A meta-analytic review of the effects of psychotherapy control conditions for anxiety disorders.
Little is known about the magnitude of improvement associated with psychotherapy control conditions for adult anxiety disorders. This information is important for the design of psychosocial treatment efficacy studies. We performed a computerized search of treatment outcome studies of anxiety disorders conducted between the first available year and 1 March 2007. In addition, we examined the reference lists from identified articles and asked international experts to identify eligible studies. We included studies that randomly assigned adult patients suffering from anxiety disorders to either cognitive-behavioral treatment or psychotherapy control condition. For each study, the two authors independently selected psychometrically sound measures of anxiety disorder severity. In addition, we collected data on attrition and treatment response. Of the 1165 studies that were initially identified, 19 studies (454 patients) met inclusion criteria and were included in the analyses. The random effects analysis yielded a pre- to post-treatment Hedges' g effect size of 0.45 (95% confidence interval 0.35-0.46, z=8.50, p<0.001). The mean weighted response and attrition rates were 25.0% and 14.2%, respectively. There was no evidence for publication bias, nor was there a significant relationship between the effect size and diagnostic group, study year or number of treatment sessions. Psychotherapy control conditions are associated with significant improvements when administered to adults suffering from anxiety disorders. In addition, they are associated with a relatively low attrition rate. These findings can inform the design of future psychotherapy outcome studies.


Influence of depression and effect of treatment with sertraline on quality of life after hospitalization for acute coronary syndrome.
Major depressive disorders complicate recovery from acute coronary syndrome in approximately 1 in 5 patients, and have been found to be associated with significant impairments of quality of life and functioning. The aim of the present analysis was to evaluate the efficacy of sertraline in improving quality of life and functioning in patients diagnosed with major depression who had recently been hospitalized for acute coronary syndrome. Three hundred sixty-nine patients hospitalized in the previous month for acute coronary syndrome (myocardial infarction, 74%; unstable angina, 26%) who also met criteria for major depressive disorder were randomized to 24 weeks of double-blind treatment with sertraline (50 to 200 mg/day) or placebo. Quality-of-life and functional status were assessed using the Quality of Life, Enjoyment, and Satisfaction scale (Q-LES-Q) and the Medical Outcomes Study SF-36. Data from the total sample, and the recurrent depression subgroup, were analyzed. Severe baseline impairment was found in the Q-LES-Q and all subscales of the SF-36. A multivariate regression analysis identified depression as the strongest predictor of baseline quality-of-life impairment (partial r, -0.37, p = 0.001). In the recurrent depression group, treatment with sertraline resulted in significantly greater improvement than placebo in the Q-LES-Q total score and SF-36 mental component summary score, as well as the SF-36 role limitations, emotional, and mental health factors. Depression has a substantial negative impact on quality of life and functioning in patients hospitalized for acute coronary syndrome. Sertraline was associated with clinically meaningful improvement in multiple quality-of-life domains in patients with acute coronary syndrome and recurrent depression.


Thrombophlebitis and pulmonary embolism with surgical intervention in the third trimester.
A case of acute deep vein thrombophlebitis and pulmonary embolism in late gestation has been presented with a discussion of diagnostic modalities, therapeutic regimens, and theoretical considerations. It is our belief that aggressive medical management is best accomplished by giving heparin intravenously as the primary anticoagulant. When medical management is best accomplished by giving heparin intravenously as the primary anticoagulant. When medical management is not effective or if embolism occurs, surgical intervention, consisting of vena caval clipping and ovarian vein ligation with scrupulous attention to detail, is indicated. Further, support to prophylaxis of abruptio placenta secondary to the mechanism espoused by Mengert et al is added by the course of this patient.


A review of analgesic and emotive breathing: a multidisciplinary approach.
The diaphragm is the primary muscle involved in breathing and other non-primarily respiratory functions such as the maintenance of correct posture and lumbar and sacroiliac movement. It intervenes to facilitate cleaning of the upper airways through coughing, facilitates the evacuation of the intestines, and promotes the redistribution of the body's blood. The diaphragm also has the ability to affect the perception of pain and the emotional state of the patient, functions that are the subject of this article. The aim of this article is to gather for the first time, within a single text, information on the nonrespiratory functions of the diaphragm muscle and its analgesic and emotional response functions. It also aims to highlight and reflect on the fact that when the diaphragm is treated manually, a daily occurrence for manual operators, it is not just an area of musculature that is treated but the entire body, including the psyche. This reflection allows for a multidisciplinary approach to the diaphragm and the collaboration of various medical and nonmedical practitioners, with the ultimate goal of regaining or improving the patient's physical and mental well-being.


An online survey of specialists' opinion on first line management options for unexplained subfertility.
The recent National Institute for Health and Care Excellence (NICE) guideline on Fertility (2012) suggests that IVF should be offered to couples with unexplained subfertility after 2 years of expectant management. The evidence on which these recommendations are based is not robust and there is a lack of agreement among specialists regarding the management of unexplained subfertility. We conducted an online survey among fertility specialists to find out the general consensus regarding the management of these couples. An e-mail questionnaire was sent to 420 reproductive medicine clinicians and 136 (32.38%) replied. Only 16% said they would always recommend IVF as the first line management for these couples, irrespective of age and duration of infertility. Of those surveyed, 39% agreed to the new NICE proposal, 33% agreed partly and 25% did not agree at all. A total of 27% of the respondents said they would definitely change their practice according to the NICE proposal but 30% said they would not; 29% said they might change their policy while the rest were unsure. This survey confirms the ongoing clinical uncertainty among fertility specialists in managing couples with unexplained subfertility.


A novel sarcoidosis risk locus for Europeans on chromosome 11q13.1.
Sarcoidosis is a complex inflammatory disease with a heterogeneous clinical picture. Among others, an acute and chronic clinical course can be distinguished, for which specific genetic risk factors are known. To identify additional risk loci for sarcoidosis and its acute and chronic subforms, we analyzed imputed data from a genome-wide association scan for these phenotypes. After quality control, the genome-wide association scan comprised nearly 1.3 million imputed single-nucleotide polymorphisms based on an Affymetrix 6.0 Gene Chip dataset of 564 German sarcoidosis cases, including 176 acute and 354 chronic cases and 1,575 control subjects. We identified chromosome 11q13.1 (rs479777) as a novel locus influencing susceptibility to sarcoidosis with genome-wide significance. The marker was significantly associated in three distinct German case-control populations and in an additional German family sample with odds ratios ranging from 0.67 to 0.77. This finding was further replicated in two independent European case-control populations from the Czech Republic (odds ratio, 0.75) and from Sweden (odds ratio, 0.79). In a meta-analysis of the included European case-control samples the marker yielded a P value of 2.68 × 10(-18). The locus was previously reported to be associated with Crohn disease, psoriasis, alopecia areata, and leprosy. For sarcoidosis, fine-mapping and expression analysis suggest KCNK4, PRDX5, PCLB3, and most promising CCDC88B as candidates for the underlying risk gene in the associated region. This study provides striking evidence for association of chromosome 11q13.1 with sarcoidosis in Europeans, and thus identified a further genetic risk locus shared by sarcoidosis, Crohn disease and psoriasis.


Prevalence of S. aureus and/or MRSA from seafood products from Indian seafood products.
Compared to the clinical sector, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the food sector is relatively low. However, their presence in seafood is a significant public health concern. In India, fish and fishery products are maximally manually handled compared to other food products. In this study, 498 fish samples were collected under various conditions (fresh, chilled or dressed) and representatives from their surroundings. These samples were screened for the prevalence of Staphylococcus aureus, determining its antimicrobial resistance, MRSA and genetic profile. It is observed that 15.0% and 3.0% of the total samples were screened positive for S. aureus and MRSA, respectively. The S. aureus strain MRSARF-10 showed higher resistance to linezolid, co-trimoxazole, cefoxitin, ofloxacin, gentamicin, rifampicin, ampicillin/sulbactam and Piperacillin-tazobactam. This MRSA, spa type t021 and SCCmec type V strain isolated from dried ribbon fish (Family Trachipteridae) carried virulence factors for exoenzymes such as aureolysin, serine, toxin genes and a novel MLST ST 243, as revealed from its draft-genome sequence. This highly pathogenic, multidrug-resistant and virulent S. aureus novel strain is circulating in the environment with chances of spreading among the seafood workers and the environment. It is further suggested that Good Hygienic Practices recommended by World Health Organization need to be followed during the different stages of seafood processing to provide pathogen-free fish and fishery products to the consumers.


Developmental plasticity of mating calls enables acoustic communication in diverse environments.
Male calls of the katydid Neoconocephalus triops exhibit substantial developmental plasticity in two parameters: (i) calls of winter males are continuous and lack the verse structure of summer calls and (ii) at equal temperatures, summer males produce calls with a substantially higher pulse rate than winter males. We raised female N. triops under conditions that reliably induced either summer or winter phenotype and tested their preferences for the call parameters that differ between summer and winter males. Neither generation was selective for the presence of verses, but females had strong preferences for pulse rates: only a narrow range of pulse rates was attractive. The attractive ranges did not differ between summer and winter females. Both male pulse rate and female preference for pulse rate changed with ambient temperature, but female preference changed more than the male calls. As a result, the summer call was attractive only at 25 degrees C, whereas the slower winter call was attractive only at 20 degrees C. Thus, developmental plasticity of male calls compensates for differences in temperature dependency between calls and preferences and enables the communication system to function in heterogeneous environments. The potential role of call plasticity during the invasion of new habitats is discussed.


