inflammatory responses.


Regulating the stability of TGFbeta receptors and Smads.
Transforming growth factor beta (TGFbeta) controls cellular behavior in embryonic and adult tissues. TGFbeta binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that together regulate gene expression. In this review, mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of TGFbeta are presented. We discuss how the activity and duration of TGFbeta receptor/Smad signaling can be regulated by post-translational modifications that affect the stability of key proteins in the pathway. We highlight links between these mechanisms and human diseases, such as tissue fibrosis and cancer.


The growth rate of metastatic non-seminomatous germ cell testicular tumours measured by marker production doubling time--I. Theoretical basis and practical application.
Changes in serum tumour marker levels in non-seminomatous germ cell testicular tumours (NSGCTT) are used to monitor tumour growth and response to treatment. A novel method of calculating the actual tumour marker production (TMP) per day is reported; estimation of the rate of change of TMP is a measure of the tumour growth or regression rate. TMP is calculated mathematically from the rate of increase in serum marker level and its natural half life. TMP is assumed to be proportional to the number of marker producing cells in the tumour. TMP was calculated over the time between orchidectomy and the start of chemotherapy. The rate of increase in TMP with time is expressed as the marker production doubling time (MPDT) and is a measure of the growth rate. In a group of 51 patients with metastatic NSGCTT, TMP varied from 0.012 to 5985 iu/l/day (AFP) and 0.08-5404 iu/l/day (HCG). MPDT varied from 0.5 to greater than 80 days (45 cases) for AFP + ve patients and from 1.8 to greater than 80 days (34 cases) for HCG + ve patients; greater than 80% of cases had a MPDT less than or equal to 32 days. In 45/51 (88%) patients, there was no discrepancy in MPDT between markers. The use of changes in serum marker level to follow tumour progression and regression is simple, but the calculation of actual TMP provides clearer information about the change in number of marker producing cells and can be used as non-invasive method for measuring the tumour growth rate of metastatic disease and response to treatment.


Laparoscopic cryoablation for renal cell carcinoma: 100-Month oncologic outcomes. Caputo PA, Ramirez D, Zargar H, Akca O, Andrade HS, O'Malley C, Remer EM, Kaouk JH. J Urol. 2015 Oct;194(4):892-896. [Epub 2015 April 23]. doi: 10.1016/j.juro.2015.03.128.
With the incidence of renal cell carcinoma on the rise treatment options for the small renal mass have broadened. Cryoablation is increasingly used as a therapeutic option for renal tumors in select cases. However, studies with long-term oncologic outcomes are sparse. We evaluated the long-term oncologic outcomes of laparoscopic renal mass cryoablation. We reviewed our laparoscopic cryoablation database for patients treated with laparoscopic cryoablation from October 1997 to February 2005. Patients with less than 3 months of followup were excluded from study. Patient and tumor characteristics, and perioperative outcomes, including complications, were recorded. Recurrence-free, cancer specific and overall survival was analyzed using Kaplan-Meier curves. A total of 142 tumors in 138 consecutive patients were treated with laparoscopic cryoablation. Mean age of the cohort was 66.35 years. Of the patients 99 (71.7%) were male and 39 (28.3%) were female. Mean body mass index was 29.15kg/m(2) and median ASA score was 3. A solitary kidney was present in 23 patients (16.2%). Mean tumor size on cross-sectional imaging was 2.4cm. The mean preoperative and postoperative estimated glomerular filtration rate was 66.72 and 61.00ml per minute, respectively. The postoperative estimated glomerular filtration rate was determined at a mean±SD of 15.17±10.99 months of followup. The median R.E.N.A.L. nephrometry score was 5. Of the 142 tumors 100 were diagnosed as renal cell carcinoma after histopathological examination of the biopsy specimen. At 3, 5, and 10 years in patients diagnosed with renal cell carcinoma estimated recurrence-free survival was 91.4%, 86.5%, and 86.5%, estimated cancer specific survival was 96.8%, 96.8%, and 92.6%, and estimated overall survival was 88.7%, 79.1%, and 53.8%, respectively. Mean followup was 98.8±54.2 months in those diagnosed with renal cell carcinoma. Mean time to recurrence was 2.3 years. The latest experienced recurrence was 4.4 years after laparoscopic cryoablation. There was a postoperative complication rate of 10.6% with a total of 15 complications. Laparoscopic cryoablation achieves good long-term oncologic outcomes for localized small renal masses. It can safely be used in patients who cannot undergo or are unwilling to accept the risks of partial nephrectomy. Mean time to recurrence was 2.3 years and all recurrences developed within 4.4 years of initial treatment.


