Candida auris on Apples: Diversity and Clinical Significance.
Candida auris is a multidrug-resistant nosocomial fungal pathogen. While the marine environment was recently identified as a natural niche for C. auris, the environment(s) that might have contributed to the development and spread of antifungal resistance in C. auris remains a mystery. Because stored fruits are often treated with fungicides to prevent postharvest spoilage, we hypothesized that stored fruits could serve as a possible selective force for and a transmission reservoir of antifungal-resistant isolates of pathogenic yeasts, including C. auris. To test this hypothesis, we screened fruits to study the diversity of pathogenic yeasts and their antifungal susceptibility profiles. Among the 62 screened apples, the surfaces of 8 were positive for C. auris, and all were stored apples. Whole-genome sequencing (WGS) showed that C. auris strains from apples were genetically diverse and exhibited broad phylogenetic distribution among the subclades within clade I. Interestingly, strains from apples had closely related strains from other sources in India, including from patients, hospitals, and marine environments, and from clinical strains from other parts of the world. A broad range of fungicides, including dimethyl inhibitors (DMIs), were detected in stored apples, and all C. auris isolates exhibited reduced sensitivity to DMIs. Interestingly, C. auris was not isolated from freshly picked apples. Together, the results suggest a potentially complex ecology for C. auris with agriculture fungicide application on stored fruits as a significant selective force for drug resistance in clinics. IMPORTANCE In 2019, the U.S. Centers for Disease Control and Prevention classified the multidrug-resistant Candida auris as one of five pathogens posing the most urgent threats to public health. At present, the environment(s) that might have contributed to the development and spread of antifungal resistance in C. auris is unknown. Here, we tested whether fruits could be a source of multidrug-resistant C. auris. We identified genetically diverse C. auris strains with reduced sensitivity to major triazole dimethyl inhibitors fungicides on the surfaces of stored apples. The successful isolation of C. auris from apples here calls for additional investigations into plants as a reservoir of C. auris. Our findings suggest that C. auris in the natural ecosystem may come in contact with agriculture fungicides and that stored fruits could be a significant niche for the selection of azole resistance in C. auris and other human fungal pathogens.


Facile and selective nanoscale labeling of peptides in solution by using photolabile protecting groups.
For the selective labeling of peptides, a novel strategy was developed that combines the advantages of solid-phase peptide synthesis with the flexibility of labeling reactions in solution. To direct a label at a distinct position within the peptide sequence, other reactive positions are blocked with photolabile protecting groups that could be easily removed after the labeling reaction. Therefore selective labeling may become feasible for the first time even in nanomol amounts.


Ischemia mobilizes histamine but not pancreastatin from ECL cells of rat stomach: evidence for a cytosolic histamine compartment.
Histamine in the rat stomach resides in enterochromaffin-like (ECL) cells and mast cells. The ECL cells are peptide-hormone-producing endocrine cells known to release histamine and chromogranin-A-derived peptides (such as pancreastatin) in response to gastrin. Ischemia (induced by clamping of the celiac artery or by gastric submucosal microinfusion of the vasoconstrictor endothelin) mobilizes large amounts of ECL-cell histamine in a burst-like manner. This report examines the ECL-cell response to ischemia and compares it with that induced by gastrin in rats. Arterial clamping (30 min) and gastric submucosal microinfusion (3 h) of endothelin, vasopressin, or adrenaline caused ischemia, manifested as a raised lactate/pyruvate ratio and mucosal damage. Whereas microinfusion of gastrin released both histamine and pancreastatin, ischemia mobilized histamine only. The mucosal concentrations of histamine and pancreastatin, the number and immunostaining intensity of the ECL cells, and the ultrastructure of the ECL cells were unchanged following ischemia. The long-term effects of ischemia and reperfusion (60-90 min) on gastric mucosa were examined in rats treated with the proton pump inhibitor omeprazole for 4 days. The activity of the ECL cells was suppressed (reflected in low histamine-forming capacity) but returned to normal within 1 week, illustrating the ability of the ECL cells to recover. We suggest that ischemia mobilizes cytosolic ECL-cell histamine without affecting the storage of histamine (and pancreastatin) in the secretory organelles and without causing lasting ECL-cell impairment.


The scope and responsibility of medicine. A forum with a purpose.
Many physicians and others are convinced that there is a pressing need for more discussion and more agreement concerning what ought to be the scope of medicine in today's society. At the present moment, there is no general consensus either within or without the profession. Yet if the responsibility is ever to be met, its scope must be recognized and somehow defined. The editors of California Medicine propose to provide a forum in this journal for discussion of the scope and responsibility of medicine. This is a forum with a purpose, and so far as is known, an innovation in medical journalism. The forum is initiated with the statements beginning on the following page. Readers and others are invited to submit their views constructively and succinctly. As many of these as space permits will be published in future issues of California Medicine as a continuation of this forum. At an appropriate time all the material will be collated and, if feasible, the distillate will be prepared in the form of a statement on "The Scope and Responsibility of Medicine" to be submitted to the Council of the California Medical Association for its consideration. The statements which follow are the concisely expressed views of distinguished scholars, educators, statesmen and practitioners in the health field. It is hoped their views on this timely and important subject will provoke thought and comment among the readers of this journal


Sequential changes in the permeability of the blood-nerve barrier over the course of ricin neuronopathy in the rat.
We examined the sequential changes in the permeability of the BNB to a 4000-molecular-weight fluoresceinated dextran over an 18-week course of ricin neuronopathy. Neuronopathy was produced by injecting ricin into the tibial nerve of 18-day-old Long-Evans rats; permeability of the BNB in proximal sciatic nerve was evaluated by fluorescence microscopy 12 hours to 18 weeks post injection. BNB breakdown occurred two days after ricin injection and continued to be present over the 18-week course of the experiment. Ultrastructural studies revealed that Wallerian-type axonal degeneration was present in proximal sciatic nerve one day post injection. The degeneration involved only a portion of the fibers and was unaccompanied by subsequent axonal regeneration or ricin-induced injury of Schwann cells, endothelial cells or perineurial cells. Immunocytochemical studies revealed that an increased number of endoneurial macrophages did not appear until after the BNB breakdown. We conclude that (1) breakdown of the BNB occurs early and is longlasting in ricin-induced neuronopathy; (2) the BNB breakdown is a consequence of ricin-induced axonal degeneration and is independent of regenerating axons, a systemic toxic effect of ricin on the BNB, or an influx of macrophages; and (3) toxicant-induced degeneration of less than half of the fibers in a nerve is sufficient to cause a localized, persistent breakdown of the BNB.


Concentrations of monoamine metabolites and chlorpromazine in cerebrospinal fluid for prediction of therapeutic response in psychotic patients treated with neuroleptic drugs.
Concentrations of the major monoaminergic transmitter metabolites HVA, MOPEG and 5-HIAA were determined in the cerebrospinal fluid (CSF) of untreated schizophrenic patients. Patients with aberrated concentrations of 5-HIAA and HVA in CSF had schizophrenia in their families in a frequency significantly higher than that of patients with normal concentrations. These results may indicate the existence of a subgroup of schizophrenic patients having a family disposition for the disorder and an aberrated transmission from central serotonin and dopamine neurons. In young healthy volunteers, aberrated monoamine metabolite concentrations in CSF were also related significantly to a history of psychiatric morbidity in the family. In psychotic patients treated with chlorpromazine significant correlations were obtained between therapeutic outcome on the one hand, and both biochemical effects related to central monoamine metabolism and chlorpromazine concentrations in the CSF on the other hand. Patients with chlorpromazine concentrations above 1 ng/ml in CSF or 40 ng/ml in plasma responded more favourably than patients with concentrations below those levels. The results indicate that biochemical and pharmacokinetic data may be of value for diagnostic classification and prediction of therapeutic outcome in drug-treated schizophrenic patients.


THE KARYOLOGY OF TEREDO UTRICULUS (GMELIN) (MOLLUSCA, PELECYPODA).
By counting spermatocyte and oocyte bivalents and mitotic metaphase chromosomes in cleaving eggs, we have determined both the haploid (n = 19) and the diploid numbers (2n = 38) respectively, for the species Teredo utriculus. An XY and XO sex-determining mechanism is absent in the species under study. chromosomes cannot be grouped into different classes according to length. It seems that, for Teredo utriculus, a high number of chromosomes is not necessarily accompanied by a high amount of chromosomal DNA.


Effects of Medication-Assisted Treatment (MAT) for Opioid Use Disorder on Functional Outcomes: A Systematic Review.
This systematic review addresses the question: What are the effects of medication-assisted treatment (MAT) that use buprenorphine, buprenorphine combined with naloxone, methadone, or naltrexone for opioid use disorder (OUD) on functional outcomes compared with wait-list, placebo, treatment without medication, any other comparator, or each other (e.g., buprenorphine versus naltrexone)? Functional outcomes investigated included cognitive (e.g., memory), physical (e.g., fatigue), occupational (e.g., employment status), social/behavioral (e.g., criminal activity), and neurological (e.g., balance) function. The authors searched five scientific research databases from inception to 2017 and reference mined existing reviews. Two independent literature reviewers screened 6,292 citations; 1,327 full-text publications were reviewed in detail and 37 studies met inclusion criteria. Critical appraisals assessed studies in detail, and quality of evidence was rated using established criteria. Results were synthesized in meta-analyses and presented in comprehensive evidence tables. Although MAT patients performed significantly better on some functional outcomes than persons with OUD who did not receive MAT, MAT patients performed worse on several cognitive measures than did matched "healthy" controls with no history of substance use disorder (SUD) or OUD. Because of the moderate-to-high risk of bias of most studies, quality of evidence is low or very low for all findings. The small number of studies reporting on outcomes of interest and the weaknesses in the body of evidence prevent making strong conclusions about MAT effects on functional outcomes. The literature shows that more research is needed that targets functional outcomes specifically, and there is, in particular, a lack of research evaluating potential differences in functional effects among medication types, the route of administration, treatment modality, and length of treatment.