Liposoluble antioxidants provide an effective radioprotective barrier.
Ionising radiation causes the massive generation of reactive oxygen species and induces cellular DNA damage. The antioxidant, protective effects of several compounds against gamma-ray-induced chromosomal damage were determined by the micronucleus test, evaluating the reduction in the frequency of micronuclei in cytokinesis-blocked human lymphocytes. The compounds studied were added to human blood at 25 microM, 5 min before or after irradiation with 2 Gy of caesium-137. The results suggest that different protective mechanisms are operating in each case. When the phenolic compounds are added before gamma-irradiation, their protective antimutagenic activity is based on their scavenging capacity against superoxide anion (O(2)(.-)) and, especially, hydroxyl radical ((.)OH), regardless of whether they are oil- or water-soluble compounds. When the phenolic compounds are added after gamma-irradiation treatment, the protective effect relies on activity against reactive oxygen species present in cells, i.e. lipoperoxy radicals (R(-)OO(.)), which are mainly responsible for continuous chromosomal oxidative damage. In addition, ionising radiation enhances lysosomal enzyme secretion and arachidonate release from membranes through lipo-oxygenase, cyclo-oxygenase and phospholipase activities, thus increasing the inflammatory cell response. Only oil-soluble compounds, such as carnosic acid, carnosol and delta-tocopherol, provide a significant protective antimutagenic activity. The most powerful water-soluble antioxidants lack the capacity to protect against gamma-ray-induced damage. The difference between anti-radical and anti-lipoperoxidant activities could explain the different behaviour of the compounds tested in terms of protecting against the lipid peroxidative processes. This anti-lipoperoxidant activity depends on several factors, but it is clear that only the lipo-antioxidants are effective in protecting human cells against oxidative damage, even when administered after exposure to ionising radiation.


Orally-administered nanomedicine systems targeting colon inflammation for the treatment of inflammatory bowel disease: latest advances.
Inflammatory bowel disease (IBD) is a chronic and idiopathic condition that results in inflammation of the gastrointestinal tract, leading to conditions such as ulcerative colitis and Crohn's disease. Commonly used treatments for IBD include anti-inflammatory drugs, immunosuppressants, and antibiotics. Fecal microbiota transplantation is also being explored as a potential treatment method; however, these drugs may lead to systemic side effects. Oral administration is preferred for IBD treatment, but accurately locating the inflamed area in the colon is challenging due to multiple physiological barriers. Nanoparticle drug delivery systems possess unique physicochemical properties that enable precise delivery to the target site for IBD treatment, exploiting the increased permeability and retention effect of inflamed intestines. The first part of this review comprehensively introduces the pathophysiological environment of IBD, covering the gastrointestinal pH, various enzymes in the pathway, transport time, intestinal mucus, intestinal epithelium, intestinal immune cells, and intestinal microbiota. The second part focuses on the latest advances in the mechanism and strategies of targeted delivery using oral nanoparticle drug delivery systems for colitis-related fields. Finally, we present challenges and potential directions for future IBD treatment with the assistance of nanotechnology.


Improved artifact rejection and isolation of compound action potentials by means of digital subtraction.
When recording compound action potentials (CAPs) elicited by stimulating near the recording site, it may prove difficult to distinguish the CAP from the shock artifact because of their overlap in time. This problem is compounded when a pair of stimulation pulses is delivered because the CAP elicited by the test pulse (T pulse) may be partially superimposed on the artifact and response elicited by the conditioning pulse (C pulse) as well as on the T pulse artifact. Methods based on digital subtraction were used to address these problems. A record was obtained with the C-T interval adjusted to be slightly less than the absolute refractory period so that the T pulse would fail to elicit a CAP. A record consisting of a C pulse artifact and response was subtracted from this record to yield a 'pure' shock artifact. In principle, subtracting this 'artifact-only' record from records obtained with single pulses removes the shock artifact and yields a 'pure' response. An extension of this method was used to isolate T pulse responses from the C pulse artifact, C pulse response, and T pulse artifact. These methods proved effective in improving the isolation of the CAPs of interest from other features of the raw records. Limitations of the techniques and their complementarity with other methods of artifact reduction are discussed.


Confirmed Transmission of Bacterial or Fungal Infection to Kidney Transplant Recipients from Donated After Cardiac Death (DCD) Donors in China: A Single-Center Analysis.
BACKGROUND We aimed to investigate blood and urine cultures of donated after cardiac death (DCD) donors and report the cases of confirmed (proven/probable) transmission of bacterial or fungal infection from donors to kidney recipients. MATERIAL AND METHODS Seventy-eight DCD donors between 2010 and 2016 were included. Sixty-one DCD donors underwent blood cultures and 22 episodes of bacteremias developed in 18 donors. Forty-three donors underwent urine cultures and 14 donors experienced 17 episodes of urinary infections. RESULTS Seven of 154 (4.5%) kidney recipients developed confirmed donor-derived bacterial or fungal infections. Inappropriate use of antibiotics in donor was a risk factor for donor-derived infection (p=0.048). The use of FK506 was more frequent in recipients without donor-derived infection than those with donor-derived infection (p=0.033). Recipients with donor-derived infection were associated with higher mortality and graft loss (42.9% and 28.6%, respectively), when compared with those without donor-derived infection (4.8% each). Three kidney recipients with donor-derived infection died; one death was due to multi-organ failure caused by Candida albicans, and two were related to rupture of the renal artery; two of them did not receive appropriate antimicrobial therapy after infection. CONCLUSIONS Our kidney recipients showed high occurrence rates of donor-derived infection. Recipients with donor-derived infection were associated with higher mortality and graft loss than those without donor-derived infection. The majority of recipients with donor-derived infection who died did not receive appropriate antimicrobial therapy after infection.


Maltreatment history and weapon carrying among early adolescents.
This study examines the role of maltreatment in weapon carrying among 12-year-old youth (N = 797) interviewed as part of the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN), an ongoing study of the antecedents and consequences of child maltreatment. Participants reported their physical and sexual abuse history and provided responses to items assessing perceived need for a weapon and weapon carrying. There were no gender differences in rates of self-reported physical or sexual abuse. Males were more likely than females to report weapon carrying and perceived need for a weapon. A mediation analysis was conducted to examine the mediating effect of perceived need for a weapon on the association between abuse and weapon carrying. Results indicated that perceived need for a weapon fully mediated the effect of physical abuse and partially mediated the effect of sexual abuse. Results are discussed in the context of self-protection theory.


Effect of disinfectant application methods on the bond strength of composite to dentin.
The use of cavity disinfectants with composite resins has raised important questions regarding their potential adverse effects on bond strength. The purpose of this study was to evaluate the effect of cavity disinfection on the bond strength of composite resin to dentin. Buccal surfaces of 64 caries-free extracted human third molars were ground flat by diamond flat-end cylinder bur, polished with a series of silicon carbide abrasive papers and mounted in autopolymerizing acrylic resin. They were randomly distributed into four groups (of 16). In group 1 (control group), dentin surfaces were treated with 35% phosphoric acid, Permagen primer and Permagen bonding resin and no disinfectant was used. In group 2, cavity disinfectant was applied and acid etching, priming and bonding procedures were performed as in group 1. In group 3, cavity disinfectant was applied after acid etching. In group 4, cavity disinfectant was applied as in group 3, but it was rinsed off before priming and bonding procedures. Then a Teflon mould 3 mm thick and 4 mm in diameter was attached to the dentin surfaces, filled with composite resin and light polymerized. After the specimens had been thermocycled, shear bond strengths were determined. Application of the disinfectant before or after acid etching significantly reduced the shear bond strength of composite to dentin (P<0.05). Rinsing off the cavity disinfectant before the bonding procedure did not affect the bond strength (P>0.05). The use of cavity disinfectant with composite resin restorations can influence the dentin bond strength.


Management of nail psoriasis.
Nail psoriasis is often difficult to cure, but may respond to a range of different approaches used alone or together. As with treatment of psoriasis affecting skin, relapse is common and therapies may need to be maintained or repeated. The exact benefits of many of these treatments are not well documented in the literature. Basic nail care is important and topical therapies represent the main modality of treatment for the majority of cases. In severe nail disease, where there is a hypertrophic element, injection therapy with triamcinolone may be helpful. PUVA and other forms of radiation may be of benefit, but as with systemic therapy, they are usually useful in the context of treatment of psoriasis elsewhere on the body.


Effects of bacterial microflora of the lower digestive tract of free-range waterfowl on influenza virus activation.
Proteolytic cleavage activation of influenza virus hemagglutinin (HA0) is required for cell entry via receptor-mediated endocytosis. Despite numerous studies describing bacterial protease-mediated influenza A viral activation in mammals, very little is known about the role of intestinal bacterial flora of birds in hemagglutinin cleavage/activation. Therefore, the cloaca of wild waterfowl was examined for (i) representative bacterial types and (ii) their ability to cleave in a "trypsin-like" manner the precursor viral hemagglutinin molecule (HA0). Using radiolabeled HA0, bacterial secretion-mediated trypsin-like conversion of HA0 to HA1 and HA2 peptide products was observed to various degrees in 42 of 44 bacterial isolates suggestive of influenza virus activation in the cloaca of wild waterfowl. However, treatment of uncleaved virus with all bacterial isolates gave rise to substantially reduced emergent virus progeny compared with what was expected. Examination of two isolates exhibiting pronounced trypsin-like conversion of HA0 to HA1 and HA2 peptide products and low infectivity revealed lipase activity to be present. Because influenza virus possesses a complex lipid envelope, the presence of lipid hydrolase activity could in part account for the observed less-than-expected level of viable progeny. A thorough characterization of respective isolate protease HA0 hydrolysis products as well as other resident activities (i.e., lipase) is ongoing such that the role of these respective contributors in virus activation/inactivation can be firmly established.