Accuracy of the Short-Form Montreal Cognitive Assessment Chinese Versions.
Background: There is a strong need for short and effective methods to screen for cognitive impairment. Recent studies have created short forms of the Montreal Cognitive Assessment (s-MoCA) in English-speaking populations. It is also important to develop a validated Chinese short version to detect cognitive impairment. Methods: Item response theory and computerized adaptive testing analytics were used to construct abbreviated MoCAs across a large neurological sample comprising 6,981 community-dwelling Chinese veterans. Results: Six MoCA items with high discrimination and appropriate difficulty were included in the s-MoCA. The Chinese short versions (sensitivity 0.89/0.90, specificity 0.72/0.77) are similar in performance to the full MoCA in identifying cognitive impairment (sensitivity 0.91, specificity 0.82). Conclusions: These short variants of the MoCA may serve as quick and effective instruments when the original MoCA cannot be feasibly administered in clinical services with a high patient burden and limited cognitive testing resources.


Shocks in ion sputtering sharpen steep surface features.
We report a regime of ion beam sputtering that occurs for sufficiently steep slopes. High slopes propagate over large distances without dissipating the steepest features. Both the propagation velocity and the dynamically selected slope are universal, independent of the details of the initial shape of the surface. The resulting behavior can be understood as the propagation of a shock front that self-selects a stable slope, as has been previously observed in thin-film fluid flows. Experiments confirm predictions of the theory. An important implication of the propagative behavior at high surface slopes is that a pattern can be fabricated at a large length scale and, through uniform ion irradiation, reduced to a smaller length scale while preserving, or even sharpening, the sharpest features.


Incidence of genital warts among U.S. service members before and after the introduction of the quadrivalent human papillomavirus vaccine.
Human papillomavirus (HPV) is the most common sexually transmitted infection among U.S. military members. The most frequent clinical manifestation of HPV is genital warts (GW). This investigation examined the annual incidence of diagnoses of GW among U.S. service members before and after the availability of the quadrivalent HPV (HPV4) vaccine in 2006. Incidence rates of GW diagnoses markedly declined among female service members in the HPV4 vaccine-eligible age range from 2007 (following introduction of the HPV4 vaccine) through 2010. In contrast, among women 25 years and older and men of all age groups, annual rates of GW diagnoses remained relatively low and stable from 2000 through 2010. The higher rates of diagnoses of GWs among female than male service members reflect the effects of routine periodic gynecologic screening. Slight increases in the incidence of GW diagnoses among men between 2010 and 2012 may in part reflect the repeal of the U.S. military's "Don't Ask Don't Tell" policy.


Task-dependent interaction between parietal and contralateral primary motor cortex during explicit versus implicit motor imagery.
Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks.


A Systematic Review of Clinical Practice Guidelines for Caries Prevention following the AGREE II Checklist.
Untreated oral diseases are detrimental to overall well-being and quality of life and are in close relationship with social and economic consequences. The presence of strong evidence for caries primary and secondary prevention is a compulsory tool for the development of clinical practice guidelines (CPGs). This paper was aimed to assess systematically the importance of clinical practice guidelines in caries prevention management considering both the adult and pediatric populations and evaluate them using the Appraisal of Guidelines for Research and Evaluation (AGREE II) Checklist. Records were extracted from EMBASE, SCOPUS, PubMed/Medline and seven other relevant guideline databases between 6 January and 14 February 2023. Two reviewers independently conducted the appraisal using the web-based platform My AGREE PLUS. Twenty-one guidelines/papers met the inclusion criteria and were reviewed. Eight CPGs included both primary and secondary prevention interventions, whereas thirteen presented a single preventive model. Overall, 12 guidelines were published in the USA. The mean AGREE II scores ranged from 35.4% to 84.3%. Of the total twenty-one included guidelines, twelve were classified as "Recommended", ranging from 56.3% to 84.3%, the others were described as "Recommended with modification", ranging from 35.4% to 68.9%. From the AGREE II analysis carried out, the CPGs included in this survey adopted a punctual methodological rigor but lacked applicative power. The present survey showed that the public, as the primary beneficiary, played a limited role in the development of the twenty-one CPGs. Hence, methodological improvement can better support high-quality CPG development in the future.


