Predicting persistence of functional abdominal pain from childhood into young adulthood.

PubMed

Horst, Sara; Shelby, Grace; Anderson, Julia; Acra, Sari; Polk, D Brent; Saville, Benjamin R; Garber, Judy; Walker, Lynn S

2014-12-01

Pediatric functional abdominal pain has been linked to functional gastrointestinal disorders (FGIDs) in adulthood, but little is known about patient characteristics in childhood that increase the risk for FGID in young adulthood. We investigated the contribution of gastrointestinal symptoms, extraintestinal somatic symptoms, and depressive symptoms in pediatric patients with functional abdominal pain and whether these predicted FGIDs later in life. In a longitudinal study, consecutive new pediatric patients, diagnosed with functional abdominal pain in a subspecialty clinic, completed a comprehensive baseline evaluation of the severity of their physical and emotional symptoms. They were contacted 5 to 15 years later and evaluated, based on Rome III symptom criteria, for abdominal pain-related FGIDs, including irritable bowel syndrome, functional dyspepsia, functional abdominal pain syndrome, and abdominal migraine. Controlling for age, sex, baseline severity of abdominal pain, and time to follow-up evaluation, multivariable logistic regression was used to evaluate the association of baseline gastrointestinal, extraintestinal somatic, and depressive symptoms in childhood with FGID in adolescence and young adulthood. Of 392 patients interviewed an average of 9.2 years after their initial evaluation, 41% (n = 162) met symptom criteria for FGID; most met the criteria for irritable bowel syndrome. Extraintestinal somatic and depressive symptoms at the initial pediatric evaluation were significant predictors of FGID later in life, after controlling for initial levels of GI symptoms. Age, sex, and abdominal pain severity at initial presentation were not significant predictors of FGID later in life. In pediatric patients with functional abdominal pain, assessment of extraintestinal and depressive symptoms may be useful in identifying those at risk for FGID in adolescence and young adulthood. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Somatization in the conceptualization of sickle cell disease.

PubMed

Wellington, Chanté; Edwards, Christopher L; McNeil, Janice; Wood, Mary; Crisp, Benjamin; Feliu, Miriam; Byrd, Goldie; McDougald, Camela; Edwards, Lekisha; Whitfield, Keith E

2010-11-01

The unpredictable nature of sickle cell disease (SCD) and its social and environmental consequences can produce an unhealthy and almost exclusive focus on physical functioning. At the upper range of this focus on health concerns is somatization. In the current study, using 156 adult patients (55.13% female, 86) with SCD, mean age 35.59 +/- 12.73, we explored the relationship of somatization to pain. We found somatization to be predictive of pain severity and current pain intensity as well as a range of averaged indices of pain over time (p < .0001). We further found somatization to be predictive of a range of negative psychological experiences to include depression, anxiety, and hostility (p < .0001). We interpret these data to suggest that patients with SCD who have a propensity to focus exclusively on their health or are more sensitive to minor changes in their health status (somatization) may also be more likely to report greater concerns about their health and higher ratings of pain.

Stress and Resilience in Functional Somatic Syndromes – A Structural Equation Modeling Approach

PubMed Central

Fischer, Susanne; Lemmer, Gunnar; Gollwitzer, Mario; Nater, Urs M.

2014-01-01

Background Stress has been suggested to play a role in the development and perpetuation of functional somatic syndromes. The mechanisms of how this might occur are not clear. Purpose We propose a multi-dimensional stress model which posits that childhood trauma increases adult stress reactivity (i.e., an individual's tendency to respond strongly to stressors) and reduces resilience (e.g., the belief in one's competence). This in turn facilitates the manifestation of functional somatic syndromes via chronic stress. We tested this model cross-sectionally and prospectively. Methods Young adults participated in a web survey at two time points. Structural equation modeling was used to test our model. The final sample consisted of 3′054 participants, and 429 of these participated in the follow-up survey. Results Our proposed model fit the data in the cross-sectional (χ2(21)  = 48.808, p<.001, CFI  = .995, TLI  = .992, RMSEA  = .021, 90% CI [.013.029]) and prospective analyses (χ2(21)  = 32.675, p<.05, CFI  = .982, TLI  = .969, RMSEA  = .036, 90% CI [.001.059]). Discussion Our findings have several clinical implications, suggesting a role for stress management training in the prevention and treatment of functional somatic syndromes. PMID:25396736

Esophageal Sensorimotor Function and Psychological Factors Each Contribute to Symptom Severity in Globus Patients.