Structural adaptation of extreme halophilic proteins through decrease of conserved hydrophobic contact surface.
Halophiles are extremophilic microorganisms growing optimally at high salt concentrations. There are two strategies used by halophiles to maintain proper osmotic pressure in their cytoplasm: accumulation of molar concentrations of potassium and chloride with extensive adaptation of the intracellular macromolecules ("salt-in" strategy) or biosynthesis and/or accumulation of organic osmotic solutes ("osmolyte" strategy). Our work was aimed at contributing to the understanding of the shared molecular mechanisms of protein haloadaptation through a detailed and systematic comparison of a sample of several three-dimensional structures of halophilic and non-halophilic proteins. Structural differences observed between the "salt-in" and the mesophilic homologous proteins were contrasted to those observed between the "osmolyte" and mesophilic pairs. The results suggest that haloadaptation strategy in the presence of molar salt concentration, but not of osmolytes, necessitates a weakening of the hydrophobic interactions, in particular at the level of conserved hydrophobic contacts. Weakening of these interactions counterbalances their strengthening by the presence of salts in solution and may help the structure preventing aggregation and/or loss of function in hypersaline environments. Considering the significant increase of biotechnology applications of halophiles, the understanding of halophilicity can provide the theoretical basis for the engineering of proteins of great interest because stable at concentrations of salts that cause the denaturation or aggregation of the majority of macromolecules.


Characterization of Mycobacterium tuberculosis antigen 5 epitopes by using a panel of 19 monoclonal antibodies.
Antigen 5 is a 35,000-dalton protein which has been purified from culture filtrates of Mycobacterium tuberculosis and shown by immunoprecipitation to be restricted in distribution to M. tuberculosis and M. bovis among 14 mycobacterial species studied. We raised 19 antigen 5-reactive monoclonal antibodies and used them to characterize epitopes of this antigen by enzyme-linked immunosorbent assay and immunoabsorbent affinity chromatography. Fifteen monoclonal antibodies, all immunoglobulin M (IgM), cross-reacted in two major patterns with culture filtrates from five species of mycobacteria and with purified mycobacterial arabinomannan and arabinogalactan. All 15 monoclonal antibodies also reacted with M. tuberculosis antigen 6. Immunoabsorbent affinity columns prepared with these antibodies yielded principally arabinomannan and arabinogalactan. Four monoclonal antibodies, three IgG2a and one IgM, reacted by enzyme-linked immunosorbent assay with antigens 5 and 6 exclusively and not with mycobacterial culture filtrates or polysaccharides. All four monoclonal antibodies yielded antigen 5 and small amounts of antigen 6 when used for immunoabsorbent affinity chromatography. We conclude from these studies that antigen 5 has two nonspecific epitopes, possibly carbohydrate in nature, and one apparent species-specific epitope which is shared with antigen 6.


Preschool sleep and depression interact to predict gray matter volume trajectories across late childhood to adolescence.
There is a close relationship between sleep and depression, and certain maladaptive outcomes of sleep problems may only be apparent in individuals with heightened levels of depression. In a sample enriched for preschool depression, we examined how sleep and depression in early childhood interact to predict later trajectories of gray matter volume. Participants (N = 161) were recruited and assessed during preschool (ages 3-6 years) and were later assessed with five waves of structural brain imaging, spanning from late childhood to adolescence. Sleep and depression were assessed using a semi-structured parent interview when the children were preschool-aged, and total gray matter volume was calculated at each scan wave. Although sleep disturbances alone did not predict gray matter volume/trajectories, preschool sleep and depression symptoms interacted to predict later total gray matter volume and the trajectory of decline in total gray matter volume. Sleep disturbances in the form of longer sleep onset latencies, increased irregularity in the child's sleep schedule, and higher levels of daytime sleepiness in early childhood were all found to interact with early childhood depression severity to predict later trajectories of cortical gray matter volume. Findings provide evidence of the interactive effects of preschool sleep and depression symptoms on later neurodevelopment.


The Targeted Delivery of Interleukin 4 Inhibits Development of Endometriotic Lesions in a Mouse Model.
Endometriosis is caused by the displacement of endometrium outside the uterus contributing heavily to infertility and debilitating pelvic pain. Ectopic adhesion and growth are believed to occur under the influence of a favorable hormonal environment and immunological factors. The objective of this study is to analyze the effect of a targeted therapy with an antibody-based pharmacodelivery of interleukin 4 (F8-IL4) in a mouse model of experimentally induced endometriosis. Endometriosis-like lesions were induced in Balb/c mice. The animals were treated intravenously with F8-IL4 or with untargeted IL4 (KSF-IL4). Twelve days after disease induction, the lesions were isolated. A significant reduction in the number of total lesions/mouse and in the total volume of lesions/mouse was observed in mice treated with F8-IL4 compared to controls (P = .029 and P = .006, respectively), while no difference was found between KSF-IL4-treated mice and their controls. Gene expression was evaluated by quantitative real-time polymerase chain reaction. Expression of genes involved in cell adhesion, extracellular matrix invasion, and neovascularization was significantly downregulated in F8-IL4-treated mice compared to their controls (integrin β1: P = .02; metalloproteinase [MMP] 3: P = .02; MMP9: P = .04; vascular endothelial growth factor: P = .04). Gene expression of inflammatory cytokines (tumor necrosis factor α, IL1β, IL1α, and IL6) did not vary in the ectopic lesions isolated from F8-IL4-treated mice compared to their controls. Immunohistochemistry demonstrated a significantly reduced expression of E-cadherin and β-catenin in the lesions of mice treated with F8-IL4. Our results show that the antibody-mediated targeted delivery of IL4 inhibits the development of endometriosis in a syngeneic mouse model by likely impairing adhesion, invasion, and vascularization of the ectopic endometrium.


Immune checkpoint inhibitor induced colitis and arthritis: A case report.
As a programmed cell death 1 (PD-1) inhibitor, camrelizumab is used in the treatment of a variety of malignancies. However, a variety of immune-mediated adverse reactions have been reported in a wide range of clinical applications, including immune-related colitis, arthritis, hepatitis, etc. This 56-year-old male patient experienced diarrhea, bloody stool, and knee pain after receiving camrelizumab for metastatic esophageal squamous cell carcinoma. Colonoscopy showed granular changes in the whole colonic mucosa and blurred or even disappeared vascular texture. Pathology showed chronic inflammation of the colonic mucosa. Magnetic resonance imaging of knee joint showed exudative inflammatory changes in bilateral knee joints. Immune checkpoint inhibitor-induced colitis and arthritis. Mesalazine oral (extended-release granules, 1000 mg/quarter in die daily). Dexamethasone sodium phosphate (once daily, 5mg in the evening) and compound cypress liquid (once daily, 100ml in the evening) were given by enema. Anti-inflammatory and analgesic treatment of bone pain plaster. The patient had diarrhea reduced to 3 times/day, no more bloody stools, and the knee pain was relieved. This article describes the cases of immune-related colitis and arthritis caused by camrelizumab, and recommends considering the risk of colitis and arthritis with camrelizumab monotherapy or combination therapy.


Prevalence, incidence, risk factors and treatment of atrial fibrillation in Australia: The Australian Diabetes, Obesity and Lifestyle (AusDiab) longitudinal, population cohort study.
We sought to describe the prevalence, incidence, risk factors and treatment (according to stroke risk) of atrial fibrillation (AF) in the national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study cohort. ECG data were available from 8273/11,247 participants of AusDiab study in 1999/2000 and from 5422 participants in 2004/2005. Minnesota coding was used to identify prevalent and incident cases of AF. 90 prevalent cases of AF (14.1 per 1000) comprising 56 men (mean age 70.5 ± 1.9 years) and 34 women (aged 78.3 ± 1.2 years) were identified in 1999-2000. AF prevalence was associated with sedentary behaviour versus physically active (PR 2.0, 95% CI 1.2-3.6). 53 incident cases of AF (2.0, 95%, CI 1.5-2.6 per 1000 person-year) were subsequently identified in 2004-2005. Increased risk of incident AF was associated with male sex, obesity, history of angina, myocardial infarction and stroke. Both increased weight gain and increased weight loss appeared to be associated with increased risks of developing AF in women, while no obvious association was observed in men. Despite their high risk for stroke, anti-thrombotic therapy was observed in only 39.3% of participants with CHA2DS2-VASC scores ≥ 2. This study contributes to a better understanding of the AF burden. With the ageing population, coordinated efforts will be needed to anticipate the future health care costs related to AF and its impacts on the health care system. This will include appropriate application of anti-thrombotic therapy according to risk of thrombo-embolic events.


Horizontal canal BPV.
Benign paroxysmal vertigo (BPV) is generally attributed to a differential density condition in the posterior semicircular canal. Although the posterior canal is implicated because of its dependent position, the possibility exists that either the horizontal or superior canal could become involved. This paper reports on seven patients with a clinical picture consistent with horizontal canal BPV. The characteristic features are brief vertigo and horizontal nystagmus precipitated by head movement into or out of one of the lateral positions. Position change toward the left lateral position induces left beating nystagmus and vice versa for position change toward the right. The direction of the nystagmus indicates a utriculopetal "endolymph flow" when the affected horizontal canal is undermost. This could be explained by particle movement or a "viscous plug" in the posterior aspect of the canal.


Exploring New Alleles Involved in Tomato Fruit Quality in an Introgression Line Library of Solanum pimpinellifolium.
We have studied a genomic library of introgression lines from the Solanum pimpinellifolium accession TO-937 into the genetic background of the "Moneymaker" cultivar in order to evaluate the accession's breeding potential. Overall, no deleterious phenotypes were observed, and the plants and fruits were phenotypically very similar to those of "Moneymaker," which confirms the feasibility of translating the current results into elite breeding programs. We identified chromosomal regions associated with traits that were both vegetative (plant vigor, trichome density) and fruit-related (morphology, organoleptic quality, color). A trichome-density locus was mapped on chromosome 10 that had not previously been associated with insect resistance, which indicates that the increment of trichomes by itself does not confer resistance. A large number of quantitative trait loci (QTLs) have been identified for fruit weight. Interestingly, fruit weight QTLs on chromosomes 1 and 10 showed a magnitude effect similar to that of QTLs previously defined as important in domestication and diversification. Low variability was observed for fruit-shape-related traits. We were, however, able to identify a QTL for shoulder height, although the effects were quite low, thus demonstrating the suitability of the current population for QTL detection. Regarding organoleptic traits, consistent QTLs were detected for soluble solid content (SSC). Interestingly, QTLs on chromosomes 2 and 9 increased SSC but did not affect fruit weight, making them quite promising for introduction in modern cultivars. Three ILs with introgressions on chromosomes 1, 2, and 10 increased the internal fruit color, making them candidates for increasing the color of modern cultivars. Comparing the QTL detection between this IL population and a recombinant inbred line population from the same cross, we found that QTL stability across generations depended on the trait, as it was very high for fruit weight but low for organoleptic traits. This difference in QTL stability may be due to a predominant additive gene action for QTLs involved in fruit weight, whereas epistatic and genetic background interactions are most likely important for the other traits.