Sinoacutine from Glaucium contortuplicatum Boiss.
A phytochemical investigation of Glaucium contortuplicatum Boiss. (Papaveraceae) resulted in the isolation of sinoacutine from this plant for the first time. Spectral evidence for the identity of the isolated compound as sinoacutine is presented.


Overgrowth syndrome in neonates: a rare case series with a review of the literature.
We present here two-term neonates presenting with right lower limb hypertrophy, a port-wine stain, acral abnormalities and clubfeet. These neonates had overlapping features of Klippel Trenaunay syndrome and congenital lipomatous overgrowth, vascular malformation, epidermal nevi and scoliosis/skeletal abnormalities. Such overgrowth syndrome has not been previously described in the literature. Both the neonates are doing well and are under regular follow-up.


[Localized edema following cytostatic therapy].
In a phase II trial for non-small cell carcinoma of the lung and squamous cell carcinoma of the head and neck 16 patients were treated with a 3 drug combination chemotherapy: Cis-platinum, VP16, and vindesine. During therapy 4 patients suffered from localized transitory edema. This side effect has not been reported yet.


Mood Impairment in Patients with Olfactory Loss Predicts a More Pronounced Recovery of Olfactory Function.
Here, we refer to our publication "Symptoms of depression change with olfactory function" [Sci Rep. 2022 Apr 5;12(1):5656]. Depression decreases with olfactory improvement, but the question remains open of whether patients who indicate more suffering regarding mood impairment exhibit a different pattern of recovery from olfactory loss compared to those who suffer less. In the course of an additional investigation of our previously published dataset, we established groups of participants (N = 171) with low (≤8 points on a depression [ADSL] scale; 47%; n = 45) and high (≥14 points on ADSL scale; 53%; n = 53) mood impairment. We found that the group that reported more sufferance on a depression [ADSL] scale improved more in change of olfactory function, and, more importantly, odor discrimination change over a period of an average of 11 months. Patients, who suffered more, as indicated by higher scores on ADSL scale, may have been more willing to commit to the study protocol, and thus their improvement was more notable.


Terahertz Optical Properties and Carrier Behaviors of Graphene Oxide Quantum Dot and Reduced Graphene Oxide Quantum Dot via Terahertz Time-Domain Spectroscopy.
Graphene quantum dots (GQDs) with a band gap have been widely applied in many fields owing to their unique optical properties. To better utilize the optical advantages of GQDs, it is important to understand their optical characteristics. Our study demonstrates the optical properties and carrier behaviors of synthesized graphene oxide quantum dot (GOQD) and reduced graphene oxide quantum dot (rGOQD) pellets via Terahertz time-domain spectroscopy (THz-TDS). The complex permittivity and optical conductivity are obtained in the terahertz region, indicating that the optical conductivity of the GOQD is higher than that of the rGOQD. Although rGOQD has a higher carrier density, approximately 1.5-times than that of GOQD, the lower charge carrier mobility of the rGOQD, which is obtained using Drude-Lorentz oscillator model fitting contributes to a decrease in optical conductivity. This lower mobility can be attributed to the more significant number of defect states within the rGOQD compared to GOQD. To the best of our knowledge, our study initially demonstrates the optical property and carrier behaviors of GOQD and rGOQD in the THz region. Moreover, this study provides important information on factors influencing carrier behavior to various fields in which carrier behavior plays an important role.


Protemblemaria perla, a new species of tube blenny (Perciformes: Chaenopsidae) from the tropical eastern Pacific.
Protemblemaria perla, from Isla del Rey, Islas Perlas, Panama, is distinctive in having a long unbranched cirrus on the posterior nostril, a U-shaped fleshy ridge bearing fleshy flaps and a pair of papillae on the nape, a relatively high number (18) of segmented dorsal-fin rays, and small rust-colored spots on the dorsal fin. Protemblemaria perla and P. punctata, from the southern Caribbean, share several morphological features and form a transisthmian species pair. Although the degree of color variation is unknown in P. perla, color varies greatly in P. bicirris and P. punctata, both of which have an orange morph.


