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Sample records for patients reveals aspects

  1. Patient preference assessment reveals disease aspects not covered by recommended outcomes in polymyositis and dermatomyositis.

    PubMed

    Alemo Munters, Li; van Vollenhoven, Ronald F; Alexanderson, Helene

    2011-01-01

    Objectives. Polymyositis (PM) and dermatomyositis (DM) are characterized by impaired muscle function with a majority of patients developing sustained disability. The aim of this study was to evaluate the patient's individual priorities (patient preference) of disabilities most important to improve in PM/DM using the MacMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR), to correlate the MACTAR to myositis outcomes and to evaluate its test-retest reliability. Methods. Twenty-eight patients with PM/DM performed recommended outcomes as well as the MACTAR, which was performed twice with one week apart. Results. Sexual activity, walking, biking, social activities, and sleep constituted the predominating disabilities. Seventy-two and 33% of the identified disabilities were not covered by items of the Health Assessment Questionnaire and the Myositis Activities Profile. Correlations between the MACTAR and health-related quality of life measures were r(s) = -0.67-0.73, correlations with measures of activities of daily living and participation in society were r(s) = 0.51-0.60 with lower correlations for other outcomes. Intraclass correlation (ICC) and weighted Kappa (K(w)) coefficients were 0.83 and 0.68, respectively, for test-retest reliability of the MACTAR. Conclusions. The MACTAR interview had promising measurement properties and identified patient preference disabilities in PM/DM that were not covered by recommended outcomes. PMID:22389795

  2. Revealed aspect of metabolic osteoarthritis.

    PubMed

    Chadha, Rishmeen

    2016-12-01

    In current scenario there is an emerging trend to consider osteoarthritis (OA) phenotypes based on their risk factors and therefore offering potential for targeted therapies. OA prevalence with other coexistence diseases, such as systemic arterial hypertension, cardiovascular disease, diabetes, and dyslipidemia are increasing. Majority of OA associated with MetS, despite overweight of patients, the occurrence of OA in joints do not bear load suggest, the chronic inflammation status existing in patients with MetS can alter the metabolism of cartilage, regardless of excessive weight. This paper indicates that factors responsible for metabolic syndrome has clear role in cartilage degeneration and further degradation. PMID:27453640

  3. [Sexual aspects of physician-patient relations].

    PubMed

    Abbondanza, M; Antonioli, G; Rostagno, M; Ruspa, G

    1990-01-01

    The emotional aspects of the doctor-patient relationship are often overlooked in clinical training, as are the sexual problems. A questionnaire was drawn up in order to obtain further information about the gynecologist's emotional reactions during pelvic examination. An analysis of the results suggests that the doctor's emotional reaction during pelvic examination is not the same in both sexes, whereas both sexes show equal concern for the patient's sexual activity. This suggests that adequate technical and emotional training is necessary in order to establish a good relationship between the gynecologist and the patient. PMID:2293076

  4. Psychiatric aspects of pain in cancer patients.

    PubMed

    Ozkan, Sedat

    2010-01-01

    The goal of this review is to discuss the psychiatric aspects of pain in cancer patients from a biopsychosocial approach. Pain in cancer patients is considered as a complex reaction causing severe suffering and involves many psychological aspects. It has many dimensions such as personality, affect, cognition and social relations. The pain experience may also be influenced by some psychological factors such as anxiety, depression and the meaning of pain. Therefore, a successful management of cancer pain requires a multidisciplinary approach. Since cancer pain is generally treated medically, the psychological impact of pain is often underestimated. However, cancer pain is usually related to high levels of psychological distress. Culture, as an important factor affecting cancer pain, will also be discussed during this review. It is crucial to understand cultural diversity in the treatment of cancer patients with pain. Research shows that a minority patients of various ethnicities have less control of their pain because of the miscommunication problem within the medical setting. By paying attention to patients' cultural diversities, problems such as miscommunication causing inadequate control of pain can be eliminated. In order to manage pain in cancer patients, cognitive-behavioral interventions may be integrated with pharmacotherapy. The main goal of these strategies is to provide a sense of control and better coping skills to deal with cancer. Patients' maladaptive thoughts or behaviors may cause physical and emotional stress. Main behavioral strategies include biofeedback, relaxation training, and hypnosis. Cognitive strategies include guided imagery, distraction, thought monitoring and problem solving. By discussing all of these aspects of cancer pain, the multidimensional characteristic of pain and the relation between cancer pain and psychiatric factors will be clarified. PMID:20590361

  5. Network Analyses Reveal Novel Aspects of ALS Pathogenesis

    PubMed Central

    Sanhueza, Mario; Chai, Andrea; Smith, Colin; McCray, Brett A.; Simpson, T. Ian; Taylor, J. Paul; Pennetta, Giuseppa

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of motor neurons, muscle atrophy and paralysis. Mutations in the human VAMP-associated protein B (hVAPB) cause a heterogeneous group of motor neuron diseases including ALS8. Despite extensive research, the molecular mechanisms underlying ALS pathogenesis remain largely unknown. Genetic screens for key interactors of hVAPB activity in the intact nervous system, however, represent a fundamental approach towards understanding the in vivo function of hVAPB and its role in ALS pathogenesis. Targeted expression of the disease-causing allele leads to neurodegeneration and progressive decline in motor performance when expressed in the adult Drosophila, eye or in its entire nervous system, respectively. By using these two phenotypic readouts, we carried out a systematic survey of the Drosophila genome to identify modifiers of hVAPB-induced neurotoxicity. Modifiers cluster in a diverse array of biological functions including processes and genes that have been previously linked to hVAPB function, such as proteolysis and vesicular trafficking. In addition to established mechanisms, the screen identified endocytic trafficking and genes controlling proliferation and apoptosis as potent modifiers of ALS8-mediated defects. Surprisingly, the list of modifiers was mostly enriched for proteins linked to lipid droplet biogenesis and dynamics. Computational analysis reveals that most modifiers can be linked into a complex network of interacting genes, and that the human genes homologous to the Drosophila modifiers can be assembled into an interacting network largely overlapping with that in flies. Identity markers of the endocytic process were also found to abnormally accumulate in ALS patients, further supporting the relevance of the fly data for human biology. Collectively, these results not only lead to a better understanding of hVAPB function but also point to potentially

  6. Network analyses reveal novel aspects of ALS pathogenesis.

    PubMed

    Sanhueza, Mario; Chai, Andrea; Smith, Colin; McCray, Brett A; Simpson, T Ian; Taylor, J Paul; Pennetta, Giuseppa

    2015-03-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of motor neurons, muscle atrophy and paralysis. Mutations in the human VAMP-associated protein B (hVAPB) cause a heterogeneous group of motor neuron diseases including ALS8. Despite extensive research, the molecular mechanisms underlying ALS pathogenesis remain largely unknown. Genetic screens for key interactors of hVAPB activity in the intact nervous system, however, represent a fundamental approach towards understanding the in vivo function of hVAPB and its role in ALS pathogenesis. Targeted expression of the disease-causing allele leads to neurodegeneration and progressive decline in motor performance when expressed in the adult Drosophila, eye or in its entire nervous system, respectively. By using these two phenotypic readouts, we carried out a systematic survey of the Drosophila genome to identify modifiers of hVAPB-induced neurotoxicity. Modifiers cluster in a diverse array of biological functions including processes and genes that have been previously linked to hVAPB function, such as proteolysis and vesicular trafficking. In addition to established mechanisms, the screen identified endocytic trafficking and genes controlling proliferation and apoptosis as potent modifiers of ALS8-mediated defects. Surprisingly, the list of modifiers was mostly enriched for proteins linked to lipid droplet biogenesis and dynamics. Computational analysis reveals that most modifiers can be linked into a complex network of interacting genes, and that the human genes homologous to the Drosophila modifiers can be assembled into an interacting network largely overlapping with that in flies. Identity markers of the endocytic process were also found to abnormally accumulate in ALS patients, further supporting the relevance of the fly data for human biology. Collectively, these results not only lead to a better understanding of hVAPB function but also point to potentially

  7. PSYCHOSOMATIC ASPECTS IN PATIENTS WITH DERMATOLOGIC DISEASES.

    PubMed

    Tsintsadze, N; Beridze, L; Tsintsadze, N; Krichun, Y; Tsivadze, N; Tsintsadze, M

    2015-06-01

    The aim of our study was to find out the magnitude of anxiety and depression in our common dermatological patients and its correlation with age, sex. For this purpose, we used Hospital Anxiety and Depression Scale HADS. The psychometric validity of HADS has been established by validating the questionnaire against the structured psychiatric interviews. A study of anxiety and depression in patients with dermatologic diseases was conducted on the basis of outpatients department in 211 patients with dermatologic diseases; among them were 107 male and 104 female, aged 16 to 75 years. Among them were patients with Acne, Alopecia Areata, Psoriasis, Vitiligo, Neurodermatitis, Scabies, Eczema and Other diseases (Atopic Dermatitis, Chronic Urticaria, Lichen Planus, Herpes Zoster, Melasma, Warts and Etc.). Based on studies of patients reveals that 65.4% of them are anxiety, depression - 56.2%, both anxiety and depression in 24.7%, there figures higher than the dates of other authorizes. As a result of a direct link research risk disorder depressive spectrum with sex, age; in woman anxiety and depression occurs more frequently than men, and anxiety occurs more frequently in young age. Especially there are hight frequencies of manifestation of abuse in patients with Psoriasis (anxiety - 83.3%, depression - 69.4%, both - 38.8%), Eczema (anxiety - 73.3%, depression - 56.6%, both - 26.7%), Acne (anxiety - 78.4%, depression - 54%, both - 21.6%), Vitiligo (anxiety - 66.7%, depression - 60%, both - 33.3%). Our study noticed higher dates of anxiety and depression than the dates of other outhorizes. PMID:26087735

  8. [Psychodynamic aspects of severalsheumatic diseases as revealed in tests].

    PubMed

    Pfitzner, R

    1976-01-01

    Three groups of patients with rheumafactor-negative diseases (Palindromic Rheumatism, Reiter's disease, Psoriatic Arthritis) took psychodiagnostic investigations. Tests administrated: MMPI, Rorschach-test, Szondi-test and TAT. The findings of the qualitative psychoanalytic investigations and interpretations of the three groups were compared with the psychological topics of patients with chronic Rheumatoid Arthritis as well as with the findings of the psychoanalytic explorations by Zander. Finally some considerations to the link as well as to the reduction of movement responses in the Rorschach-test are made. PMID:1087793

  9. Practical aspects of telehealth: doctor-patient relationship and communication.

    PubMed

    Sabesan, S; Allen, D; Caldwell, P; Loh, P K; Mozer, R; Komesaroff, P A; Talman, P; Williams, M; Shaheen, N; Grabinski, O

    2014-01-01

    The fourth in a series of articles about the practical aspects of telehealth, this paper provides advice and information for specialists to communicate effectively with patients during a telehealth video consultation. PMID:24450527

  10. House Staff Attitudes toward Psychosocial Aspects of Patient Care.

    ERIC Educational Resources Information Center

    Levinson, Wendy; And Others

    1990-01-01

    Attitudes of 120 residents from three teaching hospitals about psychosocial aspects of patient care and the feasibility of teaching psychosocial skills to residents were compared to those of 86 practicing internists, 42 psychiatrists, 29 academic general internists, and 63 surgeons. The newly developed scale was seen as useful in evaluating…

  11. Histopathological aspects described in patients with chronic hepatitis C.

    PubMed

    Petrescu, Florin; Petrescu, Octavia Ileana; Taisescu, Citto Iulian; Comănescu, Maria Victoria; Forţofoiu, Mircea Cătălin; Predescu, Ion Octavian; Roşu, Alexandra Floriana; Gheonea, Cristian; Biciuşcă, Viorel

    2015-01-01

    Chronic hepatitis C affects an estimated 170 million people worldwide and causes approximately 350 000 deaths each year. The current antiviral therapy allows the virus eradication or the permanent inhibition of the virus replication (sustained virological response, SVR), the reduction of the inflammation, and the prevention or the reduction of liver fibrogenesis (histological response). We studied the histopathological aspects found during percutaneous liver biopsy in patients with chronic hepatitis C viral infection who were treated and monitored over a period of two years. The assessment of the histological activity index through Ishak score determined the presence of: mild chronic hepatitis in 12 (23.1%) patients, moderate chronic hepatitis in 21 (40.4%) patients, and severe chronic hepatitis in 19 (36.5%) patients. The percutaneous liver biopsy performed on the patients with chronic viral hepatitis C showed a series of histological alterations, the most frequent being: portal inflammation, periportal necrosis, lobular inflammation, focal necrosis, and hepatic fibrosis (scarring). The severity degree of this histopathological aspect was correlated with the hepatitis activity index. The association of piecemeal with bridging necrosis is the deadline at which the antiviral treatment can still be effective. Evidence of early fibrosis represent the important moment for the antiviral treatment start. The specific histopathological aspects, but not pathognomonic, of chronic hepatitis C (hepatic steatosis, portal lymphoid infiltrates and bile duct damage) had a reduced incidence, occurring in only half (hepatic steatosis), a quarter (portal lymphoid infiltrates) and a fifth (destruction of biliary ducts) of all the patients with chronic viral hepatitis C, and these patterns was correlated with advanced degree of necroinflammatory process of the liver, particularly in the portal tracts. PMID:26193211

  12. Psychological aspects of diabetes care: Effecting behavioral change in patients

    PubMed Central

    Chew, Boon-How; Shariff-Ghazali, Sazlina; Fernandez, Aaron

    2014-01-01

    Patients with diabetes mellitus (DM) need psychological support throughout their life span from the time of diagnosis. The psychological make-up of the patients with DM play a central role in self-management behaviors. Without patient’s adherence to the effective therapies, there would be persistent sub-optimal control of diseases, increase diabetes-related complications, causing deterioration in quality of life, resulting in increased healthcare utilization and burden on healthcare systems. However, provision of psychosocial support is generally inadequate due to its challenging nature of needs and demands on the healthcare systems. This review article examines patient’s psychological aspects in general, elaborates in particular about emotion effects on health, and emotion in relation to other psychological domains such as cognition, self-regulation, self-efficacy and behavior. Some descriptions are also provided on willpower, resilience, illness perception and proactive coping in relating execution of new behaviors, coping with future-oriented thinking and influences of illness perception on health-related behaviors. These psychological aspects are further discussed in relation to DM and interventions for patients with DM. Equipped with the understanding of the pertinent nature of psychology in patients with DM; and knowing the links between the psychological disorders, inflammation and cardiovascular outcomes would hopefully encourages healthcare professionals in giving due attention to the psychological needs of patients with DM. PMID:25512782

  13. Psychological aspects of artificial feeding in cancer patients.

    PubMed

    Peteet, J R; Medeiros, C; Slavin, L; Walsh-Burke, K

    1981-01-01

    Anorexia and weight loss are major physical and psychological problems for patients with cancer, and nutritional support has become an increasingly important part of cancer treatment. Reports discussing the psychological aspects of parenteral feeding have emphasized the importance of the nature of the underlying illness, but special problems surrounding the use of artificial feeding in patients with cancer have not been described. Patterns of emotional response to artificial feeding in such patients are most directly influenced by two interacting sets of variables: the diagnosis and prognosis of cancer, and personality characteristics of patients and family members involved. Typically, management problems result when demoralized patients respond to artificial feeding by becoming more passive, when independent patients struggle over artificial feeding in order to maintain a sense of control, or when anxious patients or families express fears about dying in the form of extreme preoccupation with eating and maintaining weight. An understanding of these patterns has specific implications for improving the patient's cooperation and quality of life. PMID:6787227

  14. Patient ventilator interfaces: practical aspects in the chronic situation.

    PubMed

    Clini, E

    1997-02-01

    In the ventilator-dependent patient, the nonpsychological problems of the chronic phase relate mainly to aspects of the patient ventilator interface. Humidification, suctioning of secretions, and ventilatory circuit and monitoring are the three most important aspects to which careful attention is needed. Good humidification can be obtained by means of various devices, which can provide humidity directly or indirectly: in the tracheostomized patient, the heat and moisture exchanger appears to be a good method because of its antibacterial properties. Airway suctioning is frequently needed in patients receiving ventilation invasively. Suctioning of secretions might possibly be associated with the risk of major cardiorespiratory complications: bacterial colonization of the airways and the subsequent increased risk of infection should be carefully considered. Problems concerning the ventilatory circuit and monitoring can be specific in patients with a tracheal cannula and those with a nasal/facial interface. Long-term tracheostomy in itself represents a real risk for bacterial colonization, damage to the tracheal mucosa, and to functioning of the vocal cords (both for speech and swallowing): therefore, a switch from invasive to noninvasive ventilatory interface may be proposed. Most problems with the nasal mask interface concern air leakage and the skin mucosal lesions. Two major aspects must be taken into account when considering the long-term effects of noninvasive ventilatory support monitoring: the possible effect of CO2 rebreathing, and the inadequate volume/pressure delivery, so that proper ventilation cannot be achieved. Use of an oral/mouth interface is of limited interest in subjects with restrictive disorders: air gastric distension and orthodontic problems are the most common side-effects in chronic use. PMID:9151529

  15. [The psychosocial aspects of female patients with genital cancer].

    PubMed

    Buiuc, A I

    1996-01-01

    Revealing a diagnosis as cancer, usually generates various emotional and psychosocial response in the patients: anxiety, negation of reality, passivity and generalized state of shock and anguish; long term projects and personal responsibilities are annihilated, the image of death grows enormously. Genital cancer women patients also exhibits sexual problems which can seriously complicate the psychic representation of disease and impair family life. Our study comprised 20 women patients who were hospitalized, with genital cancer diagnosis (ovarian cancer, neoplasms of the cervix and of the endometrium); by anamnesis and further discussions we tried to establish the main elements which generated different psychologic reactions. The perception of the reality of the diagnosis was proved to depend on age, personality type, doctor-patient and family-patient relationship. Each stage of disease and each treatment applied generates individual psychologic reaction which can be alleviated by communication between doctor and patients, by a patient adapted language. Complexity of psychological and sometimes psychic reactions of such patients requires that a psycho-oncologist be included in the complex oncologic treatment team; deeper knowledge of the problems and employment of individual or group therapy (the patient's family included) may lead to better psychic response to the malady. PMID:9455456

  16. Metabolic aspects of adult patients with nonalcoholic fatty liver disease.

    PubMed

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-08-21

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  17. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  18. [Some aspects of homocysteine metabolism in hemodialysis patients].

    PubMed

    Bednarek-Skublewska, Anna; Buraczyńska, Monika; Wawrzycki, Sławomir; Baranowicz-Gaszczyk, Iwona; Ksiazek, Andrzej

    2002-11-01

    Homocysteine (Hcy) is a non-protein forming sulfur amino acid, synthesised from methionine (Met), whose metabolism is at the junction of two metabolic pathways: remethylation and transsulfuration. Increased Hcy serum concentration is a well established independent risk factor of cardiovascular diseases and a known feature of end stage renal disease. Hcy plasma level is influenced by folate, vitamin B6 and genetic factors. Mutation C677T in gene encoding methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in Hcy remethylation has been associated with elevated Hcy in homozygous carriers (TT genotype). Several amino acids take part in metabolism of Hcy. There are abnormalities of concentration of the non essential and essential of amino acids in serum of patients treated with hemodialysis (HD). It is possible that these abnormalities of amino acids can change the Hcy metabolism. The aim of this study was the evaluation of some aspects of Hcy metabolism. We examined the MTHFR gene polymorphism and its relationship with plasma Hcy concentration. The plasma levels of total amino acids and amino acids connected with Hcy metabolism: methionine (Met), seryne (Ser), cysteine (Cyst) and tauryne (Tau) were evaluated in hemodialysis patients. The study was conducted in 71 (35 male, 36 female) patients, mean age 56.2 +/- 12.4 years. They were dialysed for a mean duration of 87.7 +/- 84.7 months (range 2-302). The control group (CG) in which Hcy and amino acids levels were examined consisted of 12 healthy subjects. Serum (EDTA) Hcy levels were measured by EIA-Hcy ELISA kit. The MTHFR gene polymorphism was evaluated by means of the polymerase chain reaction (PCR). The amino acids were measured by chromatography in amino acid analyser AAA 400. Mean concentration of Hcy was significantly higher in patients than in CG (31.1 +/- 9.1 vs 11.9 +/- 2.9 mumol/L; p < 0.01). Genotype frequencies in patients were: 42.8% for CC, 48.5% for CT and 8.7% for TT. Mean concentration of

  19. Comparative Proteomic Study Reveals the Molecular Aspects of Delayed Ocular Symptoms Induced by Sulfur Mustard

    PubMed Central

    Pashandi, Zaiddodine; Saraygord-Afshari, Neda; Naderi-Manesh, Hossein; Naderi, Mostafa

    2015-01-01

    Objective. Sulfur mustard (SM) is a highly reactive alkylating agent which produces ocular, respiratory, and skin damages. Eyes are the most sensitive organ to SM due to high intrinsic metabolic and rapid turnover rate of corneal epithelium and aqueous-mucous interfaces of the cornea and conjunctiva. Here we investigate underlying molecular mechanism of SM exposure delayed effects which is still a controversial issue after about 30 years. Materials and Methods. Following ethical approval, we have analyzed serum proteome of ten severe SM exposed male patients with delayed eye symptoms with two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. The western blotting was used to confirm the proteins that have been identified. Results. We have identified thirteen proteins including albumin, haptoglobin, and keratin isoforms as well as immunoglobulin kappa chain which showed upregulation while transferrin and alpha 1 antitrypsin revealed downregulation in these patients in comparison with healthy control group. Conclusions. Our results elevated participation of free iron circulatory imbalance and local matrix-metalloproteinase activity in development of delayed ocular symptoms induced by SM. It demonstrates that SM induced systemic toxicity leads to some serum protein changes that continually and gradually exacerbate the ocular surface injuries. PMID:25685557

  20. Troublesome aspects of the patient-physician relationship: a study of human factors.

    PubMed

    Merrill, J M; Laux, L; Thornby, J I

    1987-10-01

    We investigated three onerous aspects of the patient-physician relationship using contemporary psychosocial research methods. A "hassle index" identified three dimensions of vexation in practice: problems with running a practice, medical conditions of patients, and social characteristics of patients. In general, hassle was found to be dependent on the type of practice, but physicians were equally annoyed by unlikeable patients irrespective of their practice site. Diagnostic errors made by resident physicians from various clinics were more related to an unlikeable medical disorder than to differences in the clinics. To clarify doctors' negative feelings toward patients, a questionnaire measuring antipathy toward specific patient types was administered to physicians. Responses indicated that physicians' antipathy was unrelated to the doctors' ethical beliefs and their medicopolitical orientation. Personality variables indicative of "extremeness" of opinion about patients included high needs for dominance, low needs for nurturance and "intraception" (the ability to analyze the behavior and motives of others), and low self-esteem. Personality profiles of physicians least vexed by medical practice reflected less psychopathology--less self-derogation, less need for emotional support, and more extroversion. Medical College Aptitude Test scores revealed that high science scores were associated with extremeness of opinion, and low scores on general information were indicative of increased susceptibility to the daily irritations of medical practice. PMID:3660036

  1. Phosphoproteome Integration Reveals Patient-Specific Networks in Prostate Cancer.

    PubMed

    Drake, Justin M; Paull, Evan O; Graham, Nicholas A; Lee, John K; Smith, Bryan A; Titz, Bjoern; Stoyanova, Tanya; Faltermeier, Claire M; Uzunangelov, Vladislav; Carlin, Daniel E; Fleming, Daniel Teo; Wong, Christopher K; Newton, Yulia; Sudha, Sud; Vashisht, Ajay A; Huang, Jiaoti; Wohlschlegel, James A; Graeber, Thomas G; Witte, Owen N; Stuart, Joshua M

    2016-08-11

    We used clinical tissue from lethal metastatic castration-resistant prostate cancer (CRPC) patients obtained at rapid autopsy to evaluate diverse genomic, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied Diffusion through Interacting Events (TieDIE), we integrated differentially expressed master transcriptional regulators, functionally mutated genes, and differentially activated kinases in CRPC tissues to synthesize a robust signaling network consisting of druggable kinase pathways. Using MSigDB hallmark gene sets, six major signaling pathways with phosphorylation of several key residues were significantly enriched in CRPC tumors after incorporation of phosphoproteomic data. Individual autopsy profiles developed using these hallmarks revealed clinically relevant pathway information potentially suitable for patient stratification and targeted therapies in late stage prostate cancer. Here, we describe phosphorylation-based cancer hallmarks using integrated personalized signatures (pCHIPS) that shed light on the diversity of activated signaling pathways in metastatic CRPC while providing an integrative, pathway-based reference for drug prioritization in individual patients. PMID:27499020

  2. Revealing the nanoparticles aspect ratio in the glass-metal nanocomposites irradiated with femtosecond laser

    PubMed Central

    Chervinskii, S.; Drevinskas, R.; Karpov, D. V.; Beresna, M.; Lipovskii, A. A.; Svirko, Yu. P.; Kazansky, P. G.

    2015-01-01

    We studied a femtosecond laser shaping of silver nanoparticles embedded in soda-lime glass. Comparing experimental absorption spectra with the modeling based on Maxwell Garnett approximation modified for spheroidal inclusions, we obtained the mean aspect ratio of the re-shaped silver nanoparticles as a function of the laser fluence. We demonstrated that under our experimental conditions the spherical shape of silver nanoparticles changed to a prolate spheroid with the aspect ratio as high as 3.5 at the laser fluence of 0.6 J/cm2. The developed approach can be employed to control the anisotropy of the glass-metal composites. PMID:26348691

  3. Revealing the nanoparticles aspect ratio in the glass-metal nanocomposites irradiated with femtosecond laser

    NASA Astrophysics Data System (ADS)

    Chervinskii, S.; Drevinskas, R.; Karpov, D. V.; Beresna, M.; Lipovskii, A. A.; Svirko, Yu. P.; Kazansky, P. G.

    2015-09-01

    We studied a femtosecond laser shaping of silver nanoparticles embedded in soda-lime glass. Comparing experimental absorption spectra with the modeling based on Maxwell Garnett approximation modified for spheroidal inclusions, we obtained the mean aspect ratio of the re-shaped silver nanoparticles as a function of the laser fluence. We demonstrated that under our experimental conditions the spherical shape of silver nanoparticles changed to a prolate spheroid with the aspect ratio as high as 3.5 at the laser fluence of 0.6 J/cm2. The developed approach can be employed to control the anisotropy of the glass-metal composites.

  4. Revealing the nanoparticles aspect ratio in the glass-metal nanocomposites irradiated with femtosecond laser.

    PubMed

    Chervinskii, S; Drevinskas, R; Karpov, D V; Beresna, M; Lipovskii, A A; Svirko, Yu P; Kazansky, P G

    2015-01-01

    We studied a femtosecond laser shaping of silver nanoparticles embedded in soda-lime glass. Comparing experimental absorption spectra with the modeling based on Maxwell Garnett approximation modified for spheroidal inclusions, we obtained the mean aspect ratio of the re-shaped silver nanoparticles as a function of the laser fluence. We demonstrated that under our experimental conditions the spherical shape of silver nanoparticles changed to a prolate spheroid with the aspect ratio as high as 3.5 at the laser fluence of 0.6 J/cm2. The developed approach can be employed to control the anisotropy of the glass-metal composites. PMID:26348691

  5. New aspects on patients affected by dysferlin deficient muscular dystrophy

    PubMed Central

    Klinge, Lars; Aboumousa, Ahmed; Eagle, Michelle; Hudson, Judith; Sarkozy, Anna; Vita, Gianluca; Charlton, Richard; Roberts, Mark; Straub, Volker; Barresi, Rita; Lochmüller, Hanns

    2009-01-01

    Mutations in the dysferlin gene lead to limb girdle muscular dystrophy 2B, Miyoshi myopathy and distal anterior compartment myopathy. A cohort of 36 patients affected by dysferlinopathy is described, in the first UK study of clinical, genetic, pathological and biochemical data. The diagnosis was established by reduction of dysferlin in the muscle biopsy and subsequent mutational analysis of the dysferlin gene. Seventeen mutations were novel; the majority of mutations were small deletions/insertions, and no mutational hotspots were identified. Sixty-one per cent of patients (22 patients) initially presented with limb girdle muscular dystrophy 2B, 31% (11 patients) with a Miyoshi phenotype, one patient with proximodistal mode of onset, one patient with muscle stiffness after exercise and one patient as a symptomatic carrier. A wider range of age of onset was noted than previously reported, with 25% of patients having first symptoms before the age of 13 years. Independent of the initial mode of presentation, in our cohort of patients the gastrocnemius muscle was the most severely affected muscle leading to an inability to stand on tiptoes, and lower limbs were affected more severely than upper limbs. As previous anecdotal evidence on patients affected by dysferlinopathy suggests good muscle prowess before onset of symptoms, we also investigated pre-symptomatic fitness levels of the patients. Fifty-three per cent of the patients were very active and sporty before the onset of symptoms which makes the clinical course of dysferlinopathy unusual within the different forms of muscular dystrophy and provides a challenge to understanding the underlying pathomechanisms in this disease. PMID:19528035

  6. Some aspects of balance disorder in patients with multiple sclerosis.

    PubMed

    Burina, Adnan; Sinanović, Osman; Smajlović, Dzevdet; Vidović, Mirjana; Brkić, Fuad

    2008-02-01

    The aim of this study was to analyze: frequency of balance disorder (vertigo and disequilibrium), frequency of abnormalities in auditory evoked potentials (AEP) and magnetic resonance imaging (MRI) changes of the brain in multiple sclerosis (MS) patients with balance disorder, relation of patient's disability status to balance disorder and relation of the changes in MRI of the brainstem to AEP abnormalities. It was analyzed 60 patients with relapsing-remitting form of MS. Two groups of patients were made consecutively under Expanded Disability Status Scale score (EDSS): A (EDSS < or =4,5) and B (EDSS > or =5,0). The study was retrospective-prospective. After the neurological exam AEP and MRI of the brain have been done. Balance disorder has been verified as initial symptom in 29 (48,4%) and out of them disequilibrium experienced 24 (83,4%) patients. During the relapses balance disorder experienced 48 (80%) patients and in 37 (77,1%) it was disequilibrium. Among them 33 (68,7%) were with lower EDSS (< or =4,5) and 15 (31,3%) with higher EDSS score (> or =5). There is no correlation between disability status and vertigo which means that vertigo is not more frequent in more disabled patients and vice-versa. The AEP were pathological in 57 (95%) patients. Of all 29 patients with vertigo AEP were pathological in 28 (96,5%) while in 31 patients without vertigo pathological AEP were in 29 (93,5%) but it is not statistical significant. The most frequent characteristic of AEP changes were prolonged inter-peak latency III-V waves (48 patients or 80%). The plaque in brainstem visualized by MRI was found in 41 (71,8%) of patients (38 or 92,6% of them had pathological AEP and in three patients AEP were normal). In group of patients with pathological AEP, 38 (66,6%) of them had plaque in brainstem. In other three patients with normal AEP it was visualized plaque in brainstem. In the group of 29 patients with balance disorder, 20 (68,9%) had plaque in brainstem as well as 21 (67

  7. Endoscopic vs external dacryocystorhinostomy-comparison from the patients' aspect

    PubMed Central

    Ozer, Serdar; Ozer, Pinar A.

    2014-01-01

    AIM To compare the success and complication rates, duration of surgeries and clinical comfort after endoscopic dacryocystorhinostomy (END-DCR) or external dacryocystorhinostomy (EXT-DCR). METHODS Fifty patients who underwent EXT- or END-DCR between January 2010-2012 were involved in the study. A questionnaire was applied to patients preoperatively, and postoperatively. Subjective success was defined by absence of epiphora, objective success by a normal nasolacrimal lavage and a positive functional endoscopic dye test (FEDT). Postoperative pain and cosmetic result of surgery were interpreted by the patients, who were also asked whether they would offer this surgery to a friend or would prefer this surgery once more if necessary. RESULTS Twenty-five patients underwent END-DCR and 25 underwent EXT-DCR. Mean duration of surgeries were 35min both for EXT-DCR (30-50) and END-DCR (35-50) (P=0.778). Intraoperative bleeding were documented in 48% of EXT-DCR and 4% of END-DCR cases (P<0.001). In total 96% of EXT-DCR and 100% of END-DCR patients had subjective success. Objective success was 100% in each group. There was no significant difference between the epiphora scorings and FDDT results in postoperative visits among the groups. END-DCR group reported less pain in first week and month (P<0.05, P<0.05). More patients in END-DCR group were happy with the cosmetic result in first week and month (P<0.001, P<0.001). More patients in END-DCR group offered this surgery to a friend (P<0.001). All patients in END-DCR group preferred this surgery once more if necessary, only 48% in EXT-DCR preferred the same method (P<0.001). CONCLUSION Although both END- and EXT-DCRs provide satisfactory outcomes with similar objective and subjective success rates, we demonstrated that the endonasal approach caused significantly less pain in early postoperative period than the external approach. Clinical comfort defined by the patients was quite higher in END-DCR group, in which patients mainly

  8. Feedback from Patients as a Means of Teaching Nontechnological Aspects of Medical Care.

    ERIC Educational Resources Information Center

    Brody, David S.

    1980-01-01

    A project to improve hospital house officers' recognition of important behavioral, psychological, and social aspects involved in medical care of chronically ill ambulatory patients and an evaluation of its effectiveness are reported. The procedure involved the use of feedback from patient interviews regarding patient satisfaction, medication…

  9. Doctor-patient dialogue--basic aspect of medical consultation.

    PubMed

    Murariu-Brujbu, Isabella Cristina; Macovei, Luana Andreea

    2013-01-01

    Family medicine is the specialty that provides ongoing primary medical care and improves the health status of the individual, of the family and of the community through preventive, educational, therapeutic and rehabilitation measures. The family doctor often makes the interdisciplinary synthesis, in a flexible manner, either alone or in most cases with interdisciplinary consultation. In the latter case, the family doctor initiates the team work and makes the final evaluation by using the longitudinal follow-up of the disease. The doctor-patient encounter represents the "confrontation" with the greatest moral weight, due to the complexity of the values involved, the status of the doctor in a society, and patient's involvement in decision making. The patient is a person who should be treated with respect, honesty, professionalism and loyalty, whatever the clinical status, severity of illness, mental competence or incompetence. A focus, on an international scale, is represented by the characteristics of a good doctor, family physician included, as the latter is the first link in the network of health services. Each model of consultation varies in a more or less subtle way in priorities assignment, and suggests slight differences regarding the role played by doctor and patient in their collaboration. The qualities of a good family physician include not only the strictly professional competences, that also apply to other medical specialties, but also duties, such as, clearly explaining to patients issues concerning their health, informing them about all the possible preventive measures of diseases, making a diagnosis, initiating and supervising a therapy. Medical responsibility lies at the crossroads between medical science and the conscience of the doctor. PMID:24505902

  10. Aspects of vulnerable patients and informed consent in clinical trials

    PubMed Central

    Kuthning, Maria; Hundt, Ferdinand

    2013-01-01

    Scope: To discuss the rationale behind informed consent in clinical trials focusing on vulnerable patients from a European and German viewpoint. Methods: Scientific literature search via PubMed, Medline, Google. Results: Voluntary informed consent is the cornerstone of policies regulating clinical trials. To enroll a patient into a clinical trial without having obtained written and signed consent is to be considered as a serious issue in the conduct of a clinical trial. Development of ethical guidance for physicians started before Christ Era with the Hippocratic Oath. Main function of consent, as articulated in all guidelines developed for clinical research, is to facilitate an individual’s freedom of choice, respect autonomy, and thus to ensure welfare of the participants in clinical trials. Minors are unable to provide legally binding informed consent, this issue is addressed through a combination of parental permission and minor’s assent. Illiteracy is a critical problem that affects all corners of our earth; it has no boundaries and exists among every race and ethnicity, age group, and economic class. New strategies to improve communication with patients including the use of videotapes or animated cartoon illustrations could be taught. Finally the time with the potential participant seems to be the best way to improve understanding. Conclusion: Discovery of life saving and life enhancing new treatments requires partnership that is based on good communication and trust between patients and researchers, sponsors, ethics committees, authorities, lawyers and politicians so that vulnerable patients can benefit from the results of well controlled clinical trials. PMID:23346043

  11. Pathogenesis and clinical aspects of pain in patients with osteoporosis.

    PubMed

    Mediati, Rocco Domenico; Vellucci, Renato; Dodaro, Lucia

    2014-09-01

    Bone pain is one of the most frequent kinds of chronic pain, mainly in elderly patients. It causes a significant worsening of functional capacity and deterioration in the quality of life in people affected. Mechanisms of pain in osteoporosis are poorly known and often extrapolated by other pathologies or other experimental model. One of principal causes would be a "hyper-remodeling" of bone, that involves osteoclasts activity and pathological modifications of bone innervation. Several studies show that osteoclasts play a significant role in bone pain etiology. Pain in osteoporosis is mainly nociceptive, if it become persistent a sensitization of peripheral and central nervous system can occur, so underlining the transition to a chronic pain syndrome. Central sensitization mechanisms are complex and involve several neuromediators and receptors (Substance P, NMDA, etc.). Most common manifestations of osteoporosis are vertebral compression fractures that cause persistent pain, though to differentiate from pain originating in structures as joint or muscle. First manifestation can be an acute pain due to pathological fracture, those of hip often causes disability. Pain in osteoporosis is an important clinical challenge. Often its complications and consequences on patient quality of life are underestimated with not negligible social implications. A balanced and early multimodal pain therapy including opioids as necessary, even in cases of acute pain, improve the functional capacity of patients and helps to prevent neurological alterations that seems to contribute in significant way in causing irreversible pain chronic syndromes. PMID:25568647

  12. The study of fkbp and ubiquitin reveals interesting aspects of Artemia stress history.

    PubMed

    Maniatsi, Stefania; Farmaki, Theodora; Abatzopoulos, Theodore J

    2015-08-01

    Research on stress responses in animals has increased greatly during the last decades. Though most studies focus on the cellular and molecular bases of the stress response mechanisms, the ecological and evolutionary aspects of stress responses gain more and more interest. Here, we use species and parthenogenetic strains of the genus Artemia, an extremophile model organism, to study, for the first time, a protein well known for its chaperone activity and its involvement in stress responses. More specifically, transcription and protein accumulation of an FK506-Binding Protein (FKBP) homologue were investigated under heat and salt stresses. Additionally, the mRNA levels of ubiquitin, a heat-inducible protein related to the proteasomal pathway, were quantitated under these conditions. Biochemical and phylogenetic analyses showed that the studied FKBP orthologue is a typical representative of the family that clusters with other crustacean sequences. The expression was increased in both fkbp and ubiquitin genes after salt and heat stresses. However, our results in combination with the fact that Artemia species and parthenogenetic strains, selected for this study, exhibit different heat or salt tolerance provide useful hints about the evolutionary significance of FKBP and ubiquitin. Regarding FKBP, mRNA expression and protein accumulation seem to depend on the environmental conditions and the evolutionary history of each Artemia population while ubiquitin has a clear and more conserved role under heat shock. PMID:25868628

  13. A potential source for cellulolytic enzyme discovery and environmental aspects revealed through metagenomics of Brazilian mangroves

    PubMed Central

    2013-01-01

    The mangroves are among the most productive and biologically important environments. The possible presence of cellulolytic enzymes and microorganisms useful for biomass degradation as well as taxonomic and functional aspects of two Brazilian mangroves were evaluated using cultivation and metagenomic approaches. From a total of 296 microorganisms with visual differences in colony morphology and growth (including bacteria, yeast and filamentous fungus), 179 (60.5%) and 117 (39.5%) were isolated from the Rio de Janeiro (RJ) and Bahia (BA) samples, respectively. RJ metagenome showed the higher number of microbial isolates, which is consistent with its most conserved state and higher diversity. The metagenomic sequencing data showed similar predominant bacterial phyla in the BA and RJ mangroves with an abundance of Proteobacteria (57.8% and 44.6%), Firmicutes (11% and 12.3%) and Actinobacteria (8.4% and 7.5%). A higher number of enzymes involved in the degradation of polycyclic aromatic compounds were found in the BA mangrove. Specific sequences involved in the cellulolytic degradation, belonging to cellulases, hemicellulases, carbohydrate binding domains, dockerins and cohesins were identified, and it was possible to isolate cultivable fungi and bacteria related to biomass decomposition and with potential applications for the production of biofuels. These results showed that the mangroves possess all fundamental molecular tools required for building the cellulosome, which is required for the efficient degradation of cellulose material and sugar release. PMID:24160319

  14. Revealing membrane potential by advanced impedance spectroscopy: theoretical and experimental aspects

    NASA Astrophysics Data System (ADS)

    Gheorghiu, M.; Bratu, D.; Olaru, A.; Polonschii, C.; Gheorghiu, E.

    2013-04-01

    In spite of recent advancement of novel optical and electrical techniques, availability of non-invasive, label-free methods to assess membrane potential of living cells is still an open issue. The theory linking membrane potential to the low frequency α dispersion exhibited by suspensions of spherical shelled particles (presenting a net charge distribution on the inner side of the shell) has been pioneered in our previous studies with emphasis on the permittivity spectra. We now report on both theoretical and experimental aspects showing that whereas α dispersion is related to a rather large variation exhibited by the permittivity spectrum the decrement presented by impedance magnitude spectrum is either extremely small, or occurs (for large cells) at very low frequencies (~mHz) explaining the lack of experimental bioimpedance data on the matter. Based on the microscopic model we indicate that an appropriate design of the experiment may enable access to membrane potential as well as to other relevant parameters when investigating living cells and charged lipid vesicles. We discuss the effect on the low frequency of permittivity and impedance spectra of: I. Parameters pertaining to cell membrane i.e. (i) membrane potential, (ii) size of the cells/vesicles, (iii) conductivity; II. Conductivity of the outer medium. A novel measuring set-up has recently been developed within the International Centre of Biodynamics allowing for sensitive low frequency (~10mHz) four point (bio)impedance assays. Its capability to test theoretical predictions is reported as well. The far reaching implications of this study applicability for life sciences (noninvasive access to the dynamics of relevant cell parameters) as well as for biosensing applications, e.g. assess the cytotoxicity of a wide range of stimuli, will be outlined.

  15. Novel aspects of COP9 signalosome functions revealed through analysis of hypomorphic csn mutants

    PubMed Central

    Parker, Jane E

    2009-01-01

    The COP9 signalosome (CSN) is a conserved eukaryotic protein complex implicated in the regulation of cullin-RING type E3 ubiquitin ligases by cleaving the small peptide RUB/Nedd8 from cullins. However, detailed analysis of CSN physiological functions in Arabidopsis has been hampered by the early seedling-lethality of csn null mutants. We and others have now identified a number of viable hypomorphic csn mutants which start to reveal novel CSN-dependent activities in adult Arabidopsis plants.1 Here, we present a detailed comparative analysis of the csn5a-1 and csn2-5 mutants as a mean to improve understanding of CSN functions in plant cells. Our observations point to CSN-independent activities of CSN5 and suggest a role of the CSN in cytoskeleton assembly/organization. PMID:19847120

  16. Important aspects of Eastern Mediterranean large-scale variability revealed from data of three fixed observatories

    NASA Astrophysics Data System (ADS)

    Bensi, Manuel; Velaoras, Dimitris; Cardin, Vanessa; Perivoliotis, Leonidas; Pethiakis, George

    2015-04-01

    Long-term variations of temperature and salinity observed in the Adriatic and Aegean Seas seem to be regulated by larger-scale circulation modes of the Eastern Mediterranean (EMed) Sea, such as the recently discovered feedback mechanisms, namely the BiOS (Bimodal Oscillating System) and the internal thermohaline pump theories. These theories are the results of interpretation of many years' observations, highlighting possible interactions between two key regions of the EMed. Although repeated oceanographic cruises carried out in the past or planned for the future are a very useful tool for understanding the interaction between the two basins (e.g. alternating dense water formation, salt ingressions), recent long time-series of high frequency (up to 1h) sampling have added valuable information to the interpretation of internal mechanisms for both areas (i.e. mesoscale eddies, evolution of fast internal processes, etc.). During the last 10 years, three deep observatories were deployed and maintained in the Adriatic, Ionian, and Aegean Seas: they are respectively, the E2-M3A, the Pylos, and the E1-M3A. All are part of the largest European network of Fixed Point Open Ocean Observatories (FixO3, http://www.fixo3.eu/). Herein, from the analysis of temperature and salinity, and potential density time series collected at the three sites from the surface down to the intermediate and deep layers, we will discuss the almost perfect anti-correlated behavior between the Adriatic and the Aegean Seas. Our data, collected almost continuously since 2006, reveal that these observatories well represent the thermohaline variability of their own areas. Interestingly, temperature and salinity in the intermediate layer suddenly increased in the South Adriatic from the end of 2011, exactly when they started decreasing in the Aegean Sea. Moreover, Pylos data used together with additional ones (e.g. Absolute dynamic topography, temperature and salinity data from other platforms) collected

  17. Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases

    PubMed Central

    Riley, B.E.; Lougheed, J.C.; Callaway, K.; Velasquez, M.; Brecht, E.; Nguyen, L.; Shaler, T.; Walker, D.; Yang, Y.; Regnstrom, K.; Diep, L.; Zhang, Z.; Chiou, S.; Bova, M.; Artis, D.R.; Yao, N.; Baker, J.; Yednock, T.; Johnston, J.A.

    2013-01-01

    Parkin is a RING-between-RING E3 ligase that functions in the covalent attachment of ubiquitin to specific substrates, and mutations in Parkin are linked to Parkinson’s disease, cancer and mycobacterial infection. The RING-between-RING family of E3 ligases are suggested to function with a canonical RING domain and a catalytic cysteine residue usually restricted to HECT E3 ligases, thus termed ‘RING/HECT hybrid’ enzymes. Here we present the 1.58 Å structure of Parkin-R0RBR, revealing the fold architecture for the four RING domains, and several unpredicted interfaces. Examination of the Parkin active site suggests a catalytic network consisting of C431 and H433. In cells, mutation of C431 eliminates Parkin-catalysed degradation of mitochondria, and capture of an ubiquitin oxyester confirms C431 as Parkin’s cellular active site. Our data confirm that Parkin is a RING/HECT hybrid, and provide the first crystal structure of an RING-between-RING E3 ligase at atomic resolution, providing insight into this disease-related protein. PMID:23770887

  18. Changes in cecal microbiota and mucosal gene expression revealed new aspects of epizootic rabbit enteropathy.

    PubMed

    Bäuerl, Christine; Collado, M Carmen; Zúñiga, Manuel; Blas, Enrique; Pérez Martínez, Gaspar

    2014-01-01

    Epizootic Rabbit Enteropathy (ERE) is a severe disease of unknown aetiology that mainly affects post-weaning animals. Its incidence can be prevented by antibiotic treatment suggesting that bacterial elements are crucial for the development of the disease. Microbial dynamics and host responses during the disease were studied. Cecal microbiota was characterized in three rabbit groups (ERE-affected, healthy and healthy pretreated with antibiotics), followed by transcriptional analysis of cytokines and mucins in the cecal mucosa and vermix by q-rtPCR. In healthy animals, cecal microbiota with or without antibiotic pretreatment was very similar and dominated by Alistipes and Ruminococcus. Proportions of both genera decreased in ERE rabbits whereas Bacteroides, Akkermansia and Rikenella increased, as well as Clostridium, γ-Proteobacteria and other opportunistic and pathogenic species. The ERE group displayed remarkable dysbiosis and reduced taxonomic diversity. Transcription rate of mucins and inflammatory cytokines was very high in ERE rabbits, except IL-2, and its analysis revealed the existence of two clearly different gene expression patterns corresponding to Inflammatory and (mucin) Secretory Profiles. Furthermore, these profiles were associated to different bacterial species, suggesting that they may correspond to different stages of the disease. Other data obtained in this work reinforced the notion that ERE morbidity and mortality is possibly caused by an overgrowth of different pathogens in the gut of animals whose immune defence mechanisms seem not to be adequately responding. PMID:25147938

  19. New Aspects of Photocurrent Generation at Graphene pn Junctions Revealed by Ultrafast Optical Measurements

    NASA Astrophysics Data System (ADS)

    Aivazian, Grant; Sun, Dong; Jones, Aaron; Ross, Jason; Yao, Wang; Cobden, David; Xu, Xiaodong

    2012-02-01

    The remarkable electrical and optical properties of graphene make it a promising material for new optoelectronic applications. However, one important, but so far unexplored, property is the role of hot carriers in charge and energy transport at graphene interfaces. Here we investigate the photocurrent (PC) dynamics at a tunable graphene pn junction using ultrafast scanning PC microscopy. Pump-probe measurements show a temperature dependent relaxation time of photogenerated carriers that increases from 1.5ps at 290K to 4ps at 20K; while the amplitude of the PC is independent of the lattice temperature. These observations imply that it is hot carriers, not phonons, which dominate ultrafast energy transport. Gate dependent measurements show many interesting features such as pump induced saturation, enhancement, and sign reversal of probe generated PC. These observations reveal that the underlying PC mechanism is a combination of the thermoelectric and built-in electric field effects. Our results enhance the understanding of non-equilibrium electron dynamics, electron-electron interactions, and electron-phonon interactions in graphene. They also determine fundamental limits on ultrafast device operation speeds (˜500 GHz) for graphene-based photodetectors.

  20. Changes in Cecal Microbiota and Mucosal Gene Expression Revealed New Aspects of Epizootic Rabbit Enteropathy

    PubMed Central

    Zúñiga, Manuel; Blas, Enrique; Pérez Martínez, Gaspar

    2014-01-01

    Epizootic Rabbit Enteropathy (ERE) is a severe disease of unknown aetiology that mainly affects post-weaning animals. Its incidence can be prevented by antibiotic treatment suggesting that bacterial elements are crucial for the development of the disease. Microbial dynamics and host responses during the disease were studied. Cecal microbiota was characterized in three rabbit groups (ERE-affected, healthy and healthy pretreated with antibiotics), followed by transcriptional analysis of cytokines and mucins in the cecal mucosa and vermix by q-rtPCR. In healthy animals, cecal microbiota with or without antibiotic pretreatment was very similar and dominated by Alistipes and Ruminococcus. Proportions of both genera decreased in ERE rabbits whereas Bacteroides, Akkermansia and Rikenella increased, as well as Clostridium, γ-Proteobacteria and other opportunistic and pathogenic species. The ERE group displayed remarkable dysbiosis and reduced taxonomic diversity. Transcription rate of mucins and inflammatory cytokines was very high in ERE rabbits, except IL-2, and its analysis revealed the existence of two clearly different gene expression patterns corresponding to Inflammatory and (mucin) Secretory Profiles. Furthermore, these profiles were associated to different bacterial species, suggesting that they may correspond to different stages of the disease. Other data obtained in this work reinforced the notion that ERE morbidity and mortality is possibly caused by an overgrowth of different pathogens in the gut of animals whose immune defence mechanisms seem not to be adequately responding. PMID:25147938

  1. ALE meta-analysis reveals dissociable networks for affective and discriminative aspects of touch.

    PubMed

    Morrison, India

    2016-04-01

    Emotionally-laden tactile stimulation-such as a caress on the skin or the feel of velvet-may represent a functionally distinct domain of touch, underpinned by specific cortical pathways. In order to determine whether, and to what extent, cortical functional neuroanatomy supports a distinction between affective and discriminative touch, an activation likelihood estimate (ALE) meta-analysis was performed. This meta-analysis statistically mapped reported functional magnetic resonance imaging (fMRI) activations from 17 published affective touch studies in which tactile stimulation was associated with positive subjective evaluation (n = 291, 34 experimental contrasts). A separate ALE meta-analysis mapped regions most likely to be activated by tactile stimulation during detection and discrimination tasks (n = 1,075, 91 experimental contrasts). These meta-analyses revealed dissociable regions for affective and discriminative touch, with posterior insula (PI) more likely to be activated for affective touch, and primary somatosensory cortices (SI) more likely to be activated for discriminative touch. Secondary somatosensory cortex had a high likelihood of engagement by both affective and discriminative touch. Further, meta-analytic connectivity (MCAM) analyses investigated network-level co-activation likelihoods independent of task or stimulus, across a range of domains and paradigms. Affective-related PI and discriminative-related SI regions co-activated with different networks, implicated in dissociable functions, but sharing somatosensory co-activations. Taken together, these meta-analytic findings suggest that affective and discriminative touch are dissociable both on the regional and network levels. However, their degree of shared activation likelihood in somatosensory cortices indicates that this dissociation reflects functional biases within tactile processing networks, rather than functionally and anatomically distinct pathways. PMID:26873519

  2. Comparison of Gait Aspects According to FES Stimulation Position Applied to Stroke Patients

    PubMed Central

    Mun, Byeong-mu; Kim, Tae-ho; Lee, Jin-hwan; Lim, Jin-youg; Seo, Dong-kwon; Lee, Dong-jin

    2014-01-01

    [Purpose] This study sought to identify the gait aspects according to the FES stimulation position in stroke patients during gait training. [Subjects and Methods] To perform gait analysis, ten stroke patients were grouped based on 4 types of gait conditions: gait without FES stimulation (non-FES), gait with FES stimulation on the tibialis anterior (Ta), gait with FES stimulation on the tibialis anterior and quadriceps (TaQ), and gait with FES stimulation on the tibialis anterior and gluteus medius (TaGm). [Results] Based on repeated measures analysis of variance of measurements of gait aspects comprised of gait speed, gait cycle, and step length according to the FES stimulation position, the FES stimulation significantly affected gait aspects. [Conclusion] In conclusion, stimulating the tibialis anterior and quadriceps and stimulating the tibialis anterior and gluteus medius are much more effective than stimulating only the tibialis anterior during gait training in stroke patients using FES. PMID:24764634

  3. Modern wound care - practical aspects of non-interventional topical treatment of patients with chronic wounds.

    PubMed

    Dissemond, Joachim; Augustin, Matthias; Eming, Sabine A; Goerge, Tobias; Horn, Thomas; Karrer, Sigrid; Schumann, Hauke; Stücker, Markus

    2014-07-01

    The treatment of patients with chronic wounds is becoming increasingly complex. It was therefore the aim of the members of the working group for wound healing (AGW) of the German Society of Dermatology (DDG) to report on the currently relevant aspects of non-interventional, topical wound treatment for daily practice. -Beside necessary procedures, such as wound cleansing and débridement, we describe commonly used wound dressings, their indications and practical use. Modern antiseptics, which are currently used in wound therapy, usually contain polyhexanide or octenidine. Physical methods, such as negative-pressure treatment, are also interesting options. It is always important to objectify and adequately treat pain symptoms which often affect these patients. Modern moist wound therapy may promote healing, reduce complications, and improve the quality of life in patients with chronic wounds. Together with the improvement of the underlying causes, modern wound therapy is an important aspect in the overall treatment regime for patients with chronic wounds. PMID:24813380

  4. Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions

    PubMed Central

    Kovacs, Erika; Harmat, Veronika; Tóth, Judit; Vértessy, Beáta G.; Módos, Károly; Kardos, József; Liliom, Károly

    2010-01-01

    Lipid-protein interactions are rarely characterized at a structural molecular level due to technical difficulties; however, the biological significance of understanding the mechanism of these interactions is outstanding. In this report, we provide mechanistic insight into the inhibitory complex formation of the lipid mediator sphingosylphosphorylcholine with calmodulin, the most central and ubiquitous regulator protein in calcium signaling. We applied crystallographic, thermodynamic, kinetic, and spectroscopic approaches using purified bovine calmodulin and bovine cerebral microsomal fraction to arrive at our conclusions. Here we present 1) a 1.6-Å resolution crystal structure of their complex, in which the sphingolipid occupies the conventional hydrophobic binding site on calmodulin; 2) a peculiar stoichiometry-dependent binding process: at low or high protein-to-lipid ratio calmodulin binds lipid micelles or a few lipid molecules in a compact globular conformation, respectively, and 3) evidence that the sphingolipid displaces calmodulin from its targets on cerebral microsomes. We have ascertained the specificity of the interaction using structurally related lipids as controls. Our observations reveal the structural basis of selective calmodulin inhibition by the sphingolipid. On the basis of the crystallographic and biophysical characterization of the calmodulin–sphingosylphosphorylcholine interaction, we propose a novel lipid-protein binding model, which might be applicable to other interactions as well.—Kovacs, E., Harmat, V., Tóth, J., Vértessy, B. G., Módos, K., Kardos, J., Liliom, K. Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions. PMID:20522785

  5. Evaluation of patients' quality of life aspects after cardiac pacemaker implantation

    PubMed Central

    de Barros, Rubens Tofano; de Carvalho, Sebastião Marcos Ribeiro; Silva, Marcos Augusto de Moraes; Borges, Juliana Bassalobre Carvalho

    2014-01-01

    Objective To evaluate patients' quality of life aspects after pacemaker implantation, relating it to gender, age, and implantation timespan. Methods A total of 107 clinically stable patients of both genders (49.5% women and 50.5% men) over 18 years old (average 69.3±12.6 years) and presenting an implantation timespan of three to 12 months (average 6.36±2.99 months) were evaluated. The evaluation included personal, clinical, and implant data as well as quality of life questionnaires (AQUAREL and SF-36). Statistical analysis was conducted using the t test and Pearson correlation, with a 5% significance level. Results The lowest SF-36 score referred to physical aspects, and the highest score referred to social aspects. In AQUAREL, the lowest score referred to dyspnea, and the highest referred to discomfort. There was a significant association between gender and quality of life in SF-36 (physical functioning and emotional aspects) and in AQUAREL (dyspnea). A negative correlation was observed between age and quality of life (functional capacity in SF-36, and discomfort in AQUAREL) in relation to implantation timespan, a correlation with vitality from SF-36. Conclusion Lower quality of life scores were found in physical aspects and dyspnea; and higher scores in social aspects and discomfort. Men presented higher quality of life scores related to physical functioning, emotional aspects and dyspnea. As age increases, quality of life worsens regarding functional capacity and discomfort; and the longer the pacemaker implantation timespan, the worse quality of life when it comes to vitality. Gender, age, and implantation timespan influence quality of life; thus, these variables must be considered in strategies for improving quality of life of patients with pacemakers. PMID:24896161

  6. A review of systems for the personal aspects of patient care.

    PubMed

    Matthews, D A; Feinstein, A R

    1988-03-01

    Because patients are appropriate judges of the personal aspects of the care received from physicians, the authors conducted lengthy interviews with 50 randomly chosen medical inpatients. They were asked to describe, in an open-ended but semistructured fashion, their favorable and unfavorable impressions and reactions to the personal aspects of care rendered by their physicians. From the specific comments made by the patients in these interviews, we constructed a detailed taxonomy of desired physician attitudes and behaviors. The taxonomy can be used in a manner analogous to a Review of Systems for teaching students and practitioners the elements of personal care and also can be applied for research in patient-physician communication. PMID:3354589

  7. Do patients with different mental disorders show specific aspects of shame?

    PubMed

    Scheel, Corinna N; Bender, Caroline; Tuschen-Caffier, Brunna; Brodführer, Anne; Matthies, Swantje; Hermann, Christiane; Geisse, Eva K; Svaldi, Jennifer; Brakemeier, Eva-Lotta; Philipsen, Alexandra; Jacob, Gitta A

    2014-12-15

    Shame is related to several mental disorders. We assume that facets of shame, namely bodily, cognitive and existential shame, may occur in typical patterns in mental and personality disorders. An excessive level of shame may lead to psychopathological symptoms. However, a lack of shame may also lead to distress, for instance as it may facilitate violation of social norms and thus may promote interpersonal problems. In this study we investigated facets of shame in females suffering from various mental disorders and personality disorders presumably associated with specific aspects of shame. Women suffering from borderline personality disorder (BPD, n=92), attention deficit hyperactivity disorder (ADHD, n=86), major depressive disorder (MDD, n=17), social anxiety disorder (SAD, n=33), and a community sample (COM, n=290) completed the SHAME questionnaire, which is a newly developed instrument to assess adaptive and maladaptive aspects of shame. BPD patients reported the highest level of existential shame compared to all other groups. Compared to the controls, SAD patients displayed stronger bodily and cognitive shame, and ADHD showed lower bodily shame. As assumed, specific aspects of shame were found in different patient groups. It may be important to specifically address these specific aspects of shame in psychotherapy. PMID:25219613

  8. A Ferromagnetic Foreign Body at the Lateral Aspect of the Mandibular Ramus in a Medically Compromised Patient.

    PubMed

    Yamamoto, K; Nakayama, Y; Yamamoto, I; Matsusue, Y; Shimotsuji, H; Kirita, T

    2016-01-01

    A case of a ferromagnetic foreign body in a medically compromised patient was reported. The patient was a 45-year-old male who consulted our department complaining of a foreign body accidentally impacted in the right cheek. X-ray examination revealed a foreign body at the lateral aspect of the right mandibular ramus. The removal of the foreign body was scheduled, but the patient did not return for the procedure. After 8 years he revisited our department for the removal of the foreign body, because it had been found to be ferromagnetic and a barrier to MRI examination. X-ray examination confirmed the foreign body was located at the same site as 8 years prior. Although the patient was suffering from liver cirrhosis with thrombocytopenia and leukopenia, the foreign body was successfully removed under general anesthesia. The foreign body was 12 × 5 × 1 mm, weighed 0.48 g, and was ferromagnetic. The patient's postoperative course was uneventful. X-ray examination confirmed the removal of the foreign body. Since the surgery, the patient has been in generally stable condition with no complications. This case was a rare example of a foreign body that needed to be removed for medical examination. PMID:27583049

  9. Patient focused care team design. Critical aspects of a cost-effective design strategy.

    PubMed

    Leander, W J

    1993-01-01

    It is the critical, yet largely unknown aspects of Patient Focused care team design--the "how" of a design process--which make LRMC's "Care Pairs" a ground-breaking innovation rather than just a distinctive-sounding name. Unfortunately, many hospital leaders of Patient Focused Care programs know the "what" of LRMC's "Care Pairs" but very little, if anything, about this "how." To create Patient Focused care teams which are "right" for your own institution, you must quantify the Costs of Continuity, Competency and Compartmentalization and their associated benefits. Without these informed trade-offs, you and your hospital will be forced to live with someone else's Patient Focused care team design. In summary, it is what you don't know about LRMC's "Care Pairs," not what you do know, that is important to your Patient Focused Care program. Hospitals just beginning to implement Patient Focused Care must understand this "how" if they are to design effective care teams which optimize the performance of their initial unit(s) within their unique environments. Hospitals like LRMC with established Patient Focused Care units must also periodically draw upon this "how" or they face the very real danger of having their Patient Focused care team design(s) become outdated, less effective and eventually detrimental. Or, said another way: "The man who does not read good books has no advantage over those who cannot." Mark Twain. "An out-of-date Patient Focused hospital has no advantage over those which remain unrestructured." The PFCA. The three critical aspects of Patient Focused care team design explored in this article are just the tip of the iceberg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:10133389

  10. Antisaccade performance in Korsakoff patients reveals deficits in oculomotor inhibition.

    PubMed

    Van der Stigchel, Stefan; Reichenbach, Roderick C L; Wester, Arie J; Nijboer, Tanja C W

    2012-01-01

    Oculomotor inhibition reflects the ability to suppress an unwanted eye movement. The goal of the present study was to assess oculomotor inhibition in patients with Korsakoff's syndrome (KS). To this end, an antisaccade task was employed in which an eye movement towards an onset stimulus has to be inhibited, and a voluntary saccade has to be executed in the opposite direction. Compared to the results of a matched control group, patients showed a higher percentage of intrusive saccades, made more antisaccade errors, and showed longer latencies on prosaccade trials. These results clearly show that oculomotor inhibition is impaired in KS. Part of these deficits in oculomotor inhibition may be explained by neuronal atrophy in the frontal areas, which is generally associated with KS. PMID:22712532

  11. A Ferromagnetic Foreign Body at the Lateral Aspect of the Mandibular Ramus in a Medically Compromised Patient

    PubMed Central

    Yamamoto, K; Nakayama, Y; Yamamoto, I; Matsusue, Y; Shimotsuji, H; Kirita, T

    2016-01-01

    A case of a ferromagnetic foreign body in a medically compromised patient was reported. The patient was a 45-year-old male who consulted our department complaining of a foreign body accidentally impacted in the right cheek. X-ray examination revealed a foreign body at the lateral aspect of the right mandibular ramus. The removal of the foreign body was scheduled, but the patient did not return for the procedure. After 8 years he revisited our department for the removal of the foreign body, because it had been found to be ferromagnetic and a barrier to MRI examination. X-ray examination confirmed the foreign body was located at the same site as 8 years prior. Although the patient was suffering from liver cirrhosis with thrombocytopenia and leukopenia, the foreign body was successfully removed under general anesthesia. The foreign body was 12 × 5 × 1 mm, weighed 0.48 g, and was ferromagnetic. The patient’s postoperative course was uneventful. X-ray examination confirmed the removal of the foreign body. Since the surgery, the patient has been in generally stable condition with no complications. This case was a rare example of a foreign body that needed to be removed for medical examination. PMID:27583049

  12. Sociodemographic aspects and quality of life of patients with sickle cell anemia

    PubMed Central

    dos Santos, Juliana Pereira; Gomes Neto, Mansueto

    2013-01-01

    Background Sickle cell anemia is a chronic inherited disease, widespread in the Brazilian population due to the high degree of miscegenation in the country. Despite the high prevalence, there are few studies describing the characteristics of patients and the impact of the disease on quality of life. Objective To describe the sociodemographic profile and the impact of the disease on the quality of life of sickle cell anemia patients. Methods Over 18-year-old patients with sickle cell anemia who attended meetings held by the Associação Baiana de Portadores de Doenças Falciformes, an association for sickle cell anemia patients in Bahia, were interviewed. Sociodemographic data were collected and the generic the Medical Outcomes 36-Item Short-Form Health Survey (SF-36) questionnaire, which is used to assess quality of life, was applied. The analysis of the descriptive statistics was performed using the Statistics Program for the Social Sciences software. Results Thirty-two mostly female (65.6%) patients were interviewed. The mean age was 31.9 ± 12.67 years, 50.0% considered themselves black, 68.8% did not work and 87.5% had per capita income below the poverty line (up to one and a half minimum wages). The SF-36 scores were: limitation by physical aspects 26.56, functional capacity 28.9, emotional aspects 30.20, social aspects, 50.0, pain 50.31, mental health 54.62, general health status 56.09 and vitality 56.71. This shows that the disease has a huge impact on the patients' quality of life. Conclusion The disease interferes in the working capacity of individuals, who mostly have low incomes and impaired access to healthcare services and significantly impacts on their quality of life. PMID:24106440

  13. RNA-Seq Analysis of Sulfur-Deprived Chlamydomonas Cells Reveals Aspects of Acclimation Critical for Cell Survival[W

    PubMed Central

    González-Ballester, David; Casero, David; Cokus, Shawn; Pellegrini, Matteo; Merchant, Sabeeha S.; Grossman, Arthur R.

    2010-01-01

    The Chlamydomonas reinhardtii transcriptome was characterized from nutrient-replete and sulfur-depleted wild-type and snrk2.1 mutant cells. This mutant is null for the regulatory Ser-Thr kinase SNRK2.1, which is required for acclimation of the alga to sulfur deprivation. The transcriptome analyses used microarray hybridization and RNA-seq technology. Quantitative RT-PCR evaluation of the results obtained by these techniques showed that RNA-seq reports a larger dynamic range of expression levels than do microarray hybridizations. Transcripts responsive to sulfur deprivation included those encoding proteins involved in sulfur acquisition and assimilation, synthesis of sulfur-containing metabolites, Cys degradation, and sulfur recycling. Furthermore, we noted potential modifications of cellular structures during sulfur deprivation, including the cell wall and complexes associated with the photosynthetic apparatus. Moreover, the data suggest that sulfur-deprived cells accumulate proteins with fewer sulfur-containing amino acids. Most of the sulfur deprivation responses are controlled by the SNRK2.1 protein kinase. The snrk2.1 mutant exhibits a set of unique responses during both sulfur-replete and sulfur-depleted conditions that are not observed in wild-type cells; the inability of this mutant to acclimate to S deprivation probably leads to elevated levels of singlet oxygen and severe oxidative stress, which ultimately causes cell death. The transcriptome results for wild-type and mutant cells strongly suggest the occurrence of massive changes in cellular physiology and metabolism as cells become depleted for sulfur and reveal aspects of acclimation that are likely critical for cell survival. PMID:20587772

  14. Oral, physical, and behavioral aspects of patient with chromosome 47, XYY syndrome.

    PubMed

    Scheidt, Lisa; Sanabe, Mariane Emi; Diniz, Michele Baffi

    2015-01-01

    Chromosome 47, XYY syndrome is usually diagnosed late. Some of the clinical characteristics of XYY syndrome may be perceptible in dental care. The slow development of cognitive and motor activities and tall stature is common in XYY patients. The aim of this article was to relate the oral, physical, and behavioral aspects of a 6-year-old patient with the chromosome 47, XYY syndrome, diagnosed by means of karyotyping. The patient presented motor difficulty, which led to a fall and traumatism in the anterior region. In the radiography, agenesia of the permanent maxillary lateral incisors, presence of taurodontism in the primary molars, and macrodontia of the maxillary central incisors and permanent molars could be observed. Once the diagnosis was made, it was possible to understand his difficulty at school, and make available appropriate monitoring by a suitable multidisciplinary team to stimulate, control, and minimize the day-to-day difficulties found by patients with this syndrome. PMID:26381641

  15. Epidemiological aspects of rheumatoid arthritis patients affected by oral bisphosphonate-related osteonecrosis of the jaws

    PubMed Central

    2012-01-01

    This literature review aims to evaluate the epidemiologic profile of patients with rheumatoid arthritis (RA) that developed a bisphosphonate-related osteonecrosis that affect the jaws (BRONJ), including demographic aspects, as well as clinical and therapeutic issues. A search of PUBMED/MEDLINE, Scopus, and Cochrane databases from January 2003 to September 2011 was conducted with the objective of identifying publications that contained case reports regarding oral BRONJ in RA patients. Patients with RA who develop oral BRONJ are usually women above 60 years taking steroids and long-term alendronate. Most of them have osteoporosis, and lesions, triggered by dental procedures, are usually detected at stage II in the mandible. Although there is no accepted treatment protocol, these patients seem to have better outcomes with conservative approaches that include antibiotic therapy, chlorhexidine, and drug discontinuation. PMID:22376948

  16. Fibroblasts of Machado Joseph Disease patients reveal autophagy impairment.

    PubMed

    Onofre, Isabel; Mendonça, Nuno; Lopes, Sara; Nobre, Rui; de Melo, Joana Barbosa; Carreira, Isabel Marques; Januário, Cristina; Gonçalves, António Freire; de Almeida, Luis Pereira

    2016-01-01

    Machado Joseph Disease (MJD) is the most frequent autosomal dominantly inherited cerebellar ataxia caused by the over-repetition of a CAG trinucleotide in the ATXN3 gene. This expansion translates into a polyglutamine tract within the ataxin-3 protein that confers a toxic gain-of-function to the mutant protein ataxin-3, contributing to protein misfolding and intracellular accumulation of aggregates and neuronal degeneration. Autophagy impairment has been shown to be one of the mechanisms that contribute for the MJD phenotype. Here we investigated whether this phenotype was present in patient-derived fibroblasts, a common somatic cell type used in the derivation of induced pluripotent stem cells and subsequent differentiation into neurons, for in vitro disease modeling. We generated and studied adult dermal fibroblasts from 5 MJD patients and 4 healthy individuals and we found that early passage MJD fibroblasts exhibited autophagy impairment with an underlying mechanism of decreased autophagosome production. The overexpression of beclin-1 on MJD fibroblasts reverted partially autophagy impairment by increasing the autophagic flux but failed to increase the levels of autophagosome production. Overall, our results provide a well-characterized MJD fibroblast resource for neurodegenerative disease research and contribute for the understanding of mutant ataxin-3 biology and its molecular consequences. PMID:27328712

  17. Fibroblasts of Machado Joseph Disease patients reveal autophagy impairment

    PubMed Central

    Onofre, Isabel; Mendonça, Nuno; Lopes, Sara; Nobre, Rui; de Melo, Joana Barbosa; Carreira, Isabel Marques; Januário, Cristina; Gonçalves, António Freire; de Almeida, Luis Pereira

    2016-01-01

    Machado Joseph Disease (MJD) is the most frequent autosomal dominantly inherited cerebellar ataxia caused by the over-repetition of a CAG trinucleotide in the ATXN3 gene. This expansion translates into a polyglutamine tract within the ataxin-3 protein that confers a toxic gain-of-function to the mutant protein ataxin-3, contributing to protein misfolding and intracellular accumulation of aggregates and neuronal degeneration. Autophagy impairment has been shown to be one of the mechanisms that contribute for the MJD phenotype. Here we investigated whether this phenotype was present in patient-derived fibroblasts, a common somatic cell type used in the derivation of induced pluripotent stem cells and subsequent differentiation into neurons, for in vitro disease modeling. We generated and studied adult dermal fibroblasts from 5 MJD patients and 4 healthy individuals and we found that early passage MJD fibroblasts exhibited autophagy impairment with an underlying mechanism of decreased autophagosome production. The overexpression of beclin-1 on MJD fibroblasts reverted partially autophagy impairment by increasing the autophagic flux but failed to increase the levels of autophagosome production. Overall, our results provide a well-characterized MJD fibroblast resource for neurodegenerative disease research and contribute for the understanding of mutant ataxin-3 biology and its molecular consequences. PMID:27328712

  18. Medico-legal aspects of dental treatment of the ageing and aged patient.

    PubMed

    Story, R D

    2015-03-01

    The medico-legal aspects of the dental management of ageing and aged patients relate mainly to the assessment of the patient's competence and the role of substitute decision makers. Dentists will assess whether or not a patient is competent to give informed consent to treatment. Lawyers use the word 'capacity' when deciding whether a person can make an important decision about their life. Competence and capacity mean the same thing. Assessment of competence and the role of substitute decision makers rests firmly on a sound understanding of the ethical basis of dental practice. This article will discuss the ethical basis of dental practice; the assessment of competence and the gaining of informed consent; the role of substitute decision makers and the nature of the decisions that are made at the end of life. PMID:25762043

  19. [The definition of illness and aspects of patient care in early Franciscan sources].