Introducing Namaste Care to the hospital environment: a pilot study.
The rising prevalence of dementia is impacting on acute hospitals and placing increased expectations on health and social care professionals to improve the support and services they are delivering. It has been recommended that good practice in dementia care relies on adopting a palliative approach to care and meeting people's physical, psychological, social and spiritual needs. Increased dementia training for staff that includes initiatives that promote dignity; enhancing communication skills and recognizing that a person with dementia may be approaching the end of their lives are needed. Our study aim was to explore whether Namaste Care is an acceptable and effective service for people with advanced dementia being cared for on an acute hospital ward. This was an exploratory qualitative interview, pilot study. Individual, semi-structured, face-to-face interviews were conducted with hospital healthcare staff working in an area of the hospital where Namaste Care had been implemented. Data were analysed using the framework approach. Eight interviews were completed with members of the multidisciplinary ward team. Two themes were identified: (I) difficulties establishing relationships with people with dementia in hospital (subthemes: lack of time and resources, lack of confidence leading to fear and anxiety); (II) the benefits of a Namaste Care service in an acute hospital setting (subthemes: a reduction in agitated behavior; connecting and communicating with patients with dementia using the senses; a way of showing people with dementia they are cared for and valued). This small-scale study indicates that Namaste Case has the potential to improve the quality of life of people with advanced dementia being cared for in an acute hospital setting. However, further research is required to explore more specifically its benefits in terms of improved symptom management and wellbeing of people with dementia on acute hospitals wards.


Association between serum triglyceride and canine pancreatic lipase immunoreactivity concentrations in miniature schnauzers.
The objective of this study was to investigate possible associations between serum triglyceride and canine pancreatic lipase immunoreactivity (cPLI) concentrations in miniature schnauzers. One hundred and ninety-five miniature schnauzers were enrolled and divided into two groups based on whether they had normal (group 1) or increased (group 2) serum triglyceride concentrations. Serum cPLI concentrations were measured and compared between groups. A significant positive correlation was seen between serum triglyceride and cPLI concentrations (Spearman r=0.321; P<0.0001). Miniature schnauzers with hypertriglyceridemia had a significantly higher median serum cPLI concentration (99.5 microg/L) than miniature schnauzers with normal serum triglyceride concentrations (median cPLI concentration 39.3 microg/L; P=0.0001). A cutoff value of 862 mg/dL was selected for serum triglyceride concentrations based on receiver operator characteristic analysis. Miniature schnauzers with severe hypertriglyceridemia (> or =862 mg/dL) were 4.5 times more likely to have a serum cPLI concentration consistent with pancreatitis (> or =200 microg/L) than miniature schnauzers with a normal serum triglyceride concentration. The present study supports an association between hypertriglyceridemia (especially when severe [> or =862 mg/dL]) and high cPLI concentrations in miniature schnauzers.


Alcohol drinking among college students: college responsibility for personal troubles.
One young adult in two has entered university education in Western countries. Many of these young students will be exposed, during this transitional period, to substantial changes in living arrangements, socialisation groups, and social activities. This kind of transition is often associated with risky behaviour such as excessive alcohol consumption. So far, however, there is little evidence about the social determinants of alcohol consumption among college students. We set out to explore how college environmental factors shape college students' drinking behaviour. In May 2010 a web questionnaire was sent to all bachelor and master students registered with an important Belgian university; 7,015 students participated (participation = 39%). The survey looked at drinking behaviour, social involvement, college environmental factors, drinking norms, and positive drinking consequences. On average each student had 1.7 drinks a day and 2.8 episodes of abusive drinking a month. We found that the more a student was exposed to college environmental factors, the greater the risk of heavy, frequent, and abusive drinking. Alcohol consumption increased for students living on campus, living in a dormitory with a higher number of room-mates, and having been in the University for a long spell. Most such environmental factors were explained by social involvement, such as participation to the student folklore, pre-partying, and normative expectations. Educational and college authorities need to acknowledge universities' responsibility in relation to their students' drinking behaviour and to commit themselves to support an environment of responsible drinking.


School Principals' Work Participation in an Extended Working Life-Are They Able to, and Do They Want to? A Quantitative Study of the Work Situation.
The objective of this study is to increase the knowledge regarding school principals' work situations by examining the associations between various factors and the school principals' assessments of their ability or wish to work until 65 years of age or longer. The 1356 participating school principals in this study were aged between 50 and 64 years of age. Individual and work factors were evaluated in relation to two dichotomized outcomes: i.e., can work and want to work beyond 65 years of age, respectively. Generalized Estimating Equations (GEE) models were used to specify bivariate and multivariate cross-sectional logistic regression models that accounted for repeated measurements. The results showed that, both in 2018 and 2019, about 83% of the school principals stated that they could work and about 50% stated that they wanted to work until 65 years of age and beyond. School principals' exhaustion symptoms and experiences of an excessive burden were statistically significantly associated with whether they both could not and did not want to work beyond 65 years of age. Additionally, the school principals' experiences of support from the executive management in the performance of their managerial duties was of primary importance for whether the school principals wanted to work until 65 years of age and beyond. To conclude, it is important that school principals receive sufficient support from the management to cope with their often very stressful leadership tasks so that they have the opportunity to be able and willing to continue working their entire working life. The study strengthens the robustness of the theoretical SwAge model regarding the investigated factors related to determinant factors for a sustainable working life and as a basis for developing practical tools for increased employability for people of older ages.


High HIV incidence in men who have sex with men following an early syphilis diagnosis: is there room for pre-exposure prophylaxis as a prevention strategy?
HIV pre-exposure prophylaxis (PrEP) is becoming a pivotal strategy for HIV prevention. Understanding the impact of risk factors for HIV transmission to identify those at highest risk would favour the implementation of PrEP, currently limited by costs. In this service evaluation, we estimated the incidence of bacterial STIs in men who have sex with men (MSM) diagnosed with early syphilis attending a London sexual health clinic according to their HIV status. In addition, we estimated the incidence of HIV infection in HIV-negative MSM, following a diagnosis of early syphilis. We undertook a retrospective case note review of all MSM patients diagnosed with early syphilis between January and June 2014. A number of sexual health screens and diagnoses of chlamydia, gonorrhoea and HIV were prospectively analysed following the syphilis diagnosis. 206 MSM were diagnosed with early syphilis. 110 (53%) were HIV-negative at baseline, 96 (47%) were HIV-positive. Only age (37 vs 32 years, p=0.0005) was significantly different according to HIV status of MSM at baseline. In HIV-negative versus HIV-positive MSM, incidence of rectal chlamydia infection at follow-up was 27 cases vs 50/100 person-years of follow-up (PYFU) (p=0.0039), 33 vs 66/100 PYFU (p=0.0044) for rectal gonorrhoea and 10 vs 26/100 PYFU (p=0.0044) for syphilis reinfection, respectively. Total follow-up for 110 HIV-negative MSM was 144 person-years. HIV incidence was 8.3/100 PYFU (CI 4.2 to 14). A diagnosis of early syphilis carries a high risk of consequent HIV seroconversion and should warrant prioritised access to prevention measures such as PrEP and regular STI screening to prevent HIV transmission.


The changing face of HIV in pregnancy in Rhode Island 2004-2009.
Meeting the needs of HIV-infected pregnant women requires understanding their backgrounds and potential barriers to care and safe pregnancy. Foreign-born women are more likely to have language, educational, and economic barriers to care, but may be even more likely to choose to keep a pregnancy. Data from HIV-infected pregnant women and their children in Rhode Island were analyzed to identify trends in demographics, viral control, terminations, miscarriages, timing of diagnosis, and adherence to followup. Between January 2004 and December 2009, 76 HIV-infected women became pregnant, with a total of 95 pregnancies. Seventy-nine percent of the women knew their HIV status prior to becoming pregnant. Fifty-four percent of the women were foreign-born and 38 percent of the 16 women who chose to terminate their pregnancies were foreign-born. While the number of HIV-infected women becoming pregnant has increased only slightly, the proportion that are foreign-born has been rising, from 41 percent between 2004 and 2005 to 57.5 percent between 2006 and 2009. A growing number of women are having multiple pregnancies after their HIV diagnosis, due to the strength of their desire for childbearing and the perception that HIV is a controllable illness that does not preclude the creation of a family.


Prevalence of perceived symptoms of dry mouth in an adult Swedish population--relation to age, sex and pharmacotherapy.
The aim of the study was to evaluate the prevalence of subjective perception of dry mouth in an adult population and to determine the prevalence of pharmacotherapy in this population. An additional aim was to assess a possible co-morbidity between symptoms of dry mouth and continuing pharmacotherapy. Four-thousand-two-hundred persons were selected at random from the national census register of the adult population of the southern part of the province of Halland, Sweden. The sample was stratified according to age and sex, and 300 men and an equal number of women aged 20, 30, 40, 50, 60, 70 and 80, were included. A newly developed questionnaire was mailed to each individual. In addition to questions about subjective perception of dry mouth, the subjects were asked to report on present diseases and continuing pharmacotherapy. Three-thousand-three-hundred and thirteen (80.5%) evaluable questionnaires were returned. The estimated prevalence of xerostomia in the population was 21.3% and 27.3% for men and women, respectively. This difference between the sexes was statistically significant. In non-medicated subjects, women tended to report a higher prevalence of xerostomia compared with men, 18.8% vs. 14.6%, and also among medicated subjects the estimated prevalence of dry mouth was higher for women than for men, 32.5% vs. 28.4%. There was a strong association between xerostomia and increasing age and also between xerostomia and continuing pharmacotherapy. The average prevalence of dry mouth among medicated and non-medicated subjects was 32.1% and 16.9%, respectively, the difference being statistically significant. There was also a strong association between xerostomia and the number of medications. In a logistic regression, the probability of reporting mouth dryness was significantly greater in older subjects and in women, and the probability increased with the number of medications taken. In conclusion, this epidemiological survey of an adult population has demonstrated that women, independent of age, do report a higher prevalence of xerostomia than men and that the symptom of dry mouth is strongly associated with age and pharmacotherapy. It is, however, not possible to discriminate between disease and pharmacotherapy as causal factors.