Antineoplastic agents. 465. Structural modification of resveratrol: sodium resverastatin phosphate.
As an extension of structure/activity investigations of resveratrol (1), phenstatin (2c), and the cancer antiangiogenesis drug sodium combretastatin A-4 phosphate (2b), syntheses of certain related stilbenes (14) and benzophenones (16) were undertaken. The trimethyl ether derivative of (Z)-resveratrol (4a) exhibited the strongest activity (GI(50) = 0.01-0.001 microg/mL) against a minipanel of human cancer cell lines. A monodemethylated derivative (14c) was converted to prodrug 14n (sodium resverastatin phosphate) for further biological evaluation. The antitubulin and antimicrobial activities of selected compounds were also evaluated.


Hyperion Image Analysis Depicts a Preliminary Landscape of Tumor Immune Microenvironment in OSCC with Lymph Node Metastasis.
Oral squamous cell carcinoma (OSCC) constitutes the most common types of oral cancer. Because its prognosis varies significantly, identification of a tumor immune microenvironment could be a critical tool for treatment planning and predicting a more accurate prognosis. This study is aimed at utilizing the Hyperion imaging system to depict a preliminary landscape of the tumor immune microenvironment in OSCC with lymph node metastasis. We collected neoplasm samples from OSCC patients. Their formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained and stained utilizing a panel of 26 clinically relevant metal-conjugated antibodies. Detection and analysis were performed for these stained cells with the Hyperion imaging system. Four patients met our inclusion criteria. We depicted a preliminary landscape of their tumor immune microenvironment and identified 25 distinct immune cell subsets from these OSCC patients based on phenotypic similarity. All these patients had decreased expression of CD8+ T cells in tumor specimens. Variety in cell subsets was seen, and more immune activated cells were found in patient A and patient B than those in patient C and patient D. Such differences in tumor immune microenvironments can contribute to forecasting of individual prognoses. The Hyperion imaging system helped to delineate a preliminary and multidimensional landscape of the tumor immune microenvironment in OSCC with lymph node metastasis and provided insights into the influence of the immune microenvironment in determination of prognoses. These results reveal possible contributory factors behind different prognoses of OSCC patients with lymph node metastasis and provide reference for individual treatment planning.


Antiradical Activity of Lignans from Cleistanthus sumatranus: Theoretical Insights into the Mechanism, Kinetics, and Solvent Effects.
Sumatranus lignans (SL) isolated from Cleistanthus sumatranus have demonstrated bioactivities, e.g., they were shown to exhibit immunosuppressive properties in previous research. Their structure suggests potential antioxidant activity that has not attracted any attention thus far. Consistently, a comprehensive analysis of the antioxidant activity of these compounds is highly desirable with the view of prospective medical applications. In this work, the mechanism and kinetics of the antiradical properties of SL against hydroperoxyl radicals were studied by using calculations based on density functional theory (DFT). In the lipid medium, it was discovered that SL reacted with HOO• through the formal hydrogen transfer mechanism with a rate constant of 101-105 M-1 s-1, whereas in aqueous media, the activity primarily occurred through the sequential proton loss electron transfer mechanism with rate constants of 102-108 M-1 s-1. In both lipidic and aqueous environments, the antiradical activity of compounds 6 and 7 exceeds that of resveratrol, ascorbic acid, and Trolox. These substances are therefore predicted to be good radical scavengers in physiological environments.


Applications of cytometry to study acute leukemia: in vitro determination of drug sensitivity and detection of minimal residual disease.
Modern clinical applications of cytometry include the determination of the most powerful antileukemic drugs in each patient at the time of diagnosis and the monitoring of residual disease during and off treatment. The precision of in vitro assays to test the susceptibility of cancer cells to cytotoxic drugs depends on the ability to maintain the cells' viability in culture. We found that bone marrow-derived allogeneic stromal cells are critical to prevent death by apoptosis of acute lymphoblastic leukemia (ALL) cells. Thus, we devised an in vitro drug sensitivity assay in which ALL cells are seeded onto stromal cells and viable leukemic cells are counted at the end of cultures by flow cytometry. Our preliminary results indicate that this assay is suitable for evaluating the drug sensitivity of leukemic lymphoblasts and testing the antileukemic activity of potentially effective compounds which have not yet been administered to patients with ALL. The identification of immunophenotypes expressed on leukemic cells but absent or extremely rare among normal hematopoietic progenitors allows close monitoring of the effects of drug treatment in vivo. Phenotypes that afford a detection level of 1 leukemic cell among 10,000 normal bone marrow cells have been identified in 90% of cases of T-ALL, 25% of B-lineage ALL, and 40% of acute myeloid leukemia (AML). In several studies, residual disease emerging during continuation therapy or off treatment almost invariably anticipated overt relapse by 1-7 months. These data indicate the reliability of immunologic techniques to detect occult leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)