    PubMed

    Puchalska-Dabrowska, Bernadetta M

    2006-01-01

    The article aims at the analysis of the definition of illness and principal forms of patient treatment in early Franciscan sources. The term "illness" as present in the texts under discussion is understood both "spritually" as the condition of a person in the state of sin and "traditionally" as a physical or mental disease. The author's research focuses mainly on the second aspect of the term. The person of a sick and the necessity of patient care is one of the key problems in Franciscan spirituality, emphasized by major documents regulating the life of the first communities of the Friars Minor and Poor Clares. Concrete examples of patient treatment found in the early Franciscan hagiography provide an interesting material for studying both history of medicine and the charisma of St. Francis and his followers. PMID:17644993

  20. Quality of life and psychosocial aspects in Greek patients with psoriasis: a cross-sectional study*

    PubMed Central

    Kouris, Anargyros; Christodoulou, Christos; Stefanaki, Christina; Livaditis, Miltiadis; Tsatovidou, Revekka; Kouskoukis, Constantinos; Petridis, Athanasios; Kontochristopoulos, George

    2015-01-01

    BACKGROUND Psoriasis is a common, long-term skin disease associated with high levels of psychological distress and a considerable adverse impact on life. The effects of psoriasis, beyond skin affliction, are seldom recognized and often undertreated. OBJECTIVE The aim of the study is to evaluate the quality of life, anxiety and depression, self-esteem and loneliness in patients with psoriasis. METHODS Eighty-four patients with psoriasis were enrolled in the study. The quality of life, depression and anxiety, loneliness and self-esteem of the patient were assessed using the Dermatology Life Quality Index, Hospital Anxiety and Depression Scale, the UCLA loneliness Scale (UCLA-Version 3) and Rosenberg's Self-esteem Scale, respectively. RESULTS The Dermatology Quality of Life Index score among psoriasis patients was 12.61 ± 4.88. They had statistically significantly higher scores according to the Hospital Anxiety and Depression Scale -anxiety subscale (p=0.032)-compared with healthy volunteers. Moreover, a statistically significant difference was found between the two groups concerning the UCLA-scale (p=0.033) and RSES-scale (p<0.0001). Female patients presented with lower self-esteem than male patients. CONCLUSION Psoriasis is a distressing, recurrent disorder that significantly impairs quality of life. Therefore, the recognition and future management of psoriasis may require the involvement of multi-disciplinary teams to manage the physical, psychological and social aspects of the condition, as is the case for systemic, long-term conditions. PMID:26734865

  1. Selected Aspects of Mental Health of Elderly Patients with Chronic Back Pain Treated in Primary Care Centers

    PubMed Central

    Cabak, Anna; Dąbrowska-Zimakowska, Anna; Tomaszewski, Paweł; Łyp, Marek; Kaczor, Ryszard; Tomaszewski, Wiesław; Fijałkowska, Barbara; Kotela, Ireneusz

    2015-01-01

    Background Improvement of the effectiveness and efficiency of chronic back pain therapy is a continuing challenge on an international scale. The aim of the present study was to tentatively assess mental health of patients with chronic back pain treated in primary care centers. Material/Methods The study enrolled 100 persons over 50 years of age. The back pain group consisted of 53 patients with chronic back pain and the control group consisted of 47 pain-free persons. The assessment of mental health used a Polish version of the international Goldberger’s General Health Questionnaire (GHQ-28). ANOVA (1- and 2-factor) analysis of variance, Tukey’s test, and Pearson’s simple correlation were used to analyze the significance of differences, with the significance level set at α=0.05. Results All patients with chronic back pain, regardless of their age and gender, displayed poorer mental well-being compared to the control group: their overall score was higher by over 7 points than in persons without back pain (F1.96=14.8; p<0.001). Men with back pain were significantly more susceptible to depression than women (F2.96=5.5; p<0.05), compared to the control group. The duration of back pain also showed a significant (p<0.05) direct correlation with the overall mental health score from the questionnaire. Mental health was considerably poorer among patients occasionally (p<0.001) and regularly (p<0.05) consuming analgesics than among persons who did not do so. Conclusions The study revealed that mental health was markedly poorer in patients with chronic back pain than in healthy controls. A preliminary assessment of aspects of mental health should be given more attention in the rehabilitation of patients with chronic back pain treated in primary care center outpatient clinics. PMID:26522877

  2. Practical aspects of prostate MRI: hardware and software considerations, protocols, and patient preparation.

    PubMed

    Starobinets, Olga; Korn, Natalie; Iqbal, Sonam; Noworolski, Susan M; Zagoria, Ronald; Kurhanewicz, John; Westphalen, Antonio C

    2016-05-01

    The use of multiparametric MRI scans for the evaluation of men with prostate cancer has increased dramatically and is likely to continue expanding as new developments come to practice. However, it has not yet gained the same level of acceptance of other imaging tests. Partly, this is because of the use of suboptimal protocols, lack of standardization, and inadequate patient preparation. In this manuscript, we describe several practical aspects of prostate MRI that may facilitate the implementation of new prostate imaging programs or the expansion of existing ones. PMID:27193785

  3. [Socio-hygienic aspects of the contingents of adult patients with pulmonary tuberculosis].

    PubMed

    Shefer, L B; Nabokova, I P

    1989-01-01

    The pattern of tuberculous patients was analyzed by groups of dispensary registration and types of the disease. A higher proportion of the patients with advanced tuberculosis from rural areas was revealed. Composition of the patients was studied by the social groups, educational level, marital status and housing conditions. It was shown that 38.7 per cent of the patients had concomitant diseases. Among them 17.2 per cent suffered from chronic alcoholism. On the whole, the number of heavy alcohol drinkers amounted to 37.8 per cent. Interrelation between the above social and hygienic factors and severity of tuberculosis was demonstrated. The patients were followed up for 3 years and marked improvement was observed in 69.4 per cent of them. The disease outcomes depended on the sex, age, social factors, bad habits and concomitant diseases, Economic losses from 1 tuberculous patient were calculated. A model of changes in the patient contingents and economic losses from the patients in regard to the treatment was constructed. PMID:2530573

  4. Psychosocial and legal aspects of oncological treatment in patients with cognitive impairment

    PubMed Central

    Kuśnierkiewicz, Maria; Kędziora, Justyna; Jaroszyk-Pawlukiewicz, Joanna; Nowak-Jaroszyk, Monika

    2013-01-01

    With society getting older and affected by many diseases, more and more people suffer from severe cognitive disorders. As practice shows, the legal situations of such people is often problematic. This is due to a number of factors, such as short time since the deterioration of patient's condition, initial symptoms ignored, social prejudice towards the idea of incapacitation or taking decisions for a patient, complicated procedures and, sometimes, insufficient knowledge of legal regulations. Cognitive disorders also occur in patients treated for cancer. To be effective, oncological treatment needs to be started as early as possible. This, however, does not meet the criteria of sudden threat to life. The present article relates to both the psychosocial and legal aspects of care of people suffering from intense disorders of memory, attention, problem solving, executive functions, and other. Surely, physicians know how to handle patients with the above dysfunctions. However, legal procedures aimed to protect patients’ rights are often unclear and time consuming. In practice, this often amounts to a dilemma whether to treat or follow the applicable law. Certainly, solutions in this regard should be clearer and better adapted to the needs arising from specific treatment needs of particular groups of patients. PMID:24936334

  5. Different Aspects of Fatigue Experienced by Patients Receiving Maintenance Dialysis in Hemodialysis Units

    PubMed Central

    Biniaz, Vajihe; Tayybi, Ali; Nemati, Eghlim; Sadeghi Shermeh, Mehdi; Ebadi, Abbas

    2013-01-01

    Background Fatigue, a common symptom reported by patients receiving dialysis, is a multidimensional and subjective experience which is readily understood by individuals but difficult to measure. Objectives This study was performed to identify the prevalence of differential aspects of fatigue among patients receiving maintenance dialysis. Patients and Methods The cross-sectional study was conducted in two hemodialysis wards in Tehran with a sample of 163 participants. In this study, the multidimensional fatigue inventory was used to determine the level of fatigue. Demographic data were also collected with self-report survey. To analyze data with SPSS statistical software, test Chi square, T-test, and ANOVA were used. P- Value less than 0.05 was considered significant. Results All the patients experienced degrees of fatigue and 50 (30.7%) of the participants experienced a high level of fatigue. Fatigue scores arrangement was founded for physical fatigue followed by reduced activity and general fatigue. Lower levels of fatigue were reported for mental fatigue and reduced motivation. There was no diversity in this study in the levels of fatigue in respects of gender and marital status and employment status. Participants with diabetic nephropathy were the most fatigued. Conclusions People with chronic kidney disease regardless of their age, gender, state of health, and duration of hemodialysis experience high levels of fatigue; it is particularly important for health providers to understand this level of fatigue which affects the daily life of patients. PMID:24350089

  6. Different aspects of dysexecutive syndrome in patients with moyamoya disease and its clinical subtypes.

    PubMed

    Fang, Lingling; Huang, Jia; Zhang, Qian; Chan, Raymond C K; Wang, Rong; Wan, Weiqing

    2016-08-01

    OBJECTIVE Dysexecutive syndrome is common in patients with moyamoya disease (MMD), a chronic cerebrovascular disease that is characterized by stenosis of the bilateral internal carotid arteries and progressive collateral revascularization, and MMD can be classified as ischemic or hemorrhagic according to the disease presentation and history. In this study, the authors aimed to determine which aspects of executive function are impaired in patients with MMD, in addition to the specific dysexecutive functions present among its clinical subtypes and the mechanisms underlying dysexecutive function in these patients. METHODS The authors administered 5 typical executive function tests (the Stroop test, the Hayling Sentence Completion Test [HSCT], the verbal fluency [VF] test, the N-back test, and the Sustained Attention to Response Task [SART]) to 49 patients with MMD and 47 IQ-, age-, education-, and social status-matched healthy controls. The dysexecutive questionnaire (DEX) was also used to assess participants' subjective feelings about their executive function. A total of 39 of the patients were evaluated by CT perfusion (CTP) before the assessments were performed, and the correlations among the performances of the patients on the above tests with the parameters of cerebral blood volume, cerebral blood flow (CBF), mean transit time (MTT), and time-to-peak (TTP) in the frontal lobes of these patients were also analyzed. RESULTS Many aspects of executive function in the patients with MMD were significantly poorer than those in the healthy controls, and the patients performed particularly poorer on the VF test, HSCT, N-back test, and SART. The patients with hemorrhagic MMD exhibited worse executive inhibition, executive processing, and semantic inhibition compared with those with ischemic MMD, but the latter group presented a worse working memory and poorer sustained attention. There were no significant differences in the DEX scores between the patients with MMD and

  7. Thromboelastography, thrombin generation test and thrombodynamics reveal hypercoagulability in patients with multiple myeloma.

    PubMed

    Gracheva, Marina A; Urnova, Evdokiya S; Sinauridze, Elena I; Tarandovskiy, Ivan D; Orel, Elena B; Poletaev, Alexander V; Mendeleeva, Larisa P; Ataullakhanov, Fazoil I; Balandina, Anna N

    2015-01-01

    Patients with multiple myeloma (MM) are at increased risk of venous thromboembolism. Therefore, adequate laboratory control of hemostasis and subsequent adjustments of anticoagulant therapy are necessary. We studied hemostasis changes using thromboelastography (TEG), thrombin generation test (TGT) and thrombodynamics (TD) in primary MM patients (PMMpt, n=25) and patients in remission (RMMpt, n=34) during blood stem cell (BSC) mobilization. TD and TEG reveal hypercoagulability in PMMpt (*p<0.05) in relation to healthy volunteers. There was no difference in any of the tests between PMMpt and RMMpt. We detected no heparin effect in 22% of patients one day after the onset of the prophylactic heparin treatment (500 IU/h) during BSC mobilization; tests shifted toward the hypercoagulability in 75% of patients one day after cyclophosphamide (4 g/m2) chemotherapy. Global hemostasis tests were in good agreement with each other, revealed hypercoagulability and heparin "resistance" in patients with MM and may be useful for therapy individualization. PMID:25907422

  8. Epidemiological analysis on 2375 patients with TMJ disorders: basic statistical aspects

    PubMed Central

    Di Paolo, Carlo; Costanzo, G. Damiana; Panti, Fabrizio; Rampello, Alessandro; Falisi, Giovanni; Pilloni, Andrea; Cascone, Piero; Iannetti, Giorgio

    2013-01-01

    Summary The aim of this work was to present data from a large sample of patients with Temporo-Mandibular Disorders (TMD) in order to clarify some aspects of the development of pathological conditions that affect large parts of the population. This preliminary work put in relation, through an epidemiological evaluation, anamnestic and clinical data collected from a sample of 2375 patients affected by TMD. Personal data were provided by questionnaire (age, sex, status, etc.), while clinical data were collected following a specific medical chart compiled in accordance with international criteria for TMD. An analysis of these data clearly showed that there were large quantities of variables involved in these disorders and which occur with a wide variety possible of clinical signs. This complexity, in accordance with the current knowledge that it is not able to clarify the etiology of these disorders, makes intricate both diagnostic then therapeutic aspects. You would find in front of a multi-factorial systemic disease that, interfering with the individual bioavailability, exposes him to the possibility of perceiving noxious stimuli which otherwise would not able to reach the pain threshold. To support this hypothesis is the data founded in this report that showed how many patients suffered, at the same time, by muscle and spinal pain associated to headache, pain that occur with high frequency from the same side. The presence of these painful conditions tends to underestimate the dysfunctional problems even if they occur with greater clinical prevalence. Further research should be carried out to clarify these controversial issues. PMID:23741538

  9. The adaptation problems of patients undergoing hemodialysis: socio-economic and clinical aspects1

    PubMed Central

    Frazão, Cecília Maria Farias de Queiroz; de Sá, Jéssica Dantas; Medeiros, Ana Beatriz de Almeida; Fernandes, Maria Isabel da Conceição Dias; Lira, Ana Luisa Brandão de Carvalho; Lopes, Marcos Venícios de Oliveira

    2014-01-01

    OBJECTIVES: to identify adaptation problems under Roy's Model in patients undergoing hemodialysis and to correlate them with the socioeconomic and clinical aspects. METHOD: a transversal study, undertaken using a questionnaire. The sample was made up of 178 individuals. The Chi-squared and Mann-Whitney U tests were undertaken. RESULTS: the adaptation problems and the socioeconomic and clinical aspects which presented statistical associations were: Hyperkalemia and age; Edema and income; Impairment of a primary sense: touch and income; Role failure and age; Sexual dysfunction and marital status and sex; Impairment of a primary sense: vision and years of education; Intolerance to activity and years of education; Chronic pain and sex and years of education; Impaired skin integrity and age: Hypocalcemia and access; Potential for injury and age and years of education; Nutrition below the organism's requirements and age; Impairment of a primary sense: hearing and sex and kinetic evaluation of urea; Mobility in gait and/or coordination restricted, and months of hemodialysis; and, Loss of ability for self-care, and months of hemodialysis and months of illness. CONCLUSION: adaptation problems in the clientele undergoing hemodialysis can be influenced by socioeconomic/clinical data. These findings contribute to the development of the profession, fostering the nurse's reflection regarding the care. PMID:25591091

  10. Quality of life aspects of patients with psoriasis using a series of herbal products.

    PubMed

    França, K; Tirant, M; Hercogovấ, J; Novotny, F; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Wollina, U; Roccia, M G; Lotti, T

    2016-01-01

    Psoriasis is a chronic inflammatory disease affecting 1-3% of the general population. Due to the chronic nature of the disease, patients suffer from substantial psychosocial impact and impaired quality of life. Dr Michaels® (also branded as Soratinex®), an Australian series of topical herbal products, has been showing promising results for the treatment of patients with chronic plaque psoriasis and consequent improvement in their quality of life. This study aims to access the changes in quality of life of patients with Psoriasis using an Australian series of herbal skin-care products Dr Michaels® (Soratinex®) for psoriasis. The aim of this study is to observe and analyze the impact of Dr Michaels® product family on the quality of life of patients with psoriasis, 566 patients completed the Dermatology Quality of Life Index (DQLI) questionnaire in their initial consultation and at 3 follow up consultations, over a 6 months period. At the end of the data collection, all patients’ answers were recorded and analyzed. The Psoriasis Area and Severity (PASI) Index were used to measure the severity and extent of psoriasis during the 3 consultations. The PASI for severe, moderate-severe, mild-moderate cases across time revealed a significant effect of the treatment within weeks, confirming the decreasing scores during the treatment. As well as PASI results, the final DLQI score showed a sensible reduction from mean =6.716 (at week 0) to 6.252 (at week 2), 4.015 (at week 6) and 2.407 (at week 10) signifying a 64.2% reduction of the initial score. This study demonstrates that Dr. Michaels® (Soratinex®) products, an Australian series of herbal-based skin products is effective for the treatment of psoriasis. This treatment also significantly improves patient’s quality of life. PMID:27498669

  11. The dexamethasone suppression test in depressed patients: clinical and biochemical aspects.

    PubMed

    Holsboer, F

    1983-07-01

    Endogenous depression (ED) is regarded as a psychiatric disease with a biological pathogenesis. Consequently patients with ED respond favourably to somatic treatment, whereas for non-endogenously depressed patients drug-treatment would be often inappropriate. Until now, psychopathologists have failed to define precisely the endogenous subtype of depression on clinical features alone. It is well established that a subgroup of depressed patients shows hypersecretion of cortisol and consequently inadequate suppression of cortisol after a test dose of dexamethasone. This dexamethasone suppression test (DST) was introduced as a laboratory marker, specifically identifying endogenously depressed individuals. This survey illustrates the present dispute about the diagnostic confidence and clinical value of the DST in a psychiatric population, and related biochemical aspects. The following conclusions are stated: (a) use of the DST to validate a theory of nosology is premature. (b) Influence of psychoactive drug medication, diet and weight loss have to be established. (c) Preliminary data suggest that abnormal DST results frequently normalize before clinical recovery and abnormal DST results may be observed before a relapse into depression is clinically apparent. From this it was concluded that the DST might be useful as predictor of clinical outcome. (d) From the association of depressive episodes with disinhibited HPA-activity, a causative role of corticotropin and glucocorticoids in the development of psychiatric illness can be hypothesized. Beside some pharmacological data no supportive evidence for this hypothesis is available. (e) Multisteroid analysis after dexamethasone has provided promising results indicating increased sensitivity of the test when based upon cortisol/11-deoxycortisol ratios and disturbed mineralocorticosteroid secretion in endogenously depressed patients. PMID:6887861

  12. Geometric analysis of Arabidopsis root apex reveals a new aspect of the ethylene signal transduction pathway in development

    NASA Technical Reports Server (NTRS)

    Cervantes, Emilio; Tocino, Angel

    2005-01-01

    Structurally, ethylene is the simplest phytohormone and regulates multiple aspects of plant growth and development. Its effects are mediated by a signal transduction cascade involving receptors, MAP kinases and transcription factors. Many morphological effects of ethylene in plant development, including root size, have been previously described. In this article a combined geometric and algebraic approach has been used to analyse the shape and the curvature in the root apex of Arabidopsis seedlings. The process requires the fitting of Bezier curves that reproduce the root apex shape, and the calculation of the corresponding curvatures. The application of the method has allowed us to identify significant differences in the root curvatures of ethylene insensitive mutants (ein2-1 and etr1-1) with respect to the wild-type Columbia.

  13. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients.

    PubMed

    Poreisz, Csaba; Boros, Klára; Antal, Andrea; Paulus, Walter

    2007-05-30

    Cortical excitability changes induced by tDCS and revealed by TMS, are increasingly being used as an index of neuronal plasticity in the human cortex. The aim of this paper is to summarize the partially adverse effects of 567 tDCS sessions over motor and non-motor cortical areas (occipital, temporal, parietal) from the last 2 years, on work performed in our laboratories. One-hundred and two of our subjects who participated in our tDCS studies completed a questionnaire. The questionnaire contained rating scales regarding the presence and severity of headache, difficulties in concentrating, acute mood changes, visual perceptual changes and any discomforting sensation like pain, tingling, itching or burning under the electrodes, during and after tDCS. Participants were healthy subjects (75.5%), migraine patients (8.8%), post-stroke patients (5.9%) and tinnitus patients (9.8%). During tDCS a mild tingling sensation was the most common reported adverse effect (70.6%), moderate fatigue was felt by 35.3% of the subjects, whereas a light itching sensation under the stimulation electrodes occurred in 30.4% of cases. After tDCS headache (11.8%), nausea (2.9%) and insomnia (0.98%) were reported, but fairly infrequently. In addition, the incidence of the itching sensation (p=0.02) and the intensity of tingling sensation (p=0.02) were significantly higher during tDCS in the group of the healthy subjects, in comparison to patients; whereas the occurrence of headache was significantly higher in the patient group (p=0.03) after the stimulation. Our results suggest that tDCS applied to motor and non-motor areas according to the present tDCS safety guidelines, is associated with relatively minor adverse effects in healthy humans and patients with varying neurological disorders. PMID:17452283

  14. Antennal RNA-sequencing analysis reveals evolutionary aspects of chemosensory proteins in the carpenter ant, Camponotus japonicus

    PubMed Central

    Hojo, Masaru K.; Ishii, Kenichi; Sakura, Midori; Yamaguchi, Katsushi; Shigenobu, Shuji; Ozaki, Mamiko

    2015-01-01

    Chemical communication is essential for the coordination of complex organisation in ant societies. Recent comparative genomic approaches have revealed that chemosensory genes are diversified in ant lineages, and suggest that this diversification is crucial for social organisation. However, how such diversified genes shape the peripheral chemosensory systems remains unknown. In this study, we annotated and analysed the gene expression profiles of chemosensory proteins (CSPs), which transport lipophilic compounds toward chemosensory receptors in the carpenter ant, Camponotus japonicus. Transcriptome analysis revealed 12 CSP genes and phylogenetic analysis showed that 3 of these are lineage-specifically expanded in the clade of ants. RNA sequencing and real-time quantitative polymerase chain reaction revealed that, among the ant specific CSP genes, two of them (CjapCSP12 and CjapCSP13) were specifically expressed in the chemosensory organs and differentially expressed amongst ant castes. Furthermore, CjapCSP12 and CjapCSP13 had a ratio of divergence at non-synonymous and synonymous sites (dN/dS) greater than 1, and they were co-expressed with CjapCSP1, which is known to bind cuticular hydrocarbons. Our results suggested that CjapCSP12 and CjapCSP13 were functionally differentiated for ant-specific chemosensory events, and that CjapCSP1, CjapCSP12, and CjapCSP13 work cooperatively in the antennal chemosensilla of worker ants. PMID:26310137

  15. Some aspects of the venom proteome of the Colubridae snake Philodryas olfersii revealed from a Duvernoy's (venom) gland transcriptome.

    PubMed

    Ching, Ana T C; Rocha, Marisa M T; Paes Leme, Adriana F; Pimenta, Daniel C; de Fátima D Furtado, Maria; Serrano, Solange M T; Ho, Paulo L; Junqueira-de-Azevedo, Inácio L M

    2006-08-01

    We investigated the putative toxins of Philodryas olfersii (Colubridae), a representative of a family of snakes neglected in venom studies despite their growing medical importance. Transcriptomic data of the venom gland complemented by proteomic analysis of the gland secretion revealed the presence of major toxin classes from the Viperidae family, including serine proteases, metalloproteases, C-type lectins, Crisps, and a C-type natriuretic peptide (CNP). Interestingly, the phylogenetic analysis of the CNP precursor showed it as a linker between two related precursors found in Viperidae and Elapidae snakes. We suggest that these precursors constitute a monophyletic group derived from the vertebrate CNPs. PMID:16857193

  16. Deep sequencing reveals microbiota dysbiosis of tongue coat in patients with liver carcinoma.

    PubMed

    Lu, Haifeng; Ren, Zhigang; Li, Ang; Zhang, Hua; Jiang, Jianwen; Xu, Shaoyan; Luo, Qixia; Zhou, Kai; Sun, Xiaoli; Zheng, Shusen; Li, Lanjuan

    2016-01-01

    Liver carcinoma (LC) is a common malignancy worldwide, associated with high morbidity and mortality. Characterizing microbiome profiles of tongue coat may provide useful insights and potential diagnostic marker for LC patients. Herein, we are the first time to investigate tongue coat microbiome of LC patients with cirrhosis based on 16S ribosomal RNA (rRNA) gene sequencing. After strict inclusion and exclusion criteria, 35 early LC patients with cirrhosis and 25 matched healthy subjects were enrolled. Microbiome diversity of tongue coat in LC patients was significantly increased shown by Shannon, Simpson and Chao 1 indexes. Microbiome on tongue coat was significantly distinguished LC patients from healthy subjects by principal component analysis. Tongue coat microbial profiles represented 38 operational taxonomic units assigned to 23 different genera, distinguishing LC patients. Linear discriminant analysis (LDA) effect size (LEfSe) reveals significant microbial dysbiosis of tongue coats in LC patients. Strikingly, Oribacterium and Fusobacterium could distinguish LC patients from healthy subjects. LEfSe outputs show microbial gene functions related to categories of nickel/iron_transport, amino_acid_transport, energy produced system and metabolism between LC patients and healthy subjects. These findings firstly identify microbiota dysbiosis of tongue coat in LC patients, may providing novel and non-invasive potential diagnostic biomarker of LC. PMID:27605161

  17. Deep sequencing reveals microbiota dysbiosis of tongue coat in patients with liver carcinoma

    PubMed Central

    Lu, Haifeng; Ren, Zhigang; Li, Ang; Zhang, Hua; Jiang, Jianwen; Xu, Shaoyan; Luo, Qixia; Zhou, Kai; Sun, Xiaoli; Zheng, Shusen; Li, Lanjuan

    2016-01-01

    Liver carcinoma (LC) is a common malignancy worldwide, associated with high morbidity and mortality. Characterizing microbiome profiles of tongue coat may provide useful insights and potential diagnostic marker for LC patients. Herein, we are the first time to investigate tongue coat microbiome of LC patients with cirrhosis based on 16S ribosomal RNA (rRNA) gene sequencing. After strict inclusion and exclusion criteria, 35 early LC patients with cirrhosis and 25 matched healthy subjects were enrolled. Microbiome diversity of tongue coat in LC patients was significantly increased shown by Shannon, Simpson and Chao 1 indexes. Microbiome on tongue coat was significantly distinguished LC patients from healthy subjects by principal component analysis. Tongue coat microbial profiles represented 38 operational taxonomic units assigned to 23 different genera, distinguishing LC patients. Linear discriminant analysis (LDA) effect size (LEfSe) reveals significant microbial dysbiosis of tongue coats in LC patients. Strikingly, Oribacterium and Fusobacterium could distinguish LC patients from healthy subjects. LEfSe outputs show microbial gene functions related to categories of nickel/iron_transport, amino_acid_transport, energy produced system and metabolism between LC patients and healthy subjects. These findings firstly identify microbiota dysbiosis of tongue coat in LC patients, may providing novel and non-invasive potential diagnostic biomarker of LC. PMID:27605161

  18. Dissociations in numerical abilities revealed by progressive cognitive decline in a patient with semantic dementia.

    PubMed

    Cappelletti, Marinella; Kopelman, Michael D; Morton, John; Butterworth, Brian

    2005-10-01

    This study describes a 3-year follow-up investigation of the deterioration of number abilities in a semantic dementia patient (IH). A few studies have previously reported the decline of number knowledge in patients with degenerative disorders, although almost never in semantic dementia (Diesfeldt, 1993; Girelli, Luzzatti, Annoni, & Vecchi, 1999; Grafman, Kempen, Rosenberg, Salazar, & Boller, 1989). These studies described the change of the patients' performance mainly in terms of increased errors in number tasks. On the other hand, dissociations between different types of number abilities, or different arithmetical operations, have been reported in patients with focal lesions. In the present investigation, the cognitive basis of number processing was revealed throughout the patient's cognitive decline. Two major results emerged from a longitudinal study: First, the patient's conceptual knowledge of arithmetic was well preserved despite severe impairment of nonarithmetic conceptual knowledge. Second, the patient's progressive decline revealed patterns of dissociations between different number abilities. These were between (1) multiplication and other arithmetical operations, which particularly emerged in the use of algorithms; (2) impaired knowledge of number facts and procedures on one hand, and conceptual knowledge of arithmetic on the other; and (3) different types of transcoding skills. The implications of these dissociations for the cognitive architecture of number processing are discussed. PMID:21038276

  19. Aspects of atmospheric pollutant origin and deposition revealed by multielemental observations at a rural location in eastern Canada

    NASA Astrophysics Data System (ADS)

    Barrie, L. A.

    1988-04-01

    During autumn 1984, at a location in central Ontario, a study of the elemental composition of aerosols and precipitation was undertaken to determine the feasibility of making daily multielemental measurements on a routine basin, to probe the potential for gaining insight into pollutant origin from multielemental composition, and to estimate trace element deposition to an acid-sensitive watershed. The concentrations of Ti, Br, Mn, In, Na, V, Al, Ca, Se, As, Sb, Pb, Fe, Mg, Cu, Zn, and Cd in aerosol and of Pb, Mg, Ca, As, Br, I, Mn, and V in precipitation were measurable routinely, using neutron activation, X ray fluorescence, and plasma emission spectroscopy. Standard high volume samplers for total aerosols below 15 μm diameter as well as dichotomous samplers and Andersen impactors for size fractionation were operated simultaneously with two wet-only precipitation collectors. Aerosol data revealed four components: one soil (Mg-Ti-Al-Ca-Fe) and three anthropogenic (Se-Sb-Pb-Cd-Br; Mass-Cu-SO4=; In-As). Ranked in order of increasing mass fraction in 2.1- to 10-μm diameter particles are the elements Pb, S, Se, Br, As, Cl, Na, V, In, Cu, Mn, Al, Ba, Ti, and Ca. A comparison of air parcel origin on high- and low-concentration days, using 3-day back trajectories, revealed major source regions of SO4=, Pb, In, As, and Al. The element In is an excellent tracer of smelter emissions to the north. Although the estimated mean ratio of In/Se in smelter emissions from central Ontario is close to that used in the regional aerosol apportionment model of Rahn and Lowenthal, its variability is greater than they propose. In 21 precipitation events, strong correlations were found between H+-SO4 =, Ca++-Mg++, NO3--NH4+-Cl--V, and Pb-Br. The mass ratio of Br/Pb was higher in precipitation (0.47) than in aerosols (0.27), possibly because of precipitation scavenging of HBr gas in addition to Br in aerosols. In ascending order, the estimated dry-deposited fraction of total deposition of

  20. New aspects of the phosphatase VHZ revealed by a high-resolution structure with vanadate and substrate screening

    PubMed Central

    Kuznetsov, Vyacheslav I.; Hengge, Alvan C.; Johnson, Sean J.

    2013-01-01

    The recently discovered 150-residue human VHZ (VH1 related protein, Z member) is one of the smallest protein tyrosine phosphatases (PTPs) known, and contains only the minimal structural elements common to all PTPs. We report a substrate screening analysis and a crystal structure of the VHZ complex with vanadate at 1.1 Å resolution, with a detailed structural comparison with other members of the protein tyrosine phosphatase family, including classical tyrosine-specific protein tyrosine phosphatases (PTPs) and dual specific phosphatases (DSPs). A screen with 360 phosphorylated peptides shows VHZ efficiently catalyzes the hydrolysis of phospho-tyrosine(pY)-containing peptides, but exhibits no activity toward phospho-serine (pS) or phospho-threonine (pT) peptides. The new structure reveals a deep and narrow active site more typical of the classical tyrosine specific PTPs. Despite the high structural and sequence similarities between VHZ and classical PTPs, its general acid IPD-loop is most likely conformationally rigid, in contrast to the flexible WPD counterpart of classical PTPs. VHZ also lacks substrate recognition domains and other domains typically found on classical PTPs. It is therefore proposed that VHZ is more properly classified as an atypical PTP rather than an atypical DSP, as has been suggested. PMID:23145819

  1. A novel molecule integrating therapeutic and diagnostic activities reveals multiple aspects of stem cell-based therapy.

    PubMed

    Hingtgen, Shawn D; Kasmieh, Randa; van de Water, Jeroen; Weissleder, Ralph; Shah, Khalid

    2010-04-01

    Stem cells are promising therapeutic delivery vehicles; however pre-clinical and clinical applications of stem cell-based therapy would benefit significantly from the ability to simultaneously determine therapeutic efficacy and pharmacokinetics of therapies delivered by engineered stem cells. In this study, we engineered and screened numerous fusion variants that contained therapeutic (TRAIL) and diagnostic (luciferase) domains designed to allow simultaneous investigation of multiple events in stem cell-based therapy in vivo. When various stem cell lines were engineered with the optimized molecule, SRL(O)L(2)TR, diagnostic imaging showed marked differences in the levels and duration of secretion between stem cell lines, while the therapeutic activity of the molecule showed the different secretion levels translated to significant variability in tumor cell killing. In vivo, simultaneous diagnostic and therapeutic monitoring revealed that stem cell-based delivery significantly improved pharmacokinetics and anti-tumor effectiveness of the therapy compared to intravenous or intratumoral delivery. As treatment for highly malignant brain tumor xenografts, tracking SRL(O)L(2)TR showed stable stem cell-mediated delivery significantly regressed peripheral and intracranial tumors. Together, the integrated diagnostic and therapeutic properties of SRL(O)L(2)TR answer critical questions necessary for successful utilization of stem cells as novel therapeutic vehicles. PMID:20127797

  2. Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions.

    PubMed

    Kovacs, Erika; Harmat, Veronika; Tóth, Judit; Vértessy, Beáta G; Módos, Károly; Kardos, József; Liliom, Károly

    2010-10-01

    Lipid-protein interactions are rarely characterized at a structural molecular level due to technical difficulties; however, the biological significance of understanding the mechanism of these interactions is outstanding. In this report, we provide mechanistic insight into the inhibitory complex formation of the lipid mediator sphingosylphosphorylcholine with calmodulin, the most central and ubiquitous regulator protein in calcium signaling. We applied crystallographic, thermodynamic, kinetic, and spectroscopic approaches using purified bovine calmodulin and bovine cerebral microsomal fraction to arrive at our conclusions. Here we present 1) a 1.6-Å resolution crystal structure of their complex, in which the sphingolipid occupies the conventional hydrophobic binding site on calmodulin; 2) a peculiar stoichiometry-dependent binding process: at low or high protein-to-lipid ratio calmodulin binds lipid micelles or a few lipid molecules in a compact globular conformation, respectively, and 3) evidence that the sphingolipid displaces calmodulin from its targets on cerebral microsomes. We have ascertained the specificity of the interaction using structurally related lipids as controls. Our observations reveal the structural basis of selective calmodulin inhibition by the sphingolipid. On the basis of the crystallographic and biophysical characterization of the calmodulin-sphingosylphosphorylcholine interaction, we propose a novel lipid-protein binding model, which might be applicable to other interactions as well. PMID:20522785

  3. Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients

    PubMed Central

    Subbiah, Vivek; Bupathi, Manojkumar; Kato, Shumei; Livingston, Andrew; Slopis, John; Anderson, Pete M.; Hong, David S.

    2015-01-01

    Background The aggressive biology of cancers arising in adolescent and young adult (AYA; ages 15–39 years) patients is thought to contribute to poor survival outcomes. Methods We used clinical next-generation sequencing (NGS) results to examine the molecular alterations and diverse biology of cancer in AYA patients referred to the Phase 1 program at UT MD Anderson Cancer Center. Results Among the 28 patients analyzed (14 female and 14 male), 12 had pediatric-type cancers, six had adult-type cancers, and ten had orphan cancers. Unique, hitherto unreported aberrations were identified in all types of cancers. Aberrations in TP53, NKX2-1, KRAS, CDKN2A, MDM4, MCL1, MYC, BCL2L2, and RB1 were demonstrated across all tumor types. Five patients harbored TP53 aberrations; three patients harbored MYC, MCL1, and CDKN2A aberrations; and two patients harbored NKX2-1, KRAS, MDM4, BCL2L2, and RB1 alterations. Several patients had multiple aberrations; a patient with wild-type gastrointestinal stromal tumor harbored five alterations (MDM4, MCL1, KIT, AKT3, and PDGRFA). Conclusions This preliminary report of NGS of cancer in AYA patients reveals diverse and unique aberrations. Further molecular profiling and a deeper understanding of the biology of these unique aberrations are warranted and may lead to targeted therapeutic interventions. PMID:26328274

  4. Predicting the Proteins of Angomonas deanei, Strigomonas culicis and Their Respective Endosymbionts Reveals New Aspects of the Trypanosomatidae Family

    PubMed Central

    Motta, Maria Cristina Machado; Martins, Allan Cezar de Azevedo; de Souza, Silvana Sant’Anna; Catta-Preta, Carolina Moura Costa; Silva, Rosane; Klein, Cecilia Coimbra; de Almeida, Luiz Gonzaga Paula; de Lima Cunha, Oberdan; Ciapina, Luciane Prioli; Brocchi, Marcelo; Colabardini, Ana Cristina; de Araujo Lima, Bruna; Machado, Carlos Renato; de Almeida Soares, Célia Maria; Probst, Christian Macagnan; de Menezes, Claudia Beatriz Afonso; Thompson, Claudia Elizabeth; Bartholomeu, Daniella Castanheira; Gradia, Daniela Fiori; Pavoni, Daniela Parada; Grisard, Edmundo C.; Fantinatti-Garboggini, Fabiana; Marchini, Fabricio Klerynton; Rodrigues-Luiz, Gabriela Flávia; Wagner, Glauber; Goldman, Gustavo Henrique; Fietto, Juliana Lopes Rangel; Elias, Maria Carolina; Goldman, Maria Helena S.; Sagot, Marie-France; Pereira, Maristela; Stoco, Patrícia H.; de Mendonça-Neto, Rondon Pessoa; Teixeira, Santuza Maria Ribeiro; Maciel, Talles Eduardo Ferreira; de Oliveira Mendes, Tiago Antônio; Ürményi, Turán P.; de Souza, Wanderley; Schenkman, Sergio; de Vasconcelos, Ana Tereza Ribeiro

    2013-01-01

    Endosymbiont-bearing trypanosomatids have been considered excellent models for the study of cell evolution because the host protozoan co-evolves with an intracellular bacterium in a mutualistic relationship. Such protozoa inhabit a single invertebrate host during their entire life cycle and exhibit special characteristics that group them in a particular phylogenetic cluster of the Trypanosomatidae family, thus classified as monoxenics. In an effort to better understand such symbiotic association, we used DNA pyrosequencing and a reference-guided assembly to generate reads that predicted 16,960 and 12,162 open reading frames (ORFs) in two symbiont-bearing trypanosomatids, Angomonas deanei (previously named as Crithidia deanei) and Strigomonas culicis (first known as Blastocrithidia culicis), respectively. Identification of each ORF was based primarily on TriTrypDB using tblastn, and each ORF was confirmed by employing getorf from EMBOSS and Newbler 2.6 when necessary. The monoxenic organisms revealed conserved housekeeping functions when compared to other trypanosomatids, especially compared with Leishmania major. However, major differences were found in ORFs corresponding to the cytoskeleton, the kinetoplast, and the paraflagellar structure. The monoxenic organisms also contain a large number of genes for cytosolic calpain-like and surface gp63 metalloproteases and a reduced number of compartmentalized cysteine proteases in comparison to other TriTryp organisms, reflecting adaptations to the presence of the symbiont. The assembled bacterial endosymbiont sequences exhibit a high A+T content with a total of 787 and 769 ORFs for the Angomonas deanei and Strigomonas culicis endosymbionts, respectively, and indicate that these organisms hold a common ancestor related to the Alcaligenaceae family. Importantly, both symbionts contain enzymes that complement essential host cell biosynthetic pathways, such as those for amino acid, lipid and purine/pyrimidine metabolism

  5. Application of a New Dual Localization-Affinity Purification Tag Reveals Novel Aspects of Protein Kinase Biology in Aspergillus nidulans

    PubMed Central

    De Souza, Colin P.; Hashmi, Shahr B.; Osmani, Aysha H.; Osmani, Stephen A.

    2014-01-01

    Filamentous fungi occupy critical environmental niches and have numerous beneficial industrial applications but devastating effects as pathogens and agents of food spoilage. As regulators of essentially all biological processes protein kinases have been intensively studied but how they regulate the often unique biology of filamentous fungi is not completely understood. Significant understanding of filamentous fungal biology has come from the study of the model organism Aspergillus nidulans using a combination of molecular genetics, biochemistry, cell biology and genomic approaches. Here we describe dual localization-affinity purification (DLAP) tags enabling endogenous N or C-terminal protein tagging for localization and biochemical studies in A. nidulans. To establish DLAP tag utility we endogenously tagged 17 protein kinases for analysis by live cell imaging and affinity purification. Proteomic analysis of purifications by mass spectrometry confirmed association of the CotA and NimXCdk1 kinases with known binding partners and verified a predicted interaction of the SldABub1/R1 spindle assembly checkpoint kinase with SldBBub3. We demonstrate that the single TOR kinase of A. nidulans locates to vacuoles and vesicles, suggesting that the function of endomembranes as major TOR cellular hubs is conserved in filamentous fungi. Comparative analysis revealed 7 kinases with mitotic specific locations including An-Cdc7 which unexpectedly located to mitotic spindle pole bodies (SPBs), the first such localization described for this family of DNA replication kinases. We show that the SepH septation kinase locates to SPBs specifically in the basal region of apical cells in a biphasic manner during mitosis and again during septation. This results in gradients of SepH between G1 SPBs which shift along hyphae as each septum forms. We propose that SepH regulates the septation initiation network (SIN) specifically at SPBs in the basal region of G1 cells and that localized gradients

  6. Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

    PubMed Central

    Fassihi, Hiva; Sethi, Mieran; Fawcett, Heather; Wing, Jonathan; Chandler, Natalie; Mohammed, Shehla; Craythorne, Emma; Morley, Ana M. S.; Lim, Rongxuan; Turner, Sally; Henshaw, Tanya; Garrood, Isabel; Giunti, Paola; Hedderly, Tammy; Abiona, Adesoji; Naik, Harsha; Harrop, Gemma; McGibbon, David; Jaspers, Nicolaas G. J.; Botta, Elena; Nardo, Tiziana; Stefanini, Miria; Young, Antony R.; Sarkany, Robert P. E.; Lehmann, Alan R.

    2016-01-01

    Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins. PMID:26884178

  7. Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect.

    PubMed

    Fassihi, Hiva; Sethi, Mieran; Fawcett, Heather; Wing, Jonathan; Chandler, Natalie; Mohammed, Shehla; Craythorne, Emma; Morley, Ana M S; Lim, Rongxuan; Turner, Sally; Henshaw, Tanya; Garrood, Isabel; Giunti, Paola; Hedderly, Tammy; Abiona, Adesoji; Naik, Harsha; Harrop, Gemma; McGibbon, David; Jaspers, Nicolaas G J; Botta, Elena; Nardo, Tiziana; Stefanini, Miria; Young, Antony R; Sarkany, Robert P E; Lehmann, Alan R

    2016-03-01

    Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins. PMID:26884178

  8. Clinical aspects of patients with traumatic lesions of the brachial plexus following surgical treatment☆

    PubMed Central

    de Moraes, Frederico Barra; Kwae, Mário Yoshihide; da Silva, Ricardo Pereira; Porto, Celmo Celeno; Magalhães, Daniel de Paiva; Paulino, Matheus Veloso

    2015-01-01

    Objective To evaluate sociodemographic and clinical aspects of patients undergoing operations due to traumatic lesions of the brachial plexus. Method This was a retrospective study in which the medical files of a convenience sample of 48 patients operated between 2000 and 2010 were reviewed. The following were evaluated: (1) range of motion (ROM) of the shoulder, elbow and wrist/hand, in degrees; (2) grade of strength of the shoulder, elbow and wrist/hand; (3) sensitivity; and (4) visual analogue scale (VAS) (from 0 to 10). The Student's t, chi-square, Friedman, Wilcoxon and Kruskal–Wallis tests were used (p < 0.05). Results The patients’ mean age was 30.6 years; 60.4% of them had suffered motorcycle accidents and 52.1%, multiple trauma. The mean length of time until surgery was 8.7 months (range: 2–48). Thirty-one patients (64.6%) presented complete rupture of the plexus. The frequent operation was neurosurgery in 39 cases (81.3%). The ROM achieved was ≥30° in 20 patients (41.6%), with a range from 30° to 90° and mean of 73° (p = 0.001). Thirteen (27.1%) already had shoulder strength ≥M3 (p = 0.001). Twenty-seven patients (56.2%) had elbow flexion ≥80°, with a range from 30° to 160° and mean of 80.6° (p < 0.001). Twenty-two had strength ≥M3 (p < 0.001). Twenty-two patients (45.8%) had wrist extension ≥30° starting from flexion of 45°, with a range from 30° to 90° and mean of 70° (p = 0.003). Twenty-seven (56.3%) presented wrist/hand extension strength ≥M3 (p = 0.002). Forty-five (93.8%) had hypoesthesia and three (6.2%) had anesthesia (p = 0.006). The initial VAS was 4.5 (range: 1.0–9.0) and the final VAS was 3.0 (range: 1.0–7.0) (p < 0.001). Conclusion Traumatic lesions of the brachial plexus were more prevalent among young adults (21–40 years), men, people living in urban areas, manual workers and motorcycle accidents, with multiple trauma and total rupture of the plexus. Neurosurgery, with a second

  9. Integrative analysis of breast cancer reveals prognostic haematopoietic activity and patient-specific immune response profiles

    PubMed Central

    Varn, Frederick S.; Andrews, Erik H.; Mullins, David W.; Cheng, Chao

    2016-01-01

    Transcriptional programmes active in haematopoietic cells enable a variety of functions including dedifferentiation, innate immunity and adaptive immunity. Understanding how these programmes function in the context of cancer can provide valuable insights into host immune response, cancer severity and potential therapy response. Here we present a method that uses the transcriptomes of over 200 murine haematopoietic cells, to infer the lineage-specific haematopoietic activity present in human breast tumours. Correlating this activity with patient survival and tumour purity reveals that the transcriptional programmes of many cell types influence patient prognosis and are found in environments of high lymphocytic infiltration. Collectively, these results allow for a detailed and personalized assessment of the patient immune response to a tumour. When combined with routinely collected patient biopsy genomic data, this method can enable a richer understanding of the complex interplay between the host immune system and cancer. PMID:26725977

  10. Integrative analysis of breast cancer reveals prognostic haematopoietic activity and patient-specific immune response profiles.

    PubMed

    Varn, Frederick S; Andrews, Erik H; Mullins, David W; Cheng, Chao

    2016-01-01

    Transcriptional programmes active in haematopoietic cells enable a variety of functions including dedifferentiation, innate immunity and adaptive immunity. Understanding how these programmes function in the context of cancer can provide valuable insights into host immune response, cancer severity and potential therapy response. Here we present a method that uses the transcriptomes of over 200 murine haematopoietic cells, to infer the lineage-specific haematopoietic activity present in human breast tumours. Correlating this activity with patient survival and tumour purity reveals that the transcriptional programmes of many cell types influence patient prognosis and are found in environments of high lymphocytic infiltration. Collectively, these results allow for a detailed and personalized assessment of the patient immune response to a tumour. When combined with routinely collected patient biopsy genomic data, this method can enable a richer understanding of the complex interplay between the host immune system and cancer. PMID:26725977

  11. Integrated Analysis of Metabolite and Transcript Levels Reveals the Metabolic Shifts That Underlie Tomato Fruit Development and Highlight Regulatory Aspects of Metabolic Network Behavior1[W

    PubMed Central

    Carrari, Fernando; Baxter, Charles; Usadel, Björn; Urbanczyk-Wochniak, Ewa; Zanor, Maria-Ines; Nunes-Nesi, Adriano; Nikiforova, Victoria; Centero, Danilo; Ratzka, Antje; Pauly, Markus; Sweetlove, Lee J.; Fernie, Alisdair R.

    2006-01-01

    Tomato (Solanum lycopersicum) is a well-studied model of fleshy fruit development and ripening. Tomato fruit development is well understood from a hormonal-regulatory perspective, and developmental changes in pigment and cell wall metabolism are also well characterized. However, more general aspects of metabolic change during fruit development have not been studied despite the importance of metabolism in the context of final composition of the ripe fruit. In this study, we quantified the abundance of a broad range of metabolites by gas chromatography-mass spectrometry, analyzed a number of the principal metabolic fluxes, and in parallel analyzed transcriptomic changes during tomato fruit development. Metabolic profiling revealed pronounced shifts in the abundance of metabolites of both primary and secondary metabolism during development. The metabolite changes were reflected in the flux analysis that revealed a general decrease in metabolic activity during ripening. However, there were several distinct patterns of metabolite profile, and statistical analysis demonstrated that metabolites in the same (or closely related) pathways changed in abundance in a coordinated manner, indicating a tight regulation of metabolic activity. The metabolite data alone allowed investigations of likely routes through the metabolic network, and, as an example, we analyze the operational feasibility of different pathways of ascorbate synthesis. When combined with the transcriptomic data, several aspects of the regulation of metabolism during fruit ripening were revealed. First, it was apparent that transcript abundance was less strictly coordinated by functional group than metabolite abundance, suggesting that posttranslational mechanisms dominate metabolic regulation. Nevertheless, there were some correlations between specific transcripts and metabolites, and several novel associations were identified that could provide potential targets for manipulation of fruit compositional traits

  12. Direct lineage reprogramming reveals disease-specific phonotypes of motor neurons from human ALS patients

    PubMed Central

    Liu, Meng-Lu; Zang, Tong; Zhang, Chun-Li

    2015-01-01

    SUMMARY Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Here we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs) exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs) with skeletal muscles. Importantly, hiMNs converted from ALS-patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS-hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification. PMID:26725112

  13. Platelet Proteome Analysis Reveals Integrin-dependent Aggregation Defects in Patients with Myelodysplastic Syndromes*

    PubMed Central

    Fröbel, Julia; Cadeddu, Ron-Patrick; Hartwig, Sonja; Bruns, Ingmar; Wilk, Christian M.; Kündgen, Andrea; Fischer, Johannes C.; Schroeder, Thomas; Steidl, Ulrich G.; Germing, Ulrich; Lehr, Stefan; Haas, Rainer; Czibere, Akos

    2013-01-01

    Bleeding complications are a significant clinical problem in patients with myelodysplastic syndromes even at sufficient platelet counts (>50,000/μl). However, the underlying pathology of this hemorrhagic diathesis is still unknown. Here, we analyzed the platelet proteome of patients with myelodysplastic syndromes by quantitative two-dimensional difference gel electrophoresis followed by mass spectrometric protein identification. Proteins identified with lower concentrations, such as Talin-1, Vinculin, Myosin-9, Filmain-A, and Actin play critical roles in integrin αIIbβ3 signaling and thus platelet aggregation. Despite normal agonist receptor expression, calcium flux, and granule release upon activation, the activation capacity of integrin αIIbβ3 was diminished in myelodysplastic syndrome platelets. Förster resonance energy transfer analysis showed a reduced co-localization of Talin-1 to the integrin's β3-subunit, which is required for receptor activation and fibrinogen binding. In addition, platelet spreading on immobilized fibrinogen was incomplete, and platelet aggregation assays confirmed a general defect in integrin-dependent platelet aggregation in patients with myelodysplastic syndromes. Our data provide novel aspects on the molecular pathology of impaired platelet function in myelodysplastic syndromes and suggest a mechanism of defective integrin αIIbβ3 signaling that may contribute to the hemorrhagic diathesis observed in these patients. PMID:23382103

  14. Super-Resolution Microscopy Reveals Altered Desmosomal Protein Organization in Tissue from Patients with Pemphigus Vulgaris.

    PubMed

    Stahley, Sara N; Warren, Maxine F; Feldman, Ron J; Swerlick, Robert A; Mattheyses, Alexa L; Kowalczyk, Andrew P

    2016-01-01

    Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease in which autoantibodies (IgG) are directed against the desmosomal cadherin desmoglein 3. To better understand how PV IgG alters desmosome morphology and function in vivo, biopsies from patients with PV were analyzed by structured illumination microscopy, a form of superresolution fluorescence microscopy. In patient tissue, desmosomal proteins were aberrantly clustered and patient IgG colocalized with markers for lipid rafts and endosomes. Additionally, steady-state levels of desmoglein 3 were decreased and desmosomes were reduced in size in patient tissue. Desmosomes at blister sites were occasionally split, with PV IgG decorating the extracellular faces of split desmosomes. Desmosome splitting was recapitulated in vitro by exposing cultured keratinocytes both to PV IgG and to mechanical stress, demonstrating that splitting at the blister interface in patient tissue is due to compromised desmosomal adhesive function. These findings indicate that desmoglein 3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in tissue of patients with PV. Further, this study reveals that superresolution optical imaging is a powerful approach for studying epidermal adhesion structures in normal and diseased skin. PMID:26763424

  15. Super-resolution microscopy reveals altered desmosomal protein organization in pemphigus vulgaris patient tissue

    PubMed Central

    Stahley, Sara N.; Warren, Maxine F.; Feldman, Ron J.; Swerlick, Robert A.; Mattheyses, Alexa L.; Kowalczyk, Andrew P.

    2015-01-01

    Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease in which autoantibodies (IgG) are directed against the desmosomal cadherin desmoglein 3 (Dsg3). In order to better understand how PV IgG alters desmosome morphology and function in vivo, PV patient biopsies were analyzed by structured illumination microscopy (SIM), a form of super-resolution fluorescence microscopy. In patient tissue, desmosomal proteins were aberrantly clustered and localized to PV IgG-containing endocytic linear arrays. Patient IgG also colocalized with markers for lipid rafts and endosomes. Additionally, steady-state levels of Dsg3 were decreased and desmosomes were reduced in size in patient tissue. Desmosomes at blister sites were occasionally split, with PV IgG decorating the extracellular faces of split desmosomes. Desmosome splitting was recapitulated in vitro by exposing cultured keratinocytes both to PV IgG and to mechanical stress, demonstrating that splitting at the blister interface in patient tissue is due to compromised desmosomal adhesive function. These findings indicate that Dsg3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in PV patient tissue. Further, this study reveals that super-resolution optical imaging is powerful approach for studying epidermal adhesion structures in normal and diseased skin. PMID:26763424

  16. Sequencing of the Reannotated LMNB2 Gene Reveals Novel Mutations in Patients with Acquired Partial Lipodystrophy

    PubMed Central

    Hegele, Robert A.; Cao, Henian; Liu, Dora M.; Costain, Gary A.; Charlton-Menys, Valentine; Rodger, N. Wilson; Durrington, Paul N.

    2006-01-01

    The etiology of acquired partial lipodystrophy (APL, also called “Barraquer-Simons syndrome”) is unknown. Genomic DNA mutations affecting the nuclear lamina protein lamin A cause inherited partial lipodystrophy but are not found in patients with APL. Because it also encodes a nuclear lamina protein (lamin B2) and its genomic structure was recently reannotated, we sequenced LMNB2 as a candidate gene in nine white patients with APL. In four patients, we found three new rare mutations in LMNB2: intron 1 −6G→T, exon 5 c.643G→A (p.R215Q; in two patients), and exon 8 c.1218G→A (p.A407T). The combined frequency of these mutations was 0.222 in the patients with APL, compared with 0.0018 in a multiethnic control sample of 1,100 subjects (P=2.1×10-7) and 0.0045 in a sample of 330 white controls (P=1.2×10-5). These novel heterozygous mutations are the first reported for LMNB2, are the first reported among patients with APL, and indicate how sequencing of a reannotated candidate gene can reveal new disease-associated mutations. PMID:16826530

  17. Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients.

    PubMed

    Audemard-Verger, A; Descloux, E; Ponard, D; Deroux, A; Fantin, B; Fieschi, C; John, M; Bouldouyre, A; Karkowsi, L; Moulis, G; Auvinet, H; Valla, F; Lechiche, C; Davido, B; Martinot, M; Biron, C; Lucht, F; Asseray, N; Froissart, A; Buzelé, R; Perlat, A; Boutboul, D; Fremeaux-Bacchi, V; Isnard, S; Bienvenu, B

    2016-05-01

    Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15-67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1-10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14

  18. Muscle modifications in fibromyalgic patients revealed by surface electromyography (SEMG) analysis

    PubMed Central

    Bazzichi, Laura; Dini, Marco; Rossi, Alessandra; Corbianco, Silvia; De Feo, Francesca; Giacomelli, Camillo; Zirafa, Cristina; Ferrari, Claudia; Rossi, Bruno; Bombardieri, Stefano

    2009-01-01

    Background Several studies have been carried out in order to investigate surface electromyography (SEMG) response on fibromyalgic (FM) patients. Some studies failed to demonstrate differences between FM patients and healthy individuals while others found differences in SEMG parameters. Different muscular region have been analyzed in FM patients and heterogeneity is also produced because of the different ways in which the SEMG technique is used. The aims of this study were to evaluate muscle modifications by SEMG analysis in FM women with respect to a sample of healthy controls and to investigate the relationships between SEMG parameters and the clinical aspects of the disease. Methods SEMG was recorded in 100 FM women (48.10 ± 11.96 yr) and in 50 healthy women (48.60 ± 11.18 yr), from the tibialis anterior and the distal part of vastus medialis muscle during isometric contraction. Initial values and rate of change of median spectral frequency (MDF) and conduction velocity (CV) of the SEMG signal were calculated. The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, tiredness were evaluated and the relationships between these data and the SEMG results were also studied. For the statistical analysis Mann-Whitney test, chi-square test and Spearman correlation were used. Results MDF absolute values and the so-called Fatigue Index (FI) were significantly lower (p < 0.001) in both muscles studied in FM patients (MDF: 93.2 μV; FI: 1.10, 0.89) with respect to healthy controls (MDF: 138.2 μV; FI: 2.41, 1.66) and a smaller reduction in the percentage values of MDF was observed in FM patients vs controls (22% vs 38%). A significant correlation was found between the SEMG parameter decrement of normalized median frequency (MNF) (%) and seriousness of FM (evaluated by means of tender points). Conclusion We have found some interesting muscle modifications in FM patients with respect to healthy controls, regarding MDF, CV and FI values which

  19. [Clinical aspects and management of patients with tuberculous meningitis. Retrospective analysis from 1994 to 2005].

    PubMed

    Bémer, P; Boutoille, D; Lepelletier, D; Chamoux, C; Guitton, C; Drugeon, H

    2006-09-01

    Tuberculous meningitis remains a devastating disease with poor prognosis in terms of mortality or invalidating after-effects. Eighteen cases of tuberculous meningitis, occurred between 1994 and 2005, were re-examined retrospectively. Among the 18 patients, 13 were aged from 14 to 64 years, and 5 were older than 64. There was no gender dominance. Factors of risk were identified in 7 patients. British Medical Research Council staging was III in 9 patients, II in 2 patients and I in 7 patients. Protein and glucose levels in the cerebrospinal fluid sample were very variable ranging from 0.4 to 10.7 g/L and 0.4 to 3.7 mmol/L respectively. The cellular reaction was also very variable ranging from 0 to 250 elements, mostly lymphocytes. Antituberculous treatment was given to 15 patients, associated with corticosteroid therapy for 9 patients. Among the 18 patients, 11 died within 1 year, 4 were treated for a recurrence occurring up to 6 years after the diagnosis, 1 presented important neuropsychic after-effects and 2 patients survived without after-effects with a time ranging between 6 months and 1 year. The deceased patients were significantly older than the others. The risk of mortality was 4.5-fold greater among stage III patients than among stage I and II patients. The use of corticosteroids significantly reduced the risk of death. PMID:17075546

  20. Patient Experience and Satisfaction with Inpatient Service: Development of Short Form Survey Instrument Measuring the Core Aspect of Inpatient Experience

    PubMed Central

    Wong, Eliza L. Y.; Coulter, Angela; Hewitson, Paul; Cheung, Annie W. L.; Yam, Carrie H. K.; Lui, Siu fai; Tam, Wilson W. S.; Yeoh, Eng-kiong

    2015-01-01

    Patient experience reflects quality of care from the patients’ perspective; therefore, patients’ experiences are important data in the evaluation of the quality of health services. The development of an abbreviated, reliable and valid instrument for measuring inpatients’ experience would reflect the key aspect of inpatient care from patients’ perspective as well as facilitate quality improvement by cultivating patient engagement and allow the trends in patient satisfaction and experience to be measured regularly. The study developed a short-form inpatient instrument and tested its ability to capture a core set of inpatients’ experiences. The Hong Kong Inpatient Experience Questionnaire (HKIEQ) was established in 2010; it is an adaptation of the General Inpatient Questionnaire of the Care Quality Commission created by the Picker Institute in United Kingdom. This study used a consensus conference and a cross-sectional validation survey to create and validate a short-form of the Hong Kong Inpatient Experience Questionnaire (SF-HKIEQ). The short-form, the SF-HKIEQ, consisted of 18 items derived from the HKIEQ. The 18 items mainly covered relational aspects of care under four dimensions of the patient’s journey: hospital staff, patient care and treatment, information on leaving the hospital, and overall impression. The SF-HKIEQ had a high degree of face validity, construct validity and internal reliability. The validated SF-HKIEQ reflects the relevant core aspects of inpatients’ experience in a hospital setting. It provides a quick reference tool for quality improvement purposes and a platform that allows both healthcare staff and patients to monitor the quality of hospital care over time. PMID:25860775

  1. A patient with a painless neck tumour revealed as a carotid paraganglioma: a case report.

    PubMed

    Peric, Barbara; Marinsek, Ziva Pohar; Skrbinc, Breda; Music, Maja; Zagar, Ivana; Hocevar, Marko

    2014-01-01

    Carotid paragangliomas are usually slowly enlarging and painless lateral neck masses. These mostly benign lesions are recognized due to their typical location, vessel displacement and specific blood supply, features that are usually seen on different imaging modalities. Surgery for carotid paraganglioma can be associated with immediate cerebrovascular complications or delayed neurological impairment.We are reporting the case of a 36-year-old man who presented with a painless mass on the right side of his neck 11 months after being treated for testicular cancer. After a fine-needle aspiration biopsy, he was diagnosed with a testicular cancer lymph node metastasis. Neck US and fluorine [F-18]-fluorodeoxy-D-glucose (FDG) PET-CT showed no signs of hypervascularity or vessel displacement. The patient underwent a level II to V functional neck dissection. During the procedure, suspicion of a carotid paraganglioma was raised and the tumour was carefully dissected from the walls of the carotid arteries with minimal blood loss and no cranial nerve dysfunction.The histology report revealed carotid paraganglioma with no metastasis in the rest of the lymph nodes. The patient's history of testicular germ cell tumour led to a functional neck dissection during which a previously unrecognized carotid paraganglioma was removed.Surgery for carotid PG can be associated with complications that have major impact on quality of life. A thorough assessment of the patient and neck mass must therefore be performed preoperatively in order to perform the surgical procedure under optimal conditions. PMID:25141773

  2. Deletion of CFTR Translation Start Site Reveals Functional Isoforms of the Protein in CF Patients

    PubMed Central

    Ramalho, Anabela S.; Lewandowska, Marzena A.; Farinha, Carlos M.; Mendes, Filipa; Gonçalves, Juan; Barreto, Celeste; Harris, Ann; Amaral, Margarida D.

    2009-01-01

    Background/Aims: Mutations in the CFTR gene cause Cystic Fibrosis (CF) the most common life-threatening autosomal recessive disease affecting Caucasians. We identified a CFTR mutation (c.120del23) abolishing the normal translation initiation codon, which occurs in two Portuguese CF patients. This study aims at functionally characterizing the effect of this novel mutation. Methods: RNA and protein techniques were applied to both native tissues from CF patients and recombinant cells expressing CFTR constructs to determine whether c.120del23 allows CFTR protein production through usage of alternative internal codons, and to characterize the putative truncated CFTR form(s). Results: Our data show that two shorter forms of CFTR protein are produced when the initiation translation codon is deleted indicating usage of internal initiation codons. The N-truncated CFTR generated by this mutation has decreased stability, very low processing efficiency, and drastically reduced function. Analysis of mutants of four methionine codons downstream to M1 (M82, M150, M152, M156) revealed that each of the codons M150/M152/M156 (exon 4) can mediate CFTR alternative translation. Conclusions: The CFTR N-terminus has an important role in avoiding CFTR turnover and in rendering effective its plasma membrane traffic. These data correlate well with the severe clinical phenotype of CF patients bearing the c.120del23 mutation. PMID:19910674

  3. Visual modeling reveals cryptic aspect in egg mimicry of Himalayan Cuckoo (Cuculus saturatus) on its host Blyth's Leaf Warbler (Phylloscopus reguloides).

    PubMed

    Yang, Can-Chao; Cai, Yan; Liang, Wei

    2011-08-01

    Brood parasitism and egg mimicry of Himalayan Cuckoo (Cuculus saturatus) on its host Blyth's Leaf Warbler (Phylloscopus reguloides) were studied in south-western China from April to July 2009. The cuckoo laid a white egg with fine brown markings on the blunt end. The eggs were conspicuously bigger than the host's own, with 2.06 g in mass and 1.91 cm(3) in volume. Visual modeling showed that the cuckoo eggs, which from the human eye appeared to mimic the host eggs to a great extent, were completely different from the host eggs in both hue and chroma. The characters of the Himalayan Cuckoo nestling, reported for the first time, included two triangular and black patches on its gape, which appeared from four days old and became darker with age and growth. While this character also exists in nestlings of Oriental Cuckoo (C. optatus), it has not been found for other Cuculus species. Our results reveal cryptic aspects in the cuckoo-host egg color matching, which are not visible to the naked human eye, and indicate that high mimetic cuckoo eggs rejected by hosts, as determined by human observers in previous studies, might not be mimetic as birds see them. PMID:21842542

  4. Sex and Age Aspects in Patients Suffering From Out-Of-Hospital Cardiac Arrest

    PubMed Central

    Piegeler, Tobias; Thoeni, Nils; Kaserer, Alexander; Brueesch, Martin; Sulser, Simon; Mueller, Stefan M.; Seifert, Burkhardt; Spahn, Donat R.; Ruetzler, Kurt

    2016-01-01

    Abstract Cardiopulmonary resuscitation (CPR) is indicated in patients suffering from out-of-hospital cardiac arrest. Several studies suggest a sex- and age-based bias in the treatment of these patients. This particular bias may have a significant impact on the patient's outcome. However, the reasons for these findings are still unclear and discussed controversially. Therefore, the aim of this study was to retrospectively analyze treatment and out-of-hospital survival rates for potential sex- and age-based differences in patients requiring out-of-hospital CPR provided by an emergency physician in the city of Zurich, Switzerland. A total of 3961 consecutive patients (2003–2009) were included in this retrospective analysis to determine the frequency of out-of-hospital CPR and prehospital survival rate, and to identify potential sex- and age-based differences regarding survival and treatment of the patients. Seven hundred fifty-seven patients required CPR during the study period. Seventeen patients had to be excluded because of incomplete or inconclusive documentation, resulting in 743 patients (511 males, 229 females) undergoing further statistical analysis. Female patients were significantly older, compared with male patients (68 ± 18 [mean ± SD] vs 64 ± 18 years, P = .012). Men were resuscitated slightly more often than women (86.4% vs 82.1%). Overall out-of-hospital mortality rate was found to be 81.2% (492/632 patients) with no differences between sexes (82.1% for males vs 79% for females, odds ratio 1.039, 95% confidence interval 0.961–1.123). No sex differences were detected in out-of-hospital treatment, as assessed by the different medications administered, initial prehospital Glasgow Coma Scale, and prehospital suspected leading diagnosis. The data of our study demonstrate that there was no sex-based bias in treating patients requiring CPR in the prehospital setting in our physician-led emergency ambulance service. PMID:27149475

  5. The Role of Enteral Nutrition in Patients with Inflammatory Bowel Disease: Current Aspects

    PubMed Central

    Triantafillidis, John K.; Vagianos, Costas; Papalois, Apostolos E.

    2015-01-01

    Enteral nutrition (EN) is considered to be of great importance in patients with inflammatory bowel disease (IBD) and nutritional problems. This comprehensive review is aiming to provide the reader with an update on the role of EN in IBD patients. EN can reduce Crohn's disease (CD) activity and maintain remission in both adults and children. Nutritional support using liquid formulas should be considered for CD patients and in serious cases of ulcerative colitis (UC), especially for those who may require prolonged cycles of corticosteroids. Given that the ultimate goal in the treatment of CD is mucosal healing, this advantage of EN over corticosteroid treatment is valuable in therapeutic decision-making. EN is indicated in active CD, in cases of steroid intolerance, in patient's refusal of steroids, in combination with steroids in undernourished individuals, and in patients with an inflammatory stenosis of the small intestine. No differences between the efficiency of elemental diets and nonelemental formulas have been noticed. EN must be the first choice compared to TPN. EN has a restricted value in the treatment of patients with large bowel CD. In conclusion, it seems important not to underestimate the role of nutrition as supportive care in patients with IBD. PMID:25793189

  6. The ethical and practical aspects of acceptance and universal patient acceptance.

    PubMed

    Corsino, Bruce V; Patthoff, Donald E

    2006-11-01

    "Acceptance" is an often presupposed, hidden core value and ethic focused on how dental and other health practitioners first accept people as possible patients. The three basic styles of patient acceptance are random, selective, and universal. Reduced public access to care results from the practice of random and selective acceptance. Only universal acceptance creates a potential pathway for improved access to care. The notion of Universal Patient Acceptance (UPA) is discussed here as one kind of applied ethical tool or clinical practice that allows for the ethic of acceptance to be more effectively pursued in daily practice. We suggest that health providers falsely surmise that they already understand and practice Universal Patient Acceptance. That myth and perspective are partly what keeps Acceptance hidden as an ethic and overlooked as a potential way to foster dialogue and indirectly promote better access to care. Without Universal Patient Acceptance, dental and health providers will continue to silently engage in practice patterns that adversely affect public access to care. The actual benefits of Universal Patient Acceptance are the subject of ongoing review and debate. Whatever those benefits might be will not likely be realized until Acceptance and Universal Patient Acceptance are included as part of dental and other health professional codes of ethics and training curricula. That is what we argue for here. PMID:17106034

  7. Practical Aspects of Botulinum Toxin-A Treatment in Patients With Overactive Bladder Syndrome.

    PubMed

    Liao, Chun-Hou; Kuo, Hann-Chorng

    2015-12-01

    Intravesical onabotulinumtoxinA (BoNT-A) injection is an effective treatment for overactive bladder syndrome (OAB) that is refractory to antimuscarinics. An injectable dose of 100 U has been suggested to achieve the optimal balance of benefit and safety in patients with OAB. BoNT-A (total volume of 10 mL) was administered as evenly distributed intradetrusor injections (5 U) across 20 sites approximately 1 cm apart (0.5 mL per site) using a flexible or rigid cystoscope. Treatment with BoNT-A was generally well tolerated by most patients, and most treatment-related adverse events were localized to the urinary tract. The prevalence of OAB increases with age, and elderly patients are more vulnerable to complications. The short-term efficacy of intravesical BoNT-A injection for refractory OAB with no treatment-related complications in the elderly population has been documented. Frail elderly patients can experience the same treatment results, such as significantly improved urgent urinary incontinence and quality of life, as young and nonfrail elderly patients with 100-U BoNT-A injections. However, increased risk of larger postvoid residual (PVR) urine and lower long-term success rates were noted in frail elderly patients; around 11% had acute urinary retention, while 60% had PVR urine volume >150 mL after treatment. In addition, intravesical injection of BoNT-A effectively decreased urgency symptoms in elderly patients with OAB and central nervous system lesions. The adverse effects were acceptable, while the long-term effects were comparable to those in patients with OAB without central nervous system lesions. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization in this vulnerable population requires careful evaluation before treatment with intravesical BoNT-A. In conclusion, the current findings indicate that intravesical BoNT-A is an effective and safe treatment for OAB in elderly patients. PMID:26739175

  8. Oncologic aspects of long-term followed incidental prostate cancer detected by cystoprostatectomy in Korean patients

    PubMed Central

    Cho, In-Chang; Kim, Jeong Eun; Kim, Sung Han; Joung, Jae Young; Seo, Ho Kyung; Chung, Jinsoo; Park, Weon Seo; Lee, Kang Hyun

    2015-01-01

    Purpose To determine the incidence and clinical features of incidentally discovered prostate adenocarcinoma in patients undergoing radical cystoprostatectomy (CPT) for bladder cancer. Methods Ninety-six consecutive patients scheduled to undergo CPT were prospectively enrolled. The prostates were excised completely during CPT. The CPT specimens were examined, and the clinicopathologic characteristics of incidental prostate cancer studied. Complete transverse sections of the prostate were taken from the apex to the base at 4-mm intervals and all prostates were examined by a single pathologist. Results The mean patient age and prostate-specific antigen level were 66.1 ± 10.0 years and 2.8 ± 5.0 ng/mL, respectively. Of the 96 patients, 35 (36.5%) had prostate cancer (PCa). Of these incidental PCas, 57.1% (20.8% of all patients undergoing CPT) were clinically significant. None of the patients who were age ≤50 years had incidental PCa. However, the incidences of PCa in the 51–60 years, 61–70 years, and ≥71 years age groups were 27.8% (5/18), 48.7% (19/39), and 35.5% (15/31), respectively, and the difference according to the age subgroup was significant (P = 0.048). During the median follow-up of 49 months, 29.2% (28/96) of patients died. There were no PCa-specific deaths, and two patients (2.1%) showed biochemical recurrences. Conclusion Incidental PCas were diagnosed in ∼40% of CPT specimens, and ∼50% of incidental PCas were clinically significant. During radical CPT in patients aged ≥60 years, the possibility of the presence of PCa and the potential oncologic risk of partial prostatectomy during CPT should be remembered. PMID:26157769

  9. Practical Aspects of Botulinum Toxin-A Treatment in Patients With Overactive Bladder Syndrome

    PubMed Central

    2015-01-01

    Intravesical onabotulinumtoxinA (BoNT-A) injection is an effective treatment for overactive bladder syndrome (OAB) that is refractory to antimuscarinics. An injectable dose of 100 U has been suggested to achieve the optimal balance of benefit and safety in patients with OAB. BoNT-A (total volume of 10 mL) was administered as evenly distributed intradetrusor injections (5 U) across 20 sites approximately 1 cm apart (0.5 mL per site) using a flexible or rigid cystoscope. Treatment with BoNT-A was generally well tolerated by most patients, and most treatment-related adverse events were localized to the urinary tract. The prevalence of OAB increases with age, and elderly patients are more vulnerable to complications. The short-term efficacy of intravesical BoNT-A injection for refractory OAB with no treatment-related complications in the elderly population has been documented. Frail elderly patients can experience the same treatment results, such as significantly improved urgent urinary incontinence and quality of life, as young and nonfrail elderly patients with 100-U BoNT-A injections. However, increased risk of larger postvoid residual (PVR) urine and lower long-term success rates were noted in frail elderly patients; around 11% had acute urinary retention, while 60% had PVR urine volume >150 mL after treatment. In addition, intravesical injection of BoNT-A effectively decreased urgency symptoms in elderly patients with OAB and central nervous system lesions. The adverse effects were acceptable, while the long-term effects were comparable to those in patients with OAB without central nervous system lesions. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization in this vulnerable population requires careful evaluation before treatment with intravesical BoNT-A. In conclusion, the current findings indicate that intravesical BoNT-A is an effective and safe treatment for OAB in elderly patients. PMID:26739175

  10. Targeted next-generation sequencing of candidate genes reveals novel mutations in patients with dilated cardiomyopathy

    PubMed Central

    ZHAO, YUE; FENG, YUE; ZHANG, YUN-MEI; DING, XIAO-XUE; SONG, YU-ZHU; ZHANG, A-MEI; LIU, LI; ZHANG, HONG; DING, JIA-HUAN; XIA, XUE-SHAN

    2015-01-01

    Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure, and it is characterized by genetic and clinical heterogeneity, even for some patients with a very poor clinical prognosis; in the majority of cases, DCM necessitates a heart transplant. Genetic mutations have long been considered to be associated with this disease. At present, mutations in over 50 genes related to DCM have been documented. This study was carried out to elucidate the characteristics of gene mutations in patients with DCM. The candidate genes that may cause DCM include MYBPC3, MYH6, MYH7, LMNA, TNNT2, TNNI3, MYPN, MYL3, TPM1, SCN5A, DES, ACTC1 and RBM20. Using next-generation sequencing (NGS) and subsequent mutation confirmation with traditional capillary Sanger sequencing analysis, possible causative non-synonymous mutations were identified in ~57% (12/21) of patients with DCM. As a result, 7 novel mutations (MYPN, p.E630K; TNNT2, p.G180A; MYH6, p.R1047C; TNNC1, p.D3V; DES, p.R386H; MYBPC3, p.C1124F; and MYL3, p.D126G), 3 variants of uncertain significance (RBM20, p.R1182H; MYH6, p.T1253M; and VCL, p.M209L), and 2 known mutations (MYH7, p.A26V and MYBPC3, p.R160W) were revealed to be associated with DCM. The mutations were most frequently found in the sarcomere (MYH6, MYBPC3, MYH7, TNNC1, TNNT2 and MYL3) and cytoskeletal (MYPN, DES and VCL) genes. As genetic testing is a useful tool in the clinical management of disease, testing for pathogenic mutations is beneficial to the treatment of patients with DCM and may assist in predicting disease risk for their family members before the onset of symptoms. PMID:26458567

  11. The Adult Patient with Eisenmenger Syndrome: A Medical Update After Dana Point Part I: Epidemiology, Clinical Aspects and Diagnostic Options

    PubMed Central

    Kaemmerer, Harald; Mebus, Siegrun; Schulze-Neick, Ingram; Eicken, Andreas; Trindade, Pedro T; Hager, Alfred; Oechslin, Erwin; Niwa, Koichiro; Lang, Irene; Hess, John

    2010-01-01

    Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death. For a long time, therapy has been limited to symptomatic options or lung or combined heart-lung transplantation. As new selective pulmonary vasodilators have become available and proven to be beneficial in various forms of pulmonary arterial hypertension, this targeted medical treatment has been expected to show promising effects with a delay of deterioration also in Eisenmenger patients. Unfortunately, data in Eisenmenger patients suffer from small patient numbers and a lack of randomized controlled studies. To optimize the quality of life and the outcome, referral of Eisenmenger patients to spezialized centers is required. In such centers, specific interdisciplinary management strategies of physicians specialized on congenital heart diseases and PAH should be warranted. This medical update emphasizes the current diagnostic and therapeutic options for Eisenmenger patients with particularly focussing on epidemiology, clinical aspects and specific diagnostic options. PMID:22043211

  12. [Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice].