Ovarian hyperstimulation syndrome.
Eighteen patients hospitalized for excessive ovarian hyperstimulation syndrome are reported. In 14 cases the ovarian hyperstimulation was induced by human menopausal -onadotropins and in 4 cases by combined treatment with clomiphene and HCG. In 5 patients the hyperstimulation was associated with conception, which resulted in 1 quintuplet delivery, 1 early quintuplet abortion, 1 twin abortion, 1 normal delivery, and 1 missed abortion. The regimen of treatment was a conservative one. The patients were hospitalized and treated with infusion of plasma expanders. Anticoagulant therapy was administered only in cases that showed clinical evidence of thromboembolic pheomena or laboratory evidence of severe hemoconcentration. The pathogenesis of the ovarian hyperstimulation syndrome, prevention, and management are discussed. This syndrome should be diagnosed early and treated intensively.


Postural control skills, proprioception, and risk of fall in long-term survivor patients treated with knee rotationplasty.
Knee A1 rotationplasty is a particular type of limb salvage surgery alternative to hip disarticulation and high transfemoral amputation for skeletally immature children with bone cancers in the distal femur. Notwithstanding optimal functional outcomes, long-term survivor patients often report frequent falls, and a sense of instability during gait, particularly on uneven terrain. This study aimed to assess the postural control, the proprioception, and the risk of fall in these patients, which have not been explored before. Eighteen long-term survivor patients participated in the study. The mean follow-up from surgery was 23 years, mean age 32 years. Patients were assessed using a specific instrumental device (Delos Postural Proprioceptive System) both for the static double-stance and the single-stance test in the open eyes and closed eyes conditions. The double-stance test showed postural instability values within the normal range for healthy individuals, whereas in the single-stance test stability index, when assessed in the average of both lower limbs, values were lower than the literature findings for older individuals. However, when separating the operated from the nonoperated limb performance, standing on the operated limb was very unstable, with a low stability index and a low degree of autonomy, indicating a certain risk of falling, whereas standing on the nonoperated limb had a performance close to normal or even superior. In conclusion, knee rotationplasty patients had very good postural control when standing on both limbs, whereas single stance on the operated limb was compromised, with particular involvement of the proprioceptive component. This may determine a higher risk of falling than their normal-age counterparts and rehabilitation intervention for prevention is indicated.


Quality assurance by service quality--an industrial approach to monitoring course delivery.
To evaluate the use of an adapted customer service quality questionnaire as a management tool in the delivery of an undergraduate phantom head course. Two questionnaires, based upon an industrial definition of quality service, were devised and distributed for completion by second year dental students attending the management of dental caries course. These were applied to the academic years 1997/98 and 1999/2000. The first questionnaire was prospective, administered prior to course commencement, and sought to ascertain the level of importance attached to each dimension of course delivery. The second was retrospective and measured the level of satisfaction with course delivery. By comparing the 1997/98 responses for both questionnaire types, areas requiring improvement were identified. Where these areas were emphasised prospectively as important by the 1999/2000 students' improvement measures were introduced. Their effect was assessed by the subsequent retrospective satisfaction questionnaire. In all cases the questionnaire return rate was 100%. Although across the academic years overall student expectations did not differ significantly (P > 0.05) the emphasis of different components was found to vary according to academic year. The application of this technique assists the course organiser to make objective decisions on improving course delivery based upon the shortfalls of the previous year and the pre-course expectations of the following academic year. The industrial model thus translated well to an educational context and should prove useful in continually improving course delivery.


Four functional profiles for fibre and mucin metabolism in the human gut microbiome.
With the emergence of metagenomic data, multiple links between the gut microbiome and the host health have been shown. Deciphering these complex interactions require evolved analysis methods focusing on the microbial ecosystem functions. Despite the fact that host or diet-derived fibres are the most abundant nutrients available in the gut, the presence of distinct functional traits regarding fibre and mucin hydrolysis, fermentation and hydrogenotrophic processes has never been investigated. After manually selecting 91 KEGG orthologies and 33 glycoside hydrolases further aggregated in 101 functional descriptors representative of fibre and mucin degradation pathways in the gut microbiome, we used nonnegative matrix factorization to mine metagenomic datasets. Four distinct metabolic profiles were further identified on a training set of 1153 samples, thoroughly validated on a large database of 2571 unseen samples from 5 external metagenomic cohorts and confirmed with metatranscriptomic data. Profiles 1 and 2 are the main contributors to the fibre-degradation-related metagenome: they present contrasted involvement in fibre degradation and sugar metabolism and are differentially linked to dysbiosis, metabolic disease and inflammation. Profile 1 takes over Profile 2 in healthy samples, and unbalance of these profiles characterize dysbiotic samples. Furthermore, high fibre diet favours a healthy balance between profiles 1 and profile 2. Profile 3 takes over profile 2 during Crohn's disease, inducing functional reorientations towards unusual metabolism such as fucose and H2S degradation or propionate, acetone and butanediol production. Profile 4 gathers under-represented functions, like methanogenesis. Two taxonomic makes up of the profiles were investigated, using either the covariation of 203 prevalent genomes or metagenomic species, both providing consistent results in line with their functional characteristics. This taxonomic characterization showed that profiles 1 and 2 were respectively mainly composed of bacteria from the phyla Bacteroidetes and Firmicutes while profile 3 is representative of Proteobacteria and profile 4 of methanogens. Integrating anaerobic microbiology knowledge with statistical learning can narrow down the metagenomic analysis to investigate functional profiles. Applying this approach to fibre degradation in the gut ended with 4 distinct functional profiles that can be easily monitored as markers of diet, dysbiosis, inflammation and disease. Video Abstract.


Cystic hypersecretory duct carcinoma of the breast.
This report describes a grossly and microscopically distinctive multicystic form of duct carcinoma of the breast which we have termed cystic hypersecretory duct carcinoma. The outstanding morphologic feature is marked secretory activity with the formation of dilated ducts and cysts containing homogeneous, eosinophilic material which resembles thyroid colloid. The inconspicuous epithelium lining the cysts gives rise to micropapillary carcinoma which also occurs in associated ducts. A biopsy that consists entirely of cystic elements, lacking the papillary component, should be termed cystic hypersecretory hyperplasia rather than carcinoma. This may be a persistent condition with the potential to evolve into carcinoma. Eight patients with cystic hypersecretory duct carcinoma were studied, ranging in age from 32 to 78 years (mean 54). In two cases there was coexistent invasive carcinoma, presenting as inflammatory carcinoma with bone metastases in one woman and with a single axillary lymph node metastasis in another. Six patients with intraductal carcinoma treated with mastectomy or local excision have remained well, the longest follow-up being 2 years. Histochemical studies were negative for thyroglobulin in all cases studied. Some lesions were positive for one or more of the following: mucin by mucicarmine stain; carcinoembryonic antigen; alpha-lactalbumin; mouse mammary tumor virus GP52 antigen. Cystic hypersecretory duct carcinoma is morphologically distinguishable from juvenile (secretory) carcinoma and from mucinous (colloid) carcinoma. Longer follow-up and study of additional cases will be necessary to determine if this lesion has distinctive clinical characteristics.


Apolipoprotein E genotype and schizophrenia.
Schizophrenic disorders are complex genetic disorders and may involve multiple genes of small effect. The presence of apolipoprotein E (apoE) is associated with several neuropsychiatric disorders. Previous studies on apoE genotype distribution in schizophrenia have reported conflicting findings. We studied the genotype frequencies in a large group of schizophrenic patients. The genotype distribution was significantly different between the schizophrenic patients and the control subjects. Persons who were sigma3 carriers have an increased risk of schizophrenia. This result suggests that apoE isoforms may play a functional role in the pathogenesis of schizophrenic disorders. Some possible mechanisms regarding the effect of apoE on the development of schizophrenia are discussed.


Impact of climate change and other factors on emerging arbovirus diseases.
While some skeptics remain unconvinced that global climate change is a reality, there is no doubt that during the past 50 years or so, patterns of emerging arbovirus diseases have changed significantly. Can this be attributed to climate change? Climate is a major factor in determining: (1) the geographic and temporal distribution of arthropods; (2) characteristics of arthropod life cycles; (3) dispersal patterns of associated arboviruses; (4) the evolution of arboviruses; and (5) the efficiency with which they are transmitted from arthropods to vertebrate hosts. Thus, under the influence of increasing temperatures and rainfall through warming of the oceans, and alteration of the natural cycles that stabilise climate, one is inevitably drawn to the conclusion that arboviruses will continue to emerge in new regions. For example, we cannot ignore the unexpected but successful establishment of chikungunya fever in northern Italy, the sudden appearance of West Nile virus in North America, the increasing frequency of Rift Valley fever epidemics in the Arabian Peninsula, and very recently, the emergence of Bluetongue virus in northern Europe. In this brief review we ask the question, are these diseases emerging because of climate change or do other factors play an equal or even more important role in their emergence?