[Employed persons caring simultaneously for children and care-dependent relatives - a scoping review].
Employed persons caring simultaneously for children and care-dependent relatives - a scoping review Abstract. Background: Due to the demographic changes with higher life expectancy, later childbirth, and an increasing number of working women, more middle-aged persons are confronted with the care needs of younger and older generations while they themselves are still employed. Aim: The objective of this manuscript is to review the body of knowledge about employed people caring simultaneously for underaged children and care-dependent relatives. Methods: The databases MEDLINE, CINAHL, Cochrane Library, GeroLit, CC Med, SOWIPORT Gesis, PsycINFO and BASE were searched without any time limitations. Publications in German and English were included into this scoping review regardless of the study design. Results: A total of 85 studies from Western countries were included. Research activity is centered in North America and there are only limited empirical findings from the German-speaking regions. Nearly 70 % of the studies used a quantitative design. Research questions address the consequences of adopting multiple roles and the compatibility of different areas of life. In total, role theoretical perspectives predominate. Conclusions: The findings show that little attention has been paid to this specific issue in German-speaking regions. The methodical limitations and inadequate theoretical differentiation of the studies led to partly contradictory results. Future research should take the complexity of this living situation into account while considering methodical approaches and theoretical foundations.


Amygdalin (Laetrile): effect on clonogenic cells from human myeloid leukemia cell lines and normal human marrow.
The effect of amygdalin on human acute myelogenous leukemia cells and normal bone marrow granulocyte-monocyte precursors was studied in vitro using soft-gel culture. A pharmaceutical and a clinical source of amygdalin were tested and beta-glucosidase was added to selected cultures to promote the hydrolysis of amygdalin. Acute myelogenous leukemia cells were obtained from two human cell lines designated KG-1 and HL-60. A 50% inhibition of colony formation by both normal and leukemic cells was observed at an amygdalin concentration of 3.5 mg/ml using both drug sources. We found the colony-forming cells from the leukemic cell lines and normal marrow to be relatively resistant to amygdalin and its metabolites in vitro, and there was no selective kill of clonogenic cells from the human leukemia cell lines as compared to normal bone marrow.


Vibrational activation in direct and precursor-mediated chemisorption of SiH(4) on Si(100).
The quantum state-resolved reactivity S(0) of SiH(4) on Si(100)-2x1 has been measured for the first time for two vibrationally excited Si-H stretch local mode states (mid R:2000 and mid R:1100) as well the ground state S(0) as a function of translational energy E(n) and surface temperature T(s). We observe evidence for both direct and precursor-mediated chemisorption pathways. As expected, increasing E(n) (or T(s)) decreases S(0) for the precursor-mediated reaction and increases S(0) for the direct chemisorption. However, vibrational excitation of the incident SiH(4) increases S(0) for both the direct and the precursor-mediated pathway with a higher S(0) for the mid R:2000 state than for the mid R:1100 state, indicating a nonstatistical reaction mechanism.


Fecal Incontinence: The Importance of a Structured Pathophysiological Model.
Fecal incontinence has an enormous social and economic impact and may significantly impair quality of life. Even though fecal incontinence is a common complaint in (aging) adults, a structured pathophysiological model of the clinical presentations of fecal incontinence is missing in current literature. The most frequent manifestations of fecal incontinence are passive fecal loss, urge incontinence, or mixed fecal incontinence. At our institution, we treat 400 patients per year with defecation disorders, including a significant number of patients with fecal incontinence. On the basis of this experience, we have tried to create a concept that merges current insight in causes and treatment options in a clinically useful algorithm. By applying the system of anamnesis and physical examination described in this article and expanding it with simple additional anorectal examination, in most patients, one can determine the type of fecal incontinence and choose a targeted therapy.


Targeting of B-cell receptor signalling in B-cell malignancies.
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma. In addition, the role of these drugs in diffuse large B-cell lymphoma and marginal zone lymphoma is under investigation, as single agents and in combination with chemotherapy. In CLL, both ibrutinib and idelalisib have an established role as first-line therapy in patients with del(17p), and in MCL, ibrutinib is a standard option for patients relapsing after chemoimmunotherapy. Unexpected toxicities have been encountered when combining these potent new agents with other drugs, including chemotherapy and lenalidomide, and based on this experience the risks and benefits of novel combinations must be evaluated carefully. In this review, we summarize the efficacy and safety results with these inhibitors and discuss novel combinations that are under study and the future role of BCR inhibitors in these disorders.


Randomized, dose-ranging study of a fluticasone propionate multidose dry powder inhaler in adolescents and adults with uncontrolled asthma not previously treated with inhaled corticosteroids.
A novel, inhalation-driven, multidose dry powder inhaler (MDPI) eliminates the need to coordinate actuation with inhalation. To characterize dose response, efficacy, and safety of fluticasone propionate (Fp) MDPI, a dose-ranging study was conducted with placebo and active comparators. This 12-week, double-blind, parallel-group study randomized patients aged ≥12 years with uncontrolled persistent asthma not previously treated with inhaled corticosteroid therapy (N = 622) to twice-daily treatment with Fp MDPI (12.5, 25, 50, or 100 µg), placebo MDPI, or open-label Fp dry powder inhaler (DPI) 100 µg. The primary efficacy endpoint was change from baseline over 12 weeks in trough (morning pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV1). Blood samples were collected from a patient subset to evaluate pharmacokinetics. Adverse events were monitored. Fp MDPI 25, 50, and 100 µg significantly improved change from baseline in trough FEV1 over 12 weeks compared with placebo (p < 0.01). There were no substantial differences in FEV1 change from baseline over 12 weeks between any Fp MDPI dose and Fp DPI 100 µg. Maximum observed concentration (Cmax) of Fp increased with increasing Fp MDPI doses; time of Cmax was similar across doses and treatments. Systemic exposures for Fp MDPI 25 and 50 µg were lower than that for Fp DPI 100 µg. The safety profile of Fp MDPI was consistent with that of Fp DPI. In this study, Fp MDPI 25 and 50 µg provided comparable efficacy and safety to Fp DPI 100 µg, with lower systemic exposure.


[Cerebellar cortical dysplasia: MRI aspects and significance].
Because it is now possible to obtain high-resolution multiplanar MR imaging of the cerebellum and because of the developing interest on the role of the cerebellum on higher brain functions, we have decided to study the process of cerebellar fissuration. All brain MRI examinations performed in children for varied neurological and neurosurgical indications, especially children with non-specific mental retardation and patients with cerebral malformation detected at initial imaging work-up, were reviewed. Fissuration and lobulation anomalies (abnormal orientation of fissures, pseudopolymicrogyria, cortical thickening, subcortical cysts and heterotopia) were identified that we called cerebellar cortical dysplasia (CCD). In order to better understand the origin of this malformation, current data on cerebellar embryogenesis and histogenesis will be reviewed, and the pathological and radiological features will be illustrated. Milder forms of CCD represent a distinct group of anomalies that should be distinguished from other types of cerebellar dysplasia (agenesis, hypoplasia or complex dysplasia with involvement of the cerebellar vermis (rhombencephalosynapsis)) or combined cerebellar and cerebral dysplasia (muscular dystrophies and lissencephaly). Recognition of cerebellar cortical dysplasia could be a first step towards a broader understanding of its pathogenesis and significance.


Visual experiences of Blaise Pascal.
The writings of Blaise Pascal (1623-1662), mathematician, physicist, and theologian, are often thought of as an ideal example of classical French prose. In fact, Pascal's scientific contributions include the principle of hydrostatics, known as Pascal's Law. In mathematics, he helped develop the probability theory and also made significant contributions to the realization of infinite series and the geometry of curves. He is also considered one of the most important French philosophers principally due to his book entitled 'Pensées'. Pascal had a religious conversion in the 1650s and following this he devoted himself more to religion than science. There is evidence that Pascal suffered from visual migraines with recurring headaches, episodes of blindness in half of his visual field, zigzag, fortification spectra, and other visual hallucinations. It is believed that the migraine aura experiences might have acted as a source of inspiration for Pascal's philosophical reflections. Pascal's sudden religious conversion, probably the most decisive moment in Pascal's personal life, during the night of the 23rd to 24th of November 1654, was accompanied by a lighted vision which he interpreted as fire which brought him the total conviction of God's 'reality and presence'. This experience may have been based on the effects of a migraine aura attack. In fact, this spiritual experience led him to dedicate the rest of his life to religious and philosophical interests.


[Injuries caused by accidents with chain saws].
Accident reports and medical statements (a total of 719) concerning chain-saw injuries were evaluated. Chain-saw wounds can be found in all parts of the body, especially the thighs and fingers. The typical chain-saw wound is a multiple superficial laceration, soft tissue wounds are usually heavily bruised and jagged , and bone lesions are rare and superficial. Among 188 finger injuries, only 15 slight bone lesions were seen. The frequency of all injuries decreases as one progresses from the thumb to the little finger and from the finger tip to the finger. The more proximal the isolated finger injury, the more frequently is it diagonal or even longitudinal. Incomplete or complete finger amputations were not observed.


Physical activity levels of allied health professionals working in a large Australian metropolitan health district - an observational study.
The aim of this observational cross-sectional study was to determine if allied health professionals working in a large metropolitan health district were meeting the minimal physical activity (PA) recommendations and the proportion that occupational PA contributed to the recommended PA levels. A secondary aim was to determine possible relationships between self-report questionnaire measures of PA and PA measured by accelerometry. Allied health professionals, working in the Sydney Local Health District (SLHD) in 2016-2017, completed the Active Australia Survey (AAS), Occupational Sitting and Physical Activity Questionnaire (OSPAQ), International Physical Activity Questionnaire Long form (IPAQ-L), and wore the ActiGraph GT1M accelerometer for 7 days consecutively. Based on accelerometry results, allied health professionals (N=126) spent a mean (SD) of 51 (23) minutes in moderate-to-vigorous physical activity (MVPA)/day, representing 171% of the total recommended MVPA/day, with work contributing 76% to this recommendation. Participants walked a mean of 10,077 (2,766) steps/day, meeting 100% of the recommended 10,000 steps/day, with work contributing 54% to this recommendation. Sedentary behaviors were predominant throughout the entire day and work day. Compared with the ActiGraph MVPA time measurements, AAS MVPA time showed a fair level of agreement [intraclass correlation coefficient (ICC)=0.44, P<0.01], while OSPAQ and IPAQ-L MVPA time showed no agreement (ICC=0.05, P=0.27; ICC=0.13, P=0.10, respectively). Allied health professionals working in a large metropolitan health district met the daily PA recommendations based on accelerometry measures but tended to overreport their MVPA on self-report questionnaires.