    PubMed

    Albillos, Agustín; Luis Calleja, José; Molina, Esther; Planas, Ramon; Romero-Gómez, Manuel; Turnes, Juan; Hernández-Guerra, Manuel

    2014-07-01

    The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy. PMID:25907434

  13. Behavioural aspects of patients with Autism Spectrum Disorders (ASD) that affect their dental management

    PubMed Central

    Limeres-Posse, Jacobo; Castaño-Novoa, Patricia; Abeleira-Pazos, Maite; Ramos-Barbosa, Isabel

    2014-01-01

    Dental treatment in patients with Autism Spectrum Disorders (ASD) can be complicated due to the presence of behavioral alterations. In this group, there are no specific behavioral profiles that allow dentist to anticipate the attitude that a patient will show during a visit. Thus, behavioral attitudes have been described that vary from total permissiveness and collaboration during even bloody procedures, to the absolute impossibility in conducting a simple oral examination. There is no effective behavioral management technique for all ASD patients. Prior information, such as the type of ASD or the presence of certain concurrent pathologies can help predict the patient’s likely behavior. Therefore, gathering all the information in a preliminary interview with the parents/guardians of the patient is recommended. Knowing these factors will allow individualized behavioral management strategies to be designed and facilitates the planning of dental treatment. Key words:Dentistry, autism, ASD, behavior management. PMID:24608219

  14. Important aspects of self-management education in patients with diabetes.

    PubMed

    Stam, D M; Graham, J P

    1997-07-01

    The Diabetes Control and Complications Trial has shown that the long-term complication of diabetes can be decreased with intensive glycemic control. However, comprehensive patient education is required to provide the patient with the self-management skills necessary to achieve this level of glycemic control. Epidemiologic data indicate that large numbers of patients do not receive the proper care or education necessary to develop such self-management abilities. In order to convey the importance of patient education, the American Diabetes Association (ADA) has labeled self-management education as a cornerstone of therapy for patients with diabetes. Standards of care have also been defined by the ADA. Within the current U.S. health care system, however, limitations are present that may affect the quality of care and ability to provide adequate patient education. Therefore, it is the responsibility of the health care provider to improve the education process in an attempt to maintain standards of care outlined by the ADA. When developing a diabetes self-management training program, the ADA national standards can be used as a guideline. PMID:10168174

  15. Whole Exome Sequencing Reveals Novel PHEX Splice Site Mutations in Patients with Hypophosphatemic Rickets

    PubMed Central

    Gillies, Christopher; Sampson, Matthew G.; Kher, Vijay; Sethi, Sidharth K.; Otto, Edgar A.

    2015-01-01

    Objective Hypophosphatemic rickets (HR) is a heterogeneous genetic phosphate wasting disorder. The disease is most commonly caused by mutations in the PHEX gene located on the X-chromosome or by mutations in CLCN5, DMP1, ENPP1, FGF23, and SLC34A3. The aims of this study were to perform molecular diagnostics for four patients with HR of Indian origin (two independent families) and to describe their clinical features. Methods We performed whole exome sequencing (WES) for the affected mother of two boys who also displayed the typical features of HR, including bone malformations and phosphate wasting. B-lymphoblast cell lines were established by EBV transformation and subsequent RT-PCR to investigate an uncommon splice site variant found by WES. An in silico analysis was done to obtain accurate nucleotide frequency occurrences of consensus splice positions other than the canonical sites of all human exons. Additionally, we applied direct Sanger sequencing for all exons and exon/intron boundaries of the PHEX gene for an affected girl from an independent second Indian family. Results WES revealed a novel PHEX splice acceptor mutation in intron 9 (c.1080-3C>A) in a family with 3 affected individuals with HR. The effect on splicing of this mutation was further investigated by RT-PCR using RNA obtained from a patient’s EBV-transformed lymphoblast cell line. RT-PCR revealed an aberrant splice transcript skipping exons 10-14 which was not observed in control samples, confirming the diagnosis of X-linked dominant hypophosphatemia (XLH). The in silico analysis of all human splice sites adjacent to all 327,293 exons across 81,814 transcripts among 20,345 human genes revealed that cytosine is, with 64.3%, the most frequent nucleobase at the minus 3 splice acceptor position, followed by thymidine with 28.7%, adenine with 6.3%, and guanine with 0.8%. We generated frequency tables and pictograms for the extended donor and acceptor splice consensus regions by analyzing all human

  16. Technical Aspects on the Use of Ultrasonic Bone Shaver in Spine Surgery: Experience in 307 Patients

    PubMed Central

    Hazer, Derya Burcu; Yaşar, Barış; Rosberg, Hans-Eric; Akbaş, Aytaç

    2016-01-01

    Aim. We discuss technical points, the safety, and efficacy of ultrasonic bone shaver in various spinal surgeries within our own series. Methods. Between June 2010 and January 2014, 307 patients with various spinal diseases were operated on with the use of an ultrasonic bone curette with microhook shaver (UBShaver). Patients' data were recorded and analyzed retrospectively. The technique for the use of the device is described for each spine surgery procedure. Results. Among the 307 patients, 33 (10.7%) cases had cervical disorder, 17 (5.5%) thoracic disorder, 3 (0.9%) foramen magnum disorder, and 254 (82.7%) lumbar disorders. Various surgical techniques were performed either assisted or alone by UBShaver. The duration of the operations and the need for blood replacement were relatively low. The one-year follow-up with Neck Disability Index (NDI) and Oswestry Disability Index (ODI) scores were improved. We had 5 cases of dural tears (1.6%) in patients with lumbar spinal disease. No neurological deficit was found in any patients. Conclusion. We recommend this device as an assistant tool in various spine surgeries and as a primary tool in foraminotomies. It is a safe device in spine surgery with very low complication rate. PMID:27195299

  17. Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection

    PubMed Central

    Maji, Abhijit; Misra, Richa; Kumar Mondal, Anupam; Kumar, Dhirendra; Bajaj, Divya; Singhal, Anshika; Arora, Gunjan; Bhaduri, Asani; Sajid, Andaleeb; Bhatia, Sugandha; Singh, Sompal; Singh, Harshvardhan; Rao, Vivek; Dash, Debasis; Baby Shalini, E; Sarojini Michael, Joy; Chaudhary, Anil; Gokhale, Rajesh S.; Singh, Yogendra

    2015-01-01

    Extrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes. PMID:26469538

  18. [Comparative aspects of using neuroprotectors in the management of patients with ischemic stroke].

    PubMed

    Ershov, V I

    2011-01-01

    Comparative efficacy of neuroprotective preparations: actovegin, cerebrolysin and ceraxon was studied in 73 patients in the most acute phase of ischemic stroke. A control group included 33 patients in the most acute phase of ischemic stroke who received only basic treatment without neuroprotectors. Patient's state was assessed with the NIHSS, the original scale of E.I. Gusev and V.I. Skvortsova and the Barthel index. Ceraxon in daily dosage 2 g and cerebrolysin in daily dosage 10 ml during 10 days after the development of ischemic stroke led to the significantly better regression of neurological symptoms to the 21st day of disease compared to the control group. Barthel index scores did not differ in the groups studied. PMID:22224244

  19. Aspects of Hyperglycemia Contribution to Arterial Stiffness and Cardiovascular Complications in Patients With Type 1 Diabetes.

    PubMed

    Gordin, Daniel; Groop, Per-Henrik

    2016-09-01

    Controlling the blood glucose level is of outmost importance for the prevention of the micro- and macrovascular diabetic complications observed in patients with type 1 diabetes (T1D). Although the pathogenesis behind the complex cascade of complications is far from solved, one possible mechanism could be a negative effect of glucose on the arteries resulting in a stiffening of the arteries and ultimately in vascular complications. Intriguingly, patients with T1D have been shown to suffer from premature arterial aging compared to nondiabetic subjects-an association that is even more evident in the presence of diabetic complications such as diabetic nephropathy. Arterial stiffness has in several patient populations been shown to independently predict cardiovascular disease. However, interventional studies aimed at attenuating arterial stiffness to reduce cardiovascular disease in T1D are yet to come. Moreover, most of the data on pharmacological treatments of arterial stiffening are directed toward pathophysiological pathways other than hyperglycemia. Interestingly, the sodium-glucose transport-2 (SGLT2) inhibitor empagliflozin was recently shown to reduce both blood pressure and arterial stiffness in patients with type 2 diabetes. Whether, these effects can also be replicated in patients with T1D is an intriguing question. Tight metabolic and antihypertensive control are still of central importance for the prevention and the treatment of diabetic complications. However, the need for a noninvasive intermediate marker to identify at risk patients for aggressive treatment is evident. One such tool might be arterial stiffness linking diabetes to increased cardiovascular risk. Future research efforts exploring large-scale databases will play a key role in the identification of other clinically useful markers. PMID:26956240

  20. New aspects of delirium in elderly patients with critical limb ischemia

    PubMed Central

    van Eijsden, Willem A; Raats, Jelle W; Mulder, Paul GH; van der Laan, Lijckle

    2015-01-01

    Objective The primary objective was to identify possible risk factors for delirium in patients with critical limb ischemia undergoing surgery. The secondary objective was to study the effect of delirium on complications, the length of hospital stay, health care costs, and mortality. Methods All patients 65 years or older with critical limb ischemia undergoing surgery from February 2013 to July 2014 at Amphia Hospital, were included and followed up until December 31, 2014. Delirium was scored using the Delirium Observation Screening Scale (DOSS). Perioperative risk factors (age, comorbidity, factors of frailty, operation type, hemoglobulin, and transfusion) were collected and analyzed using logistic regression. Secondary outcomes were the number of complications, total hospital stay, extra health care costs per delirium, and mortality within 3 months and 6 months of surgery. Results We included 92 patients with critical limb ischemia undergoing surgery. Twenty-nine (32%) patients developed a delirium during admission, of whom 17 (59%) developed delirium preoperatively. After multivariable analysis, only diabetes mellitus (odds ratio [OR] =6.23; 95% confidence interval [CI]: 1.11–52.2; P=0.035) and Short Nutritional Assessment Questionnaire for Residential Care (SNAQ-RC) ≥3 (OR =5.55; 95% CI: 1.07–42.0; P=0.039) was significantly associated with the onset of delirium. Delirium was associated with longer hospital stay (P=0.001), increased health care costs, and higher mortality after 6 months (P<0.001). Conclusion Delirium is a common adverse event in patients with critical limb ischemia undergoing surgery with devastating outcome in the long term. Most patients developed delirium preoperatively, which indicates the need for early recognition and preventive strategies in the preoperative period. This study identified undernourishment and diabetes mellitus as independent risk factors for delirium. PMID:26451094

  1. Heterogeneity of pancreatic cancer metastases in a single patient revealed by quantitative proteomics.

    PubMed

    Kim, Min-Sik; Zhong, Yi; Yachida, Shinichi; Rajeshkumar, N V; Abel, Melissa L; Marimuthu, Arivusudar; Mudgal, Keshav; Hruban, Ralph H; Poling, Justin S; Tyner, Jeffrey W; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Pandey, Akhilesh

    2014-11-01

    Many patients with pancreatic cancer have metastases to distant organs at the time of initial presentation. Recent studies examining the evolution of pancreatic cancer at the genetic level have shown that clonal complexity of metastatic pancreatic cancer is already initiated within primary tumors, and organ-specific metastases are derived from different subclones. However, we do not yet understand to what extent the evolution of pancreatic cancer contributes to proteomic and signaling alterations. We hypothesized that genetic heterogeneity of metastatic pancreatic cancer results in heterogeneity at the proteome level. To address this, we employed a model system in which cells isolated from three sites of metastasis (liver, lung, and peritoneum) from a single patient were compared. We used a SILAC-based accurate quantitative proteomic strategy combined with high-resolution mass spectrometry to analyze the total proteome and tyrosine phosphoproteome of each of the distal metastases. Our data revealed distinct patterns of both overall proteome expression and tyrosine kinase activities across the three different metastatic lesions. This heterogeneity was significant because it led to differential sensitivity of the neoplastic cells to small molecule inhibitors targeting various kinases and other pathways. For example, R428, a tyrosine kinase inhibitor that targets Axl receptor tyrosine kinase, was able to inhibit cells derived from lung and liver metastases much more effectively than cells from the peritoneal metastasis. Finally, we confirmed that administration of R428 in mice bearing xenografts of cells derived from the three different metastatic sites significantly diminished tumors formed from liver- and lung-metastasis-derived cell lines as compared with tumors derived from the peritoneal metastasis cell line. Overall, our data provide proof-of-principle support that personalized therapy of multiple organ metastases in a single patient should involve the

  2. Technical aspects of nuclear microprobe analysis of senile plaques from alzheimer patients

    NASA Astrophysics Data System (ADS)

    Larsson, N. P.-O.; Tapper, U. A. S.; Sturesson, K.; Odselius, R.; Brun, A.

    1990-04-01

    Alzheimer's disease, a common form of senile dementia, has been proposed to be caused by aluminium. One of the interesting structures to be studied, senile plaque cores in the brain, have centres of only about 10 μm. We have investigated the possibility of applying nuclear microprobes to sections containing senile plaques. An alternative staining procedure, TMToluidin blue staining using a spray technique, is also presented. An outline is given of a procedure for preparing senile plaque specimens for nuclear microprobe analysis. This includes a technique for accurate ion beam positioning, utilizing electron microscopy-grids. The subject may be of general interest since sample preparation is one of the most important aspects in microprobe analysis of biological matter.

  3. [A coughing patients makes a visit to the otorhinolaryngologist's office: the practical aspects of diagnostics and treatment].

    PubMed

    Nosulya, E V

    2016-01-01

    This article summarizes the modern concepts of the most common causes and mechanism underlying the development of cough. The significance of pathogenetic cough-suppressant therapy is emphasized with special reference to the following aspects: the importance of reducing the thickness or bronchial secretions, its more efficient removal from the lumen of the respiratory passages, creation of the prerequisites for regression of the inflammatory process, lowering the intensity of cough, improvement of subjective feelings and the quality of life of a given patient. The advantages of the application of the compounded preparations containing synergic components responsible for the high therapeutic effectiveness of these medicines is demonstrated as exemplified by the ingredients of the ascoril expectorant. It is concluded that this medication should be recommended for the treatment of patients suffering from cough of the known nature. PMID:27367353

  4. Ethical Aspects of Geriatric Patients' Rights to Refuse Treatment and to Receive Limited Medical Resources.

    ERIC Educational Resources Information Center

    Howe, Edmund G.

    1988-01-01

    Discusses two of the most formidable bioethical challenges over the next decades which relate to disabilities and aging: elders' exercise of autonomy and the just allocation of resources to older patients. Offers suggestions for developing principles for the treatment of elders. (Author/ABL)

  5. Leprosy Reactions in Patients Coinfected with HIV: Clinical Aspects and Outcomes in Two Comparative Cohorts in the Amazon Region, Brazil

    PubMed Central

    Pires, Carla Andréa Avelar; Jucá Neto, Fernando Octávio Machado; de Albuquerque, Nahima Castelo; Macedo, Geraldo Mariano Moraes; Batista, Keila de Nazaré Madureira; Xavier, Marília Brasil

    2015-01-01

    Background Leprosy, caused by Mycobacterium leprae, can lead to scarring and deformities. Human immunodeficiency virus (HIV), a lymphotropic virus with high rates of replication, leads to cell death in various stages of infection. These diseases have major social and quality of life costs, and although the relevance of their comorbidity is recognized, several aspects are still not fully understood. Methodology/Principal Findings Two cohorts of patients with leprosy in an endemic region of the Amazon were observed. We compared 40 patients with leprosy and HIV (Group 1) and 107 leprosy patients with no comorbidity (Group 2) for a minimum of 2 years. Group 1 predominantly experienced the paucibacillary classification, accounting for 70% of cases, whereas Group 2 primarily experienced the multibacillary classification (80.4% of cases). There was no significant difference in the prevalence of leprosy reactions among the two groups (37.5% for Group 1 vs. 56.1% for Group 2), and the most frequent reaction was Type 1. The appearance of Group 1 patients’ reversal reaction skin lesions was consistent with each clinical form: typically erythematous and infiltrated, with similar progression as those patients without HIV, which responded to prednisone. Patients in both groups primarily experienced a single episode (73.3% in Group 1 and 75% in Group 2), and Group 1 had shorter reaction periods (≤3 months; 93.3%), moderate severity (80%), with 93.3% of the patients in the state of acquired immune deficiency syndrome, and 46.7% presenting the reaction at the time of the immune reconstitution inflammatory syndrome. Conclusions/Significance This study used a large sample and makes a significant contribution to the clinical outcomes of patients in the reactive state with comorbid HIV and leprosy. The data indicate that these diseases, although concurrent, have independent courses. PMID:26029928

  6. Nasal septal deformities in chronic rhinosinusitis patients: clinical and radiological aspects.

    PubMed

    Poje, G; Zinreich, J S; Skitarelić, N; Đurić Vuković, K; Passàli, G C; Passàli, D; Mladina, R

    2014-04-01

    Septal deformities are very frequent in patients suffering from chronic rhinosinusitis (CRS). The question is whether or not some types of septal deformities are involved more frequently in this process or not. The authors observed the incidence of particular types of septal deformities in a group of CRS patients using Mladina classification. The same has been done with a control group that consisted of healthy volunteers. In the literature, type 7 has been found very frequently, i.e. in nearly 30% of all CRS cases. Herein, type 7 was mostly composed of types 3 and 5. Type 3 can be accurately recognised on axial MSCT scans, while type 5 can be accurately recognised on coronal views. Concomitant septal surgery at the time of endoscopic sinus surgery is recommended. PMID:24843222

  7. Demographic variables, clinical aspects, and medicolegal implications in a population of patients with adjustment disorder

    PubMed Central

    Anastasia, Annalisa; Colletti, Chiara; Cuoco, Valentina; Quartini, Adele; Urso, Stefania; Rinaldi, Raffaella; Bersani, Giuseppe

    2016-01-01

    Introduction Although adjustment disorder (AD) is considered as residual diagnosis and receives little attention in research, it plays an important role in clinical practice and also assumes an increasingly important role in the field of legal medicine, where the majority of diagnostic frameworks (eg, mobbing) often refer to AD. Our study aimed to look for specific stressor differences among demographic and clinical variables in a naturalistic setting of patients with AD. Methods A restrospective statistical analysis of the data of patients diagnosed with AD from November 2009 to September 2012, identified via manual search from the archive of the outpatient setting at the University Unit of Psychiatry “A. Fiorini” Hospital, Terracina (Latina, Italy), was performed. Results The sample consisted of 93 patients (46 males and 47 females), aged between 26 and 85, with medium–high educational level who were mainly employed. In most cases (54.80%), a diagnosis of AD with mixed anxiety and depressed mood was made. In all, 72% of the sample reported a negative family history for psychiatric disorders. In 22.60%, a previous history of psychopathology, especially mood disorders (76.19%), was reported. The main stressors linked to the development of AD were represented by working problems (32.30%), family problems (23.70%), and/or somatic disease (22.60%) with significant differences with respect to age and sex. Half of the patients were subjected to a single first examination; 24.47% requested a copy of medical records. Conclusion Confirming previous data from previous reports, our results suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications. PMID:27099504

  8. [Critically ill patients with decompensated liver cirrhosis - New aspects and intensive care management].

    PubMed

    Maschmeier, Miriam; Hüsing, Anna; Schmidt, Hartmut; Kabar, Iyad

    2015-10-01

    The prevalence of liver cirrhosis in the German population is about 1 %. Clinically, compensated liver cirrhosis should be distinguished from decompensated cirrhosis with poor prognosis. Decompensated cirrhosis is defined by the occurrence of complications and consequences of portal hypertension (such as ascites, variceal bleeding, hepatic encephalopathy and hepatorenal syndrome) and progressive liver failure. Optimizing the management of these patients in the intensive care unit could essentially improve their outcome. PMID:26445254

  9. Cartilage-hair hypoplasia in Finland: epidemiological and genetic aspects of 107 patients.

    PubMed

    Mäkitie, O

    1992-09-01

    Cartilage-hair hypoplasia (CHH) is an autosomal recessive form of metaphyseal chondrodysplasia characterised by short limbed short stature, hypoplastic hair growth, and impaired cell mediated immunity and erythrocyte production. The syndrome is exceptionally prevalent among the Finns and among the Old Order Amish in the United States; sporadic cases have been reported from other countries. An epidemiological and genetic study of CHH in Finland showed 107 patients, 46 males and 61 females, in 85 families. Eighteen of them had died, seven before the age of 1 year. The living patients ranged in age from 1 to 51 years, median 21 years. The incidence was estimated to be 1:23,000 live births. Consanguinity was found in two families and interfamilial relationships in 20 families. Geographical distribution of the birth places of the patients and their great grandparents showed accumulation in a small area in western Finland and regional clusters were seen in other parts of the country as well. The result of the segregation analysis was in accordance with recessive inheritance with reduced penetrance. PMID:1404295

  10. Laboratory aspects of "Mycobacterium genavense," a proposed species isolated from AIDS patients.

    PubMed Central

    Coyle, M B; Carlson, L C; Wallis, C K; Leonard, R B; Raisys, V A; Kilburn, J O; Samadpour, M; Böttger, E C

    1992-01-01

    "Mycobacterium genavense" is a proposed new species recently reported to cause disseminated infections in 18 patients with AIDS in Europe. We have recovered "M. genavense" as slowly growing fastidious mycobacteria in blood cultures of seven patients with AIDS. In the original studies of "M. genavense," the fastidious organism grew only in BACTEC 13A vials. The Seattle, Washington, isolates of "M. genavense" also failed to grow when subcultured from 13A vials to routine solid media, but dysgonic colonies were produced on Middlebrook 7H11 agar supplemented with mycobactin J. The mycolic acid pattern of patients' isolates closely resembled that of the type strain of Mycobacterium simiae when analyzed by one- and two-dimensional thin-layer chromatography and by high-performance liquid chromatography. Whole-cell fatty acid analyses by gas-liquid chromatography distinguished the isolates from M. simiae but misidentified them as Mycobacterium fortuitum. Sequence determinations of the hypervariable regions of the 16S rRNA gene indicate that these organisms belong to the recently proposed new species "M. genavense." Growth from Middlebrook 7H11 agar supplemented with mycobactin J consistently yielded positive tests for catalase (semiquantitative and at 68 degrees C), pyrazinamidase, and urease which enable mycobacteriology laboratories to presumptively identify "M. genavense" without nucleic acid analyses. The failure of "M. genavense" to grow on conventional mycobacterial solid media suggests that mycobacterial blood cultures should include a broth medium incubated for at least 8 weeks. Images PMID:1280652

  11. Therapeutic and clinical aspects of portal vein thrombosis in patients with cirrhosis

    PubMed Central

    Primignani, Massimo; Tosetti, Giulia; La Mura, Vincenzo

    2015-01-01

    Portal vein thrombosis (PVT) is a frequent complication in cirrhosis, particularly in advanced stages of the disease. As for general venous thromboembolism, risk factors for PVT are slow blood flow, vessel wall damage and hypercoagulability, all features of advanced cirrhosis. Actually, the old dogma of a hemorrhagic tendency in cirrhosis has been challenged by new laboratory tools and the clinical evidence that venous thrombosis also occurs in cirrhosis. The impaired hepatic synthesis of both pro- and anticoagulants leads to a rebalanced hemostasis, more liable to be tipped towards thrombosis or even bleeding. Conventional anticoagulant drugs (low molecular weight heparin or vitamin K antagonists) may be used in cirrhosis patients with PVT, particularly in those eligible for liver transplantation, to prevent thrombosis progression thus permitting/facilitating liver transplant. However, several doubts exist on the level of anticoagulation achieved as estimated by coagulation tests, on the efficacy of treatment monitoring and on the correct timing for discontinuation in non-transplant candidates, while in transplant candidates there is expert consensus on continuing anticoagulation until transplantation. The recent introduction of direct acting oral anticoagulant drugs (DOACs) in other clinical settings generates much interest on their possible application in patients with cirrhosis and PVT. However, DOACs were not evaluated yet in patients with liver disease and cannot be recommended for the present time. PMID:26689354

  12. Rectal forceps biopsy procedure in cystic fibrosis: technical aspects and patients perspective for clinical trials feasibility

    PubMed Central

    2013-01-01

    Background Measurements of CFTR function in rectal biopsies ex vivo have been used for diagnosis and prognosis of Cystic Fibrosis (CF) disease. Here, we aimed to evaluate this procedure regarding: i) viability of the rectal specimens obtained by biopsy forceps for ex vivo bioelectrical and biochemical laboratory analyses; and ii) overall assessment (comfort, invasiveness, pain, sedation requirement, etc.) of the rectal forceps biopsy procedure from the patients perspective to assess its feasibility as an outcome measure in clinical trials. Methods We compared three bowel preparation solutions (NaCl 0.9%, glycerol 12%, mannitol), and two biopsy forceps (standard and jumbo) in 580 rectal specimens from 132 individuals (CF and non-CF). Assessment of the overall rectal biopsy procedure (obtained by biopsy forceps) by patients was carried out by telephone surveys to 75 individuals who underwent the sigmoidoscopy procedure. Results Integrity and friability of the tissue specimens correlate with their transepithelial resistance (r = −0.438 and −0.305, respectively) and are influenced by the bowel preparation solution and biopsy forceps used, being NaCl and jumbo forceps the most compatible methods with the electrophysiological analysis. The great majority of the individuals (76%) did not report major discomfort due to the short procedure time (max 15 min) and considered it relatively painless (79%). Importantly, most (88%) accept repeating it at least for one more time and 53% for more than 4 times. Conclusions Obtaining rectal biopsies with a flexible endoscope and jumbo forceps after bowel preparation with NaCl solution is a safe procedure that can be adopted for both adults and children of any age, yielding viable specimens for CFTR bioelectrical/biochemical analyses. The procedure is well tolerated by patients, demonstrating its feasibility as an outcome measure in clinical trials. PMID:23688510

  13. [QUALITY OF LIFE AND PSYCHOLOGICAL ASPECTS IN PATIENTS WITH CHRONIC LEG ULCER].

    PubMed

    Situm, Mirna; Kolić, Maja; Spoljar, Sanja

    2016-03-01

    Wound represents a disruption of anathomic and physiologic continuity of the skin. Regarding to the healing process, wounds can be classified as acute or chronic wounds. Quality of life is primarily concerned with the impact of chronic wounds. A wound is considered chronic if healing does not occur within expected period of time regarding to its etiology and localization. Chronic wounds can be classified as typical and atypical. The majority of wounds (95 percent) are typical ones which include ischaemic, neurotrophic and hypostatic ulcer and two separate entities: diabetic foot and decubital ulcers. An 80 percent of chronic wounds localized on lower leg are result of chronic venous insufficiency, in 5-10 percent cause is of arterial etiology, whereas the remainder is mostly neuropathic ulcer. Chronic wounds represent a significant burden to patients, health care professionals and the entire health care system. Chronic wounds affect the elderly population and it is estimated that 1-2 percent of western population suffer from it. This estimate is expected to rise due to an increasing population of the elderly and the diabetic and obesity epidemic. The WHO definition of health is "A state of complite physical, mental and social well-being and not merely the absence of disease or infirmity". Based on this definition, quality of life in relation to health may be defined as "the functional effect of an illness and it's consequent therapy upon a patient, as perceived by the patient". The domains that contribute to this effect are physical, psychological and social functioning. The patient's own perceptions of an illness were found to play an important role in explainig quality of life. Chronic wounds significantly decrease the quality of life in a number of ways such as reduced mobility, pain, unpleasant odor, sleep disturbances, social isolation and frustration, and inability to perform everyday duties. Among the most common psychological reactions to chronic diseases

  14. Psychological aspects and coping in haemophilic patients: a case-control study.

    PubMed

    Canclini, M; Saviolo-Negrin, N; Zanon, E; Bertoletti, R; Girolami, A; Pagnan, A

    2003-09-01

    Although enormous progress has been made in recent years in the field of haemophilia, some problems still await solution, such as the risk of sudden haemorrhage, the sequelae of haemophilic arthropathy and social activities. We, therefore, carried out a case-control study in which some psychological dimensions (social expectations, tendency to depression, state of anxiety and self-esteem) were evaluated in a group of 60 haemophiliacs. A control group was formed of 78 healthy subjects matched for age, socio-economic class and level of education. The methodology used was the administration of self-assessment questionnaires which investigate and provide a quantitative measure of psychological dimensions. The results can be subjected to statistical analysis. Three self-assessment questionnaires were used: (i) the Marlowe-Crowne scale, (ii) the Beck Inventory version modified by Cusinato and (iii) the S.T.A.I.-form. Our aim was to evaluate: (i) whether there are significant differences in the considered psychological aspects between haemophiliacs and healthy subjects; (ii) whether there is a significant correlation between the psychological dimensions considered in the haemophiliacs and in the healthy subjects. The results showed that the haemophiliacs have a good psychological adaptation to their disease with the exception of their greater tendency to have less self-esteem than do the healthy subjects. As far as concerns the second aim, we found than self-esteem correlated with all the psychological variables investigated. This information could indicate the enormous importance that the psychological variable 'self-esteem' plays in haemophiliacs with respect to whether or not they develop depressive disorders and/or anxiety states. PMID:14511304

  15. Psychological aspects of weekend headache sufferers in comparison with migraine patients.

    PubMed

    Nattero, G; De Lorenzo, C; Biale, L; Allais, G; Torre, E; Ancona, M

    1989-02-01

    Sometimes the relaxation after stress may trigger a migraine attack. This is the principle that underlies that particular variant of migraine called "weekend headache". We hypothesize the presence in weekend headache prone subjects of a particular psychological background, different from that of common migraine sufferers. In order to detect possible differences supporting our hypothesis, we studied 104 new outpatients: 46 patients suffering from headache only on weekends (23 males and 23 females) and 58 matched common migraineurs (26 males and 32 females) with no weekend predilection. The psychological assessment was performed using the following psychometric tools: MMPI, BDI, STAIX1-X2. A clinical assessment of each patient was also carried out. Significant differences were found after statistically analyzing the test results. Most of the MMPI scales were found to be more elevated in both male and female weekend headache sufferers. From a clinical point of view, the weekend headache attacks proved to be similar to those of common migraine, but with a significantly higher incidence of concomitant symptoms. Our study confirms the important role that psychological factors play in the pathogenesis and clinical development of migraine and leads us to conclude that a psychic tension component is associated with the vascular one in weekend headache. PMID:2708043

  16. [Treatment for Patients with Charcot-Marie-Tooth Disease: Orthopaedic Aspects].

    PubMed

    Watanabe, Kota

    2016-01-01

    The orthopedic manifestations in patients with Charcot-Marie-Tooth disease include deformity and dysfunction of the extremities and spine. Conservative treatment is the first choice. Orthosis and rehabilitation can improve function, and are important for the prevention of joint contractures. Foot problems are most commonly observed and require surgical treatment. Foot deformities include pes cavus, cavovarus, claw toes, or drop foot. Single or combined surgeries selected for soft tissues are plantar release, tendon transfer, or Achilles tendon lengthening, and those for bones are osteotomies and joint fusions. The upper limb initially demonstrates loss of power of the intrinsic hand muscles followed by symmetrical atrophy of the forearm muscle groups. The typical hand deformity is claw hand. Tendon transfer, joint fusion, soft tissue release, or nerve decompression procedures are performed for correction of hand deformities. Acetabular dysplasia in the hip joints is sometimes observed and osteotomy is selected as surgical treatment in such cases. The associated spinal deformity is scoliosis with or without kyphosis. Similar to treatment of idiopathic scoliosis, posterior spinal fusion is performed in patients with progressive spinal deformities. PMID:26764299

  17. Patient Demonstration Videos in Predoctoral Endodontic Education: Aspects Perceived as Beneficial by Students.

    PubMed

    Edrees, Hadeel Y; Ohlin, Johan; Ahlquist, Michael; Tessma, Mesfin K; Zary, Nabil

    2015-08-01

    The aim of this study was to assess the perceived benefits of video-mediated demonstrations in learning endodontics. Participants in the study were 75 third-year students enrolled in the undergraduate dentistry program at Karolinska Institute, Stockholm, Sweden. After the endodontic preclinical course, the students were introduced to the treatment protocol in the clinic by watching two live patient-demonstrated videos. The first video demonstrated how to communicate with the patient and perform diagnosis and root canal instrumentation. The second video illustrated how to perform bacterial sampling and root canal filling. After the students watched each video, a questionnaire was used to evaluate their opinions about various steps of the endodontic treatment protocol and the benefit of such educational material for their practice. Of the total 75 students, 72 completed the first questionnaire (96% response rate), and 65 completed the second questionnaire (87% response rate). The results showed that the students perceived high value in the video demonstrations related to treatment procedure. A statistically significant difference was observed between the perceived benefits of the first and second sessions in communication and treatment procedure (p<0.001). Further studies are needed to assess improvement in the design and delivery format for video demonstrations to enhance their effectiveness as a teaching modality for endodontics. PMID:26246531

  18. Patient's view of dialysis care: development of a taxonomy and rating of importance of different aspects of care. CHOICE study. Choices for Healthy Outcomes in Caring for ESRD.

    PubMed

    Rubin, H R; Jenckes, M; Fink, N E; Meyer, K; Wu, A W; Bass, E B; Levin, N; Powe, N R

    1997-12-01

    Quality assessment efforts to enhance public accountability in dialysis care and to support provider efforts to improve care have lacked patient input. To develop brief patient evaluation or satisfaction surveys suitable for busy clinical settings, knowing patients' priorities can be helpful in deciding which aspects of care should be tracked. We conducted a study to identify salient attributes of dialysis care and to rank the importance of these attributes from the perspective of dialysis patients. We analyzed the content of patient focus group transcripts to characterize dialysis care from the patients' perspective. We then surveyed 86 patients to determine how patients would rank the importance of each aspect to quality of dialysis care. The 18 broad aspects of care identified in the focus group included: (1) care provided by nephrologists, (2) care provided by other physicians (nonnephrologists), (3) care provided by dialysis center nurses, (4) care provided by social workers and psychologists, (5) care provided by dieticians, (6) clergy, (7) care provided by technicians and physician assistants/nurse practitioners, (8) care provided by dialysis center staff in general, (9) supplies, (10) treatment choice and effectiveness, (11) patient education and training, (12) self-care, (13) dialysis machines, (14) unit environment and policies, (15) cost containment, (16) billing, (17) cost of care, and (18) health outcomes. Items ranked in the top 10 by both groups of patients included issues related to nephrologists, other doctors, nurses, and patient education and training. Compared with hemodialysis patients, peritoneal dialysis patients gave higher ratings to hospital doctors' and nurses' attention to cleanliness when working with access sites, how correct the nephrologist's instructions to patients are, whether emergency room doctors check with nephrologists, the amount of information patients get about their diet, and how well nurses answer patients' questions

  19. Deficits of Affect Mentalization in Patients with Drug Addiction: Theoretical and Clinical Aspects

    PubMed Central

    Savov, Svetoslav; Atanassov, Nikola

    2013-01-01

    Traditionally treated with wariness, drug addictions have provoked a serious interest in psychodynamically oriented clinicians in recent decades. This paper discusses the development of contemporary psychodynamic conceptualizations of addictions, focusing specifically on mentalization-based theories. The concept of mentalization refers to a complex form of self-regulation which includes attribution of psychological meaning to one's own behavior and affective states, as well as those of the others. We hypothesize that drug-addicted patients have severe impairments in mentalizing, associated with developmental deficits, characteristic for the borderline personality disorder and psychosomatic conditions. Psychodynamic models of mentalization and their corresponding research operationalizations are reviewed, and implications for a contemporary understanding of drug addictions and psychotherapy are drawn. The authors propose that mentalization-oriented theories provide an adequate conceptualization, which is open to empirical testing and has clear and pragmatic guidelines for treatment. PMID:25969831

  20. New aspects of treatment of renal bone disease in dialysis patients.

    PubMed

    Spasovski, G

    2007-07-01

    The abnormalities in bone and mineral metabolism in chronic kidney disease patients are associated with an increased risk of fractures, vascular calcifications and cardiovascular diseases. A few decades ago hyperphosphatemia and the common development of secondary hyperparathyroidism were thought to be the main problem to deal with. Since dietary phosphate restriction and haemodialysis were not proven to be sufficient measures to reduce phosphorus, phosphate-binding therapy has been widely instituted as a treatment option. Various types of phosphate binders employed over the years have contributed to the changing spectrum of renal osteodystrophy from high to low bone turnover along with the shift from hypocalcemia and negative calcium balance towards hypercalcemia and the positive calcium balance. Thus, hypercalcemia instead of hyperphosphatemia is nowadays associated with the increased risk of vascular calcification, morbidity and mortality in the dialysis population. Besides the very expensive non-calcium based phosphate binders, at least two common tools may be helpful in the treatment of hypercalcemia and adynamic bone. A reduced daily use of calcium carbonate/acetate up to 1g per main meal is an easily manageable and inexpensive tool. The second option for stimulation of parathyroid gland activity and bone turnover is the lowering of the dialysate calcium concentration. In conclusion, an aggressive treatment of hyperphosphatemia and calcium overload might lead towards an opposite effect of hypoparathyroidism and hypercalcemia. Reasonable treatment strategies based on a careful monitoring should be employed in order to prevent related consequences and to contribute to a better long-term quality of life and survival of dialysis patients. PMID:17932468

  1. Exome sequencing reveals a novel missense mutation in the KIAA0196 gene in a Japanese patient with SPG8.

    PubMed

    Ichinose, Yuta; Koh, Kishin; Fukumoto, Megumi; Yamashiro, Nobuo; Kobayashi, Fumikazu; Miwa, Michiaki; Nagasaka, Takamura; Shindo, Kazumasa; Ishiura, Hiroyuki; Tsuji, Shoji; Takiyama, Dr Yoshihisa

    2016-05-01

    Exome sequencing revealed a novel missense mutation (c.2152G>A, p.E713K) in the KIAA0196 gene in a Japanese patient with SPG8. To date, only 10 mutations in the KIAA0196 gene have been reported in the world. We describe the clinical and genetic findings in our patient with SPG8, which is a rare dominant hereditary spastic paraplegia. Notably, our patient showed mild upper limb ataxia, which is a relatively atypical symptom of SPG8. Thus, our patient showed a wide clinical spectrum of SPG8. PMID:26967522

  2. [Fingolimod treatment for multiple sclerosis patients. Infectiological aspects and recommendations for vaccinations].

    PubMed

    Winkelmann, A; Löbermann, M; Reisinger, E C; Zettl, U K

    2012-02-01

    Since April 2011 fingolimod (FTY 720, Gilenya®), a new oral treatment, is available for relapsing-remitting multiple sclerosis (MS) in Germany. Adverse effects in pre-marketing clinical controlled multicenter studies have led to specific precautions that have to be followed before initiating treatment. According to the European Union prescribing information fingolimod is not to be used as a first-line treatment, but is licensed as a second-line option or escalating therapy of MS. During treatment physical and neurological examinations as well as regular blood counts should be performed. The immunosuppressive mode of action of fingolimod requires increased awareness of infectious complications. Due to two fatal herpetic infections during the TRANSFORMS trial all patients without a history of chicken pox or without vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV. Comparably to other immunosuppressive treatment strategies the immune response to vaccines may be hampered during treatment with fingolimod. Thus, on the one hand, vaccination gaps should be closed before initiation of fingolimod treatment and, on the other hand, success of vaccinations during fingolimod therapy may have to be checked by antibody titre assessment. PMID:21845450

  3. Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis.

    PubMed

    Lau, Susanna K P; Lee, Kim-Chung; Lo, George C S; Ding, Vanessa S Y; Chow, Wang-Ngai; Ke, Tony Y H; Curreem, Shirly O T; To, Kelvin K W; Ho, Deborah T Y; Sridhar, Siddharth; Wong, Sally C Y; Chan, Jasper F W; Hung, Ivan F N; Sze, Kong-Hung; Lam, Ching-Wan; Yuen, Kwok-Yung; Woo, Patrick C Y

    2016-01-01

    To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis. PMID:26927094

  4. Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

    PubMed Central

    Lau, Susanna K. P.; Lee, Kim-Chung; Lo, George C. S.; Ding, Vanessa S. Y.; Chow, Wang-Ngai; Ke, Tony Y. H.; Curreem, Shirly O. T.; To, Kelvin K. W.; Ho, Deborah T. Y.; Sridhar, Siddharth; Wong, Sally C. Y.; Chan, Jasper F. W.; Hung, Ivan F. N.; Sze, Kong-Hung; Lam, Ching-Wan; Yuen, Kwok-Yung; Woo, Patrick C. Y.

    2016-01-01

    To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis. PMID:26927094

  5. ‘Two Pains Together’: Patient Perspectives on Psychological Aspects of Chronic Pain while Living with HIV

    PubMed Central

    Merlin, Jessica S.; Walcott, Melonie; Ritchie, Christine; Herbey, Ivan; Kertesz, Stefan G.; Chamot, Eric; Saag, Michael; Turan, Janet M.

    2014-01-01

    Objective Chronic pain is common in HIV-infected individuals. Understanding HIV-infected patients’ chronic pain experience not just from a biological, but also from a psychological perspective, is a critical first step toward improving care for this population. Our objective was to explore HIV-infected patients’ perspectives on psychological aspects of chronic pain using in-depth qualitative interviews. Methods Investigators engaged in an iterative process of independent and group coding until theme saturation was reached. Results Of the 25 patients with chronic pain interviewed, 20 were male, 15 were younger than age 50, and 15 were African-American. Key themes that emerged included the close relationship between mood and pain; mood and pain in the context of living with HIV; use of alcohol/drugs to self-medicate for pain; and the challenge of receiving prescription pain medications while dealing with substance use disorders. Conclusions The results suggest that psychological approaches to chronic pain treatment may be well received by HIV-infected patients. PMID:25365306

  6. Cortico-cortical networks in patients with ideomotor apraxia as revealed by EEG coherence analysis

    PubMed Central

    Wheaton, Lewis A.; Bohlhalter, Stephan; Nolte, Guido; Shibasaki, Hiroshi; Hattori, Noriaki; Fridman, Esteban; Vorbach, Sherry; Grafman, Jordan; Hallett, Mark

    2008-01-01

    We sought to determine whether coherent networks which circumvent lesioned cortex are seen in patients with ideomotor apraxia (IMA) while performing tool use pantomimes. Five normal subjects and five patients with IMA (three patients with corticobasal degeneration and two with left hemisphere stroke) underwent 64-channel EEG recording while performing three tool-use pantomimes with their left hand in a self-paced manner. Beta band (20–22 Hz) coherence indicates that normal subjects have a dominant left hemisphere network responsible for praxis preparation, which was absent in patients. Corticobasal degeneration patients showed significant coherence increase between left parietal - right premotor areas. Left hemisphere stroke patients showed significant coherence increases in a right parietofrontal network. The right hemisphere appears to store useable praxis representations in IMA patients with left hemisphere damage. PMID:18249498

  7. Psychosocial aspects of dialysis and renal transplant.

    PubMed

    Haq, I; Zainulabdin, F; Naqvi, A; Rizvi, A H; Ahmed, S H

    1991-05-01

    Keeping in view our socio cultural millieu, the psychological aspects of twenty renal transplants recipients and equal number of patients on dialysis were studied. Socio psychiatric profile in the dialysis and transplanted patients revealed that the frequency of anxiety, depression and hypochondriasis was significantly less (P less than 0.01) in the transplanted group. On Bender Gestalt Scale the transplanted group achieved normal status in significantly higher (P less than 0.05) number compared to the dialysis patients. It was concluded that transplanted patients showed marked improvement in social functioning, psychological symptoms and enduring personality traits compared to patients on maintenance dialysis. PMID:1861361

  8. German cohort of HCV mono-infected and HCV/HIV co-infected patients reveals relative under-treatment of co-infected patients

    PubMed Central

    2014-01-01

    Background Current German and European HIV guidelines recommend early evaluation of HCV treatment in all HIV/HCV co-infected patients. However, there are still considerable barriers to initiate HCV therapy in everyday clinical practice. This study evaluates baseline characteristics, “intention-to-treat” pattern and outcome of therapy of HCV/HIV co-infected patients in direct comparison to HCV mono-infected patients in a “real-life” setting. Methods A large, single-center cohort of 172 unselected HCV patients seen at the Infectious Diseases Unit at the University Medical Center Hamburg-Eppendorf from 2000–2011, 88 of whom HCV/HIV co-infected, was retrospectively analyzed by chart review with special focus on demographic, clinical and virologic aspects as well as treatment outcome. Results Antiviral HCV combination therapy with PEG-interferon plus weight-adapted ribavirin was initiated in 88/172 (52%) patients of the entire cohort and in n = 36 (40%) of all HCV/HIV co-infected patients (group A) compared to n = 52 (61%) of the HCV mono-infected group (group B) (p = 0.006). There were no significant differences of the demographics or severity of the liver disease between the two groups with the exception of slightly higher baseline viral loads in group A. A sustained virologic response (SVR) was observed in 50% (n = 18) of all treated HIV/HCV co-infected patients versus 52% (n = 27) of all treated HCV mono-infected patients (p = 0.859). Genotype 1 was the most frequent genotype in both groups (group A: n = 37, group B: n = 49) and the SVR rates for these patients were only slightly lower in the group of co-infected patients (group A: n = 33%, group B: 40% p = 0.626). During the course of treatment HCV/HIV co-infected patients received less ribavirin than mono-infected patients. Conclusion Overall, treatment was only initiated in half of the patients of the entire cohort and in an even smaller proportion of HCV/HIV co

  9. Whole Genome Sequencing Reveals Complex Evolution Patterns of Multidrug-Resistant Mycobacterium tuberculosis Beijing Strains in Patients

    PubMed Central

    Merker, Matthias; Kohl, Thomas A.; Roetzer, Andreas; Truebe, Leona; Richter, Elvira; Rüsch-Gerdes, Sabine; Fattorini, Lanfranco; Oggioni, Marco R.; Cox, Helen; Varaine, Francis; Niemann, Stefan

    2013-01-01

    Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains represent a major threat for tuberculosis (TB) control. Treatment of MDR-TB patients is long and less effective, resulting in a significant number of treatment failures. The development of further resistances leads to extensively drug-resistant (XDR) variants. However, data on the individual reasons for treatment failure, e.g. an induced mutational burst, and on the evolution of bacteria in the patient are only sparsely available. To address this question, we investigated the intra-patient evolution of serial MTBC isolates obtained from three MDR-TB patients undergoing longitudinal treatment, finally leading to XDR-TB. Sequential isolates displayed identical IS6110 fingerprint patterns, suggesting the absence of exogenous re-infection. We utilized whole genome sequencing (WGS) to screen for variations in three isolates from Patient A and four isolates from Patient B and C, respectively. Acquired polymorphisms were subsequently validated in up to 15 serial isolates by Sanger sequencing. We determined eight (Patient A) and nine (Patient B) polymorphisms, which occurred in a stepwise manner during the course of the therapy and were linked to resistance or a potential compensatory mechanism. For both patients, our analysis revealed the long-term co-existence of clonal subpopulations that displayed different drug resistance allele combinations. Out of these, the most resistant clone was fixed in the population. In contrast, baseline and follow-up isolates of Patient C were distinguished each by eleven unique polymorphisms, indicating an exogenous re-infection with an XDR strain not detected by IS6110 RFLP typing. Our study demonstrates that intra-patient microevolution of MDR-MTBC strains under longitudinal treatment is more complex than previously anticipated. However, a mutator phenotype was not detected. The presence of different subpopulations might confound phenotypic and molecular drug

  10. Revealing a cancer diagnosis to patients: attitudes of patients, families, friends, nurses, and physicians in Lebanon—results of a cross-sectional study

    PubMed Central

    Farhat, F.; Othman, A.; el Baba, G.; Kattan, J.

    2015-01-01

    Background Disclosure of a cancer diagnosis to patients is a major problem for physicians in Lebanon. Our survey aimed to identify the attitudes of patients, families and friends, nurses, and physicians regarding disclosure of a cancer diagnosis. Methods Study participants included 343 physicians, nurses, cancer patients, families, and friends from clinics in two major hospitals in Lebanon. All completed a 29-item questionnaire that assessed, by demographic group, the information provided about cancer, opinions about the disclosure of the diagnosis to cancer patients, perceived consequences to patients, and the roles of family, friends, and religion. Results Overall, 7.8% of the patients were convinced that cancer is incurable. Nearly 82% preferred to be informed about their diagnosis. Similarly, 83% of physicians were in favour of disclosing a cancer diagnosis to their patients. However, only 14% of the physicians said that they revealed the truth to the patients themselves, with only 9% doing so immediately after confirmation of the diagnosis. Disclosure of a cancer diagnosis was preferred before the start of the treatment by 59% of the patients and immediately after confirmation of the diagnosis by 72% of the physicians. Overall, 86% of physicians, 51% of nurses, and 69% of patients and their families believed that religion helped with the acceptance of a cancer diagnosis. A role for family in accepting the diagnosis was reported by 74% of the patients, 56% of the nurses, and 88% of the physicians. All participants considered that fear was the most difficult feeling (63%) experienced by cancer patients, followed by pain (29%), pity (8%), and death (1%), with no statistically significant difference between the answers given by the participant groups. Conclusions The social background in Lebanese society is the main obstacle to revealing the truth to cancer patients. Lebanese patients seem to prefer direct communication of the truth, but families take the opposite

  11. Analysis of sporadic tuberous sclerosis patients with the TSC2 cDNA reveals several gene rearrangements and deletions

    SciTech Connect

    Wilson, P.J.; Short, M.P.; Bove, C.

    1994-09-01

    Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by hamartomas and hamartias in many organs including brain, skin, heart and kidneys. Two TSC genes have been localized through linkage analysis, TSC1 to 9q34 and TSC2 to 16p13.3. TSC2 was recently cloned. The distribution of sporadic TSC patients between TSC1 and TSC2 is at present unknown, but tests of genetic heterogeneity in families suggest that each is equally represented. Genetic heterogeneity may account for some of the variation in clinical expression; however, there is no evidence at present to support differences in clinical phenotypes between the 2 genetic loci. With the isolation of the TSC2 gene we have commenced mutation studies of our familial and sporadic TSC patients. Thus far six chromosome 16-linked families have been screened with the TSC2 cDNA and no detectable changes were observed using Southern analysis. In addition, 85 sporadic TSC patients were analyzed by Southern analysis. Using multiple restriction digests, nine patients revealed altered patterns, including three patients that appeared to have complete deletions. RT-PCR was performed on these patients confirming that the TSC2 gene was deleted. However, the remaining patients showed normal patterns, indicating that they either have TSC1 mutations or they possess more subtle small deletions or point mutations. At present we are designing an SSCP-based approach to determine the nature of the mutations in our 16 linked TSC families.

  12. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients

    PubMed Central

    Chabon, Jacob J.; Simmons, Andrew D.; Lovejoy, Alexander F.; Esfahani, Mohammad S.; Newman, Aaron M.; Haringsma, Henry J.; Kurtz, David M.; Stehr, Henning; Scherer, Florian; Karlovich, Chris A.; Harding, Thomas C.; Durkin, Kathleen A.; Otterson, Gregory A.; Purcell, W. Thomas; Camidge, D. Ross; Goldman, Jonathan W.; Sequist, Lecia V.; Piotrowska, Zofia; Wakelee, Heather A.; Neal, Joel W.; Alizadeh, Ash A.; Diehn, Maximilian

    2016-01-01

    Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment. PMID:27283993

  13. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients.

    PubMed

    Chabon, Jacob J; Simmons, Andrew D; Lovejoy, Alexander F; Esfahani, Mohammad S; Newman, Aaron M; Haringsma, Henry J; Kurtz, David M; Stehr, Henning; Scherer, Florian; Karlovich, Chris A; Harding, Thomas C; Durkin, Kathleen A; Otterson, Gregory A; Purcell, W Thomas; Camidge, D Ross; Goldman, Jonathan W; Sequist, Lecia V; Piotrowska, Zofia; Wakelee, Heather A; Neal, Joel W; Alizadeh, Ash A; Diehn, Maximilian

    2016-01-01

    Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment. PMID:27283993

  14. Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

    PubMed Central

    Chen, Yu-Chen; Zhang, Jian; Li, Xiao-Wei; Xia, Wenqing; Feng, Xu; Gao, Bo; Ju, Sheng-Hong; Wang, Jian; Salvi, Richard; Teng, Gao-Jun

    2014-01-01

    Objective The neural mechanisms that give rise to the phantom sound of tinnitus are poorly understood. This study aims to investigate whether aberrant spontaneous brain activity exists in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI) technique. Materials and methods A total of 31 patients with chronic tinnitus patients and 32 healthy age-, sex-, and education-matched healthy controls were prospectively examined. Both groups had normal hearing thresholds. We calculated the amplitude of low-frequency fluctuations (ALFFs) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between fMRI information and clinical data of tinnitus. Results Compared with healthy controls, we observed significant increased ALFF within several selected regions including the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG), and right angular gyrus; decreased ALFF was detected in the left cuneus, right middle occipital gyrus and bilateral thalamus. Moreover, tinnitus distress correlated positively with increased ALFF in right MTG and right SFG; tinnitus duration correlated positively with higher ALFF values in right SFG. Conclusions The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients. PMID:25379434

  15. Revealing and Resolving Patient Safety Defects: The Impact of Leadership WalkRounds on Frontline Caregiver Assessments of Patient Safety

    PubMed Central

    Frankel, Allan; Grillo, Sarah Pratt; Pittman, Mary; Thomas, Eric J; Horowitz, Lisa; Page, Martha; Sexton, Bryan

    2008-01-01

    Objective To evaluate the impact of rigorous WalkRounds on frontline caregiver assessments of safety climate, and to clarify the steps and implementation of rigorous WalkRounds. Data Sources/Study Setting Primary outcome variables were baseline and post WalkRounds safety climate scores from the Safety Attitudes Questionnaire (SAQ). Secondary outcomes were safety issues elicited through WalkRounds. Study period was August 2002 to April 2005; seven hospitals in Massachusetts agreed to participate; and the project was implemented in all patient care areas. Study Design Prospective study of the impact of rigorously applied WalkRounds on frontline caregivers assessments of safety climate in their patient care area. WalkRounds were conducted weekly and according to the seven-step WalkRounds Guide. The SAQ was administered at baseline and approximately 18 months post-WalkRounds implementation to all caregivers in patient care areas. Results Two of seven hospitals complied with the rigorous WalkRounds approach; hospital A was an academic teaching center and hospital B a community teaching hospital. Of 21 patient care areas, SAQ surveys were received from 62 percent of respondents at baseline and 60 percent post WalkRounds. At baseline, 10 of 21 care areas (48 percent) had safety climate scores below 60 percent, whereas post-WalkRounds three care areas (14 percent) had safety climate scores below 60 percent without improving by 10 points or more. Safety climate scale scores in hospital A were 62 percent at baseline and 77 percent post-WalkRounds (t=2.67, p=.03), and in hospital B were 46 percent at baseline and 56 percent post WalkRounds (t=2.06, p=.06). Main safety issues by category were equipment/facility (A [26 percent] and B [33 percent]) and communication (A [24 percent] and B [18 percent]). Conclusions WalkRounds implementation requires significant organizational will; sustainability requires outstanding project management and leadership engagement. In the patient

  16. Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer.

    PubMed

    Wang, Rui; Stone, Rebecca L; Kaelber, Jason T; Rochat, Ryan H; Nick, Alpa M; Vijayan, K Vinod; Afshar-Kharghan, Vahid; Schmid, Michael F; Dong, Jing-Fei; Sood, Anil K; Chiu, Wah

    2015-11-17

    Thrombocytosis and platelet hyperreactivity are known to be associated with malignancy; however, there have been no ultrastructure studies of platelets from patients with ovarian cancer. Here, we used electron cryotomography (cryo-ET) to examine frozen-hydrated platelets from patients with invasive ovarian cancer (n = 12) and control subjects either with benign adnexal mass (n = 5) or free from disease (n = 6). Qualitative inspections of the tomograms indicate significant morphological differences between the cancer and control platelets, including disruption of the microtubule marginal band. Quantitative analysis of subcellular features in 120 platelet electron tomograms from these two groups showed statistically significant differences in mitochondria, as well as microtubules. These structural variations in the platelets from the patients with cancer may be correlated with the altered platelet functions associated with malignancy. Cryo-ET of platelets shows potential as a noninvasive biomarker technology for ovarian cancer and other platelet-related diseases. PMID:26578771

  17. Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes.

    PubMed

    Kondo, Takayuki; Funayama, Misato; Miyake, Michiyo; Tsukita, Kayoko; Era, Takumi; Osaka, Hitoshi; Ayaki, Takashi; Takahashi, Ryosuke; Inoue, Haruhisa

    2016-01-01

    Alexander disease is a fatal neurological illness characterized by white-matter degeneration and formation of Rosenthal fibers, which contain glial fibrillary acidic protein as astrocytic inclusion. Alexander disease is mainly caused by a gene mutation encoding glial fibrillary acidic protein, although the underlying pathomechanism remains unclear. We established induced pluripotent stem cells from Alexander disease patients, and differentiated induced pluripotent stem cells into astrocytes. Alexander disease patient astrocytes exhibited Rosenthal fiber-like structures, a key Alexander disease pathology, and increased inflammatory cytokine release compared to healthy control. These results suggested that Alexander disease astrocytes contribute to leukodystrophy and a variety of symptoms as an inflammatory source in the Alexander disease patient brain. Astrocytes, differentiated from induced pluripotent stem cells of Alexander disease, could be a cellular model for future translational medicine. PMID:27402089

  18. Metagenomics Reveals Dysbiosis and a Potentially Pathogenic N. flavescens Strain in Duodenum of Adult Celiac Patients

    PubMed Central

    D'Argenio, Valeria; Casaburi, Giorgio; Precone, Vincenza; Pagliuca, Chiara; Colicchio, Roberta; Sarnataro, Daniela; Discepolo, Valentina; Kim, Sangman M; Russo, Ilaria; Del Vecchio Blanco, Giovanna; Horner, David S; Chiara, Matteo; Pesole, Graziano; Salvatore, Paola; Monteleone, Giovanni; Ciacci, Carolina; Caporaso, Gregory J; Jabrì, Bana; Salvatore, Francesco; Sacchetti, Lucia

    2016-01-01

    OBJECTIVES: Celiac disease (CD)-associated duodenal dysbiosis has not yet been clearly defined, and the mechanisms by which CD-associated dysbiosis could concur to CD development or exacerbation are unknown. In this study, we analyzed the duodenal microbiome of CD patients. METHODS: The microbiome was evaluated in duodenal biopsy samples of 20 adult patients with active CD, 6 CD patients on a gluten-free diet, and 15 controls by DNA sequencing of 16S ribosomal RNA libraries. Bacterial species were cultured, isolated and identified by mass spectrometry. Isolated bacterial species were used to infect CaCo-2 cells, and to stimulate normal duodenal explants and cultured human and murine dendritic cells (DCs). Inflammatory markers and cytokines were evaluated by immunofluorescence and ELISA, respectively. RESULTS: Proteobacteria was the most abundant and Firmicutes and Actinobacteria the least abundant phyla in the microbiome profiles of active CD patients. Members of the Neisseria genus (Betaproteobacteria class) were significantly more abundant in active CD patients than in the other two groups (P=0.03). Neisseria flavescens (CD-Nf) was the most abundant Neisseria species in active CD duodenum. Whole-genome sequencing of CD-Nf and control-Nf showed genetic diversity of the iron acquisition systems and of some hemoglobin-related genes. CD-Nf was able to escape the lysosomal compartment in CaCo-2 cells and to induce an inflammatory response in DCs and in ex-vivo mucosal explants. CONCLUSIONS: Marked dysbiosis and an abundance of a peculiar CD-Nf strain characterize the duodenal microbiome in active CD patients thus suggesting that the CD-associated microbiota could contribute to the many inflammatory signals in this disorder. PMID:27045926

  19. Intragenic and large NIPBL rearrangements revealed by MLPA in Cornelia de Lange patients

    PubMed Central

    Russo, Silvia; Masciadri, Maura; Gervasini, Cristina; Azzollini, Jacopo; Cereda, Anna; Zampino, Giuseppe; Haas, Oskar; Scarano, Gioacchino; Di Rocco, Maja; Finelli, Palma; Tenconi, Romano; Selicorni, Angelo; Larizza, Lidia

    2012-01-01

    Cornelia de Lange syndrome (CdLS) is a rare multisystemic congenital anomaly disorder that is characterised by intellectual disability and growth retardation, congenital heart defects, intestinal anomalies, facial dysmorphism (including synophyris and high arched eyebrows) and limb reduction defects. Mutations in three cohesin-associated genes encoding a key regulator (NIPBL, chr 5p13.2) and one structural component of the cohesin ring (SMC1A, chr Xp11) occur in about 65% of CdLS patients. NIPBL is the major causative gene, and accounts for 40–60% of CdLS patients as shown by a number of mutational screening studies that indicate a wide mutational repertoire of mainly small deletions and point mutations. Only a few data are available concerning the occurrence of large NIPBL rearrangements or intragenic deletions or duplications involving whole exons. We used multiplex ligation-dependent probe amplification (MLPA) to study 132 CdLS patients negative to the standard mutation NIPBL test out of a cohort of 200 CdLS patients. A total of 7 out of 132 patients were found to carry NIPBL alterations, including two large gene deletions extending beyond the gene, four intragenic multi- or single-exon deletions and one single-exon duplication. These findings show that MLPA leads to a 5.3% increase in the detection of mutations when used in addition to the standard NIPBL scan, and contributes per se to the molecular diagnosis of 3.5% (7/200) of clinically diagnosed CdLS patients. It is recommended that MLPA be included in the CdLS diagnostic flow chart. PMID:22353942

  20. Differential Proteomics of Urinary Exovesicles from Classical Galactosemic Patients Reveals Subclinical Kidney Insufficiency.

    PubMed

    Staubach, Simon; Pekmez, Murat; Hanisch, Franz-Georg

    2016-06-01

    Classical galactosemia is caused by a nearly complete deficiency of galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712), resulting in a severely impaired galactose metabolism with galactose-1-phosphate and galactitol accumulation. Even on a galactose-restricted diet, patients develop serious long-term complications of the central nervous system and ovaries that may result from chronic cell-toxic effects exerted by endogenous galactose. To address the question of whether disease-associated cellular perturbations could affect the kidney function of the patients, we performed differential proteomics of detergent-resistant membranes from urinary exovesicles. Galactosemic samples (showing drastic shifts from high-mannose to complex-type N-glycosylation on exosomal N-glycoproteins) and healthy, sex-matched controls were analyzed in quadruplex iTRAQ experiments performed in biological and technical replicates. Particularly in the female patient group, the most striking finding was a drastic increase of abundant serum (glyco)proteins, like albumin, leucine-rich α-2-glycoprotein, fetuin, immunoglobulins, prostaglandin H2 d-isomerase, and α-1-microglobulin protein (AMBP), pointing to a subclinical failure of kidney filter function in galactosemic patients and resulting in a heavy overload of exosomal membranes with adsorbed serum (glyco)proteins. Several of these proteins are connected to TBMN and IgAN, proteinuria, and renal damage. The impairment of renal protein filtration was also indicated by increased protein contents derived from extracellular matrices and lysosomes. PMID:27103203

  1. Quantitative electroencephalography reveals different physiological profiles between benign and remitting-relapsing multiple sclerosis patients

    PubMed Central

    Vazquez-Marrufo, Manuel; Gonzalez-Rosa, Javier J; Vaquero, Encarnacion; Duque, Pablo; Borges, Monica; Gomez, Carlos; Izquierdo, Guillermo

    2008-01-01

    Background A possible method of finding physiological markers of multiple sclerosis (MS) is the application of EEG quantification (QEEG) of brain activity when the subject is stressed by the demands of a cognitive task. In particular, modulations of the spectral content that take place in the EEG of patients with multiple sclerosis remitting-relapsing (RRMS) and benign multiple sclerosis (BMS) during a visuo-spatial task need to be observed. Methods The sample consisted of 19 patients with RRMS, 10 with BMS, and 21 control subjects. All patients were free of medication and had not relapsed within the last month. The power spectral density (PSD) of different EEG bands was calculated by Fast-Fourier-Transformation (FFT), those analysed being delta, theta, alpha, beta and gamma. Z-transformation was performed to observe individual profiles in each experimental group for spectral modulations. Lastly, correlation analyses was performed between QEEG values and other variables from participants in the study (age, EDSS, years of evolution and cognitive performance). Results Nearly half (42%) the RRMS patients showed a statistically significant increase of two or more standard deviations (SD) compared to the control mean value for the beta-2 and gamma bands (F = 2.074, p = 0.004). These alterations were localized to the anterior regions of the right hemisphere, and bilaterally to the posterior areas of the scalp. None of the BMS patients or control subjects had values outside the range of ± 2 SD. There were no significant correlations between these values and the other variables analysed (age, EDSS, years of evolution or behavioural performance). Conclusion During the attentional processing, changes in the high EEG spectrum (beta-2 and gamma) in MS patients exhibit physiological alterations that are not normally detected by spontaneous EEG analysis. The different spectral pattern between pathological and controls groups could represent specific changes for the RRMS

  2. Low-temperature infiltration identified using infrared thermography in patients with subcutaneous edema revealed ultrasonographically: A case report.

    PubMed

    Oya, Maiko; Takahashi, Toshiaki; Tanabe, Hidenori; Oe, Makoto; Murayama, Ryoko; Yabunaka, Koichi; Matsui, Yuko; Sanada, Hiromi

    2016-01-01

    Infiltration is a frequent complication of infusion therapy. We previously demonstrated the usefulness of infrared thermography as an objective method of detecting infiltration in healthy people. However, whether thermography can detect infiltration in clinical settings remains unknown. Therefore, we report two cases where thermography was useful in detecting infiltration at puncture sites. In both cases, tissue changes were verified ultrasonographically. The patients were a 56-year-old male with cholangitis and a 76-year-old female with hepatoma. In both cases, infiltration symptoms such as swelling and erythema occurred one day after the insertion of a peripheral intravenous catheter. Thermographic images from both patients revealed low-temperature areas spreading from the puncture sites; however, these changes were not observed in other patients. The temperature difference between the low-temperature areas and their surrounding skin surface exceeded 1.0°C. Concurrently, ultrasound images revealed that tissues surrounding the vein had a cobblestone appearance, indicating edema. In both patients, subcutaneous tissue changes suggested infiltration and both had low-temperature areas spreading from the puncture sites. Thus, subcutaneous edema may indicate infusion leakage, resulting in a decrease in the temperature of the associated skin surface. These cases suggest that infrared thermography is an effective method of objectively and noninvasively detecting infiltration. PMID:27210893

  3. Altered Spontaneous Activity in Patients with Persistent Somatoform Pain Disorder Revealed by Regional Homogeneity

    PubMed Central

    Yan, Chao; Lu, Jing; Li, Xuzhou; Tang, Chaozheng; Fan, Mingxia; Luo, Yanli

    2016-01-01

    Persistent somatoform pain disorder (PSPD) is a mental disorder un-associated with any somatic injury and can cause severe somatosensory and emotional impairments in patients. However, so far, the neuro-pathophysiological mechanism of the functional impairments in PSPD is still unclear. The present study assesses the difference in regional spontaneous activity between PSPD and healthy controls (HC) during a resting state, in order to elucidate the neural mechanisms underlying PSPD. Resting-state functional Magnetic Resonance Imaging data were obtained from 13 PSPD patients and 23 age- and gender-matched HC subjects in this study. Kendall’s coefficient of concordance was used to measure regional homogeneity (ReHo), and a two-sample t-test was subsequently performed to investigate the ReHo difference between PSPD and HC. Additionally, the correlations between the mean ReHo of each survived area and the clinical assessments were further analyzed. Compared with the HC group, patients with PSPD exhibited decreased ReHo in the bilateral primary somatosensory cortex, posterior cerebellum, and occipital lobe, while increased ReHo in the prefrontal cortex (PFC) and default mode network (including the medial PFC, right inferior parietal lobe (IPL), and left supramarginal gyrus). In addition, significant positive correlations were found between the mean ReHo of both right IPL and left supramarginal gyrus and participants’ Self-Rating Anxiety Scale (SAS) scores, and between the mean ReHo of the left middle frontal gyrus and Visual Analogue Scale (VAS) scores. Our results suggest that abnormal spontaneous brain activity in specific brain regions during a resting state may be associated with the dysfunctions in pain, memory and emotional processing commonly observed in patients with PSPD. These findings help us to understand the neural mechanisms underlying PSPD and suggest that the ReHo metric could be used as a clinical marker for PSPD. PMID:26977802

  4. Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients.

    PubMed

    Ollero, Mario; Astarita, Giuseppe; Guerrera, Ida Chiara; Sermet-Gaudelus, Isabelle; Trudel, Stéphanie; Piomelli, Daniele; Edelman, Aleksander

    2011-05-01

    Cystic fibrosis (CF) is associated with abnormal lipid metabolism. We have recently shown variations in plasma levels of several phosphatidylcholine (PC) and lysophopshatidylcholine (LPC) species related to disease severity in CF patients. Here our goal was to search for blood plasma lipid signatures characteristic of CF patients bearing the same mutation (F508del) and different phenotypes, and to study their correlation with forced expiratory volume in 1 s (FEV1) and Pseudomonas aeruginosa chronic infection, evaluated at the time of testing (t = 0) and three years later (t = 3). Samples from 44 F508del homozygotes were subjected to a lipidomic approach based on LC-ESI-MS. Twelve free fatty acids were positively correlated with FEV1 at t = 0 (n = 29). Four of them (C20:3n-9, C20:5n-3, C22:5n-3, and C22:6n-3) were also positively correlated with FEV1 three years later, along with PC(32:2) and PC(36:4) (n = 31). Oleoylethanolamide (OEA) was negatively correlated with FEV1 progression (n = 17). Chronically infected patients at t = 0 showed lower PC(32:2), PC(38:5), and C18:3n-3 and higher cholesterol, cholesterol esters, and triacylglycerols (TAG). Chronically infected patients at t = 3 showed significantly lower levels of LPC(18:0). These results suggest a potential prognostic value for some lipid signatures in, to our knowledge, the first longitudinal study aimed at identifying lipid biomarkers for CF. PMID:21335323

  5. Altered Spontaneous Activity in Patients with Persistent Somatoform Pain Disorder Revealed by Regional Homogeneity.

    PubMed

    Huang, Tianming; Zhao, Zhiyong; Yan, Chao; Lu, Jing; Li, Xuzhou; Tang, Chaozheng; Fan, Mingxia; Luo, Yanli

    2016-01-01

    Persistent somatoform pain disorder (PSPD) is a mental disorder un-associated with any somatic injury and can cause severe somatosensory and emotional impairments in patients. However, so far, the neuro-pathophysiological mechanism of the functional impairments in PSPD is still unclear. The present study assesses the difference in regional spontaneous activity between PSPD and healthy controls (HC) during a resting state, in order to elucidate the neural mechanisms underlying PSPD. Resting-state functional Magnetic Resonance Imaging data were obtained from 13 PSPD patients and 23 age- and gender-matched HC subjects in this study. Kendall's coefficient of concordance was used to measure regional homogeneity (ReHo), and a two-sample t-test was subsequently performed to investigate the ReHo difference between PSPD and HC. Additionally, the correlations between the mean ReHo of each survived area and the clinical assessments were further analyzed. Compared with the HC group, patients with PSPD exhibited decreased ReHo in the bilateral primary somatosensory cortex, posterior cerebellum, and occipital lobe, while increased ReHo in the prefrontal cortex (PFC) and default mode network (including the medial PFC, right inferior parietal lobe (IPL), and left supramarginal gyrus). In addition, significant positive correlations were found between the mean ReHo of both right IPL and left supramarginal gyrus and participants' Self-Rating Anxiety Scale (SAS) scores, and between the mean ReHo of the left middle frontal gyrus and Visual Analogue Scale (VAS) scores. Our results suggest that abnormal spontaneous brain activity in specific brain regions during a resting state may be associated with the dysfunctions in pain, memory and emotional processing commonly observed in patients with PSPD. These findings help us to understand the neural mechanisms underlying PSPD and suggest that the ReHo metric could be used as a clinical marker for PSPD. PMID:26977802

  6. Plasmid metagenomics reveals multiple antibiotic resistance gene classes among the gut microbiomes of hospitalised patients.