Three-year outcomes for maintenance therapies in recurrent depression.
We conducted a randomized 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy. A five-cell design was used to determine whether a maintenance form of interpersonal psychotherapy alone or in combination with medication could play a significant role in the prevention of recurrence. A second question was whether maintaining antidepressant medication at the dosage used to treat the acute episode rather than decreasing to a "maintenance" dosage would provide prophylaxis superior to that observed in earlier trials in which a maintenance dosage strategy was employed. Survival analysis demonstrated a highly significant prophylactic effect for active imipramine hydrochloride maintained at an average dose of 200 mg and a modest prophylactic effect for monthly interpersonal psychotherapy. We conclude that active imipramine hydrochloride maintained at an average dose of 200 mg is an effective means of preventing recurrence and that monthly interpersonal psychotherapy serves to lengthen the time between episodes in patients not receiving active medication.


Non-linear partitioning and organic volatility distributions of urban aerosols.
Gas-to-particle partitioning of organic aerosols (OA) is represented in most models by Raoult's law, and depends on the existing mass of particles into which organic gases can dissolve. This raises the possibility of non-linear response of particle-phase OA mass to the emissions of precursor volatile organic compounds (VOCs) that contribute to this partitioning mass. Implications for air quality management are evident: a strong non-linear dependence would suggest that reductions in VOC emission would have a more-than-proportionate benefit in lowering ambient OA concentrations. Chamber measurements on simple VOC mixtures generally confirm the non-linear scaling between OA and VOCs, usually stated as a mass-dependence of the measured OA yields. However, for realistic ambient conditions including urban settings, no single component dominates the composition of the organic particles, and deviations from linearity are presumed to be small. Here we re-examine the linearity question using volatility spectra from several sources: (1) chamber studies of selected aerosols, (2) volatility inferred for aerosols sampled in two megacities, Mexico City and Paris, and (3) an explicit chemistry model (GECKO-A). These few available volatility distributions suggest that urban OA may be only slightly super-linear, with most values of the normalized sensitivity exponent in the range 1.1-1.3, also substantially lower than seen in chambers for some specific aerosols. The rather low exponents suggest that OA concentrations in megacities are not an inevitable convergence of non-linear effects, but can be addressed (much like in smaller urban areas) by proportionate reductions in emissions.


Gravitropism of Arabidopsis thaliana roots requires the polarization of PIN2 toward the root tip in meristematic cortical cells.
In the root, the transport of auxin from the tip to the elongation zone, referred to here as shootward, governs gravitropic bending. Shootward polar auxin transport, and hence gravitropism, depends on the polar deployment of the PIN-FORMED auxin efflux carrier PIN2. In Arabidopsis thaliana, PIN2 has the expected shootward localization in epidermis and lateral root cap; however, this carrier is localized toward the root tip (rootward) in cortical cells of the meristem, a deployment whose function is enigmatic. We use pharmacological and genetic tools to cause a shootward relocation of PIN2 in meristematic cortical cells without detectably altering PIN2 polarization in other cell types or PIN1 polarization. This relocation of cortical PIN2 was negatively regulated by the membrane trafficking factor GNOM and by the regulatory A1 subunit of type 2-A protein phosphatase (PP2AA1) but did not require the PINOID protein kinase. When GNOM was inhibited, PINOID abundance increased and PP2AA1 was partially immobilized, indicating both proteins are subject to GNOM-dependent regulation. Shootward PIN2 specifically in the cortex was accompanied by enhanced shootward polar auxin transport and by diminished gravitropism. These results demonstrate that auxin flow in the root cortex is important for optimal gravitropic response.


Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood.
With several therapeutic approaches in development for Huntington's disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response. We performed next-generation sequencing-based transcriptome analysis of total RNA from peripheral blood of 91 mutation carriers (27 presymptomatic and, 64 symptomatic) and 33 controls. Transcriptome analysis by DeepSAGE identified 167 genes significantly associated with clinical total motor score in Huntington's disease patients. Relative to previous studies, this yielded novel genes and confirmed previously identified genes, such as H2AFY, an overlap in results that has proven difficult in the past. Pathway analysis showed enrichment of genes of the immune system and target genes of miRNAs, which are downregulated in Huntington's disease models. Using a highly parallelized microfluidics array chip (Fluidigm), we validated 12 of the top 20 significant genes in our discovery cohort and 7 in a second independent cohort. The five genes (PROK2, ZNF238, AQP9, CYSTM1 and ANXA3) that were validated independently in both cohorts present a candidate biomarker panel for stage determination and therapeutic readout in Huntington's disease. Finally we suggest a first empiric formula predicting total motor score from the expression levels of our biomarker panel. Our data support the view that peripheral blood is a useful source to identify biomarkers for Huntington's disease and monitor disease progression in future clinical trials.


Potential mechanisms underpinning the nutritional modulation of periodontal inflammation.
Periodontitis results from an inappropriate host response to pathogenic biofilms. Because traditional management approaches have failed to reduce disease prevalence, the research focus has shifted toward managing host-mediated inflammation. In this article, the author reviews the role of nutrition in the development and resolution of inflammation. The author reviewed the biomedical literature to elucidate mechanisms by which dietary factors affect inflammatory processes and to establish what evidence exists for macronutritional and micronutritional modulation of inflammation at a cellular and molecular level. Hyperinflammation characterizes the periodontitis phenotype, and oxidative stress is a key orchestration point for the diverse signaling pathways, which control inflammation. Oxidative stress is modulated by diet, as well as by infection. Recent research has demonstrated that subtle shifts in nutritional status are associated independently with the prevalence of periodontitis. Moreover, the results of contemporary animal and human studies have demonstrated the role of specific micronutrients in the modulation of the host's inflammatory response by reducing inflammatory biomarkers and bone loss. The scientific community is starting to realize the health benefits of diets containing foods naturally rich in antioxidants and omega-3 polyunsaturated fatty acids, as well as the dangers of diets that are high in refined carbohydrates. Nutritional intervention studies in patients with inflammatory periodontitis are needed to evaluate the effect of nutritional approaches to periodontal management.


Benefits and harms of lower blood pressure treatment targets: systematic review and meta-analysis of randomised placebo-controlled trials.
To assess the effect of antihypertensive treatment in the 130-140 mm Hg systolic blood pressure range. Systematic review and meta-analysis. PubMed, CDSR and DARE were searched for the systematic reviews, which were manually browsed for clinical trials. PubMed and Cochrane Central Register of Controlled Trials were searched for trials directly in February 2018. Randomised double-blind trials with ≥1000 patient-years of follow-up, comparing any antihypertensive agent against placebo. Two reviewers extracted study-level data, and assessed risk of bias using Cochrane Collaborations risk of bias assessment tool, independently. Primary outcomes were all-cause mortality, major cardiovascular events and discontinuation due to adverse events. Secondary outcomes were cardiovascular mortality, myocardial infarction, stroke, heart failure, hypotension-related adverse events and renal impairment. Eighteen trials, including 92 567 participants (34% women, mean age 63 years), fulfilled the inclusion criteria. Primary preventive antihypertensive treatment was associated with a neutral effect on all-cause mortality (relative risk 1.00, 95% CI 0.95 to 1.06) and major cardiovascular events (1.01, 0.96 to 1.06), but an increased risk of discontinuation due to adverse events (1.23, 1.03 to 1.47). None of the secondary efficacy outcomes were significantly reduced, but the risk of hypotension-related adverse events increased with treatment (1.71, 1.32 to 2.22). In coronary artery disease secondary prevention, antihypertensive treatment was associated with reduced risk of all-cause mortality (0.91, 0.83 to 0.99) and major cardiovascular events (0.85, 0.77 to 0.94), but doubled the risk of adverse events leading to discontinuation (2.05, 1.62 to 2.61). Primary preventive blood pressure lowering in the 130-140 mm Hg systolic blood pressure range adds no cardiovascular benefit, but increases the risk of adverse events. In the secondary prevention, benefits should be weighed against harms. CRD42018088642.


Estimation of exposure-attributable fractions from time series: A simulation study.
Burden analysis in public health often involves the estimation of exposure-attributable fractions from observed time series. When the entire population is exposed, the association between the exposure and outcome must be carefully modelled before the attributable fractions can be estimated. This article derives asymptotic convergences for the estimation of attributable fractions for commonly used time series models (ARMAX, Poisson, negative binomial, and Serfling), using for the most part the delta method. For the Poisson regression, the estimation of the attributable fraction is achieved by a Monte Carlo algorithm, taking into account both an estimation and a prediction error. A simulation study compares these estimations in the case of an epidemic exposure and highlights the importance of thorough analysis of the data: When the outcome is generated under an additive model, the additive models are satisfactory, and the multiplicative models are poor, and vice versa. However, the Serfling model performs poorly in all cases. Of note, a misspecification in the form or delay of the association between the exposure and the outcome leads to mediocre estimation of the attributable fraction. An application to the fraction of French outpatient antibiotic use attributable to influenza between 2003 and 2010 illustrates the asymptotic convergences. This study suggests that the Serfling model should be avoided when estimating attributable fractions while the model of choice should be selected after careful investigation of the association between the exposure and outcome.


[Molecular analysis of certain derivatives of mutants with the unstable white-starka allele].
Molecular analysis of several mutations of the white locus was performed. The mutations were obtained as a result of mutagenesis in the unstable white-starka locus described previously. A large insert (approximately 15 kb in length) downstream of the first exon of the white gene was shown to be partly excised. Simultaneous excisions of various regions from the natural regulatory region of the white locus were also observed. Restriction enzyme analysis showed that the observed mutations and reversions resulted from large deletions from the regulatory gene region. Southern and Northern blot hybridization showed the presence of unknown regulatory regions within and outside the insert.