A3 adenosine receptors modulate hypoxia-inducible factor-1alpha expression in human A375 melanoma cells.
Hypoxia-inducible factor-1 (HIF-1) is a key regulator of genes crucial to many aspects of cancer biology. The purine nucleoside, adenosine, accumulates within many tissues under hypoxic conditions, including that of tumors. Because the levels of both HIF-1 and adenosine are elevated within the hypoxic environment of solid tumors, we investigated whether adenosine may regulate HIF-1. Here we show that, under hypoxic conditions (< 2% O2), adenosine upregulates HIF-1alpha protein expression in a dose-dependent and time-dependent manner, exclusively through the A3 receptor subtype. The response to adenosine was generated at the cell surface because the inhibition of A3 receptor expression, by using small interfering RNA, abolished nucleoside effects. A3 receptor stimulation in hypoxia also increases angiopoietin-2 (Ang-2) protein accumulation through the induction of HIF-1alpha. In particular, we found that A3 receptor stimulation activates p44/p42 and p38 mitogen-activated protein kinases, which are required for A3-induced increase of HIF-1alpha and Ang-2. Collectively, these results suggest a cooperation between hypoxic and adenosine signals that ultimately may lead to the increase in HIF-1-mediated effects in cancer cells.


Histone H3 phosphorylation in the rat pineal gland: adrenergic regulation and diurnal variation.
In this study, we investigated phosphorylation of Ser10 in histone H3 by norepinephrine (NE) in the rat pineal gland. In whole-animal studies, we demonstrated a marked increase in histone H3 phosphorylation in the rat pineal gland during the first half of the dark period. Exposure to light during this period caused a rapid decline in histone H3 phosphorylation with an estimated t1/2 of less than 15 min, indicating a high level of dephosphorylation activity. Corresponding studies in cultured pineal cells revealed that treatment with NE produced an increase in histone H3 phosphorylation that peaked between 2 and 3 h and declined rapidly by 4 h. The NE-induced histone H3 phosphorylation was blocked by cotreatment with propranolol or KT5720, a protein kinase A inhibitor, but not by prazosin or other kinase inhibitors. Moreover, only treatment with dibutyryl cAMP but not other kinase activators mimicked the effect of NE on histone H3 phosphorylation. The NE-stimulated H3 phosphorylation was markedly increased by cotreatment with a serine/threonine phosphatase inhibitor, tautomycin or okadaic acid, supporting a high level of ongoing histone H3 dephosphorylation activity. Together, our results indicate that histone H3 phosphorylation is a naturally occurring event at night in the rat pineal gland that is driven almost exclusively by a NE-->beta-adrenergic-->cAMP/protein kinase A signaling mechanism. This transient histone H3 phosphorylation probably reflects the nocturnal activation of multiple adrenergic-regulated genes in the rat pineal gland.


Effects of ketoprofen alone or in combination with local anesthesia during the castration of bull calves on plasma cortisol, immunological, and inflammatory responses.
To determine the effects of the anti-inflammatory ketoprofen, alone or with local anesthesia (LA) during castration on cortisol, immune, and acute phase responses, 40 Friesian calves (215 +/- 3.5 kg) were assigned as follows: 1) control, 2) surgical castration (SURG), 3) SURG following ketoprofen (3 mg/kg BW i.v.; SURG + K), 4) SURG following LA (9 mL of 2% lidocaine hydrochloride to each testis; SURG + LA), or 5) SURG following LA and K (SURG + LA + K). Total cortisol response was greater (P < 0.05) in SURG, SURG + LA, and SURG + K + LA calves than in control calves and was not different between control and SURG + K calves. The interval to peak cortisol was longer (P < 0.05) for SURG + K + LA calves than for either SURG or SURG + K calves. On d 3, KLH-induced interferon-gamma production was lower (P < 0.05) in SURG calves than in control calves, whereas concanavalin A-induced interferon-gamma production was lower (P < 0.05) in all castration groups than in control. On d 1 after surgery, fibrinogen was higher (P < 0.05) in SURG and SURG + LA calves than in control calves, whereas SURG + LA + K calves had lower (P < 0.05) fibrinogen than did SURG calves. Haptoglobin was higher (P < 0.05) in SURG calves on d 1, 3, and 7 than in control calves. On d 1 after surgery, SURG + K and SURG + LA + K calves had lower (P < 0.05) haptoglobin concentrations than SURG calves, whereas SURG + K calves had lower (P < 0.05) levels than SURG calves on d 3. In conclusion, surgical castration induced a significant elevation in cortisol secretion; the rise in cortisol was reduced to control levels by the administration of ketoprofen but not local anaesthetic. Thus, systemic analgesia using ketoprofen is more effective than local anesthesia during castration to alleviate the associated stress response.