Hybrid antimicrobial enzyme and silver nanoparticle coatings for medical instruments.
We report a method for the synthesis of antimicrobial coatings on medical instruments that combines the bacteriolytic activity of lysozyme and the biocidal properties of silver nanoparticles. Colloidal suspensions of lysozyme and silver nanoparticles were electrophoretically deposited onto the surface of stainless steel surgical blades and needles. Electrodeposited films firmly adhered to stainless steel surfaces even after extensive washing and retained the hydrolytic properties of lysozyme. The antimicrobial efficacy of coatings was tested by using blades and needles in an in vitro lytic assay designed to mimic the normal application of the instruments. Coated blades and needles were used to make incisions and punctures, respectively, into agarose infused with bacterial cells. Cell lysis was seen at the contact sites, demonstrating that antimicrobial activity is transferred into the media, as well as retained on the surface of the blades and needles. Blade coatings also exhibited antimicrobial activity against a range of bacterial species. In particular, coated blades demonstrated potent bactericidal activity, reducing cell viability by at least 3 log within 1.5 h for Klebsiella pneumoniae, Bacillus anthracis Sterne, and Bacillus subtilis and within 3 h for Staphylococcus aureus and Acinetobacter baylyi. The results confirmed that complex antimicrobial coatings can be created using facile methods for silver nanoparticle synthesis and electrodeposition.


Myelofibrosis in Western Australia: an epidemiological study of 29 cases.
Survival figures and other epidemiological features are described for 29 patients with myelofibrosis living in Western Australia during the period 1959 to 1963. These patients form part of a larger series of 509 patients with leukaemia and allied disorders. The diagnostic incidence rate was found to be 0.5 per 100,000 population, the mortality rate was 0.4 per 100,000 and the prevalence 1.8 per 100,000. Comparison with related myeloproliferative disorders shows that myelofibrosis occurs somewhat less frequently than chronic granulocytic leukaemia and considerably less so than polycythaemia vera. The sex ratio indicates a small male preponderance and the age distribution is similar to that in other descriptions. Survival times for all patients accord with those reported in the literature, but this series showed a marked female advantage in survival. Findings in other series are described.


Ehrlichia SLiM Ligand Mimetic Activates Notch Signaling in Human Monocytes.
Ehrlichia chaffeensis evades innate host defenses by reprogramming the mononuclear phagocyte through mechanisms that involve the exploitation of multiple evolutionarily conserved cellular signaling pathways, including Notch. This immune evasion strategy is directed in part by tandem repeat protein (TRP) effectors. Specifically, the TRP120 effector activates and regulates Notch signaling through interactions with the Notch receptor and the negative regulator, F-Box and WD repeat domain-containing 7 (FBW7). However, the specific molecular interactions and motifs required for E. chaffeensis TRP120-Notch receptor interaction and activation have not been defined. To investigate the molecular basis of TRP120 Notch activation, we compared TRP120 with endogenous canonical/noncanonical Notch ligands and identified a short region of sequence homology within the tandem repeat (TR) domain. TRP120 was predicted to share biological function with Notch ligands, and a function-associated sequence in the TR domain was identified. To investigate TRP120-Notch receptor interactions, colocalization between TRP120 and endogenous Notch-1 was observed. Moreover, direct interactions between full-length TRP120, the TRP120 TR domain containing the putative Notch ligand sequence, and the Notch receptor LBR were demonstrated. To molecularly define the TRP120 Notch activation motif, peptide mapping was used to identify an 11-amino acid short linear motif (SLiM) located within the TRP120 TR that activated Notch signaling and downstream gene expression. Peptide mutants of the Notch SLiM or anti-Notch SLiM antibody reduced or eliminated Notch activation and NICD nuclear translocation. This investigation reveals a novel molecularly defined pathogen encoded Notch SLiM mimetic that activates Notch signaling consistent with endogenous ligands. IMPORTANCE E. chaffeensis infects and replicates in mononuclear phagocytes, but how it evades innate immune defenses of this indispensable primary innate immune cell is not well understood. This investigation revealed the molecular details of a ligand mimicry cellular reprogramming strategy that involved a short linear motif (SLiM), which enabled E. chaffeensis to exploit host cell signaling to establish and maintain infection. E. chaffeensis TRP120 is a moonlighting effector that has been associated with cellular activation and other functions, including ubiquitin ligase activity. Herein, we identified and demonstrated that a SLiM present within each tandem repeat of TRP120 activated Notch signaling. Notch is an evolutionarily conserved signaling pathway responsible for many cell functions, including cell fate, development, and innate immunity. This study is significant because it revealed the first molecularly defined pathogen encoded SLiM that appears to have evolved de novo to mimic endogenous Notch ligands. Understanding Notch activation during E. chaffeensis infection provides a model to study pathogen exploitation of signaling pathways and will be useful in developing molecularly targeted countermeasures for inhibiting infection by a multitude of disease-causing pathogens that exploit cell signaling through molecular mimicry.


The impact of surgical timing on neurological outcomes and survival in patients with complete paralysis caused by spinal tumours: evaluation of surgery on patients with complete paralysis due to neoplastic epidural spinal cord compression.
The aim of this study was to explore the prognostic factors for postoperative neurological recovery and survival in patients with complete paralysis due to neoplastic epidural spinal cord compression. The medical records of 135 patients with complete paralysis due to neoplastic cord compression were retrospectively reviewed. Potential factors including the timing of surgery, muscular tone, and tumour characteristics were analyzed in relation to neurological recovery using logistical regression analysis. The association between neurological recovery and survival was analyzed using a Cox model. A nomogram was formulated to predict recovery. A total of 52 patients (38.5%) achieved American Spinal Injury Association Impairment Scale (AIS) D or E recovery postoperatively. The timing of surgery (p = 0.003) was found to be significant in univariate analysis. In multivariate analysis, surgery within one week was associated with better neurological recovery than surgery within three weeks (p = 0.002), with a trend towards being associated with a better neurological recovery than surgery within one to two weeks (p = 0.597) and two to three weeks (p = 0.055). Age (p = 0.039) and muscle tone (p = 0.018) were also significant predictors. In Cox regression analysis, good neurological recovery (p = 0.004), benign tumours (p = 0.039), and primary tumours (p = 0.005) were associated with longer survival. Calibration graphs showed that the nomogram did well with an ideal model. The bootstrap-corrected C-index for neurological recovery was 0.72. In patients with complete paralysis due to neoplastic spinal cord compression, whose treatment is delayed for more than 48 hours from the onset of symptoms, surgery within one week is still beneficial. Surgery undertaken at this time may still offer neurological recovery and longer survival. The identification of the association between these factors and neurological recovery may help guide treatment for these patients. Cite this article: Bone Joint J 2019;101-B:872-879.


[Anti-mutagenicity activity of dehydroepiandrosterone].
The chemopreventive activity and mechanism of dehydroepiandrosterone (DHEA) were studied. Model of 7, 12-dimethylbenz (alpha) anthracene (DMBA) induced breast carcinoma in Sprague-Dawley rats, uitra-violet (UV)-induced DNA damage and Salmonella mutation assay were used. In DMBA-induced rat mammary tumor model, the rats were orally given daily DHEA for 2 weeks before DMBA and continued for 10 weeks after DMBA administration. The results showed significant inhibition of tumor development by DHEA. The incidence of mammary carcinoma also decreased significantly on daily dose of oral 25 mg/kg DHEA with the mean tumor volume per rat also remarkably reduced by 92%. Moreover, 25 mg/kg DHEA treatment could significantly increase the carcinoma latency for about 3.5 weeks as compared with the control. Using polymerase chain reaction (PCR) assay, in vitro 10(-9) mol/L DHEA showed significant inhibitory effect on UV-induced DNA damage by 90%. In Ames test, DHEA was found to decrease DMBA and benzo (alpha) pyrene-induced TA98 and TA100 His(+) revertants markedly and the number of Salmonella clones were significantly reduced by 53.2% and 73.0% on dose of 5 microgram DHEA/plate. It was also shown that in vitro 10(-7) mol/L DHEA could also effectively inhibit the G-6-PDH activity, which might play an important role in its chemoprophylaxis activities. The results strongly prove that DHEA is a potent cancer chemoprophylaxis agent, which exhibits inhibitory potential on mutation and chemical carcinogen in vivo and in vitro.


Passive inhalation of marijuana smoke: urinalysis and room air levels of delta-9-tetrahydrocannabinol.
In two separate studies, 5 drug-free male volunteers with a history of marijuana use were passively exposed to the sidestream smoke of 4 and 16 marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol [THC]) for 1 h each day for 6 consecutive days. A third study was similarly performed with 2 marijuana-naive subjects passively exposed to the smoke of 16 marijuana cigarettes. Passive smoke exposure was conducted in a small, unventilated room. Room air levels of THC and CO were monitored frequently. All urine specimens were collected and analyzed by EMIT d.a.u. assay, Abuscreen radioimmunoassay and GC/MS. The studies show that significant amounts of THC were absorbed by all subjects at the higher level of passive smoke exposure (eg., smoke from 16 marijuana cigarettes), resulting in urinary excretion of significant amounts of cannabinoid metabolites. However, it seems improbable that subjects would unknowingly tolerate the noxious smoke conditions produced by this exposure. At the lower level of passive marijuana-smoke exposure, specimens tested positive only infrequently or were negative. Room air levels of THC during passive smoke exposure appeared to be the most critical factor in determining whether a subject produced cannabinoid-positive urine specimens.


Sex-role reversal of a monogamous pipefish without higher potential reproductive rate in females.
In monogamous animals, males are usually the predominant competitors for mates. However, a strictly monogamous pipefish Corythoichthys haematopterus exceptionally exhibits a reversed sex role. To understand why its sex role is reversed, we measured the adult sex ratio and the potential reproductive rate (PRR), two principal factors influencing the operational sex ratio (OSR), in a natural population of southern Japan. The adult sex ratio was biased towards females throughout the breeding season, but the PRR, which increased with water temperature, did not show sexual difference. We found that an alternative index of the OSR (Sf/Sm: sex ratio of 'time in') calculated from the monthly data was consistently biased towards females. The female-biased OSR associated with sex-role reversal has been reported in some polyandrous or promiscuous pipefish, but factors biasing the OSR differed between these pipefish and C. haematopterus. We concluded that the similar PRR between the sexes in C. haematopterus does not confer reproductive benefit of polygamous mating on either sex, resulting in strict monogamous mating, and its female-biased adult sex ratio promotes female-female competition for a mate, resulting in sex-role reversal.