    PubMed

    Jitwasinkul, Tossawan; Suriyaphol, Prapat; Tangphatsornruang, Sithichoke; Hansen, Martin Asser; Hansen, Lars Hestbjerg; Sørensen, Søren Johannes; Permpikul, Chairat; Rongrungruang, Yong; Tribuddharat, Chanwit

    2016-09-01

    Antibiotic resistance genes are rapidly spread between pathogens and the normal flora, with plasmids playing an important role in their circulation. This study aimed to investigate antibiotic resistance plasmids in the gut microbiome of hospitalised patients. Stool samples were collected from seven inpatients at Siriraj Hospital (Bangkok, Thailand) and were compared with a sample from a healthy volunteer. Plasmids from the gut microbiomes extracted from the stool samples were subjected to high-throughput DNA sequencing (GS Junior). Newbler-assembled DNA reads were categorised into known and unknown sequences (using >80% alignment length as the cut-off), and ResFinder was used to classify the antibiotic resistance gene pools. Plasmid replicon modules were used for plasmid typing. Forty-six genes conferring resistance to several classes of antibiotics were identified in the stool samples. Several antibiotic resistance genes were shared by the patients; interestingly, most were reported previously in food animals and healthy humans. Four antibiotic resistance genes were found in the healthy subject. One gene (aph3-III) was identified in the patients and the healthy subject and was related to that in cattle. Uncommon genes of hospital origin such as blaTEM-124-like and fosA, which confer resistance to extended-spectrum β-lactams and fosfomycin, respectively, were identified. The resistance genes did not match the patients' drug treatments. In conclusion, several plasmid types were identified in the gut microbiome; however, it was difficult to link these to the antibiotic resistance genes identified. That the antibiotic resistance genes came from hospital and community environments is worrying. PMID:27530840

  7. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    PubMed Central

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  8. Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments

    PubMed Central

    Yi, Lunzhao; Shi, Shuting; Wang, Yang; Huang, Wei; Xia, Zi-an; Xing, Zhihua; Peng, Weijun; Wang, Zhe

    2016-01-01

    Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment. PMID:26883691

  9. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

    PubMed

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  10. Myelodysplastic Syndrome Revealed by Systems Immunology in a Melanoma Patient Undergoing Anti-PD-1 Therapy.

    PubMed

    Greenplate, Allison R; Johnson, Douglas B; Roussel, Mikael; Savona, Michael R; Sosman, Jeffrey A; Puzanov, Igor; Ferrell, P Brent; Irish, Jonathan M

    2016-06-01

    Antibodies aimed at blocking the interaction between programmed cell death-1 (PD-1) and its ligands have shown impressive efficacy in a variety of malignancies and are generally well tolerated. Research has focused intensely on T cells and their interaction with cells within melanoma tumors, while relatively little is understood about the systems immunology of the cells in the blood during checkpoint inhibitor therapy. Longitudinal cytomic analysis using mass cytometry can characterize all the cells in a small sample of blood and has the potential to reveal key shifts in the cellular milieu occurring during treatment. We report a case of advanced melanoma in which mass cytometry detected abnormal myeloid cells resulting from myelodysplastic syndrome (MDS) in the blood following treatment with an anti-PD-1 agent. Myeloid blasts comprised <1% of peripheral blood mononuclear cells (PBMC) 1 month after the start of treatment. Six months after starting therapy, myeloid blasts comprised 5% of PBMCs, and a bone marrow biopsy confirmed refractory anemia with excess blasts-2 (RAEB-2). Longitudinal mass cytometry immunophenotyping comprehensively characterized blast phenotype evolution and revealed elevated PD-1 expression on the surface of nonblast myeloid cells. These findings highlight the clinical significance of cytomic monitoring, indicate that the myeloid compartment should be monitored during checkpoint inhibitor therapy, and emphasize the value of systems immunology in medicine. Cancer Immunol Res; 4(6); 474-80. ©2016 AACR. PMID:26966176

  11. Barcoded sequencing reveals diverse intrauterine microbiomes in patients suffering with endometrial polyps

    PubMed Central

    Fang, Rui-Li; Chen, Lin-Xing; Shu, Wen-Sheng; Yao, Shu-Zhong; Wang, Si-Wen; Chen, Yu-Qing

    2016-01-01

    Results of this study showed that the bacterial composition in vagina (V) greatly differed from intrauterine microbiome (I). Microbiomes were present in all intrauterine samples of healthy women (Group H (I)) and patients with endometrial polyps (EP) (including Group EP (I) and Group EP/chronic endometritis (CE) (I)). Indeed, the intrauterine bacteria population in Group EP/CE (I) were more diverse than those in Groups EP (I) and H (I). The result also confirmed the bacterial composition differences between vagina and uterus as well as the intrauterine microbiome alteration in the patients, compared to the healthy. Although bacteria of Proteobacteria, Firmicutes and Actinobacteria, dominated the intrauterine microbiome in all samples, however, proportions of Firmicutes from Group EP/CE (I) and Group EP (I) were much higher than that from Group H (I), in contrast, the proportions of Proteobacteria were far lower than the healthy. At the genus level, compared to Group H (I), it is found that proportions of Lactobacillus, Gardnerella, Bifidobacterium, Streptococcus, and Alteromonas were significantly higher, and that of Pseudomonas were significantly lower in Group EP/CE (I) or Group EP (I). In addition, lower proportions of Enterobacter and Sphingomonas and a higher proportion of Prevotella were also observed in Group EP/CE (I). In conclusion, uterine microbiomes between patients with EP and the healthy are significantly different and all the potentially important variation of uterine microbes may cause EP, but not definitively related to CE. Further experiments should be performed to test these relationships to endometritis occurrence. PMID:27186283

  12. Barcoded sequencing reveals diverse intrauterine microbiomes in patients suffering with endometrial polyps.

    PubMed

    Fang, Rui-Li; Chen, Lin-Xing; Shu, Wen-Sheng; Yao, Shu-Zhong; Wang, Si-Wen; Chen, Yu-Qing

    2016-01-01

    Results of this study showed that the bacterial composition in vagina (V) greatly differed from intrauterine microbiome (I). Microbiomes were present in all intrauterine samples of healthy women (Group H (I)) and patients with endometrial polyps (EP) (including Group EP (I) and Group EP/chronic endometritis (CE) (I)). Indeed, the intrauterine bacteria population in Group EP/CE (I) were more diverse than those in Groups EP (I) and H (I). The result also confirmed the bacterial composition differences between vagina and uterus as well as the intrauterine microbiome alteration in the patients, compared to the healthy. Although bacteria of Proteobacteria, Firmicutes and Actinobacteria, dominated the intrauterine microbiome in all samples, however, proportions of Firmicutes from Group EP/CE (I) and Group EP (I) were much higher than that from Group H (I), in contrast, the proportions of Proteobacteria were far lower than the healthy. At the genus level, compared to Group H (I), it is found that proportions of Lactobacillus, Gardnerella, Bifidobacterium, Streptococcus, and Alteromonas were significantly higher, and that of Pseudomonas were significantly lower in Group EP/CE (I) or Group EP (I). In addition, lower proportions of Enterobacter and Sphingomonas and a higher proportion of Prevotella were also observed in Group EP/CE (I). In conclusion, uterine microbiomes between patients with EP and the healthy are significantly different and all the potentially important variation of uterine microbes may cause EP, but not definitively related to CE. Further experiments should be performed to test these relationships to endometritis occurrence. PMID:27186283

  13. Metabolomic Screening of Tumor Tissue and Serum in Glioma Patients Reveals Diagnostic and Prognostic Information

    PubMed Central

    Mörén, Lina; Bergenheim, A. Tommy; Ghasimi, Soma; Brännström, Thomas; Johansson, Mikael; Antti, Henrik

    2015-01-01

    Glioma grading and classification, today based on histological features, is not always easy to interpret and diagnosis partly relies on the personal experience of the neuropathologists. The most important feature of the classification is the aimed correlation between tumor grade and prognosis. However, in the clinical reality, large variations exist in the survival of patients concerning both glioblastomas and low-grade gliomas. Thus, there is a need for biomarkers for a more reliable classification of glioma tumors as well as for prognosis. We analyzed relative metabolite concentrations in serum samples from 96 fasting glioma patients and 81 corresponding tumor samples with different diagnosis (glioblastoma, oligodendroglioma) and grade (World Health Organization (WHO) grade II, III and IV) using gas chromatography-time of flight mass spectrometry (GC-TOFMS). The acquired data was analyzed and evaluated by pattern recognition based on chemometric bioinformatics tools. We detected feature patterns in the metabolomics data in both tumor and serum that distinguished glioblastomas from oligodendrogliomas (ptumor = 2.46 × 10−8, pserum = 1.3 × 10−5) and oligodendroglioma grade II from oligodendroglioma grade III (ptumor = 0.01, pserum = 0.0008). Interestingly, we also found patterns in both tumor and serum with individual metabolite features that were both elevated and decreased in patients that lived long after being diagnosed with glioblastoma compared to those who died shortly after diagnosis (ptumor = 0.006, pserum = 0.004; AUROCCtumor = 0.846 (0.647–1.000), AUROCCserum = 0.958 (0.870–1.000)). Metabolic patterns could also distinguish long and short survival in patients diagnosed with oligodendroglioma (ptumor = 0.01, pserum = 0.001; AUROCCtumor = 1 (1.000–1.000), AUROCCserum = 1 (1.000–1.000)). In summary, we found different metabolic feature patterns in tumor tissue and serum for glioma diagnosis, grade and survival, which indicates that, following

  14. Acute stroke revealing Takayasu's arteritis in a patient with Crohn's disease.

    PubMed

    Lavie, Gil; Zalmanovich, Anat; Golan, Yitzhak; Jonas Kimchi, Tali; Barenboim, Erez

    2016-08-01

    A 36-year-old Caucasian male with Crohn's disease exhibited acute ischaemic stroke as the first manifestation of Takayasu's arteritis. Stroke as the first clinical manifestation of Takayasu's arteritis has been rarely reported. Though rare in Western countries, Takayasu's arteritis should be considered as a possibility in young patients presenting with stroke. Both Takayasu's arteritis and Crohn's disease may increase the risk of ischaemic stroke. Furthermore, their coexistence is much higher than that expected by chance and suggest a pathophysiological link between these diseases. PMID:27075786

  15. An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient

    PubMed Central

    Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

    2016-01-01

    Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

  16. An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient.

    PubMed

    Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

    2016-01-01

    Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

  17. Dynamic functional connectivity reveals altered variability in functional connectivity among patients with major depressive disorder.

    PubMed

    Demirtaş, Murat; Tornador, Cristian; Falcón, Carles; López-Solà, Marina; Hernández-Ribas, Rosa; Pujol, Jesús; Menchón, José M; Ritter, Petra; Cardoner, Narcis; Soriano-Mas, Carles; Deco, Gustavo

    2016-08-01

    Resting-state fMRI (RS-fMRI) has become a useful tool to investigate the connectivity structure of mental health disorders. In the case of major depressive disorder (MDD), recent studies regarding the RS-fMRI have found abnormal connectivity in several regions of the brain, particularly in the default mode network (DMN). Thus, the relevance of the DMN to self-referential thoughts and ruminations has made the use of the resting-state approach particularly important for MDD. The majority of such research has relied on the grand averaged functional connectivity measures based on the temporal correlations between the BOLD time series of various brain regions. We, in our study, investigated the variations in the functional connectivity over time at global and local level using RS-fMRI BOLD time series of 27 MDD patients and 27 healthy control subjects. We found that global synchronization and temporal stability were significantly increased in the MDD patients. Furthermore, the participants with MDD showed significantly increased overall average (static) functional connectivity (sFC) but decreased variability of functional connectivity (vFC) within specific networks. Static FC increased to predominance among the regions pertaining to the default mode network (DMN), while the decreased variability of FC was observed in the connections between the DMN and the frontoparietal network. Hum Brain Mapp 37:2918-2930, 2016. © 2016 Wiley Periodicals, Inc. PMID:27120982

  18. Patient-Specific Simulations Reveal Significant Differences in Mechanical Stimuli in Venous and Arterial Coronary Grafts.

    PubMed

    Ramachandra, Abhay B; Kahn, Andrew M; Marsden, Alison L

    2016-08-01

    Mechanical stimuli are key to understanding disease progression and clinically observed differences in failure rates between arterial and venous grafts following coronary artery bypass graft surgery. We quantify biologically relevant mechanical stimuli, not available from standard imaging, in patient-specific simulations incorporating non-invasive clinical data. We couple CFD with closed-loop circulatory physiology models to quantify biologically relevant indices, including wall shear, oscillatory shear, and wall strain. We account for vessel-specific material properties in simulating vessel wall deformation. Wall shear was significantly lower (p = 0.014*) and atheroprone area significantly higher (p = 0.040*) in venous compared to arterial grafts. Wall strain in venous grafts was significantly lower (p = 0.003*) than in arterial grafts while no significant difference was observed in oscillatory shear index. Simulations demonstrate significant differences in mechanical stimuli acting on venous vs. arterial grafts, in line with clinically observed graft failure rates, offering a promising avenue for stratifying patients at risk for graft failure. PMID:27447176

  19. Exome sequencing reveals recurrent germ line variants in patients with familial Waldenström macroglobulinemia.

    PubMed

    Roccaro, Aldo M; Sacco, Antonio; Shi, Jiantao; Chiarini, Marco; Perilla-Glen, Adriana; Manier, Salomon; Glavey, Siobhan; Aljawai, Yosra; Mishima, Yuji; Kawano, Yawara; Moschetta, Michele; Correll, Mick; Improgo, Ma Reina; Brown, Jennifer R; Imberti, Luisa; Rossi, Giuseppe; Castillo, Jorge J; Treon, Steven P; Freedman, Matthew L; Van Allen, Eliezer M; Hide, Winston; Hiller, Elaine; Rainville, Irene; Ghobrial, Irene M

    2016-05-26

    Familial aggregation of Waldenström macroglobulinemia (WM) cases, and the clustering of B-cell lymphoproliferative disorders among first-degree relatives of WM patients, has been reported. Nevertheless, the possible contribution of inherited susceptibility to familial WM remains unrevealed. We performed whole exome sequencing on germ line DNA obtained from 4 family members in which coinheritance for WM was documented in 3 of them, and screened additional independent 246 cases by using gene-specific mutation sequencing. Among the shared germ line variants, LAPTM5(c403t) and HCLS1(g496a) were the most recurrent, being present in 3/3 affected members of the index family, detected in 8% of the unrelated familial cases, and present in 0.5% of the nonfamilial cases and in <0.05 of a control population. LAPTM5 and HCLS1 appeared as relevant WM candidate genes that characterized familial WM individuals and were also functionally relevant to the tumor clone. These findings highlight potentially novel contributors for the genetic predisposition to familial WM and indicate that LAPTM5(c403t) and HCLS1(g496a) may represent predisposition alleles in patients with familial WM. PMID:26903547

  20. Immunophenotyping of Stage III Melanoma Reveals Parameters Associated with Patient Prognosis.

    PubMed

    Jacquelot, Nicolas; Roberti, María Paula; Enot, David P; Rusakiewicz, Sylvie; Semeraro, Michaela; Jégou, Sarah; Flores, Camila; Chen, Lieping; Kwon, Byoung S; Borg, Christophe; Weide, Benjamin; Aubin, François; Dalle, Stéphane; Kohrt, Holbrook; Ayyoub, Maha; Kroemer, Guido; Marabelle, Aurélien; Cavalcanti, Andréa; Eggermont, Alexander; Zitvogel, Laurence

    2016-05-01

    Stage III metastatic melanomas require adequate adjuvant immunotherapy to prevent relapses. Prognostic factors are awaited to optimize the clinical management of these patients. The magnitude of metastatic lymph node invasion and the BRAF(V600) activating mutation have clinical significance. Based on a comprehensive immunophenotyping of 252 parameters per patient in paired blood and metastatic lymph nodes performed in 39 metastatic melanomas, we found that blood markers were as contributive as tumor-infiltrated lymphocyte immunotypes, and parameters associated with lymphocyte exhaustion/suppression showed higher clinical significance than those related to activation or lineage. High frequencies of CD45RA(+)CD4(+) and CD3(-)CD56(-) tumor-infiltrated lymphocytes appear to be independent prognostic factors of short progression-free survival. High NKG2D expression on CD8(+)tumor-infiltrated lymphocytes, low level of regulatory T-cell tumor-infiltrated lymphocytes, and low PD-L1 expression on circulating T cells were retained in the multivariate Cox analysis model to predict prolonged overall survival. Prospective studies are needed to determine whether such immunological markers may guide adjuvant therapies in stage III metastatic melanomas. PMID:26829031

  1. DTI and VBM reveal white matter changes without associated gray matter changes in patients with idiopathic restless legs syndrome

    PubMed Central

    Belke, Marcus; Heverhagen, Johannes T; Keil, Boris; Rosenow, Felix; Oertel, Wolfgang H; Stiasny-Kolster, Karin; Knake, Susanne; Menzler, Katja

    2015-01-01

    Background and Purpose We evaluated cerebral white and gray matter changes in patients with iRLS in order to shed light on the pathophysiology of this disease. Methods Twelve patients with iRLS were compared to 12 age- and sex-matched controls using whole-head diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) techniques. Evaluation of the DTI scans included the voxelwise analysis of the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Results Diffusion tensor imaging revealed areas of altered FA in subcortical white matter bilaterally, mainly in temporal regions as well as in the right internal capsule, the pons, and the right cerebellum. These changes overlapped with changes in RD. Voxel-based morphometry did not reveal any gray matter alterations. Conclusions We showed altered diffusion properties in several white matter regions in patients with iRLS. White matter changes could mainly be attributed to changes in RD, a parameter thought to reflect altered myelination. Areas with altered white matter microstructure included areas in the internal capsule which include the corticospinal tract to the lower limbs, thereby supporting studies that suggest changes in sensorimotor pathways associated with RLS. PMID:26442748

  2. EEG oscillatory states as neuro-phenomenology of consciousness as revealed from patients in vegetative and minimally conscious states.

    PubMed

    Fingelkurts, Alexander A; Fingelkurts, Andrew A; Bagnato, Sergio; Boccagni, Cristina; Galardi, Giuseppe

    2012-03-01

    The value of resting electroencephalogram (EEG) in revealing neural constitutes of consciousness (NCC) was examined. We quantified the dynamic repertoire, duration and oscillatory type of EEG microstates in eyes-closed rest in relation to the degree of expression of clinical self-consciousness. For NCC a model was suggested that contrasted normal, severely disturbed state of consciousness and state without consciousness. Patients with disorders of consciousness were used. Results suggested that the repertoire, duration and oscillatory type of EEG microstates in resting condition quantitatively related to the level of consciousness expression in brain-damaged patients and healthy-conscious subjects. Specifically, results demonstrated that (a) decreased number of EEG microstate types was associated with altered states of consciousness, (b) unawareness was associated with the lack of diversity in EEG alpha-rhythmic microstates, and (c) the probability for the occurrence and duration of delta-, theta- and slow-alpha-rhythmic microstates were associated with unawareness, whereas the probability for the occurrence and duration of fast-alpha-rhythmic microstates were associated with consciousness. In conclusion, resting EEG has a potential value in revealing NCC. This work may have implications for clinical care and medical-legal decisions in patients with disorders of consciousness. PMID:22054641

  3. Bloodstream Infections in Patients With Pulmonary Arterial Hypertension Treated With Intravenous Prostanoids: Insights From the REVEAL REGISTRY®

    PubMed Central

    Kitterman, Natalie; Poms, Abby; Miller, Dave P.; Lombardi, Sandra; Farber, Harrison W.; Barst, Robyn J.

    2012-01-01

    Objective To evaluate the rate of and potential risk factors for bloodstream infections (BSIs) using data from the REVEAL (Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension [PAH] Disease Management) REGISTRY®, which provides current information about patients with PAH. Patients and Methods Patients were enrolled from March 30, 2006, through December 8, 2009, and data on reported BSIs were collected through the third quarter of 2010. Bloodstream infection rates were calculated per 1000 patient-days of risk. Results Of 3518 patients enrolled, 1146 patients received intravenous (IV) prostanoid therapy for more than 1 day (no BSI, n=1023; ≥1 BSI, n=123; total BSI episodes, n=166). Bloodstream infections rates were significantly increased in patients receiving IV treprostinil vs IV epoprostenol (0.36 vs 0.12 per 1000 treatment days; P<.001), primarily due to gram-negative organisms (0.20 vs 0.03 per 1000 treatment days; P<.001). Multivariate analysis adjusting for age, causes of PAH, and year of BSI found that treatment with IV treprostinil was associated with a 3.08-fold increase (95% confidence interval, 2.05-4.62; P<.001) in BSIs of any type and a 6.86-fold increase (95% confidence interval, 3.60-13.07; P<.001) in gram-negative BSIs compared with treatment with IV epoprostenol. Conclusion Compared with IV epoprostenol therapy, treatment with IV treprostinil is associated with a significantly higher rate of gram-negative BSIs; observed differences in BSI rate did not seem to be due to any other analyzed factors. Trial Registration clinicaltrials.gov Identifier: NCT00370214 PMID:22883740

  4. RNA-seq analysis of lung adenocarcinomas reveals different gene expression profiles between smoking and nonsmoking patients.

    PubMed

    Li, Yafang; Xiao, Xiangjun; Ji, Xuemei; Liu, Bin; Amos, Christopher I

    2015-11-01

    Lung adenocarcinoma is caused by the combination of genetic and environmental effects, and smoking plays an important role in the disease development. Exploring the gene expression profile and identifying genes that are shared or vary between smokers and nonsmokers with lung adenocarcinoma will provide insights into the etiology of this complex cancer. We obtained RNA-seq data from paired normal and tumor tissues from 34 nonsmoking and 34 smoking patients with lung adenocarcinoma (GEO: GSE40419). R Bioconductor, edgeR, was adopted to conduct differential gene expression analysis between paired normal and tumor tissues. A generalized linear model was applied to identify genes that were differentially expressed in nonsmoker and smoker patients as well as genes that varied between these two groups. We identified 2273 genes that showed differential expression with FDR < 0.05 and |logFC| >1 in nonsmoker tumor versus normal tissues; 3030 genes in the smoking group; and 1967 genes were common to both groups. Sixty-eight and 70% of the identified genes were downregulated in nonsmoking and smoking groups, respectively. The 20 genes such as SPP1, SPINK1, and FAM83A with largest fold changes in smokers also showed similar large and highly significant fold changes in nonsmokers and vice versa, showing commonalities in expression changes for adenocarcinomas in both smokers and nonsmokers for these genes. We also identified 175 genes that were significantly differently expressed between tumor samples from nonsmoker and smoker patients. Gene expression profile varied substantially between smoker and nonsmoker patients with lung adenocarcinoma. Smoking patients overall showed far more complicated disease mechanism and have more dysregulation in their gene expression profiles. Our study reveals pathogenetic differences in smoking and nonsmoking patients with lung adenocarcinoma from transcriptome analysis. We provided a list of candidate genes for further study for disease

  5. Hard Internet Truths: 34,748 Online Reviews Reveal What Patients Really Want from Doctors.

    PubMed

    King, Ron Harman; Stanley, Jonathan; Baum, Neil

    2016-01-01

    For all of us living in the Internet age, it's hard to underestimate the power of online reviews. Before booking a reservation at a new hotel or restaurant, who doesn't consult websites such as TripAdvisor and Open Table? Who would gamble $100 on a dinner out or $200 on a hotel stay before first seeing what other diners and patrons had to say about their experiences? Patients who are looking for a healthcare provider are no different than those customers looking for a restaurant or a hotel; they want opinions from others who have previously availed themselves of that restaurant or hotel. This article addresses the importance of online reputation management and offers ideas and suggestions for healthcare providers to control and protect their online reputations. PMID:27249884

  6. Phylogenetic analyses of the subgenus Mollienesia (Poecilia, Poeciliidae, Teleostei) reveal taxonomic inconsistencies, cryptic biodiversity, and spatio-temporal aspects of diversification in Middle America.

    PubMed

    Palacios, Maura; Voelker, Gary; Arias Rodriguez, Lenin; Mateos, Mariana; Tobler, Michael

    2016-10-01

    The subgenus Mollienesia is a diverse group of freshwater fishes, including species that have served as important models across multiple biological disciplines. Nonetheless, the taxonomic history of this group has been conflictive and convoluted, in part because the evolutionary relationships have not been rigorously resolved. We conducted a comprehensive molecular phylogenetic analysis of the subgenus Mollienesia to identify taxonomic discrepancies and potentially identify undescribed species, estimate ancestral areas of origin and estimate dates of divergence, as well as explore biogeographical patterns. Our findings confirm the presence of three main clades composed of the P. latipinna, P. sphenops, and P. mexicana species complexes. Unlike previously hypothesized morphology-based analyses, species found on the Caribbean Islands are not part of Mollienesia, but are more closely related to species of the subgenus Limia. Our study also revealed several taxonomic inconsistencies and distinct lineages in the P. mexicana species complex that may represent undescribed species. The diversity in the subgenus Mollienesia is a result of dynamic geologic activity leading to vicariant events, dispersal across geologic blocks, and ecological speciation. PMID:27472959

  7. Simulations reveal adverse hemodynamics in patients with multiple systemic to pulmonary shunts.

    PubMed

    Esmaily-Moghadam, Mahdi; Murtuza, Bari; Hsia, Tain-Yen; Marsden, Alison

    2015-03-01

    For newborns diagnosed with pulmonary atresia or severe pulmonary stenosis leading to insufficient pulmonary blood flow, cyanosis can be mitigated with placement of a modified Blalock-Taussig shunt (MBTS) between the innominate and pulmonary arteries. In some clinical scenarios, patients receive two systemic-to-pulmonary connections, either by leaving the patent ductus arteriosus (PDA) open or by adding an additional central shunt (CS) in conjunction with the MBTS. This practice has been motivated by the thinking that an additional source of pulmonary blood flow could beneficially increase pulmonary flow and provide the security of an alternate pathway in case of thrombosis. However, there have been clinical reports of premature shunt occlusion when more than one shunt is employed, leading to speculation that multiple shunts may in fact lead to unfavorable hemodynamics and increased mortality. In this study, we hypothesize that multiple shunts may lead to undesirable flow competition, resulting in increased residence time (RT) and elevated risk of thrombosis, as well as pulmonary overcirculation. Computational fluid dynamics-based multiscale simulations were performed to compare a range of shunt configurations and systematically quantify flow competition, pulmonary circulation, and other clinically relevant parameters. In total, 23 cases were evaluated by systematically changing the PDA/CS diameter, pulmonary vascular resistance (PVR), and MBTS position and compared by quantifying oxygen delivery (OD) to the systemic and coronary beds, wall shear stress (WSS), oscillatory shear index (OSI), WSS gradient (WSSG), and RT in the pulmonary artery (PA), and MBTS. Results showed that smaller PDA/CS diameters can lead to flow conditions consistent with increased thrombus formation due to flow competition in the PA, and larger PDA/CS diameters can lead to insufficient OD due to pulmonary hyperfusion. In the worst case scenario, it was found that multiple shunts can lead to

  8. Surface plasmon resonance reveals a different pattern of proinsulin autoantibodies concentration and affinity in diabetic patients.

    PubMed

    Trabucchi, Aldana; Guerra, Luciano L; Faccinetti, Natalia I; Iacono, Rubén F; Poskus, Edgardo; Valdez, Silvina N

    2012-01-01

    Type 1 diabetes mellitus (DM) is characterized by autoimmune aggression against pancreatic beta cells resulting in absolute deficiency of insulin secretion. The first detectable sign of emerging autoimmunity during the preclinical asymptomatic period is the appearance of diabetes-related autoantibodies. In children at risk for type 1 DM, high-affinity Insulin autoantibodies reactive to proinsulin, are associated with diabetes risk. Autoantibodies are usually measured by radioligand binding assay (RBA) that provides quasi-quantitative values reflecting potency (product between concentration and affinity) of specific autoantibodies. Aiming to improve the characterization of the specific humoral immune response, we selected surface plasmon resonance (SPR) as an alternative method to measure proinsulin autoantibodies (PAA). This novel technology has allowed real time detection of antibodies interaction and kinetic analysis. Herein, we have employed SPR to characterize the PAA present in sera from 28 childhood-onset (mean age 8.31±4.20) and 23 adult-onset diabetic patients (≥65 years old, BMI<30) in terms of concentration and affinity. When evaluating comparatively samples from both groups, childhood-onset diabetic patients presented lower PAA concentrations and higher affinities (median 67.12×10(-9) M and 3.50×10(7) M(-1), respectively) than the adults (median 167.4×10(-9) M and 0.84×10(7) M(-1), respectively). These results are consistent with those from the reference method RBA (Standard Deviation score median 9.49 for childhood-onset group and 5.04 for adult-onset group) where the binding can be directly related to the intrinsic affinity of the antibody, suggesting that there is a different etiopathogenic pathway between both types of clinical presentation of the disease. This technology has shown to be a useful tool for the characterization of PAAs parameters as an alternative to radioimmunoassay, with high versatility and reproducibility associated to low

  9. Genome-wide transcriptional analyses of Chinese patients reveal cell migration is attenuated in IDH1-mutant glioblastomas.

    PubMed

    Hu, Huimin; Wang, Zheng; Liu, Yanwei; Zhang, Chuanbao; Li, Mingyang; Zhang, Wenlong; Wang, Kuanyu; Cai, Jinquan; Cheng, Wen; Huang, Hua; Jiang, Tao

    2015-02-28

    Patients with isocitrate dehydrogenase 1 (IDH1)-mutant glioblastoma exhibit increased survival compared with those with wild-type IDH1 tumors. The magnitude of this finding has led to the use of IDH1 mutations as diagnostic and prognostic biomarkers. However, the mechanisms underlying the reported correlation between the IDH1 mutation and increased survival have not been fully revealed. In this work, based on genome-wide transcriptional analyses of 69 Chinese patients with glioblastoma, we have found that the focal adhesion pathway is significantly downregulated in IDH1-mutant glioblastomas. The impaired focal adhesion leads to compromised cell migration and tumor invasion, contributing to the optimistic prognosis of these patients. Moreover, the signature genes of HIF-1α, the downstream factor of mutated IDH1, are found to be suppressed in IDH1-mutant gliomas. Given the role of HIF-1α in cell migration, we conclude that the attenuation of HIF-1α-dependent glioblastoma cell infiltration contributes to the better outcomes of patients with IDH1-mutant gliomas. PMID:25511738

  10. Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation

    PubMed Central

    Yoo, Hee Jeong; Kim, Kyung; Kim, In Hyang; Rho, Seong-Hwan; Park, Jong-Eun; Lee, Ki Young; Kim, Soon Ae; Choi, Byung Yoon; Kim, Namshin

    2015-01-01

    Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000–720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES) to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes. PMID:25768348

  11. Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de novo variants besides an overt CREBBP mutation.

    PubMed

    Yoo, Hee Jeong; Kim, Kyung; Kim, In Hyang; Rho, Seong-Hwan; Park, Jong-Eun; Lee, Ki Young; Kim, Soon Ae; Choi, Byung Yoon; Kim, Namshin

    2015-01-01

    Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000-720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES) to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes. PMID:25768348

  12. Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival

    PubMed Central

    BUSH, STEPHEN H.; TOLLIN, SHARON; MARCHION, DOUGLAS C.; XIONG, YIN; ABBASI, FOROUGH; RAMIREZ, INGRID J.; ZGHEIB, NADIM BOU; BOAC, BERNADETTE; JUDSON, PATRICIA L.; CHON, HYE SOOK; WENHAM, ROBERT M.; APTE, SACHIN M.; CUBITT, CHRISTOPHER L.; BERGLUND, ANDERS E.; HAVRILESKY, LAURA J.; LANCASTER, JOHNATHAN M.

    2016-01-01

    Experimental and epidemiological data support the potential activity of acetaminophen against ovarian cancer (OVCA). In this study, we sought to confirm the activity of acetaminophen in OVCA cell lines and to investigate the molecular basis of response. A total of 16 OVCA cell lines underwent pretreatment (baseline) genome-wide expression measurements and were then treated with and analyzed for acetaminophen sensitivity. Pearson's correlation analysis was performed to identify genes that were associated with OVCA acetaminophen response. The identified genes were subjected to pathway analysis, and the expression of each represented pathway was summarized using principal component analysis. OVCA acetaminophen response pathways were analyzed in 4 external clinico-genomic datasets from 820 women for associations with overall survival from OVCA. Acetaminophen exhibited antiproliferative activity against all tested OVCA cell lines, with half maximal inhibitory concentration values ranging from 63.2 to 403 µM. Pearson's correlation followed by biological pathway analysis identified 13 pathways to be associated with acetaminophen sensitivity (P<0.01). Associations were observed between patient survival from OVCA and expression of the following pathways: Development/angiotensin signaling via β-arrestin (P=0.04), protein folding and maturation/angiotensin system maturation (P=0.02), signal transduction/c-Jun N-terminal kinase (JNK) pathway (P=0.03) and androstenedione and testosterone biosynthesis and metabolism (P=0.02). We confirmed that acetaminophen was active against OVCA cells in vitro. Furthermore, we identified 4 molecular signaling pathways associated with acetaminophen response that may also affect overall survival in women with OVCA, including the JNK pathway, which has been previously implicated in the mechanism of action of acetaminophen and is predictive of decreased survival in women with OVCA. PMID:26998291

  13. Identification of aspects of functioning, disability and health relevant to patients experiencing vertigo: a qualitative study using the international classification of functioning, disability and health

    PubMed Central

    2012-01-01

    Purpose Aims of this study were to identify aspects of functioning and health relevant to patients with vertigo expressed by ICF categories and to explore the potential of the ICF to describe the patient perspective in vertigo. Methods We conducted a series of qualitative semi-structured face-to-face interviews using a descriptive approach. Data was analyzed using the meaning condensation procedure and then linked to categories of the International Classification of Functioning, Disability and Health (ICF). Results From May to July 2010 12 interviews were carried out until saturation was reached. Four hundred and seventy-one single concepts were extracted which were linked to 142 different ICF categories. 40 of those belonged to the component body functions, 62 to the component activity and participation, and 40 to the component environmental factors. Besides the most prominent aspect “dizziness” most participants reported problems within “Emotional functions (b152), problems related to mobility and carrying out the daily routine. Almost all participants reported “Immediate family (e310)” as a relevant modifying environmental factor. Conclusions From the patients’ perspective, vertigo has impact on multifaceted aspects of functioning and disability, mainly body functions and activities and participation. Modifying contextual factors have to be taken into account to cover the complex interaction between the health condition of vertigo on the individuals’ daily life. The results of this study will contribute to developing standards for the measurement of functioning, disability and health relevant for patients suffering from vertigo. PMID:22738067

  14. Nutritional aspects in patients with functional gastrointestinal disorders and motor dysfunction in the gut. Working team report of the Swedish Motility Group (SMoG).

    PubMed

    Simrén, M; Abrahamsson, H; Bosaeus, I; Brummer, R J; Dolk, A; Lindberg, G; Nyhlin, H; Ohlsson, B; Sjölund, K; Törnblom, H

    2007-05-01

    In reviews regarding the management of patients with functional gastrointestinal disorders and motility disturbances within the gut nutritional aspects and dietary advice is often put forward as being of great importance. However, there are relatively few high-quality, interventional studies in the literature supporting an important role for general dietary advice to improve symptoms in these patients. Nutritional supplementation to patients with malnutrition due to severe dysfunction of the gastrointestinal tract is of course less controversial, even though different views on how this should be performed exist. The content of this article is based on presentations given by the authors during the second meeting of the Swedish Motility Group held in Gothenburg in March 2005, and aims to give an overview on the role of dietary advice and nutritional supplementation to patients with gastrointestinal dysfunction of different severity. PMID:17368120

  15. Psoriasis and Diabetes: A Multicenter Study in 222078 Type 2 Diabetes Patients Reveals High Levels of Depression

    PubMed Central

    Schwandt, Anke; Bergis, Dominik; Dapp, Albrecht; Ebner, Stefan; Jehle, Peter M.; Köppen, Stefan; Risse, Alexander; Zimny, Stefan; Holl, Reinhard W.

    2015-01-01

    Objective. This study aimed to investigate the association between psoriasis and disease outcome in type 2 diabetes (T2D). Methods. 222078 T2D patients (≥10 years old) from the prospective, multicenter diabetes patient registry were analyzed. Specific search items were used to identify psoriasis patients. Multiple regression models were fitted and adjusted for demographic confounder. Results. 232 T2D patients had comorbid psoriasis. After adjusting psoriasis patients revealed a higher BMI (31.8 [31.0; 32.6] versus 30.6 [30.5; 30.6] kg/m2, p = 0.004) and HbA1c (64.8 [62.1; 67.6] versus 59.0 [58.9; 59.1] mmol/mol, p < 0.0001). Insulin was used more frequently (62.3 [55.7; 68.5] versus 50.9 [50.7; 51.1] %, p = 0.001), only OAD/GLP-1 was similar, and nonpharmacological treatment was less common (13.3 [9.5; 18.3] versus 21.9 [21.7; 22.1] %, p = 0.002). Severe hypoglycemia (0.31 [0.238; 0.399] versus 0.06 [0.057; 0.060] events per patient-year, p < 0.0001), hypertension (86.1 [81.1; 90.0] versus 68.0 [67.8; 68.2] %, p < 0.0001), and thyroid disease (14.0 [10.1; 19.2] versus 4.6 [4.5; 4.7] %, p < 0.0001) were more prevalent. Depression occurred more often (10.5 [7.1; 15.2] versus 2.8 [2.7; 2.8] %, p < 0.0001). Conclusions. Clinical diabetes characteristics in psoriasis T2D patients were clearly worse compared to patients without psoriasis. Comorbid conditions and depression were more prevalent, and more intensive diabetes therapy was required. PMID:26357664

  16. Human Monoclonal Islet Cell Antibodies From a Patient with Insulin- Dependent Diabetes Mellitus Reveal Glutamate Decarboxylase as the Target Antigen

    NASA Astrophysics Data System (ADS)

    Richter, Wiltrud; Endl, Josef; Eiermann, Thomas H.; Brandt, Michael; Kientsch-Engel, Rosemarie; Thivolet, Charles; Jungfer, Herbert; Scherbaum, Werner A.

    1992-09-01

    The autoimmune phenomena associated with destruction of the β cell in pancreatic islets and development of type 1 (insulin-dependent) diabetes mellitus (IDDM) include circulating islet cell antibodies. We have immortalized peripheral blood lymphocytes from prediabetic individuals and patients with newly diagnosed IDDM by Epstein-Barr virus transformation. IgG-positive cells were selected by anti-human IgG-coupled magnetic beads and expanded in cell culture. Supernatants were screened for cytoplasmic islet cell antibodies using the conventional indirect immunofluorescence test on cryostat sections of human pancreas. Six islet cell-specific B-cell lines, originating from a patient with newly diagnosed IDDM, could be stabilized on a monoclonal level. All six monoclonal islet cell antibodies (MICA 1-6) were of the IgG class. None of the MICA reacted with human thyroid, adrenal gland, anterior pituitary, liver, lung, stomach, and intestine tissues but all six reacted with pancreatic islets of different mammalian species and, in addition, with neurons of rat cerebellar cortex. MICA 1-6 were shown to recognize four distinct antigenic epitopes in islets. Islet cell antibody-positive diabetic sera but not normal human sera blocked the binding of the monoclonal antibodies to their target epitopes. Immunoprecipitation of 35S-labeled human islet cell extracts revealed that a protein of identical size to the enzyme glutamate decarboxylase (EC 4.1.1.15) was a target of all MICA. Furthermore, antigen immunotrapped by the MICA from brain homogenates showed glutamate decarboxylase enzyme activity. MICA 1-6 therefore reveal glutamate decarboxylase as the predominant target antigen of cytoplasmic islet cell autoantibodies in a patient with newly diagnosed IDDM.

  17. Assessment of the redox status in patients with metabolic syndrome and type 2 diabetes reveals great variations

    PubMed Central

    SPANIDIS, YPATIOS; MPESIOS, ANASTASIOS; STAGOS, DIMITRIOS; GOUTZOURELAS, NIKOLAOS; BAR-OR, DAVID; KARAPETSA, MARIA; ZAKYNTHINOS, EPAMINONDAS; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDES M.; LEON, GEORGE; KOURETAS, DEMETRIOS

    2016-01-01

    The aim of the present study was to examine the effectiveness of a new redox status marker, the static oxidation reduction potential (sORP), for assessing oxidative stress in 75 patients with metabolic syndrome (MetS) and type 2 diabetes (T2D). A total of 35 normal subjects were used as the controls. Moreover, conventional markers of oxidative stress were assessed, such as thiobarbituric acid reactive substances (TBARS), protein carbonyls, the total antioxidant capacity in plasma, glutathione (GSH) levels and catalase (CAT) activity in erythrocytes. The results revealed that sORP was significantly higher (by 13.4%) in the patients with MetS and T2D compared to the controls, indicating an increase in oxidative stress. This finding was also supported by the significantly lower levels (by 27.7%) of GSH and the higher levels (by 23.3%) of CAT activity in the patients with MetS and T2D compared to the controls. Moreover, our results indicated a great variation in oxidative stress markers between the different patients with MetS and T2D, particarly as regards the GSH levels. Thus, the patients with MetS and T2D were divided into 2 subgroups, one with low GSH levels (n=31; GSH <3 µmol/g Hb) and another with high GSH levels (n=35; GSH >4 µmol/g Hb). The comparison of the markers between the 2 subgroups indicated that in the low GSH group, the GSH levels were significantly lower (by 51.7 and 52.9%) than those in the high GSH group and the controls, respectively. Furthermore, sORP in the low GSH group was significantly higher (by 8.1%) compared to the high GSH group, suggesting its sensitivity for assessing oxidative stress in patients wtih MetS and T2D. Moreover, this variation in oxidative stress levels between the different patients with T2D suggests that the assessment of the redox status may be important in prediabetic conditions, since there is evidence indicating that differences in the redox status in pre-diabetes may result in different outcomes. PMID:26998009

  18. Event-Related Potentials Reveal Preserved Attention Allocation but Impaired Emotion Regulation in Patients with Epilepsy and Comorbid Negative Affect

    PubMed Central

    De Taeye, Leen; Pourtois, Gilles; Meurs, Alfred; Boon, Paul; Vonck, Kristl; Carrette, Evelien; Raedt, Robrecht

    2015-01-01

    Patients with epilepsy have a high prevalence of comorbid mood disorders. This study aims to evaluate whether negative affect in epilepsy is associated with dysfunction of emotion regulation. Event-related potentials (ERPs) are used in order to unravel the exact electrophysiological time course and investigate whether a possible dysfunction arises during early (attention) and/or late (regulation) stages of emotion control. Fifty epileptic patients with (n = 25) versus without (n = 25) comorbid negative affect plus twenty-five matched controls were recruited. ERPs were recorded while subjects performed a face- or house-matching task in which fearful, sad or neutral faces were presented either at attended or unattended spatial locations. Two ERP components were analyzed: the early vertex positive potential (VPP) which is normally enhanced for faces, and the late positive potential (LPP) that is typically larger for emotional stimuli. All participants had larger amplitude of the early face-sensitive VPP for attended faces compared to houses, regardless of their emotional content. By contrast, in patients with negative affect only, the amplitude of the LPP was significantly increased for unattended negative emotional expressions. These VPP results indicate that epilepsy with or without negative affect does not interfere with the early structural encoding and attention selection of faces. However, the LPP results suggest abnormal regulation processes during the processing of unattended emotional faces in patients with epilepsy and comorbid negative affect. In conclusion, this ERP study reveals that early object-based attention processes are not compromised by epilepsy, but instead, when combined with negative affect, this neurological disease is associated with dysfunction during the later stages of emotion regulation. As such, these new neurophysiological findings shed light on the complex interplay of epilepsy with negative affect during the processing of emotional

  19. Personality traits in established schizophrenia: aspects of usability and differences between patients and controls using the Swedish universities Scales of Personality

    PubMed Central

    Fagerberg, Tomas; Söderman, Erik; Gustavsson, J. Petter; Agartz, Ingrid; Jönsson, Erik G.

    2016-01-01

    Abstract Background: Personality is considered as an important aspect that can affect symptoms and social function in persons with schizophrenia. The personality questionnaire Swedish universities Scales of Personality (SSP) has not previously been used in psychotic disorder. Aims: To investigate if SSP has a similar internal consistency and factor structure in a psychosis population as among healthy controls and if patients with psychotic disorders differ from non-psychotic individuals in their responses to the SSP. Methods: Patients with psychotic disorders (n = 107) and healthy controls (n = 119) completed SSP. SSP scores were analyzed for internal consistency and case-control differences by Cronbach’s alfa and multiple analysis of covariance, respectively. Results: Internal consistencies among patients were overall similar to that of controls. The patients scored significantly higher in seven (Somatic trait anxiety, Psychic trait anxiety, Stress susceptibility, Lack of assertiveness, Detachment, Embitterment, Mistrust) and lower in three (Physical trait aggression, Verbal trait aggression, Adventure seeking) of the 13 scales of the inventory. In three scales (Impulsiveness, Social desirability and Trait irritability) there was no significant difference between the scoring of patients and healthy controls. Conclusion: The reliability estimates suggest that SSP can be used by patients with psychotic disorders in stable remission. Patients score higher on neuroticism-related scales and lower on aggression-related scales than controls, which is in accordance with earlier studies where other personality inventories were used. PMID:27103375

  20. Aspects of Spirituality in Medical Doctors and Their Relation to Specific Views of Illness and Dealing with Their Patients' Individual Situation

    PubMed Central

    Büssing, Arndt; Hirdes, Almut Tabea; Baumann, Klaus; Hvidt, Niels Christian; Heusser, Peter

    2013-01-01

    We intended to analyse which aspects of spirituality are of relevance for medical doctors in a mostly secular society and how their spiritual/religious attitudes are related to specific views of illness, their dealing with patients' individual situation, and finally physicians' life satisfaction. Data from an anonymous survey enrolling 237 medical doctors from Germany (mean age 45.7 ± 9.6, 58% male, 42% female) indicated that secular forms of spirituality scored highest, while specific religious orientation had the lowest scores. Physicians with a specific specialization in complementary/alternative medicine (CAM) or anthroposophic medicine differed from their conventional counterparts with respect to specific aspects of spirituality; however, the specific views associated with these specialisations were only weakly to moderately correlated with physicians' view on the meaning of illness and how they assume that they would deal with their patients' individual situation. Of interest, the specific aspects of spirituality were negatively correlated with the view of “illness as a meaningless interruption” of life, indicating that physicians with a spiritual attitude would see illness also as a chance for an “individual development” and associated with a “biographical meaning” rather than just a “useless interruption” of life. PMID:23956779

  1. Revealing Educationally Critical Aspects of Rate

    ERIC Educational Resources Information Center

    Herbert, Sandra; Pierce, Robyn

    2012-01-01

    Rate (of change) is an important but complicated mathematical concept describing a ratio comparing two different numeric, measurable quantities. Research referring to students' difficulties with this concept spans more than 20 years. It suggests that problems experienced by some calculus students are likely a result of pre-existing limited or…

  2. Azacitidine in CMML: matched-pair analyses of daily-life patients reveal modest effects on clinical course and survival.

    PubMed

    Pleyer, Lisa; Germing, Ulrich; Sperr, Wolfgang R; Linkesch, Werner; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Schreder, Martin; Pfeilstocker, Michael; Lang, Alois; Sliwa, Thamer; Geissler, Dietmar; Schlick, Konstantin; Placher-Sorko, Gudrun; Theiler, Georg; Thaler, Josef; Mitrovic, Martina; Neureiter, Daniel; Valent, Peter; Greil, Richard

    2014-04-01

    Recent data suggest that azacitidine may be beneficial in CMML. We report on 48 CMML-patients treated with azacitidine. Overall response rates were high (70% according to IWG-criteria, including 22% complete responses). Monocyte count and cytogenetics adversely affected survival, whereas age, WHO-type, FAB-type, and spleen size did not. Matched-pair analyses revealed a trend for higher two-year-survival for azacitidine as compared to best supportive care (62% vs. 41%, p=0.067) and longer OS for azacitidine first-line vs. hydroxyurea first-line (p=0.072, median OS 27.7 vs. 6.2 months). This report reinforces existing evidence that azacitidine is safe and efficacious in both myelodysplastic and myeloproliferative CMML. PMID:24522248

  3. [Clinical diagnostic and organizational aspects of providing care to patients with pulmonary sarcoidosis in the Armed Forces].

    PubMed

    Ovchinnikov, Iu V; Kriukov, E V; Zaĭtsev, A A; Antipushina, D N

    2014-11-01

    The data on the epidemiology and aetiology of sarcoidosis, the current classifications are presented. The basic provisions of the legal framework of medical management of patients suffering from sarcoidosis are given. The authors provided an analysis of the characteristics of diagnosis and treatment of sarcoidosis in the military, based on which we propose an algorithm of examination of patients with respiratory sarcoidosis in military health care facilities the Russian Defence Ministry, the recommended treatment regimens and order dynamic observation of patients. Invited to provide skilled care to patients with respiratory sarcoidosis selection based on the Main Military Clinical Burdenko Hospital specialized centre (department with bunks for the treatment of patients with sarcoidosis). PMID:25816680

  4. Molecular Analysis in a Patient With Waldenström's Macroglobulinemia Reveals a Rare Case of Biclonality.

    PubMed

    Schulz; David; Farkas; Crisan

    1996-09-01

    Background: The immunoglobulin and T-cell receptor gene rearrangement test is used to identify monoclonal populations in B- and T-cell malignancies and has become an important adjunct to morphologic analysis and immunophenotyping by flow cytometry. Waldenström's macroglobulinemia (WM) is typically a monoclonal proliferation of B cells with morphology of plasmacytoid lymphocytes and production of monoclonal IgM. Methods and Results: We report a case of WM with biclonal gammopathy (IgM kappa and IgM lambda) involving the blood and a diffuse lymphoplasmacytic infiltrate in the bone marrow in an 83-year-old man. Immunophenotyping of the blood and bone marrow aspirate revealed B cells expressing IgM lambda surface immunoglobulins and CD5+, CD19+, and CD20+ surface markers. Gene-rearrangement analysis with the Southern blot technique revealed multiple rearranged bands in each lane of restricted patient DNA after probing with both immunoglobulin heavy (J(H))- and light (J(kappa))-chain gene probes. Conclusions: Biclonal gammopathy in WM and biclonal B-cell proliferations as determined by gene-rearrangement studies are rare entities, and few evaluations of them are reported in the literature. To our knowledge, this case is the first one of biclonal WM to have been evaluated by serum protein immunofixation, immunohistologic staining, immunophenotyping by flow cytometry, and immunoglobulin gene-rearrangement analysis. PMID:10462556

  5. [Hemodynamic and methabolic aspects of sodium nitroprusside pharmacodynamics during buccal administration in patients with arterial hypertension of cerebral ischemic genesis].

    PubMed

    Vizir, V A; Kechin, I L; Fedorova, E P

    2006-01-01

    The authors presented in the article efficiency of new formulation of Natrium Nitroprusodum used buccaly in patients with cerebral-ischemic form of arterial hypertention and stage II hypertention. It has been shown both in an acute experiment and after monothrerapy having been used. The medication proved to have positive effect on brachiocephalic vessel blood flow indices in patients of both groups using pulse doplergraphy. The use of Natrium Nitroprussidum used buccaly in patients with cerebral-ischemic form of arterial hypertention and hyportensive disease differentiates in terms of indices characterising the formation, transport and utilisation of energetic products, products of POL and antioxidant ferments. PMID:16689085

  6. A Targetable Fluorescent Sensor Reveals that Copper-Deficient SCO1 and SCO2 Patient Cells Prioritize Mitochondrial Copper Homeostasis

    PubMed Central

    Dodani, Sheel C.; Leary, Scot C.; Cobine, Paul A.; Winge, Dennis R.; Chang, Christopher J.

    2011-01-01

    We present the design, synthesis, spectroscopy, and biological applications of Mitochondrial Coppersensor-1 (Mito-CS1), a new type of targetable fluorescent sensor for imaging exchangeable mitochondrial copper pools in living cells. Mito-CS1 is a bifunctional reporter that combines a Cu+-responsive fluorescent platform with a mitochondrial-targeting triphenylphosphonium moiety for localizing the probe to this organelle. Molecular imaging with Mito-CS1 establishes that this new chemical tool can detect changes in labile mitochondrial Cu+ in a model HEK 293T cell line as well as in human fibroblasts. Moreover, we utilized Mito-CS1 in a combined imaging and biochemical study in fibroblasts derived from patients with mutations in the two synthesis of cytochrome c oxidase 1 and 2 proteins (SCO1 and SCO2), each of which is required for assembly and metallation of functionally active cytochrome c oxidase (COX). Interestingly, we observe that although defects in these mitochondrial metallochaperones lead to a global copper deficiency at the whole cell level, total copper and exchangeable mitochondrial Cu+ pools in SCO1 and SCO2 patient fibroblasts are largely unaltered relative to wildtype controls. Our findings reveal that the cell maintains copper homeostasis in mitochondria even in situations of copper deficiency and mitochondrial metallochaperone malfunction, illustrating the importance of regulating copper stores in this energy-producing organelle. PMID:21563821

  7. Comparison of an expanded ataxia interactome with patient medical records reveals a relationship between macular degeneration and ataxia

    PubMed Central

    Kahle, Juliette J.; Gulbahce, Natali; Shaw, Chad A.; Lim, Janghoo; Hill, David E.; Barabási, Albert-László; Zoghbi, Huda Y.

    2011-01-01

    Spinocerebellar ataxias 6 and 7 (SCA6 and SCA7) are neurodegenerative disorders caused by expansion of CAG repeats encoding polyglutamine (polyQ) tracts in CACNA1A, the alpha1A subunit of the P/Q-type calcium channel, and ataxin-7 (ATXN7), a component of a chromatin-remodeling complex, respectively. We hypothesized that finding new protein partners for ATXN7 and CACNA1A would provide insight into the biology of their respective diseases and their relationship to other ataxia-causing proteins. We identified 118 protein interactions for CACNA1A and ATXN7 linking them to other ataxia-causing proteins and the ataxia network. To begin to understand the biological relevance of these protein interactions within the ataxia network, we used OMIM to identify diseases associated with the expanded ataxia network. We then used Medicare patient records to determine if any of these diseases co-occur with hereditary ataxia. We found that patients with ataxia are at 3.03-fold greater risk of these diseases than Medicare patients overall. One of the diseases comorbid with ataxia is macular degeneration (MD). The ataxia network is significantly (P= 7.37 × 10−5) enriched for proteins that interact with known MD-causing proteins, forming a MD subnetwork. We found that at least two of the proteins in the MD subnetwork have altered expression in the retina of Ataxin-7266Q/+ mice suggesting an in vivo functional relationship with ATXN7. Together these data reveal novel protein interactions and suggest potential pathways that can contribute to the pathophysiology of ataxia, MD, and diseases comorbid with ataxia. PMID:21078624

  8. Using patient serum to epitope map soybean glycinins reveals common epitopes shared with many legumes and tree nuts.

    PubMed

    Saeed, Hanaa; Gagnon, Christine; Cober, Elroy; Gleddie, Steve

    2016-02-01

    Soybean consumption is increasing in many Western diets; however, recent reviews suggest that the prevalence of soy allergy can be as high as 0.5% for the general population and up to 13% for children. The immunoglobulin-E (IgE) binding of sera from six soy-sensitive adult human subjects to soybean proteins separated by 2D gel electrophoresis was studied. Synthetic peptide sets spanning the mature glycinin subunit A2 and A3 primary sequences were used to map the IgE-binding regions. Putative epitopes identified in this study were also localized on glycinin hexamer models using bioinformatics software. We identified linear IgE-binding epitopes of the major storage protein Gly m 6 by screening individual soy-sensitive patient sera. These epitopes were then further analysed by 3D in silico model localization and compared to other plant storage protein epitopes. Web-based software applications were also used to study the ability to accurately predict epitopes with mixed results. A total of nine putative IgE-binding epitopes were identified in the glycinin A3 (A3.1-A3.3) and A2 (A2.1-A2.6) subunits. Most patients' sera IgE bound to only one or two epitopes, except for one patient's serum which bound to four different A2 epitopes. Two epitopes (A3.2 and A2.4) overlapped with a previously identified epitope hot spot of 11S globulins from other plant species. Most epitopes were predicted to be exposed on the surface of the 3D model of the glycinin hexamer. Amino acid sequence alignments of soybean acidic glycinins and other plant globulins revealed one dominant epitope hot spot among the four reported hot spots. This study may be helpful for future development of soy allergy immunotherapy and diagnosis. PMID:26766775

  9. [Responsiveness and resistance of spinal cord structures in patients with closed thoracic and lumbar spinal injuries: neurophysiological and clinical aspects].

    PubMed

    Shein, A P; Krivoruchko, G A; Chukhareva, N A; Liulin, S V

    2000-01-01

    The study was undertaken to explore the time course of parameters of neuromotor dysfunction in patients with thoracic and lumbar spinal fractures characterized by the varying degrees of neurological symptoms. The study was based on the results of complex neurophysiological testing (global and stimulation electroneuromyography (EMG) in 45 patients with thoracic and lumbar spinal fractures who had been admitted to the "VTO" Russian Research Center without complications. The patients were divided into 2 groups: 1) 17 patients without neurological disorders and 2) 28 with mild neurological ones. There was evidence that there were no complicated vertebral injuries. Group 1 patients were found to have steady-state changes in the EMG structure, lower voluntary and involuntary activities (M responses) of the muscles of the hip, leg, and foot, enhanced reflex excitability of leg muscles, EMG signs of spasticity and irritation of segmental radicular structures, long-term asymmetry virtually in all EMG parameters. It was also ascertained that the group of patients with uncomplicated vertebral fractures was represented by individuals having more fitness or those belonging to the so-called "muscular" somato-type. The findings lead to the conclusion that the VTO treatment of vertebrospinal injuries, that is based on the use of a refinement of an external spinal fixation apparatus, creates necessary prerequisites for prevention of further development of neurological deficit and for the optimal course of compensatory-reparative processes in the damaged spinal cord structures. PMID:10723262

  10. Acute effects of surgery on emotion and personality of brain tumor patients: surgery impact, histological aspects, and recovery

    PubMed Central

    Campanella, Fabio; Fabbro, Franco; Ius, Tamara; Shallice, Tim; Skrap, Miran

    2015-01-01

    Background Cognitive effects of brain surgery for the removal of intracranial tumors are still under investigation. For many basic sensory/motor or language-based functions, focal, albeit transient, cognitive deficits have been reported low-grade gliomas (LGGs); however, the effects of surgery on higher-level cognitive functions are still largely unknown. It has recently been shown that, following brain tumors, damage to different brain regions causes a variety of deficits at different levels in the perception and interpretation of emotions and intentions. However, the effects of different tumor histologies and, more importantly, the effects of surgery on these functions have not been examined. Methods The performance of 66 patients affected by high-grade glioma (HGG), LGG, and meningioma on 4 tasks tapping different levels of perception and interpretations of emotion and intentions was assessed before, immediately after, and (for LGG patients) 4 months following surgery. Results Results showed that HGG patients were generally already impaired in the more perceptual tasks before surgery and did not show surgery effects. Conversely, LGG patients, who were unimpaired before surgery, showed a significant deficit in perceptual tasks immediately after surgery that was recovered within few months. Meningioma patients were substantially unimpaired in all tasks. Conclusions These results show that surgery can be relatively safe for LGG patients with regard to the higher-level, more complex cognitive functions and can provide further useful information to the neurosurgeon and improve communication with both the patient and the relatives about possible changes that can occur immediately after surgery. PMID:25921022

  11. Legal aspects.

    PubMed

    Escher, A

    1975-01-01

    The manufacture, application, use and disposal of fluorescent whitening agents (FWAs) may give rise to legal questions relating mainly to environmental protection and the effects on man and animals. In addition to legal aspects, certain commercial aspects such as the law of competition and the obligations of industry, including compensation for damage caused by FWAs, are discussed. PMID:1064546

  12. [Psychological aspects of remission induced by intensive insulin therapy in type I diabetes. A retrospective study of 44 patients].

    PubMed

    Ziegler, O; Kolopp, M; Kahn, J P; Floquet, B; Goudot, C; Beyel, P; Drouin, P; Debry, G

    1991-01-01

    The psychological consequences of induced remission of type 1 diabetes, have not yet been investigated thoroughly. We studied the psychological status of 44 patients (16 women, 28 men), age 21 years +/- 8 months (mean +/- SD), whose remission lasted 12 +/- 9 months. Patients' psychological reactions were analyzed retrospectively, using a 20 items standardized questionnaire, investigating 3 successive periods: 1) initial intensive insulin therapy; 2) remission; 3) permanent insulin therapy. 8% of the subjects only considered the remission phase useless, whereas 49% expressed a positive appraisal. Hope was predominant feeling, 25% of the patients believing in a completed recovery of diabetes. Perceived therapeutic constraints were, in decreasing order: regimen, way of life's regularity, self monitoring of blood glucose. When starting permanent insulin therapy, opposite answers were given: 49% negative feelings, 33% positive feelings and 18% ambivalent feelings. During this period, insulin injections represented the major therapeutic constraint, followed by self monitoring of blood glucose. To summarize, induced remission does not appear to be psychologically harmful and is considered useful by a large majority of patients. Effective psychological support has to be offered to help those patients to cope with their irrational hopes of healing and to dampen their deception at the end of the remission period. PMID:1752345

  13. Concerns regarding the financial aspects of kidney transplantation: perspectives of pre-transplant patients and their family members

    PubMed Central

    Ganji, Sumitha; Ephraim, Patti L.; Ameling, Jessica M.; Purnell, Tanjala S.; Lewis-Boyer, LaPricia L.; Boulware, L. Ebony

    2015-01-01

    Background African American and non-African American pre-transplant patients’ and their families’ concerns about the financial costs of kidney transplantation have not been well studied. Methods We conducted structured group interviews among pre-transplant patients (seven African American, five non-African American) and their family members (six African American, five non-African American) to identify their concerns about transplant health insurance coverage, out-of-pocket expenses, and living donor expenses. We reviewed transcribed group audio recordings and identified common discussion themes. Results African American and non-African American patients and family members expressed uncertainty about which transplant-related costs were covered by health insurance and wanted information about how to choose insurance policies accordingly. Patients were particularly concerned about the impact of pre-existing illness on securing optimal health insurance, while family members wanted information about non-insurance-based financial resources. Both patients and family members expressed concern about paying for immunosuppressant medications and about gradual loss of insurance benefits after transplantation. Both patients and family members also expressed concern about potential financial hardships for living donors. Conclusion African American and non-African American pre-transplant patients and families expressed a broad range of concerns about transplant health insurance policies, out-of-pocket expenses, non-insurance-based financial resources, and resources to address donors’ financial burden. Efforts to improve education and develop more comprehensive transplant insurance policies are needed to facilitate informed decision-making for potential transplant recipients and donors. PMID:25066730

  14. Embracing the Sparse, Noisy, and Interrelated Aspects of Patient Demographics for use in Clinical Medical Record Linkage

    PubMed Central

    Ash, Stephen M.; Ip-Lin, King

    2015-01-01

    Duplicate patient records in health information systems have received increased attention in recent time due to regulatory incentives to integrate the healthcare enterprise. Historically, most patient record matching systems have been limited to simple applications of the Fellegi-Sunter theory of record linkage with edit distance based string similarity measurements. String similarity approaches ignore the rich semantic information present by reducing it to a simple syntactic comparison of characters. This work describes an updated approach to building clinical medical record linkage systems, which embraces the unavoidable problems present in real-world patient matching. Using a ground truth dataset of a real patient population, we demonstrate that systems built in this fashion improve recall by 76% with little reduction in precision. This result empirically demonstrates the size of the gap between sophisticated systems and naïve approaches. Additionally, it accentuates the difficulty in estimating the false negative error in this setting as previous research has reported much higher levels of recall, due, in part, to measuring from biased samples. PMID:26306279

  15. Geometrical aspects of patient-specific modelling of the intervertebral disc: collagen fibre orientation and residual stress distribution.

    PubMed

    Marini, Giacomo; Studer, Harald; Huber, Gerd; Püschel, Klaus; Ferguson, Stephen J

    2016-06-01

    Patient-specific modelling of the spine is a powerful tool to explore the prevention and the treatment of injuries and pathologies. Albeit several methods have been proposed for the discretization of the bony structures, the efficient representation of the intervertebral disc anisotropy remains a challenge, especially with complex geometries. Furthermore, the swelling of the disc's nucleus pulposus is normally added to the model after geometry definition, at the cost of changes of the material properties and an unrealistic description of the prestressed state. The aim of this study was to develop techniques, which preserve the patient-specific geometry of the disc and allow the representation of the system anisotropy and residual stresses, independent of the system discretization. Depending on the modelling features, the developed approaches resulted in a response of patient-specific models that was in good agreement with the physiological response observed in corresponding experiments. The proposed methods represent a first step towards the development of patient-specific models of the disc which respect both the geometry and the mechanical properties of the specific disc. PMID:26243011

  16. Embracing the Sparse, Noisy, and Interrelated Aspects of Patient Demographics for use in Clinical Medical Record Linkage.

    PubMed

    Ash, Stephen M; Ip-Lin, King

    2015-01-01

    Duplicate patient records in health information systems have received increased attention in recent time due to regulatory incentives to integrate the healthcare enterprise. Historically, most patient record matching systems have been limited to simple applications of the Fellegi-Sunter theory of record linkage with edit distance based string similarity measurements. String similarity approaches ignore the rich semantic information present by reducing it to a simple syntactic comparison of characters. This work describes an updated approach to building clinical medical record linkage systems, which embraces the unavoidable problems present in real-world patient matching. Using a ground truth dataset of a real patient population, we demonstrate that systems built in this fashion improve recall by 76% with little reduction in precision. This result empirically demonstrates the size of the gap between sophisticated systems and naïve approaches. Additionally, it accentuates the difficulty in estimating the false negative error in this setting as previous research has reported much higher levels of recall, due, in part, to measuring from biased samples. PMID:26306279

  17. A longitudinal cohort study of Finnish patients with primary Sjögren's syndrome: clinical, immunological, and epidemiological aspects

    PubMed Central

    Pertovaara, M; Pukkala, E; Laippala, P; Miettinen, A; Pasternack, A

    2001-01-01

    OBJECTIVE—To evaluate outcome in a cohort of Finnish patients with primary Sjögren's syndrome (pSS).
METHODS—Clinical and laboratory data from the time of diagnosis and follow up were collected from 110 patients with pSS (107 women, three men) diagnosed in 1977-1992 in central Finland. The standardised incidence ratio for cancers was determined as the ratio of the observed number of cases to the expected number based on regional population rates. Eighty one of the 93 patients still alive were interviewed, and clinical and laboratory examinations performed in 1994-1997.
RESULTS—The mean (SD) erythrocyte sedimentation rate (33 (22) v 45 (28) mm/1st h), serum IgG (18.8 (7.4) v 22.5 (8.5) g/l), and serum IgM (1.6 (1.1) v 2.0 (1.2) g/l) at the control visit were significantly (p<0.0001) lower than those at baseline. A similar change was observed in a subgroup of patients never treated with glucocorticosteroids or disease modifying antirheumatic drugs. Three non-Hodgkin's lymphomas were diagnosed (standardised incidence ratio 13; 95% confidence interval 2.7 to 38). In a logistic regression model, the patients with pSS with subsequent lymphoma were found to have higher baseline levels of serum β2 microglobulin than the others (odds ratio 1.9; 95% confidence interval 1.1 to 3.4).
CONCLUSION—The results suggest that mean concentrations of serum IgG and IgM in patients with pSS decline with time, possibly reflecting diminishing inflammatory activity. As in previous studies, the incidence of non-Hodgkin's lymphomas in this cohort of patients with pSS was significantly higher than in the reference population.

 PMID:11302868

  18. Immunoepidemiological profiling of onchocerciasis patients reveals associations with microfilaria loads and ivermectin intake on both individual and community levels.

    PubMed

    Arndts, Kathrin; Specht, Sabine; Debrah, Alexander Y; Tamarozzi, Francesca; Klarmann Schulz, Ute; Mand, Sabine; Batsa, Linda; Kwarteng, Alexander; Taylor, Mark; Adjei, Ohene; Martin, Coralie; Layland, Laura E; Hoerauf, Achim

    2014-02-01

    Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF(+) or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community

  19. Bacterial Community Shift in Treated Periodontitis Patients Revealed by Ion Torrent 16S rRNA Gene Amplicon Sequencing

    PubMed Central

    Jünemann, Sebastian; Prior, Karola; Szczepanowski, Rafael; Harks, Inga; Ehmke, Benjamin; Goesmann, Alexander; Stoye, Jens; Harmsen, Dag

    2012-01-01

    Periodontitis, one of the most common diseases in the world, is caused by a mixture of pathogenic bacteria and inflammatory host responses and often treated by antimicrobials as an adjunct to scaling and root planing (SRP). Our study aims to elucidate explorative and descriptive temporal shifts in bacterial communities between patients treated by SRP alone versus SRP plus antibiotics. This is the first metagenomic study using an Ion Torrent Personal Genome Machine (PGM). Eight subgingival plaque samples from four patients with chronic periodontitis, taken before and two months after intervention were analyzed. Amplicons from the V6 hypervariable region of the 16S rRNA gene were generated and sequenced each on a 314 chip. Sequencing reads were clustered into operational taxonomic units (OTUs, 3% distance), described by community metrics, and taxonomically classified. Reads ranging from 599,933 to 650,416 per sample were clustered into 1,648 to 2,659 non-singleton OTUs, respectively. Increased diversity (Shannon and Simpson) in all samples after therapy was observed regardless of the treatment type whereas richness (ACE) showed no correlation. Taxonomic analysis revealed different microbial shifts between both therapy approaches at all taxonomic levels. Most remarkably, the genera Porphyromonas, Tannerella, Treponema, and Filifactor all harboring periodontal pathogenic species were removed almost only in the group treated with SPR and antibiotics. For the species T. forsythia and P. gingivalis results were corroborated by real-time PCR analysis. In the future, hypothesis free metagenomic analysis could be the key in understanding polymicrobial diseases and be used for therapy monitoring. Therefore, as read length continues to increase and cost to decrease, rapid benchtop sequencers like the PGM might finally be used in routine diagnostic. PMID:22870235

  20. Sequential Waves of Gene Expression in Patients with Clinically Defined Dengue Illnesses Reveal Subtle Disease Phases and Predict Disease Severity

    PubMed Central

    Sun, Peifang; García, Josefina; Comach, Guillermo; Vahey, Maryanne T.; Wang, Zhining; Forshey, Brett M.; Morrison, Amy C.; Sierra, Gloria; Bazan, Isabel; Rocha, Claudio; Vilcarromero, Stalin; Blair, Patrick J.; Scott, Thomas W.; Camacho, Daria E.; Ockenhouse, Christian F.; Halsey, Eric S.; Kochel, Tadeusz J.

    2013-01-01

    Background Dengue virus (DENV) infection can range in severity from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Changes in host gene expression, temporally through the progression of DENV infection, especially during the early days, remains poorly characterized. Early diagnostic markers for DHF are also lacking. Methodology/Principal Findings In this study, we investigated host gene expression in a cohort of DENV-infected subjects clinically diagnosed as DF (n = 51) and DHF (n = 13) from Maracay, Venezuela. Blood specimens were collected daily from these subjects from enrollment to early defervescence and at one convalescent time-point. Using convalescent expression levels as baseline, two distinct groups of genes were identified: the “early” group, which included genes associated with innate immunity, type I interferon, cytokine-mediated signaling, chemotaxis, and complement activity peaked at day 0–1 and declined on day 3–4; the second “late” group, comprised of genes associated with cell cycle, emerged from day 4 and peaked at day 5–6. The up-regulation of innate immune response genes coincided with the down-regulation of genes associated with viral replication during day 0–3. Furthermore, DHF patients had lower expression of genes associated with antigen processing and presentation, MHC class II receptor, NK and T cell activities, compared to that of DF patients. These results suggested that the innate and adaptive immunity during the early days of the disease are vital in suppressing DENV replication and in affecting outcome of disease severity. Gene signatures of DHF were identified as early as day 1. Conclusions/Significance Our study reveals a broad and dynamic picture of host responses in DENV infected subjects. Host response to DENV infection can now be understood as two distinct phases with unique transcriptional markers. The DHF signatures identified during day 1–3 may have

  1. Congenitally Missing Maxillary Lateral Incisors: Functional and Periodontal Aspects in Patients Treated with Implants or Space Closure and Tooth Re-Contouring

    PubMed Central

    Marchi, Luciana Manzotti De; Pini, Núbia Inocencya Pavesi; Hayacibara, Roberto Massayuki; Silva, Rafael Santos; Pascotto, Renata Corrêa

    2012-01-01

    To evaluate functional and periodontal aspects in patients with unilateral or bilateral congenitally missing maxillary lateral incisors, treated with either implants or space closure and tooth re-contouring. The sample consisted of 68 volunteers, divided into 3 groups: SCR - space closure and tooth re-contouring with composite resin (n = 26); SOI – implants placed in the area of agenesis (n = 20); and CG - control group (n = 22). A modified Helkimo questionnaire and the Research Diagnostic Criteria for Temporomandibular Disorders were used by a single, previously calibrated evaluator to assess signs and symptoms of temporomandibular joint disorder. The periodontal assessment involved the following aspects: plaque index, bleeding upon probing, pocket depth greater than 3 mm, gingival recession, abfraction, periodontal biotype and papilla index. The data were analyzed using Fisher's exact test and the nonparametric Mann-Whitney and Kruskal-Wallis tests (α=.05). No differences in periodontal status were found between treatments. None of the groups were associated with signs and symptoms of temporomandibular joint disorder. Both treatment alternatives for patients with congenitally missing maxillary lateral incisors were satisfactory and achieved functional and periodontal results similar to those of the control group. PMID:23346262

  2. [Analysis of logistical and organizational aspects of a cruise for patients with chronic respiratory insufficiency. The RESpIRA Expedition and the COPD Cruise].