PubMed

Rommel, Nathalie; Van Oudenhove, Lukas; Arts, Joris; Caenepeel, Philip; Tack, Jan; Pauwels, Ans

2016-10-01

Altered upper esophageal sphincter (UES) and esophageal body (EB) sensorimotor function and psychosocial factors may both be involved in symptom generation in globus, but their common impact is not yet assessed. The aim of the study is (1) to compare UES and EB sensitivity and compliance of globus patients with healthy controls (HC); (2) to study the association of globus symptom severity (GSS) with UES and EB sensitivity and compliance, UES motor function and psychosocial factors. In 58 globus patients, GSS, somatization, and anxiety disorders were determined using validated questionnaires. In 26 HC and 42/58 patients, UES and EB sensitivity and compliance were assessed twice using barostat measurements. UES function of 27 globus patients was evaluated using high-resolution manometry. Bivariate correlations and a general linear model tested the association of these factors with GSS. UES and EB compliance did not differ between globus patients and HC. Upon repeated distension, UES habituation was seen in both groups, whereas EB sensitization (23.3±1.3 vs. 19.5±1.5 mm Hg, P<0.0001) only occurred in globus patients, (P=0.038). UES compliance (ρ=0.37, P=0.04), change in EB compliance upon repeated distension (ρ=0.45, P=0.007), somatization (ρ=0.43, P=0.003), panic disorder (t=3.04, P=0.004), and post-traumatic stress severity (ρ=0.40, P=0.005) were associated with GSS. UES compliance and somatization were independently associated with GSS. A trend (P=0.061) was found for the association of GSS with change in EB compliance. UES compliance, change in EB compliance, and somatization explain 40% of the variance in GSS. This indicates that globus is a complex disorder of the brain-gut axis rather than a "psychosomatic" disorder or a peripheral esophageal disorder.

Cost-utility of a specific collaborative group intervention for patients with functional somatic syndromes.

PubMed

Konnopka, Alexander; König, Hans-Helmut; Kaufmann, Claudia; Egger, Nina; Wild, Beate; Szecsenyi, Joachim; Herzog, Wolfgang; Schellberg, Dieter; Schaefert, Rainer

2016-11-01

Collaborative group intervention (CGI) in patients with functional somatic syndromes (FSS) has been shown to improve mental quality of life. To analyse incremental cost-utility of CGI compared to enhanced medical care in patients with FSS. An economic evaluation alongside a cluster-randomised controlled trial was performed. 35 general practitioners (GPs) recruited 300 FSS patients. Patients in the CGI arm were offered 10 group sessions within 3months and 2 booster sessions 6 and 12months after baseline. Costs were assessed via questionnaire. Quality adjusted life years (QALYs) were calculated using the SF-6D index, derived from the 36-item short-form health survey (SF-36). We calculated patients' net-monetary-benefit (NMB), estimated the treatment effect via regression, and generated cost-effectiveness acceptability curves. Using intention-to-treat analysis, total costs during the 12-month study period were 5777EUR in the intervention, and 6858EUR in the control group. Controlling for possible confounders, we found a small, but significant positive intervention effect on QALYs (+0.017; p=0.019) and an insignificant cost saving resulting from a cost-increase in the control group (-10.5%; p=0.278). NMB regression showed that the probability of CGI to be cost-effective was 69% for a willingness to pay (WTP) of 0EUR/QALY, increased to 92% for a WTP of 50,000EUR/QALY and reached the level of 95% at a WTP of 70,375EUR/QALY. Subgroup analyses yielded that CGI was only cost-effective in severe somatic symptom severity (PHQ-15≥15). CGI has a high probability to be a cost-effective treatment for FSS, in particular for patients with severe somatic symptom severity. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship of Somatic Symptoms With Depression Severity, Quality of Life, and Health Resources Utilization in Patients With Major Depressive Disorder Seeking Primary Health Care in Spain

