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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. 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

  14. 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

  15. 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

  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. [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

  19. 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

  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. 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

  1. 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

  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. 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

  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 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

  15. 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

  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 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

  6. 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

  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. 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

  13. [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

  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. 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

  10. 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

  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. 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

  16. 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

  17. [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

  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. 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

  19. 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

  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

    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

  4. 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

  5. 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

  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

    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 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

  17. 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

  18. 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

  19. 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

  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. 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

  2. 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…

  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. 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

  8. 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

  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. 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

  15. 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

  16. 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

  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. 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

  20. 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

  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. 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

  7. 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

  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. 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

  5. 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

  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 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