    PubMed

    Díaz Lobato, S; Mayoralas Alises, S; Gómez Mendieta, M A; Sanz Baena, S; Martín Sánchez, R; Díaz-Agero, P

    2003-06-01

    Patients with chronic respiratory insufficiency who are receiving domiciliary oxygen therapy and mechanical ventilation report great difficulty in taking complex trips involving several destinations and prolonged stays away from home. Such patients share a common need for home equipment whose technology is relatively sophisticated, a condition that limits their freedom of movement. We are referring to systems for delivering oxygen therapy and mechanical respirators. Given that such patients have problems traveling by air, we hypothesized that a cruise would be an ideal alternative, given that travel would take place in the hotel itself. A cruise would facilitate the logistics of the journey, given that the equipment would have to be set up at only one setting. Working with these assumptions, we have thus far organized two cruises for chronic respiratory insufficiency patients: the "RESpIRA Expedition" and the "COPD Cruise". Our experience shows that the organizational problems to be coped with are patient recruitment, financing and choice of itinerary. With those aspects clear, organizers must then obtain the authorization of the cruise operator, including the approval of the medical and safety personnel on board. After obtaining permission for the cruise and as soon as the organizers know how many patients will travel, a list of oxygen therapy equipment (respirators and disposable supplies) must be compiled. Finally, equipment suppliers must be found. Afterwards, all that remains is to enjoy the trip. The participation of physicians responsible for domiciliary oxygen therapy and mechanical ventilation programs is essential for making patients feel safe and for assuring solutions for technical and medical problems that might arise. PMID:12797943

  3. [The current aspects of the pharmacological correction of hyperglycemia in patients with non-insulin-dependent diabetes mellitus (type 2)].

    PubMed

    Gorbenko, N I

    1999-01-01

    Data on the mechanisms of developing of hyperglycemia in patients with diabetes mellitus (type 2) are analyzed and reviewed. The current concept of hypoglycemic therapy aimed both at amelioration of hyperglycemia symptoms and reduction of the risk of diabetic micro- and macroangiopathies is considered. The main directions of pharmacological action of hypoglycemic drugs (both in use and in the stage of design) and data of the efficiency and possible incidental action are presented. PMID:10572759

  4. Depletion of interfering antibodies in chronic hepatitis C patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity

    PubMed Central

    Zhang, Pei; Zhong, Lilin; Struble, Evi Budo; Watanabe, Hisayoshi; Kachko, Alla; Mihalik, Kathleen; Virata-Theimer, Maria Luisa; Alter, Harvey J.; Feinstone, Stephen; Major, Marian

    2009-01-01

    Using human immune globulins made from antihepatitis C virus (HCV)-positive plasma, we recently identified two antibody epitopes in the E2 protein at residues 412–426 (epitope I) and 434–446 (epitope II). Whereas epitope I is highly conserved among genotypes, epitope II varies. We discovered that epitope I was implicated in HCV neutralization whereas the binding of non-neutralizing antibody to epitope II disrupted virus neutralization mediated by antibody binding at epitope I. These findings suggested that, if this interfering mechanism operates in vivo during HCV infection, a neutralizing antibody against epitope I can be restrained by an interfering antibody, which may account for the persistence of HCV even in the presence of an abundance of neutralizing antibodies. We tested this hypothesis by affinity depletion and peptide-blocking of epitope-II-specific antibodies in plasma of a chronically HCV-infected patient and recombinant E1E2 vaccinated chimpanzees. We demonstrate that, by removing the restraints imposed by the interfering antibodies to epitope-II, neutralizing activity can be revealed in plasma that previously failed to neutralize viral stock in cell culture. Further, cross-genotype neutralization could be generated from monospecific plasma. Our studies contribute to understanding the mechanisms of antibody-mediated neutralization and interference and provide a practical approach to the development of more potent and broadly reactive hepatitis C immune globulins. PMID:19380744

  5. Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients

    PubMed Central

    de Miranda, Noel F. C. C.; Georgiou, Konstantinos; Chen, Longyun; Wu, Chenglin; Gao, Zhibo; Zaravinos, Apostolos; Lisboa, Susana; Enblad, Gunilla; Teixeira, Manuel R.; Zeng, Yixin

    2014-01-01

    Next-generation sequencing studies on diffuse large B-cell lymphomas (DLBCLs) have revealed novel targets of genetic aberrations but also high intercohort heterogeneity. Previous studies have suggested that the prevalence of disease subgroups and cytogenetic profiles differ between Western and Asian patients. To characterize the coding genome of Chinese DLBCL, we performed whole-exome sequencing of DNA derived from 31 tumors and respective peripheral blood samples. The mutation prevalence of B2M, CD70, DTX1, LYN, TMSB4X, and UBE2A was investigated in an additional 105 tumor samples. We discovered 11 novel targets of recurrent mutations in DLBCL that included functionally relevant genes such as LYN and TMSB4X. Additional genes were found mutated at high frequency (≥10%) in the Chinese cohort including DTX1, which was the most prevalent mutation target in the Notch pathway. We furthermore demonstrated that mutations in DTX1 impair its function as a negative regulator of Notch. Novel and previous unappreciated targets of somatic mutations in DLBCL identified in this study support the existence of additional/alternative tumorigenic pathways in these tumors. The observed differences with previous reports might be explained by the genetic heterogeneity of DLBCL, the germline genetic makeup of Chinese individuals, and/or exposure to distinct etiological agents. PMID:25171927

  6. A professional response to demands for accountability: practical recommendations regarding ethical aspects of patient care. Working Group on Accountability.

    PubMed

    Emanuel, L L

    1996-01-15

    Forceful new demands for accountability in medicine are arising from many interested parties. To maintain professional standards, physicians need to establish which demands are desirable and which are not. We adopt a model of stratified accountability that includes three major components: the accountable parties, the subject matter, and the processes for accountability. To begin describing the model, we focus on physicians and health care institutions. We focus on the ethical dimensions of medical practice, both because the difficulty of measuring such behaviors makes this a test case for accountability and because of the importance of ethical standards in maintaining patient trust. We first identify eight widely endorsed content areas for accountability in ethical conduct: medical decision making, confidentiality, fiduciary obligations (including conflicts of interest), responsibilities arising from patient vulnerability, personal standards, equity among patients, cultural representation, and procedures for resolving dilemmas. We then identify the currently most valid and reliable methods for assessing conduct: surveys among all involved parties, testing methods used for accreditation, limited audits, publication of policy, and careful use of report cards. A prototypical survey and report card are illustrated. However, we also note the need for improved accountability assessment methods. We next identify mechanisms for taking responsibility: sharing information, exchanging perspectives, making adjustments, and enforcing standards when necessary. Finally, because this report only begins to describe a small part of the accountability model, we urge explicit identification and development of professional standards for accountability in the many other areas of medicine. PMID:8534000

  7. Patients' complaints: some aspects of the evaluation of physicians' conduct by the Danish National Board of Health.

    PubMed

    Segest, E

    1992-01-01

    This study comprises all complaints made by patients to the Danish National Board of Health in 1984-1985. All disciplinary cases regarding physicians' conduct are evaluated by the board. A quantitative evaluation was carried out of the 1,062 complaints received by the board in the period under study. Special attention was given to some topics. It is emphasized that adverse outcome termed fortuitous has been narrowed over time, but more investigation is needed, in order to have a more objective foundation from which to determine whether an adverse outcome really is fortuitous or whether it is due to negligence. A central registration of cases of adverse outcome is suggested. The problem of allocating responsibility is very much open to debate, but more adequate case journal keeping is also mentioned. It was surprising that violations of information and consent requirements are often sanctioned very mildly, and more attention to this sphere is appropriate in order to ensure patients' rights. In this connection regular inquiries into patient satisfaction should be considered as a feedback mechanism. PMID:1522779

  8. Distinctive aspects of peptic ulcer disease, Dieulafoy's lesion, and Mallory-Weiss syndrome in patients with advanced alcoholic liver disease or cirrhosis

    PubMed Central

    Nojkov, Borko; Cappell, Mitchell S

    2016-01-01

    AIM: To systematically review the data on distinctive aspects of peptic ulcer disease (PUD), Dieulafoy’s lesion (DL), and Mallory-Weiss syndrome (MWS) in patients with advanced alcoholic liver disease (aALD), including alcoholic hepatitis or alcoholic cirrhosis. METHODS: Computerized literature search performed via PubMed using the following medical subject heading terms and keywords: “alcoholic liver disease”, “alcoholic hepatitis”,“ alcoholic cirrhosis”, “cirrhosis”, “liver disease”, “upper gastrointestinal bleeding”, “non-variceal upper gastrointestinal bleeding”, “PUD”, ‘‘DL’’, ‘‘Mallory-Weiss tear”, and “MWS’’. RESULTS: While the majority of acute gastrointestinal (GI) bleeding with aALD is related to portal hypertension, about 30%-40% of acute GI bleeding in patients with aALD is unrelated to portal hypertension. Such bleeding constitutes an important complication of aALD because of its frequency, severity, and associated mortality. Patients with cirrhosis have a markedly increased risk of PUD, which further increases with the progression of cirrhosis. Patients with cirrhosis or aALD and peptic ulcer bleeding (PUB) have worse clinical outcomes than other patients with PUB, including uncontrolled bleeding, rebleeding, and mortality. Alcohol consumption, nonsteroidal anti-inflammatory drug use, and portal hypertension may have a pathogenic role in the development of PUD in patients with aALD. Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients. The frequency of bleeding from DL appears to be increased in patients with aALD. DL may be associated with an especially high mortality in these patients. MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism, and is associated with aALD. Patients with aALD have more severe MWS bleeding and are more likely to rebleed when compared to non

  9. Regulatory aspects of Phase 3 endpoints for new inhaled antibiotics for cystic fibrosis patients with chronic Pseudomonas aeruginosa infections.

    PubMed

    Montgomery, Alan Bruce; Abuan, Tammy; Yeager, Melissa A

    2012-08-01

    Available regulatory guidelines for developing inhaled anti-infective therapies offer general advice, but specific guidance often provides conflicting and outdated advice in regard to clinical trial design. For instance, the availability of two approved drugs makes the conduct of placebo-controlled trials longer than 28 days problematic. Comparator drugs require use per the product label, making comparator trials difficult to blind as taste, foaming, regimen, device, and delivery time differences are present. Currently, there is no consensus on the most appropriate endpoints for evaluation of aerosolized antimicrobials. FEV(1) is a surrogate endpoint that it is a predictor of mortality--it is standardized, reproducible, noninvasive, simple, and inexpensive to perform but small statistically significant changes may not be clinically important. FEV(1) improvement also has a ceiling effect in patients with mild lung function impairment and spirometry cannot be reliably done in patients under the age of 6 years. A patient-reported outcome is a promising clinical endpoint. However, there is not currently an accepted tool that can be used as a primary endpoint for the FDA or the EMA, although the latter recognizes the CFQ-R as a validated secondary endpoint and the FDA grandfathered acceptance of the CFQ-R respiratory domain in the pivotal aztreonam for inhalation study. Exacerbations are an important clinical endpoint that reflects morbidity and are a major driver of cost of care, but they occur infrequently and a standardized definition has not been reached. Furthermore, an exacerbation endpoint may fail even with an otherwise effective antibiotic therapy. Regulatory authorities will have a difficult time approving any new inhaled antibiotic based on one clinical endpoint alone. PMID:22857271

  10. Transcatheter arterial embolization in patients with kidney diseases: an overview of the technical aspects and clinical indications.

    PubMed

    Loffroy, Romaric; Rao, Pramod; Kwak, Byung-Kook; Ota, Shinichi; De Lin, Ming; Liapi, Eleni; Geschwind, Jean-François

    2010-01-01

    Therapeutic embolization is defined as the voluntary occlusion of one or several vessels, and this is achieved by inserting material into the lumen to obtain transient or permanent thrombosis in the downstream vascular bed. There are a number of indications for this approach in urological practice, in particular for the patients with parenchymatous or vascular kidney disease. In this review, we present the different embolization techniques and the principally employed occluding agents, and then we present the principal clinical indications and we discuss other pathologies that may benefit from this non-invasive therapy. The complications, side effects and main precautions associated with this approach are also described. PMID:20461179

  11. Phenotypic and Molecular Aspects of Staphylococcus spp. Isolated from Hospitalized Patients and Beef in the Brazilian Amazon.

    PubMed

    Pieri, Fabio A; Vargas, Taise F; Galvão, Newton N; Nogueira, Paulo A; Orlandi, Patrícia P

    2016-03-01

    The aim of this study was to characterize and compare Staphylococcus spp. isolated from hospitalized patients and beef marketed in the city of Porto Velho-RO, Brazil. The isolates were subjected to antibiogram tests, adherence capacity tests, detection of the mecA gene, and epidemiological investigation by the random amplified polymorphic DNA (RAPD) technique, using the primers M13 and H12. Among the 123 Staphylococcus spp. isolates, 50 were identified as S. aureus and 73 as coagulase-negative Staphylococcus; among the latter, 7 species were identified. It was observed that the coagulase-negative Staphylococcus isolates showed greater adhesion ability than S. aureus. The profile of antimicrobial susceptibility was different among isolates, all of which were susceptible to vancomycin and linezolid, and had high penicillin resistance rates, varying according to the bacterial class and the source. In this study, all strains were negative for mecA gene detection; however, 36% of S. aureus and 17% of coagulase-negative Staphylococcus were resistant to oxacillin. The genetic relationship of these bacteria, analyzed by RAPD, was able to discriminate the species of coagulase-negative Staphylococcus strains of S. aureus along its origin. It was concluded that the isolates of Staphylococcus spp. derived from beef and human infections differ genetically. Thus, it is suggested that isolates from beef, which were grouped within hospital isolates, were probably carried via contact with beef in hospital professionals or patients. PMID:26824600

  12. [Monitoring pregnant patients from risk countries with sickle cell disease and thalassemia. Clinical aspects, screening and prenatal diagnosis].

    PubMed

    Dickerhoff, R; Kulozik, A E; Kohne, E

    1993-04-01

    At the present time, about 3.5 million people from Turkey, Greece, Italy, the Middle East, Africa and Asia are living in Germany. They are potential carriers of beta-thalassaemia and haemoglobinopathies such as sickle cell disease. These diseases are new for most of us and represent a challenge to physicians, taking care of these patients. Not only do we have to learn about the clinical problems of homozygous patients and how to handle them, we also have to become acquainted with the problems related to the heterozygous carrier stage. The large number of asymptomatic pregnant carriers of beta-globin anomalies is a particular challenge for obstetricians. They need to identify carriers through haemoglobin electrophoresis screening, inform the carrier about the meaning of being a carrier, screen the woman's partner, refer for genetic counselling and suggest and explain prenatal diagnosis in case the partner is also a carrier. There is as yet no cure for thalassaemia and sickle cell disease, except for bone marrow transplantation in a few selected cases. Therefore, prenatal diagnosis presents a valuable method of preventing severe chronic diseases. Screening does not only allow genetic counselling, the information gained has also clinical implications for carriers of beta-thalassaemia. In this paper a summary is given of the pathophysiological and clinical features of thalassaemia and sickle cell disease and molecular biology methods to diagnose thalassaemias and sickle cell disease are discussed. In addition, a screening programme for pregnant women from countries at risk is suggested to enable physicians to give optimal care and initiate prenatal diagnosis. PMID:8491363

  13. [Hygienic aspects with regard to nursing of home care patients with AIDS, chronic diseases and mental handicaps].

    PubMed

    Sonntag, H G; Flassak, H; Throm, W

    1995-04-01

    A human handicap is defined as a broad, hard and long lasting restriction of the mental development and the social integration. Groups of handicapped persons can be divided into mentally, psychologically, physically, sensory (blind, deaf) handicapped as well as into multiple disabled and chronically sick persons and those in need of care (old). New groups with demands for aid are among others people suffering from AIDS, psychologically sick (old) and people getting old as well as mentally, physically und multiple handicapped persons, people suffering from cancer, severely ill and dying people. For all handicapped people should be demanded the possibility of living almost normal lives. For all persons directly concerned as well as their families such a normal life should include: the right of self-determination and autonomy, the demand for complex styles of living and nearby care/support, the providing of respective infrastructures such as barrier free living and access to public institutions, access to public transport and homes fitting for handicapped persons, the demand for out-patient treatment by a complex range of various possibilities of support and finally, the providing of alternative forms of living in contrast to the traditional way of life of handicapped people like families or homes. Three important living areas can be derived from these ideas, namely: living conditions, education/professional and working field, social life/social environment. These important living areas require preventive measures, mainly advice and information centres, places to go early recognition and early promotion of handicapped people and those in risk of a handicap (especially children) as well as medical, professional and social rehabilitation or integration. Concerning the spectrum of support, aid and care in the homely area up to now already exists a variety of offers by out-patient services (information services, social units, mobile support services

  14. Project REENCONTRO: ethical aspects of genetic identification in families separated by the compulsory isolation of leprosy patients in Brazil.

    PubMed

    Fonseca, Claudia Lee Williams; Biondi, Flávia Costa; Maricato, Glaucia Cristina; Schuler-Faccini, Lavínia

    2015-07-01

    In this paper, we discuss the experience of a team of geneticists, working in partnership with a Brazilian social movement aimed at promoting the rights of victims of Hansen's disease. These university researchers propose to use DNA test results to ascertain kinship connections and thereby reunite families that were sundered apart by draconian state policies of the mid-twentieth century that decreed the forced segregation of leprosy patients and the institutionalization of their children. The team's aim is to help revert stigma and reinforce positive group identity as well as to facilitate judicial claims to moral and financial reparation from the Brazilian state. We will discuss how, notwithstanding the voluntary nature of tests, mediated at all times through the social movement, the geneticists take care to follow clear ethical guidelines in the collection and stocking of DNA samples as well as in the devolution of test results. The subsequent inclusion of anthropologists in the team brings to the fore new ethical dilemmas ranging from procedures in field research to the possible consequences of research results. PMID:25966990

  15. Revealing Rembrandt

    PubMed Central

    Parker, Andrew J.

    2014-01-01

    The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI). Our results emphasized the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt's portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings. PMID:24795552

  16. Comprehensive analysis of Stargardt macular dystrophy patients reveals new genotype-phenotype correlations and unexpected diagnostic revisions

    PubMed Central

    Zaneveld, Jacques; Siddiqui, Sorath; Li, Huajin; Wang, Xia; Wang, Hui; Wang, Keqing; Li, Hui; Ren, Huanan; Lopez, Irma; Dorfman, Allison; Khan, Ayesha; Wang, Feng; Salvo, Jason; Gelowani, Violet; Li, Yumei; Sui, Ruifang; Koenekoop, Robert; Chen, Rui

    2014-01-01

    Purpose Stargardt macular dystrophy (STGD) results in early central vision loss. We sought to explain the genetic cause of STGD in a cohort of 88 patients from three different cultural backgrounds. Methods Next Generation Sequencing using a novel capture panel was used to search for disease causing mutations. Unsolved patients were clinically re-examined and tested for copy number variations (CNVs) as well as intronic mutations. Results We determined the cause of disease in 67% of our patients. Our analysis identified 35 novel ABCA4 alleles. Eleven patients had mutations in genes not previously reported to cause STGD. Finally, 45% of our unsolved patients had single deleterious mutations in ABCA4, a recessive disease gene. No likely pathogenic CNVs were identified. Conclusions This study expands our knowledge of STGD by identifying dozens of novel STGD causing alleles. The frequency of patients with single mutations in ABCA4 is higher than controls, indicating these mutations contribute to disease. Eleven patients were explained by mutations outside ABCA4 underlining the need to genotype all retinal disease genes to maximize genetic diagnostic rates. Few ABCA4 mutations were observed in our French Canadian patients. This population may contain an unidentified founder mutation. Our results indicate that CNVs are unlikely to be a major cause of STGD. PMID:25474345

  17. Fungal DNA Detected in Blood Samples of Patients Who Received Contaminated Methylprednisolone Injections Reveals Increased Complexity of Causative Agents

    PubMed Central

    Zhao, Yanan; Armeanu, Emilian; DiVerniero, Richard; Lewis, Terri A.; Dobson, Richard C.; Kontoyiannis, Dimitrios P.; Roilides, Emmanuel; Walsh, Thomas J.

    2014-01-01

    Using Exserohilum rostratum-specific and panfungal real-time PCR, we studied 24 blood samples and 2 synovial fluid specimens from 20 patients with persistent or worsening pain following injections of contaminated methylprednisolone. Seven blood specimens from 6 patients were significantly positive for fungal DNA by panfungal PCR, with multiple fungal species identified. PMID:24719442

  18. [Pulmonary Echinococcosis: Surgical Aspects].

    PubMed

    Eichhorn, M E; Hoffmann, H; Dienemann, H

    2015-10-01

    Pulmonary cystic echinococcosis is a very rare disease in Germany. It is caused by the larvae of the dog tapeworm (echinococcus granulosus). The liver is the most affected organ, followed by the lungs. Surgery remains the main therapeutic approach for pulmonary CE. Whenever possible, parenchyma-preserving lung surgery should be preferred over anatomic lung resections. To ensure best therapeutic results, surgery needs to be performed under precise consideration of important infectiological aspects and patients should be treated in specialised centres based on interdisciplinary consensus. In addition to surgical aspects, this review summarises special infectiological features of this disease, which are crucial to the surgical approach. PMID:26351761

  19. Quantitative proteomics of the human skin secretome reveal a reduction in immune defense mediators in ectodermal dysplasia patients.

    PubMed

    Burian, Marc; Velic, Ana; Matic, Katarina; Günther, Stephanie; Kraft, Beatrice; Gonser, Lena; Forchhammer, Stephan; Tiffert, Yvonne; Naumer, Christian; Krohn, Michael; Berneburg, Mark; Yazdi, Amir S; Maček, Boris; Schittek, Birgit

    2015-03-01

    In healthy human skin host defense molecules such as antimicrobial peptides (AMPs) contribute to skin immune homeostasis. In patients with the congenital disease ectodermal dysplasia (ED) skin integrity is disturbed and as a result patients have recurrent skin infections. The disease is characterized by developmental abnormalities of ectodermal derivatives and absent or reduced sweating. We hypothesized that ED patients have a reduced skin immune defense because of the reduced ability to sweat. Therefore, we performed a label-free quantitative proteome analysis of wash solution of human skin from ED patients or healthy individuals. A clear-cut difference between both cohorts could be observed in cellular processes related to immunity and host defense. In line with the extensive underrepresentation of proteins of the immune system, dermcidin, a sweat-derived AMP, was reduced in its abundance in the skin secretome of ED patients. In contrast, proteins involved in metabolic/catabolic and biosynthetic processes were enriched in the skin secretome of ED patients. In summary, our proteome profiling provides insights into the actual situation of healthy versus diseased skin. The systematic reduction in immune system and defense-related proteins may contribute to the high susceptibility of ED patients to skin infections and altered skin colonization. PMID:25347115

  20. Gender effect on pre-attentive change detection in major depressive disorder patients revealed by auditory MMN.

    PubMed

    Qiao, Zhengxue; Yang, Aiying; Qiu, Xiaohui; Yang, Xiuxian; Zhang, Congpei; Zhu, Xiongzhao; He, Jincai; Wang, Lin; Bai, Bing; Sun, Hailian; Zhao, Lun; Yang, Yanjie

    2015-10-30

    Gender differences in rates of major depressive disorder (MDD) are well established, but gender differences in cognitive function have been little studied. Auditory mismatch negativity (MMN) was used to investigate gender differences in pre-attentive information processing in first episode MDD. In the deviant-standard reverse oddball paradigm, duration auditory MMN was obtained in 30 patients (15 males) and 30 age-/education-matched controls. Over frontal-central areas, mean amplitude of increment MMN (to a 150-ms deviant tone) was smaller in female than male patients; there was no sex difference in decrement MMN (to a 50-ms deviant tone). Neither increment nor decrement MMN differed between female and male patients over temporal areas. Frontal-central MMN and temporal MMN did not differ between male and female controls in any condition. Over frontal-central areas, mean amplitude of increment MMN was smaller in female patients than female controls; there was no difference in decrement MMN. Neither increment nor decrement MMN differed between female patients and female controls over temporal areas. Frontal-central MMN and temporal MMN did not differ between male patients and male controls. Mean amplitude of increment MMN in female patients did not correlate with symptoms, suggesting this sex-specific deficit is a trait- not a state-dependent phenomenon. PMID:26056015

  1. Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)

    PubMed Central

    Preston, Ioana R.; Roberts, Kari E.; Miller, Dave P.; Sen, Ginny P.; Selej, Mona; Benton, Wade W.; Hill, Nicholas S.

    2015-01-01

    Background— Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Methods and Results— Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. Conclusions— No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. PMID:26510696

  2. Deep sequencing reveals mutagenic effects of ribavirin during monotherapy of hepatitis C virus genotype 1-infected patients.

    PubMed

    Dietz, Julia; Schelhorn, Sven-Eric; Fitting, Daniel; Mihm, Ulrike; Susser, Simone; Welker, Martin-Walter; Füller, Caterina; Däumer, Martin; Teuber, Gerlinde; Wedemeyer, Heiner; Berg, Thomas; Lengauer, Thomas; Zeuzem, Stefan; Herrmann, Eva; Sarrazin, Christoph

    2013-06-01

    The preeminent mode of action of the broad-spectrum antiviral nucleoside ribavirin in the therapy of chronic hepatitis C is currently unresolved. Particularly under contest are possible mutagenic effects of ribavirin that may lead to viral extinction by lethal mutagenesis of the hepatitis C virus (HCV) genome. We applied ultradeep sequencing to determine ribavirin-induced sequence changes in the HCV coding region (nucleotides [nt] 330 to 9351) of patients treated with 6-week ribavirin monotherapy (n = 6) in comparison to placebo (n = 6). Baseline HCV RNA levels maximally declined on average by -0.8 or -0.1 log10 IU/ml in ribavirin- versus placebo-treated patients. No general increase in rates of nucleotide substitutions in ribavirin-treated patients was observed. However, more HCV genome positions with high G-to-A and C-to-U transition rates were detected between baseline and treatment week 6 in ribavirin-treated patients in comparison to placebo-treated patients (rate of 0.0041 transitions per base pair versus rate of 0.0022 transitions per base pair; P = 0.049). Similarly, the sensitive detection of low-frequency minority variants by statistical filtering indicated significantly more positions with G-to-A and C-to-U transitions in ribavirin-treated patients than in placebo-treated patients (rate of 0.0331 transitions versus rate of 0.0186 transitions per G/C-containing position at baseline; P = 0.018). In contrast, non-ribavirin-associated A-to-G and U-to-C transitions were not enriched in the ribavirin group (P = 0.152). We conclude that ribavirin exerts a mutagenic effect on the virus in patients with chronic hepatitis C by facilitating G-to-A and C-to-U nucleotide transitions. PMID:23536652

  3. Deep Sequencing Reveals Mutagenic Effects of Ribavirin during Monotherapy of Hepatitis C Virus Genotype 1-Infected Patients

    PubMed Central

    Dietz, Julia; Schelhorn, Sven-Eric; Fitting, Daniel; Mihm, Ulrike; Susser, Simone; Welker, Martin-Walter; Füller, Caterina; Däumer, Martin; Teuber, Gerlinde; Wedemeyer, Heiner; Berg, Thomas; Lengauer, Thomas; Zeuzem, Stefan; Herrmann, Eva

    2013-01-01

    The preeminent mode of action of the broad-spectrum antiviral nucleoside ribavirin in the therapy of chronic hepatitis C is currently unresolved. Particularly under contest are possible mutagenic effects of ribavirin that may lead to viral extinction by lethal mutagenesis of the hepatitis C virus (HCV) genome. We applied ultradeep sequencing to determine ribavirin-induced sequence changes in the HCV coding region (nucleotides [nt] 330 to 9351) of patients treated with 6-week ribavirin monotherapy (n = 6) in comparison to placebo (n = 6). Baseline HCV RNA levels maximally declined on average by −0.8 or −0.1 log10 IU/ml in ribavirin- versus placebo-treated patients. No general increase in rates of nucleotide substitutions in ribavirin-treated patients was observed. However, more HCV genome positions with high G-to-A and C-to-U transition rates were detected between baseline and treatment week 6 in ribavirin-treated patients in comparison to placebo-treated patients (rate of 0.0041 transitions per base pair versus rate of 0.0022 transitions per base pair; P = 0.049). Similarly, the sensitive detection of low-frequency minority variants by statistical filtering indicated significantly more positions with G-to-A and C-to-U transitions in ribavirin-treated patients than in placebo-treated patients (rate of 0.0331 transitions versus rate of 0.0186 transitions per G/C-containing position at baseline; P = 0.018). In contrast, non-ribavirin-associated A-to-G and U-to-C transitions were not enriched in the ribavirin group (P = 0.152). We conclude that ribavirin exerts a mutagenic effect on the virus in patients with chronic hepatitis C by facilitating G-to-A and C-to-U nucleotide transitions. PMID:23536652

  4. Valence-based Word-Face Stroop task reveals differential emotional interference in patients with major depression.

    PubMed

    Başgöze, Zeynep; Gönül, Ali Saffet; Baskak, Bora; Gökçay, Didem

    2015-10-30

    Word-Face Stroop task creates emotional conflict between affective words and affective faces. In this task, healthy participants consistently slow down while responding to incongruent cases. Such interference related slowdown is associated with recruitment of inhibitory processes to eliminate task-irrelevant information. We created a valence-based Word-Face Stroop task, in which participants were asked to indicate whether the words in the foreground are positive, negative or neutral. Healthy participants were faster and more accurate than un-medicated patients with major depression disorder (MDD). In addition, a significant congruence by group interaction is observed: healthy participants slowed down for incongruent cases, but MDD patients did not. Furthermore, for the negative words, healthy individuals made more errors while responding to incongruent cases but MDD patients made the lowest number of errors for this category. The emotional percepts of the patients were intact, because correct response rates in word valence judgments for positive/negative words, and reaction times for happy/sad faces had similar patterns with those of controls. These findings are supported by the analytical rumination interpretation of depression: patients lose speed/accuracy in laboratory tasks due to processing load spent during continuous rumination. However, for tasks in line with their preoccupation, continual practice makes the patients more vigilant and adept. PMID:26272019

  5. Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues.

    PubMed

    Koski, Anniina; Bramante, Simona; Kipar, Anja; Oksanen, Minna; Juhila, Juuso; Vassilev, Lotta; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli

    2015-10-01

    In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients. PMID:26156245

  6. Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia.

    PubMed

    Griffith, Malachi; Griffith, Obi L; Krysiak, Kilannin; Skidmore, Zachary L; Christopher, Matthew J; Klco, Jeffery M; Ramu, Avinash; Lamprecht, Tamara L; Wagner, Alex H; Campbell, Katie M; Lesurf, Robert; Hundal, Jasreet; Zhang, Jin; Spies, Nicholas C; Ainscough, Benjamin J; Larson, David E; Heath, Sharon E; Fronick, Catrina; O'Laughlin, Shelly; Fulton, Robert S; Magrini, Vincent; McGrath, Sean; Smith, Scott M; Miller, Christopher A; Maher, Christopher A; Payton, Jacqueline E; Walker, Jason R; Eldred, James M; Walter, Matthew J; Link, Daniel C; Graubert, Timothy A; Westervelt, Peter; Kulkarni, Shashikant; DiPersio, John F; Mardis, Elaine R; Wilson, Richard K; Ley, Timothy J

    2016-07-01

    The genomic events responsible for the pathogenesis of relapsed adult B-lymphoblastic leukemia (B-ALL) are not yet clear. We performed integrative analysis of whole-genome, whole-exome, custom capture, whole-transcriptome (RNA-seq), and locus-specific genomic assays across nine time points from a patient with primary de novo B-ALL. Comprehensive genome and transcriptome characterization revealed a dramatic tumor evolution during progression, yielding a tumor with complex clonal architecture at second relapse. We observed and validated point mutations in EP300 and NF1, a highly expressed EP300-ZNF384 gene fusion, a microdeletion in IKZF1, a focal deletion affecting SETD2, and large deletions affecting RB1, PAX5, NF1, and ETV6. Although the genome analysis revealed events of potential biological relevance, no clinically actionable treatment options were evident at the time of the second relapse. However, transcriptome analysis identified aberrant overexpression of the targetable protein kinase encoded by the FLT3 gene. Although the patient had refractory disease after salvage therapy for the second relapse, treatment with the FLT3 inhibitor sunitinib rapidly induced a near complete molecular response, permitting the patient to proceed to a matched-unrelated donor stem cell transplantation. The patient remains in complete remission more than 4 years later. Analysis of this patient's relapse genome revealed an unexpected, actionable therapeutic target that led to a specific therapy associated with a rapid clinical response. For some patients with relapsed or refractory cancers, this approach may indicate a novel therapeutic intervention that could alter outcome. PMID:27181063

  7. Treatment of spinal muscular atrophy cells with drugs that upregulate SMN expression reveals inter- and intra-patient variability

    PubMed Central

    Also-Rallo, Eva; Alías, Laura; Martínez-Hernández, Rebeca; Caselles, Lidia; Barceló, María J; Baiget, Montserrat; Bernal, Sara; Tizzano, Eduardo F

    2011-01-01

    Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by mutations in the SMN1 gene. The homologous copy (SMN2) is always present in SMA patients. SMN1 gene transcripts are usually full-length (FL), but exon 7 is spliced out in a high proportion of SMN2 transcripts (delta7) (Δ7). Advances in drug therapy for SMA have shown that an increase in SMN mRNA and protein levels can be achieved in vitro. We performed a systematic analysis of SMN expression in primary fibroblasts and EBV-transformed lymphoblasts from seven SMA patients with varying clinical severity and different SMN1 genotypes to determine expression differences in two accessible tissues (skin and blood). The basal expression of SMN mRNA FL and Δ7 in fibroblasts and lymphoblasts was analyzed by quantitative real-time PCR. The FL-SMN and FL/Δ7 SMN ratios were higher in control cells than in patients. Furthermore, we investigated the response of these cell lines to hydroxyurea, valproate and phenylbutyrate, drugs previously reported to upregulate SMN2. The response to treatments with these compounds was heterogeneous. We found both intra-patient and inter-patient variability even within haploidentical siblings, suggesting that tissue and individual factors may affect the response to these compounds. To optimize the stratification of patients in clinical trials, in vitro studies should be performed before enrolment so as to define each patient as a responder or non-responder to the compound under investigation. PMID:21610752

  8. Treatment of spinal muscular atrophy cells with drugs that upregulate SMN expression reveals inter- and intra-patient variability.

    PubMed

    Also-Rallo, Eva; Alías, Laura; Martínez-Hernández, Rebeca; Caselles, Lidia; Barceló, María J; Baiget, Montserrat; Bernal, Sara; Tizzano, Eduardo F

    2011-10-01

    Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by mutations in the SMN1 gene. The homologous copy (SMN2) is always present in SMA patients. SMN1 gene transcripts are usually full-length (FL), but exon 7 is spliced out in a high proportion of SMN2 transcripts (delta7) (Δ7). Advances in drug therapy for SMA have shown that an increase in SMN mRNA and protein levels can be achieved in vitro. We performed a systematic analysis of SMN expression in primary fibroblasts and EBV-transformed lymphoblasts from seven SMA patients with varying clinical severity and different SMN1 genotypes to determine expression differences in two accessible tissues (skin and blood). The basal expression of SMN mRNA FL and Δ7 in fibroblasts and lymphoblasts was analyzed by quantitative real-time PCR. The FL-SMN and FL/Δ7 SMN ratios were higher in control cells than in patients. Furthermore, we investigated the response of these cell lines to hydroxyurea, valproate and phenylbutyrate, drugs previously reported to upregulate SMN2. The response to treatments with these compounds was heterogeneous. We found both intra-patient and inter-patient variability even within haploidentical siblings, suggesting that tissue and individual factors may affect the response to these compounds. To optimize the stratification of patients in clinical trials, in vitro studies should be performed before enrolment so as to define each patient as a responder or non-responder to the compound under investigation. PMID:21610752

  9. Regional Coherence Alterations Revealed by Resting-State fMRI in Post-Stroke Patients with Cognitive Dysfunction

    PubMed Central

    Peng, Cheng-Yu; Chen, Yu-Chen; Cui, Ying; Zhao, Deng-Ling; Jiao, Yun; Tang, Tian-Yu; Ju, Shenghong; Teng, Gao-Jun

    2016-01-01

    Objectives Post-stroke cognitive dysfunction greatly influences patients’ quality of life after stroke. However, its neurophysiological basis remains unknown. This study utilized resting-state functional magnetic resonance imaging (fMRI) to investigate the alterations in regional coherence in patients after subcortical stroke. Methods Resting-state fMRI measurements were acquired from 16 post-stroke patients with poor cognitive function (PSPC), 16 post-stroke patients with good cognitive function (PSGC) and 30 well-matched healthy controls (HC). Regional homogeneity (ReHo) was used to detect alterations in regional coherence. Abnormalities in regional coherence correlated with scores on neuropsychological scales. Results Compared to the HC and the PSGC, the PSPC showed remarkably decreased ReHo in the bilateral anterior cingulate cortex and the left posterior cingulate cortex/precuneus. ReHo in the bilateral anterior cingulate cortex positively correlated with the scores on the Symbol Digit Modalities Test (r = 0.399, P = 0.036) and the Complex Figure Test-delayed recall subtest (r = 0.397, P = 0.036) in all post-stroke patients. Moreover, ReHo in the left posterior cingulate cortex/precuneus positively correlated with the scores on the Forward Digit Span Test (r = 0.485, P = 0.009) in all post-stroke patients. Conclusions Aberrant regional coherence was observed in the anterior and posterior cingulate cortices in post-stroke patients with cognitive dysfunction. ReHo could represent a promising indicator of neurobiological deficiencies in post-stroke patients. PMID:27454170

  10. Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients.

    PubMed

    Chen, Cai; Bartenhagen, Christoph; Gombert, Michael; Okpanyi, Vera; Binder, Vera; Röttgers, Silja; Bradtke, Jutta; Teigler-Schlegel, Andrea; Harbott, Jochen; Ginzel, Sebastian; Thiele, Ralf; Husemann, Peter; Krell, Pina F I; Borkhardt, Arndt; Dugas, Martin; Hu, Jianda; Fischer, Ute

    2015-09-01

    20% of children suffering from high hyperdiploid acute lymphoblastic leukemia develop recurrent disease. The molecular mechanisms are largely unknown. Here, we analyzed the genetic landscape of five patients at relapse, who developed recurrent disease without prior high-risk indication using whole-exome- and whole-genome-sequencing. Oncogenic mutations of RAS pathway genes (NRAS, KRAS, FLT3, n=4) and deactivating mutations of major epigenetic regulators (CREBBP, EP300, each n=2 and ARID4B, EZH2, MACROD2, MLL2, each n=1) were prominent in these cases and virtually absent in non-recurrent cases (n=6) or other pediatric acute lymphoblastic leukemia cases (n=18). In relapse nucleotide variations were detected in cell fate determining transcription factors (GLIS1, AKNA). Structural genomic alterations affected genes regulating B-cell development (IKZF1, PBX1, RUNX1). Eleven novel translocations involved the genes ART4, C12orf60, MACROD2, TBL1XR1, LRRN4, KIAA1467, and ELMO1/MIR1200. Typically, patients harbored only single structural variations, except for one patient who displayed massive rearrangements in the context of a germline tumor suppressor TP53 mutation and a Li-Fraumeni syndrome-like family history. Another patient harbored a germline mutation in the DNA repair factor ATM. In summary, the relapse patients of our cohort were characterized by somatic mutations affecting the RAS pathway, epigenetic and developmental programs and germline mutations in DNA repair pathways. PMID:26189108

  11. LC/MS-based polar metabolite profiling reveals gender differences in serum from patients with myocardial infarction.

    PubMed

    Lee, Jueun; Jung, Youngae; Park, Ju Yeon; Lee, Sang-Hak; Ryu, Do Hyun; Hwang, Geum-Sook

    2015-11-10

    Myocardial infarction (MI), a leading cause of death worldwide, results from prolonged myocardial ischemia with necrosis of myocytes due to a blood supply obstruction to an area of the heart. Many studies have reported gender-related differences in the clinical features of MI, but the reasons for these differences remain unclear. In this study, we applied ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) and various statistical methods-such as multivariate, pathway, and correlation analyses-to identify gender-specific metabolic patterns in polar metabolites in serum from healthy individuals and patients with MI. Patients with diagnosed MI (n=68), and age- and body mass index-matched healthy individuals (n=68), were included in this study. The partial least-squares discriminant analysis (PLS-DA) model was generated from metabolic profiling data, and the score plots showed a significant gender-related difference in patients with MI. Many pathways were associated with amino acids and purines; amino acids, acylcarnitines, and purines differed significantly between male and female patients with MI. This approach could be utilized to observe gender-specific metabolic pattern differences between healthy controls and patients with MI. PMID:26299524

  12. Next Generation Sequencing Reveals Skewing of the T and B Cell Receptor Repertoires in Patients with Wiskott–Aldrich Syndrome

    PubMed Central

    O’Connell, Amy E.; Volpi, Stefano; Dobbs, Kerry; Fiorini, Claudia; Tsitsikov, Erdyni; de Boer, Helen; Barlan, Isil B.; Despotovic, Jenny M.; Espinosa-Rosales, Francisco J.; Hanson, I. Celine; Kanariou, Maria G.; Martínez-Beckerat, Roxana; Mayorga-Sirera, Alvaro; Mejia-Carvajal, Carmen; Radwan, Nesrine; Weiss, Aaron R.; Pai, Sung-Yun; Lee, Yu Nee; Notarangelo, Luigi D.

    2014-01-01

    The Wiskott–Aldrich syndrome (WAS) is due to mutations of the WAS gene encoding for the cytoskeletal WAS protein, leading to abnormal downstream signaling from the T cell and B cell antigen receptors (TCR and BCR). We hypothesized that the impaired signaling through the TCR and BCR in WAS would subsequently lead to aberrations in the immune repertoire of WAS patients. Using next generation sequencing (NGS), the T cell receptor β and B cell immunoglobulin heavy chain (IGH) repertoires of eight patients with WAS and six controls were sequenced. Clonal expansions were identified within memory CD4+ cells as well as in total, naïve and memory CD8+ cells from WAS patients. In the B cell compartment, WAS patient IGH repertoires were also clonally expanded and showed skewed usage of IGHV and IGHJ genes, and increased usage of IGHG constant genes, compared with controls. To our knowledge, this is the first study that demonstrates significant abnormalities of the immune repertoire in WAS patients using NGS. PMID:25101082

  13. What Does a Hospital Survey on Patient Safety Reveal About Patient Safety Culture of Surgical Units Compared With That of Other Units?

    PubMed

    Shu, Qin; Cai, Miao; Tao, Hong-Bing; Cheng, Zhao-Hui; Chen, Jing; Hu, Yin-Huan; Li, Gang

    2015-07-01

    The objective of this study was to examine the strengths and weaknesses of surgical units as compared with other units, and to provide an opportunity to improve patient safety culture in surgical settings by suggesting targeted actions using Hospital Survey on Patient Safety Culture (HSOPSC) investigation.A Hospital Survey on Patient Safety questionnaire was conducted to physicians and nurses in a tertiary hospital in Shandong China. 12 patient safety culture dimensions and 2 outcome variables were measured.A total of 23.5% of respondents came from surgical units, and 76.5% worked in other units. The "overall perceptions of safety" (48.1% vs 40.4%, P < 0.001) and "frequency of events reported" (63.7% vs 60.7%, P = 0.001) of surgical units were higher than those of other units. However, the communication openness (38.7% vs 42.5%, P < 0.001) of surgical units was lower than in other units. Medical workers in surgical units reported more events than those in other units, and more respondents in the surgical units assess "patient safety grade" to be good/excellent. Three dimensions were considered as strengths, whereas 5 other dimensions were considered to be weaknesses in surgical units. Six dimensions have potential to aid in improving events reporting and patient safety grade. Appropriate working times will also contribute to ensuring patient safety. Medical staff with longer years of experience reported more events.Surgical units outperform the nonsurgical ones in overall perception of safety and the number of events reported but underperform in the openness of communication. Four strategies, namely deepening the understanding about patient safety of supervisors, narrowing the communication gap within and across clinical units, recruiting more workers, and employing the event reporting system and building a nonpunitive culture, are recommended to improve patient safety in surgical units in the context of 1 hospital. PMID:26166083

  14. Exome sequencing reveals homozygous TRIM2 mutation in a patient with early onset CMT and bilateral vocal cord paralysis

    PubMed Central

    Pehlivan, Davut; Akdemir, Zeynep Coban; Karaca, Ender; Bayram, Yavuz; Jhangiani, Shalini; Yildiz, Edibe; Muzny, Donna; Uluc, Kayihan; Gibbs, Richard A.; Elcioglu, Nursel; Lupski, James R.; Harel, Tamar

    2015-01-01

    Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited distal symmetric polyneuropathies associated with mutations in genes encoding components essential for normal functioning of the Schwann cell and axon. TRIM2, encoding a ligase that ubiquitinates the neurofilament light chain, was recently associated with early onset neuropathy in a single patient. We report a TRIM2 homozygous missense mutation (c.2000A>C; p.D667A) in a patient with peripheral neuropathy and bilateral vocal cord paralysis, allowing for further delineation of the associated phenotypic spectrum. PMID:25893792

  15. Metabolomic Profiling of Plasma from Patients with Tuberculosis by Use of Untargeted Mass Spectrometry Reveals Novel Biomarkers for Diagnosis

    PubMed Central

    Lee, Kim-Chung; Curreem, Shirly O. T.; To, Kelvin K. W.; Hung, Ivan F. N.; Ho, Deborah T. Y.; Sridhar, Siddharth; Li, Iris W. S.; Ding, Vanessa S. Y.; Koo, Eleanor W. F.; Wong, Chi-Fong; Tam, Sidney; Lam, Ching-Wan; Yuen, Kwok-Yung

    2015-01-01

    Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (n = 46) with those of community-acquired pneumonia (CAP) patients (n = 30) and controls without active infection (n = 30) using ultrahigh-performance liquid chromatography–electrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate and univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(R)-HETE], ceramide (d18:1/16:0), cholesterol sulfate, and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, were identified and found to have significantly higher levels in TB patients than those in CAP patients and controls. In a comparison of TB patients and controls, the four metabolites demonstrated area under the receiver operating characteristic curve (AUC) values of 0.914, 0.912, 0.905, and 0.856, sensitivities of 84.8%, 84.8%, 87.0%, and 89.1%, specificities of 90.0%, 86.7%, 86.7%, and 80.0%, and fold changes of 4.19, 26.15, 6.09, and 1.83, respectively. In a comparison of TB and CAP patients, the four metabolites demonstrated AUC values of 0.793, 0.717, 0.802, and 0.894, sensitivities of 89.1%, 71.7%, 80.4%, and 84.8%, specificities of 63.3%, 66.7%, 70.0%, and 83.3%, and fold changes of 4.69, 3.82, 3.75, and 2.16, respectively. 4α-Formyl-4β-methyl-5α-cholesta-8-en-3β-ol combined with 12(R)-HETE or cholesterol sulfate offered ≥70% sensitivity and ≥90% specificity for differentiating TB patients from controls or CAP patients. These novel plasma biomarkers, especially 12(R)-HETE and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, alone or in

  16. Isolated cholangiolitis revealed by 18F-FDG-PET/CT in a patient with fever of unknown origin.

    PubMed

    Codreanu, Ion; Zhuang, Hongming

    2011-01-01

    Cholangiolitis, inflammation of the cholangioles, is difficult to diagnose by conventional imaging modalities. We report a case of cholangiolitis revealed by fluorine-18 fluoro desoxyglucose positron emission tomography-computerized tomography ((18)F-FDG-PET/CT) after about 9 months of recurrent fevers. A 20 years old girl with a history of recurrent fevers and repeated workups at different hospitals, which didn't diagnosed the source of fever, was admitted with a recent episode of fever. An (18)F-FDG-PET/CT was requested, which demonstrated focal hypermetabolic activity in the lateral segment of the left lobe of the liver. A liver biopsy showed inflammation of small biliary ducts consistent of cholangiolitis. Enterococcus casseliflavus was found on performed cultures. This represents the first case of cholangiolitis revealed by (18)F-FDG-PET/CT imaging. PMID:21512668

  17. Screening of GNAL variants in Brazilian patients with isolated dystonia reveals a novel mutation with partial loss of function.

    PubMed

    Dos Santos, Camila Oliveira; Masuho, Ikuo; da Silva-Júnior, Francisco Pereira; Barbosa, Egberto Reis; Silva, Sonia Maria Cesar Azevedo; Borges, Vanderci; Ferraz, Henrique Ballalai; Rocha, Maria Sheila Guimarães; Limongi, João Carlos Papaterra; Martemyanov, Kirill A; de Carvalho Aguiar, Patricia

    2016-04-01

    GNAL was identified as a cause of dystonia in patients from North America, Europe and Asia. In this study, we aimed to investigate the prevalence of GNAL variants in Brazilian patients with dystonia. Ninety-one patients with isolated idiopathic dystonia, negative for THAP1 and TOR1A mutations, were screened for GNAL variants by Sanger sequencing. Functional characterization of the Gαolf protein variant was performed using the bioluminescence resonance energy transfer assay. A novel heterozygous nonsynonymous variant (p. F133L) was identified in a patient with cervical and laryngeal dystonia since the third decade of life, with no family history. This variant was not identified in healthy Brazilian controls and was not described in 63,000 exomas of the ExAC database. The F133L mutant exhibited significantly elevated levels of basal BRET and severely diminished amplitude of response elicited by dopamine, that both indicate substantial functional impairment of Gαolf in transducing receptor signals, which could be involved in dystonia pathophysiology. GNAL mutations are not a common cause of dystonia in the Brazilian population and have a lower prevalence than THAP1 and TOR1A mutations. We present a novel variant that results in partial Gαolf loss of function. PMID:26810727

  18. To treat or not to treat: metabolomics reveals biomarkers for treatment indication in chronic lymphocytic leukaemia patients

    PubMed Central

    Ferrarini, Alessia; Rupérez, Francisco J.; Kulczynska, Agnieszka; Bolkun, Lukasz; Kloczko, Janusz; Kretowski, Adam; Urbanowicz, Alina; Ciborowski, Michal; Barbas, Coral

    2016-01-01

    In chronic lymphocytic leukaemia (CLL), the clinical course of patients is heterogeneous. Some present an aggressive disease onset and require immediate therapy, while others remain without treatment for years. Current disease staging systems developed by Rai and Binet may be useful in forecasting patient survival time, but do not discriminate between stable and progressive forms of the disease in the early stages. Recently ample attention has been directed towards identifying new disease prognostic markers capable of predicting clinical aggressiveness at diagnosis. In the present study serum samples from stable (n = 51) and progressive (n = 42) CLL patients and controls (n = 45) were used with aim to discover metabolic indicators of disease status. First an LC-MS based metabolic fingerprinting method was used to analyse selected samples in order to find a potential markers discriminating aggressive from indolent patients. Ten of these discovered markers were validated on the whole set of samples with an independent analytical technique. Linoleamide (p = 0.002) in addition to various acylcarnitines (p = 0.001–0.000001) showed to be significant markers of CLL in its aggressive form. Acetylcarnitine (p = 0.05) and hexannoylcarnitine (p = 0.005) were also distinguishable markers of indolent subjects. Forming a panel of selected acylcarnitines and fatty acid amides, it was possible to reach a potentially highly specific and sensitive diagnostic approach (AUC = 0.766). PMID:26988915

  19. Mechanical Perturbations of the Walking Surface Reveal Unaltered Axial Trunk Stiffness in Chronic Low Back Pain Patients

    PubMed Central

    Meijer, Onno G.

    2016-01-01

    Introduction Patients with chronic low back pain (CLBP) often demonstrate altered timing of thorax rotations in the transverse plane during gait. Increased axial trunk stiffness has been claimed to cause this movement pattern. Objectives The objective of this study was to assess whether axial trunk stiffness is increased in gait in CLBP patients. Methods 15 CLBP patients and 15 healthy controls walked on a treadmill that imposed rotational perturbations in the transverse plane. The effect of these perturbations on transverse pelvis, thorax and trunk (thorax relative to pelvis) rotations was evaluated in terms of residual rotations, i.e., the deviation of these movements from the unperturbed patterns. In view of the heterogeneity of the CLBP group, we additionally performed a subgroup comparison between seven patients and seven controls with maximal between-group contrast for timing of thorax rotations. Results Rotations of the walking surface had a clear effect on transverse pelvis, thorax and trunk rotations in all groups. No significant between-group differences on residual transverse pelvis, thorax and trunk rotations were observed. Conclusion Axial trunk stiffness in gait does not appear to be increased in CLBP. Altered timing of thorax rotations in CLBP does not seem to be a result of increased axial trunk stiffness. PMID:27310528

  20. Protein array profiling of tic patient sera reveals a broad range and enhanced immune response against Group A Streptococcus antigens.

    PubMed

    Bombaci, Mauro; Grifantini, Renata; Mora, Marirosa; Reguzzi, Valerio; Petracca, Roberto; Meoni, Eva; Balloni, Sergio; Zingaretti, Chiara; Falugi, Fabiana; Manetti, Andrea G O; Margarit, Immaculada; Musser, James M; Cardona, Francesco; Orefici, Graziella; Grandi, Guido; Bensi, Giuliano

    2009-01-01

    The human pathogen Group A Streptococcus (Streptococcus pyogenes, GAS) is widely recognized as a major cause of common pharyngitis as well as of severe invasive diseases and non-suppurative sequelae associated with the existence of GAS antigens eliciting host autoantibodies. It has been proposed that a subset of paediatric disorders characterized by tics and obsessive-compulsive symptoms would exacerbate in association with relapses of GAS-associated pharyngitis. This hypothesis is however still controversial. In the attempt to shed light on the contribution of GAS infections to the onset of neuropsychiatric or behavioral disorders affecting as many as 3% of children and adolescents, we tested the antibody response of tic patient sera to a representative panel of GAS antigens. In particular, 102 recombinant proteins were spotted on nitrocellulose-coated glass slides and probed against 61 sera collected from young patients with typical tic neuropsychiatric symptoms but with no overt GAS infection. Sera from 35 children with neither tic disorder nor overt GAS infection were also analyzed. The protein recognition patterns of these two sera groups were compared with those obtained using 239 sera from children with GAS-associated pharyngitis. This comparative analysis identified 25 antigens recognized by sera of the three patient groups and 21 antigens recognized by tic and pharyngitis sera, but poorly or not recognized by sera from children without tic. Interestingly, these antigens appeared to be, in quantitative terms, more immunogenic in tic than in pharyngitis patients. Additionally, a third group of antigens appeared to be preferentially and specifically recognized by tic sera. These findings provide the first evidence that tic patient sera exhibit immunological profiles typical of individuals who elicited a broad, specific and strong immune response against GAS. This may be relevant in the context of one of the hypothesis proposing that GAS antigen

  1. White Matter Abnormalities in Patients with Focal Cortical Dysplasia Revealed by Diffusion Tensor Imaging Analysis in a Voxelwise Approach

    PubMed Central

    Fonseca, Viviane de Carvalho; Yasuda, Clarissa Lin; Tedeschi, Guilherme Garlipp; Betting, Luiz Eduardo; Cendes, Fernando

    2012-01-01

    Background: Diffusion tensor imaging (DTI) allows the analysis of changes in microstructure, through the quantification of the spread and direction of water molecules in tissues. We used fractional anisotropy (FA) maps to compare the integrity of WM between patients and controls. The objective of the present study was to investigate WM abnormalities in patients with frontal lobe epilepsy secondary to focal cortical dysplasia (FCD). Materials and Methods: We included 31 controls (12 women, 33.1 ± 9.6 years, mean ± SD) and 22 patients (11 women, 30.4 ± 10.0 years), recruited from our outpatient clinic. They had clinical and EEG diagnosis of frontal lobe epilepsy, secondary to FCD detected on MRI. Patients and controls underwent 3T MRI, including the DTI sequence, obtained in 32 directions and b value of 1000 s/mm2. To process the DTI we used the following softwares: MRIcroN and FSL/TBSS (tract-based spatial statistics). We used a threshold-free cluster enhancement with significance at p < 0.05, fully corrected for multiple comparisons across space. Results: Areas with FA reduction in patients were identified in both hemispheres, mainly in the frontal lobes, cingulum, and forceps minor (p = 0.014), caudate e anterior thalamic radiation (p = 0.034), superior longitudinal fasciculus (p = 0.044), uncinate fasciculus, and inferior fronto-occipital fasciculus (p = 0.042). Conclusion: Our results showed a widespread pattern of WM microstructural abnormalities extending beyond the main lesion seen on MRI (frontal lobe), which may be related to frequent seizures or to the extent of MRI-invisible portion of FCD. PMID:22855684

  2. Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

    PubMed Central

    Zhu, Ling; Wu, Guangyao; Zhou, Xin; Li, Jielan; Wen, Zhi; Lin, Fuchun

    2015-01-01

    Background Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging. Methods A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity. Results Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores. Conclusion Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as

  3. Regulatory aspects

    NASA Astrophysics Data System (ADS)

    Stern, Arthur M.

    1986-07-01

    At this time, there is no US legislation that is specifically aimed at regulating the environmental release of genetically engineered organisms or their modified components, either during the research and development stage or during application. There are some statutes, administered by several federal agencies, whose language is broad enough to allow the extension of intended coverage to include certain aspects of biotechnology. The one possible exception is FIFRA, which has already brought about the registration of several natural microbial pesticides but which also has provision for requiring the registration of “strain improved” microbial pesticides. Nevertheless, there may be gaps in coverage even if all pertinent statutes were to be actively applied to the control of environmental release of genetically modified substances. The decision to regulate biotechnology under TSCA was justified, in part, on the basis of its intended role as a gap-filling piece of environmental legislation. The advantage of regulating biotechnology under TSCA is that this statute, unlike others, is concerned with all media of exposure (air, water, soil, sediment, biota) that may pose health and environmental hazards. Experience may show that extending existing legislation to regulate biotechnology is a poor compromise compared to the promulgation of new legislation specifically designed for this purpose. It appears that many other countries are ultimately going to take the latter course to regulate biotechnology.

  4. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease

    PubMed Central

    Bouquet, Jerome; Soloski, Mark J.; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W.; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher

    2016-01-01

    ABSTRACT Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the “window period” of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. PMID:26873097

  5. Higher Dimensional Meta-State Analysis Reveals Reduced Resting fMRI Connectivity Dynamism in Schizophrenia Patients

    PubMed Central

    Miller, Robyn L.; Yaesoubi, Maziar; Turner, Jessica A.; Mathalon, Daniel; Preda, Adrian; Pearlson, Godfrey; Adali, Tulay; Calhoun, Vince D.

    2016-01-01

    Resting-state functional brain imaging studies of network connectivity have long assumed that functional connections are stationary on the timescale of a typical scan. Interest in moving beyond this simplifying assumption has emerged only recently. The great hope is that training the right lens on time-varying properties of whole-brain network connectivity will shed additional light on previously concealed brain activation patterns characteristic of serious neurological or psychiatric disorders. We present evidence that multiple explicitly dynamical properties of time-varying whole-brain network connectivity are strongly associated with schizophrenia, a complex mental illness whose symptomatic presentation can vary enormously across subjects. As with so much brain-imaging research, a central challenge for dynamic network connectivity lies in determining transformations of the data that both reduce its dimensionality and expose features that are strongly predictive of important population characteristics. Our paper introduces an elegant, simple method of reducing and organizing data around which a large constellation of mutually informative and intuitive dynamical analyses can be performed. This framework combines a discrete multidimensional data-driven representation of connectivity space with four core dynamism measures computed from large-scale properties of each subject’s trajectory, ie., properties not identifiable with any specific moment in time and therefore reasonable to employ in settings lacking inter-subject time-alignment, such as resting-state functional imaging studies. Our analysis exposes pronounced differences between schizophrenia patients (Nsz = 151) and healthy controls (Nhc = 163). Time-varying whole-brain network connectivity patterns are found to be markedly less dynamically active in schizophrenia patients, an effect that is even more pronounced in patients with high levels of hallucinatory behavior. To the best of our knowledge this is

  6. Whole genome sequencing reveals potential targets for therapy in patients with refractory KRAS mutated metastatic colorectal cancer

    PubMed Central

    2014-01-01

    Background The outcome of patients with metastatic colorectal carcinoma (mCRC) following first line therapy is poor, with median survival of less than one year. The purpose of this study was to identify candidate therapeutically targetable somatic events in mCRC patient samples by whole genome sequencing (WGS), so as to obtain targeted treatment strategies for individual patients. Methods Four patients were recruited, all of whom had received > 2 prior therapy regimens. Percutaneous needle biopsies of metastases were performed with whole blood collection for the extraction of constitutional DNA. One tumor was not included in this study as the quality of tumor tissue was not sufficient for further analysis. WGS was performed using Illumina paired end chemistry on HiSeq2000 sequencing systems, which yielded coverage of greater than 30X for all samples. NGS data were processed and analyzed to detect somatic genomic alterations including point mutations, indels, copy number alterations, translocations and rearrangements. Results All 3 tumor samples had KRAS mutations, while 2 tumors contained mutations in the APC gene and the PIK3CA gene. Although we did not identify a TCF7L2-VTI1A translocation, we did detect a TCF7L2 mutation in one tumor. Among the other interesting mutated genes was INPPL1, an important gene involved in PI3 kinase signaling. Functional studies demonstrated that inhibition of INPPL1 reduced growth of CRC cells, suggesting that INPPL1 may promote growth in CRC. Conclusions Our study further supports potential molecularly defined therapeutic contexts that might provide insights into treatment strategies for refractory mCRC. New insights into the role of INPPL1 in colon tumor cell growth have also been identified. Continued development of appropriate targeted agents towards specific events may be warranted to help improve outcomes in CRC. PMID:24943349

  7. Higher Dimensional Meta-State Analysis Reveals Reduced Resting fMRI Connectivity Dynamism in Schizophrenia Patients.

    PubMed

    Miller, Robyn L; Yaesoubi, Maziar; Turner, Jessica A; Mathalon, Daniel; Preda, Adrian; Pearlson, Godfrey; Adali, Tulay; Calhoun, Vince D

    2016-01-01

    Resting-state functional brain imaging studies of network connectivity have long assumed that functional connections are stationary on the timescale of a typical scan. Interest in moving beyond this simplifying assumption has emerged only recently. The great hope is that training the right lens on time-varying properties of whole-brain network connectivity will shed additional light on previously concealed brain activation patterns characteristic of serious neurological or psychiatric disorders. We present evidence that multiple explicitly dynamical properties of time-varying whole-brain network connectivity are strongly associated with schizophrenia, a complex mental illness whose symptomatic presentation can vary enormously across subjects. As with so much brain-imaging research, a central challenge for dynamic network connectivity lies in determining transformations of the data that both reduce its dimensionality and expose features that are strongly predictive of important population characteristics. Our paper introduces an elegant, simple method of reducing and organizing data around which a large constellation of mutually informative and intuitive dynamical analyses can be performed. This framework combines a discrete multidimensional data-driven representation of connectivity space with four core dynamism measures computed from large-scale properties of each subject's trajectory, ie., properties not identifiable with any specific moment in time and therefore reasonable to employ in settings lacking inter-subject time-alignment, such as resting-state functional imaging studies. Our analysis exposes pronounced differences between schizophrenia patients (Nsz = 151) and healthy controls (Nhc = 163). Time-varying whole-brain network connectivity patterns are found to be markedly less dynamically active in schizophrenia patients, an effect that is even more pronounced in patients with high levels of hallucinatory behavior. To the best of our knowledge this is the

  8. Induced pluripotent stem cells reveal functional differences between drugs currently investigated in patients with hutchinson-gilford progeria syndrome.

    PubMed

    Blondel, Sophie; Jaskowiak, Anne-Laure; Egesipe, Anne-Laure; Le Corf, Amelie; Navarro, Claire; Cordette, Véronique; Martinat, Cécile; Laabi, Yacine; Djabali, Karima; de Sandre-Giovannoli, Annachiara; Levy, Nicolas; Peschanski, Marc; Nissan, Xavier

    2014-04-01

    Hutchinson-Gilford progeria syndrome is a rare congenital disease characterized by premature aging in children. Identification of the mutation and related molecular mechanisms has rapidly led to independent clinical trials testing different marketed drugs with a preclinically documented impact on those mechanisms. However, the extensive functional effects of those drugs remain essentially unexplored. We have undertaken a systematic comparative study of the three main treatments currently administered or proposed to progeria-affected children, namely, a farnesyltransferase inhibitor, the combination of an aminobisphosphonate and a statin (zoledronate and pravastatin), and the macrolide antibiotic rapamycin. This work was based on the assumption that mesodermal stem cells, which are derived from Hutchinson-Gilford progeria syndrome-induced pluripotent stem cells expressing major defects associated with the disease, may be instrumental to revealing such effects. Whereas all three treatments significantly improved misshapen cell nuclei typically associated with progeria, differences were observed in terms of functional improvement in prelamin A farnesylation, progerin expression, defective cell proliferation, premature osteogenic differentiation, and ATP production. Finally, we have evaluated the effect of the different drug combinations on this cellular model. This study revealed no additional benefit compared with single-drug treatments, whereas a cytostatic effect equivalent to that of a farnesyltransferase inhibitor alone was systematically observed. Altogether, these results reveal the complexity of the modes of action of different drugs, even when they have been selected on the basis of a similar mechanistic hypothesis, and underscore the use of induced pluripotent stem cell derivatives as a critical and powerful tool for standardized, comparative pharmacological studies. PMID:24598781

  9. Induced Pluripotent Stem Cells Reveal Functional Differences Between Drugs Currently Investigated in Patients With Hutchinson-Gilford Progeria Syndrome

    PubMed Central

    Blondel, Sophie; Jaskowiak, Anne-Laure; Egesipe, Anne-Laure; Le Corf, Amelie; Navarro, Claire; Cordette, Véronique; Martinat, Cécile; Laabi, Yacine; Djabali, Karima; de Sandre-Giovannoli, Annachiara; Levy, Nicolas; Peschanski, Marc

    2014-01-01

    Hutchinson-Gilford progeria syndrome is a rare congenital disease characterized by premature aging in children. Identification of the mutation and related molecular mechanisms has rapidly led to independent clinical trials testing different marketed drugs with a preclinically documented impact on those mechanisms. However, the extensive functional effects of those drugs remain essentially unexplored. We have undertaken a systematic comparative study of the three main treatments currently administered or proposed to progeria-affected children, namely, a farnesyltransferase inhibitor, the combination of an aminobisphosphonate and a statin (zoledronate and pravastatin), and the macrolide antibiotic rapamycin. This work was based on the assumption that mesodermal stem cells, which are derived from Hutchinson-Gilford progeria syndrome-induced pluripotent stem cells expressing major defects associated with the disease, may be instrumental to revealing such effects. Whereas all three treatments significantly improved misshapen cell nuclei typically associated with progeria, differences were observed in terms of functional improvement in prelamin A farnesylation, progerin expression, defective cell proliferation, premature osteogenic differentiation, and ATP production. Finally, we have evaluated the effect of the different drug combinations on this cellular model. This study revealed no additional benefit compared with single-drug treatments, whereas a cytostatic effect equivalent to that of a farnesyltransferase inhibitor alone was systematically observed. Altogether, these results reveal the complexity of the modes of action of different drugs, even when they have been selected on the basis of a similar mechanistic hypothesis, and underscore the use of induced pluripotent stem cell derivatives as a critical and powerful tool for standardized, comparative pharmacological studies. PMID:24598781

  10. Re-analysis of metagenomic sequences from acute flaccid myelitis patients reveals alternatives to enterovirus D68 infection

    PubMed Central

    Breitwieser, Florian P.; Pardo, Carlos A.; Salzberg, Steven L.

    2015-01-01

    Metagenomic sequence data can be used to detect the presence of infectious viruses and bacteria, but normal microbial flora make this process challenging. We re-analyzed metagenomic RNA sequence data collected during a recent outbreak of acute flaccid myelitis (AFM), caused in some cases by infection with enterovirus D68. We found that among the patients whose symptoms were previously attributed to enterovirus D68, one patient had clear evidence of infection with Haemophilus influenzae, and a second patient had a severe Staphylococcus aureus infection caused by a methicillin-resistant strain. Neither of these bacteria were identified in the original study. These observations may have relevance in cases that present with flaccid paralysis because bacterial infections, co-infections or post-infection immune responses may trigger pathogenic processes that may present as poliomyelitis-like syndromes and may mimic AFM.  A separate finding was that large numbers of human sequences were present in each of the publicly released samples, although the original study reported that human sequences had been removed before deposition. PMID:26309730

  11. Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations.

    PubMed

    Toh, Soo Ting; Jin, Yu; Liu, Lizhen; Wang, Jingbo; Babrzadeh, Farbod; Gharizadeh, Baback; Ronaghi, Mostafa; Toh, Han Chong; Chow, Pierce Kah-Hoe; Chung, Alexander Y-F; Ooi, London L-P-J; Lee, Caroline G-L

    2013-04-01

    Chronic hepatitis B virus (HBV) infection is epidemiologically associated with hepatocellular carcinoma (HCC), but its role in HCC remains poorly understood due to technological limitations. In this study, we systematically characterize HBV in HCC patients. HBV sequences were enriched from 48 HCC patients using an oligo-bead-based strategy, pooled together and sequenced using the FLX-Genome-Sequencer. In the tumors, preferential integration of HBV into promoters of genes (P < 0.001) and significant enrichment of integration into chromosome 10 (P < 0.01) were observed. Integration into chromosome 10 was significantly associated with poorly differentiated tumors (P < 0.05). Notably, in the tumors, recurrent integration into the promoter of the human telomerase reverse transcriptase (TERT) gene was found to correlate with increased TERT expression. The preferred region within the HBV genome involved in integration and viral structural alteration is at the 3'-end of hepatitis B virus X protein (HBx), where viral replication/transcription initiates. Upon integration, the 3'-end of the HBx is often deleted. HBx-human chimeric transcripts, the most common type of chimeric transcripts, can be expressed as chimeric proteins. Sequence variation resulting in non-conservative amino acid substitutions are commonly observed in HBV genome. This study highlights HBV as highly mutable in HCC patients with preferential regions within the host and virus genome for HBV integration/structural alterations. PMID:23276797

  12. Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations

    PubMed Central

    2011-01-01

    Background Usher Syndrome type II (USH2) is an autosomal recessive disorder, characterized by moderate to severe hearing impairment and retinitis pigmentosa (RP). Among the three genes implicated, mutations in the USH2A gene account for 74-90% of the USH2 cases. Methods To identify the genetic cause of the disease and determine the frequency of USH2A mutations in a cohort of 88 unrelated USH Spanish patients, we carried out a mutation screening of the 72 coding exons of this gene by direct sequencing. Moreover, we performed functional minigene studies for those changes that were predicted to affect splicing. Results As a result, a total of 144 DNA sequence variants were identified. Based upon previous studies, allele frequencies, segregation analysis, bioinformatics' predictions and in vitro experiments, 37 variants (23 of them novel) were classified as pathogenic mutations. Conclusions This report provide a wide spectrum of USH2A mutations and clinical features, including atypical Usher syndrome phenotypes resembling Usher syndrome type I. Considering only the patients clearly diagnosed with Usher syndrome type II, and results obtained in this and previous studies, we can state that mutations in USH2A are responsible for 76.1% of USH2 disease in patients of Spanish origin. PMID:22004887

  13. Changes in low-frequency fluctuations in patients with antisocial personality disorder revealed by resting-state functional MRI.

    PubMed

    Liu, Huasheng; Liao, Jian; Jiang, Weixiong; Wang, Wei

    2014-01-01

    Antisocial Personality Disorder (APD) is a personality disorder that is most commonly associated with the legal and criminal justice systems. The study of the brain in APD has important implications in legal contexts and in helping ensure social stability. However, the neural contribution to the high prevalence of APD is still unclear. In this study, we used resting-state functional magnetic resonance imaging (fMRI) to investigate the underlying neural mechanisms of APD. Thirty-two healthy individuals and thirty-five patients with APD were recruited. The amplitude of low-frequency fluctuations (ALFF) was analyzed for the whole brain of all subjects. Our results showed that APD patients had a significant reduction in the ALFF in the right orbitofrontal cortex, the left temporal pole, the right inferior temporal gyrus, and the left cerebellum posterior lobe compared to normal controls. We observed that the right orbitofrontal cortex had a negative correlation between ALFF values and MMPI psychopathic deviate scores. Alterations in ALFF in these specific brain regions suggest that APD patients may be associated with abnormal activities in the fronto-temporal network. We propose that our results may contribute in a clinical and forensic context to a better understanding of APD. PMID:24598769

  14. Thirty-five voices in search of an author: what focus groups reveal about patients experiences in managed care settings.