PubMed Central

García-Campayo, Javier; Ayuso-Mateos, José Luis; Caballero, Luis; Romera, Irene; Aragonés, Enric; Rodríguez-Artalejo, Fernando; Quail, Deborah; Gilaberte, Inmaculada

2008-01-01

Objective: To investigate the relationship between the characteristics of somatic symptoms and depression severity, quality of life (QOL), and health resources utilization in patients with major depressive disorder (MDD) in primary care setting. Method: This cross-sectional, nationwide epidemiologic study, carried out in 1150 primary care patients with DSM-IV–defined MDD, evaluated the characteristics of somatic symptoms by means of the Standardized Polyvalent Psychiatric Interview. Depression severity and QOL were evaluated by means of the Zung Self-Rating Depression Scale (SDS) and the Physical and Mental Component Summaries of the Medical Outcomes Study 12-item Short-Form Health Survey. Health resources utilization was measured in terms of doctor consultations and hospitalizations. The associations were assessed by means of adjusted analyses. The study was carried out from April 2004 to July 2004. Results: Disability associated with somatic symptoms and number of somatic symptoms were strongly associated with increased depression severity (2.45 and 0.29 increase in SDS score, respectively) and health resources utilization (odds ratios of 1.42 and 1.04, respectively). Associated disability, frequency, and persistence during leisure time of somatic symptoms were strongly associated with poorer QOL. In contrast, we found a weaker relationship between duration and intensity of somatic symptoms and depression severity, QOL, and health resources utilization. Conclusions: Of the studied somatic symptom characteristics, somatic symptom–associated disability and number of somatic symptoms are strongly associated with increased depression severity and health resources utilization, as well as with decreased QOL. Our results may help physicians identify relevant characteristics of somatic symptoms to more effectively diagnose and treat depression in primary care patients. PMID:19158973

Visual and somatic sensory feedback of brain activity for intuitive surgical robot manipulation.

PubMed

Miura, Satoshi; Matsumoto, Yuya; Kobayashi, Yo; Kawamura, Kazuya; Nakashima, Yasutaka; Fujie, Masakatsu G

2015-01-01

This paper presents a method to evaluate the hand-eye coordination of the master-slave surgical robot by measuring the activation of the intraparietal sulcus in users brain activity during controlling virtual manipulation. The objective is to examine the changes in activity of the intraparietal sulcus when the user's visual or somatic feedback is passed through or intercepted. The hypothesis is that the intraparietal sulcus activates significantly when both the visual and somatic sense pass feedback, but deactivates when either visual or somatic is intercepted. The brain activity of three subjects was measured by the functional near-infrared spectroscopic-topography brain imaging while they used a hand controller to move a virtual arm of a surgical simulator. The experiment was performed several times with three conditions: (i) the user controlled the virtual arm naturally under both visual and somatic feedback passed, (ii) the user moved with closed eyes under only somatic feedback passed, (iii) the user only gazed at the screen under only visual feedback passed. Brain activity showed significantly better control of the virtual arm naturally (p<;0.05) when compared with moving with closed eyes or only gazing among all participants. In conclusion, the brain can activate according to visual and somatic sensory feedback agreement.

Excess costs from functional somatic syndromes in Germany - An analysis using entropy balancing.

PubMed

Grupp, Helen; Kaufmann, Claudia; König, Hans-Helmut; Bleibler, Florian; Wild, Beate; Szecsenyi, Joachim; Herzog, Wolfgang; Schellberg, Dieter; Schäfert, Rainer; Konnopka, Alexander