Cognitive Impairment Is Reflected by an Increased Difference between Real and Imagined Timed Up and Go Test Performance.
Recent research suggests using an imaginary version of the Timed Up and Go test (TUG) for a first assessment of cognitive impairment. By using the time difference between a real (TUGr) and an imagined (TUGi) TUG task, the objective of this study was to examine the effect of cognitive impairment on motor imagery ability. Fifty-two participants (mean age 69.3 ± 4.0 years) with mild cognitive impairment or subjective cognitive impairment were included in this study. The time difference between the TUGr and the TUGi was used as the main outcome. The Trail Making Test part B (TMT B), the ratio between TMT A and TMT B, and the Montreal Cognitive Assessment (MoCA) battery were the main independent variables. The difference between TUGr and TUGi performance time and the TMT B performance time increased with decreasing cognitive function (p < 0.01). There was no relationship between TUGr and TUGi performance time and TMT B/A ratio. There were significant correlations between TUG time differences and the MoCA score (r = -0.489, p < 0.01), the TMT B (r = 0.364, p < 0.01), and the TMT B/A ratio (r = 0.377, p < 0.01). The combination of TUGr and TUGi may have added value in assessing cognitive impairment, which is a possible pre-stage of dementia.


Generalized periodontitis associated with Chédiak-Higashi syndrome.
Chédiak-Higashi syndrome (CHS) is a rare immunodeficient disorder. Patients with CHS are prone to severe periodontitis. To date, limited improvement following periodontal therapy has been reported. Thus, successful clinical outcomes in patients with CHS are of interest. A 12-year-old girl was referred to the Department of Pediatric Dentistry, Hôtel-Dieu/Garancière Hospital, for acute gingival inflammation and periodontal destruction. After a periodontal examination, the patient was sent to the Department of Medicine, Robert Debré Hospital, for a hematologic examination and was diagnosed with CHS. She has been receiving medical and dental treatments since that time. The medical treatment consisted of continuous, long-term antibiotherapy. Supportive periodontal therapy was initiated with 4-month recall periods. We report the diagnosis process and the 9-year follow-up. Radiographs and a periodontal examination showed deep probing pockets and extensive alveolar bone resorption. Hematologic and immunologic investigations showed normal values. Peripheral blood smears showed giant granules in neutrophils and leukocytes characteristic of CHS. Clinical improvement was observed after the initial periodontal therapy. No periodontitis recurrence was noted over a period of 9 years. This case report shows that it is possible to treat periodontitis and maintain the periodontal health of a patient with a mild CHS phenotype over a long period. Patient compliance, regular dental follow-ups, and long-term systemic antibiotic treatments may be useful in stabilizing the periodontal condition of patients with CHS. Dentists must be aware that aggressive periodontitis, combined with general clinical signs, in young patients may reflect rare systemic disorders requiring biologic investigation.


Spectral peak frequency in low-frequency band in cross spectra of blood pressure and heart rate fluctuations in young type 1 diabetic patients.
In this study we tested whether joint evaluation of the frequency (f(cs)) at which maxima of power in the cross-spectra between the variability in systolic blood pressure and inter-beat intervals in the range of 0.06-0.12 Hz occur together with the quantification of baroreflex sensitivity (BRS) may improve early detection of autonomic dysfunction in type 1 diabetes mellitus (T1DM). We measured 14 T1DM patients (age 20.3-24.2 years, DM duration 10.4-14.2 years, without any signs of autonomic neuropathy) and 14 age-matched controls (Co). Finger arterial blood pressure was continuously recorded by Finapres for one hour. BRS and f(cs) were determined by the spectral method. Receiver-operating curves (ROC) were calculated for f(cs), BRS, and a combination of both factors determined as F(z)=1/(1+exp(-z)), z=3.09-0.013*BRS-0.027*f(cs). T1DM had significantly lower f(cs) than Co (T1DM: 88.8+/-6.7 vs. Co: 93.7+/-3.8 mHz; p<0.05), and a tendency towards lower BRS compared to Co (T1DM: 10.3+/-4.4 vs. Co: 14.6+/-7.1 ms/mm Hg; p=0.06). The ROC for Fz showed the highest sensitivity and specificity (71.4 % and 71.4 %) in comparison with BRS (64.3 % and 71.4 %) or f(cs) (64.3 % and 64.3 %). The presented method of evaluation of BRS and f(cs) forming an integrated factor Fz could provide further improvement in the risk stratification of diabetic patients.


Nano-sized cobalt based Fischer-Tropsch catalysts for gas-to-liquid process applications.
Nano-sized cobalt supported catalysts were prepared for Fischer-Tropsch synthesis in gas-to-liquid (GTL) process. The dependence of crystallite size and reducibility of Co3O4 on the supports were investigated with FTS activity. XRD peaks revealed nano crystallites (< 5.47 nm) of Co3O4 crystallites. TEM showed round shaped particles with size less than 5 nm. Support with higher acidity decreased crystallite size of Co3O4. XRD data of used catalysts showed Co3O4 crystallites smaller than 3.5 nm which do not reduce easily to Co(0) state. The crystallite size of Co3O4 plays a role in its reduction to Co(0). TPR results showed that the reduction temperature shifts to higher temperature due to metal-support interaction. The variation in the activity of the catalysts depends on the support which in turn affects the crystallite size, dispersion, reducibility and activity of Co species in Fischer-Tropsch Synthesis (FTS). In this study, Co/Al2O3 showed higher CO conversion than the other catalysts. However, the C5+ production was in order Co/SiO2 (78.1%) > Co/Al2O3 (70.0%) > Co/R_TiO2 (61%) > Co/A_TiO2 (57.5%).


Induction of donor-specific tolerance to islet allografts in nonhuman primates.
Pancreatic tissue grafting is by far the most physiological therapeutic solution to the insulin deficiency of diabetes. Recent clinical trials have indicated somewhat successful use of nonsteroidal immunosuppressive regimens and a successful nonhuman primate trial using CD154 for costimulation blockade was reported. However, these protocols need to be replaced with safe and efficacious ones in which long-term allotolerance would make these treatments routine in a clinical setting. With the specific objective of testing whether peripheral infusions of stem cells or stem cell fractions in conjunction with islet allografting would induce allograft tolerance, we have established a macaque diabetic model. The macaques were rendered diabetic by streptozotocin and required daily doses of insulin to maintain lower blood glucose levels. The diabetic macaques then received islets and stem cells from unrelated and MHC-mismatched donors without any immunosuppression. In our initial analysis, 5 of 7 macaques that received stem cell infusions at the time of islet allografting have shown allograft survival longer than the group of macaques that received islets without the stem cell infusion. One of these five macaques has been normoglycemic for 10 months, with no exogenous insulin. This macaque received stem cell population enriched for CD34+ cells with depletion of CD18 cells, which have shown low or no allostimulatory potential in mixed lymphocyte cultures. Increased levels in insulin and C-peptide levels were shown in the macaques after islet transplantation.


Are tumoral factors responsible for host tissue wasting in cancer cachexia?
Both cytokines and tumor factors have been implicated in tissue loss in cancer cachexia. Loss of adipose tissue is most likely due to the tumor (and host) factor zinc-alpha2-glycoprotein because of its direct lipolytic effect, ability to sensitize adipocytes to lipolytic stimuli and increased expression in cachexia. TNF-alpha and the tumor factor proteolysis-inducing factor are the major contenders for skeletal muscle atrophy; both increase protein degradation through the ubiquitin-proteasome pathway and depress protein synthesis through phosphorylation of eukaryotic initiation factor 2 alpha. However, while most studies report proteolysis-inducing factor levels to correlate with the appearance of cachexia, there is some disagreement regarding a correlation between serum levels of TNF-alpha and weight loss. Furthermore, only antagonists to proteolysis inducing factor prevent muscle loss in cancer patients, suggesting that tumor factors are the most important.


A pilot study comparing the effect of orally administered esomeprazole and omeprazole on gastric fluid pH in horses.
AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments. Gastric fluid samples were collected using a gastroscope on Days 1, 3, 5, 8 and 10, with food and water withheld for 16 hours prior to collection of samples. The pH of all samples was measured immediately after collection. RESULTS Mean pH (3.38; SD 1.75) of the gastric fluid samples in the horses that received the placebo was lower than in the horses that received esomeprazole (6.28; SD 1.75) or omeprazole (6.13; SD 1.75) (p<0.001). There was no difference in the mean pH between horses receiving esomeprazole and those receiving omeprazole (p=0.56). CONCLUSIONS AND CLINICAL RELEVANCE Under these study conditions, esomeprazole paste was equally as effective as omeprazole paste in increasing gastric pH in horses. Enteric coated esomeprazole, may be a therapeutic alternative to omeprazole for the prevention of gastric ulcers in horses.


Infective endocarditis due to Staphylococcus aureus involving three cardiac valves. A case study.
A 20-year-old woman, diagnosed with coarctation of the aorta, situs viscerum inversus, and bicuspid aortic valve, underwent corrective surgery for the coarctation. After a postoperative neurological state that suggested a spinal lesion, corticosteroid therapy was initiated and the patient was discharged early from the unit to begin a motor rehabilitation program. Following the dehiscence of the thoracotomy surgical wound, a severe infective clinical picture, sustained by methicillin-resistant S. Aureus (MRSA), became evident with a diagnosis of bacterial endocarditis involving the aortic, mitral and tricuspid valves and caused the patient's death due to septic shock complicated by ARDS. According to the authors, the early discharge of the patients after such a complex operation, the eccessive lengthening of the steroid therapy that would have contribuited to delay the diagnosis, causing the lack of preventing identification of the first signs of infection and the impossibility for the patient to have another operation (involving 3 valves) are conclusive elements that led to the above mentioned complications.


Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes.
CXC chemokine ligand 10 (CXCL10) plays a pivotal role in the self-perpetuation of the inflammatory processes in patients with autoimmune thyroid disease. Treatment with methimazole (MMI) reduces serum CXCL10 in patients with Graves' disease. In isolated human thyrocytes, tumor necrosis factor (TNF)alpha demonstrates a potent synergistic effect on interferon (IFN)gamma-induced CXCL10 secretion. We investigated the mechanism underlying the synergism between IFNgamma and TNFalpha and the effect of MMI on CXCL10 secretion in human thyrocytes. A peroxisome proliferator-activated receptor gamma agonist, rosiglitazone (RGZ), a known inhibitor of T helper 1 (Th1)-mediated responses, was also studied for comparison. Experiments were carried out in human thyrocytes isolated from internodular parenchyma of thyroid tissues derived from patients who had undergone surgery for multinodular goiter. ELISA was used to measure CXCL10 levels in culture supernatant. Flow cytometry was used to assess IFNgamma membrane receptor expression. Specific mRNA analysis was performed by Taqman real-time PCR. Immunofluorescence was performed to detect nuclear translocation of nuclear factor-kappaB (NF-kappaB). In human thyrocytes, the synergistic effect of TNFalpha with IFNgamma on CXCL10 secretion is due to the upregulation of IFNgamma receptor expression. MMI decreased cytokine-induced CXCL10 secretion by reducing TNFalpha-induced upregulation of the IFNgamma receptor. RGZ decreased the cytokine-induced CXCL10 secretion by impairing NF-kappaB translocation, without affecting IFNgamma receptor. MMI and RGZ targeted thyrocytes with the same pharmacological potency, likely acting throughout different mechanisms. Targeting T helper 1-mediated autoimmune thyroid disease with drugs that impair different intracellular pathways could be a novel pharmacological tool.


Development of a porcine excisional wound model.
To develop a porcine model for cutaneous tangential excisional wounds. This was a prospective, longitudinal, blinded experiment on four isoflurane-anesthetized swine. Forty standardized excisional wounds (1 square inch each) were created with an electric dermatome set at a depth of 300, 600, 750, or 900 microm. Full-thickness wounds were created with a surgical blade (n = 8 for each depth). Wounds were treated with polyurethane film. Full-thickness punch biopsies were taken after one, two, three, four, five, and 14 days for blinded histopathological evaluation. The main outcome was the percent wound reepithelialization (REP) calculated by dividing the length of neoepidermis in cross-section by the specimen's diameter (interobserver correlation = 0.99). Analysis of variance was used to compare percent REP among wound depths. This study had 80% power to detect a 33% difference in REP across groups (two-tailed alpha = 0.05). There were significant differences in percent REP across wound depths for days 2-5 (p < 0.001 for all days). The more superficial wounds (300 to 600 microm) were mostly reepithelialized by day 4, whereas wounds ranging in depth from 750 to 900 micro m were mostly healed by day 5. Full-thickness wounds had no evidence of REP even after 14 days. The authors describe an excisional wound model in swine. Rapid reepithelialization occurs within three to five days in wounds <900 microm deep.


Infrared analysis of bone in health and disease.
Infrared spectroscopy, microspectroscopy, and microspectroscopic imaging have been used to probe the composition and physicochemical status of mineral and matrix of bone in normal and diseased tissues using a series of validated parameters that reflect quantitative and qualitative properties. In this review, emphasis is placed on changes in bone's composition and physiochemical status during osteoporosis and the impact of currently used therapeutics on these parameters, although the impact of infrared microscopy in other pathological states is briefly discussed.


Crystallization in Confinement.
Many crystallization processes of great importance, including frost heave, biomineralization, the synthesis of nanomaterials, and scale formation, occur in small volumes rather than bulk solution. Here, the influence of confinement on crystallization processes is described, drawing together information from fields as diverse as bioinspired mineralization, templating, pharmaceuticals, colloidal crystallization, and geochemistry. Experiments are principally conducted within confining systems that offer well-defined environments, varying from droplets in microfluidic devices, to cylindrical pores in filtration membranes, to nanoporous glasses and carbon nanotubes. Dramatic effects are observed, including a stabilization of metastable polymorphs, a depression of freezing points, and the formation of crystals with preferred orientations, modified morphologies, and even structures not seen in bulk. Confinement is also shown to influence crystallization processes over length scales ranging from the atomic to hundreds of micrometers, and to originate from a wide range of mechanisms. The development of an enhanced understanding of the influence of confinement on crystal nucleation and growth will not only provide superior insight into crystallization processes in many real-world environments, but will also enable this phenomenon to be used to control crystallization in applications including nanomaterial synthesis, heavy metal remediation, and the prevention of weathering.


Leiomyosarcoma: computed tomographic findings.
The computed tomographic (CT) findings in 118 patients with the diagnosis of leiomyosarcoma were reviewed. The tumor masses visualized in these patients were often quite large; extensive necrotic or cystic change was a frequent finding. Calcification was not observed in these tumors. The liver was the most common site of metastasis in these patients, with marked necrosis of the liver lesions a common finding. Other manifestations of tumor spread included pulmonary metastases, mesenteric or omental metastases, retroperitoneal lymphadenopathy, soft-tissue metastases, bone metastases, splenic metastases, and ascites. The metastatic lesions were often centrally necrotic. Although the CT appearance of leiomyosarcoma is not specific, these findings, when present, suggest consideration of this diagnosis.


Cyclic GMP signaling in podocytes.
Natriuretic peptides (NP), together with nitric oxide (NO) are powerful relaxing factors acting via a common second messenger, cyclic GMP (cGMP). Together with other vasoactive modulators, these vasorelaxing factors play an essential role in regulating the function of kidney glomeruli. The presence of NP receptors in podocytes has been well documented. Recently, also mRNA for soluble guanylate cyclase, the NO receptor, has been shown in these cells. Stimulation of podocytes with atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), and NO donors results in considerable upregulation of cellular cGMP synthesis. The podocyte foot processes contain a highly organized network of microfilaments adhering to the glomerular basement membrane (GBM). Changes in podocyte cytoskeleton accompanied by detachment of the cells from the GBM are closely associated with many glomerulopathies. The contractile apparatus in the podocyte foot processes seems to be an obvious target for the cyclic GMP signaling cascade. However, little is known about implications of the cGMP synthesis in these cells. We briefly review the current art regarding generation and modulation of cyclic GMP levels in podocytes. We discuss also the possible targets for this secondary messenger as well as its functional role in podocytes.


Developmental and neurologic sequelae of neonatal hyperviscosity syndrome.
One hundred eleven consecutive infants with neonatal hyperviscosity were identified by screening all newborns for polycythemia in an 18-month period. These polycythemic infants were matched with non-polycythemic newborns for birth weight, gestational age, Apgar scores, and sex. Maternal, intrapartum, and neonatal data were analyzed for associated morbidity. Maternal preeclampsia was more common among the hyperviscous patients than among control subjects. Hypoglycemia was also significantly increased among the hyperviscous patients. Follow-up studies at 1 to 3 years of age revealed a significantly higher incidence (38% vs 11%) of motor and neurologic abnormalities in the infants with neonatal hyperviscosity. The data suggested that concurrent hypoglycemia increased the risk of a poor outcome in hyperviscous infants inasmuch as 55% of infants with both characteristics were abnormal at follow-up. This, however, was not significantly different from the outcome of infants with hyperviscosity alone (P greater than .05 but less than .1). Further studies will be needed to confirm or deny this relationship.


Histological findings after placement of a self-expanding stent in rectal carcinoma with complete obstruction--case report.
Patients with acute obstruction due to colorectal carcinomas frequently require emergency surgery. However, such emergency procedures are associated with various complications, a high mortality rate and a poor prognosis. If the obstruction could be immediately relieved, the patient could later undergo an elective operation with a much better prognosis. Recently, expanding metallic stents have been used to treat obstruction due to colorectal carcinoma. In the case reported here, we initially inserted a colonoscopic retrograde bowel drainage tube per anus to achieve decompression. We then placed a self-expanding metallic stent, since we anticipated a prolonged preoperative period due to high fever, congestive heart failure, cerebral infarction, and persistent high blood sugar concentrations. The patient had no complications for 57 days after placement of the stent, and eventually underwent an elective operation. Histologically, the side of the cancerous lesion compressed by the stent was thin and consisted solely of a serosal layer. Implantation of a metallic stent is safe for the treatment of acute malignant obstruction. Stent placement is indicated not only as a palliative treatment for inoperable or recurrent cases, but also as a preoperative procedure before elective surgical resection.


A comparative analysis of arranging in-flight oxygen aboard commercial air carriers.
As air travel has become more commonplace in today's society, so too has air travel by oxygen-using individuals. Because there is little oversight or standardization of in-flight oxygen by the Federal Aviation Administration, individual airlines' policies and practices may vary greatly. On the premise that such variation may cause confusion by prospective air travelers, we undertook the current study to describe individual air carriers' policies and practices and to provide guidance to future air travelers. Data were collected by a series of telephone calls placed by the study investigators to all commercial air carriers listed in the 1997 Cleveland Metropolitan Yellow Pages. The callers were registered respiratory therapists who identified themselves as inexperienced oxygen-requiring travelers wishing to arrange in-flight oxygen for an upcoming trip. Standard questions were asked of each carrier that included the following: Did the carrier have a special "help desk" to assist with oxygen arrangements? What oxygen systems, liter flow options, and interface devices were available? What was the charge for oxygen? How was the charged determined? What documentation from the physician was required? How much notification was required by the airline before the actual flight? In addition to recording these responses, the total amount of time spent on the telephone by the caller was logged along with the number of telephone calls and number of people spoken to in arranging in-flight oxygen. To compare oxygen charges between airlines, we calculated charges based on a "standard trip," which was defined as a nonstop, round-trip lasting 6 h in which the traveler used a flow rate of 2 L/min. Of the 33 commercial air carriers listed in the directory, 11 were US-based carriers and 22 were international-based carriers. Seventy-six percent of the airlines offered in-flight oxygen. For the 25 carriers offering in-flight oxygen, mean phone time required to make the arrangements was 9.96+/-4.8 min (range, 3 to 20 min). No more than two telephone calls were required to make oxygen arrangements. Most carriers required 48- to 72-h advance notice, with a single carrier requiring 1-month advance notice. Most carriers required some notification of oxygen needs by the traveler's physician. There was a great variation in oxygen device and liter flow availability. Liter flow options ranged from only two flow rates (36% of carriers) to a range of 1 to 15 L/min (one carrier). All carriers offered nasal cannula, which was the only device available for 21 carriers (84%). Actual charges for in-flight oxygen also varied greatly. Six carriers supplied oxygen free and 18 carriers charged a fee (range, $64 to $1,500). One airline allowed the traveler to bring one "E" cylinder with no fee assessed. For 14 of the 18 carriers that charged, the charge for the standard trip ranged from $100 to $250. (1) As expected from the lack of standard regulations, the availability, costs, and ease of implementing in-flight oxygen vary greatly among commercial air carriers. (2) Because the expense of in-flight oxygen is usually borne by the traveler (rather than by insurers), prospective travelers should consider charges for oxygen use when choosing an airline. (3) In the context that the current study shows substantial variation in oxygen policies, costs, and services among commercial air carriers and that such policies may change over time, our findings encourage the prospective air traveler needing in-flight oxygen to "shop around."