    PubMed

    Frankel, Richard M; Hourigan, Nancy Treger

    2004-01-01

    Surprisingly little direct information from patients is available in the medical literature. Focus groups, which came into use in the 1940s, provide a simple, cost effective way of exploring attitudes and values within market segments or targeted groups. In healthcare, focus groups are being used to track patients' experiences, expectations and satisfaction in order to optimize quality and cost effectiveness. This study reports on a collaboration of three upstate New York Health Maintenance Organizations (HMOs) that used the same focus group format and questions to identify' best practices' and opportunities for improvement. Participants across groups reported similar experiences despite differences in geography and plan organization. Members' most positive comments were about costs, preventive services, ease of paper work and access to sick care, all administrative functions of the health plans. The most negative focused on retaining one's physician, telephone access, providers' medical skills, provider behavior and notification of results, all related to interpersonal/communication issues. We conclude that focus groups are useful for understanding and responding to the 'voice of the customer'. They also have some distinct advantages over forced-choice questionnaires, especially in trying to discover the range of patients' experiences and expectations, though they are not without their challenges. PMID:16808688

  15. Changes in Low-Frequency Fluctuations in Patients with Antisocial Personality Disorder Revealed by Resting-State Functional MRI

    PubMed Central

    Jiang, Weixiong; Wang, Wei

    2014-01-01

    Antisocial Personality Disorder (APD) is a personality disorder that is most commonly associated with the legal and criminal justice systems. The study of the brain in APD has important implications in legal contexts and in helping ensure social stability. However, the neural contribution to the high prevalence of APD is still unclear. In this study, we used resting-state functional magnetic resonance imaging (fMRI) to investigate the underlying neural mechanisms of APD. Thirty-two healthy individuals and thirty-five patients with APD were recruited. The amplitude of low-frequency fluctuations (ALFF) was analyzed for the whole brain of all subjects. Our results showed that APD patients had a significant reduction in the ALFF in the right orbitofrontal cortex, the left temporal pole, the right inferior temporal gyrus, and the left cerebellum posterior lobe compared to normal controls. We observed that the right orbitofrontal cortex had a negative correlation between ALFF values and MMPI psychopathic deviate scores. Alterations in ALFF in these specific brain regions suggest that APD patients may be associated with abnormal activities in the fronto-temporal network. We propose that our results may contribute in a clinical and forensic context to a better understanding of APD. PMID:24598769

  16. Eye-tracking reveals a slowdown of social context processing during intention attribution in patients with schizophrenia

    PubMed Central

    Roux, Paul; Brunet-Gouet, Eric; Passerieux, Christine; Ramus, Franck

    2016-01-01

    Background Schizophrenia is associated with poor theory of mind (ToM), particularly in the attribution of intentions to others. It is also associated with abnormal gaze behaviours and contextual processing. This study investigated to what extent impaired ToM in patients with schizophrenia is related to abnormal processing of social context. Methods We evaluated ToM using a nonverbal intention attribution task based on comic strips depicting social/nonsocial and contextual/noncontextual events while eye movements were recorded. Eye-tracking was used to assess processing time dedicated to visual cues contained in regions of interest identified in a pilot study. We measured cognitive contextual control on a separate task. Results We tested 29 patients with schizophrenia and 29 controls. Compared with controls, patients were slower in intention attribution but not in physical reasoning. They looked longer than controls at contextual cues displayed in the first 2 context pictures of the comic strips, and this difference was greater for intention attribution than for physical reasoning. We found no group difference in time spent looking at noncontextual cues. Patients’ impairment in contextual control did not explain their increased reaction time and gaze duration on contextual cues during intention attribution. Limitations Difficulty may not have been equivalent between intention attribution and physical reasoning conditions. Conclusion Overall, schizophrenia was characterized by a delay in intention attribution related to a slowdown of social context processing that was not explained by worse executive contextual control. PMID:26836621

  17. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

    SciTech Connect

    Willing, B.; Halfvarson, J.; Dicksved, J.; Rosenquist, M.; Jarnerot, G.; Engstrand, L.; Tysk, C.; Jansson, J. K

    2008-08-15

    Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.

  18. Mesenchymal stem cells from osteoporotic patients reveal reduced migration and invasion upon stimulation with BMP-2 or BMP-7.

    PubMed

    Haasters, Florian; Docheva, Denitsa; Gassner, Christoph; Popov, Cvetan; Böcker, Wolfgang; Mutschler, Wolf; Schieker, Matthias; Prall, Wolf Christian

    2014-09-12

    Fractures to the osteoporotic bone feature a delay in callus formation and reduced enchondral ossification. Human mesenchymal stem cells (hMSC), the cellular source of fracture healing, are recruited to the fracture site by cytokines, such as BMP-2 and BMP-7. Aim of the study was to scrutinize hMSC for osteoporosis associated alterations in BMP mediated migration and invasion as well as in extracellular matrix (ECM) binding integrin expression. HMSC were isolated from 18 healthy or osteoporotic donors. Migration was assessed using a collagen IV coated micro-slide linear gradient chamber and time-lapse microscopy. Invasion was analyzed utilizing an ECM coated transmembrane invasion assay. Quantitative real-time RT PCR was performed for the ECM binding integrins α1, α2, α3, α4, α5, α11, αv and β1. HMSC from osteoporotic patients showed a significant increase of migration upon BMP-2 or FCS stimulation, as well as a significant increase of invasion upon BMP-2, BMP-7 or FCS stimulation. Nevertheless, the migration and invasion capacity was significantly decreased compared to healthy controls. Out of all integrins analyzed, collagen binding integrin α2 was significantly downregulated in hMSC from osteoporotic patients. In conclusion, we here demonstrate for the first time osteoporosis associated alterations in BMP mediated hMSC recruitment. These findings may underlie the reduced healing of osteoporotic fractures. Nevertheless, the maintained migration and invasion response upon BMP stimulation illustrates the therapeutic potential of these clinically approved substances in the treatment of osteoporotic fractures. Another therapeutic target may be the downregulation of the collagen binding integrin α2 in hMSC from osteoporotic patients. PMID:25152406

  19. Candidate genes for congenital diaphragmatic hernia from animalmodels: sequencing of fog2 and pdgfra reveals rare variants indiaphragmatic hernia patients

    SciTech Connect

    Bleyl, S.B.; Moshrefi, A.; Shaw, G.M.; Saijoh, Y.; Schoenwolf,G.C.; Pennacchio, L.A.; Slavotinek, A.M.

    2007-05-11

    Congenital diaphragmatic hernia (CDH) is a common, lifethreatening birth defect. Although there is strong evidence implicatinggenetic factors in its pathogenesis, few causative genes have beenidentified, and in isolated CDH, only one de novo, nonsense mutation hasbeen reported in FOG2 in a female with posterior diaphragmaticeventration. We report here that the homozygous null mouse for the Pdgfragene has posterolateral diaphragmatic defects and thus is a model forhuman CDH. We hypothesized that mutations in this gene could cause humanCDH. We sequenced PDGFRa and FOG2 in 96 patients with CDH, of which 53had isolated CDH (55.2 percent), 36 had CDH and additional anomalies(37.5 percent), and 7 had CDH and known chromosome aberrations (7.3percent). For FOG2, we identified novel sequence alterations predictingp.M703L and p.T843A in two patients with isolated CDH that were absent in526 and 564 control chromosomes respectively. These altered amino acidswere highly conserved. However, due to the lack of available parental DNAsamples we were not able to determine if the sequence alterations were denovo. For PDGFRa, we found a single variant predicting p.L967V in apatient with CDH and multiple anomalies that was absent in 768 controlchromosomes. This patient also had one cell with trisomy 15 on skinfibroblast culture, a finding of uncertain significance. Although ourstudy identified sequence variants in FOG2 and PDGFRa, we have notdefinitively established the variants as mutations and we found noevidence that CDH commonly results from mutations in thesegenes.

  20. Genomic Expression Analysis Reveals Strategies of Burkholderia cenocepacia to Adapt to Cystic Fibrosis Patients' Airways and Antimicrobial Therapy

    PubMed Central

    Mira, Nuno P.; Madeira, Andreia; Moreira, Ana Sílvia; Coutinho, Carla P.; Sá-Correia, Isabel

    2011-01-01

    Pulmonary colonization of cystic fibrosis (CF) patients with Burkholderia cenocepacia or other bacteria of the Burkholderia cepacia complex (Bcc) is associated with worse prognosis and increased risk of death. During colonization, the bacteria may evolve under the stressing selection pressures exerted in the CF lung, in particular, those resulting from challenges of the host immune defenses, antimicrobial therapy, nutrient availability and oxygen limitation. Understanding the adaptive mechanisms that promote successful colonization and long-term survival of B. cenocepacia in the CF lung is essential for an improved therapeutic outcome of chronic infections. To get mechanistic insights into these adaptive strategies a transcriptomic analysis, based on DNA microarrays, was explored in this study. The genomic expression levels in two clonal variants isolated during long-term colonization of a CF patient who died from the cepacia syndrome were compared. One of the isolates examined, IST439, is the first B. cenocepacia isolate retrieved from the patient and the other isolate, IST4113, was obtained three years later and is more resistant to different classes of antimicrobials. Approximately 1000 genes were found to be differently expressed in the two clonal variants reflecting a marked reprogramming of genomic expression. The up-regulated genes in IST4113 include those involved in translation, iron uptake (in particular, in ornibactin biosynthesis), efflux of drugs and in adhesion to epithelial lung tissue and to mucin. Alterations related with adaptation to the nutritional environment of the CF lung and to an oxygen-limited environment are also suggested to be a key feature of transcriptional reprogramming occurring during long-term colonization, antibiotic therapy and the progression of the disease. PMID:22216120

  1. CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder.

    PubMed

    Barone, Rita; Sturiale, Luisella; Fiumara, Agata; Palmigiano, Angelo; Bua, Rosaria O; Rizzo, Renata; Zappia, Mario; Garozzo, Domenico

    2016-04-01

    Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2-gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. PMID:26286102

  2. A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer.

    PubMed

    Wu, Fang-Lan; Lu, De-Cheng; Ying, Yan-Ping; Huang, Jin-Jiao; Zhou, Ai-Min; Jiang, Dun-Ke; Chen, Mao-Wei; Yang, Xi; Zhou, Jia; Huang, Hui-Qiao; Zeng, Hong-Yan

    2015-04-01

    The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80-0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08-1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91-1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82-1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63-1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy. PMID:25906091

  3. [Total parenteral nutrition in critical patients. The metabolic-nutritional aspects and effects on immune function of 2 different isocaloric-isonitrogenous regimens].

    PubMed

    Da Pont, M C; Pezzana, A; Demagistris, A; Balzola, F; Cassader, M; Boggio Bertinet, D; Balzola, F

    1994-03-01

    show that the two regimens had a similar impact on nutritional status in both groups. The i.v. infusion of the fat emulsion didn't alter lipid profile and was not associated with an impairment of some aspects of the immune function. In conclusion, our results confirm that fat emulsions represent an important component of i.v. nutritional support regimens and should continue to be used when and where indicated in short-term TPN. However, long-term effects of i.v. infusion of fat emulsions on the immune systems should be further investigated, in a more substantial number of patients. PMID:8204701

  4. Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes

    PubMed Central

    Abu-Safieh, Leen; Alrashed, May; Anazi, Shamsa; Alkuraya, Hisham; Khan, Arif O.; Al-Owain, Mohammed; Al-Zahrani, Jawahir; Al-Abdi, Lama; Hashem, Mais; Al-Tarimi, Salwa; Sebai, Mohammed-Adeeb; Shamia, Ahmed; Ray-zack, Mohamed D.; Nassan, Malik; Al-Hassnan, Zuhair N.; Rahbeeni, Zuhair; Waheeb, Saad; Alkharashi, Abdullah; Abboud, Emad; Al-Hazzaa, Selwa A.F.; Alkuraya, Fowzan S.

    2013-01-01

    Retinal dystrophy (RD) is a heterogeneous group of hereditary diseases caused by loss of photoreceptor function and contributes significantly to the etiology of blindness globally but especially in the industrialized world. The extreme locus and allelic heterogeneity of these disorders poses a major diagnostic challenge and often impedes the ability to provide a molecular diagnosis that can inform counseling and gene-specific treatment strategies. In a large cohort of nearly 150 RD families, we used genomic approaches in the form of autozygome-guided mutation analysis and exome sequencing to identify the likely causative genetic lesion in the majority of cases. Additionally, our study revealed six novel candidate disease genes (C21orf2, EMC1, KIAA1549, GPR125, ACBD5, and DTHD1), two of which (ACBD5 and DTHD1) were observed in the context of syndromic forms of RD that are described for the first time. PMID:23105016

  5. 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors.

    PubMed

    Onion, David; Argent, Richard H; Reece-Smith, Alexander M; Craze, Madeleine L; Pineda, Robert G; Clarke, Philip A; Ratan, Hari L; Parsons, Simon L; Lobo, Dileep N; Duffy, John P; Atherton, John C; McKenzie, Andrew J; Kumari, Rajendra; King, Peter; Hall, Brett M; Grabowska, Anna M

    2016-04-01

    There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor-derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non-small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753-63. ©2016 AACR. PMID:26873730

  6. Meta-Analysis of Public Microarray Datasets Reveals Voltage-Gated Calcium Gene Signatures in Clinical Cancer Patients

    PubMed Central

    Wang, Chih-Yang; Lai, Ming-Derg; Phan, Nam Nhut; Sun, Zhengda; Lin, Yen-Chang

    2015-01-01

    Voltage-gated calcium channels (VGCCs) are well documented to play roles in cell proliferation, migration, and apoptosis; however, whether VGCCs regulate the onset and progression of cancer is still under investigation. The VGCC family consists of five members, which are L-type, N-type, T-type, R-type and P/Q type. To date, no holistic approach has been used to screen VGCC family genes in different types of cancer. We analyzed the transcript expression of VGCCs in clinical cancer tissue samples by accessing ONCOMINE (www.oncomine.org), a web-based microarray database, to perform a systematic analysis. Every member of the VGCCs was examined across 21 different types of cancer by comparing mRNA expression in cancer to that in normal tissue. A previous study showed that altered expression of mRNA in cancer tissue may play an oncogenic role and promote tumor development; therefore, in the present findings, we focus only on the overexpression of VGCCs in different types of cancer. This bioinformatics analysis revealed that different subtypes of VGCCs (CACNA1C, CACNA1D, CACNA1B, CACNA1G, and CACNA1I) are implicated in the development and progression of diverse types of cancer and show dramatic up-regulation in breast cancer. CACNA1F only showed high expression in testis cancer, whereas CACNA1A, CACNA1C, and CACNA1D were highly expressed in most types of cancer. The current analysis revealed that specific VGCCs likely play essential roles in specific types of cancer. Collectively, we identified several VGCC targets and classified them according to different cancer subtypes for prospective studies on the underlying carcinogenic mechanisms. The present findings suggest that VGCCs are possible targets for prospective investigation in cancer treatment. PMID:26147197

  7. Meta-Analysis of Public Microarray Datasets Reveals Voltage-Gated Calcium Gene Signatures in Clinical Cancer Patients.

    PubMed

    Wang, Chih-Yang; Lai, Ming-Derg; Phan, Nam Nhut; Sun, Zhengda; Lin, Yen-Chang

    2015-01-01

    Voltage-gated calcium channels (VGCCs) are well documented to play roles in cell proliferation, migration, and apoptosis; however, whether VGCCs regulate the onset and progression of cancer is still under investigation. The VGCC family consists of five members, which are L-type, N-type, T-type, R-type and P/Q type. To date, no holistic approach has been used to screen VGCC family genes in different types of cancer. We analyzed the transcript expression of VGCCs in clinical cancer tissue samples by accessing ONCOMINE (www.oncomine.org), a web-based microarray database, to perform a systematic analysis. Every member of the VGCCs was examined across 21 different types of cancer by comparing mRNA expression in cancer to that in normal tissue. A previous study showed that altered expression of mRNA in cancer tissue may play an oncogenic role and promote tumor development; therefore, in the present findings, we focus only on the overexpression of VGCCs in different types of cancer. This bioinformatics analysis revealed that different subtypes of VGCCs (CACNA1C, CACNA1D, CACNA1B, CACNA1G, and CACNA1I) are implicated in the development and progression of diverse types of cancer and show dramatic up-regulation in breast cancer. CACNA1F only showed high expression in testis cancer, whereas CACNA1A, CACNA1C, and CACNA1D were highly expressed in most types of cancer. The current analysis revealed that specific VGCCs likely play essential roles in specific types of cancer. Collectively, we identified several VGCC targets and classified them according to different cancer subtypes for prospective studies on the underlying carcinogenic mechanisms. The present findings suggest that VGCCs are possible targets for prospective investigation in cancer treatment. PMID:26147197

  8. [A primary epileptogenic tuber revealed after corpus callosotomy in a patient with tuberous sclerosis complex and multiple tubers].

    PubMed

    Sato, Keisuke; Iwasaki, Masaki; Uematsu, Mitsugu; Nakasato, Nobukazu; Tominaga, Teiji

    2013-05-01

    Identification of primary epileptogenic tuber is often challenging in patients with bilateral multiple tubers in tuberous sclerosis complex. We report a 3 year old girl with tuberous sclerosis complex presenting with intractable epilepsy and multiple tubers, who was successfully treated by corpus callosotomy and subsequent resective surgery. She initially presented with West syndrome which was intractable to ACTH therapy and multiple antiepileptic medications. Her EEG was characterized by generalized and multifocal spikes, and by non-focal changes at seizure onset. Ictal single photon emission computed tomography(SPECT)showed no focal hyperperfusion. Total corpus callosotomy was performed to alleviate her drop attacks. Post-operatively, interictal spikes were completely lateralized to the right hemisphere. Since her seizures were still kept uncontrolled with medications, second pre-surgical evaluation was planned and ictal SPECT disclosed focal hyperperfusion at a tuber in the right frontal lobe. After complete resection of the right frontal tuber, she was completely seizure free on antiepileptic medications for 1 year with no additional neurological deficits. Generalized or multifocal electroencephalographic(EEG)spikes are occasionally lateralized to one hemisphere after corpus callosotomy, which may help identifying the primary epileptogenic focus. Repeat pre-surgical evaluation is important after corpus callosotomy in patients with generalized or multifocal epileptiforms in EEG. PMID:23648659

  9. Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease.

    PubMed

    Mardinoglu, Adil; Agren, Rasmus; Kampf, Caroline; Asplund, Anna; Uhlen, Mathias; Nielsen, Jens

    2014-01-01

    Several liver disorders result from perturbations in the metabolism of hepatocytes, and their underlying mechanisms can be outlined through the use of genome-scale metabolic models (GEMs). Here we reconstruct a consensus GEM for hepatocytes, which we call iHepatocytes2322, that extends previous models by including an extensive description of lipid metabolism. We build iHepatocytes2322 using Human Metabolic Reaction 2.0 database and proteomics data in Human Protein Atlas, which experimentally validates the incorporated reactions. The reconstruction process enables improved annotation of the proteomics data using the network centric view of iHepatocytes2322. We then use iHepatocytes2322 to analyse transcriptomics data obtained from patients with non-alcoholic fatty liver disease. We show that blood concentrations of chondroitin and heparan sulphates are suitable for diagnosing non-alcoholic steatohepatitis and for the staging of non-alcoholic fatty liver disease. Furthermore, we observe serine deficiency in patients with NASH and identify PSPH, SHMT1 and BCAT1 as potential therapeutic targets for the treatment of non-alcoholic steatohepatitis. PMID:24419221

  10. Targeted Next-Generation Sequencing Reveals Hot Spots and Doubly Heterozygous Mutations in Chinese Patients with Familial Cardiomyopathy

    PubMed Central

    Zhao, Yue; Feng, Yue; Zhang, Yun-Mei; Ding, Xiao-Xue; Song, Yu-Zhu; Zhang, A-Mei; Liu, Li; Zhang, Hong; Ding, Jia-Huan; Xia, Xue-Shan

    2015-01-01

    As a common cardiac disease mainly caused by gene mutations in sarcomeric cytoskeletal, calcium-handling, nuclear envelope, desmosomal, and transcription factor genes, inherited cardiomyopathy is becoming one of the major etiological factors of sudden cardiac death (SCD) and heart failure (HF). This disease is characterized by remarkable genetic heterogeneity, which makes it difficult to screen for pathogenic mutations using Sanger sequencing. In the present study, three probands, one with familial hypertrophic cardiomyopathy (FHCM) and two with familial dilated cardiomyopathy (FDCM), were recruited together with their respective family members. Using next-generation sequencing technology (NGS), 24 genes frequently known to be related to inherited cardiomyopathy were screened. Two hot spots (TNNI3-p.Arg145Gly, and LMNA-p.Arg190Trp) and double (LMNA-p.Arg190Trp plus MYH7-p.Arg1045His) heterozygous mutations were found to be highly correlated with familial cardiomyopathy. FDCM patients with doubly heterozygous mutations show a notably severe phenotype as we could confirm in our study; this indicates that the double mutations had a dose effect. In addition, it is proposed that genetic testing using NGS technology can be used as a cost-effective screening tool and help guide the treatment of patients with familial cardiomyopathy particularly regarding the risk of family members who are clinically asymptomatic. PMID:26199943

  11. Transcriptional Analysis of Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promising Target for Repigmenting Vitiligo Patients.

    PubMed

    Regazzetti, Claire; Joly, Florence; Marty, Carine; Rivier, Michel; Mehul, Bruno; Reiniche, Pascale; Mounier, Carine; Rival, Yves; Piwnica, David; Cavalié, Marine; Chignon-Sicard, Bérengère; Ballotti, Robert; Voegel, Johannes; Passeron, Thierry

    2015-12-01

    Vitiligo affects 1% of the worldwide population. Halting disease progression and repigmenting the lesional skin represent the two faces of therapeutic challenge in vitiligo. We performed transcriptome analysis on lesional, perilesional, and non-depigmented skin from vitiligo patients and on matched skin from healthy subjects. We found a significant increase in CXCL10 in non-depigmented and perilesional vitiligo skin compared with levels in healthy control skin; however, neither CXCL10 nor other immune factors were deregulated in depigmented vitiligo skin. Interestingly, the WNT pathway, which is involved in melanocyte differentiation, was altered specifically in vitiligo skin. We demonstrated that oxidative stress decreases WNT expression/activation in keratinocytes and melanocytes. We developed an ex vivo skin model and confirmed the decrease activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated ex vivo depigmented skin from vitiligo patients and successfully induced differentiation of resident stem cells into pre-melanocytes. Our results shed light on the previously unrecognized role of decreased WNT activation in the prevention of melanocyte differentiation in depigmented vitiligo skin. Furthermore, these results support further clinical exploration of WNT agonists to repigment vitiligo lesions. PMID:26322948

  12. The mental representation of singular and plural nouns in Algerian Arabic as revealed through auditory priming in agrammatic aphasic patients.

    PubMed

    Mimouni, Z; Kehayia, E; Jarema, G

    1998-01-01

    Working within the theoretical framework of prosodic nonconcatenative morphology developed by McCarthy (1975) for Semitic languages, we addressed, in the present paper, the issues of lexical representation, morphological relatedness, and modes of access in Algerian Arabic--a dialect of Standard Arabic--in an auditory morphological priming experiment. More specifically, we investigated the process of word recognition of singular and plural nouns in the performance of 24 non-brain-damaged subjects and 2 Algerian-speaking agrammatic aphasics. Plurals in Arabic involve either suffixation as in the sound plural (e.g., lbas "dress"/lbasat "dresses"), or stem-internal changes as in the broken plurals (e.g., kursi "chair"/krasa "chairs"). Our findings reveal a differential processing of the two forms, indicating whole word access for broken plurals and decomposition into word and suffix for suffixed plurals. Further, the evidence suggests for Algerian Arabic an architecture of the lexicon reflecting a family-like organization which takes into account language-specific features. PMID:9448932

  13. Microsatellite-based genotyping of Candida parapsilosis sensu stricto isolates reveals dominance and persistence of a particular epidemiological clone among neonatal intensive care unit patients.

    PubMed

    Romeo, Orazio; Delfino, Demetrio; Cascio, Antonio; Lo Passo, Carla; Amorini, Maria; Romeo, Daniela; Pernice, Ida

    2013-01-01

    In this study, using multilocus microsatellite analysis, we report the genetic characterization of 27 Candida parapsilosis isolates recovered in two different periods of time (2007-2009 and 2011-2012) from infants hospitalized in the neonatal intensive care unit of a hospital in Messina, Italy. The results revealed the persistence and dominance of a particular infectious genotype among NICU patients and highlight the power of the used microsatellite markers in clarifying epidemiologic associations, detect micro-evolutionary variations and facilitating the recognition of outbreaks. PMID:23022715

  14. Whole-exome sequencing of a patient with severe and complex hemostatic abnormalities reveals a possible contributing frameshift mutation in C3AR1

    PubMed Central

    Leinøe, Eva; Nielsen, Ove Juul; Jønson, Lars; Rossing, Maria

    2016-01-01

    The increasing availability of genome-wide analysis has made it possible to rapidly sequence the exome of patients with undiagnosed or unresolved medical conditions. Here, we present the case of a 64-yr-old male patient with schistocytes in the peripheral blood smear and a complex and life-threatening coagulation disorder causing recurrent venous thromboembolic events, severe thrombocytopenia, and subdural hematomas. Whole-exome sequencing revealed a frameshift mutation (C3AR1 c.355-356dup, p.Asp119Alafs*19) resulting in a premature stop codon in C3AR1 (Complement Component 3a Receptor 1). Based on this finding, atypical hemolytic uremic syndrome was suspected because of a genetic predisposition, and a targeted treatment regime with eculizumab was initiated. Life-threatening hemostatic abnormalities would most likely have persisted had it not been for the implementation of whole-exome sequencing in this particular clinical setting. PMID:27551680

  15. [Surgery for dysgnathia: medico-legal aspects].

    PubMed

    Mangoni, E D

    1990-01-01

    Recent developments in surgical treatments of dentofacial deformities, regarding the modern and far-reaching views of health protection, are taken into account by the Author. He refers to the normative provisions revealing the interest of the legal health system in this pathology. He asserts the rightfulness of the treatment and the hypotheses of unlawfulness; he mentions aspects of personal identification of a patient surgically treated whose physiognomy is modified, in the light of identification regulations. Special profiles of the patient's consent and participation in options on alternative treatments are outlined; basic deontological rules are recalled as well (risks/benefits proportion, technical ability of dentist and auxiliaries, fitness of place, accurate anaesthesiological planning). PMID:2291707

  16. Genome-Wide Association Study Reveals a Polymorphism in the Podocyte Receptor RANK for the Decline of Renal Function in Coronary Patients

    PubMed Central

    Rein, Philipp; Saely, Christoph H.; Kinz, Elena; Vonbank, Alexander; Fraunberger, Peter; Drexel, Heinz

    2014-01-01

    Impaired kidney function is a significant health problem and a major concern in clinical routine and is routinely determined by decreased glomerular filtration rate (GFR). In contrast to single assessment of a patients' kidney function providing only limited information on patients' health, serial measurements of GFR clearly improves the validity of diagnosis. The decline of kidney function has recently been reported to be predictive for mortality and vascular events in coronary patients. However, it has not been investigated for genetic association in GWA studies. This study investigates for the first time the association of cardiometabolic polymorphisms with the decline of estimated GFR during a 4 year follow up in 583 coronary patients, using the Cardio-Metabo Chip. We revealed a suggestive association with 3 polymorphisms, surpassing genome-wide significance (p = 4.0 e-7). The top hit rs17069906 (p = 5.6 e-10) is located within the genomic region of RANK, recently demonstrated to be an important player in the adaptive recovery response in podocytes and suggested as a promising therapeutic target in glomerular diseases. PMID:25478860

  17. Traditional and targeted exome sequencing reveals common, rare and novel functional deleterious variants in RET signaling complex in a cohort of living US patients with urinary tract malformations

    PubMed Central

    Chatterjee, Rajshekhar; Ramos, Enrique; Hoffman, Mary; VanWinkle, Jessica; Martin, Daniel R; Davis, Thomas K; Hoshi, Masato; Hmiel, Stanley P; Beck, Anne; Hruska, Keith; Coplen, Doug; Liapis, Helen; Mitra, Robi; Druley, Todd; Austin, Paul; Jain, Sanjay

    2013-01-01

    Signaling by the glial cell line-derived neurotrophic factor (GDNF)-RET receptor tyrosine kinase and SPRY1, a RET repressor, is essential for early urinary tract development. Individual or a combination of GDNF, RET and SPRY1 mutant alleles in mice cause renal malformations reminiscent of congenital anomalies of the kidney or urinary tract (CAKUT) in humans and distinct from renal agenesis phenotype in complete GDNF or RET null mice. We sequenced GDNF, SPRY1 and RET in 122 unrelated living CAKUT patients to discover deleterious mutations that cause CAKUT. Novel or rare deleterious mutations in GDNF or RET were found in 6 unrelated patients. A family with duplicated collecting system had a novel mutation, RETR831Q, which showed markedly decreased GDNF dependent MAPK activity. Two patients with RET-G691S polymorphism harbored additional rare non-synonymous variants GDNF-R93W and RET-R982C. The patient with double RET-G691S/R982C genotype had multiple defects including renal dysplasia, megaureters and cryptorchidism. Presence of both mutations were necessary to affect RET activity. Targeted whole exome and next-generation sequencing revealed a novel deleterious mutation G443D in GFRα1, the co-receptor for RET, in this patient. Pedigree analysis indicated that the GFRα1 mutation was inherited from the unaffected mother and the RET mutations from the unaffected father. Our studies indicate that 5% of living CAKUT patients harbor deleterious rare variants or novel mutations in GDNF-GFRα1-RET pathway. We provide evidence for the coexistence of deleterious rare and common variants in genes in the same pathway as a cause of CAKUT and discovered novel phenotypes associated with the RET pathway. PMID:22729463

  18. Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation.

    PubMed

    Kim, Sang Hu; Clark, Shawn T; Surendra, Anuradha; Copeland, Julia K; Wang, Pauline W; Ammar, Ron; Collins, Cathy; Tullis, D Elizabeth; Nislow, Corey; Hwang, David M; Guttman, David S; Cowen, Leah E

    2015-11-01

    The microbiome shapes diverse facets of human biology and disease, with the importance of fungi only beginning to be appreciated. Microbial communities infiltrate diverse anatomical sites as with the respiratory tract of healthy humans and those with diseases such as cystic fibrosis, where chronic colonization and infection lead to clinical decline. Although fungi are frequently recovered from cystic fibrosis patient sputum samples and have been associated with deterioration of lung function, understanding of species and population dynamics remains in its infancy. Here, we coupled high-throughput sequencing of the ribosomal RNA internal transcribed spacer 1 (ITS1) with phenotypic and genotypic analyses of fungi from 89 sputum samples from 28 cystic fibrosis patients. Fungal communities defined by sequencing were concordant with those defined by culture-based analyses of 1,603 isolates from the same samples. Different patients harbored distinct fungal communities. There were detectable trends, however, including colonization with Candida and Aspergillus species, which was not perturbed by clinical exacerbation or treatment. We identified considerable inter- and intra-species phenotypic variation in traits important for host adaptation, including antifungal drug resistance and morphogenesis. While variation in drug resistance was largely between species, striking variation in morphogenesis emerged within Candida species. Filamentation was uncoupled from inducing cues in 28 Candida isolates recovered from six patients. The filamentous isolates were resistant to the filamentation-repressive effects of Pseudomonas aeruginosa, implicating inter-kingdom interactions as the selective force. Genome sequencing revealed that all but one of the filamentous isolates harbored mutations in the transcriptional repressor NRG1; such mutations were necessary and sufficient for the filamentous phenotype. Six independent nrg1 mutations arose in Candida isolates from different patients

  19. Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation

    PubMed Central

    Kim, Sang Hu; Clark, Shawn T.; Surendra, Anuradha; Copeland, Julia K.; Wang, Pauline W.; Ammar, Ron; Collins, Cathy; Tullis, D. Elizabeth; Nislow, Corey; Hwang, David M.; Guttman, David S.; Cowen, Leah E.

    2015-01-01

    The microbiome shapes diverse facets of human biology and disease, with the importance of fungi only beginning to be appreciated. Microbial communities infiltrate diverse anatomical sites as with the respiratory tract of healthy humans and those with diseases such as cystic fibrosis, where chronic colonization and infection lead to clinical decline. Although fungi are frequently recovered from cystic fibrosis patient sputum samples and have been associated with deterioration of lung function, understanding of species and population dynamics remains in its infancy. Here, we coupled high-throughput sequencing of the ribosomal RNA internal transcribed spacer 1 (ITS1) with phenotypic and genotypic analyses of fungi from 89 sputum samples from 28 cystic fibrosis patients. Fungal communities defined by sequencing were concordant with those defined by culture-based analyses of 1,603 isolates from the same samples. Different patients harbored distinct fungal communities. There were detectable trends, however, including colonization with Candida and Aspergillus species, which was not perturbed by clinical exacerbation or treatment. We identified considerable inter- and intra-species phenotypic variation in traits important for host adaptation, including antifungal drug resistance and morphogenesis. While variation in drug resistance was largely between species, striking variation in morphogenesis emerged within Candida species. Filamentation was uncoupled from inducing cues in 28 Candida isolates recovered from six patients. The filamentous isolates were resistant to the filamentation-repressive effects of Pseudomonas aeruginosa, implicating inter-kingdom interactions as the selective force. Genome sequencing revealed that all but one of the filamentous isolates harbored mutations in the transcriptional repressor NRG1; such mutations were necessary and sufficient for the filamentous phenotype. Six independent nrg1 mutations arose in Candida isolates from different patients

  20. Genetic signatures of Mycobacterium tuberculosis Nonthaburi genotype revealed by whole genome analysis of isolates from tuberculous meningitis patients in Thailand

    PubMed Central

    Coker, Olabisi Oluwabukola; Ngamphiw, Chumpol; Tongsima, Sissades; Regmi, Sanjib Mani; Clark, Taane G.; Ong, Rick Twee Hee; Teo, Yik-Ying; Prammananan, Therdsak; Palittapongarnpim, Prasit

    2016-01-01

    Genome sequencing plays a key role in understanding the genetic diversity of Mycobacterium tuberculosis (M.tb). The genotype-specific character of M. tb contributes to tuberculosis severity and emergence of drug resistance. Strains of M. tb complex can be classified into seven lineages. The Nonthaburi (NB) genotype, belonging to the Indo-Oceanic lineage (lineage 1), has a unique spoligotype and IS6110-RFLP pattern but has not previously undergone a detailed whole genome analysis. In addition, there is not much information available on the whole genome analysis of M. tb isolates from tuberculous meningitis (TBM) patients in public databases. Isolates CSF3053, 46-5069 and 43-13838 of NB genotype were obtained from the cerebrospinal fluids of TBM Thai patients in Siriraj Hospital, Bangkok. The whole genomes were subjected to high throughput sequencing. The sequence data of each isolate were assembled into draft genome. The sequences were also aligned to reference genome, to determine genomic variations. Single nucleotide polymorphisms (SNPs) were obtained and grouped according to the functions of the genes containing them. They were compared with SNPs from 1,601 genomes, representing the seven lineages of M. tb complex, to determine the uniqueness of NB genotype. Susceptibility to first-line, second-line and other antituberculosis drugs were determined and related to the SNPs previously reported in drug-resistant related genes. The assembled genomes have an average size of 4,364,461 bp, 4,154 genes, 48 RNAs and 64 pseudogenes. A 500 base pairs deletion, which includes ppe50, was found in all isolates. RD239, specific for members of Indo Oceanic lineage, and RD147c were identified. A total of 2,202 SNPs were common to the isolates and used to classify the NB strains as members of sublineage 1.2.1. Compared with 1,601 genomes from the seven lineages of M. tb complex, mutation G2342203C was found novel to the isolates in this study. Three mutations (T28910C, C1180580T

  1. Modeling human retinal development with patient-specific iPS cells reveals multiple roles for VSX2

    PubMed Central

    Phillips, M. Joseph; Perez, Enio T.; Martin, Jessica M.; Reshel, Samantha T.; Wallace, Kyle A.; Capowski, Elizabeth E.; Singh, Ruchira; Wright, Lynda S.; Clark, Eric M.; Barney, Patrick M.; Stewart, Ron; Dickerson, Sarah J.; Miller, Michael J.; Percin, E. Ferda; Thomson, James A.; Gamm, David M.

    2014-01-01

    Human induced pluripotent stem cells (hiPSCs) have been shown to differentiate along the retinal lineage in a manner that mimics normal mammalian development. Under certain culture conditions hiPSCs form optic vesicle-like structures (OVs), which contain proliferating progenitors capable of yielding all neural retina (NR) cell types over time. Such observations imply conserved roles for regulators of retinogenesis in hiPSC-derived cultures and the developing embryo. However, whether and to what extent this assumption holds true has remained largely uninvestigated. We examined the role of a key NR transcription factor, Visual System Homeobox 2 (VSX2), using hiPSCs derived from a patient with microphthalmia caused by an R200Q mutation in the VSX2 homeodomain region. No differences were noted between (R200Q)VSX2 and sibling control hiPSCs prior to OV generation. Thereafter, (R200Q)VSX2 hiPSC-OVs displayed a significant growth deficit compared to control hiPSC-OVs, as well as increased production of retinal pigmented epithelium (RPE) at the expense of NR cell derivatives. Furthermore, (R200Q)VSX2 hiPSC-OVs failed to produce bipolar cells, a distinctive feature previously observed in Vsx2 mutant mice. (R200Q)VSX2 hiPSC-OVs also demonstrated delayed photoreceptor maturation, which could be overcome via exogenous expression of wildtype VSX2 at early stages of retinal differentiation. Finally, RNAseq analysis on isolated hiPSC-OVs implicated key transcription factors and extracellular signaling pathways as potential downstream effectors of VSX2-mediated gene regulation. Our results establish hiPSC-OVs as versatile model systems to study retinal development at stages not previously accessible in humans, and support the bona fide nature of hiPSC-OV-derived retinal progeny. PMID:24532057

  2. Deep Sequencing of Protease Inhibitor Resistant HIV Patient Isolates Reveals Patterns of Correlated Mutations in Gag and Protease

    PubMed Central

    Tan, Zhiqiang; Oliveira, Glenn; Yuan, Jinyun; Okulicz, Jason F.; Torbett, Bruce E.; Levy, Ronald M.

    2015-01-01

    While the role of drug resistance mutations in HIV protease has been studied comprehensively, mutations in its substrate, Gag, have not been extensively cataloged. Using deep sequencing, we analyzed a unique collection of longitudinal viral samples from 93 patients who have been treated with therapies containing protease inhibitors (PIs). Due to the high sequence coverage within each sample, the frequencies of mutations at individual positions were calculated with high precision. We used this information to characterize the variability in the Gag polyprotein and its effects on PI-therapy outcomes. To examine covariation of mutations between two different sites using deep sequencing data, we developed an approach to estimate the tight bounds on the two-site bivariate probabilities in each viral sample, and the mutual information between pairs of positions based on all the bounds. Utilizing the new methodology we found that mutations in the matrix and p6 proteins contribute to continued therapy failure and have a major role in the network of strongly correlated mutations in the Gag polyprotein, as well as between Gag and protease. Although covariation is not direct evidence of structural propensities, we found the strongest correlations between residues on capsid and matrix of the same Gag protein were often due to structural proximity. This suggests that some of the strongest inter-protein Gag correlations are the result of structural proximity. Moreover, the strong covariation between residues in matrix and capsid at the N-terminus with p1 and p6 at the C-terminus is consistent with residue-residue contacts between these proteins at some point in the viral life cycle. PMID:25894830

  3. Regulatory aspects on nanomedicines.

    PubMed

    Sainz, Vanessa; Conniot, João; Matos, Ana I; Peres, Carina; Zupancic, Eva; Moura, Liane; Silva, Liana C; Florindo, Helena F; Gaspar, Rogério S

    2015-12-18

    Nanomedicines have been in the forefront of pharmaceutical research in the last decades, creating new challenges for research community, industry, and regulators. There is a strong demand for the fast development of scientific and technological tools to address unmet medical needs, thus improving human health care and life quality. Tremendous advances in the biomaterials and nanotechnology fields have prompted their use as promising tools to overcome important drawbacks, mostly associated to the non-specific effects of conventional therapeutic approaches. However, the wide range of application of nanomedicines demands a profound knowledge and characterization of these complex products. Their properties need to be extensively understood to avoid unpredicted effects on patients, such as potential immune reactivity. Research policy and alliances have been bringing together scientists, regulators, industry, and, more frequently in recent years, patient representatives and patient advocacy institutions. In order to successfully enhance the development of new technologies, improved strategies for research-based corporate organizations, more integrated research tools dealing with appropriate translational requirements aiming at clinical development, and proactive regulatory policies are essential in the near future. This review focuses on the most important aspects currently recognized as key factors for the regulation of nanomedicines, discussing the efforts under development by industry and regulatory agencies to promote their translation into the market. Regulatory Science aspects driving a faster and safer development of nanomedicines will be a central issue for the next years. PMID:26260323

  4. Functional connectivity-based signatures of schizophrenia revealed by multiclass pattern analysis of resting-state fMRI from schizophrenic patients and their healthy siblings

    PubMed Central

    2013-01-01

    Background Recently, a growing number of neuroimaging studies have begun to investigate the brains of schizophrenic patients and their healthy siblings to identify heritable biomarkers of this complex disorder. The objective of this study was to use multiclass pattern analysis to investigate the inheritable characters of schizophrenia at the individual level, by comparing whole-brain resting-state functional connectivity of patients with schizophrenia to their healthy siblings. Methods Twenty-four schizophrenic patients, twenty-five healthy siblings and twenty-two matched healthy controls underwent the resting-state functional Magnetic Resonance Imaging (rs-fMRI) scanning. A linear support vector machine along with principal component analysis was used to solve the multi-classification problem. By reconstructing the functional connectivities with high discriminative power, three types of functional connectivity-based signatures were identified: (i) state connectivity patterns, which characterize the nature of disruption in the brain network of patients with schizophrenia; (ii) trait connectivity patterns, reflecting shared connectivities of dysfunction in patients with schizophrenia and their healthy siblings, thereby providing a possible neuroendophenotype and revealing the genetic vulnerability to develop schizophrenia; and (iii) compensatory connectivity patterns, which underlie special brain connectivities by which healthy siblings might compensate for an increased genetic risk for developing schizophrenia. Results Our multiclass pattern analysis achieved 62.0% accuracy via leave-one-out cross-validation (p < 0.001). The identified state patterns related to the default mode network, the executive control network and the cerebellum. For the trait patterns, functional connectivities between the cerebellum and the prefrontal lobe, the middle temporal gyrus, the thalamus and the middle temporal poles were identified. Connectivities among the right precuneus

  5. Transcriptome Reveals 1400-Fold Upregulation of APOA4-APOC3 and 1100-Fold Downregulation of GIF in the Patients with Polycythemia-Induced Gastric Injury

    PubMed Central

    Dan, Zeng; Gusang, Lamu; Dawa, Ciren; Nie, Yuqiang

    2015-01-01

    High-altitude polycythemia (HAPC) inducing gastric mucosal lesion (GML) is still out of control and molecular mechanisms remain widely unknown. To address the issues, endoscopy and histopathological analyses were performed. Meanwhile, microarray-based transcriptome profiling was conducted in the gastric mucosa from 3 pairs of healthy subjects and HAPC-induced GML patients. HAPC caused morphological changes and pathological damages of the gastric mucosa of GML patients. A total of 10304 differentially expressed genes (DEGs) were identified, including 4941 up-regulated and 5363 down-regulated DEGs in gastric mucosa of GML patients compared with healthy controls (fold change ≥2, P<0.01 and FDR <0.01). Particularly, apolipoprotein genes APOA4 and APOC3 were 1473-fold and 1468-fold up-regulated in GML patients compared with the controls. In contrast, gastric intrinsic factor (GIF) was 1102-fold down-regulated in GML patients compared with the controls. APOA4 (chr11:116691770–116691711), APOC3 (chr11:116703530–116703589) and GIF (chr11:59603362–59603303) genes are all located on chromosome 11. APOA4 and APOC3 act as an inhibitor of gastric acid secretion while gastric acid promotes ulceration. GIF deficiency activates a program of acute anemia, which may antagonize polycythemia while polycythemia raises the risk of GML. Therefore, the present findings reveal that HAPC-induced GML inspires the protection responses by up-regulating APOA4 and APOC3, and down-regulating GIF. These results may offer the basic information for the treatment of HAPC-induced gastric lesion in the future. PMID:26485402

  6. Demonstration of Trophozoites of G. Lamblia in Ileal Mucosal Biopsy Specimens May Reveal Giardiasis in Patients With Significantly Inflamed Parasite-free Duodenal Mucosa.

    PubMed

    Oberhuber, Georg; Mesteri, Ildiko; Kopf, Wolfram; Müller, Heiko

    2016-09-01

    In the majority of individuals, infestation with trophozoites of Giardia lamblia (synonymous G. duodenalis or G. intestinalis) leads to a self-limited disease. Whereas most duodenal biopsies with chronic giardiasis show little or no inflammatory reaction, some patients may develop a severe disease with significant mucosal inflammation and various degrees of villous blunting. Occasionally, the histologic changes may resemble those of celiac disease. In this paper, we describe 11 patients, 5 of them female, with chronic giardiasis and demonstrable G. lamblia in ileal biopsies. The median age was 45 years (35 to 62 y), with male patients being at least 10 years younger than female patients. All of the duodenal biopsies showed at least mild villous blunting (grading: mild, marked, or total). In the mucosa an increased number of plasma cells and lymphocytes was observed. Furthermore, varying numbers of granulocytes were found in the lamina propria and in the epithelial layer. In 1 case only, the number of intraepithelial lymphocytes was >40/100 epithelial cells thus mirroring the histologic picture of celiac disease with a flat mucosa (with negative celiac disease-specific serological findings). Interestingly enough, all mucosal biopsy specimens from the duodenum were parasite free. Therefore, giardiasis could only be revealed by the demonstration of trophozoites of G. lamblia in biopsy specimens from the terminal ileum, which had been taken simultaneously or several weeks later. In contrast to duodenal biopsies, the ileal mucosa appeared either normal or only mildly inflamed in this setting. All patients but 1 were symptomatic, with chronic diarrhea being the leading symptom. Symptoms resolved after antibiotic therapy. This study demonstrates that giardiasis may be associated with a significant duodenal pathology in biopsy specimens without discernible parasites. In the cases described here infestation with G. lamblia was only proven histologically by examination of

  7. Proteomic Analysis in Type 2 Diabetes Patients before and after a Very Low Calorie Diet Reveals Potential Disease State and Intervention Specific Biomarkers

    PubMed Central

    Dharuri, Harish K.; Jeyakar, Skhandhan; Snel, Marieke; Juhasz, Peter; Lynch, Moira; Hines, Wade; Li, Xiaohong; Jazet, Ingrid M.; Adourian, Aram; Hilbers, Peter A. J.; Smit, Johannes W. A.; Van Dijk, Ko Willems

    2014-01-01

    Very low calorie diets (VLCD) with and without exercise programs lead to major metabolic improvements in obese type 2 diabetes patients. The mechanisms underlying these improvements have so far not been elucidated fully. To further investigate the mechanisms of a VLCD with or without exercise and to uncover possible biomarkers associated with these interventions, blood samples were collected from 27 obese type 2 diabetes patients before and after a 16-week VLCD (Modifast ∼450 kcal/day). Thirteen of these patients followed an exercise program in addition to the VCLD. Plasma was obtained from 27 lean and 27 obese controls as well. Proteomic analysis was performed using mass spectrometry (MS) and targeted multiple reaction monitoring (MRM) and a large scale isobaric tags for relative and absolute quantitation (iTRAQ) approach. After the 16-week VLCD, there was a significant decrease in body weight and HbA1c in all patients, without differences between the two intervention groups. Targeted MRM analysis revealed differences in several proteins, which could be divided in diabetes-associated (fibrinogen, transthyretin), obesity-associated (complement C3), and diet-associated markers (apolipoproteins, especially apolipoprotein A-IV). To further investigate the effects of exercise, large scale iTRAQ analysis was performed. However, no proteins were found showing an exercise effect. Thus, in this study, specific proteins were found to be differentially expressed in type 2 diabetes patients versus controls and before and after a VLCD. These proteins are potential disease state and intervention specific biomarkers. Trial Registration Controlled-Trials.com ISRCTN76920690 PMID:25415563

  8. Gene expression profiling reveals differences in microenvironment interaction between patients with chronic lymphocytic leukemia expressing high versus low ZAP70 mRNA

    PubMed Central

    Stamatopoulos, Basile; Haibe-Kains, Benjamin; Equeter, Carole; Meuleman, Nathalie; Sorée, Anne; De Bruyn, Cécile; Hanosset, Delphine; Bron, Dominique; Martiat, Philippe; Lagneaux, Laurence

    2009-01-01

    Background Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia, but mechanisms by which its higher expression leads to a poor outcome must still be fully explained. Design and Methods In an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B cells from chronic lymphocytic leukemia patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Two groups of 7 patients were compared, selected on the basis of either high or low ZAP70 mRNA expression. Results Twenty-seven genes were differentially expressed with an FDR<10%, and several genes were significant predictors of treatment-free survival (TFS) and/or overall survival; PDE8A and FCRL family genes (down-regulated in ZAP70+ patients) could predict TFS and overall survival; ITGA4 mRNA (up-regulated in ZAP70+ patients) could significantly predict overall survival. Importantly, gene set enrichment analysis revealed overrepresentation of adhesion/migration genes. We therefore investigated in vitro adhesion/migration capacity of chronic lymphocytic leukemia cells into a stromal microenvironment or in response to conditioned medium. We showed that ZAP70+ cells had better adhesion/migration capacities and only ZAP70+ patient cells responded to microenvironment contact by CXCR4 downregulation. Conclusions We concluded that several prognostic factors are the reflection of microenvironment interactions and that the increased adhesion/migratory capacity of ZAP70+ cells in their microenvironment can explain their better survival and thus the aggressiveness of the disease. PMID:19377082

  9. PTCH 1 staining of pancreatic neuroendocrine tumor (PNET) samples from patients with and without multiple endocrine neoplasia (MEN-1) syndrome reveals a potential therapeutic target

    PubMed Central

    Gurung, Buddha; Hua, Xianxin; Runske, Melissa; Bennett, Bonita; LiVolsi, Virginia; Roses, Robert; Fraker, Douglas A; Metz, David C

    2015-01-01

    Pancreatic neuroendocrine tumors (PNETs) are rare, indolent tumors that may occur sporadically or develop in association with well-recognized hereditary syndromes, particularly multiple endocrine neoplasia type 1 (MEN-1). We previously demonstrated that the hedgehog (HH) signaling pathway was aberrantly up-regulated in a mouse model that phenocopies the human MEN-1 syndrome, Men1l/l;RipCre, and that inhibition of this pathway suppresses MEN-1 tumor cell proliferation. We hypothesized that the HH signaling pathway is similarly upregulated in human PNETs. We performed immunohistochemical (IHC) staining for PTCH1 in human fresh and archival PNET specimens to examine whether human sporadic and MEN-1-associated PNETs revealed similar abnormalities as in our mouse model and correlated the results with clinical and demographic factors of the study cohort. PTCH1 staining was positive in 12 of 22 PNET patients (55%). Four of 5 MEN-1 patients stained for PTCH1 (p = 0.32 as compared with sporadic disease patients). Nine of 16 patients with metastatic disease stained for PTCH1 as compared with zero of 3 with localized disease only (p = 0.21). No demographic or clinical features appeared to be predictive of PTCH 1 positivity and PTCH 1 positivity per se was not predictive of clinical outcome. PTCH1, a marker of HH pathway up regulation, is detectable in both primary and metastatic tumors in more than 50% of PNET patients. Although no clinical or demographic factors predict PTCH1 positivity and PTCH1 positivity does not predict clinical outcome, the frequency of expression alone indicates that perturbation of this pathway with agents such as Vismodegib, an inhibitor of Smoothened (SMO), should be examined in future clinical trials. PMID:25482929

  10. Investigation of fasciculation and elongation protein ζ-1 (FEZ1) in peripheral blood reveals differences in gene expression in patients with schizophrenia

    PubMed Central

    Vachev, TI; Stoyanova, VK; Ivanov, HY; Minkov, IN; Popov, NT

    2015-01-01

    Schizophrenia (SZ) is a chronic neuropsychiatric disorder characterized by affective, neuromorphological and cognitive impairment, deteriorated social functioning and psychosis with underlying molecular abnormalities, including gene expression changes. Observations have suggested that fasciculation and elongation protein ζ-1 (FEZ1) may be implicated in the pathogenesis of schizophrenia. Nevertheless, our current knowledge of the expression of FEZ1 in peripheral blood of schizophrenia patients remains unclear. The purpose of this study was to identify the characteristic gene expression patterns of FEZ1 in peripheral blood samples from schizophrenia patients. We performed quantitative reverse-transcriptase (qRT-PCR) analysis using peripheral blood from drug-free schizophrenia patients (n = 29) and age and gender-matched general population controls (n = 24). For the identification of FEZ1 gene expression patterns, we applied a comparative threshold cycle (CT) method. A statistically significant difference of FEZ1 mRNA level was revealed in schizophrenia subjects compared to healthy controls (p = 0.0034). To the best of our knowledge, this study is the first describing a down-regulation of FEZ1 gene expression in peripheral blood of patients with schizophrenia. Our results suggested a possible functional role of FEZ1 in the pathogenesis of schizophrenia and confirmed the utility of peripheral blood samples for molecular profiling of psychiatric disorders including schizophrenia. The current study describes FEZ1 gene expression changes in peripheral blood of patients with schizophrenia with significantly down-regulation of FEZ1 mRNA. Thus, our results provide support for a model of SZ pathogenesis that includes the effects of FEZ1 expression. PMID:26929903

  11. Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency.

    PubMed

    Jamsheer, Aleksander; Olech, Ewelina M; Kozłowski, Kazimierz; Niedziela, Marek; Sowińska-Seidler, Anna; Obara-Moszyńska, Monika; Latos-Bieleńska, Anna; Karczewski, Marek; Zemojtel, Tomasz

    2016-07-01

    Desbuquois dysplasia type 2 (DBQD2) is a rare recessively inherited skeletal genetic disorder characterized by severe prenatal and postnatal growth retardation, generalized joint laxity with dislocation of large joints and facial dysmorphism. The condition was recently described to result from autosomal recessive mutations in XYLT1, encoding the enzyme xylosyltransferase-1. In this paper, we report on a Polish patient with DBQD2 who presented with severe short stature of prenatal onset, joint laxity, psychomotor retardation and multiple radiological abnormalities including short metacarpals, advanced bone age and exaggerated trochanters. Endocrinological examinations revealed that sleep-induced growth hormone (GH) release and GH peak in clonidine- and glucagon-induced provocative tests as well as insulin-like growth factor 1 (IGF-1) and IGF-binding protein-3 levels were all markedly decreased, confirming deficiency of GH secretion. Bone age, unlikely to GH deficiency, was significantly advanced. To establish the diagnosis at a molecular level, we performed whole-exome sequencing and bioinformatic analysis in the index patient, which revealed compound heterozygous XYLT1 mutations: c.595C>T(p.Gln199*) and c.1651C>T(p.Arg551Cys), both of which are novel. Sanger sequencing showed that the former mutation was inherited from the healthy mother, whereas the latter one most probably occurred de novo. Our study describes the first case of DBQD2 resulting from compound heterozygous XYLT1 mutation, expands the mutational spectrum of the disease and provides evidence that the severe growth retardation and microsomia observed in DBQD2 patients may result not only from the skeletal dysplasia itself but also from GH and IGF-1 deficiency. PMID:27030147

  12. Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease

    PubMed Central

    Bade, Geetanjali; Khan, Meraj Alam; Srivastava, Akhilesh Kumar; Khare, Parul; Solaiappan, Krishna Kumar; Guleria, Randeep; Palaniyar, Nades; Talwar, Anjana

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process. PMID:25125975

  13. Revealing very small FLT3 ITD mutated clones by ultra-deep sequencing analysis has important clinical implications in AML patients

    PubMed Central

    Zuffa, Elisa; Franchini, Eugenia; Papayannidis, Cristina; Baldazzi, Carmen; Simonetti, Giorgia; Testoni, Nicoletta; Abbenante, Maria Chiara; Paolini, Stefania; Sartor, Chiara; Parisi, Sarah; Marconi, Giovanni; Cattina, Federica; Bochicchio, Maria Teresa; Venturi, Claudia; Ottaviani, Emanuela; Cavo, Michele; Martinelli, Giovanni

    2015-01-01

    FLT3 internal tandem duplication (ITD), one of the most frequent mutations in Acute Myeloid Leukemia (AML), is reported to be an unstable marker, as it can evolve from FLT3 ITD- to ITD+ during the disease course. A single-gene sensitive mutational screening approach may be helpful for better clarifying the exact timing of mutation occurrence, especially when FLT3 ITD appears to occur late, at disease progression. We developed an amplicon-based ultra-deep-sequencing (UDS) approach for FLT3 mutational screening. We exploited this highly sensitive technology for the retrospective screening of diagnosis, relapse and follow-up samples of 5 out of 256 cytogenetically normal (CN-) AML who were FLT3 wild-type at presentation, but tested ITD+ at relapse or disease progression. Our study revealed that all patients carried a small ITD+ clone at diagnosis, which was undetectable by routine analysis (0,2–2% abundance). The dynamics of ITD+ clones from diagnosis to disease progression, assessed by UDS, reflected clonal evolution under treatment pressure. UDS appears as a valuable tool for FLT3 mutational screening and for the assessment of minimal residual disease (MRD) during follow-up, by detecting small ITD+ clones that may survive chemotherapy, evolve over time and definitely worsen the prognosis of CN-AML patients. PMID:26384303

  14. RNA-seq analysis of hippocampal tissues reveals novel candidate genes for drug refractory epilepsy in patients with MTLE-HS.

    PubMed

    Dixit, Aparna Banerjee; Banerjee, Jyotirmoy; Srivastava, Arpna; Tripathi, Manjari; Sarkar, Chitra; Kakkar, Aanchal; Jain, Mukesh; Chandra, P Sarat

    2016-05-01

    Array-based profiling studies have shown implication of aberrant gene expression patterns in epileptogenesis. We have performed transcriptome analysis of hippocampal tissues resected from patients with MTLE-HS using RNAseq approach. Healthy tissues from tumour margins obtained during tumour surgeries were used as non-epileptic controls. RNA sequencing was performed using standard protocols on Illumina HiSeq 2500 platform. Differential gene expression analysis of the RNAseq data revealed 56 significantly regulated genes in MTLE patients. Gene cluster analysis identified 3 important hubs of genes mostly linked to, neuroinflammation and innate immunity, synaptic transmission and neuronal network modulation which are supportive of intrinsic severity hypothesis of pharmacoresistance. This study identified various genes like FN1 which is central in our analysis, NEUROD6, RELN, TGFβR2, NLRP1, SCRT1, CSNK2B, SCN1B, CABP1, KIF5A and antisense RNAs like AQP4-AS1 and KIRREL3-AS2 providing important insight into the understanding of the pathophysiology or genomic basis of drug refractory epilepsy due to MTS. PMID:27094248

  15. Personality aspects in multiple sclerosis.

    PubMed

    Diana, R; Grosz, A; Mancini, E

    1985-12-01

    To test the claim that peculiar personality bias is detectable in multiple sclerosis (MS) we used the Szondi test to investigate the psychodynamic aspects of 110 MS patients in comparison with 200 healthy subjects. MS patients appeared to have a greater need for love in a passive form than normal people, rigid defense mechanisms, difficulty in resolving their inner conflicts either by sublimation or by internalization of satisfactory new emotional experiences, feelings of autoaggressiveness, and many symptoms of depression. Some of these aspects correlate with the severity of the disease, others seem to date back to early childhood as peculiar personality patterns. An investigation of childhood events in 110 controls confirmed that MS patients had had many more unhappy experiences in childhood than might commonly be expected. Further, the oft-reported psychiatric troubles preceding MS clinical onset suggest that at least in some MS patients there are specific gaps in personality structure dating back to early phases of their development. PMID:4086262

  16. The clinical spectrum of the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Clinical features in 20 patients and aspects of pathophysiology.

    PubMed

    Martin, R W; Duffy, J; Engel, A G; Lie, J T; Bowles, C A; Moyer, T P; Gleich, G J

    1990-07-15

    We describe the clinical spectrum of the L-tryptophan-associated eosinophilia-myalgia syndrome in 20 patients. In all but one case, patients met the Centers for Disease Control (CDC) case definition for the syndrome: peripheral blood eosinophilia (eosinophil count greater than 1.0 x 10(9)/L) and generalized, disabling myalgias without other recognized causes. Three patients with eosinophilia and myalgia developed eosinophilic fasciitis, and 4 other patients developed, respectively, pneumonitis and myocarditis, neuropathy culminating in respiratory failure, encephalopathy, and fibrosis about the common bile duct. No relation was apparent between dose or duration of L-tryptophan exposure and the eosinophilia-myalgia syndrome. No organic contaminants were identified in L-tryptophan preparations taken by patients or asymptomatic users when these preparations were examined by chromatography or mass spectroscopy. Biopsy specimens in 12 patients showed a mononuclear exudate with a variable admixture of eosinophils in affected tissues, including skin, fascia, muscle, and some viscera. Eosinophil toxic granule proteins, major basic protein, and eosinophil-derived neurotoxin were elevated in the serum and urine of patients compared with normal control subjects (P less than 0.01 and P less than 0.02, respectively). Immunofluorescence showed major basic protein deposited outside of eosinophils in affected tissues, indicating that toxic granule proteins are released in diseased organs. Treatment included withdrawal of L-tryptophan in all cases. Corticosteroids were prescribed for 16 patients and diuretics alone for 1 patient; no drugs were prescribed for 3 patients. Four patients have recovered fully, others are stable or slowly recovering, and 1 is gravely ill despite prolonged treatment. PMID:2360751

  17. Genomewide Histone H3 Lysine 9 Acetylation Profiling in CD4+ T Cells Revealed Endoplasmic Reticulum Stress Deficiency in Patients with Acute-on-chronic Liver Failure.

    PubMed

    Jin, L; Wang, K; Liu, H; Chen, T; Yang, Y; Ma, X; Wang, J; Li, Y; Du, D; Zhao, Y; He, Y

    2015-11-01

    Acute-on-chronic liver failure (ACLF) displayed 'sepsis-like' immune paralysis. Little is known about the role of CD4+ T lymphocytes, the primary regulator of innate and adopted immune system, played in ACLF. Acetylation of histone H3 lysine 9 (H3K9ac), a key epigenetic modification, tightly controls gene transcription. Whether and how does H3K9ac modification regulate CD4+ T cells in ACLF remains unclear. PBMCs were isolated from patients with ACLF, immune tolerance of chronic hepatitis B (CHB-T) and immune active of chronic hepatitis B (CHB-A). Then, CD4+ T lymphocytes were purified by magnetic microbeads, and the purity was confirmed by flow cytometry. H3K9ac variations were analysed in CD4+ T cells using chromatin immunoprecipitation microarray and then confirmed by quantitative PCR. Whole-genome H3K9 acetylation analyses were conducted by bioinformatics. A total of 70 genes were differently modified in H3K9ac between CHB-A and ACLF groups, while 44 genes were differently modified in H3K9ac between CHB-T and ACLF groups. Clustering algorithm analysis showed patients with ACLF displayed 'sepsis-like' immune paralysis. Functional analysis showed endoplasmic reticulum (ER) stress, or downstream pathway-related genes, such as BIP, ATF4, PER1, CSNK1D, IRF3, BNIP1, AKT1 and UBC, were differentially modified in ACLF. We profiled H3K9 acetyl modification in CD4+ T lymphocytes from HBV-infected patients with three different immune states, that is ACLF, immune tolerance and immune active phases. ACLF displayed 'sepsis-like' immune paralysis. ER stress in CD4+ T lymphocytes attributed to ACLF. This study provides some useful clues for revealing the mechanisms underlying ACLF. PMID:26173605

  18. Cohort Study of Airway Mycobiome in Adult Cystic Fibrosis Patients: Differences in Community Structure between Fungi and Bacteria Reveal Predominance of Transient Fungal Elements.

    PubMed

    Kramer, Rolf; Sauer-Heilborn, Annette; Welte, Tobias; Guzman, Carlos A; Abraham, Wolf-Rainer; Höfle, Manfred G

    2015-09-01

    The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult patients with cystic fibrosis (CF) during nonexacerbation periods and under continuous antibiotic treatment. Molecular fingerprinting based on single-strand conformation polymorphism (SSCP) analysis revealed fundamental differences between bacterial and fungal communities. Both groups of microorganisms were taxonomically classified by identification of gene sequences (16S rRNA and internal transcript spacer), and prevalences of single taxa were determined for the entire cohort. Major bacterial pathogens were frequently observed, whereas fungi of known pathogenicity in CF were detected only in low numbers. Fungal species richness increased without reaching a constant level (saturation), whereas bacterial richness showed saturation after 50 patients were analyzed. In contrast to bacteria, a large number of fungal species were observed together with high fluctuations over time and among patients. These findings demonstrated that the mycobiome was dominated by transient species, which strongly suggested that the main driving force was their presence in inhaled air rather than colonization. Considering the high exposure of human airways to fungal spores, we concluded that fungi have low colonization abilities in CF, and colonization by pathogenic fungal species may be considered a rare event. A comprehensive understanding of the conditions promoting fungal colonization may offer the opportunity to prevent colonization and substantially reduce or even eliminate fungus-related disease progression in CF. PMID:26135861

  19. Cohort Study of Airway Mycobiome in Adult Cystic Fibrosis Patients: Differences in Community Structure between Fungi and Bacteria Reveal Predominance of Transient Fungal Elements

    PubMed Central

    Sauer-Heilborn, Annette; Welte, Tobias; Guzman, Carlos A.; Abraham, Wolf-Rainer; Höfle, Manfred G.

    2015-01-01

    The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult patients with cystic fibrosis (CF) during nonexacerbation periods and under continuous antibiotic treatment. Molecular fingerprinting based on single-strand conformation polymorphism (SSCP) analysis revealed fundamental differences between bacterial and fungal communities. Both groups of microorganisms were taxonomically classified by identification of gene sequences (16S rRNA and internal transcript spacer), and prevalences of single taxa were determined for the entire cohort. Major bacterial pathogens were frequently observed, whereas fungi of known pathogenicity in CF were detected only in low numbers. Fungal species richness increased without reaching a constant level (saturation), whereas bacterial richness showed saturation after 50 patients were analyzed. In contrast to bacteria, a large number of fungal species were observed together with high fluctuations over time and among patients. These findings demonstrated that the mycobiome was dominated by transient species, which strongly suggested that the main driving force was their presence in inhaled air rather than colonization. Considering the high exposure of human airways to fungal spores, we concluded that fungi have low colonization abilities in CF, and colonization by pathogenic fungal species may be considered a rare event. A comprehensive understanding of the conditions promoting fungal colonization may offer the opportunity to prevent colonization and substantially reduce or even eliminate fungus-related disease progression in CF. PMID:26135861

  20. Clinicopathological aspects of the neuropathy of neurogastrointestinal encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie-Tooth presentation.

    PubMed

    Said, Gérard; Lacroix, Catherine; Planté-Bordeneuve, Violaine; Messing, Bernard; Slama, Abdelhamid; Crenn, Pascal; Nivelon-Chevallier, Annie; Bedenne, Laurent; Soichot, Pierre; Manceau, E; Rigaud, Daniel; Guiochon-Mantel, Anne; Matuchansky, Claude

    2005-06-01

    We report on four patients with severe polyneuropathy associated with intestinal pseudoobstruction (MNGIE). Three patients presented characteristic supranuclear ophthalmoplegia, and hyperdense signals on T2 weighted cerebral MRI and dystrophic mitochondria in Schwann cells and in endothelial cells in nerve biopsy specimens. Two of these patients had a Charcot-Marie-Tooth (CMT) presentation. All three were heterozygous for a recessively transmitted double substitution in the TP gene: Glu286Lys/Glu289Ala, Asp156Gly/Leu177Pro and Glu289Ala/Gly387Asp. The fourth patient, who was the only patient of this series with an affected sib, had no oculomotor manifestations, nor T2 hyperdense signals on brain MRI, and no TP gene mutation and or morphological abnormalities of mitochondria on electron microscopic examination. He was the only patient of this series with an affected sib. The three patients with the full MNGIE syndrome died before the age of 30 years. Detailed results of nerve pathology show that severe axonal degeneration is associated with segmental abnormalities of the myelin sheath in this syndrome which appears genetically heterogeneous. Our findings suggest that only ophthalmoplegia and hyperdense signals on cerebral MRI are directly related to the mitochondriopathy. PMID:15742109

  1. Immunotherapy in all aspects.

    PubMed

    Hanci, Deniz; Şahin, Ethem; Muluk, Nuray Bayar; Cingi, Cemal

    2016-06-01

    Allergen immunotherapy is a form of long-term treatment that decreases symptoms for many people with allergic rhinitis, allergic asthma, conjunctivitis (eye allergy) or stinging insect allergy. In this review, we presented the important topics in immunotherapy. The important aspects of immunotherapy are considered to be "Immunologıcal responses to immunotherapy"; "The principal types of immunotherapy"; "Effectiveness"; "Indications"; "Contraindications"; "Allergen immunotherapy in children"; "Safety"; and "Anaphylactic reactions after immunotherapy". The principal types of immunotherapy are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy. Both of them can be used in indicated cases. When using SCIT, physicians must be more careful because of reported rare fatal cases. The risks and benefits of continuing allergen immunotherapy in patients who have experienced severe systemic reactions should be carefully considered. PMID:25673026

  2. AIRTRAQ8 OPTICAL LARYNGOSCOPE FOR TRACHEAL INTUBATION IN A PATIENT WITH AN UNCOMMON GIANT LIPOMA ON THE POSTERIOR ASPECT OF NECK AND ADDITIONAL RISK FACTORS OF ANTICIPATED DIFFICULT AIRWAY: A CASE REPORT.

    PubMed

    Dimitriou, Vassilios; El Kouny, Amr; Al Harbi, Mohammed; Wambi, Freddie; Tawfeeq, Nasser; Tanweer, Aziz; Al Atassi, Abdulallem; Geldhof, Georges

    2015-10-01

    Patients with restricted neck movement present a difficult airway situation because of improper positioning and inadequate extension of the atlanto-occipital joint. The Airtraq optical laryngoscope is a new single use device that permits an indirect view of the glottis without the need to achieve a direct line of sight by conventional use of the 'sniffing position'. We present and discuss a case of uncommon giant lipoma (16 x 12 x 10 cm) in the posterior aspect of the neck in addition with other independent factors of anticipated difficult airway, intubated successfully in the semi-lateral position with the use of Airtraq. PMID:26860029

  3. Prehospital antiplatelet use and functional status on admission of patients with non-haemorrhagic moyamoya disease: a nationwide retrospective cohort study (J-ASPECT study)

    PubMed Central

    Onozuka, Daisuke; Hagihara, Akihito; Nishimura, Kunihiro; Kada, Akiko; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Suzuki, Akifumi; Kataoka, Hiroharu; Nakamura, Fumiaki; Kamitani, Satoru; Nishimura, Ataru; Kurogi, Ryota; Sayama, Tetsuro; Iihara, Koji

    2016-01-01

    Objectives To elucidate the association between antiplatelet use in patients with non-haemorrhagic moyamoya disease before hospital admission and good functional status on admission in Japan. Design Retrospective, multicentre, non-randomised, observational study. Setting Nationwide registry data in Japan. Participants A total of 1925 patients with non-haemorrhagic moyamoya disease admitted between 1 April 2012 and 31 March 2014 in Japan. Main outcome measure We performed propensity score-matched analysis to examine the association between prehospital antiplatelet use and no significant disability on hospital admission, as defined by a modified Rankin Scale score of 0 or 1. Results Propensity-matched patients who received prehospital antiplatelet drugs were associated with a good outcome on hospital admission (OR adjusted for all covariates, 3.82; 95% CI 1.22 to 11.99) compared with those who did not receive antiplatelet drugs prior to hospital admission. Conclusions Prehospital antiplatelet use was significantly associated with good functional status on hospital admission among patients with non-haemorrhagic moyamoya disease in Japan. Our results suggest that prehospital antiplatelet use should be considered when evaluating outcomes of patients with non-haemorrhagic moyamoya disease. PMID:27008684

  4. Functional analysis reveals splicing mutations of the CASQ2 gene in patients with CPVT: implication for genetic counselling and clinical management.

    PubMed

    Roux-Buisson, Nathalie; Rendu, John; Denjoy, Isabelle; Guicheney, Pascale; Goldenberg, Alice; David, Nadine; Faivre, Laurence; Barthez, Olivier; Danieli, Gian Antonio; Marty, Isabelle; Lunardi, Joel; Fauré, Julien

    2011-09-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and severe arrhythmogenic disorder. Although usually transmitted in a recessive form, few cases of dominant mutations have been reported. Thirteen mutations in the CASQ2 gene have been reported so far in association with CPVT. We performed molecular analysis of the CASQ2 gene in 43 probands with CPVT and identified eight mutations in five patients. Six mutations were novel: one was a single nucleotide deletion, three affected consensus splice sites, and two had unknown consequences: the c.939 + 5G>C and the synonymous c.381C>T variations. We demonstrated that these two variations affected CASQ2 splicing using a splicing minigene assay. These data increased significantly the number of CASQ2 mutations described in association with CPVT, revealed the high prevalence of splicing and truncating mutations in this gene and brought new insight regarding the dominant inheritance of the disease. Moreover, our report of the first splicing abnormalities in CASQ2 caused by intronic mutation or synonymous change underlines the absolute necessity to perform extensive molecular analysis for genetic diagnosis and counseling of CPVT. PMID:21618644

  5. Next generation sequencing of stage IV squamous cell lung cancers reveals an association of PI3K aberrations and evidence of clonal heterogeneity in patients with brain metastases

    PubMed Central

    Paik, Paul K.; Shen, Ronglai; Won, Helen; Rekhtman, Natasha; Wang, Lu; Sima, Camelia S.; Arora, Arshi; Seshan, Venkatraman; Ladanyi, Marc; Berger, Michael F.; Kris, Mark G.

    2015-01-01

    Large-scale genomic characterization of squamous cell lung cancers (SQCLC) has revealed several putative oncogenic drivers. There are, however, little data to suggest that these alterations have clinical relevance. We performed comprehensive genomic profiling of 79 stage IV SQCLCs (including next-generation sequencing) and analyzed differences in the clinical characteristics of two major SQCLC subtypes: FGFR1 amplified and PI3K aberrant. Patients with PI3K aberrant tumors had aggressive disease marked by worse survival (median OS 8.6 vs. 19.1 mo, p<0.001), higher metastatic burden (>3 organs 18% vs. 3%, p=0.025), and greater incidence of brain metastases (27% vs. 0% in others, p<0.001). We performed whole-exome and RNA sequencing on paired brain metastases and primary lung cancers to elucidate the metastatic process to brain. SQCLC primaries that gave rise to brain metastases exhibited truncal PTEN loss. SQCLC brain metastases exhibited a high degree of genetic heterogeneity and evidence of clonal differences between their primary sites. PMID:25929848

  6. M1 and M2 macrophage proteolytic and angiogenic profile analysis in atherosclerotic patients reveals a distinctive profile in type 2 diabetes.

    PubMed

    Roma-Lavisse, Charlotte; Tagzirt, Madjid; Zawadzki, Christophe; Lorenzi, Rodrigo; Vincentelli, André; Haulon, Stephan; Juthier, Francis; Rauch, Antoine; Corseaux, Delphine; Staels, Bart; Jude, Brigitte; Van Belle, Eric; Susen, Sophie; Chinetti-Gbaguidi, Giulia; Dupont, Annabelle

    2015-07-01

    This study aimed to investigate atherosclerotic mediators' expression levels in M1 and M2 macrophages and to focus on the influence of diabetes on M1/M2 profiles. Macrophages from 36 atherosclerotic patients (19 diabetics and 17 non-diabetics) were cultured with interleukin-1β (IL-1β) or IL-4 to induce M1 or M2 phenotype, respectively. The atherosclerotic mediators' expression was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results showed that M1 and M2 macrophages differentially expressed mediators involved in proteolysis and angiogenesis processes. The proteolytic balance (matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1), MMP-9/plasminogen activator inhibitor-1 (PAI-1) and MMP-9/tissue factor pathway inhibitor-2 (TFPI-2) ratios) was higher in M1 versus M2, whereas M2 macrophages presented higher angiogenesis properties (increased vascular endothelial growth factor/TFPI-2 and tissue factor/TFPI-2 ratios). Moreover, M1 macrophages from diabetics displayed more important proangiogenic and proteolytic activities than non-diabetics. This study reveals that M1 and M2 macrophages could differentially modulate major atherosclerosis-related pathological processes. Moreover, M1 macrophages from diabetics display a deleterious phenotype that could explain the higher plaque vulnerability observed in these subjects. PMID:25966737

  7. Aspects of physical medicine and rehabilitation in the treatment of deconditioned patients in the acute care setting: the role of skeletal muscle.