2017-06-01

The aim of this study was to calculate disorder-specific excess costs in patients with functional somatic syndromes (FSS). We compared 6-month direct and indirect costs in a patient group with FSS (n=273) to a control group of the general adult population in Germany without FSS (n=2914). Data on the patient group were collected between 2007 and 2009 in a randomized controlled trial (speciAL). Data on the control group were obtained from a telephone survey, representative for the general German population, conducted in 2014. Covariate balance between the patient group and the control group was achieved using entropy balancing. Excess costs were calculated by estimating generalized linear models and two-part models for direct costs and indirect costs. Further, we estimated excess costs according to the level of somatic symptom severity (SSS). FSS patients differed significantly from the control group regarding 6-month costs of outpatient physicians (+€280) and other outpatient providers (+€74). According to SSS, significantly higher outpatient physician costs were found for mild (+€151), moderate (+€306) and severe (+€376) SSS. We also found significantly higher costs of other outpatient providers in patients with mild, moderate and severe SSS. Regarding costs of rehabilitation and hospital treatments, FSS patients did not differ significantly from the control group for any level of SSS. Indirect costs were significantly higher in patients with severe SSS (+€760). FSS were of major importance in the outpatient sector. Further, we found significantly higher indirect costs in patients with severe SSS. Copyright © 2017 Elsevier Inc. All rights reserved.

Illness behavior.

PubMed

Sirri, Laura; Grandi, Silvana

2012-01-01

The term illness behavior was introduced by Mechanic and Volkart to describe the individuals' different ways to respond to their own health status. Pilowsky's concept of abnormal illness behavior encompasses several clinical conditions characterized by a maladaptive mode of experiencing, perceiving, evaluating and responding to one's own health status. The concept of somatization was criticized because it implies the presence of psychological distress or an underlying psychiatric disturbance when an organic cause for somatic symptoms is not found. Thus, more atheoretical terms , such as functional somatic symptoms and medically unexplained symptoms, were introduced. Both Kellner's Symptom Questionnaire and Derogatis' Symptom Checklist-90 include a scale for somatic symptoms, and other questionnaires were specifically designed to measure their frequency and severity. Kellner's Illness Attitude Scales appear to be the gold standard for the measurement of the hypochondriacal spectrum, which includes several clinical conditions, such as nosophobia, thanatophobia and health anxiety. The assessment of illness denial should consider that a certain degree of denial may sometimes prevent patients from overwhelming psychological distress resulting from life-threatening or stigmatized diseases. Denial may concern both physical and psychiatric symptoms. Specific instruments are available for both types of denial. The cognitive and emotional representations developed by subjects when they have to cope with an illness or a perceived health threat are subsumed under the concept of illness perception and may be assessed by the Brief Illness Perception Questionnaire. Copyright © 2012 S. Karger AG, Basel.

Hexavalent chromium induces apoptosis in male somatic and spermatogonial stem cells via redox imbalance

PubMed Central

Das, Joydeep; Kang, Min-Hee; Kim, Eunsu; Kwon, Deug-Nam; Choi, Yun-Jung; Kim, Jin-Hoi

2015-01-01

Hexavalent chromium [Cr(VI)], an environmental toxicant, causes severe male reproductive abnormalities. However, the actual mechanisms of toxicity are not clearly understood and have not been studied in detail. The present in vitro study aimed to investigate the mechanism of reproductive toxicity of Cr(VI) in male somatic cells (mouse TM3 Leydig cells and TM4 Sertoli cells) and spermatogonial stem cells (SSCs) because damage to or dysfunction of these cells can directly affect spermatogenesis, resulting in male infertility. Cr(VI) by inducing oxidative stress was cytotoxic to both male somatic cells and SSCs in a dose-dependent manner, and induced mitochondria-dependent apoptosis. Although the mechanism of Cr(VI)-induced cytotoxicity was similar in both somatic cells, the differences in sensitivity of TM3 and TM4 cells to Cr(VI) could be attributed, at least in part, to cell-specific regulation of P-AKT1, P-ERK1/2, and P-P53 proteins. Cr(VI) affected the differentiation and self-renewal mechanisms of SSCs, disrupted steroidogenesis in TM3 cells, while in TM4 cells, the expression of tight junction signaling and cell receptor molecules was affected as well as the secretory functions were impaired. In conclusion, our results show that Cr(VI) is cytotoxic and impairs the physiological functions of male somatic cells and SSCs. PMID:26355036

Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA).