Association of Piebaldism with Café-au-Lait Macules.
A 45-day-old infant was brought by his parents to the dermatology outpatient department with chief complaints of asymptomatic, depigmented lesions that had been present on his skin since birth. On mucocutaneous examination, large rhomboid-shaped depigmented macules were noted on the abdomen and lower extremities bilaterally (Figure 1). A depigmented macule was present on the forehead, with white hair (leukotrichia; a "developing forelock") (Figure 2). Three hyperpigmented lesions (café-au-lait macules [CALMs]) were also noted on the chest (Figure 1a). There was no history of consanguinity, and the family history was negative. The infant was otherwise normal for his age. A diagnosis of "piebaldism with CALMs" was made, and his parents were counseled about the disease and its progression, and possible treatment options as the child grew. They were also informed about a currently unquantifiable risk of future development of Legius syndrome or neurofibromatosis type 1 (NF1), and were counseled for regular follow-up.


Evaluation of Nonalcoholic Fatty Liver Disease in C57BL/6J Mice by Using MRI and Histopathologic Analyses.
Nonalcoholic fatty liver disease (NAFLD) can lead to cirrhosis, hepatocellular carcinoma, and ultimately death. Magnetic resonance techniques are accurate, noninvasive methods for evaluating hepatic steatosis but, in animals, have not been fully validated against histologic findings. We sought to validate the MRI fat-signal fraction (MRI-FSF) used for diagnosing NAFLD in human nonclinical trials by comparing MRI data with histopathologic findings in C57BL/6J mice (n = 24) fed normal chow (controls) or a methionine- and choline-deficient (MCD) diet to induce NAFLD. Axial T2-weighted fast spin-echo images were used to examine the entire liver. For histopathologic analyses, liver slides were evaluated for hepatic steatosis according to the NAFLD activity score. Pearson correlation coefficient and receiver operating characteristics analyses were performed. According to the fat-fraction signal, the mean percentage of liver fat in mice with induced NAFLD was 57%, which correlated with the histologically determined steatosis grade. The proton-density fat fraction effectively distinguished severe from mild hepatic steatosis, with an AUC of 0.92. Evaluation accuracy decreased when lobular inflammation and hepatocellular ballooning were considered. This study showed strong concurrence between MRI-FSF and histopathologic steatosis in a murine model of NAFLD. MRI-FSF had moderate sensitivity and specificity in this context. These results confirm that the MRI is a useful biomarker of hepatic steatosis in NAFLD in murine model.


Mode-locked thulium-bismuth codoped fiber laser using graphene saturable absorber in ring cavity.
We demonstrate mode locking of a thulium-bismuth codoped fiber laser (TBFL) operating at 1901.6 nm, using a graphene-based saturable absorber (SA). In this work, a single layer graphene is mechanically exfoliated using the scotch tape method and directly transferred onto the surface of a fiber pigtail to fabricate the SA. The obtained Raman spectrum characteristic indicates that the graphene on the core surface has a single layer. At 1552 nm pump power of 869 mW, the mode-locked TBFL self starts to generate an optical pulse train with a repetition rate of 16.7 MHz and pulse width of 0.37 ps. This is a simple, low-cost, stable, and convenient laser oscillator for applications where eye-safe and low-photon-energy light sources are required, such as sensing and biomedical diagnostics.