    PubMed

    Quittan, Michael

    2016-02-01

    Skeletal muscles are essential for movement as well as for survival. Knowledge about the organ skeletal muscle is underrepresented. Ageing and multiple chronic diseases are accompanied by loss of muscle mass, termed "muscle wasting". Nevertheless, muscles are one of the target organs within the rehabilitation process. This review highlights the role of skeletal muscles from various aspects, diagnostic procedures to quantify muscle mass and strength and, most importantly, lists countermeasures to muscle wasting. Although structured and progressive strength training is the cornerstone in the treatment of muscle wasting, several other methods exist to slow down or reverse the process of muscle wasting. Among them are neuromuscular electrical stimulation and alternative exercise modes, positioning, stretching and, as an emerging field, drug therapy. PMID:26758982

  8. [Ovarian torsion revealing an ovarian cavernous hemangioma in a child].

    PubMed

    M'pemba Loufoua-Lemay, A-B; Peko, J-F; Mbongo, J-A; Mokoko, J-C; Nzingoula, S

    2003-11-01

    The authors report one case of cavernous hemangioma of the left ovary, which was revealed by ovarian torsion. Such benign tumors of the blood vessels are rare in ovaries during childhood. This hemangioma was observed in a 13-year-old patient, who presented with abdominal and pelvic pain and vomiting. The pelvic mass was noted and sonography revealed a cystic tumor. An annexectomia was realized. Histology showed narcotized ovary cells, with an increased number of vascular channels composed of thin walled vessels, whose wall consisted of an endothelium. This aspect evoked a cavernous hemangioma of the ovary. PMID:14613693

  9. [Psychological changes in intensive care patients with acute Guillain-Barré syndrome--psychoanalytic aspects of loss of communication and adjustment].

    PubMed

    Weiss, H

    1991-04-01

    Ten patients who had been hospitalized with acute Guillain-Barré-syndrome (GBS) were monitored during their course of treatment and were asked in short intervals through semi-structured interviews how they experienced their illness. States of anxiety were especially evident at the initial phase of the disease, during the dissemination and maximum intensity of paralysis. In contrast, depressive symptoms were primarily noticeable during the phase of remission. As a rule, the degree of anxiety correlated in intensity and duration with the degree of severity of the neurological deficit. Five patients experienced a temporary derealization, among those, three patients showed productive-psychotic symptoms (optical and acoustical hallucinations, delusional reactions). Frequently, dreams were reported, which were associated with elementary experiences of anxiety and in part took on an overwhelming realistic character. Finally, the psychic changes are interpreted in context with the extreme condition of the disease which does not only signify a situation of forced dependence and regression for the patient but also results in--through loss of mobility and communication (cranial nerve dysfunction, artificial respiration)--a fundamental change in the perception of reality. PMID:2055586

  10. Physical and mathematical aspects of blood-glucose- and insulin-level kinetics in patients with coronary heart disease and high risk of its development

    NASA Astrophysics Data System (ADS)

    Denisova, Tatyana P.; Malinova, Lidia I.; Malinov, Igor A.

    2001-05-01

    The intravenous glucose tolerance test was performed to estimate the kinetics of blood glucose and insulin levels. Glucose was injected in individual standardized dose (0.5 g. per 1 kg of body weight). Three groups of patients were checked up: 1) patients with coronary heart disease verified by cicatricial alterations in myocardium found by electrocardiographic and echocardiographic methods; 2) children of patients with transmural myocardial infarction practically healthy at the moment of study; 3) persons practically healthy at the moment of study without any indications on cardiovascular diseases and non-insulin dependent diabetes mellitus among all ancestors and relatives who frequently were long-livers. Last groups didn't differ by age and sex. Peripheral blood glucose level, immunoreactive and free insulin (tested by muscular tissue) were studied just before glucose injection (on an empty stomach) and 4 times after it. The received discrete data were approximated by high degree polynomials, the estimation of blood glucose and insulin time functions symmetric was performed. The deceleration of degradation of insulin circulating in peripheral blood and the time decrease of second phase of insulin secretion were analytically established. This fact proves the complicated mechanism of insulin alterations in atherosclerosis, consisting not only of insulin resistance of peripheral tissues but of decrease of plastic processes in insulin- generating cells.

  11. [Communication in health care - legal aspects].

    PubMed

    Mina, András

    2016-04-24

    This paper is focusing on the legal aspects of communication in health care, especially on doctor-patient relationship, responsibility for information, communication of adverse events, and legal declarations. PMID:27084442

  12. Targeted Next-Generation Sequencing of a 12.5 Mb Homozygous Region Reveals ANO10 Mutations in Patients with Autosomal-Recessive Cerebellar Ataxia

    PubMed Central

    Vermeer, Sascha; Hoischen, Alexander; Meijer, Rowdy P.P.; Gilissen, Christian; Neveling, Kornelia; Wieskamp, Nienke; de Brouwer, Arjan; Koenig, Michel; Anheim, Mathieu; Assoum, Mirna; Drouot, Nathalie; Todorovic, Slobodanka; Milic-Rasic, Vedrana; Lochmüller, Hanns; Stevanin, Giovanni; Goizet, Cyril; David, Albert; Durr, Alexandra; Brice, Alexis; Kremer, Berry; van de Warrenburg, Bart P.C.; Schijvenaars, Mascha M.V.A.P.; Heister, Angelien; Kwint, Michael; Arts, Peer; van der Wijst, Jenny; Veltman, Joris; Kamsteeg, Erik-Jan; Scheffer, Hans; Knoers, Nine

    2010-01-01

    Autosomal-recessive cerebellar ataxias comprise a clinically and genetically heterogeneous group of neurodegenerative disorders. In contrast to their dominant counterparts, unraveling the molecular background of these ataxias has proven to be more complicated and the currently known mutations provide incomplete coverage for genotyping of patients. By combining SNP array-based linkage analysis and targeted resequencing of relevant sequences in the linkage interval with the use of next-generation sequencing technology, we identified a mutation in a gene and have shown its association with autosomal-recessive cerebellar ataxia. In a Dutch consanguineous family with three affected siblings a homozygous 12.5 Mb region on chromosome 3 was targeted by array-based sequence capture. Prioritization of all detected sequence variants led to four candidate genes, one of which contained a variant with a high base pair conservation score (phyloP score: 5.26). This variant was a leucine-to-arginine substitution in the DUF 590 domain of a 16K transmembrane protein, a putative calcium-activated chloride channel encoded by anoctamin 10 (ANO10). The analysis of ANO10 by Sanger sequencing revealed three additional mutations: a homozygous mutation (c.1150_1151del [p.Leu384fs]) in a Serbian family and a compound-heterozygous splice-site mutation (c.1476+1G>T) and a frameshift mutation (c.1604del [p.Leu535X]) in a French family. This illustrates the power of using initial homozygosity mapping with next-generation sequencing technology to identify genes involved in autosomal-recessive diseases. Moreover, identifying a putative calcium-dependent chloride channel involved in cerebellar ataxia adds another pathway to the list of pathophysiological mechanisms that may cause cerebellar ataxia. PMID:21092923

  13. The associations of body mass index with physical and mental aspects of health-related quality of life in Chinese patients with type 2 diabetes mellitus: results from a cross-sectional survey

    PubMed Central

    2013-01-01

    Background This study aimed to determine the associations of various clinical factors with generic health-related quality of life (HRQOL) scores among Hong Kong Chinese patients with type 2 diabetes mellitus (T2DM) in the outpatient primary care setting using the short-form 12 (SF-12). Methods A cross-sectional survey of 488 Chinese adults with T2DM recruited from a primary care outpatient clinic was conducted from May to August 2008. Data on the standard Chinese (HK) SF-12 Health Survey and patients’ socio-demographics were collected from face-to-face interviews. Glycaemic control, body mass index (BMI), chronic co-morbidities, diabetic complications and treatment modalities were determined for each patient through medical records. Associations of socio-demographic and clinical factors with physical component summary (PCS-12) and mental component summary scores (MCS-12) were evaluated using multiple linear regression. Results The socio-demographic correlates of PCS-12 and MCS-12 were age, gender and BMI. After adjustment for socio-demographic variables, the BMI was negatively associated with PCS-12 but positively associated with MCS-12. The presence of diabetic complications was associated with lower PCS-12 (regression coefficient:-3.0 points, p < 0.05) while being on insulin treatment was associated with lower MCS-12 (regression coefficient:-5.8 points, p < 0.05). In contrast, glycaemic control, duration of T2DM and treatment with oral hypoglycaemic drugs were not significantly associated with PCS-12 or MCS-12. Conclusions Among T2DM subjects in the primary care setting, impairments in the physical aspect of HRQOL were evident in subjects who were obese or had diabetic complications whereas defects in the mental aspect of HRQOL were observed in patients with lower BMI or receiving insulin injections. PMID:23964785

  14. [Medical decision making: some aspects].

    PubMed

    Steurer, J

    2004-09-22

    Three main aspects of medical decision making will be shortly described in this article. Comprehensible information is required to make decisions. The question is, how much information is needed to make decisions, and a third aspect in this article concerns the decision maker. Research in the field of information transfer has shown that medical information, as presented in most journals, is difficult to understand. According to the classic decision theory, decisions are taken after collecting all available information. More recent research in decision making proves the hypothesis that human beings are able to decide correctly with much less information than presumed earlier. In medicine the patient is the decision maker, and the primary task of physicians is to inform the patient about his health status and enable him to reach a conclusion. PMID:15500244

  15. Quinolinic Acid Responses during Interferon-α-Induced Depressive Symptomatology in Patients with Chronic Hepatitis C Infection - A Novel Aspect for Depression and Inflammatory Hypothesis

    PubMed Central

    Baranyi, Andreas; Meinitzer, Andreas; Breitenecker, Robert J.; Amouzadeh-Ghadikolai, Omid; Stauber, Rudolf; Rothenhäusler, Hans-Bernd

    2015-01-01

    Background The aim of this exploratory study is to gain for the first time a more comprehensive picture of the impact of changes of quinolinic acid concentrations on depressive symptomatology during and after IFN-α therapy. Methods The quinolinic acid concentrations of 35 HCV patients are examined in a prospective survey over the entire period of IFN-α treatment as well as three months later at six different times (baseline, one, three, six and nine months after the beginning of IFN-α treatment, and after the end of treatment). Results During IFN-α treatment Hamilton Depression Rating Scale scores rise significantly. At the same time there is greater activity of indoleamine 2,3-dioxygenase, with a resulting increase in plasma kynurenine concentrations. Compared to baseline values quinolinic acid concentrations increase significantly during therapy, reflecting an increased neurotoxic challenge. In addition, patients with higher scores in the Hamilton Depression Rating Scale at six and nine months after starting therapy show significantly higher levels of quinolinic acid concentration. Conclusions The increase of quinolinic acid during IFN-α therapy might contribute to depressive symptomatology through the neurotoxic challenge caused by quinolinic acid. Subsequently, our exploratory study results support the inflammatory hypothesis of depression. The awareness of relevant risk factors of IFN-α treatment-induced depression is essential to develop preventative treatment strategies. PMID:26368809

  16. Effect of energy repletion on dynamic aspects of protein metabolism of malnourished adolescent and young adult patients with cystic fibrosis during the first 12 days of treatment.

    PubMed

    Pencharz, P; Hill, R; Archibald, E

    1986-01-01

    The short-term effect of nutritional rehabilitation on whole body protein metabolism of six malnourished (energy depleted) adolescent and young adult cystic fibrosis (CF) patients was examined during the first 12 days of treatment. Refeeding was accomplished using continuous nasogastric administration of an elemental diet. Intakes were 1.65 SD 0.3 g protein/kg/day and 85.3 SD 19.2 kcal/kg/day. Turnover measurements were carried out on four occasions, during the control period on a normal diet and days 4, 8, and 12 on the elemental diet. In response to refeeding, whole body amino nitrogen flux (Q) fell consistently over the study (p less than 0.05). Protein synthesis (S) and breakdown (B) also fell but their values did not reach statistical significance. On the other hand, there was a prompt increase in ratios S/Q and B/Q in response to tube feeding discernible on days 4 and 8 (p less than 0.05), but which returned to baseline by day 12. We conclude that malnourished CF patients who are still eating well have increased rates of protein turnover. There is a prompt response of protein metabolism to energy repletion with a progressive decline in rates during the first 12 days of treatment. PMID:3755167

  17. Psychosocial aspects of cancer pain.

    PubMed

    Stiefel, F

    1993-05-01

    Pain, and especially cancer pain, is not a pure nociceptive, physical experience, but involves different dimensions of man, such as personality, affect, cognition, behavior and social relations. Cancer pain is best conceptualized as the convergence of multiple activated systems with feedback mechanisms to a complex, multidimensional model. The psychosocial aspects of this multidimensional model will be analyzed with special emphasis on results from recent research. Although most research has been conducted on the role of affect and cognition in cancer pain, data on other factors such as personality, behavior or social aspects exist and will be presented. In the second part of this paper the implications of these results for therapeutic strategies in clinical work will be discussed. Although a considerable body of knowledge exists to support the hypothesis of a multidimensional model of cancer pain, where psychosocial variables play an important role, only a few studies address the issue of to what degree different factors exercise their influence. This may be different from patient to patient and may change over the course of the disease. Whatever importance these single variables in the multidimensional model of cancer pain may have, the patient is best treated when none of these aspects is neglected in the assessment and all are taken care of in the treatment. A multidisciplinary team, with a psychiatrist as one of the team members, is often best prepared to fulfill this task. PMID:8149139

  18. The solution structures of native and patient monomeric human IgA1 reveal asymmetric extended structures: implications for function and IgAN disease

    PubMed Central

    Hui, Gar Kay; Wright, David W.; Vennard, Owen L.; Rayner, Lucy E.; Pang, Melisa; Yeo, See Cheng; Gor, Jayesh; Molyneux, Karen; Barratt, Jonathan; Perkins, Stephen J.

    2015-01-01

    Native IgA1, for which no crystal structure is known, contains an O-galactosylated 23-residue hinge region that joins its Fab and Fc regions. IgA nephropathy (IgAN) is a leading cause of chronic kidney disease in developed countries. Because IgA1 in IgAN often has a poorly O-galactosylated hinge region, the solution structures of monomeric IgA1 from a healthy subject and three IgAN patients with four different O-galactosylation levels were studied. Analytical ultracentrifugation showed that all four IgA1 samples were monomeric with similar sedimentation coefficients, s020,w. X-ray scattering showed that the radius of gyration (Rg) slightly increased with IgA1 concentration, indicating self-association, although their distance distribution curves, P(r), were unchanged with concentration. Neutron scattering indicated similar Rg values and P(r) curves, although IgA1 showed a propensity to aggregate in heavy water buffer. A new atomistic modelling procedure based on comparisons with 177000 conformationally-randomized IgA1 structures with the individual experimental scattering curves revealed similar extended Y-shaped solution structures for all four differentially-glycosylated IgA1 molecules. The final models indicated that the N-glycans at Asn263 were folded back against the Fc surface, the C-terminal tailpiece conformations were undefined and hinge O-galactosylation had little effect on the solution structure. The solution structures for full-length IgA1 showed extended hinges and the Fab and Fc regions were positioned asymmetrically to provide ample space for the functionally-important binding of two FcαR receptors to its Fc region. Whereas no link between O-galactosylation and the IgA1 solution structure was detected, an increase in IgA1 aggregation with reduced O-galactosylation may relate to IgAN. PMID:26268558

  19. Understanding adoption of a personal health record in rural health care clinics: revealing barriers and facilitators of adoption including attributions about potential patient portal users and self-reported characteristics of early adopting users.

    PubMed

    Butler, Jorie M; Carter, Marjorie; Hayden, Candace; Gibson, Bryan; Weir, Charlene; Snow, Laverne; Morales, Jose; Smith, Anne; Bateman, Kim; Gundlapalli, Adi V; Samore, Matthew

    2013-01-01

    Personal health records (PHRs) are important for improving patient care. An important prerequisite to realize benefits of PHR use is patient recruitment. To understand clinic barriers to adoption, we used Rogers' Diffusion of Innovations theory to frame an examination of clinic staff perceptions of a new PHR and perceptions of likely patient portal users. Clinic staff reported many relative advantages and observable benefits of the PHR but also some distinct problems. Attributions about potential patient users included demographic, computer use, and personality characteristics staff expected in likely users. Analysis of patient survey data of early adopters compared to non-users revealed discrepancies between clinic staff expectations and early adopters' self-reports. Implications for improving adoption of PHRs include ensuring compatibility with existing systems and avoiding recruitment biases. PMID:24551328

  20. [Transcultural aspects of depression].

    PubMed

    Aichberger, M C; Schouler-Ocak, M; Rapp, M A; Heinz, A

    2008-04-01

    For many decades it was assumed that depressive disorders are mainly a problem of Western societies. However, a World Bank report published in 1993 revealed that Major Depression is already the fifth leading contributor to the Global Burden of Disease (GBD) among women in developmentally disadvantaged countries. The core symptoms of depression are disorders of affect, conduct and somatic complaints. In Western societies, the key symptom of depression is regarded to be a disorder of affect. However, in other cultural settings, different symptoms may be more central for depression. Nowadays mental health specialists have regular contact with patients from different cultural backgrounds. In order to achieve optimal results in diagnosing and treating mental disorders, it is important to consider the cultural background of a patient and her or his explanatory model of the disease. Transcultural psychiatry and psychotherapy aims at developing culture-sensitive concepts for treatment and mental health services and tries to increase insight in culture-related psychopathology and epidemiology. PMID:18345470

  1. Repeated measurements of cerebral blood flow in the left superior temporal gyrus reveal tonic hyperactivity in patients with auditory verbal hallucinations: a possible trait marker

    PubMed Central

    Homan, Philipp; Kindler, Jochen; Hauf, Martinus; Walther, Sebastian; Hubl, Daniela; Dierks, Thomas

    2013-01-01

    Background: The left superior temporal gyrus (STG) has been suggested to play a key role in auditory verbal hallucinations (AVH) in patients with schizophrenia. Methods: Eleven medicated subjects with schizophrenia and medication-resistant AVH and 19 healthy controls underwent perfusion magnetic resonance (MR) imaging with arterial spin labeling (ASL). Three additional repeated measurements were conducted in the patients. Patients underwent a treatment with transcranial magnetic stimulation (TMS) between the first 2 measurements. The main outcome measure was the pooled cerebral blood flow (CBF), which consisted of the regional CBF measurement in the left STG and the global CBF measurement in the whole brain. Results: Regional CBF in the left STG in patients was significantly higher compared to controls (p < 0.0001) and to the global CBF in patients (p < 0.004) at baseline. Regional CBF in the left STG remained significantly increased compared to the global CBF in patients across time (p < 0.0007), and it remained increased in patients after TMS compared to the baseline CBF in controls (p < 0.0001). After TMS, PANSS (p = 0.003) and PSYRATS (p = 0.01) scores decreased significantly in patients. Conclusions: This study demonstrated tonically increased regional CBF in the left STG in patients with schizophrenia and auditory hallucinations despite a decrease in symptoms after TMS. These findings were consistent with what has previously been termed a trait marker of AVH in schizophrenia. PMID:23805093

  2. Revealing Mercury

    NASA Astrophysics Data System (ADS)

    Prockter, L. M.; Solomon, S. C.; Head, J. W.; Watters, T. R.; Murchie, S. L.; Robinson, M. S.; Chapman, C. R.; McNutt, R. L.

    2009-04-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, developed under NASA's Discovery Program, launched in August 2004. En route to insertion into orbit about Mercury in 2011, MESSENGER flies by Mercury three times. The first and second of these encounters were accomplished in January and October of 2008. These flybys viewed portions of Mercury's surface that were not observed by Mariner 10 during its reconnaissance of somewhat less than half of the planet in 1974-1975. All MESSENGER instruments operated during each flyby and returned a wealth of new data. Many of the new observations were focused on the planet's geology, including monochrome imaging at resolutions as high as 100 m/pixel, multispectral imaging in 11 filters at resolutions as high as 500 m/pixel, laser altimetry tracks extending over several thousands of kilometers, and high-resolution spectral measurements of several types of terrain. Here we present an overview of the first inferences on the global geology of Mercury from the MESSENGER observations. Whereas evidence for volcanism was equivocal from Mariner 10 data, the new MESSENGER images and altimetry provide compelling evidence that volcanism was widespread and protracted on Mercury. Color imaging reveals three common spectral units on the surface: a higher-reflectance, relatively red material occurring as a distinct class of smooth plains, typically with distinct embayment relationships interpreted to indicate volcanic emplacement; a lower-reflectance, relatively blue material typically excavated by impact craters and therefore inferred to be more common at depth; and a spectrally intermediate terrain that constitutes much of the uppermost crust. Three more minor spectral units are also seen: fresh crater ejecta, reddish material associated with rimless depressions interpreted to be volcanic centers, and high-reflectance deposits seen in some crater floors. Preliminary measurements of crater size

  3. [Clinical aspects of trigeminal neuralgia].

    PubMed

    Laurent, B; Keravel, Y; Sindou, M

    2009-04-01

    Primary trigeminal neuralgia, termed "classical" in the international nomenclature, is an epilepsy-like disease. Diagnosis is easy when the disorder typical in presentation, based on clinical features and responsiveness to anticonvulsants. However, diagnosis can be difficult when atypical and/or in the long-duration forms. Furthermore, trigeminal neuralgia - even if typical in its clinical aspects - may be caused by a specific lesion and reveal a pathology. In other words, it may be symptomatic (secondary). Imaging, especially MRI, is of prime importance in identifying the cause and guiding the appropriate treatment. PMID:19328503

  4. Task and Resting-State fMRI Reveal Altered Salience Responses to Positive Stimuli in Patients with Major Depressive Disorder.

    PubMed

    Yang, Yang; Zhong, Ning; Imamura, Kazuyuki; Lu, Shengfu; Li, Mi; Zhou, Haiyan; Li, Huaizhou; Yang, Xiaojing; Wan, Zhijiang; Wang, Gang; Hu, Bin; Li, Kuncheng

    2016-01-01

    Altered brain function in patients with major depressive disorder (MDD) has been repeatedly demonstrated by task-based and resting-state studies, respectively. However, less is known concerning whether overlapped abnormalities in functional activities across modalities exist in MDD patients. To find out the answer, we implemented an fMRI experiment and collected both task and resting-state data from 19 MDD patients and 19 matched, healthy, controls. A distraction paradigm involving emotionally valenced pictures was applied to induce affective responses in subjects. As a result, concurrent deficits were found in arousing activation during a positive task in both the reward circuit and salience network (SN) that is composed of the dorsal part of anterior cingulate cortex (dACC) and bilateral anterior insulae (AI) in only the MDD group. Subsequent amplitude of low frequency fluctuations (ALFF) and functional connectivity analyses based on resting-state data exhibited consistent alterations in the bilateral AI of MDD patients, and indicated patients' difficulties in regulating the balance between central executive network (CEN) and default mode network (DMN) due to altered connectivity among the CEN, DMN, and SN. Our findings provide new evidence demonstrating impaired salience processing and resulting alterations in responses to positive stimuli in MDD patients. Furthermore, brain abnormalities synchronized across functional states in MDD patients can be evidenced by a combination of task and resting-state fMRI analyses. PMID:27192082

  5. Distribution of interleukin-10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation

    PubMed Central

    Scrivo, R; Conigliaro, P; Riccieri, V; Di Franco, M; Alessandri, C; Spadaro, A; Perricone, R; Valesini, G

    2015-01-01

    Evidence exists that interleukin (IL)-10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL-20, IL-24 and IL-19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL-20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL-24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL-19 serum levels were higher in HC and OA compared with PsA and RA patients; IL-19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL-19 serum levels after biological treatment. Therefore, IL-19 seems to be involved mainly in the joint inflammation, whereas IL-20 and IL-24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies. PMID:25178435

  6. Smartphone application for rheumatoid arthritis self-management: cross-sectional study revealed the usefulness, willingness to use and patients' needs.

    PubMed

    Azevedo, Rita; Bernardes, Miguel; Fonseca, João; Lima, Aurea

    2015-10-01

    Patient-centered smartphone applications have potential to support rheumatoid arthritis (RA) self-management but remain almost unexplored in literature. Therefore, this study evaluated the usefulness of a smartphone application to support RA self-management, the willingness of RA patients to use and pay for it and the features the application should have. In this cross-sectional study, a questionnaire was developed to collect information on population, device ownership, usefulness and willingness to use and pay for a RA self-management application and application features. Descriptive statistics, Chi-square, Fisher's exact test, t test or Mann-Whitney's test and multivariate analysis were used. One hundred RA patients answered the questionnaire. Patients' mean age was 57 ± 11.9 years, most were females (91 %), with multiple drug regimens and a 40 % treatment non-compliance rate. Most patients believed that could have a more active role in self-management (94 %) and reported it would be useful to develop a RA self-management application (86 %). Patients willing to use an application (83 %) were younger, with a possible more active role in self-management, with access to a smartphone, and using short message service, electronic mail and Internet. Multivariate analysis confirmed these results, except the associations regarding access to a smartphone and use of electronic mail and Internet. Fifty-eight patients (82 %) were willing to pay for a RA self-management application and the most requested feature for it was information in a simple format. This study suggested the usefulness and patients' willingness to use and pay for a RA self-management application and provided insight on patients' needs. PMID:25903352

  7. High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients.

    PubMed

    Frémont, Marc; Coomans, Danny; Massart, Sebastien; De Meirleir, Kenny

    2013-08-01

    Human intestinal microbiota plays an important role in the maintenance of host health by providing energy, nutrients, and immunological protection. Intestinal dysfunction is a frequent complaint in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, and previous reports suggest that dysbiosis, i.e. the overgrowth of abnormal populations of bacteria in the gut, is linked to the pathogenesis of the disease. We used high-throughput 16S rRNA gene sequencing to investigate the presence of specific alterations in the gut microbiota of ME/CFS patients from Belgium and Norway. 43 ME/CFS patients and 36 healthy controls were included in the study. Bacterial DNA was extracted from stool samples, PCR amplification was performed on 16S rRNA gene regions, and PCR amplicons were sequenced using Roche FLX 454 sequencer. The composition of the gut microbiota was found to differ between Belgian controls and Norwegian controls: Norwegians showed higher percentages of specific Firmicutes populations (Roseburia, Holdemania) and lower proportions of most Bacteroidetes genera. A highly significant separation could be achieved between Norwegian controls and Norwegian patients: patients presented increased proportions of Lactonifactor and Alistipes, as well as a decrease in several Firmicutes populations. In Belgian subjects the patient/control separation was less pronounced, however some abnormalities observed in Norwegian patients were also found in Belgian patients. These results show that intestinal microbiota is altered in ME/CFS. High-throughput sequencing is a useful tool to diagnose dysbiosis in patients and could help designing treatments based on gut microbiota modulation (antibiotics, pre and probiotics supplementation). PMID:23791918

  8. Blood Pressure is Associated With Cerebral Blood Flow Alterations in Patients With T2DM as Revealed by Perfusion Functional MRI

    PubMed Central

    Xia, Wenqing; Rao, Hengyi; Spaeth, Andrea M.; Huang, Rong; Tian, Sai; Cai, Rongrong; Sun, Jie; Wang, Shaohua

    2015-01-01

    Abstract Type 2 diabetes mellitus (T2DM) and hypertension are both associated with cognitive impairment and brain function abnormalities. We investigated whether abnormal cerebral blood flow (CBF) patterns exists in T2DM patients and possible relationships between aberrant CBF and cognitive performance. Furthermore, we examined the influence of hypertension on CBF alterations in T2DM patients. T2DM patients (n = 38) and non-T2DM subjects (n = 40) were recruited from clinics, hospitals, and normal community health screenings. Cerebral blood flow images were collected and analyzed using arterial spin labeling perfusion functional magnetic resonance imaging (fMRI). Regions with major CBF differences between T2DM patients and non-T2DM controls were detected via 1-way ANOVA. The interaction effects between hypertension and T2DM for CBF alterations were also examined. Correlation analyses illustrated the association between CBF values and cognitive performance and between CBF and blood pressure. Compared with non-T2DM controls, T2DM patients exhibited decreased CBF, primarily in the visual area and the default mode network (DMN); decreased CBF in these regions was correlated with cognitive performance. There was a significant interaction effect between hypertension and diabetes for CBF in the precuneus and the middle occipital gyrus. Additionally, blood pressure correlated negatively with CBF in T2DM patients. T2DM patients exhibited reduced CBF in the visual area and DMN. Hypertension may facilitate a CBF decrease in the setting of diabetes. T2DM patients may benefit from blood pressure control to maintain their brain perfusion through CBF preservation. PMID:26632913

  9. Differences in regional homogeneity between patients with Crohn's disease with and without abdominal pain revealed by resting-state functional magnetic resonance imaging.

    PubMed

    Bao, Chun-Hui; Liu, Peng; Liu, Hui-Rong; Wu, Lu-Yi; Jin, Xiao-Ming; Wang, Si-Yao; Shi, Yin; Zhang, Jian-Ye; Zeng, Xiao-Qing; Ma, Li-Li; Qin, Wei; Zhao, Ji-Meng; Calhoun, Vince D; Tian, Jie; Wu, Huan-Gan

    2016-05-01

    Abnormal pain processing in the central nervous system may be related to abdominal pain in patients with Crohn's disease (CD). The purpose of this study was to investigate changes in resting-state brain activity in patients with CD in remission and its relationship with the presence of abdominal pain. Twenty-five patients with CD and with abdominal pain, 25 patients with CD and without abdominal pain, and 32 healthy subjects were scanned using a 3.0-T functional magnetic resonance imaging scanner. Regional homogeneity (ReHo) was used to assess resting-state brain activity. Daily pain scores were collected 1 week before functional magnetic resonance imaging. We found that patients with abdominal pain exhibited lower ReHo values in the insula, middle cingulate cortex (MCC), and supplementary motor area and higher ReHo values in the temporal pole. In contrast, patients without abdominal pain exhibited lower ReHo values in the hippocampal/parahippocampal cortex and higher ReHo values in the dorsomedial prefrontal cortex (all P < 0.05, corrected). The ReHo values of the insula and MCC were significantly negatively correlated with daily pain scores for patients with abdominal pain (r = -0.53, P = 0.008 and r = -0.61, P = 0.002, respectively). These findings suggest that resting-state brain activities are different between remissive patients with CD with and without abdominal pain and that abnormal activities in insula and MCC are closely related to the severity of abdominal pain. PMID:26761381

  10. Task and Resting-State fMRI Reveal Altered Salience Responses to Positive Stimuli in Patients with Major Depressive Disorder

    PubMed Central

    Yang, Yang; Zhong, Ning; Imamura, Kazuyuki; Lu, Shengfu; Li, Mi; Zhou, Haiyan; Li, Huaizhou; Yang, Xiaojing; Wan, Zhijiang; Wang, Gang; Hu, Bin; Li, Kuncheng

    2016-01-01

    Altered brain function in patients with major depressive disorder (MDD) has been repeatedly demonstrated by task-based and resting-state studies, respectively. However, less is known concerning whether overlapped abnormalities in functional activities across modalities exist in MDD patients. To find out the answer, we implemented an fMRI experiment and collected both task and resting-state data from 19 MDD patients and 19 matched, healthy, controls. A distraction paradigm involving emotionally valenced pictures was applied to induce affective responses in subjects. As a result, concurrent deficits were found in arousing activation during a positive task in both the reward circuit and salience network (SN) that is composed of the dorsal part of anterior cingulate cortex (dACC) and bilateral anterior insulae (AI) in only the MDD group. Subsequent amplitude of low frequency fluctuations (ALFF) and functional connectivity analyses based on resting-state data exhibited consistent alterations in the bilateral AI of MDD patients, and indicated patients’ difficulties in regulating the balance between central executive network (CEN) and default mode network (DMN) due to altered connectivity among the CEN, DMN, and SN. Our findings provide new evidence demonstrating impaired salience processing and resulting alterations in responses to positive stimuli in MDD patients. Furthermore, brain abnormalities synchronized across functional states in MDD patients can be evidenced by a combination of task and resting-state fMRI analyses. PMID:27192082

  11. A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients

    PubMed Central

    Freyhult, Eva; Bodolea, Constantin; Ekegren, Titti; Larsson, Anders; Gustafsson, Mats G.; Katila, Lenka; Bergquist, Jonas; Gordh, Torsten; Landegren, Ulf; Kamali-Moghaddam, Masood

    2016-01-01

    The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest. PMID:26914813

  12. Brittle diabetes: psychopathological aspects.

    PubMed

    Pelizza, Lorenzo; Bonazzi, Federica; Scaltriti, Sara; Milli, Bruna; Giuseppina, Chierici

    2014-01-01

    Background. The term "brittle" is used to described an uncommon subgroup of type I diabetics whose lives are disrupted by severe glycaemic instability with repeated and prolonged hospitalization. Psychosocial problems are the major perceived underlying causes of brittle behaviour. Aim of this study is a systematic psychopathological assessement of brittleness using specific parameters of general psychopathology and personality traits following the multiaxial format (axis I and II) of the current DSM-IV-TR diagnostic criteria for mental disorders. Methods. Patients comprised 21 brittle type I diabetics and a case-control group of 21 stable diabetics, matched for age, gender, years of education, and diabetes duration. General psychopathology and the DSM-IV-TR personality traits/disorders were assessed using the Syptom Checklist-90-R (SCL-90-R) and the Millon Clinical Multiaxial Inventory-III (MCMI-III). Results. The comparison for SCL-90-R parameters exclusively revealed higher scores in "Phobic Anxiety" subscale in brittle diabetics. No differences in all the other SCL-90-R primary symptom dimensions and in the three SCL-90-R global distress indices were observed between the two diabetic groups, as well as in the all MCMI-III clinical syndrome categories corresponding to DSM-IV-TR specific psychiatric disorders. However, brittle patients presented lower scores in MCMI-III compulsive personality traits and higher scores in paranoid, schizoid, schizotypal, antisocial, borderline, narcissistic, avoidant, dependent, depressive, and passive-aggressive personality traits. Conclusions. In this study, brittle diabetics show no differencies in terms of global severity of psychopathological distress and axis I specific DSM-IV-TR diagnoses in comparison with non-brittle subjects (except for phobic anxiety). Differently, brittle diabetics are characterized from less functional and maladaptive personality features and suffer more frequently and intensively from specific

  13. A new monoclonal antibody DAG-6F4 against human alpha-dystroglycan reveals reduced core protein in some, but not all, dystroglycanopathy patients.

    PubMed

    Humphrey, Emma L; Lacey, Erica; Le, Lam T; Feng, Lucy; Sciandra, Francesca; Morris, Charlotte R; Hewitt, Jane E; Holt, Ian; Brancaccio, Andrea; Barresi, Rita; Sewry, Caroline A; Brown, Susan C; Morris, Glenn E

    2015-01-01

    We generated a novel monoclonal antibody, DAG-6F4, against alpha-dystroglycan which immunolabels the sarcolemma in human muscle biopsies. Its seven amino-acid epitope, PNQRPEL, was identified using phage-displayed peptides and is located immediately after the highly-glycosylated mucin domain of alpha-dystroglycan. On Western blots of recombinant alpha-dystroglycan, epitope accessibility was reduced, but not entirely prevented, by glycosylation. DAG-6F4 immunolabelling was markedly reduced in muscle biopsies from Duchenne muscular dystrophy patients consistent with disruption of the dystroglycan complex. In a range of dystroglycanopathy patients with reduced/altered glycosylation, staining by DAG-6F4 was often less reduced than staining by IIH6 (antibody against the glycan epitope added by LARGE and commonly used to identify glycosylated alpha-dystroglycan). Whereas IIH6 was reduced in all patients, DAG-6F4 was hardly changed in a LARGE patient, less reduced than IIH6 in limb-girdle muscular dystrophy type 2I, but as reduced as IIH6 in some congenital muscular dystrophy patients. Although absence of the LARGE-dependent laminin-binding site appears not to affect alpha-dystroglycan stability at the sarcolemma, the results suggest that further reduction in aDG glycosylation may reduce its stability. These studies suggest that DAG-6F4 may be a useful addition to the antibody repertoire for evaluating the dystroglycan complex in neuromuscular disorders. PMID:25387694

  14. [Legal aspects of sports injuries].

    PubMed

    Allard, R H B

    2005-05-01

    Victims of sports injuries have to be advised about aspects of legal liablity, especially in case of luxation or avulsion of teeth, since there still may be dental consequences years later. The transference of information by the first-aid-dentist to the sportsman's own dentist should take place with care. If the patient has no family dentist, the first-aid-dentist should at least keep the sportsman free of pain, for example by starting endodontic treatment. Because sports injuries mostly occur beyond normal practice-hours, there may be reasons to deviate from the clinical guideline. PMID:15932047

  15. [Hospital infection--ethical aspects].

    PubMed

    Hossne, W S

    1995-01-01

    The author focuses the question of hospital infection, analysing the background on which the control committees were created. The hospital infection is discussed under bioethical principles and the Medical Ethics Code, examining the aspects related to the government, the Hospital Directorship, the Committee and the Control Service of Hospital Infection, and the assisting physician. A closer integration between the activities of the Program of Control of Hospital Infections and those of the Medical Ethics Committee is proposed, aiming at the patient and at the community, "targets of total medical attention". PMID:7550409

  16. High Aspect Ratio Wrinkles

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Cheng; Crosby, Alfred

    2015-03-01

    Buckling-induced surface undulations are widely found in living creatures, for instance, gut villi and the surface of flower petal cells. These undulations provide unique functionalities with their extremely high aspect ratios. For the synthetic systems, sinusoidal wrinkles that are induced by buckling a thin film attached on a soft substrate have been proposed to many applications. However, the impact of the synthetic wrinkles have been restricted by limited aspect ratios, ranging from 0 to 0.35. Within this range, wrinkle aspect ratio is known to increase with increasing compressive strain until a critical strain is reached, at which point wrinkles transition to localizations, such as folds or period doublings. Inspired by the living creatures, we propose that wrinkles can be stabilized in high aspect ratio by manipulating the strain energy in the substrate. We experimentally demonstrate this idea by forming a secondary crosslinking network in the wrinkled surface and successfully achieve aspect ratio as large as 0.8. This work not only provides insights for the mechanism of high aspect ratio structures seen in living creatures, but also demonstrates significant promise for future wrinkle-based applications.

  17. Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes.

    PubMed

    Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

    2016-04-29

    Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function. PMID:26933035

  18. Genome-wide CNV analysis in 221 unrelated patients and targeted high-throughput sequencing reveal novel causative candidate genes for colorectal adenomatous polyposis.

    PubMed

    Horpaopan, Sukanya; Spier, Isabel; Zink, Alexander M; Altmüller, Janine; Holzapfel, Stefanie; Laner, Andreas; Vogt, Stefanie; Uhlhaas, Siegfried; Heilmann, Stefanie; Stienen, Dietlinde; Pasternack, Sandra M; Keppler, Kathleen; Adam, Ronja; Kayser, Katrin; Moebus, Susanne; Draaken, Markus; Degenhardt, Franziska; Engels, Hartmut; Hofmann, Andrea; Nöthen, Markus M; Steinke, Verena; Perez-Bouza, Alberto; Herms, Stefan; Holinski-Feder, Elke; Fröhlich, Holger; Thiele, Holger; Hoffmann, Per; Aretz, Stefan

    2015-03-15

    To uncover novel causative genes in patients with unexplained adenomatous polyposis, a model disease for colorectal cancer, we performed a genome-wide analysis of germline copy number variants (CNV) in a large, well characterized APC and MUTYH mutation negative patient cohort followed by a targeted next generation sequencing (NGS) approach. Genomic DNA from 221 unrelated German patients was genotyped on high-resolution SNP arrays. Putative CNVs were filtered according to stringent criteria, compared with those of 531 population-based German controls, and validated by qPCR. Candidate genes were prioritized using in silico, expression, and segregation analyses, data mining and enrichment analyses of genes and pathways. In 27% of the 221 unrelated patients, a total of 77 protein coding genes displayed rare, nonrecurrent, germline CNVs. The set included 26 candidates with molecular and cellular functions related to tumorigenesis. Targeted high-throughput sequencing found truncating point mutations in 12% (10/77) of the prioritized genes. No clear evidence was found for autosomal recessive subtypes. Six patients had potentially causative mutations in more than one of the 26 genes. Combined with data from recent studies of early-onset colorectal and breast cancer, recurrent potential loss-of-function alterations were detected in CNTN6, FOCAD (KIAA1797), HSPH1, KIF26B, MCM3AP, YBEY and in three genes from the ARHGAP family. In the canonical Wnt pathway oncogene CTNNB1 (β-catenin), two potential gain-of-function mutations were found. In conclusion, the present study identified a group of rarely affected genes which are likely to predispose to colorectal adenoma formation and confirmed previously published candidates for tumor predisposition as etiologically relevant. PMID:25219767

  19. Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma

    PubMed Central

    Cai, Jinquan; Sun, Ying; Wang, Guangzhi; Li, Yongli; Li, Ruiyan; Feng, Yan; Han, Bo; Li, Jianlong; Tian, Yu; Yi, Liye; Jiang, Chuanlu

    2016-01-01

    Background Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM. Method The mRNA expression profiles of all MMP genes were obtained from the Chinese Glioma Genome Atlas (CGGA), the Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the GSE16011 dataset. MGMT methylation status was also examined by pyrosequencing. The correlation of MMP9 expression with tumor progression was explored in glioma specimens of all grades. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the association of MMP9 expression with survival and response to temozolomide. Results MMP9 was the only significant prognostic factor in three datasets for primary glioblastoma patients. Our results indicated that MMP9 expression is correlated with glioma grade (p<0.0001). Additionally, low expression of MMP9 was correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066), and MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS: p = 0.032). Additionally, the GBM patients with low MMP9 expression benefited from temozolomide (TMZ) chemotherapy regardless of the MGMT methylation status. Conclusions Patients with primary GBMs with low MMP9 expression may have longer survival and may benefit from temozolomide chemotherapy. PMID:27022952

  20. MHC class II tetramer analyses in AE37-vaccinated prostate cancer patients reveal vaccine-specific polyfunctional and long-lasting CD4(+) T-cells.

    PubMed

    Anastasopoulou, Eleftheria A; Voutsas, Ioannis F; Papamichail, Michael; Baxevanis, Constantin N; Perez, Sonia A

    2016-07-01

    Realizing the basis for generating long-lasting clinical responses in cancer patients after therapeutic vaccinations provides the means to further ameliorate clinical efficacy. Peptide cancer vaccines stimulating CD4(+) T helper cells are often promising for inducing immunological memory and persistent CD8(+) cytotoxic T cell responses. Recent reports from our clinical trial with the AE37 vaccine, which is a HER2 hybrid polypeptide, documented its efficacy to induce CD4(+) T cell immunity, which was associated with clinical improvements preferentially among HLA-DRB1*11(+) prostate cancer patients. Here, we performed in-depth investigation of the CD4(+) T cell response against the AE37 vaccine. We used the DR11/AE37 tetramer in combination with multicolor flow cytometry to identify and characterize AE37-specific CD4(+) T cells regarding memory and Tregs phenotype in HLA-DRB1*11(+) vaccinated patients. To verify vaccine-specific immunological memory in vivo, we also assessed AE37-specific CD4(+) T cells in defined CD4(+) memory subsets by cell sorting. Finally, vaccine-induced AE37-specific CD4(+) T cells were assessed regarding their functional profile. AE37-specific memory CD4(+) T cells could be detected in peptide-stimulated cultures from prostate cancer patients following vaccination even 4 y post-vaccination. The vast majority of vaccine-induced AE37-specific CD4(+) T cells exhibited a multifunctional, mostly Th1 cytokine signature, with the potential of granzyme B production. In contrast, we found relatively low frequencies of Tregs among AE37-specific CD4(+) T cells. This is the first report on the identification of vaccine-induced HER2-specific multifunctional long-lasting CD4(+) T cells in vaccinated prostate cancer patients. PMID:27622033

  1. [Psychosomatic and somatopsychic aspects of progressive chronic polyarthritis (author's transl)].

    PubMed

    Pieringer, W

    1978-01-01

    By means of psychiatric depth-psychological investigations in more than 100 patients with PCP the somatopsychic aspect of the disease is described, which manifests itself in two thirds of the patients as an inhibited to agitated humble-depressive psychosyndrome. On the basis of family anamneses and analytical inquiries the somatopsychic aspects of the disease is described in more the half of the patients as consistent continuation of a specific way of life, so that psychosomatic and somatopsychic aspects of the disease are mentioned as one strategy persuing the same fictitious goal. Both aspects appear as functions of a seemingly threatened psychic-physical motivity. PMID:281059

  2. Epidemiological aspects of heart diseases

    PubMed Central

    Shi, Aimin; Tao, Ziqi; Wei, Peng; Zhao, Jing

    2016-01-01

    Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Coronary heart disease (CHD) is the main cause of mortality in heart patients following stroke, rheumatic heart disease and myocardial infarctions. Approximately 80% of individuals succumb to CVDs, due to poor living conditions in low and middle income families and malnutrition. Infectious diseases, human immunodeficiency, tuberculosis, malaria, high blood pressure or hypertension, obesity and overweight, and nutritional disorders including smoking, excessive alcohol consumption, high salt and sugar intake, as well as other factors are responsible for CVDs and CHDs in young as well as elderly individuals. The focus of the present review are recent epidemiological aspects of CVD and CHD as well as the usefulness of a Mediterranean diet for heart patients and the prevention of heart diseases. PMID:27602082

  3. Genomic analysis of an emerging multiresistant Staphylococcus aureus strain rapidly spreading in cystic fibrosis patients revealed the presence of an antibiotic inducible bacteriophage

    PubMed Central

    Rolain, Jean-Marc; François, Patrice; Hernandez, David; Bittar, Fadi; Richet, Hervé; Fournous, Ghislain; Mattenberger, Yves; Bosdure, Emmanuelle; Stremler, Nathalie; Dubus, Jean-Christophe; Sarles, Jacques; Reynaud-Gaubert, Martine; Boniface, Stephanie; Schrenzel, Jacques; Raoult, Didier

    2009-01-01

    Background Staphylococcus aureus is a major human pathogen responsible for a variety of nosocomial and community-acquired infections. Recent reports show that the prevalence of Methicillin-Resistant S. aureus (MRSA) infections in cystic fibrosis (CF) patients is increasing. In 2006 in Marseille, France, we have detected an atypical MRSA strain with a specific antibiotic susceptibility profile and a unique growth phenotype. Because of the clinical importance of the spread of such strain among CF patients we decided to sequence the genome of one representative isolate (strain CF-Marseille) to compare this to the published genome sequences. We also conducted a retrospective epidemiological analysis on all S. aureus isolated from 2002 to 2007 in CF patients from our institution. Results CF-Marseille is multidrug resistant, has a hetero-Glycopeptide-Intermediate resistance S. aureus phenotype, grows on Cepacia agar with intense orange pigmentation and has a thickened cell wall. Phylogenetic analyses using Complete Genome Hybridization and Multi Locus VNTR Assay showed that CF-Marseille was closely related to strain Mu50, representing vancomycin-resistant S. aureus. Analysis of CF-Marseille shows a similar core genome to that of previously sequenced MRSA strains but with a different genomic organization due to the presence of specific mobile genetic elements i.e. a new SCCmec type IV mosaic cassette that has integrated the pUB110 plasmid, and a new phage closely related to phiETA3. Moreover this phage could be seen by electron microscopy when mobilized with several antibiotics commonly used in CF patients including, tobramycin, ciprofloxacin, cotrimoxazole, or imipenem. Phylogenetic analysis of phenotypically similar h-GISA in our study also suggests that CF patients are colonized by polyclonal populations of MRSA that represents an incredible reservoir for lateral gene transfer. Conclusion In conclusion, we demonstrated the emergence and spreading of a new isolate of

  4. Simultaneous robotic-assisted adrenalectomy and partial nephrectomy: technical aspects.

    PubMed

    Sharma, Aditya Prakash; Devana, Sudheer Kumar; Bora, Girdhar Singh; Mavuduru, Ravimohan; Mandal, Arup Kumar

    2016-06-01

    Robot-assisted partial nephrectomy has become a safe and feasible procedure for small renal masses (SRM). Similarly, robot-assisted adrenalectomy has also been well established. Robotic surgery has provided the possibility to manage complex cases that are considered technically challenging for traditional laparoscopy. We describe in this video the details of performing simultaneous robotic adrenalectomy with partial nephrectomy highlighting the technical aspects of the same. A 62-year-old gentleman presented to us with incidentally detected left renal complex cyst (Bosniak IIF) and a concomitant left adrenal mass. Hormonal evaluation of adrenal tumor revealed raised levels of serum estrogen and DHEAS. A robotic-assisted simultaneous procedure was planned. Patient was positioned in right lateral position. After port placement, robot was brought from the shoulder of the patient and docked. We first excised the adrenal tumor followed by the renal cyst. Total operative time was 180 min with warm ischemia time of 20 min for renal cyst excision. Drain was removed on post-operative day 2. Patient was discharged on post-operative day 3. Histopathology revealed adrenocortical adenoma and benign hemorrhagic renal cyst. We found simultaneous ipsilateral adrenalectomy with partial nephrectomy using robotic assistance is feasible and safe with minimal morbidity. Port placement in such cases should be individualized according to the location of the SRM. The robot provides the ergonomic advantage and 3D vision for better anatomic definition as compared to laparoscopy. PMID:26861448

  5. Label-free, live optical imaging of reprogrammed bipolar disorder patient-derived cells reveals a functional correlate of lithium responsiveness.

    PubMed

    Wang, J L; Shamah, S M; Sun, A X; Waldman, I D; Haggarty, S J; Perlis, R H

    2014-01-01

    Development of novel treatments and diagnostic tools for psychiatric illness has been hindered by the absence of cellular models of disease. With the advent of cellular reprogramming, it may be possible to recapitulate the disease biology of psychiatric disorders using patient skin cells transdifferentiated to neurons. However, efficiently identifying and characterizing relevant neuronal phenotypes in the absence of well-defined pathophysiology remains a challenge. In this study, we collected fibroblast samples from patients with bipolar 1 disorder, characterized by their lithium response (n=12), and healthy control subjects (n=6). We identified a cellular phenotype in reprogrammed neurons using a label-free imaging assay based on a nanostructured photonic crystal biosensor and found that an optical measure of cell adhesion was associated with clinical response to lithium treatment. This cellular phenotype may represent a useful biomarker to evaluate drug response and screen for novel therapeutics. PMID:25158003

  6. Multiphasic approach reveals genetic diversity of environmental and patient isolates of Mycobacterium mucogenicum and Mycobacterium phocaicum associated with an outbreak of bacteremias at a Texas hospital.

    PubMed

    Cooksey, Robert C; Jhung, Michael A; Yakrus, Mitchell A; Butler, W Ray; Adékambi, Toidi; Morlock, Glenn P; Williams, Margaret; Shams, Alicia M; Jensen, Bette J; Morey, Roger E; Charles, Nadege; Toney, Sean R; Jost, Kenneth C; Dunbar, Denise F; Bennett, Vickie; Kuan, Marcella; Srinivasan, Arjun

    2008-04-01

    Between March and May 2006, a Texas hospital identified five Mycobacterium mucogenicum bloodstream infections among hospitalized oncology patients using fluorescence high-performance liquid chromatography analysis of mycolic acids. Isolates from blood cultures were compared to 16 isolates from environmental sites or water associated with this ward. These isolates were further characterized by hsp65, 16S rRNA, and rpoB gene sequencing, hsp65 PCR restriction analysis, and molecular typing methods, including repetitive element PCR, random amplified polymorphic DNA PCR, and pulsed-field gel electrophoresis (PFGE) of large restriction fragments. Three of five patient isolates were confirmed as M. mucogenicum and were in a single cluster as determined by all identification and typing methods. The remaining two patient isolates were identified as different strains of Mycobacterium phocaicum by rpoB sequence analysis. One of these matched an environmental isolate from a swab of a hand shower in the patient's room, while none of the clinical isolates of M. mucogenicum matched environmental strains. Among the other 15 environmental isolates, 11 were identified as M. mucogenicum and 4 as M. phocaicum strains, all of which were unrelated by typing methods. Although the 16S rRNA gene sequences matched for all 14 M. mucogenicum isolates, there were two each of the hsp65 and rpoB sequevars, seven PCR typing patterns, and 12 PFGE patterns. Among the seven M. phocaicum isolates were three 16S rRNA sequevars, two hsp65 sequevars, two rpoB sequevars, six PCR typing patterns, and six PFGE patterns. This outbreak represents the first case of catheter-associated bacteremia caused by M. phocaicum and the first report of clinical isolates from a U.S. hospital. The investigation highlights important differences in the available typing methods for mycobacteria and demonstrates the genetic diversity of these organisms even within narrow confines of time and space. PMID:18310417

  7. 1H-NMR-Based Metabolic Analysis of Human Serum Reveals Novel Markers of Myocardial Energy Expenditure in Heart Failure Patients

    PubMed Central

    Su, Liang; Lai, Wenyan; Wang, Peng; Xie, Zhibing; Xie, Zhiquan; Zeng, Qingchun; Ren, Hao; Xu, Dingli

    2014-01-01

    Objective Elevated myocardial energy expenditure (MEE) is related with reduced left ventricular ejection fraction, and has also been documented as an independent predictor of cardiovascular mortality. However, the serum small-molecule metabolite profiles and pathophysiological mechanisms of elevated MEE in heart failure (HF) are still lacking. Herein, we used 1H-NMR-based metabolomics analysis to screen for potential biomarkers of MEE in HF. Methods A total of 61 subjects were enrolled, including 46 patients with heart failure and 15 age-matched controls. Venous serum samples were collected from subjects after an 8-hour fast. An INOVA 600 MHz nuclear magnetic resonance spectrometer with Carr-Purcell-Melboom-Gill (CPMG) pulse sequence was employed for the metabolomics analysis and MEE was calculated using colored Doppler echocardiography. Metabolomics data were processed using orthogonal signal correction and regression analysis was performed using the partial least squares method. Results The mean MEE levels of HF patients and controls were 139.61±58.18 cal/min and 61.09±23.54 cal/min, respectively. Serum metabolomics varied with MEE changed, and 3-hydroxybutyrate, acetone and succinate were significantly elevated with the increasing MEE. Importantly, these three metabolites were independent of administration of angiotensin converting enzyme inhibitor, β-receptor blockers, diuretics and statins (P>0.05). Conclusions These results suggested that in patients with heart failure, MEE elevation was associated with significant changes in serum metabolomics profiles, especially the concentration of 3-hydroxybutyrate, acetone and succinate. These compounds could be used as potential serum biomarkers to study myocardial energy mechanism in HF patients. PMID:24505394

  8. Psychiatric aspects of Parkinson's disease

    PubMed Central

    Grover, Sandeep; Somaiya, Mansi; Kumar, Santhosh; Avasthi, Ajit

    2015-01-01

    Parkinson's disease (PD) is essentially characterized by the motor symptoms in the form of resting tremor, rigidity and bradykinesia. However, over the years it has been recognized that motor symptoms are just the “tip of the iceberg” of clinical manifestations of PD. Besides motor symptoms, PD characterized by many non-motor symptoms, which include cognitive decline, psychiatric disturbances (depression, psychosis and impulse control), sleep difficulties, autonomic failures (gastrointestinal, cardiovascular, urinary, thermoregulation) and pain syndrome. This review evaluates the various aspects of psychiatric disorders including cognitive decline and sleep disturbances in patients with PD. The prevalence rate of various psychiatric disorders is high in patients with PD. In terms of risk factors, various demographic, clinical and treatment-related variables have been shown to be associated with higher risk of development of psychiatric morbidity. Evidence also suggests that the presence of psychiatric morbidity is associated with poorer outcome. Randomized controlled trials, evaluating the various pharmacological and non-pharmacological treatments for management of psychiatric morbidity in patients with PD are meager. Available evidence suggests that tricyclic antidepressants like desipramine and nortriptyline are efficacious for management of depression. Among the antipsychotics, clozapine is considered to be the best choice for management of psychosis in patients with PD. Among the various cognitive enhancers, evidence suggest efficacy of rivastigmine in management of dementia in patients with PD. To conclude, this review suggests that psychiatric morbidity is highly prevalent in patients with PD. Hence, a multidisciplinary approach must be followed to improve the overall outcome of PD. Further studies are required to evaluate the efficacy of various other measures for management of psychiatric morbidity in patients with PD. PMID:25552854

  9. Psychiatric aspects of Parkinson's disease.

    PubMed

    Grover, Sandeep; Somaiya, Mansi; Kumar, Santhosh; Avasthi, Ajit

    2015-01-01

    Parkinson's disease (PD) is essentially characterized by the motor symptoms in the form of resting tremor, rigidity and bradykinesia. However, over the years it has been recognized that motor symptoms are just the "tip of the iceberg" of clinical manifestations of PD. Besides motor symptoms, PD characterized by many non-motor symptoms, which include cognitive decline, psychiatric disturbances (depression, psychosis and impulse control), sleep difficulties, autonomic failures (gastrointestinal, cardiovascular, urinary, thermoregulation) and pain syndrome. This review evaluates the various aspects of psychiatric disorders including cognitive decline and sleep disturbances in patients with PD. The prevalence rate of various psychiatric disorders is high in patients with PD. In terms of risk factors, various demographic, clinical and treatment-related variables have been shown to be associated with higher risk of development of psychiatric morbidity. Evidence also suggests that the presence of psychiatric morbidity is associated with poorer outcome. Randomized controlled trials, evaluating the various pharmacological and non-pharmacological treatments for management of psychiatric morbidity in patients with PD are meager. Available evidence suggests that tricyclic antidepressants like desipramine and nortriptyline are efficacious for management of depression. Among the antipsychotics, clozapine is considered to be the best choice for management of psychosis in patients with PD. Among the various cognitive enhancers, evidence suggest efficacy of rivastigmine in management of dementia in patients with PD. To conclude, this review suggests that psychiatric morbidity is highly prevalent in patients with PD. Hence, a multidisciplinary approach must be followed to improve the overall outcome of PD. Further studies are required to evaluate the efficacy of various other measures for management of psychiatric morbidity in patients with PD. PMID:25552854

  10. Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas

    PubMed Central

    Zhang, Wensheng; Edwards, Andrea; Fang, Zhide; Flemington, Erik K.; Zhang, Kun

    2016-01-01

    Patients with HPV-positive head neck squamous cell carcinomas (HNSCC) usually have a better prognosis than the HPV-negative cases while the underlying mechanism remains far from being well understood. We investigated this issue by an integrative analysis of clinically-annotated multi-omics HNSCC data released by the Cancer Genome Atlas. As confirmatory results, we found: (1) Co-occurrence of mutant TP53 and HPV infection was rare; (2) Regardless of HPV status, HNSCCs of wild-type TP53 implied a good survival chance for patients and had fewer genome-wide somatic mutations than those with a mutation burden on the gene. Our analysis further led to some novel observations. They included: (1) The genes involved in “DNA mismatch repair” pathway were up-regulated in HPV-positive tumors compared to normal tissue samples and HPV-negative cases, and thus constituted a strong predictive signature for the identification of HPV infection; (2) HPV infection could disrupt some regulatory miRNA-mRNA correlations operational in the HPV-negative tumors. In light of these results, we proposed a hypothesis for the favorable clinical outcomes of HPV-positive HNSCC patients. That is, the replication of HPV genome and/or its invasion into the genomes of cancer cells may enhance DNA repair mechanisms, which in turn limit the accumulation of lethal somatic mutations. PMID:27108969

  11. Integrative Genomics and Transcriptomics Analysis Reveals Potential Mechanisms for Favorable Prognosis of Patients with HPV-Positive Head and Neck Carcinomas.

    PubMed

    Zhang, Wensheng; Edwards, Andrea; Fang, Zhide; Flemington, Erik K; Zhang, Kun

    2016-01-01

    Patients with HPV-positive head neck squamous cell carcinomas (HNSCC) usually have a better prognosis than the HPV-negative cases while the underlying mechanism remains far from being well understood. We investigated this issue by an integrative analysis of clinically-annotated multi-omics HNSCC data released by the Cancer Genome Atlas. As confirmatory results, we found: (1) Co-occurrence of mutant TP53 and HPV infection was rare; (2) Regardless of HPV status, HNSCCs of wild-type TP53 implied a good survival chance for patients and had fewer genome-wide somatic mutations than those with a mutation burden on the gene. Our analysis further led to some novel observations. They included: (1) The genes involved in "DNA mismatch repair" pathway were up-regulated in HPV-positive tumors compared to normal tissue samples and HPV-negative cases, and thus constituted a strong predictive signature for the identification of HPV infection; (2) HPV infection could disrupt some regulatory miRNA-mRNA correlations operational in the HPV-negative tumors. In light of these results, we proposed a hypothesis for the favorable clinical outcomes of HPV-positive HNSCC patients. That is, the replication of HPV genome and/or its invasion into the genomes of cancer cells may enhance DNA repair mechanisms, which in turn limit the accumulation of lethal somatic mutations. PMID:27108969

  12. Disparity between dorsal and ventral networks in patients with obsessive-compulsive disorder: evidence revealed by graph theoretical analysis based on cortical thickness from MRI

    PubMed Central

    Kim, Seung-Goo; Jung, Wi Hoon; Kim, Sung Nyun; Jang, Joon Hwan; Kwon, Jun Soo

    2013-01-01

    As one of the most widely accepted neuroanatomical models on obsessive-compulsive disorder (OCD), it has been hypothesized that imbalance between an excitatory direct (ventral) pathway and an inhibitory indirect (dorsal) pathway in cortico-striato-thalamic circuit underlies the emergence of OCD. Here we examine the structural network in drug-free patients with OCD in terms of graph theoretical measures for the first time. We used a measure called efficiency which quantifies how a node transfers information efficiently. To construct brain networks, cortical thickness was automatically estimated using T1-weighted magnetic resonance imaging. We found that the network of the OCD patients was as efficient as that of healthy controls so that the both networks were in the small-world regime. More importantly, however, disparity between the dorsal and the ventral networks in the OCD patients was found in terms of graph theoretical measures, suggesting a positive evidence to the imbalance theory on the underlying pathophysiology of OCD. PMID:23840184

  13. A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in De-escalated Antibiotic Therapy in Critically Ill Patients

    PubMed Central

    Roberts, Jason A.; Stove, Veronique; Verstraete, Alain G.; Lipman, Jeffrey; De Waele, Jan J.

    2015-01-01

    De-escalation of empirical antibiotic therapy is often included in antimicrobial stewardship programs in critically ill patients, but differences in target attainment when antibiotics are switched are rarely considered. The primary objective of this study was to compare the fractional target attainments of contemporary dosing of empirical broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics for a number pathogens for which de-escalation may be considered. The secondary objective was to determine whether alternative dosing strategies improve target attainment. We performed a simulation study using published population pharmacokinetic (PK) studies in critically ill patients for a number of broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics. Simulations were undertaken using a data set obtained from critically ill patients with sepsis without absolute renal failure (n = 49). The probability of target attainment of antibiotic therapy for different microorganisms for which de-escalation was applied was analyzed. EUCAST MIC distribution data were used to calculate fractional target attainment. The probability that therapeutic exposure will be achieved was lower for the narrower-spectrum antibiotics with conventional dosing than for the broad-spectrum alternatives and could drastically be improved with higher dosages and different modes of administrations. For a selection of microorganisms, the probability that therapeutic exposure will be achieved was overall lower for the narrower-spectrum antibiotics using conventional dosing than for the broad-spectrum antibiotics. PMID:26014946

  14. Verb aspect, event structure, and coreferential processing

    PubMed Central

    Ferretti, Todd R.; Rohde, Hannah; Kehler, Andrew; Crutchley, Melanie

    2012-01-01

    We used an off-line story continuation task and an online ERP reading task to investigate coreferential processing following sentences that portrayed transfer-of-possession events as either ongoing or completed, using imperfective and perfective verb aspect (e.g., Amanda was shifting/shifted some poker chips to Scott). The story continuation task demonstrated that people were more likely to begin continuations with references to the Goal than to the Source, but that perfective aspect strengthened this bias. In the ERP task we probed expectations for Source and Goal referents by employing pronouns that matched one of the referents in gender. The ERP results were consistent with the biases revealed in the story continuation task and demonstrate that the difference in Goal bias for the two forms of aspect was manifested differently in the brain. These results provide novel behavioral and neurocognitive evidence that verb aspect influences the construction of situation models during language comprehension. PMID:22690039

  15. Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE.

    PubMed

    das Chagas Medeiros, M M; Bezerra, M Campos; Braga, F N Holanda Ferreira; da Justa Feijão, M R Melo; Gois, A C Rodrigues; Rebouças, V C do Rosário; de Carvalho, T M Amorim Zaranza; Carvalho, L N Solon; Ribeiro, Át Mendes

    2016-04-01

    The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality. PMID:26405022

  16. Cognitive aspects of color

    NASA Astrophysics Data System (ADS)

    Derefeldt, Gunilla A. M.; Menu, Jean-Pierre; Swartling, Tiina

    1995-04-01

    This report surveys cognitive aspects of color in terms of behavioral, neuropsychological, and neurophysiological data. Color is usually defined as psychophysical color or as perceived color. Behavioral data on categorical color perception, absolute judgement of colors, color coding, visual search, and visual awareness refer to the more cognitive aspects of color. These are of major importance in visual synthesis and spatial organization, as already shown by the Gestalt psychologists. Neuropsychological and neurophysiological findings provide evidence for an interrelation between cognitive color and spatial organization. Color also enhances planning strategies, as has been shown by studies on color and eye movements. Memory colors and the color- language connections in the brain also belong among the cognitive aspects of color.

  17. 16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation.

    PubMed

    Montassier, Emmanuel; Batard, Eric; Massart, Sébastien; Gastinne, Thomas; Carton, Thomas; Caillon, Jocelyne; Le Fresne, Sophie; Caroff, Nathalie; Hardouin, Jean Benoit; Moreau, Philippe; Potel, Gilles; Le Vacon, Françoise; de La Cochetière, Marie France

    2014-04-01

    Gastrointestinal disturbances are a side-effect frequently associated with haematological malignancies due to the intensive cytotoxic treatment given in connection with bone marrow transplantation (BMT). However, intestinal microbiota changes during chemotherapy remain poorly described, probably due to the use of culture-based and low-resolution molecular methods in previous studies. The objective of our study was to apply a next generation DNA sequencing technology to analyse chemotherapy-induced changes in faecal microbiota. We included eight patients with non-Hodgkin's lymphoma undergoing one course of BMT conditioning chemotherapy. We collected a prechemotherapy faecal sample, the day before chemotherapy was initiated, and a postchemotherapy sample, collected 1 week after the initiation of chemotherapy. Total DNA was extracted from faecal samples, denaturing high-performance liquid chromatography based on amplification of the V6 to V8 region of the 16S ribosomal RNA (rRNA) gene, and 454-pyrosequencing of the 16 S rRNA gene, using PCR primers targeting the V5 and V6 hypervariable 16S rRNA gene regions were performed. Raw sequence data were screened, trimmed, and filtered using the QIIME pipeline. We observed a steep reduction in alpha diversity and significant differences in the composition of the intestinal microbiota in response to chemotherapy. Chemotherapy was associated with a drastic drop in Faecalibacterium and accompanied by an increase of Escherichia. The chemotherapy-induced shift in the intestinal microbiota could induce severe side effects in immunocompromised cancer patients. Our study is a first step in identifying patients at risk for gastrointestinal disturbances and to promote strategies to prevent this drastic shift in intestinal microbiota. PMID:24402367

  18. Deep Sequencing of the Trypanosoma cruzi GP63 Surface Proteases Reveals Diversity and Diversifying Selection among Chronic and Congenital Chagas Disease Patients

    PubMed Central

    Llewellyn, Martin S.; Messenger, Louisa A.; Luquetti, Alejandro O.; Garcia, Lineth; Torrico, Faustino; Tavares, Suelene B. N.; Cheaib, Bachar; Derome, Nicolas; Delepine, Marc; Baulard, Céline; Deleuze, Jean-Francois; Sauer, Sascha; Miles, Michael A.

    2015-01-01

    Background Chagas disease results from infection with the diploid protozoan parasite Trypanosoma cruzi. T. cruzi is highly genetically diverse, and multiclonal infections in individual hosts are common, but little studied. In this study, we explore T. cruzi infection multiclonality in the context of age, sex and clinical profile among a cohort of chronic patients, as well as paired congenital cases from Cochabamba, Bolivia and Goias, Brazil using amplicon deep sequencing technology. Methodology/ Principal Findings A 450bp fragment of the trypomastigote TcGP63I surface protease gene was amplified and sequenced across 70 chronic and 22 congenital cases on the Illumina MiSeq platform. In addition, a second, mitochondrial target—ND5—was sequenced across the same cohort of cases. Several million reads were generated, and sequencing read depths were normalized within patient cohorts (Goias chronic, n = 43, Goias congenital n = 2, Bolivia chronic, n = 27; Bolivia congenital, n = 20), Among chronic cases, analyses of variance indicated no clear correlation between intra-host sequence diversity and age, sex or symptoms, while principal coordinate analyses showed no clustering by symptoms between patients. Between congenital pairs, we found evidence for the transmission of multiple sequence types from mother to infant, as well as widespread instances of novel genotypes in infants. Finally, non-synonymous to synonymous (dn:ds) nucleotide substitution ratios among sequences of TcGP63Ia and TcGP63Ib subfamilies within each cohort provided powerful evidence of strong diversifying selection at this locus. Conclusions/Significance Our results shed light on the diversity of parasite DTUs within each patient, as well as the extent to which parasite strains pass between mother and foetus in congenital cases. Although we were unable to find any evidence that parasite diversity accumulates with age in our study cohorts, putative diversifying selection within members of the TcGP63I

  19. An in silico Approach Reveals Associations between Genetic and Epigenetic Factors within Regulatory Elements in B Cells from Primary Sjögren's Syndrome Patients.

    PubMed

    Konsta, Orsia D; Le Dantec, Christelle; Charras, Amandine; Brooks, Wesley H; Arleevskaya, Marina I; Bordron, Anne; Renaudineau, Yves

    2015-01-01

    Recent advances in genetics have highlighted several regions and candidate genes associated with primary Sjögren's syndrome (SS), a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear that epigenetic deregulations are present during SS and restricted to specific cell type subsets, such as lymphocytes and salivary gland epithelial cells. In this study, 72 single nucleotide polymorphisms (SNPs) associated with 43 SS gene risk factors were selected from publicly available and peer reviewed literature for further in silico analysis. SS risk variant location was tested revealing a broad distribution in coding sequences (5.6%), intronic sequences (55.6%), upstream/downstream genic regions (30.5%), and intergenic regions (8.3%). Moreover, a significant enrichment of regulatory motifs (promoter, enhancer, insulator, DNAse peak, and expression quantitative trait loci) characterizes SS risk variants (94.4%). Next, screening SNPs in high linkage disequilibrium (r (2) ≥ 0.8 in Caucasians) revealed 645 new variants including 5 SNPs with missense mutations, and indicated an enrichment of transcriptionally active motifs according to the cell type (B cells > monocytes > T cells ≫ A549). Finally, we looked at SS risk variants for histone markers in B cells (GM12878), monocytes (CD14(+)) and epithelial cells (A548). Active histone markers were associated with SS risk variants at both promoters and enhancers in B cells, and within enhancers in monocytes. In conclusion and based on the obtained in silico results that need further confirmation, associations were observed between SS genetic risk factors and epigenetic factors and these associations predominate in B cells, such as those observed at the FAM167A-BLK locus. PMID:26379672

  20. Medical Aspects of Surfing.

    ERIC Educational Resources Information Center

    Renneker, Mark

    1987-01-01

    The medical aspects of surfing include ear and eye injuries and sprains and strains of the lower back and neck, as well as skin cancer from exposure to the sun. Treatment, rehabilitation, and prevention of these problems are discussed. Surfing is recommended as part of an exercise program for reasonably healthy people. (Author/MT)

  1. Sociological Aspects of Deafness.

    ERIC Educational Resources Information Center

    World Federation of the Deaf, Rome (Italy).

    Nine conference papers treat the sociological aspects of deafness. Included are "Individuals Being Deaf and Blind and Living with a Well Hearing Society" by A. Marx (German Federal Republic), "A Deaf Man's Experiences in a Hearing World" by A. B. Simon(U.S.A.), "Problem of Text Books and School Appliances for Vocational Education of Deaf Adults"…

  2. Aspects of Marine Ecology.

    ERIC Educational Resources Information Center

    Awkerman, Gary L.

    This publication is designed for use in standard science curricula to develop oceanologic manifestations of certain science topics. Included are teacher guides, student activities, and demonstrations to impart ocean science understanding, specifically, aspects of marine ecology, to high school students. The course objectives include the ability of…

  3. Aspects of Language.

    ERIC Educational Resources Information Center

    Bolinger, Dwight

    A survey of the substance of linguistics and of the activities of linguists is presented in an attempt to acquaint ordinary readers with the various aspects of la"guage. A discussion of the human tendency toward speech, of the traits of language, and of phonetic elements prepares the way for an analysis of the structure of languag e in terms of…

  4. Psychological Aspects of Aging.

    ERIC Educational Resources Information Center

    Mooney, Craig M.