PubMed

Hotta, Osamu; Tanaka, Ayaki; Torigoe, Akira; Imai, Kazuaki; Ieiri, Norio

2017-02-01

The epipharynx is an immunologically active site even under normal conditions, and enhanced immunologic activation is prone to occur in response to an upper respiratory infection, air pollution, and possibly to vaccine adjuvants. Due to the potential link between the central nervous system and immune function, a relationship between epipharyngitis and autonomic nervous disturbance as well as autoimmune disease has been suggested. Various functional somatic symptoms have been described after human papillomavirus (HPV) vaccination, although a causal relationship has not been established. We examined the epipharynx in young women showing functional somatic symptoms following HPV vaccination. Surprisingly, despite having minimal symptoms involving the pharynx, all patients were found to have severe epipharyngitis. In addition, significant improvement in symptoms was seen in most patients who underwent epipharyngeal treatment. Thus, we speculate that the chronic epipharyngitis potentially caused by the vaccine adjuvant may be involved in the pathogenesis of functional somatic syndrome (FSS) post-HPV vaccination. Further, we suggest that epipharyngeal treatment may be effective for various types of FSS regardless of the initial cause, as well as for some autoimmune diseases, and that this may be an important direction in future research.

Changes in illness perceptions mediated the effect of cognitive behavioural therapy in severe functional somatic syndromes.

PubMed

Christensen, Sara Sletten; Frostholm, Lisbeth; Ørnbøl, Eva; Schröder, Andreas

2015-04-01

Although there is substantial evidence that cognitive behavioural therapy alleviates symptoms in functional somatic syndromes, the mechanisms of change are less investigated. This study examined whether changes in illness perceptions mediated the effect of cognitive behavioural therapy. We analysed additional data from a randomised controlled trial comparing completers of cognitive behavioural group therapy (46 patients) to an enhanced usual care group (66 patients). Proposed mediators (illness perceptions) and primary (physical health) and secondary (somatic symptoms and illness worry) outcomes were assessed by means of questionnaires at referral, baseline, end of treatment, and 10 and 16 months after randomisation. Multiple mediation analysis determined whether (1) changes in specific illness perceptions during treatment mediated the effect of cognitive behavioural therapy (primary analysis), and (2) whether changes in illness perceptions during the whole trial period were associated with improved outcome (secondary analysis). Improvements in illness perceptions during treatment partially mediated the effect of cognitive behavioural therapy on physical health one year after treatment (sum of indirect effects 1.556, BCa 95% CI (0.006; 3.620)). Improving perceived control was particularly important. Changes in illness perceptions from baseline to 16 months after randomisation were associated with clinically meaningful improvements in physical health, somatic symptoms and illness worry during the same period. Our results suggest that changing patients' illness perceptions is an important process in cognitive behavioural therapy for functional somatic syndromes. Challenging patients' own understanding of their illness may hence be a key element of successful treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Anxiety, depression, and somatization in DSM-III hypochondriasis.

PubMed

Kellner, R; Abbott, P; Winslow, W W; Pathak, D

1989-01-01

To assess the severity of distress and of somatization in hypochondriasis, the authors administered several validated self-rating scales of depression, anxiety, somatic symptoms, and anger/hostility to 21 psychiatric outpatients with the DSM-III diagnosis of hypochondriasis and to matched groups of other nonpsychotic psychiatric patients, family practice patients, and employees. Anxiety and somatic symptoms were highest in hypochondriacal patients; depression and anger/hostility did not differ from those of other psychiatric patients but were higher than in the other groups. The findings do not support the theory that hypochondriasis is a defense against anxiety or that it is a masked depression or depressive equivalent. The findings are consistent with the view that the interaction of severe anxiety and severe somatic symptoms is a common feature of the psychopathology of hypochondriasis.

Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment.

PubMed

Löwe, Bernd; Spitzer, Robert L; Williams, Janet B W; Mussell, Monika; Schellberg, Dieter; Kroenke, Kurt

2008-01-01

To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment. Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment. In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment. Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

Predictors of a functional somatic syndrome diagnosis in patients with persistent functional somatic symptoms.