Should the vent hole of posterior implant crowns be placed on the lateral surface? An in vitro study of the hydrodynamic feature of cement extrusion and retention ability.
Although placing a vent hole on the occlusal surface of the implant crown can reduce cervical marginal cement extrusion, it has disadvantages. Transferring the hole to the buccal or lingual surface of the posterior implant crown could therefore be an alternative solution. This study investigated the effect of transferring the vent hole to the lateral side of the implant posterior crown on the hydrodynamics of excess cement extrusion and the crown's retention ability. Specially fabricated posterior implant crowns were divided into five groups: crowns with an occlusal hole (OH), occlusal lateral hole (OLH), middle lateral hole (MLH), cervical lateral hole (CLH), and no hole (NH). Each set of implant analog-abutment-crown specimens was wrapped in a polymethylacrylate base. The base of the implant crown was divided into four 90-degree quadrants along the diagonal of the square base with a pen mark. Cement was used to bond the crowns and the abutments, and the weight of cement extrusions at the vent holes and the abutment cervical margins were calculated. The distribution of cement extrusion at the margin was photographed in each quadrant, and the areas of surface coverage of cement extrusion were compared with ImageJ software. Retentive strength was measured as the dislocation force using a universal testing machine. One-way analysis of variance was used for result analysis. The cervical marginal cement extrusions of crowns with lateral holes (OLH, MLH, and CLH) were significantly less than that of NH crowns (P<0.05), but more than that of OH crowns (P<0.05). Subgroup analysis among the lateral hole groups indicated that the higher the position of the lateral hole, the lower the weight of the cement extrusion, and the smaller the total distribution area of cement extrusion. The cement extrusion distribution area was larger in the quadrant with the hole than in those opposite and next to the hole. Retention strength comparison indicated no significant difference between crowns with NH, OH, or lateral holes. Transferring the vent hole of the posterior implant crown to the lateral side could reduce cement extrusion at the cervical margin while reducing retention strength deterioration and the esthetic drawbacks caused by occlusal hole opening.


Clark v. Arizona: diminishing the right of mentally ill individuals to a full and fair defense.
In Clark v. Arizona, the U.S. Supreme Court was faced with two main questions: Does Arizona's insanity defense statute, with its abridged M'Naughten standard, violate the Fourteenth Amendment? And does Arizona case law, with its complete prohibition on the use of mental disease or defect evidence to combat required mens rea elements of a crime, violate due process? In a six-three decision, the Court answered both of these questions in the negative.


Reconciling repertoire shift with affinity maturation: the role of deleterious mutations.
The shift in Ab repertoire, from Abs dominating certain primary B cell responses to genetically unrelated Abs dominating subsequent "memory" responses, challenges the accepted paradigm of affinity maturation. We used mathematical modeling and computer simulations of the dynamics of B cell responses, hypermutation, selection, and memory cell formation to test hypotheses attempting to explain repertoire shift. We show that repertoire shift can be explained within the framework of the affinity maturation paradigm, only when we recognize the destructive nature of hypermutation: B cells with a high initial affinity for the Ag are less likely to improve through random mutations.


Oxidized lipoproteins may play a role in neuronal cell death in Alzheimer disease.
Oxidative stress in the central nervous system (CNS) may cause oxidation of lipoprotein particles. The oxidized lipoproteins may damage cellular and subcellular membranes, leading to tissue injury and cell death. Human low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) are oxidized by transition metal ions, such as Cu2+. Using PC 12 cells, we tested the cytotoxicity of oxidized LDL and VLDL. Cell death was increased in a dose-dependent manner. Antioxidants added to the incubation medium, such as vitamins E or C, or resveratrol showed some protection. Results indicated that oxidized lipoproteins may serve as an oxidative stressor, which may initiate the neuronal cell death leading to the manifestation of Alzheimer disease (AD).


Pityriasis rosea like drug rash - a need to identify the disease in childhood.
Pityriasis rosea is a common dermatosis named by Gibert in 1860. It is an acute self limiting papulosquamous disease, probably infective in origin affecting healthy adolescents and young adults. It is characterized by distinctive skin eruptions and minimal constitutional symptoms. Drug induced pityriasis rosea tend to occur in older generation and resolution seen only after withdrawal of the offending drug. We report a case of 12-year-old boy with erythematous papules distributed over trunk and proximal arms after nimesulide therapy consistent with a clinical diagnosis of atypical pityriasis rosea. The relation of drug and development of pityriasis rosea is confirmed by dechallenge test of the suspected drug.