Biopsy of the gastrointestinal tract.
Gastrointestinal biopsy is a potentially powerful tool, but it is easy to do it incorrectly. If clinicians are careless in performing or submitting biopsies, or if they blindly believe whatever the histopathology report says, they are abdicating their responsibility to the client and patient. Two comments seem most appropriate. First, the goal of endoscopy is not to be able to place the tip of an endoscope in a particular location; rather, the goal of endoscopy is to be able to access a particular location and then take a diagnostic specimen well enough that surgery can be avoided. Second, attention to detail is worth at least as much if not more than technology.


Primary lymphoma of the central nervous system and HTLV-I infection.
Only a few cases of AIDS-related primary lymphomas of the central nervous system (CNS) show a T-cell phenotype. We have recently studied two intravenous drug users with HIV infection who had primary CNS T-cell lymphomas. In both cases, the enzyme immunoassay (EIA) for HTLV gave a positive result. In the first case, study by western-blot (WB) and specific PCR confirmed the human T-cell lymphotropic virus type I (HTLV-I) infection and serological study by EIA for HTLV of his mother was negative. In the second case, analysis of ante-mortem serum samples by two different WBs showed an indeterminate pattern suggestive of HTLV-I infection, but adequate samples for PCR were not available. We speculate about the possibility that the horizontal transmission of HTLV-I infection could have facilitated the devepolment of a primary CNS T-cell lymphoma in these HIV patients, although they cannot be strictly considered as ATLL cases.


Brain and Behavioral Evidence for Reweighting of Vestibular Inputs with Long-Duration Spaceflight.
Microgravity alters vestibular signaling. In-flight adaptation to altered vestibular afferents is reflected in post-spaceflight aftereffects, evidenced by declines in vestibularly mediated behaviors (e.g., walking/standing balance), until readaptation to Earth's 1G environment occurs. Here we examine how spaceflight affects neural processing of applied vestibular stimulation. We used fMRI to measure brain activity in response to vestibular stimulation in 15 astronauts pre- and post-spaceflight. We also measured vestibularly-mediated behaviors, including balance, mobility, and rod-and-frame test performance. Data were collected twice preflight and four times postflight. As expected, vestibular stimulation at the preflight sessions elicited activation of the parietal opercular area ("vestibular cortex") and deactivation of somatosensory and visual cortices. Pre- to postflight, we found widespread reductions in this somatosensory and visual cortical deactivation, supporting sensory compensation and reweighting with spaceflight. These pre- to postflight changes in brain activity correlated with changes in eyes closed standing balance, and greater pre- to postflight reductions in deactivation of the visual cortices associated with less postflight balance decline. The observed brain changes recovered to baseline values by 3 months postflight. Together, these findings provide evidence for sensory reweighting and adaptive cortical neuroplasticity with spaceflight. These results have implications for better understanding compensation and adaptation to vestibular functional disruption.


SDC1-TGM2-FLOT1-BHMT complex determines radiosensitivity of glioblastoma by influencing the fusion of autophagosomes with lysosomes.
Rationale: Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Radiotherapy has long been an important treatment for GBM. Despite recent advances in tumor radiotherapy, the prognosis of GBM remains poor due to radioresistance. Autophagy has been reported as a basic factor to prolong the survival of tumor under radiation stress, but the molecular mechanism of how autophagy contributes to GBM radioresistance was still lacking. Methods: We established radioresistant GBM cells and identified their protein profiles by Tandem mass tag (TMT) quantitative proteomic analysis, then chose the radioresistant genes based on the TMT analysis of GBM cells and differentially expressed genes (DEGs) analysis of GEO database. Colony formation, flow cytometry, qPCR, western blotting, mRFP-GFP-LC3, transmission electron microscopy, immunofluorescence, and co-IP assays were conducted to investigate the regulation mechanisms among these new-found molecules. Results: Syndecan 1 (SDC1) and Transglutaminase 2 (TGM2) were both overexpressed in the radioresistant GBM cells and tissues, contributing to the dismal prognosis of radiotherapy. Mechanically, after irradiation, SDC1 carried TGM2 from cell membrane into cytoplasm, and transported to lysosomes by binding to flotillin 1 (FLOT1), then TGM2 recognized the betaine homocysteine methyltransferase (BHMT) on autophagosomes to coordinate the encounter between autophagosomes and lysosomes. Conclusions: The SDC1-TGM2-FLOT1-BHMT copolymer, a novel member of the protein complexes involved in the fusion of lysosomes and autophagosomes, maintained the autophagic flux in the irradiated tumor cells and ultimately enhanced radioresistance of GBM, which provides new insights of the molecular mechanism and therapeutic targets of radioresistant GBM.


Heat shock protein 70 regulates cellular redox status by modulating glutathione-related enzyme activities.
Heat shock protein (Hsp) 70 has been reported to protect various cells and tissues from ischemic damage. However, the molecular mechanisms of the protection are incompletely understood. Ischemia induces significant alterations in cellular redox status that plays a critical role in cell survival/death pathways. We investigated the effects of Hsp70 overexpression on cellular redox status in Madin-Darby canine kidney (MDCK) cells under both hypoxic and ischemic conditions with 3 different approaches: reactive oxygen species (ROS) measurement by a fluorescence probe, redox environment evaluation by a hydroxylamine spin probe, and redox status assessment by the glutathione/glutathione disulfide (GSH/GSSG) ratio. Results from each of these approaches showed that the redox status in Hsp70 cells was more reducing than that in control cells under either hypoxic or oxygen and glucose deprivation (OGD) conditions. In order to determine the mechanisms that mediated the alterations in redox state in Hsp70 cells, we measured the activities of glutathione peroxidase (GPx) and glutathione reductase (GR), two GSH-related antioxidant enzymes. We found that OGD exposure increased GPx and GR activities 47% and 55% from their basal levels (no stress) in Hsp70 cells, compared to only 18% and 0% increase in control cells, respectively. These data, for the first time, indicate that Hsp70 modulates the activities of GPx and GR that regulate cellular redox status in response to ischemic stress, which may be important in Hsp70's cytoprotective effects.


Congenital hypothyroidism: influence of disease severity and L-thyroxine treatment on intellectual, motor, and school-associated outcomes in young adults.
To describe intellectual, motor, and school-associated outcome in young adults with early treated congenital hypothyroidism (CH) and to study the association between long-term outcome and CH variables acting at different points in time during early development (CH severity and early L-thyroxine treatment levels [0-6 years]). Neuropsychological tests were administered to all 49 subjects with CH identified during the first 3 years of the Norwegian neonatal screening program (1979-1981) at a mean age of 20 years and to 41 sibling control subjects (mean age: 21 years). The CH group attained significantly lower scores than control subjects on intellectual, motor, and school-associated tests (total IQ: 102.4 [standard deviation: 13] vs 111.4 [standard deviation: 13]). Twelve (24%) of the 49 CH subjects had not completed senior high school, in contrast to 6% of the control subjects. CH severity (pretreatment serum thyroxine [T4]) correlated primarily with motor tests, whereas early L-thyroxine treatment levels were related to verbal IQ and school-associated tests. In multiple regression analysis, initial L-thyroxine dose (beta = 0.32) and mean serum T4 level during the second year (beta = 0.48) predicted Verbal IQ, whereas mean serum T4 level during the second year (beta = 0.44) predicted Arithmetic. Long-term outcome revealed enduring cognitive and motor deficits in young adults with CH relative to control subjects. Verbal functions and Arithmetic were associated with L-thyroxine treatment variables, suggesting that more optimal treatment might be possible. Motor outcome was associated with CH severity, indicating a prenatal effect.


Pyruvate dehydrogenase kinase 4 exhibits a novel role in the activation of mutant KRAS, regulating cell growth in lung and colorectal tumour cells.
RAS signalling is involved in the control of several metabolic pathways including glycolysis, mitochondrial respiration and glutamine metabolism. Importantly, we have found here that loss of PDHK4, a key regulator of the pyruvate dehydrogenase complex, caused a profound cell growth inhibition in tumour cells harbouring KRAS mutations. Using isogenic cells and a panel of colorectal and lung cell lines we demonstrated that KRAS mutant cells showed a dependency on PDHK4 whereas KRAS wild-type cells were significantly resistant to PDHK4 knockdown. We have found that PDHK4 plays a role in the post-translational regulation of mutant KRAS activity. Depletion of PDHK4 causes disruption of KRAS cellular localization, a reduction in KRAS activity which, in turn, results in reduced MAPK signalling. Interestingly, PDHK4 and KRAS depletion resulted in a similar metabolic phenotype consisting of a reduction of glucose and fatty acid oxidation. Moreover, stable expression of PDHK4 increased localization of activated KRAS at the plasma membrane and induced tumour cell growth in vitro and in vivo. Taken together these data support a model where PDHK4 regulates KRAS signalling and its tumorigenic properties and suggest that inhibition of PDHK4 could represent a novel therapeutic strategy to target KRAS mutant colorectal and lung cancers.


Dissociation of food and opiate preference by a genetic mutation in zebrafish.
Both natural rewards and addictive substances have the ability to reinforce behaviors. It has been unclear whether identical neural pathways mediate the actions of both. In addition, little is known about these behaviors and the underlying neural mechanisms in a genetically tractable vertebrate, the zebrafish Danio rerio. Using a conditioned place preference paradigm, we demonstrate that wildtype zebrafish exhibit a robust preference for food as well as the opiate drug morphine that can be blocked by the opioid receptor antagonist naloxone. Moreover, we show that the too few mutant, which disrupts a conserved zinc finger-containing gene and exhibits a reduction of selective groups of dopaminergic and serotonergic neurons in the basal diencephalon, displays normal food preference but shows no preference for morphine. Pretreatment with dopamine receptor antagonists abolishes morphine preference in the wildtype. These studies demonstrate that zebrafish display measurable preference behavior for reward and show that the preference for natural reward and addictive drug is dissociable by a single-gene mutation that alters subregions of brain monoamine neurotransmitter systems. Future genetic analysis in zebrafish shall uncover further molecular and cellular mechanisms underlying the formation and function of neural circuitry that regulate opiate and food preference behavior.