PubMed

Kingma, Eva M; de Jonge, Peter; Ormel, Johan; Rosmalen, Judith G M

2013-06-01

Functional somatic syndromes (FSS) are characterized by the existence of multiple persistent functional somatic symptoms. Not many patients fulfilling the criteria for an FSS, receive a formal diagnosis, and it is unknown which factors explain this discrepancy. Patients that tend to worry and patients that gather more health information may have an increased chance of an FSS diagnosis. We hypothesized that high intelligence and high neuroticism increase the probability of an FSS diagnosis in patients with persistent functional somatic symptoms. This study aims to investigate patient factors that might be important in the process of syndrome labeling. Our study was performed in a large, representative population cohort (n = 976) in Groningen, The Netherlands, and included two assessment waves. Intelligence was measured using the General Aptitude Test Battery version B 1002-B. Neuroticism was measured using the 12-item neuroticism scale of the Eysenck Personality Questionnaire-Revised. Functional somatic symptoms were measured with the somatization section of the Composite International Diagnostic Interview. Current FSS diagnosis was assessed with a questionnaire. We performed multivariable logistic regression analyses including sum scores of neuroticism, intelligence scores, sex, number of functional somatic symptoms, and age as potential predictors of having an FSS diagnosis. From the 976 participants that completed measurements at follow-up, 289 (26.4 %) participants reported at least one persistent functional somatic symptom, and these subjects were included in the main analyses (38.4 % males, mean age of 55.2 years (SD = 10.7), 36-82 years). High numbers of functional somatic symptoms ((OR) = 1.320; 95 % (CI) = 1.097-1.588), female sex (OR = 9.068; 95 % CI = 4.061-20.251), and high intelligence (OR = 1.402; 95 % CI = 1.001-1.963) were associated with an FSS diagnosis, while age (OR = 0.989; 95 % CI = 960-1.019) and neuroticism (OR = 0.956; 95 % CI = 0.872-1.048) were not. This study suggests that high intelligence, but not high neuroticism, increases the chance of syndrome labeling in patients with persistent functional somatic symptoms.

Somatic symptoms: an important index in predicting the outcome of depression at six-month and two-year follow-up points among outpatients with major depressive disorder.

PubMed

Hung, Ching-I; Liu, Chia-Yih; Wang, Shuu-Jiun; Juang, Yeong-Yuh; Yang, Ching-Hui

2010-09-01

Few studies have simultaneously compared the ability of depression, anxiety, and somatic symptoms to predict the outcome of major depressive disorder (MDD). This study aimed to compare the MDD outcome predictive ability of depression, anxiety, and somatic severity at 6-month and 2-year follow-ups. One-hundred and thirty-five outpatients (men/women=34/101) with MDD were enrolled. Depression and anxiety were evaluated by the Hamilton Depression Rating Scale, Hospital Anxiety and Depression Scale, and depression subscale of the Depression and Somatic Symptoms Scale (DSSS). Somatic severity was evaluated by the somatic subscale of the DSSS. Subjects undergoing pharmacotherapy in the follow-up month were categorized into the treatment group; the others were categorized into the no-treatment group. Multiple linear regressions were used to identify the scales most powerful in predicting MDD outcome. Among the 135 subjects, 119 and 106 completed the 6-month and 2-year follow-ups, respectively. Somatic severity at baseline was correlated with the outcomes of the three scales at the two follow-ups. After controlling for demographic variables, somatic severity independently predicted most outcomes of the three scales at the two follow-ups in the no-treatment group and the cost of pharmacotherapy and DSSS score at the 6-month follow-up in the treatment group. Division of the subjects into treatment and no-treatment groups was not based on randomization and bias might have been introduced. Somatic severity was the most powerful index in predicting MDD outcome. Psychometric scales with appropriate somatic symptom items may be more accurate in predicting MDD outcome. 2010 Elsevier B.V. All rights reserved.

Somatization Increases Disability Independent of Comorbidity

PubMed Central

Orav, E. John; Bates, David W.; Barsky, Arthur J.