    1980-01-01

    Psychological aspects of aging, based on gerontological hypotheses and research, are presented under three headings: intellectual abilities; emotional capacities; and motor capabilities. Consequences are discussed. Well-being throughout life depends on fulfillment of fundamental human needs; existential needs for nourishment, stimulation, rest,…

  5. When natural mutants do not fit our expectations: the intriguing case of patients with XRCC4 mutations revealed by whole-exome sequencing

    PubMed Central

    de Villartay, Jean-Pierre

    2015-01-01

    Mutations in the XRCC4 gene have been recently identified through whole-exome sequencing (WES). While the overall clinical presentation of the patients (severe short stature, microcephaly, gonadal failure) generally conforms with what is expected for the defect of a critical non-homologous end-joining (NHEJ) DNA repair factor, the absence of consequence on the proper development of the immune system is rather surprising, given the role of NHEJ in V(D)J recombination. Several hypotheses can be envisioned to explain this discrepancy. Overall, these findings highlight the power of WES in identifying new molecular causes for human diseases while providing with new exciting scientific question to address. PMID:25962386

  6. Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

    PubMed Central

    Alves, Chrystian J.; Dariolli, Rafael; Jorge, Frederico M.; Monteiro, Matheus R.; Maximino, Jessica R.; Martins, Roberto S.; Strauss, Bryan E.; Krieger, José E.; Callegaro, Dagoberto; Chadi, Gerson

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that leads to widespread motor neuron death, general palsy and respiratory failure. The most prevalent sporadic ALS form is not genetically inherited. Attempts to translate therapeutic strategies have failed because the described mechanisms of disease are based on animal models carrying specific gene mutations and thus do not address sporadic ALS. In order to achieve a better approach to study the human disease, human induced pluripotent stem cell (hiPSC)-differentiated motor neurons were obtained from motor nerve fibroblasts of sporadic ALS and non-ALS subjects using the STEMCCA Cre-Excisable Constitutive Polycistronic Lentivirus system and submitted to microarray analyses using a whole human genome platform. DAVID analyses of differentially expressed genes identified molecular function and biological process-related genes through Gene Ontology. REVIGO highlighted the related functions mRNA and DNA binding, GTP binding, transcription (co)-repressor activity, lipoprotein receptor binding, synapse organization, intracellular transport, mitotic cell cycle and cell death. KEGG showed pathways associated with Parkinson's disease and oxidative phosphorylation, highlighting iron homeostasis, neurotrophic functions, endosomal trafficking and ERK signaling. The analysis of most dysregulated genes and those representative of the majority of categorized genes indicates a strong association between mitochondrial function and cellular processes possibly related to motor neuron degeneration. In conclusion, iPSC-derived motor neurons from motor nerve fibroblasts of sporadic ALS patients may recapitulate key mechanisms of neurodegeneration and may offer an opportunity for translational investigation of sporadic ALS. Large gene profiling of differentiated motor neurons from sporadic ALS patients highlights mitochondrial participation in the establishment of autonomous mechanisms associated with sporadic ALS

  7. Comprehensive analysis of miRNA expression in T-cell subsets of rheumatoid arthritis patients reveals defined signatures of naive and memory Tregs

    PubMed Central

    Smigielska-Czepiel, K; van den Berg, A; Jellema, P; van der Lei, R J; Bijzet, J; Kluiver, J; Boots, A M H; Brouwer, E; Kroesen, B-J

    2014-01-01

    Disturbed expression of microRNAs (miRNAs) in regulatory T cells (Tregs) leads to development of autoimmunity in experimental mouse models. However, the miRNA expression signature characterizing Tregs of autoimmune diseases, such as rheumatoid arthritis (RA) has not been determined yet. In this study, we have used a microarray approach to comprehensively analyze miRNA expression signatures of both naive Tregs (CD4+CD45RO-CD25++) and memory Tregs (CD4+CD45RO+CD25+++), as well as conventional naive (CD4+CD45RO−CD25−) and memory (CD4+CD45RO+CD25−) T cells (Tconvs) derived from peripheral blood of RA patients and matched healthy controls. Differential expression of selected miRNAs was validated by TaqMan-based quantitative reverse transcription-PCR. We found a positive correlation between increased expression of miR-451 in T cells of RA patients and disease activity score (DAS28), erythrocyte sedimentation rate levels and serum levels of interleukin-6. Moreover, we found characteristic, disease- and treatment-independent, global miRNA expression signatures defining naive Tregs, memory Tregs, naive Tconvs and memory Tconvs. The analysis allowed us to define miRNAs characteristic for a general naive phenotype (for example, miR-92a) and a general memory phenotype (for example, miR-21, miR-155). Importantly, the analysis allowed us to define miRNAs that are specifically expressed in both naive and memory Tregs, defining as such miRNA signature characterizing the Treg phenotype (that is, miR-146a, miR-3162, miR-1202, miR-1246 and miR-4281). PMID:24401767

  8. Shared and distinct anatomical correlates of semantic and phonemic fluency revealed by lesion-symptom mapping in patients with ischemic stroke.

    PubMed

    Biesbroek, J Matthijs; van Zandvoort, Martine J E; Kappelle, L Jaap; Velthuis, Birgitta K; Biessels, Geert Jan; Postma, Albert

    2016-05-01

    Semantic and phonemic fluency tasks are frequently used to test executive functioning, speed and attention, and access to the mental lexicon. In semantic fluency tasks, subjects are required to generate words belonging to a category (e.g., animals) within a limited time window, whereas in phonemic fluency tasks subjects have to generate words starting with a given letter. Anatomical correlates of semantic and phonemic fluency are currently assumed to overlap in left frontal structures, reflecting shared executive processes, and to be distinct in left temporal and right frontal structures, reflecting involvement of distinct memory processes and search strategies. Definite evidence for this assumption is lacking. To further establish the anatomical correlates of semantic and phonemic fluency, we applied assumption-free voxel-based and region-of-interest-based lesion-symptom mapping in 93 patients with ischemic stroke. Fluency was assessed by asking patients to name animals (semantic), and words starting with the letter N and A (phonemic). Our findings indicate that anatomical correlates of semantic and phonemic fluency overlap in the left inferior frontal gyrus and insula, reflecting shared underlying cognitive processes. Phonemic fluency additionally draws on the left rolandic operculum, which might reflect a search through phonological memory, and the middle frontal gyrus. Semantic fluency additionally draws on left medial temporal regions, probably reflecting a search through semantic memory, and the right inferior frontal gyrus, which might reflect the application of a visuospatial mental imagery strategy in semantic fluency. These findings establish shared and distinct anatomical correlates of semantic and phonemic fluency. PMID:25939335

  9. A favorable role of prolactin in human breast cancer reveals novel pathway-based gene signatures indicative of tumor differentiation and favorable patient outcome.

    PubMed

    Hachim, Ibrahim Y; Shams, Anwar; Lebrun, Jean-Jacques; Ali, Suhad

    2016-07-01

    Prolactin (PRL) hormone is known to play a key role in mammary gland development allowing for successful lactation. The role of this hormone in breast tumorigenesis is still controversial. Here, we evaluated PRL protein and gene expression levels in human breast cancer using tissue microarray of 100 breast cancer cases, as well as different publically available human breast cancer gene profiling databases. Interestingly, our results showed a significant downregulation of PRL expression in breast cancer compared to normal adjacent tissue. Moreover, expression of PRL was associated with more differentiated tumors, early stage, smaller tumor size and absence of distant metastasis. Importantly, our results indicate that higher PRL mRNA levels are significantly associated with prolonged relapse-free survival (RFS) in breast cancer patients (P=3.7 x 10(-9)). Additionally, examining expression of PRL pathway-based gene signature composed of PRL, PRLR, Jak2 and Stat5a showed a significant association with more differentiated tumors (P<.00001), prolonged RFS (P=1.8 x 10(-6)) as well as overall survival (OS) (P=.0026). As well, our results indicate that PRL-directed differentiation program in mammary epithelial cells offer good prognosis in human breast cancer. Indeed, expression of a gene signature composed of PRL-upregulated genes showed a significant association with well-differentiated tumors (P<.00001). Whereas expression of a gene signature composed of PRL-downregulated genes showed a significant association with shortened distant metastasis-free survival (DMFS) (P=.0086). Altogether our results highlight that PRL hormone and its signaling pathway may play an important role in maintaining tumor differentiation state and in turn better patient outcome. PMID:26980025

  10. [Biliary pathology. Key aspects of the problem].

    PubMed

    Il'chenko, A A

    2011-01-01

    Based on the clinical experience gained in the Department of Pathology biliary tract, Central Research Institute of Gastroenterology, were reviewed key aspects of biliary pathology on the issues of classification, diagnosis, treatment, and tactics for management of patients with various diseases of the biliary tract. PMID:21560643

  11. Psychosomatic Aspects of Cancer: An Overview.

    ERIC Educational Resources Information Center

    Murray, John B.

    1980-01-01

    It is suggested in this literature review on the psychosomatic aspects of cancer that psychoanalytic interpretations which focused on intrapsychic elements have given way to considerations of rehabilitation and assistance with the complex emotional reactions of patients and their families to terminal illness and death. (Author/DB)

  12. Aesthetic aspects of abdominal wall and external genital reconstructive surgery in bladder exstrophy-epispadias complex.

    PubMed

    VanderBrink, Brian A; Stock, Jeffrey A; Hanna, Moneer K

    2006-03-01

    Long-term follow-up of patients born with classical bladder exstrophy-epispadias complex (EEC) reveals that many of them suffer from poor self-image, and the aesthetic aspects of the genitalia and lower abdomen acquire greater significance with age. In this article, we review the aesthetic outcomes in performing puboplasty, umbilicoplasty, and genitoplasty in patients born with EEC. Retrospective review of the cosmetic and functional outcomes in 116 patients born with EEC treated by puboplasty, umbilicoplasty, or genitoplasty was performed. Satisfaction with the cosmetic and functional outcomes of these three reconstructive surgeries was high following initial reconstructive efforts (> 90%). Attention to cosmesis during abdominal wall and genital reconstruction for EEC helps to improve a patient's perception of body image and self-esteem. Our experience with these procedures over the past 25 years demonstrated that the efforts directed toward aesthetics have been well worthwhile. PMID:16527001

  13. Googling Stroke ASPECTS to Determine Disability: Exploratory Analysis from VISTA-Acute Collaboration

    PubMed Central

    Beare, Richard; Chen, Jian; Phan, Thanh G.

    2015-01-01

    The summed Alberta Stroke Program Early CT Score (ASPECTS) is useful for predicting stroke outcome. The anatomical information in the CT template is rarely used for this purpose because traditional regression methods are not adept at handling collinearity (relatedness) among brain regions. While penalized logistic regression (PLR) can handle collinearity, it does not provide an intuitive understanding of the interaction among network structures in a way that eigenvector method such as PageRank can (used in Google search engine). In this exploratory analysis we applied graph theoretical analysis to explore the relationship among ASPECTS regions with respect to disability outcome. The Virtual International Stroke Trials Archive (VISTA) was searched for patients who had infarct in at least one ASPECTS region (ASPECTS ≤9, ASPECTS=10 were excluded), and disability (modified Rankin score/mRS). A directed graph was created from a cross correlation matrix (thresholded at false discovery rate of 0.01) of the ASPECTS regions and demographic variables and disability (mRS>2). We estimated the network-based importance of each ASPECTS region by comparing PageRank and node strength measures. These results were compared with those from PLR. There were 185 subjects, average age 67.5± 12.8 years (55% Males). Model 1: demographic variables having no direct connection with disability, the highest PageRank was M2 (0.225, bootstrap 95% CI 0.215-0.347). Model 2: demographic variables having direct connection with disability, the highest PageRank were M2 (0.205, bootstrap 95% CI 0.194-0.367) and M5 (0.125, bootstrap 95% CI 0.096-0.204). Both models illustrate the importance of M2 region to disability. The PageRank method reveals complex interaction among ASPECTS regions with respects to disability. This approach may help to understand the infarcted brain network involved in stroke disability. PMID:25961856

  14. Exploring Prostate Cancer Genome Reveals Simultaneous Losses of PTEN, FAS and PAPSS2 in Patients with PSA Recurrence after Radical Prostatectomy

    PubMed Central

    Ibeawuchi, Chinyere; Schmidt, Hartmut; Voss, Reinhard; Titze, Ulf; Abbas, Mahmoud; Neumann, Joerg; Eltze, Elke; Hoogland, Agnes Marije; Jenster, Guido; Brandt, Burkhard; Semjonow, Axel

    2015-01-01

    The multifocal nature of prostate cancer (PCa) creates a challenge to patients’ outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients’ clinico-pathological information, specific prognostic biomarker can be identified. Our study utilized the Affymetrix SNP 6.0 Genome-wide assay to investigate forty-three fresh frozen PCa tissue foci from twenty-three patients. With a long clinical follow-up period that ranged from 2.0–9.7 (mean 5.4) years, copy number variation (CNV) data was evaluated for association with patients’ PSA status during follow-up. From our results, the loss of unique genes on 10q23.31 and 10q23.2–10q23.31 were identified to be significantly associated to PSA recurrence (p < 0.05). The implication of PTEN and FAS loss (10q23.31) support previous reports due to their critical roles in prostate carcinogenesis. Furthermore, we hypothesize that the PAPSS2 gene (10q23.2–10q23.31) may be functionally relevant in post-operative PSA recurrence because of its reported role in androgen biosynthesis. It is suggestive that the loss of the susceptible region on chromosome 10q, which implicates PTEN, FAS and PAPSS2 may serve as genetic predictors of PSA recurrence after radical prostatectomy. PMID:25679447

  15. Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients.

    PubMed

    Haschemi Nassab, Mani; Rhein, Mathias; Hagemeier, Lars; Kaeser, Marius; Muschler, Marc; Glahn, Alexander; Pich, Andreas; Heberlein, Annemarie; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge; Hillemacher, Thomas

    2016-01-01

    Acetaldehyde, the carcinogenic metabolite of ethanol known to provoke aversive symptoms of alcohol consumption, is predominantly eliminated by aldehyde dehydrogenase 2 (ALDH2). Reduced ALDH2 activity correlates with low alcohol tolerance and low risk for alcohol dependence. The ALDH2 promoter polymorphism rs886205 (A>G) is associated with decreased promoter activity, but a molecular mechanism and allele-dependent ALDH2 protein expression has not been described yet. On the basis of allele-dependent epigenetic effects, we analyzed the rs886205 genotype, methylation rates of cytosine-phosphatidyl-guanine (CpG)-sites within a regulatory promoter region and ALDH2 protein levels in 82 alcohol-dependent patients during a 2-week withdrawal and compared them to 34 matched controls. Patients without the G-allele of rs886205 showed higher methylation of the promoter region than controls and readily adapted epigenetically as well as on protein level during withdrawal, while patients with the G-allele displayed retarded methylation readjustment and no change in ALDH2 protein levels. Our data provide novel insights into an unknown genetic-epigenetic interaction, revealing impaired ALDH2 protein expression in patients with the G-allele of rs886205. Additionally, we checked for an association between rs886205 and protection against alcohol dependence and found a trend association between the G-allele and protection against alcohol dependence that needs replication in a larger Caucasian cohort. PMID:26339786

  16. Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms.

    PubMed Central

    Tromp, G; Wu, Y; Prockop, D J; Madhatheri, S L; Kleinert, C; Earley, J J; Zhuang, J; Norrgård, O; Darling, R C; Abbott, W M

    1993-01-01

    Detailed DNA sequencing of the triple-helical domain of type III procollagen was carried out on cDNA prepared from 54 patients with aortic aneurysms. The 43 male and 11 female patients originated from 50 different families and five different nationalities. 43 patients had at least one additional blood relative who had aneurysms. Five overlapping asymmetric PCR products, covering all the coding sequences of the triple-helical domain of type III procollagen, were sequenced with 28 specific sequencing primers. Analysis of the sequencing gels revealed only two nucleotide changes that altered the structure of the protein. One was a substitution of threonine for proline at amino acid position 501 and its functional importance was not clearly established. The other was a substitution of arginine for an obligatory glycine at amino acid position 136. In 40 of the 54 patients, detection of a polymorphism in the mRNA established that both alleles were expressed. The results indicate that mutations in type III procollagen are the cause of only about 2% of aortic aneurysms. Images PMID:8514866

  17. REVEAL-1, a phase 2 dose regimen optimization study of vosaroxin in older poor-risk patients with previously untreated acute myeloid leukaemia

    PubMed Central

    Stuart, Robert K; Cripe, Larry D; Maris, Michael B; Cooper, Maureen A; Stone, Richard M; Dakhil, Shaker R; Turturro, Francesco; Stock, Wendy; Mason, James; Shami, Paul J; Strickland, Stephen A; Costa, Luciano J; Borthakur, Gautam; Michelson, Glenn C; Fox, Judith A; Leavitt, Richard D; Ravandi, Farhad

    2015-01-01

    This phase 2 study (N = 116) evaluated single-agent vosaroxin, a first-in-class anticancer quinolone derivative, in patients ≥60 years of age with previously untreated unfavourable prognosis acute myeloid leukaemia. Dose regimen optimization was explored in sequential cohorts (A: 72 mg/m2 d 1, 8, 15; B: 72 mg/m2 d 1, 8; C: 72 mg/m2 or 90 mg/m2 d 1, 4). The primary endpoint was combined complete remission rate (complete remission [CR] plus CR with incomplete platelet recovery [CRp]). Common (>20%) grade ≥3 adverse events were thrombocytopenia, febrile neutropenia, anaemia, neutropenia, sepsis, pneumonia, stomatitis and hypokalaemia. Overall CR and CR/CRp rates were 29% and 32%; median overall survival (OS) was 7·0 months; 1-year OS was 34%. Schedule C (72 mg/m2) had the most favourable safety and efficacy profile, with faster haematological recovery (median 27 d) and lowest incidence of aggregate sepsis (24%) and 30-d (7%) and 60-d (17%) all-cause mortality; at this dose and schedule, CR and CR/CRp rates were 31% and 35%, median OS was 7·7 months and 1-year OS was 38%. Overall, vosaroxin resulted in low early mortality and an encouraging response rate; vosaroxin 72 mg/m2 d 1, 4 is recommended for further study in this population. Registered at www.clinicaltrials.gov: #NCT00607997. PMID:25403830

  18. LC-MS metabolomics of psoriasis patients reveals disease severity-dependent increases in circulating amino acids that are ameliorated by anti-TNFα treatment.

    PubMed

    Kamleh, Muhammad Anas; Snowden, Stuart G; Grapov, Dmitry; Blackburn, Gavin J; Watson, David G; Xu, Ning; Ståhle, Mona; Wheelock, Craig E

    2015-01-01

    Psoriasis is an immune-mediated highly heterogeneous skin disease in which genetic as well as environmental factors play important roles. In spite of the local manifestations of the disease, psoriasis may progress to affect organs deeper than the skin. These effects are documented by epidemiological studies, but they are not yet mechanistically understood. In order to provide insight into the systemic effects of psoriasis, we performed a nontargeted high-resolution LC-MS metabolomics analysis to measure plasma metabolites from individuals with mild or severe psoriasis as well as healthy controls. Additionally, the effects of the anti-TNFα drug Etanercept on metabolic profiles were investigated in patients with severe psoriasis. Our analyses identified significant psoriasis-associated perturbations in three metabolic pathways: (1) arginine and proline, (2) glycine, serine and threonine, and (3) alanine, aspartate, and glutamate. Etanercept treatment reversed the majority of psoriasis-associated trends in circulating metabolites, shifting the metabolic phenotypes of severe psoriasis toward that of healthy controls. Circulating metabolite levels pre- and post-Etanercept treatment correlated with psoriasis area and severity index (PASI) clinical scoring (R(2) = 0.80; p < 0.0001). Although the responsible mechanism(s) are unclear, these results suggest that psoriasis severity-associated metabolic perturbations may stem from increased demand for collagen synthesis and keratinocyte hyperproliferation or potentially the incidence of cachexia. Data suggest that levels of circulating amino acids are useful for monitoring both the severity of disease as well as therapeutic response to anti-TNFα treatment. PMID:25361234

  19. Immune Aspects of Female Infertility

    PubMed Central

    Brazdova, Andrea; Senechal, Helene; Peltre, Gabriel; Poncet, Pascal

    2016-01-01

    Immune infertility, in terms of reproductive failure, has become a serious health issue involving approximately 1 out of 5 couples at reproductive age. Semen that is defined as a complex fluid containing sperm, cellular vesicles and other cells and components, could sensitize the female genital tract. The immune rejection of male semen in the female reproductive tract is explained as the failure of natural tolerance leading to local and/or systemic immune response. Present active immune mechanism may induce high levels of anti-seminal/sperm antibodies. It has already been proven that iso-immunization is associated with infertility. Comprehensive studies with regards to the identification of antibody-targets and the determination of specific antibody class contribute to the development of effective immuno-therapy and, on the other hand, potential immuno-contraception, and then of course to complex patient diagnosis. This review summarizes the aspects of female immune infertility. PMID:27123194

  20. Psychiatric Aspects of Organ Transplantation

    PubMed Central

    Kalra, G.; Desousa, A.

    2011-01-01

    Surgical transplantation of human organs from deceased as well as living donors to sick and dying patients began after the Second World War. Over the past 50 years the transplantation of human organs, tissues and cells has become a worldwide practice which has extended, and greatly enhanced the quality of hundreds of thousands of lives. The field of transplantation medicine provides an important chance for liaison between psychiatric professionals and other transplant physicians and surgeons. The discrepancy between the ever-increasing demand for organs but the decreasing supply makes it important to evaluate and prioritize individuals who are in dire need of the organ. However, this also gives rise to certain ethical questions. The following paper discusses various psychiatric aspects of organ transplantation in general. PMID:25013589

  1. Ergonomical aspects of anaesthetic practice.

    PubMed

    Raghavendra Rao, R S

    2016-05-01

    Anaesthesiologist's service begins as a general physician, goes on as an investigator cum data analyser leading to the architectural planning of a forthcoming surgical event, but only after articulately convincing the subject along with his kith and kin. In the era of rapid developments in the field of medicine which includes relevant developments in anaesthetic care, an adequate work environment has to be provided to the anaesthesia team so that all anaesthetic procedures can be carried out safely and efficiently and an optimal workflow can be established in the operating room environment. Such ecological state demands an updated knowledge and ergonomics to aid him. Unfortunately, ergonomics is an area of anaesthesia that has received little attention and should be addressed through more education and training for workplace well-ness. Hence, an attempt is made to discuss few aspects on ergonomics for the interface between anaesthesiologist-machine-patient systems regarded as human-machine-system. PMID:27212716

  2. Ergonomical aspects of anaesthetic practice

    PubMed Central

    Raghavendra Rao, RS

    2016-01-01

    Anaesthesiologist's service begins as a general physician, goes on as an investigator cum data analyser leading to the architectural planning of a forthcoming surgical event, but only after articulately convincing the subject along with his kith and kin. In the era of rapid developments in the field of medicine which includes relevant developments in anaesthetic care, an adequate work environment has to be provided to the anaesthesia team so that all anaesthetic procedures can be carried out safely and efficiently and an optimal workflow can be established in the operating room environment. Such ecological state demands an updated knowledge and ergonomics to aid him. Unfortunately, ergonomics is an area of anaesthesia that has received little attention and should be addressed through more education and training for workplace well-ness. Hence, an attempt is made to discuss few aspects on ergonomics for the interface between anaesthesiologist-machine-patient systems regarded as human-machine-system. PMID:27212716

  3. Psychosocial Aspects of Obesity.

    PubMed

    Beck, Amy R

    2016-01-01

    This article is the sixth in a series of the comorbidities of childhood obesity and reviews psychosocial aspects with a focus on weight-based victimization and discrimination stemming from weight bias and stigma. Outcomes from these bullying and discriminatory experiences are pervasive and impact youth across all settings, including school. Lastly, this article provides recommendations on how to reduce bias and stigma to better serve these students in the school environment. PMID:26739931

  4. Aspects of B physics

    SciTech Connect

    Gaillard, M.K.

    1987-10-14

    Various aspects of weak decays are commented on. Probing of the standard model and of phenomena beyond the standard model are discussed, followed by a theoretical view of B mesons and some experimental observations on B mesons. The point is made that any data on B decay would be interesting in that it would provide powerful new constraints in analyses of the standard model and extensions thereof. (LEW)

  5. The patient-sensor interface

    PubMed Central

    Crockett, G. S.

    1970-01-01

    During the assessment of monitoring equipment on acute medical cases in a general ward, a quantitative investigation of technical faults revealed that 44% of these occurred at the patient-sensor interface. While the attachment of the equipment was accepted by the patient and was suitable for application by nursing staff, this degree of technical breakdown indicates that more progress is necessary in the design of this aspect of monitoring equipment before it is possible to have a reliable system. ImagesFig. 1 PMID:5476136

  6. Psychosocial Aspects of Scleroderma.

    PubMed

    Kwakkenbos, Linda; Delisle, Vanessa C; Fox, Rina S; Gholizadeh, Shadi; Jewett, Lisa R; Levis, Brooke; Milette, Katherine; Mills, Sarah D; Malcarne, Vanessa L; Thombs, Brett D

    2015-08-01

    Patients with systemic sclerosis (SSc; also called scleroderma) have to cope with not only the physical impacts of the disease but also the emotional and social consequences of living with the condition. Because there is no cure for SSc, improving quality of life is a primary focus of treatment and an important clinical challenge. This article summarizes significant problems faced by patients with SSc, including depression, anxiety, fatigue, sleep disruption, pain, pruritus, body image dissatisfaction, and sexual dysfunction, and describes options to help patients cope with the consequences of the disease. PMID:26210133

  7. Aspects of emergent symmetries

    NASA Astrophysics Data System (ADS)

    Gomes, Pedro R. S.

    2016-03-01

    These are intended to be review notes on emergent symmetries, i.e. symmetries which manifest themselves in specific sectors of energy in many systems. The emphasis is on the physical aspects rather than computation methods. We include some background material and go through more recent problems in field theory, statistical mechanics and condensed matter. These problems illustrate how some important symmetries, such as Lorentz invariance and supersymmetry, usually believed to be fundamental, can arise naturally in low-energy regimes of systems involving a large number of degrees of freedom. The aim is to discuss how these examples could help us to face other complex and fundamental problems.

  8. Ceramics with decorative aspect

    NASA Astrophysics Data System (ADS)

    Voica, Cezara

    2009-08-01

    The last decades brought the development of bone china techniques used for producing the decorative articles. These products can be glazed with a transparent and thin glaze layer, even with more special (decorative) ones which gives new aesthetic aspect. The present article presents the results obtained after the studies performed for matte glazes for decorative bone china. As microcrystalization agent were used zinc oxide; the content of this oxide bring some changes of the basic glaze thus the chemical composition must be adjusted as the fluxes would present the desired properties after the heating process.

  9. Breast Cancer 2012 - New Aspects.

    PubMed

    Kolberg, H-C; Lüftner, D; Lux, M P; Maass, N; Schütz, F; Fasching, P A; Fehm, T; Janni, W; Kümmel, S

    2012-07-01

    Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, however potentially promising combinations do not always achieve a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also inherited genetic properties of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Also health-economic aspects are more frequently being taken into consideration so that health-economic considerations may also play a part. This review is based on information from the recent annual congresses. The latest of these are the 34th San Antonio Breast Cancer Symposium 2011 and the ASCO Annual Meeting 2012. Among their highlights are the clinically significant results from the CLEOPATRA, BOLERO-2, EMILIA and SWOG S0226 trials on the therapy for metastatic breast cancer as well as further state-of-the-art data on the adjuvant use of bisphosphonates within the framework of the ABCSG-12, ZO-FAST, NSABP-B34 and GAIN trials. PMID:25324576

  10. Psychological aspects of juvenile fibromyalgia syndrome: a literature review.

    PubMed

    Goulart, Rubens; Pessoa, Cinthia; Lombardi, Império

    2016-01-01

    Juvenile fibromyalgia syndrome (JFMS) is a non-inflammatory chronic pain condition that occurs mainly in girls aged 9-15 years. JFMS is characterized by constant widespread pain in different parts of the body, poor sleep quality, daytime sleepiness and an altered mood. Concomitant psychological and organic factors result in a diminished capacity to cope with pain. The quality of life of individuals with chronic pain and their caregivers is severely restricted and the occurrence of symptoms of anxiety and depression is common in this population. The aim of the present study was to perform a systematic review of the literature on psychosocial factors related to JFMS. The findings reveal differences in opinion between patients and family members regarding the effect of the condition, as mothers tend to classify JFMS as more severe than the patients themselves. Individuals with JFMS seem to share the same personality traits and there seems to be a type of family environment that is favorable to the occurrence of this condition. Psychological and functional aspects should be treated with methods that can help patients and family members alter their coping strategies regarding day-to-day problems, attenuate the dysfunctional consequences of pain and fatigue and diminish the risk of catastrophizing that individuals submitted to constant pain develop in relation to their surrounding environment. PMID:27267336

  11. Aspects of Gond astronomy

    NASA Astrophysics Data System (ADS)

    Vahia, M. N.; Halkare, Ganesh

    2013-03-01

    The Gond community is considered to be one of the most ancient tribes of India with a continuing history of several thousand years. They are also known for their largely isolated history which they have retained through the millennia. Several of their intellectual traditions therefore are a record of parallel aspects of human intellectual growth, and still preserve their original flavour and have not been homogenised by the later traditions of India. In view of this, the Gonds provide a special window to the different currents that constitute contemporary India. In the present study, we summarise their mythology, genetics and script. We then investigate their astronomical traditions and try to understand this community through a survey of 15 Gond villages spread over Maharashtra, Andhra Pradesh and Madhya Pradesh. We show that they have a distinctly different view of the sky from the conventional astronomical ideas encountered elsewhere in India, which is both interesting and informative. We briefly comment on other aspects of their life as culled from our encounters with different members of the Gond community.

  12. Postmenopausal osteoporosis: microradiographic aspects.

    PubMed

    Dhem, A; Nyssen-Behets, C; Coppens, J

    1998-01-01

    A comparative microradiographic and histologic analysis of undecalcified bone samples was performed in men and women aged 18-98 years. These morphological methods showed that besides usual lamellar bone remodelling, all the so-called inert surfaces, namely both haversian and vascular canals as well as trabecular surfaces, were involved in weathering alterations of the superficial lamellae, resulting in eroded outlines devoid of osteoclast. These aspects, recorded in all pieces of our material, were visible from the earliest adult age and were randomly distributed. Except the grade of osteoporosis at a given age, the microradiographic and histologic aspects were similar in both aged men and women and did not allow sex distinction. These observations were consistent with the hypothesis of a particular destructive process affecting all the quiescent lamellar bone surfaces without osteoclast or cell participation. This kind of erosion, termed delitescence, could be at least partially responsible for the age-related and postmenopausal bone loss. In order to explain the increasing osteoporosis after menopause, it has been suggested that the estrogen deficiency could increase the percentage of dead osteocytes. Thereby the reduced cellular control on the bone surface could impair the remodeling process and fail to adapt the bone structure by repairing the microscopic lesions. PMID:11315966

  13. Electrocardiograph abnormalities revealed during laparoscopy

    PubMed Central

    Nijjer, Sukhjinder; Dubrey, Simon William

    2010-01-01

    This brief case presents a well patient in whom an electrocardiograph abnormality consistent with an accessory pathway was found during a routine procedure. We present the electrocardiographs, explain the underlying condition, and consider why the abnormality was revealed in this manner. PMID:22419949

  14. [Responsibility and legal aspects of implantology].

    PubMed

    Giltay, G B; Malvoz, R E

    2001-01-01

    Medico-legal aspects regarding oral implantology are to be found in the Civil Right and governed by the Belgian civil code (article 1382) and by the specific nature of the relationship between the practitioner and the patient. Both the patient and the practitioner are to fulfill a number of obligations. One of these, is the compulsory 'informed consent' to be obtained from the patient. However, this consent is preceded by the information given and repeated by the practitioner to the patient regarding the proposed treatment. This article describes precautions and obligations to observe by the practitioner in order to minimize the possibility of being sued by a patient. Various anamnestic question lists are provided in this article. PMID:11508124

  15. Myasthenia Gravis: Medical Aspects

    PubMed Central

    Zeldowicz, Ludmila R.; Buckler, William St. John

    1965-01-01

    The diagnosis of myasthenia gravis is often difficult and calls for a broader use of pharmacological and electrodiagnostic tests. The decamethonium-edrophonium test, which has proved superior to other procedures for this purpose, is based on neurophysiological principles and depicts the behaviour of the neuromuscular junction. A state of resistance to depolarizing agents in the limited form of myasthenia and a state of a non-depolarizing (competitive) block in advanced cases has been shown. This test has demonstrated that the neuromuscular defect exists throughout the skeletal musculature, including muscles clinically unaffected. It produced no false-positive results either in normal or neurasthenic persons or in patients with neurological diseases with myasthenic symptoms. In a patient with botulism and in a patient with ocular palsies from brain-stem encephalitis the edrophonium test gave a false-positive result, while the decamethonium-edrophonium test was negative. Diagnosis, treatment and management of myasthenic emergencies are described. PMID:14323662

  16. Aspects of Plant Intelligence

    PubMed Central

    TREWAVAS, ANTHONY

    2003-01-01

    Intelligence is not a term commonly used when plants are discussed. However, I believe that this is an omission based not on a true assessment of the ability of plants to compute complex aspects of their environment, but solely a reflection of a sessile lifestyle. This article, which is admittedly controversial, attempts to raise many issues that surround this area. To commence use of the term intelligence with regard to plant behaviour will lead to a better understanding of the complexity of plant signal transduction and the discrimination and sensitivity with which plants construct images of their environment, and raises critical questions concerning how plants compute responses at the whole‐plant level. Approaches to investigating learning and memory in plants will also be considered. PMID:12740212

  17. Various aspects of gravity

    NASA Astrophysics Data System (ADS)

    Jankiewicz, Marcin

    2007-12-01

    This thesis summarizes research projects that I have been involved in during my graduate studies at Vanderbilt University. My research spanned different areas of theoretical high energy physics with gravity as a common denominator. I explore both fundamental and phenomenological aspects of: (i) mathematical physics where I have studied relations between partition functions of certain class of conformal field theories and Fischer-Griess Monster group; (ii) cosmology, where I performed a numerical study of a horizon size modes of scalar field; (iii) a black hole physics project involving possible extensions of the non-hair theorem in a presence of exotic types of scalar field; and (iv) a study of phenomenological space-time foam models and their relation to Planck scale physics.

  18. Aspects, Wrappers and Events

    NASA Technical Reports Server (NTRS)

    Filman, Robert E.

    2003-01-01

    This viewgraph presentation provides information on Object Infrastructure Framework (OIF), an Aspect-Oriented Programming (AOP) system. The presentation begins with an introduction to the difficulties and requirements of distributed computing, including functional and non-functional requirements (ilities). The architecture of Distributed Object Technology includes stubs, proxies for implementation objects, and skeletons, proxies for client applications. The key OIF ideas (injecting behavior, annotated communications, thread contexts, and pragma) are discussed. OIF is an AOP mechanism; AOP is centered on: 1) Separate expression of crosscutting concerns; 2) Mechanisms to weave the separate expressions into a unified system. AOP is software engineering technology for separately expressing systematic properties while nevertheless producing running systems that embody these properties.

  19. Geometrical aspects of entanglement

    SciTech Connect

    Leinaas, Jon Magne; Myrheim, Jan; Ovrum, Eirik

    2006-07-15

    We study geometrical aspects of entanglement, with the Hilbert-Schmidt norm defining the metric on the set of density matrices. We focus first on the simplest case of two two-level systems and show that a 'relativistic' formulation leads to a complete analysis of the question of separability. Our approach is based on Schmidt decomposition of density matrices for a composite system and nonunitary transformations to a standard form. The positivity of the density matrices is crucial for the method to work. A similar approach works to some extent in higher dimensions, but is a less powerful tool. We further present a numerical method for examining separability and illustrate the method by a numerical study of bound entanglement in a composite system of two three-level systems.

  20. Nutritional aspect of nephrolithiasis

    PubMed Central

    Saxena, Anita; Sharma, R. K.

    2010-01-01

    Nephrolithiasis is associated with a variety of abnormalities in urinary composition. These abnormal urinary risk factors are due to dietary indiscretions, physiological-metabolic disturbances or both. Stone disease is morbid and costly, and the recurrence rates may be as high as 30-50% after 5 years. Efforts to prevent stone formation are, therefore, essential. Dietary factors play an important role in kidney stone formation. Tailored dietary recommendations based on metabolic evaluation should be offered to patients for the prevention of recurrence of stone formation. Dietary intervention and subsequent evaluations of therapeutic efficacy should be based on results from multiple 24-h urine collections. Urine flow of >1 ml/kg/h almost eliminates the risk of supersaturation for calcium oxalate, calcium phosphate and uric acid, thus protecting from the formation of corresponding kidney stones. In patients with cystenuria, the required urine flow may even be higher and, in cases such as primary xanthinuria, high fluid intake is required. Milk intake in these patients should be within the RDA of calcium and protein. In children, recommendation of a high fluid intake has only limited success. Nevertheless, each patient should be advised about adequate fluid intake to increase urine volume in accordance with body size. Although children with hypocitraturia may benefit from therapeutic agents that raise the urine citrate concentration, all children bearing residual fragments should be counseled on adequate fluid intake along with potassium citrate treatment to prevent stone regrowth or formation. PMID:21369385

  1. Urgent-start peritoneal dialysis: nursing aspects.

    PubMed

    Groenhoff, Cheryl; Delgado, Edna; McClernon, Marilyn; Davis, Alicia; Malone, Latasha; Majirsky, Janet; Guest, Steven

    2014-01-01

    Urgent-start peritoneal dialysis (PD) refers to the initiation of dialysis soon after a PD catheter placement and is a treatment option available to the late-referred patient with advanced kidney disease. This article reviews nursing aspects of urgent-start PD and can serve as a guide for this evolving clinical pathway that can provide renal replacement therapy for a critical segment of the population with Stage 5 chronic kidney disease who require renal replacement therapy. PMID:25244889

  2. [Fascioliasis hepatis--computed tomographic aspect].

    PubMed

    Goebel, N; Markwalder, K; Siegenthaler, W

    1984-12-01

    In a patient with liver fascioliasis (already excreting eggs with the faeces) a CT scan of the liver showed after i. v. contrast injection a relatively characteristic aspect with multiple, small, hypodense areas, partly in formations of bunches of grapes, partly in a street-like arrangement towards the portal vein - bile duct - areas. 9 months later the hypodense lesions had markedly decreased. PMID:6518725

  3. Induced abortion: epidemiological aspects.

    PubMed Central

    Baird, D

    1975-01-01

    Sir Dugald Baird sketches the history of abortion legislation in Great Britain from the beginning of the century. In his views the 1967 Abortion Act has been one of the most important and beneficial pieces of social legislation enacted in Britain in the last 100 years. It has, however, brought problems both of administration in the hospitals and to individual doctors and nurses, particularly when the patients are young single women and even schoolgirls. One of the consequences of the Abortion Act has been a fall in maternal mortality and perinatal mortality rates. Abortion does not seem to be followed by serious emotional sequelae. Nevertheless recent changes in sexual mores have introduced new and serious social problems which are discussed in relation to the role of the doctor in his relationship with patients seeking abortion. PMID:765461

  4. Aspects of aluminum toxicity

    SciTech Connect

    Hewitt, C.D.; Savory, J.; Wills, M.R. )

    1990-06-01

    Aluminum is the most abundant metal in the earth's crust. The widespread occurrence of aluminum, both in the environment and in foodstuffs, makes it virtually impossible for man to avoid exposure to this metal ion. Attention was first drawn to the potential role of aluminum as a toxic metal over 50 years ago, but was dismissed as a toxic agent as recently as 15 years ago. The accumulation of aluminum, in some patients with chronic renal failure, is associated with the development of toxic phenomena; dialysis encephalopathy, osteomalacic dialysis osteodystrophy, and an anemia. Aluminum accumulation also occurs in patients who are not on dialysis, predominantly infants and children with immature or impaired renal function. Aluminum has also been implicated as a toxic agent in the etiology of Alzheimer's disease, Guamiam amyotrophic lateral sclerosis, and parkinsonism-dementia. 119 references.

  5. Colorectal carcinoma: Pathologic aspects

    PubMed Central

    Fleming, Matthew; Ravula, Sreelakshmi; Tatishchev, Sergei F.

    2012-01-01

    Colorectal carcinoma is one of the most common cancers and one of the leading causes of cancer-related death in the United States. Pathologic examination of biopsy, polypectomy and resection specimens is crucial to appropriate patient managemnt, prognosis assessment and family counseling. Molecular testing plays an increasingly important role in the era of personalized medicine. This review article focuses on the histopathology and molecular pathology of colorectal carcinoma and its precursor lesions, with an emphasis on their clinical relevance. PMID:22943008

  6. [Behavioral aspects of chronic pain syndromes].

    PubMed

    Oliveira, J T

    2000-06-01

    The knowledge of biological pain mechanisms are not sufficient for the understanding of patients with chronic pain syndromes such as low back, cervicobrachial and muscle pain. Psychological and psychosocial aspects play important roles in the setting and perpetuation of symptoms. Mood and anxiety disorders, secondary gains such as early retirement and financial compensations, must all be acknowledged by the physician as possible contributors to the symptoms. Abnormal illness behavior may better characterize patients with chronic pain syndromes. Behavior observation, which is akin to medical practice, is therefore a powerful tool in the diagnosis and management of these syndromes. Physicians ought be very careful in not reinforcing the patients already strong organic convictions regarding their symptoms, avoiding making decisions based on patients complaints and alleged disabilities, and assigning poorly defined and disputable diagnosis labels. Society needs also to refrain from policies that encourage abnormal illness behaviors. PMID:10849642

  7. Psychosocial aspects of abortion

    PubMed Central

    Illsley, Raymond; Hall, Marion H.

    1976-01-01

    The literature on psychosocial aspects of abortion is confusing. Individual publications must be interpreted in the context of cultural, religious, and legal constraints obtaining in a particular society at a given time, with due attention to the status and availability of alternatives to abortion that might be chosen by a woman with an “unwanted” pregnancy. A review of the literature shows that, where careful pre- and post-abortion assessments are made, the evidence is that psychological benefit commonly results, and serious adverse emotional sequelae are rare. The outcome of refused abortion seems less satisfactory, with regrets and distress frequently occurring. Research on the administration of abortion services suggests that counselling is often of value, that distress is frequently caused by delays in deciding upon and in carrying out abortions, and by unsympathetic attitudes of service providers. The phenomenon of repeated abortion seeking should be seen in the context of the availability and cost of contraception and sterilization. The place of sterilization with abortion requires careful study. A recommendation is made for observational descriptive research on populations of women with potentially unwanted pregnancies in different cultures, with comparisons of management systems and an evaluation of their impact on service users. PMID:1085671

  8. Strategic Aspects of Communication

    NASA Astrophysics Data System (ADS)

    Hagen, Edward; Hammerstein, Peter; Hess, Nicole

    Rarely do human behavioral scientists and scholars study language, music, and other forms of communication as strategies—a means to some end. Some even deny that communication is the primary function of these phenomena. Here we draw upon selections of our earlier work to briefly define the strategy concept and sketch how decision theory, developed to explain the behavior of rational actors, is applied to evolved agents. Communication can then be interpreted as a strategy that advances the "fitness interests" of such agents. When this perspective is applied to agents with conflicts of interest, deception emerges as an important aspect of communication. We briefly review costly signaling, one solution to the problem of honest communication among agents with conflicts of interest. We also explore the subversion of cooperative signals by parasites and by plants defending themselves against herbivores, and we touch on biases in human gossip. Experiments with artificial embodied and communicating agents confirm that when there are conflicts of interest among agents, deception readily evolves. Finally, we consider signaling among super-organisms and the possible implications for understanding human music and language.

  9. Electrical aspects of rainout

    SciTech Connect

    Rosenkilde, C.E.

    1981-11-23

    Rainout commonly denotes the aggregate of phenomena associated with precipitation scavenging of radioactivity from a cloud of nuclear debris that is within a natural rain cloud. (In contrast, the term, washout, is applicable when the nuclear cloud is below the rain cloud and the term, fallout, commonly denotes the direct gravitational settling of contaminated solid material from a nuclear cloud.) Nuclear debris aerosols may be scavenged within natural clouds by a variety of different physical processes which may involve diffusion, convection, impaction, nucleation, phoresis, turbulence, and/or electricity among others. Processes which involve electrical aspects are scrutinized for their susceptibility to the intimate presence of the radioactive-cloud environment. This particular choice of electrical processes is not accidental. Nearly all of the listed processes were examined earlier by Williams. His rough estimates suggested that electrical effects, and to a lesser extent turbulence, could enhance the scavenging of those submicron aerosols which reside in the size-range that bridges the minimum in the scavenging rate coefficient which is commonly called the Greenfield gap. This minimum in the scavenging-rate coefficient is created by the simultaneous reduction of scavenging via diffusion and the reduction of scavenging via inertial impaction. However, Williams omitted the specific influence of a radioactive environment. This report aims to remedy this omission.

  10. Meta-Analysis of Transcriptome Data Related to Hippocampus Biopsies and iPSC-Derived Neuronal Cells from Alzheimer's Disease Patients Reveals an Association with FOXA1 and FOXA2 Gene Regulatory Networks.

    PubMed

    Wruck, Wasco; Schröter, Friederike; Adjaye, James

    2016-01-01

    Although the incidence of Alzheimer's disease (AD) is continuously increasing in the aging population worldwide, effective therapies are not available. The interplay between causative genetic and environmental factors is partially understood. Meta-analyses have been performed on aspects such as polymorphisms, cytokines, and cognitive training. Here, we propose a meta-analysis approach based on hierarchical clustering analysis of a reliable training set of hippocampus biopsies, which is condensed to a gene expression signature. This gene expression signature was applied to various test sets of brain biopsies and iPSC-derived neuronal cell models to demonstrate its ability to distinguish AD samples from control. Thus, our identified AD-gene signature may form the basis for determination of biomarkers that are urgently needed to overcome current diagnostic shortfalls. Intriguingly, the well-described AD-related genes APP and APOE are not within the signature because their gene expression profiles show a lower correlation to the disease phenotype than genes from the signature. This is in line with the differing characteristics of the disease as early-/late-onset or with/without genetic predisposition. To investigate the gene signature's systemic role(s), signaling pathways, gene ontologies, and transcription factors were analyzed which revealed over-representation of response to stress, regulation of cellular metabolic processes, and reactive oxygen species. Additionally, our results clearly point to an important role of FOXA1 and FOXA2 gene regulatory networks in the etiology of AD. This finding is in corroboration with the recently reported major role of the dopaminergic system in the development of AD and its regulation by FOXA1 and FOXA2. PMID:26890743

  11. [Forensic medicine aspects of resuscitation].

    PubMed

    Bauer, G

    1987-12-15

    Nowadays, in almost all cases of clinical death, there is at least a remote chance of resuscitation, of restoring breathing and circulation by means of modern methods of cardiopulmonary resuscitation. Statistically, there are more cases of cardiocirculatory arrest due to an internal cause than to a traumatic cause. Just as medical activity in general, resuscitation is increasingly discussed in its legal and ethical aspects. The duty to exercise due care and proper qualification require a very specific approach in the case of resuscitation, as the chain of persons potentially involved in life saving stretches from the medical layman to the specialist trained to deal with emergency situations. As opposed to conditions in other countries, in Austria the duty to render aid and assistance as statutory provision of the penal code can be of great importance in such cases. Criteria and definition, especially in the ad hoc establishment of death, assume a special significance in resuscitation. Over the past years, resuscitation measures within the complex of the procurement of death have repeatedly been put up for discussion. Examples from US judicature may help to define the problem more clearly and also to offer solutions for similar cases. Such decisions should essentially be guided by the consideration of the presumed will of the patient who no longer is in a position to exercise the right of self-determination. PMID:3326291

  12. [Epidemiology and clinical aspects of cold urticaria].

    PubMed

    Möller, A; Henning, M; Zuberbier, T; Czarnetzki-Henz, B M

    1996-07-01

    To study the frequency and clinical aspects of cold urticaria in Central Europe, patient data from a university dermatology clinic and a private dermatology office between 1984-94 were analysed and the patients re-examined if possible. The incidence of cold urticaria was found to be 0.05%. Of the 56 patients with cold urticaria (31 women, 25 men), 49 had idiopathic cold urticaria. The mean age was 41.0 +/- 15.6 year, the mean duration of disease 7.9 +/- 5.8 years. Atopy was found in 46.5% of patients, and 23.2% of the patients suffered from other types of urticaria (cholinergic, chronic idiopathic, dermographic, aquagenic and heat-induced). Laboratory examinations were only rarely abnormal. 44 patients were treated with antihistamines, with generally only moderate symptomatic improvement. Treatment with antibiotics (penicillin, 1-2 mil IU/d over 2-4 weeks, n = 18, or tetracyclines, 2 g/d over 2 weeks, n = 10) induced full remission in 13 patients and symptomatic improvement in 8. During an average of 6.5 year-follow-up, 20 of 43 symptomatic patients went into spontaneous remission. The good therapeutic response to antibiotics in this study underlines the need for a better elucidation of the cause of cold urticaria, in view of possible infectious causes. PMID:8926165

  13. [Psychiatric aspects of autocastration].

    PubMed

    Gyuris, Jenô

    2011-01-01

    In 1982, first time in Hungary, the author published the detailed description of a transsexual, schizophrenic patient performing autocastration and reviewed the literature. Later,in 1988, he described 2 more cases of them, this time jointly observed and treated with urologist. As since the early 1980's no publication dealing with autocastration has appeared in Hungary, the author now reviews the current literature as well as the other recent possibilities of therapeutical microreplantation and individual and family therapeutical possibilities. A part of the paper introduces the current international literature of female autocastration. PMID:21653998

  14. [Psychosocial aspects of preeclampsia].

    PubMed

    Szita, Bernadett; Baji, Ildikó; Rigó, János

    2015-12-13

    Distress conditions during pregnancy may contribute to the development of preeclampsia by altering functions of the neuroendocrine and immune systems, e.g. activation of the hypothalamic-pituitary-adrenal axis and increase in plasma proinflammatory cytokines. Preeclampsia may also precipitate mental health problems due to long-term hospitalization or unpredictable and uncontrollable events such as preterm labor and newborn complications. Besides, preeclampsia may induce persistent neurocognitive complaints with a negative impact on patients' quality of life. As growing evidence indicates that poor maternal mental health has an adverse effect on pregnancy outcome and fetal development, psychosocial interventions may be beneficial for women with preeclampsia. PMID:26639644

  15. [Practical Aspects of Sclerotherapy].

    PubMed

    Stücker, Markus; Dörler, Martin

    2016-06-01

    Sclerotherapy is an important part of the treatment of varicose veins. It may also be performed in patients with contraindications for operative procedures. By adjusting the mode of application (liquid or foam) and the concentration it can be used for the treatment of all vein types. In comparison to other treatment options it is especially well suited for the treatment of spider veins and reticular veins, pudendal varicosity and so called "feeding" varicose veins in the proximity of venous leg ulcers. A current European guideline, which was approved by 23 European phlebologic societies, supports the good international standardization of this treatment technique. PMID:27379853

  16. Cultural aspects of suicide.

    PubMed

    Maharajh, Hari D; Abdool, Petal S

    2005-09-01

    Undefined cultural factors cannot be dismissed and significantly contribute to the worldwide incidence of death by suicide. Culture is an all embracing term and defines the relationship of an individual to his environment. This study seeks to investigate the effect of culture on suicide both regionally and internationally. Culture-bound syndrome with suicidal behaviours specific to a particular culture or geographical region are discussed. Opinions are divided as to the status of religious martyrs. The law itself is silent on many aspects of suicidal behaviour and despite decriminalization of suicide as self-murder, the latter remains on the statutes of many developing countries. The Caribbean region is of concern due to its steady rise in mean suicide rate, especially in Trinidad and Tobago where socio-cultural factors are instrumental in influencing suicidal behaviour. These include transgenerational cultural conflicts, psycho-social problems, media exposure, unemployment, social distress, religion and family structure. The methods used are attributed to accessibility and lethality. Ingestion of poisonous substances is most popular followed by hanging. The gender differences seen with regard to suicidality can also be attributed to gender related psychopathology and psychosocial differences in help-seeking behaviour. These are influenced by the cultural environment to which the individual is exposed. Culture provides coping strategies to individuals; as civilization advances many of these coping mechanisms are lost unclothing the genetic predisposition of vulnerable groups. In the management of suicidal behaviour, a system of therapeutic re-culturation is needed with an emphasis on relevant culture- based therapies. PMID:16155688

  17. [Psychosomatic aspects of endometriosis].

    PubMed

    Lütje, W; Brandenburg, U

    2003-01-01

    Endometriosis is a varied and unspecific disorder, which can be detected by way of subtle diagnostics in almost every woman. In one case it is a minor accidental finding, in another case it is a cancer-like, mostly incurable, chronic painful a disease, which often has sterility and aggressive therapies as subsequence. For the origin of endometriosis many causes are discussed. The theory of retrograde menstruation through an hyperperistaltic-dystocic uterus presents on one hand an organic explanation-concept. From the psychosomatic point of view this unphysiological menstruation could also be seen as the result of an unsolved conflict, which might be connected with the gender-role or personal, familiar and social attitudes about menstruation. The exo- and endogenic supply with hormones in a time with less pregnancies and therefore more menstruation is also a contributing factor to the origin and development of this disturbance. Beside the theory of endometriosis as an autoimmune disease also implicates psychosomatic thoughts. Though there is always a repeatedly talk the "cancer of the career-woman", there are however very few psychosomatic research projects regarding endometriosis. Therefore it is a characteristic of this disease, that finding and feeling are very often controversial. This emphasizes the importance of psychosomatic, psychosexual, social and biographical aspects in connection with endometriosis. This point of view makes a relative plausible and comfortable explanation for the CPPS and sterility uncertain. Without question diagnosis and therapy of endometriosis followed on one hand by stigmatization and on the other hand by often restriction of quality of life leads to a lot of subsequent psychosocial problems. PMID:14505264

  18. Integrative Analyses of Uterine Transcriptome and MicroRNAome Reveal Compromised LIF-STAT3 Signaling and Progesterone Response in the Endometrium of Patients with Recurrent/Repeated Implantation Failure (RIF)

    PubMed Central

    Lim, Eun Jin; Park, Miseon; Yoon, Jung Ah; Kim, Yeon Sun; Kim, Eun-Kyung; Shin, Ji-Eun; Kim, Ji Hyang; Kwon, Hwang; Song, Haengseok; Choi, Dong-Hee

    2016-01-01

    Intimate two-way interactions between the implantation-competent blastocyst and receptive uterus are prerequisite for successful embryo implantation. In humans, recurrent/repeated implantation failure (RIF) may occur due to altered uterine receptivity with aberrant gene expression in the endometrium as well as genetic defects in embryos. Several studies have been performed to understand dynamic changes of uterine transcriptome during menstrual cycles in humans. However, uterine transcriptome of the patients with RIF has not been clearly investigated yet. Here we show that several signaling pathways as well as many genes and microRNAs are dysregulated in the endometrium of patients with RIF (RIFE). Whereas unsupervised hierarchical clustering showed that overall mRNA and microRNA profiles of RIFE were similar to those of endometria of healthy women, many genes were significantly dysregulated in RIFE (cut off at 1.5 fold change). The majority (~75%) of differentially expressed genes in RIFE including S100 calcium binding protein P (S100P), Chemokine (C-X-C motif) ligand 13 (CXCL13) and SIX homeobox 1 (SIX1) were down-regulated, suggesting that reduced uterine expression of these genes is associated with RIF. Gene Set Enrichment analyses (GSEA) for mRNA microarrays revealed that various signaling pathways including Leukemia inhibitory factor (LIF) signaling and a P4 response were dysregulated in RIFE although expression levels of Estrogen receptor α (ERα) and Progesterone receptor (PR) were not significantly altered in RIFE. Furthermore, expression and phosphorylation of Signal transducer and activator of transcription 3 (STAT3) are reduced and a gene set associated with Janus kinase (JAK)-STAT signaling pathway is systemically down-regulated in these patients. Pairwise analyses of microRNA arrays with prediction of dysregulated microRNAs based on mRNA expression datasets demonstrated that 6 microRNAs are aberrantly regulated in RIFE. Collectively, we here suggest

  19. Genetic aspects of pancreatitis.

    PubMed

    Whitcomb, David C

    2010-01-01

    Acute pancreatitis and chronic pancreatitis are complex inflammatory disorders of the pancreas with unpredictable severity, complications, and clinical courses. Growing evidence for genetic risk and modifying factors, plus strong evidence that only a minority of patients with these disorders are heavy alcohol drinkers, has revolutionized our concept of these diseases. Once considered a self-inflicted injury, pancreatitis is now recognized as a complex inflammatory condition like inflammatory bowel disease. Genetic linkage and candidate gene studies have identified six pancreas-targeting factors that are associated with changes in susceptibility to acute and/or chronic pancreatitis, including cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2), serine protease inhibitor Kazal 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsinogen C (CTRC) and calcium-sensing receptor (CASR). Patients with mutations in these genes are at increased risk of pancreatitis caused by a variety of stresses including hyperlipidemia and hypercalcemia. Multiple studies are reporting new polymorphisms, as well as complex gene x gene and gene x environmental interactions. PMID:20059346

  20. [Medical aspects of fasting].

    PubMed

    Gavrankapetanović, F

    1997-01-01

    Fasting (arabic-savm) was proclaimed through islam, and thus it is an obligation for Holly Prophet Muhammad s.a.v.s.-Peace be to Him-in the second year after Hijra (in 624 after Milad-born of Isa a.s.). There is a month of fasting-Ramadan-each lunar (hijra) year. So, it was 1415th fasting this year. Former Prophets have brought obligative messages on fasting to their people; so there are also certain forms of fasting with other religions i.e. with Catholics, Jews, Orthodox. These kinds of fasting above differ from muslim fasting, but they also appear obligative. All revelations have brought fasting as obligative. From medical point of view, fasting has two basical components: psychical and physical. Psychical sphere correlate closely with its fundamental ideological message. Allah dz.s. says in Quran: "... Fasting is obligative for you, as it was obligative to your precedents, as to avoid sins; during very few days (II, II, 183 & 184)." Will strength, control of passions, effort and self-discipline makes a pure faithfull person, who purify its mind and body through fasting. Thinking about The Creator is more intensive, character is more solid; and spirit and will get stronger. We will mention the hadith saying: "Essaihune humus saimun!" That means: "Travellers at the Earth are fasters (of my ummet)." The commentary of this hadith, in the Collection of 1001 hadiths (Bin bir hadis), number 485, says: "There are no travelling dervishs or monks in islam; thus there is no such a kind of relligousity in islam. In stead, it is changed by fasting and constant attending of mosque. That was proclaimed as obligation, although there were few cases of travelling in the name of relligousity, like travelling dervishs and sheichs." In this paper, the author discusses medical aspects of fasting and its positive characteristics in the respect of healthy life style and prevention of many sicks. The author mentions positive influence of fasting to certain system and organs of human

  1. Aspects of flux compactification

    NASA Astrophysics Data System (ADS)

    Liu, Tao

    In this thesis, we study three main aspects of flux compactifications: (1) classify supergravity solutions from flux compactification; (2) construct flux-deformed geometry and 4D low-energy theory to describe these flux vacua; and (3) study 4D particle phenomenology and cosmology of flux vacua. In the first part, we review G-structure, the basic tool to study supersymmetric flux solutions, and some typical solutions obtained in heterotic, type IIA and type IIB string theories. Then we present a comprehensive classification of supersymmetric vacua of M-theory compactification on 7D manifolds with general four-form fluxes. We analyze the cases where the resulting four-dimensional vacua have N = 1, 2, 3, 4 supersymmetry and the internal space allows for SU(2)-, SU(3)- or G 2-structures. In particular, we find for N = 2 supersymmetry, that the external space-time is Minkowski and the base manifold of the internal space is conformally Kahler for SU(2) structures, while for SU(3) structures the internal space has to be Einstein-Sasaki and no internal fluxes are allowed. Moreover, we provide a new vacuum with N = 1 supersymmetry and SU(3) structure, where all fluxes are non-zero and the first order differential equations are solved. In the second part, we simply review the methods used to construct one subclass of fluxed-deformed geometry or the so-called "twisted manifold", and the associated 4D effective theory describing these flux vacua. Then by employing (generalized) Scherk-Schwarz reduction, we construct the geometric twisting for Calabi-Yau manifolds of Voisin-Borcea type (K 3 x T2)/ Z2 and study the superpotential in a type IIA orientifold based on this geometry. The twists modify the direct product by fibering the K 3 over T2 while preserving the Z2 involution. As an important application, the Voisin-Borcea class contains T6/( Z2 x Z2 ), the usual setting for intersecting D6 brane model building. Past work in this context considered only those twists inherited

  2. [Acne vulgaris: endocrine aspects].

    PubMed

    Dekkers, O M; Thio, B H; Romijn, J A; Smit, J W A

    2006-06-10

    Androgens play an important part in the development of acne vulgaris. Androgen levels in patients with acne are higher than those in controls and people with the androgen insensitivity syndrome do not develop acne. Local factors other than androgen plasma levels, also play a part in the development of acne. The skin contains enzymes that convert precursor hormones to the more potent androgens such as testosterone and dihydrotestosterone. Androgen synthesis can therefore be regulated locally. The effects of androgens on the skin are the result of circulating androgens and enzyme activity in local tissues and androgen receptors. Acne is a clinical manifestation of some endocrine diseases. The polycystic ovary syndrome has the highest prevalence. In women with acne that persists after puberty, in 10-200% of cases polycystic ovary syndrome is later diagnosed. The mechanism of hormonal anti-acne therapy may work by blocking the androgen-production (oestrogens) or by blocking the androgen receptor (cyproterone, spironolactone). PMID:16821451

  3. Clinical aspects of telemedicine

    NASA Technical Reports Server (NTRS)

    Merrell, Ronald C.

    1991-01-01

    Communication among physicians is an essential in order to combine our experiences for the elucidation and application of new knowledge and for the accurate and uniform application of established medical practice. This communication requires an adequate understanding of the culture of the patient and the social context of disease and indeed the culture of the physician. Malnutrition in Bangladesh means caloric insufficiency, and a program to lower cholesterol would be impertinent, while a program to enhance the nutrition of patients in Texas by an international effort to import more grain would be ludicrous. In the same vein a public health effort to combat alcoholic cirrhosis in Mecca would be as silly as a program to increase fiber in the diet of the Bantu. Clinical communication must acknowledge the culture of the issue at hand and the differences in the experiential base of the physicians. Not only do geography and culture affect the potential differences in the experiential bases, but the world utilizes very different traditions of education and science in training physicians. We are influenced by the diseases we treat, and learn to look for the expected at least as much as we are attentive to the unexpected. A physician in Siberia would be much more likely to recognize frostbite than one from Buenos Aires, and the Argentine doctor would much more likely consider Chaga's Disease to explain abdominal pain than a colleague in Zurich. Beyond these obvious issues in communication among physicians we must deal with the many languages and idioms used in the world. An overview of using Telemedicine SpaceBridge after the earthquake in the Republic of Armenia in 1988 is presented.

  4. Legal aspects of telepathology.

    PubMed

    Dierks, C

    2000-01-01

    In some legal surroundings telepathology is considered a breach of registrational barriers. The recommendation of the G 8 states in Europe for required legislation in telemedicine suggests to recognise that the localization of the remote health care professional defines the site not only of licensure but also of liability. This approach must be considered helpful, since it can solve many problems brought about by the doubtful results of private international law and conventions like the European Union (EU) and Lugano Convention. Under today's conditions in private international law it must be considered essential to agree upon a choice of law and stipulate a court of jurisdiction when doing telepathology. However, the opposing aims of insuring the patients claims and avoiding jurisdictions that exceed the local expectations of the medical professional must be reconciled. Data protection and data security are other crucial topics that require attention. Generally speaking, the principles of minimum data exchange, anonymity, pseudonymity and cryptography must be established as a basis for all telepathology procedures. Only when personal data is needed, its use can be legitimated. Written consent of the patient is advised. To guarantee a cross-border security level the regulations of the EU-Data Protection Directive need to be transformed into national law. In practise, cross-border dataflow shall only take place where the security level can be maintained even within the other country. Finally, reimbursement questions must be answered to establish a sound economical basis for telepathology. The spatial distance between the participants may yield the question, whether the service has been rendered to an extent necessary and sufficient for reimbursement. If reimbursement takes place on a cross-border or cross-regional level, severe disturbances of the health systems can occur. Regulation schemes or treaties need therefore to be developed to avoid such disturbances and

  5. Genetic aspects of pheochromocytoma.

    PubMed

    Kolačkov, Katarzyna; Tupikowski, Krzysztof; Bednarek-Tupikowska, Grażyna

    2012-01-01

    Pheochromocytomas are derived from chromaffin cells of the adrenal medulla which synthesize and secrete catecholamines, thus affecting the cardiovascular system and metabolic processes. Pheochromocytoma is a tumor of the following multicarcinoma hereditary syndromes: type 2 multiple endocrine neoplasia, von Hippel-Lindau disease, type 1 neurofibromatosis and the pheochromocytomas/paragangliomas syndrome. Pheochromocytomas are relatively rare, and because of non-specific manifestation of these tumors and the possible lack of signs and symptoms for extended periods of time, the diagnosis may be delayed, which may, in turn, lead to death. Pheochromocytomas may occur sporadically. However, due to the frequent incidence of hereditary forms of these cancers, the presymptomatic genetic testing of family members with a positive family history is indicated, thus allowing for selecting people with higher risk of cancer. Early detection of the syndrome and the coexisting tumors (which may be malignant) may lead to a correct diagnosis, regular surveillance, preventive examinations and implementation of appropriate early treatment. Recent examinations have shown significant involvement of RET, VHL, NF1, SDHB and SDHD as well as the newly discovered KIF1Bβ, TMEM127 and MAX genes in pathogenesis of these tumors. The microarray-gene expression studies, based on the analysis of cellular pathways, have revealed two distinct clusters indicating two different routes of tumorgenesis. The genotype-phenotype correlations are still being studied and future research can give us clearer information about the function of these genes, which may prove crucial from the clinical point of view. PMID:23457139

  6. Technical aspects of PACS in Korea

    NASA Astrophysics Data System (ADS)

    Kim, JongHyo

    2002-05-01

    Korea is one of the fastest growing countries in the number of filmless hospitals. More than 70 hospitals have converted to filmless environments by adopting full PAC systems during the last two years. The patient care environment in Korean hospitals was not favorable to PACS implementation. In many out patient clinics, doctors had to see more than hundred patients a day. It was not rare for a radiologist to read several hundred of exams a day. Also, the PACS teams were mandated to acquire full scale PACS capable of incorporating not only radiological images but also color images produced in other imaging departments. In order to take root in Korean environment, the PACS in Korea had to pass through some technical modifications that included introduction of recent hardware technologies and development of new software features. This paper describes various technical aspects of PAC systems in Korea that have met difficult requirements and enabled wide spread of PAC systems to real clinical practice.

  7. Specific aspects of erectile dysfunction in sexology.

    PubMed

    Borrás-Valls, J J; Gonzalez-Correales, R

    2004-10-01

    The sexology of erectile dysfunction (ED) is approached from a perspective that integrates medical, psychological, and social aspects. This article reviews the clinical intervention in sexology beginning with the diagnostic evaluation, where the organic and psychological factors (predisposing, precipitating, and perpetuating) contributing to ED are determined. A description of the differential diagnosis process follows, which establishes the relevance of organic factors in order to organize therapeutic strategies. There are three possible treatment processes: psychological intervention with the patient, intervention on the partner relationship, or intervention with the partner. Referral criteria are also described, such as when patients with ED should be referred to a sexologist, and to whom sexologists should refer patients with ED. PMID:15496855

  8. Nutritional aspects of depression.

    PubMed

    Lang, Undine E; Beglinger, Christoph; Schweinfurth, Nina; Walter, Marc; Borgwardt, Stefan

    2015-01-01

    Several nutrition, food and dietary compounds have been suggested to be involved in the onset and maintenance of depressive disorders and in the severity of depressive symptoms. Nutritional compounds might modulate depression associated biomarkers and parallel the development of depression, obesity and diabetes. In this context, recent studies revealed new mediators of both energy homeostasis and mood changes (i.e. IGF-1, NPY, BDNF, ghrelin, leptin, CCK, GLP-1, AGE, glucose metabolism and microbiota) acting in gut brain circuits. In this context several healthy foods such as olive oil, fish, fruits, vegetables, nuts, legumes, poultry, dairy and unprocessed meat have been inversely associated with depression risk and even have been postulated to improve depressive symptoms. In contrast, unhealthy western dietary patterns including the consumption of sweetened beverage, refined food, fried food, processed meat, refined grain, and high fat diary, biscuits, snacking and pastries have been shown to be associated with an increased risk of depression in longitudinal studies. However, it is always difficult to conclude a real prospective causal relationship from these mostly retrospective studies as depressed individuals might also change their eating habits secondarily to their depression. Additionally specific selected nutritional compounds, e.g. calcium, chromium, folate, PUFAs, vitamin D, B12, zinc, magnesium and D-serine have been postulated to be used as ad-on strategies in antidepressant treatment. In this context, dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and treatment strategy for depression. At last, several medications (pioglitazone, metformin, exenatide, atorvastatin, gram-negative antibiotics), which have traditionally been used to treat metabolic disorders showed a certain potential to treat depression in first randomized controlled clinical trials. PMID:26402520

  9. Pharmacological aspects of (-)-deprenyl.

    PubMed

    Magyar, K; Pálfi, M; Tábi, T; Kalász, H; Szende, B; Szöko, E

    2004-08-01

    Deprenyl, the selective irreversible inhibitor of monoamine oxidase-B (MAO-B), has been synthesised as a potential antidepressant, however, due to its dopamine potentiating capacity, became a registered drug in the treatment of Parkinson's disease. Deprenyl possesses a wide range of pharmacological activities; some of them are not related to its MAO-B inhibitory potency. Beside its dopamine potentiating effect, it renders protection against a number of dopaminergic, cholinergic and noradrenergic neurotoxins with a complex mechanism of action. By inducing antioxidant enzymes and decreasing the formation of reactive oxygen species, deprenyl is able to combat an oxidative challenge implicated as a common causative factor in neurodegenerative diseases. In a dose substantially lower than required for MAO-B inhibition (10(-9)-10(-13) M), deprenyl interferes with early apoptotic signalling events induced by various kinds of insults in cell cultures of neuroectodermal origin, thus protecting cells from apoptotic death. Deprenyl requires metabolic conversion to a hitherto unidentified metabolite to exert its antiapoptotic effect, which serves to protect the integrity of the mitochondrion by inducing transcriptional and translational changes. Pharmacokinetic and metabolism studies have revealed that deprenyl undergoes intensive first pass metabolism, and its major metabolites also possess pharmacological activities. The ratio of the parent compound and its metabolites reaching the systemic circulation and the brain are highly dependent on the routes of administration. Therefore, in the treatment of neurodegenerative diseases, reconsideration of the dosing schedule, by lowering the dose of deprenyl and choosing the most appropriate route of administration, would diminish undesired adverse effects, with unaltered neuroprotective potency. PMID:15279565

  10. Robots in Space -Psychological Aspects

    NASA Technical Reports Server (NTRS)

    Sipes, Walter E.

    2006-01-01

    A viewgraph presentation on the psychological aspects of developing robots to perform routine operations associated with monitoring, inspection, maintenance and repair in space is shown. The topics include: 1) Purpose; 2) Vision; 3) Current Robots in Space; 4) Ground Based Robots; 5) AERCam; 6) Rotating Bladder Robot (ROBLR); 7) DART; 8) Robonaut; 9) Full Immersion Telepresence Testbed; 10) ERA; and 11) Psychological Aspects

  11. Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects.

    PubMed

    Fernandes, Marilyse B L; Maximino, Luciana P; Perosa, Gimol B; Abramides, Dagma V M; Passos-Bueno, Maria Rita; Yacubian-Fernandes, Adriano

    2016-06-01

    Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc. PMID:27028366

  12. Aspect-Oriented Design with Reusable Aspect Models

    NASA Astrophysics Data System (ADS)

    Kienzle, Jörg; Al Abed, Wisam; Fleurey, Franck; Jézéquel, Jean-Marc; Klein, Jacques

    The idea behind Aspect-Oriented Modeling (AOM) is to apply aspect-oriented techniques to (software) models with the aim of modularizing crosscutting concerns. This can be done within different modeling notations, at different levels of abstraction, and at different moments during the software development process. This paper demonstrates the applicability of AOM during the software design phase by presenting parts of an aspect-oriented design of a crisis management system. The design solution proposed in this paper is based on the Reusable Aspect Models (RAM) approach, which allows a modeler to express the structure and behavior of a complex system using class, state and sequence diagrams encapsulated in several aspect models. The paper describes how the model of the "create mission" functionality of the server backend can be decomposed into 23 inter-dependent aspect models. The presentation of the design is followed by a discussion on the lessons learned from the case study. Next, RAM is compared to 8 other AOM approaches according to 6 criteria: language, concern composition, asymmetric and symmetric composition, maturity, and tool support. To conclude the paper, a discussion section points out the features of RAM that specifically support reuse.

  13. Photodynamic therapy--aspects of pain management.

    PubMed

    Fink, Christine; Enk, Alexander; Gholam, Patrick

    2015-01-01

    Topical photodynamic therapy (PDT) is a highly effective and safe treatment method for actinic keratoses with an excellent cosmetic outcome and is commonly used for the therapy of large areas of photodamaged skin with multiple clinically manifest and subclinical lesions. However, the major drawback of photodynamic therapy is the pain experienced during the treatment that can be intense and sometimes even intolerable for patients, requiring interruption or termination of the process. Several strategies for controlling pain during photodynamic therapy have been studied but few effective methods are currently available. Therefore, this review puts the spotlight on predictors on pain intensity and aspects of pain management during photodynamic therapy. PMID:25640485

  14. Self poisoning in Sri Lanka: motivational aspects.

    PubMed

    Hettiarachchi, J; Kodituwakku, G C

    1989-01-01

    Sri Lanka is a developing Asian country with high suicide rate due to self poisoning, related to a high fatality rate. A study of motivational aspects of self poisoning in 97 consecutive patients showed that there is no greater intention of suicide in them than those from the developed countries. Interpersonal disputes involving domestic problems and love affairs are the main precipitating causes. Improving family relations may help in the prevention of self-poisoning. However the impulsive nature of the act might prove prevention a difficult task. PMID:2767925

  15. Administrative Aspects of Human Experimentation.

    ERIC Educational Resources Information Center

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  16. Topological Aspects of Information Retrieval.

    ERIC Educational Resources Information Center

    Egghe, Leo; Rousseau, Ronald

    1998-01-01

    Discusses topological aspects of theoretical information retrieval, including retrieval topology; similarity topology; pseudo-metric topology; document spaces as topological spaces; Boolean information retrieval as a subsystem of any topological system; and proofs of theorems. (LRW)

  17. CLINICAL ASPECTS OF VETERINARY LISTERIOSIS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This invited presentation updates the clinical aspects of Listeria monocytogenes in food animals. It summarizes the epidemiology and diagnostic methods. Virtually all domesticated animal species are susceptible to listeric infection, with a large proportion of healthy asymptomatic animals shedding...

  18. A Digital Solar Aspect Sensor

    NASA Technical Reports Server (NTRS)

    Albus, James S.

    1961-01-01

    The solar aspect sensor described herein performs the analog-to-digital conversion of data optically. To accomplish this, it uses a binary "Gray code" light mask to produce a digital indication, in vehicle-fixed coordinates, of the elevation and azimuth angles of incident light from the sun. This digital solar aspect sensor system, in Explorer X, provided measurements of both elevation and a