The effect of N-terminal fragments of immunophilin on phospholipid composition of rat brain.
Rat brain slices have been incubated in the presence of water-soluble synthetic peptide fragments corresponding to residues 1-9 and 1-15 of the N-terminus of immunophilin and the effects on the phospholipid composition examined. During a 2 h incubation in the presence of 1 nM, 0-1 mu M and 10 mu M concentrations of the peptides there were significant and dose-dependent decreases in the amounts of phosphatidylcholine and phosphatidylethanolamine and increases in the amounts of phosphatidylserine and, to a lesser extent, phosphatidylinositol, cardiolipin and lysophosphatidylcholine. The overall decrease in the neutral phospholipids and increase in the acidic phospholipids tended to counteract any change in the phospholipid composition of the tissue. The results are discussed in terms of the possible effects of immunophilin on modulating phospholipid turnover in brain cell membranes.


Correlation between normal range of serum alanine aminotransferase level and metabolic syndrome: A community-based study.
Serum alanine aminotransferase (ALT) is a biomarker of hepatocyte damage. However, the relationship between normal range of serum ALT level and metabolic syndrome (MetS) has not been completely understood. This study aimed to investigate the correlation between normal range of serum ALT level and MetS.A total of 2453 participants from the Beijing Community Pre-Diabetes study were enrolled. Multiple linear regression analysis was performed to calculate the regression coefficient. Normal serum ALT levels were divided into quartiles. Logistic regression model was used to compare the relative risk of MetS, and the receiver operating characteristic (ROC) curve to calculate the optimal ALT boundary value for predicting MetS.The frequency of MetS increased with the ALT level within the normal range. Compared with the first group, the risk of MetS was greater in the other quartiles of ALT level in males, the difference was significant for the fourth group. For females, the risk of MetS increased with ALT level within the normal range as well, with all differences showing statistical significance. The optimal ALT boundary value of the ROC curve for males and females was 24.5 and 14.5 U/L, respectively.ALT was related to metabolic factors and used as one of the indicators to assess the morbidity risk of metabolic diseases.


Partial reconstruction of the ergot alkaloid pathway by heterologous gene expression in Aspergillus nidulans.
Ergot alkaloids are pharmaceutically and agriculturally important secondary metabolites produced by several species of fungi. Ergot alkaloid pathways vary among different fungal lineages, but the pathway intermediate chanoclavine-I is evolutionarily conserved among ergot alkaloid producers. At least four genes, dmaW, easF, easE, and easC, are necessary for pathway steps prior to chanoclavine-I; however, the sufficiency of these genes for chanoclavine-I synthesis has not been established. A fragment of genomic DNA containing dmaW, easF, easE, and easC was amplified from the human-pathogenic, ergot alkaloid-producing fungus Aspergillus fumigatus and transformed into Aspergillus nidulans, a model fungus that does not contain any of the ergot alkaloid synthesis genes. HPLC and LC-MS analyses demonstrated that transformed A. nidulans strains produced chanoclavine-I and an earlier pathway intermediate. Aspergillus nidulans transformants containing dmaW, easF, and either easE or easC did not produce chanoclavine-I but did produce an early pathway intermediate and, in the case of the easC transformant, an additional ergot alkaloid-like compound. We conclude that dmaW, easF, easE, and easC are sufficient for the synthesis of chanoclavine-I in A. nidulans and expressing ergot alkaloid pathway genes in A. nidulans provides a novel approach to understanding the early steps in ergot alkaloid synthesis.


A helicase-independent activity of eIF4A in promoting mRNA recruitment to the human ribosome.
In the scanning model of translation initiation, the decoding site and latch of the 40S subunit must open to allow the recruitment and migration of messenger RNA (mRNA); however, the precise molecular details for how initiation factors regulate mRNA accommodation into the decoding site have not yet been elucidated. Eukaryotic initiation factor (eIF) 3j is a subunit of eIF3 that binds to the mRNA entry channel and A-site of the 40S subunit. Previous studies have shown that a reduced affinity of eIF3j for the 43S preinitiation complex (PIC) occurs on eIF4F-dependent mRNA recruitment. Because eIF3j and mRNA bind anticooperatively to the 43S PIC, reduced eIF3j affinity likely reflects a state of full accommodation of mRNA into the decoding site. Here, we have used a fluorescence-based anisotropy assay to quantitatively determine how initiation components coordinate their activities to reduce the affinity of eIF3j during the recruitment of mRNA to the 43S PIC. Unexpectedly, we show that a full reduction in eIF3j affinity for the 43S PIC requires an ATP-dependent, but unwinding-independent, activity of eIF4A. This result suggests that in addition to its helicase activity, eIF4A uses the free energy of ATP binding and hydrolysis as a regulatory switch to control the conformation of the 43S PIC during mRNA recruitment. Therefore, our results define eIF4A as a universal initiation factor in cap-dependent translation initiation that functions beyond its role in RNA unwinding.


Prevalence of Helicobacter pylori cagA, iceA and babA2 alleles in Brazilian patients with upper gastrointestinal diseases.
Helicobacter pylori is an important human pathogen associated with gastrointestinal diseases such as gastritis, gastric and duodenal ulcer (peptic ulcer disease, PUD), and gastric cancer. A number of pathogenic factors have been described for this bacterium, and some of them have been proposed as markers for the prediction of the clinical outcome. However, with the exception of the cag and vacA status, there is no universal consensus regarding the importance of the other virulence factors. Therefore, the aim of this study was to investigate the status of H. pylori strains regarding the babA and iceA alleles, as well as the cagA genotype, to reveal any association between these genotypes and clinical outcomes in Brazilian patients. The great majority (92.6%) of the strains were typed as iceA1, while 40.4% were found to possess the babA2 allele. The cagA gene was detected in 73.4% of the strains. The iceA2 and cagA genotypes were associated with PUD, while iceA1 was negatively correlated with PUD. However, considering the high percentage of strains typed as iceA1, these associations must be treated with caution. No clinical entity was associated with the babA2 allele. These results suggest that iceA1 is not a good marker for the diseases associated with H. pylori infection in Brazil. Further studies are needed in order to elucidate the relevance of the babA status, because other studies performed in Brazil have associated the babA2 allele with clinical outcomes. These results also indicate the existence of regional differences in the H. pylori genotypes and their association with clinical outcomes.


Factors contributing to the swimmer puppy syndrome found in Labrador retrievers.
Swimmer puppy syndrome is a disease found in neonatal puppies mainly characterized by the inability to stand, but its direct cause is unknown. Since swimmer puppies were observed infrequently but continuously among the Labrador retriever colony at the Hokkaido Guide Dogs for the Blind Association in Japan, based on their birth record and pedigree, factors related to the onset of swimmer puppy syndrome in Labrador retrievers were examined. The total number of offspring over seven years was 436, of which 16 were swimmer puppies. Most of the affected puppies except one recovered steadily. As for the swimmer puppies, the litter size was significantly lower, and the body weights on the 10th and 28th day after delivery were significantly higher than the non-symptomatic puppies. These results suggested that the onset may be related to weight gain in the neonatal stages due to a small litter size. According to the genetic analysis, 26 ancestors common to the affected individuals were confirmed, but the causative individual could not be identified with the inbreeding coefficient. The heritability of the swimmer-puppy onset trait was 0.80, and the heritability for the the 10th-day body-weight trait was equally high at 0.78, both of which strongly suggest genetic involvement. In this study, the onset of swimmer puppy syndrome in the Labrador retrievers was associated with litter size and early weight gain, and result of study suggests that genetic influence might be involved.


PowerPlex® Fusion 6C System: evaluation study for analysis of casework and database samples.
To report on the successful analysis of amplicons obtained with PowerPlex® Fusion 6C System, a highly robust 27-plex genotyping kit developed for human identification laboratories, on the Applied Biosystems® 3500 Genetic Analyzer. We performed characterization and evaluation studies following the Scientific Working Group on DNA Analysis Methods (SWGDAM) validation guidelines, examining several critical areas of kit performance. We report the results of sensitivity, robustness, heterozygous peak height ratio, precision, concordance, caseworks, and mixture interpretations. We tested sensitivity, using serial dilutions of control DNA. The minimum amount of input DNA resulting in a full profile was 125 pg. Inhibition, inducted by urea, showsed a progressively fragmentation of DNA and a full profile was obtained until 1M of inhibitor factor. To test the profile quality, casework samples were extracted with different extraction methods: Chelex®100, QIAmp DNA Micro Kit and Phenol-Chloroform extraction. The results demonstrated that extraction chemistries do not have affect on amplification performance. Concordance check was performed by typing some casework samples and comparing the typing results with those obtained with other available kits. Thus, concordance was expected and supported by the data. Reliable DNA typing results can be obtained using this new kit, demonstrating its effectiveness and utility in forensic analysis.


Robotic colposacropexy.
To review the role of robot- assisted laparoscopic colposacropexy (RALCS) as a treatment for pelvic organ prolapse (POP) accordingly with the available literature and our own experience. We have analyzed the studies with the results of robot-assisted colposacropexy (RALCS) and others in which this technique is compared with the abdominal (ACS) and/or the laparoscopic approach (LCS), including our own series. The main data collected are surgical time, blood loss, complications, clinical outcomes, quality of life and the different costs of LCS versus RALCS. We have reviewed the last systematic reviews and meta-analysis. Clinical outcomes were similar within both RALCS and LCS, surgical time was a bit longer for the robot-assisted compared with laparoscopy, blood loss was similar, as complications. The costs of RALCS were significantly higher than those of LCS, although we must conseconsider that the different studies used different variables to measure them. Considering that comparative studies are necessary, it is reasonable to assume that RALCS is a feasible and secure technique for the treatment of POP.


WIMIN: Who We Are and What We Do.
Women in Molecular Imaging Network (WIMIN) is an interest group of the World Molecular Imaging Society (WMIS) aimed at advancing the careers of women in science. WIMIN represents women in the field of molecular imaging through all stages of their career development and promotes their advancement to leadership positions within the society and their careers. WIMIN's roles include training and mentoring, and building bridges with other interest groups within WMIS and beyond as well as identifying challenges for advancement of female scientists and solutions to overcome them. In addition to ongoing WIMIN-sponsored programs to be described here, a number of exciting new programs will be initiated in 2017. WIMIN is committed to advancing the futures of female scientists in molecular imaging and welcomes all new membership.