B-prolymphocytic leukaemia with t(11;14) revisited: a splenomegalic form of mantle cell lymphoma evolving with leukaemia.
We reviewed eight cases that were diagnosed before 1995 with B-prolymphocytic leukaemia (B-PLL) harbouring t(11;14)(q13;q32) and/or cyclin D1 staining. Thirteen B-PLL patients without t(11;14) were selected as controls. Peripheral blood, bone marrow and histological sections were re-examined without cytogenetic information. Final diagnosis was made using morphology, cytogenetics, immunophenotype and immunohistochemistry. Clinical characteristics were similar for both groups except for younger age, male predominance and extranodal involvement in cases with t(11;14). CD5 was more frequently positive in the t(11;14)+ group (80%) than in the t(11;14)- group (31%). Surface membrane immunoglobulin was strongly expressed by all t(11;14)+ cases, but only 45% of t(11;14)- cases. Histopathological and cytological review of cases with t(11;14) showed an infiltrate with a mixture of cells, some resembling prolymphocytes and others with mantle cell lymphoma (MCL) morphology. Blood films of cases with t(11;14) showed features suggestive of B-PLL in three, and in others, a mixture of cells resembling MCL and nucleolated ones; none corresponded to the blastoid form of MCL. We suggest that 'B-PLL' with t(11;14) may represent a splenomegalic form of MCL evolving with leukaemia. These cases illustrate the importance of tissue diagnosis with cyclin D1 staining and fluorescence in situ hybridization analysis in B-cell leukaemia with prolymphocytic features.


The Life and Work of Dr. Beadie Eugene Conner: An African American Physician in Jim Crow Texas.
[[On a bright, sunny day in late May 1980, commencement exercises were underway at Meharry Medical College in Nashville, Tennessee. More than 250 physicians, dentists, nurses, candidates in health administration, dental hygienists, and medical technicians prepared to receive their certifications from the second-oldest historically black medical school in the country. Wearing a brown gabardine suit, Dr. Beadie Eugene Conner prepared to be called up to the podium along with some former classmates of Meharry's class of 1930 to receive a plaque commemorating fifty years of public service. As he made his way up to the podium, tears began to well up in his eyes as he thought about his mother who would be so proud of him, his deceased wife, Willie Ruel, their daughter, Georgia, and the many years that had passed since he received his medical degree. The event contributed to the retired doctor's desire to write an autobiography. Though never completed, rough drafts of the manuscript's early chapters (along with other existing personal documents) provide an invaluable window into the interesting life of an important African American physician in twentieth-century Texas.1 The Conner family's emphasis on education started long before Beadie was born. The earliest relatives of Dr. Conner so far identified are William Conner and Rachel Sterling Conner of Blount County, in eastern Tennessee. Family records indicate that William was born a slave in Knox County, Tennessee, sometime in 1814. He had already purchased his freedom by 1843 when he married Rachel Sterling, a woman born in 1829 into a free black family. William and Rachel lived on a Blount County farm through the Civil War years, raising six boys and one girl. Beadie Conner's father, David Alexander Conner, was the fourth oldest son, born in 1859. After William died in 1866, Rachel moved the family to Louisville (a community in Blount County not to be confused with the city in Kentucky), where she kept house while David and his two youngest brothers attended school. By the late 1870s, the family had relocated to Knoxville before breaking up and going their separate ways. Among David's siblings, his sister became a schoolteacher, two brothers served as ministers, one brother became a successful mortician, and his youngest brother, George Sherman Conner (destined to become a role model for young Beadie), started out as a teacher in Paris, Texas, before becoming a physician and important community leader in Waco.2 Much had transpired in David Alexander Conner's life by the time his twin children Beadie and Beatrice were born on July 8, 1902, in Miller County, Arkansas, on a farm along the banks of the Red River. A widower living with six children from his previous marriage, he had met Queen Fowler Newlin, a short, beautiful woman of French and Choctaw extraction while attending a Baptist convention in Hope, Arkansas, in 1900. After a brief correspondence and courtship, the two married in 1901. Queen had five children from her previous marriage, thus Beadie and Beatrice became the youngest additions to a family already containing eleven brothers and sisters...]]


Repeated systematic surveillance of Kawasaki disease in Ontario from 1995 to 2006.
Rising incidences of Kawasaki disease (KD) have been reported worldwide. Reported herein are the results of 4 triennial KD surveillances conducted in Ontario. Between 1995 and 2006 all hospitals in Ontario were asked on 4 occasions to identify all patients with discharge diagnoses of KD and report incident cases. The latest surveillance identified 697 new KD patients (100% response rate) for a total of 2378 KD patients through all 4 surveillances. Yearly incidence was 26.2/100,000 for <5 years old, 6.7/100,000 for 5-9 years old and 0.9/100,000 for 10-14 years old. KD incidence significantly increased from 1995 to 2006, although the increase seemed to plateau between the 3rd and 4th surveillance. There was an increase in the proportion of patients diagnosed with incomplete KD and a significant reduction in the rate of coronary artery abnormalities, possibly due to better disease recognition and treatment. Hospitals reporting <20 cases per surveillance were found to be more likely to report cases with incomplete KD. These patients were also less likely to be treated with i.v. immunoglobulin and aspirin but were more likely to be treated with antibiotics, suggesting uncertainties regarding diagnosis and management of KD patients in those centers. The incidence of KD in Ontario is possibly one of the highest outside of Asia and has been rising since 1995. Although the most recent surveillance demonstrated improved cardiac outcomes, treatment delays or absence thereof continue to be a problem. Effective diagnosis and prompt treatment remain critical aspects of KD management.


An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha.
Posttranslational modifications are instrumental to achieve gene- and tissue-specific regulatory outcomes by transcription factors. Nuclear receptors are dynamically modulated by several types of posttranslational modifications including phosphorylation, methylation, acetylation, ubiquitination, and sumoylation. The estrogen-related receptor alpha (ERRalpha, NR3B1) is phosphorylated on multiple sites, and sumoylated in the amino-terminal region in a phosphorylation-dependent manner. Here we demonstrate that ERRalpha interacts with and is acetylated by p300 coactivator associated factor (PCAF) in vitro and in mouse liver. Purified PCAF acetylated the DNA-binding domain of ERRalpha on four highly-conserved lysines. In addition, coexpression of PCAF reduced the transcriptional activity of ERRalpha and, reciprocally, a deacetylase screen identified histone deacetylase 8 (HDAC8) and sirtuin 1 homolog (Sirt1) as independent enhancers of ERRalpha transcriptional function. HDAC8 and Sirt1 were also demonstrated to interact directly with ERRalpha in vivo and to deacetylate and increase the DNA binding affinity of ERRalpha in vitro. The removal of PCAF increases the DNA binding of ERRalpha in vivo, whereas the removal of Sirt1 and HDAC8 decreases it as assessed by chromatin immunoprecipitation assay. Altogether, our results show that ERRalpha is an acetylated protein and imply the existence of a dynamic acetylation/deacetylation switch involved in the control of ERRalpha transcriptional activity.


Text messaging and lottery incentive to improve colorectal cancer screening outreach at a community health center: A randomized controlled trial.
Efforts to boost colorectal cancer (CRC) screening rates in underserved populations have been limited by effectiveness and scalability. We evaluate the impact of adding a lottery-based financial incentive to a text messaging program that asks patients to opt-in to receive mailed fecal immunochemical testing (FIT). This is a two-arm pragmatic randomized controlled trial at a community health center in Southwest Philadelphia from April to July 2017. We included CRC screening-eligible patients between ages 50-74 years who had a mobile phone, active health insurance, and at least one visit to the clinic in the past 12 months. Patients received a text message about CRC screening with the opportunity to opt-in to receive mailed FIT. They were randomized 1:1 to the following: (1) text messaging outreach alone (text), or (2) text messaging with lottery for a 1-in-5 chance of winning $100 after FIT completion (text + lottery). The primary outcome was the percentage of patients completing the mailed FIT within 3 months of initial outreach. 281 patients were included in the intent-to-treat analysis. The FIT completion rate was 12.1% (95% CI, 6.7%-17.5%) in the text message arm and 12.1% (95% CI, 6.7%-17.5%) in the lottery arm, with no statistical difference between arms. The majority of post-intervention interview respondents found text messaging to be acceptable and convenient. Opt-in text messaging is a feasible option to promote the uptake of mailed FIT screening, but the addition of a lottery-based incentive did not improve completion rates. Trial Registration: clinicaltrials.gov (NCT03072095).


Carbon paste biosensor based on crude soybean seed hull extracts for phenol detection.
In this study, a novel biosensor based on enzyme extracts from soybean seed hulls has been prepared, which demonstrated promising results in the detection of hydrogen peroxide and phenol. The biosensor preparation is straightforward and inexpensive, and the response time is 50 s. The optimum conditions of pH and temperature are a pH of 7.4 and a temperature of 20 degrees C. Contrary to expectations, the biosensor showed narrow pH and temperature optimums. The effects of enzyme loading and type of mediator were also investigated. The biosensor showed a linear response up to 500 microM phenol.


Iron as a Central Player and Promising Target in Cancer Progression.
Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.


Polymorphism of C lambda genes and units of duplication in the genus Mus.
The number of Ig C lambda genes in nine geographically widespread species from the four subgenera in the genus Mus was estimated from the number of Bam HI and Eco RI restriction fragments that hybridize under high stringency conditions to cDNA probes of BALB/c inbred mouse origin (Mus musculus domesticus). Three closely related species in the subgenus Mus, M. musculus, M. spretus, and M. spicelegus, show considerable variation in the number of C lambda genes. Estimates of gene numbers in these animals range from two C lambda genes in M. spretus from Puerto Real, Spain to 12 C lambda genes in M. musculus musculus from Studenec, Czechoslovakia. Strains of mice carrying either six or 10 C lambda genes were derived from a single population of M. musculus domesticus from Centreville, MD. The hybridization patterns of mice exhibiting C lambda gene amplification indicate that duplications are of relatively recent origin and probably occurred by reiteration of a DNA segment closely related to the 6.5 kb [C lambda 3 - C lambda 1] unit found in BALB/c inbred mice. Three more distantly related species in the subgenus Mus, and a species representing the Nannomys subgenus all appear to carry only four C lambda genes. DNA of species representing the Coelomys and Pyromys subgenera hybridized weakly to the C lambda cDNA probes, but these animals also have no more than four C lambda genes. Thus, there may be a base number of four C lambda genes in most species in the genus Mus. All inbred strains of mice so far examined also have only four C lambda genes, but no feral M. musculus examined have fewer than six C lambda genes. One explanation of the discrepancy in the number of genes between inbred and feral M. musculus is that C lambda genes were deleted during the process of inbreeding.