Botulinum toxin: from spasticity reliever to a neuromotor re-learning tool.
Botulinum toxin is becoming increasingly popular as the drug of choice for relief of spasticity in a wide range of conditions, from stroke to strabismus to vaginismus. Besides this role as spasticity reliever, several recent clinical reports claim that in stroke, cerebral palsy, spinal cord injury (SCI), and dystonias, BoTx brings about significant improvement in function--attributed to synaptic plasticity of the muscular afferents. The authors' research had shown that BoTx also generates synaptic plasticity in spinal alpha-motoneurons-interneurons. The article describes how BoTx facilitates relearning by Hebbian and Contrastive Hebbian modes and how it can be used as a neuro-relearning tool to enhance and hasten motor recovery in the aforementioned disorders.


Effects of cardioplegic reperfusion on ATP recovery of rod-shaped myocytes isolated from rat ventricles.
ATP content [ATP] and fraction of rod-shaped myocytes (Rrod) were measured in ventricular myocytes isolated from the rat heart. [ATP] (nmol (10(6) cells)-1) and Rrod (%) were 72.0 and 60.5, respectively, and significantly reduced to 18.8 and 41.8 by no-flow ischemia for 30 min. Reperfusion for 15 min with cardioplegic solutions restored [ATP] of rod-shaped myocytes to the control level.


Long-range orientation correlation in water.
Strong short-range intermolecular interactions result in position and orientation correlations between nearest neighbour molecules in isotropic liquids, but it is generally assumed that such correlations extend at most a few molecular diameters. Results from second-harmonic light scattering experiments presented here reveal long-range molecular orientation correlations in liquid water, where the molecular dipole orientation distribution has the form of a nearly pure transverse vector field. Spatial scales in the range 200-2000 nm are probed by the angle-dependent measurements and the observed correlations are thought to result from rotation-translation coupling in acoustic phonons in the liquid.


Polar head group interactions in mixed Langmuir monolayers.
We have investigated the miscibility in the mixed monolayers of cholesterol (Ch)-octyl cyano biphenyl (8CB) and cholesteryl acetate (ChA)-8CB using surface manometry and epifluorescence microscopic techniques. The main skeleton is the same both in Ch and ChA, whereas the polar head group is alcohol in Ch and ester in ChA. The 8CB molecule has a polar cyano as a terminal group and we probe its interaction with the polar group of Ch or ChA molecules in the mixed monolayers. Both Ch-8CB and ChA-8CB mixed monolayers exhibit two collapse pressures. In the case of the Ch-8CB mixed monolayer, the lower collapse pressure varies after 0.6 mole fraction (MF) of Ch in 8CB and the higher collapse pressure is nearly independent of composition. In ChA-8CB mixed monolayer, the lower collapse pressure varies continuously with the composition of ChA while the higher collapse pressure is nearly independent of the composition of ChA. In both these mixed monolayers, above the lower collapse pressure, 8CB gets squeezed out of the monolayer and forms multilayers. We find that in the case of Ch-8CB there is a phase separation in the monolayer occurring in the range of 0.15-0.9 MF of Ch. However, in ChA-8CB, the monolayer phase is miscible in all the proportions (except at very high concentration of ChA) below the lower collapse pressure. We attribute this better miscibility in the ChA-8CB compared to the Ch-8CB to the role played by the ester and cyano polar head group interactions.


Aerobic exercise as therapy for cancer fatigue.
Fatigue and impairment of physical performance are common and severe problems of cancer patients. We describe the effect of an aerobic exercise program designed for cancer patients suffering from these symptoms. Five cancer patients (4 female, 1 male, age 18 to 55), participated in the training program. Fatigue had been present for a time ranging between 5 wk and 18 months and hindered the patients from carrying out normal daily activities. The training program consisted of walking daily on a treadmill with an intensity corresponding to a lactate concentration of 3 +/- 0.5 mmol.L-1 and was carried out for 6 wk. By the end of the exercise program we observed an improvement in maximal physical performance (from 6.4 +/- 0.4 km.h-1 to 7.5 +/- 0.9 km.h-1, P < 0.05) and maximal walked distance (from 1640 +/- 724 m to 3300 +/- 953 m, P < 0.05). Heart rate and lactate concentration by an equivalent submaximal workload (5 km.h-1) were significant reduced (from 138 +/- 21 beats.min-1 to 113 +/- 20 beats.min-1, P < 0.05, and from 2.6 +/- 1.4 mmol.L-1 to 1.3 +/- 0.6 mmol.L-1, P < 0.05); all patients experienced a clear reduction of fatigue and could carry out normal daily activities again without substantial limitations. We conclude that an aerobic exercise program of precisely defined intensity, duration, and frequency can be prescribed as therapy for primary fatigue in cancer patients.


Lidar-measured atmospheric N₂ vibrational-rotational Raman spectra and consequent temperature retrieval.
We have built a spectrally resolved Raman lidar to measure atmospheric N₂ Stokes vibrational-rotational Raman spectra. The lidar applies a double-grating polychromator with a reciprocal linear dispersion of ~0.12 nm mm(-1) for the wavelength separation and a 32-channel linear-array photomultiplier tube for sampling the spectral signals. The lidar can together measure the individual S- and O-branch line signals from J = 0 (2) through 14 (16). A comparison shows an excellent agreement between the lidar-measured and theoretically-calculated spectra. Based on the signal ratio of two individual lines (e.g., S-branch J = 6 and 12), the atmospheric temperature profiles are derived without requiring a calibration from another reference temperature. In terms of the envelope shape of an even-J section of the measured S-branch lines, we have also developed a new temperature retrieval approach without needing a calibration from reference temperature data. Both the approaches can give rise to reasonable temperature profiles comparable to that from local radiosonde.


Level of agreement of point-of-care and laboratory HbA1c measurements in the preoperative outpatient clinic in non-diabetic patients who are overweight or obese.
Implementation of point-of-care HbA1c devices in the preoperative outpatient clinic might facilitate the early diagnosis of glycemic disturbances in overweight or obese patients undergoing surgery, but validation studies in this setting do not exist. We determined the level of agreement between a point-of-care and laboratory HbA1c test in non-diabetic patients visiting the outpatient clinic for preoperative risk profiling. Point-of-care HbA1c levels were measured in whole blood obtained by a finger prick (Siemens DCA Vantage HbA1c analyzer) and in hemolysed EDTA blood in the central laboratory (LAB). Bland Altman and Clarke's error grid analysis were used to analyze the agreement between the point-of-care and laboratory measurements. Patients (n = 49) were 55 ± 11 years old, 47% were male with a body mass index (BMI) of 30.6 ± 3.4 kg/m2. The mean HbA1c was 38.1 ± 3.7 mmol/mol or 5.6 ± 0.3%. One patient was diagnosed with a HbA1c indicative for diabetes mellitus (6.7%). Bland Altman analysis revealed a bias of - 0.53 ± 1.81 mmol/mol with limits of agreement of - 4.09 to 3.03 mmol/mol and a bias of - 0.05 ± 0.17% with limits of agreement - 0.39 to 0.28%. The percentage error was 9.2% and 5.9% for HbA1c expressed in mmol/mol and %, respectively. Clarke's error grid analysis showed that 48 out of 49 measurements were located in area A (98%). Point-of-care HbA1c measurements showed a high level of agreement with the laboratory test in the outpatient setting, and may be used for preoperative risk profiling in patients prone to cardiometabolic complications.Trial registration: Netherlands Trial Register NTR3057.


NMR imaging of intracranial hemorrhage.
Twenty-one intracranial hemorrhagic lesions were imaged at 0.15 and 0.6 T using inversion recovery (IR), spin echo (SE), and multiple SE (Carr-Purcell-Meiboom-Gill, CPMG) pulse sequences. Two subarachnoid hemorrhages (SAH), nine acute intraparenchymal hemorrhages (IPH), ten chronic IPH, and one subdural hematoma were studied. Acute SAH could not be identified on the T1-weighted, IR images but was clearly seen on a T2-weighted, CPMG image. Acute (7 days or less) intraparenchymal hematoma showed signal intensity on IR and CPMG images similar to white matter. The T1 and T2 times of acute intraparenchymal hematoma were also similar to white matter. Some small acute hematomas could not be distinguished from white matter on IR and CPMG images. Acute hemorrhagic tissue showed image intensities and relaxation times similar to gray matter. All acute hemorrhages were identified on CT. Chronic IPH lesions (14 days or more) showed high signal intensity, greater than white matter, on IR, SE, and CPMG images. The T1 of the chronic lesions was similar to the acute lesions but T2 was significantly longer (p less than 0.05). Available evidence suggests that the nonspecificity of acute IPH signal and relaxation times may not be restricted to our pulse sequences or magnetic field strengths.


Surgical treatment of intractable esophagitis.
An operative technique combining a 360-degree fundoplication which is stabilized by anchoring the gastroesophageal junction to the middle arcuate ligament was used in a series of 140 patients since 1973. The patients were evaluated 1 year or more after surgery with clinical and radiographic assessment, regardless of complaints. Clinical results have been good in 91%. There has been no operative mortality and minor transient morbidity. X-rays done at least 1 year after surgery were compared with results obtained in 88 patients who had a modification of Hill's posterior gastropexy performed during the earlier years of this experience. The incidence of x-ray abnormalities with the posterior gastropexy was reduced from 23.5% to 5% when fundoplication was used in combination with a posterior gastropexy. The anchorage of the esophagogastric junction to the middle arcuate ligament allows a relatively loose fundoplication and thereby has reduced the incidence of disabling gas-bloat. Stabilizing the fundoplication prevents the occurrence of other complications related to fundoplication such as disruption, migration, and obstruction. This technique avoids the use of sutures in the esophageal wall, thus reducing the potential for perforation, fistula, or injury to the vagus nerves.


Concomitant abuse of clonidine and heroin.
We have reported the case of a 36-year-old woman who abused heroin and clonidine concomitantly. To our knowledge, this practice has never been reported in the medical literature, although it may be relatively common in certain communities. It may place the heroin abuser's health at additional risk and complicate therapy for overdose and withdrawal.


Carcinoma of the lung with marked hyperamylasemia and elevated serum calcitonin.
Ectopic production of multiple peptide hormones is a frequent concomitant of neoplasia. An elderly man with metastatic small cell carcinoma of the lung presented with back pain, a right hilar mass, and was demonstrated to have markedly elevated serum calcitonin and amylase levels. Polyacrylamide gel electrophoresis revealed a striking elevation of a "salivary type" isoamylase. We report this case as an unusual association of production of both a peptide hormone and a nonhormonal peptide in a patient with a tumor of "neural crest" origin.