[Effect of diets with different content of polyunsaturated fatty acids on ATPase activity in different rat tissues].
The authors studied the effect of the diets with varying content of polyunsaturated fatty acids (PUFA) on ATPase activity in the heart, kidneys and lungs of Wistar rats. During 3 weeks the rats received different diets. Group I was kept on the diet poor in PUFA, Group II on the diet rich in linoleic acid, and Group III on the diet rich in linolenic acid. The content of PUFA in food has no effect on ATPase activity in the lungs. The maximal activity of Mg-ATPase in the heart was seen in the Group III rats, while the minimal in the Group I rats (P less than 0.05). On the contrary, Na, K-ATPase activity was minimal in the Group III rats (P-0.05). Examination of ATPase activity in the kidneys has demonstrated no substantial difference between Groups II and III as regards Mg-ATPase activity, whereas Mg-ATPase activity in the Group I animals was significantly reduced (P less than 0.02). As Na, K-ATPase activity in the kidneys increased (Group II, P-0.05) excretion of Na and K with urine considerably diminished.


The neural mechanism for Latent (fusion maldevelopment) nystagmus.
Latent nystagmus (LN) is the by-product of fusion maldevelopment in infancy. Because fusion maldevelopment--in the form of strabismus and amblyopia--is common, LN is a prevalent form of pathologic nystagmus encountered in clinical practice. It originates as an afferent visual pathway disorder. To unravel the mechanism for LN, we studied patients and nonhuman primates with maldeveloped fusion. These experiments have revealed that loss of binocular connections within striate cortex (area V1) in the first months of life is the necessary and sufficient cause of LN. The severity of LN increases systematically with longer durations of binocular decorrelation and greater losses of V1 connections. Decorrelation durations that exceed the equivalent of 2-3 months in human development result in an LN prevalence of 100%. No manipulation of brain stem motor pathways is required. The binocular maldevelopment originating in area V1 is passed on to downstream extrastriate regions of cerebral cortex that drive conjugate gaze, notably MSTd. Conjugate gaze is stable when MSTd neurons of the right and left cerebral hemispheres have balanced binocular activity. Fusion maldevelopment in infancy causes unbalanced monocular activity. If input from one eye dominates and the other is suppressed, MSTd in one hemisphere becomes more active. Acting through downstream projections to the ipsilateral nucleus of the optic tract, the eyes are driven conjugately to that side. The unbalanced MSTd drive is evident as the nasalward gaze-holding bias of LN when viewing with either eye.


Multidrug-resistant Serratia marcescens bacteriuria related to urologic instrumentation.
An outbreak of urinary tract infections caused by multidrug-resistant Serratia marcescens lasted for 12 months and was found to be related to urologic instrumentation. Thirty-four patients had primary infections; four had cross-infections. Only six patients had indwelling bladder catheters. The median interval between instrumentation and initial isolation of Serratia was six days. Seventy-three percent of patients were symptomatic, two were bacteremic. No common instruments, personnel, or wards were identified, and environmental cultures failed to reveal the epidemic strain of Serratia. The outbreak ended when the instrument disinfectant was changed. Serotyping was identical in nine of ten isolates. Intraspecies conjugation demonstrated resistance transfer of gentamicin, tobramycin, carbenicillin, chloramphenicol, and co-trimoxazole. The enzyme 6'-N-acetyl transferase was responsible for gentamicin-inactivation in patient isolates and a transconjugate. Although no significant spread of this multidrug-resistance plasmid to other Enterobacteriaceae occurred in the hospital, two instances of apparent in vivo transfer to other bladder organisms occurred.


High correlation between in vivo [123I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats.
6-Hydroxydopamine (6-OHDA) is widely used in pre-clinical animal studies to induce degeneration of midbrain dopamine neurons to create animal models of Parkinson's disease. The aim of our study was to evaluate the potential of combined single-photon emission computed tomography/computed tomography (SPECT/CT) for the detection of differences in 6-OHDA-induced partial lesions in a dose- and time-dependent manner using the dopamine transporter (DAT) ligand 2β-carbomethoxy-3β-(4-[123I]iodophenyl)tropane ([123I]β-CIT). Rats were unilaterally lesioned with intrastriatal injections of 8 or 2 × 10 μg 6-OHDA. At 2 or 4 weeks post-lesion, 40 to 50 MBq [123I]β-CIT was administered intravenously and rats were imaged with small-animal SPECT/CT under isoflurane anesthesia. The striatum was delineated and mean striatal activity in the lesioned side was compared to the intact side. After the [123I]β-CIT SPECT/CT scan, the rats were tested for amphetamine-induced rotation asymmetry, and their brains were immunohistochemically stained for DAT and tyrosine hydroxylase (TH). The fiber density of DAT- and TH-stained striata was estimated, and TH-immunoreactive cells in the rat substantia nigra pars compacta (SNpc) were stereologically counted. The striatal uptake of [123I]β-CIT differed significantly between the lesion groups and the results were highly correlated to both striatal DAT- and TH-immunoreactive fiber densities and to TH-immunoreactive cell numbers in the rat SNpc. No clear progression of the lesion could be seen. [123I]β-CIT SPECT/CT is a valuable tool in predicting the condition of the rat midbrain dopaminergic pathway in the unilateral partial 6-OHDA lesion model of Parkinson's disease and it offers many advantages, allowing repeated non-invasive analysis of living animals.


Sirolimus prolongs recovery from delayed graft function after cadaveric renal transplantation.
Sirolimus, lacking known nephrotoxicity, appeared to be an ideal immunosuppressive agent in the setting of delayed graft function (DGF) after renal transplantation. Coincident with our use of sirolimus however, we noticed prolongation of DGF. To investigate possible causes of prolonged DGF, extensive donor, recipient, transplant, and post-transplant data were collected on 132 consecutive cases of DGF at the University of California, San Francisco between 1/1/97 and 6/30/01. Cox proportional hazards analysis of time to graft function was used in univariate and multivariate models to identify factors that prolong DGF. Sirolimus had a large and highly significant effect on time to graft function (hazard ratio 0.48, p = 0.0007). The hazard ratio indicates that a recipient on sirolimus is half as likely to resolve DGF or twice as likely to remain on dialysis as a recipient without sirolimus. Two other factors had less potent but still significant association with DGF duration: recipient sensitization (hazard ratio 0.66, p = 0.037), and Novartis score (hazard ratio 0.93 per 1.0 increase; p = 0.034). Sirolimus retained its profound negative association with time to graft function in all multivariate models. Because sirolimus appears to prolong DGF, it may not be the optimal immunosuppressive choice in the DGF setting.


Molecular cytogenetics and cytogenomics of brain diseases.
Molecular cytogenetics is a promising field of biomedical research that has recently revolutionized our thinking on genome structure and behavior. This is in part due to discoveries of human genomic variations and their contribution to biodiversity and disease. Since these studies were primarily targeted at variation of the genome structure, it appears apposite to cover them by molecular cytogenomics. Human brain diseases, which encompass pathogenic conditions from severe neurodegenerative diseases and major psychiatric disorders to brain tumors, are a heavy burden for the patients and their relatives. It has been suggested that most of them, if not all, are of genetic nature and several recent studies have supported the hypothesis assuming them to be associated with genomic instabilities (i.e. single-gene mutations, gross and subtle chromosome imbalances, aneuploidy). The present review is focused on the intriguing relationship between genomic instability and human brain diseases. Looking through the data, we were able to conclude that both interindividual and intercellular genomic variations could be pathogenic representing, therefore, a possible mechanism for human brain malfunctioning. Nevertheless, there are still numerous gaps in our knowledge concerning the link between genomic variations and brain diseases, which, hopefully, will be filled by forthcoming studies. In this light, the present review considers perspectives of this dynamically developing field of neurogenetics and genomics.


Characterization of measles viruses in establishment of persistent infections in human lymphoid cell line.
Human lymphoid cells (NC-37) were infected with attenuated measles vaccine virus (Schwarz, AIK-C, and CAM-70 strains), subacute sclerosing panencephalitis virus (Mantooth and Halle strains), neurovirulent TYCSA strain, and wild type virus (Edmonston and Toyoshima strains) at an input multiplicity of 0-01. These strains were divided into two groups by their capacity to establish carrier states. CAM-70, Toyoshima, and Edmonston strains did not set up persistent infections in NC-37 cells, whereas AIK-C strain induced chronic cyclic infection and the Schwarz, TYCSA, Mantooth and Halle strains could set up persistent infections and furthermore two types of persistent infections were recognizable. Cells persistently infected with Schwarz strain contained nucleocapsid structures in both nucleus and cytoplasm, and produced infectious virus of 10(4) to 10(5) p.f.u./ml over 100 days after the inoculation of the virus but the cap-formation of measles antigens on the cell membrane was seldom observed. However, in cells persistently infected with TYCSA strain, nucleocapsid structures were rarely observed in the nucleus, but the cap-formation of measles antigens on the cell membrane was often observed. The titre of carried virus was always higher than the number of cells in the range of 10(6) to 10(7) p.f.u./ml. Mantooth strain was similar to Schwarz strain and Halle strain was similar to TYCSA strain in the properties of their carrier states. These carrier states were stable and the cells grew normally for over one year.


[Chronological development of the sphenoidal sinus].
In this paper are exposed the main characteristics of the sphenoidal sinus rise, through a follow-up of its growth during the life-span of the first 20 years of life. For so doing the AA. studied the antero-posterior diameters, the vertical greatest diameter and the several distances detaching this sinus from other important anatomical references, as well the various degrees of pneumatization that the cavity may reach according as the years go over.