2008-01-01

Background Somatoform disorders are an important factor in functional disability and role impairment, though their independent contribution to disability has been unclear because of prevalent medical and psychiatric comorbidity. Objectives To assess the extent of the overlap of somatization with other psychiatric disorders and medical problems, to compare the functional disability and role impairment of somatizing and non-somatizing patients, and to determine the independent contribution of somatization to functional disability and role impairment. Design Patients were surveyed with self-report questionnaires assessing somatization, psychiatric disorder, and role impairment. Medical morbidity was indexed with a computerized medical record audit. Participants Consecutive adults making scheduled visits to their primary care physicians at two hospital-affiliated primary care practices on randomly chosen days. Measurements Intermediate activities of daily living, social activities, and occupational disability. Results Patients with somatization, as well as those with serious medical and psychiatric illnesses, had significantly more impairment of activities of daily life and social activities. When these predictors were considered simultaneously in a multivariable regression, the association with somatization remained highly significant and was comparable to or greater than many major medical conditions. Conclusions Patients with somatization had substantially greater functional disability and role impairment than non-somatizing patients. The degree of disability was equal to or greater than that associated with many major, chronic medical disorders. Adjusting the results for psychiatric and medical co-morbidity had little effect on these findings. PMID:19031038

[Hypochondriac symptoms in late-onset depression: the relationship between hypochondria and somatic state of patients].

PubMed

Ivanets, N N; Avdeeva, T I; Kinkul'kina, M A

2013-01-01

Authors studied 276 women with late-onset depression. Concomitant chronic somatic diseases were identified in 90%. The presence of disease and its nosological definition did not impact on the development of hypochondriac symptoms in patients with late-onset depression. Patients with hypochondriac late-onset depression more often had disability pension due to somatic disease because they more often referred to internists in case of similar objective severity of somatic pathology. It was singled out three variants of the relationship between hypochondria and somatic state: hypernosognostic (a complete coincidence of hypochondria content with actual somatic pathology; anosognostic (a lack of coincidence) and disharmonic (a partial coincidence). The themes of hypochondria in late-nset depressions were correlated with a total number of somatic diseases and their severity. At the same time, there was no correlation between the content of hypochondria and the character of somatic disease.

Is the impact of depressive complaints on the use of general health care services dependent on severity of somatic morbidity?

PubMed

Koopmans, Gerrit T; Lamers, Leida M

2006-07-01

The aim of this study was to examine the effects of depressive complaints and chronic medical illnesses on prospective somatic health care utilization and the possible heterogeneity of the effect of depressive complaints across levels of medical illness severity. Data from a community-based sample of adults (n=9428) were used, of whom a health survey and claims data, indicating health care use, were available. Assessments of depressive complaints and somatic illnesses were based on self-report. Binomial regression analyses were used to study the expected relations. Depressive complaints and somatic morbidity were both positively related to general health care utilization. Somatic morbidity has an attenuating effect on the impact of depressive complaints: If it becomes more severe, the impact of depressive complaints on utilization is reduced. Depressive complaints are especially related to the use of paramedic services, use of prescription drugs, and consultations of medical specialists. Depressive complaints predict somatic health care utilization, but somatic morbidity attenuates this relation. Future research on this subject should include interaction effects of depressive complaints and somatic morbidity. Interventions aiming to reduce excess use related to mental distress should be primarily targeted on subjects with mental distress who have no comorbid somatic morbidity.

Functional enucleation of porcine oocytes for somatic cell nuclear transfer using femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Kuetemeyer, K.; Lucas-Hahn, A.; Petersen, B.; Hassel, P.; Lemme, E.; Niemann, H.; Heisterkamp, A.

2010-02-01

Cloning of several mammalian species has been achieved by somatic cell nuclear transfer over the last decade. However, this method still results in very low efficiencies originating from biological and technical aspects. The highly-invasive mechanical enucleation belongs to the technical aspects and requires considerable micromanipulation skill. In this paper, we present a novel non-invasive method for combined oocyte imaging and automated functional enucleation using femtosecond (fs) laser pulses. After three-dimensional imaging of Hoechst-labeled porcine oocytes by multiphoton microscopy, our self-developed software automatically determined the metaphase plate position and shape. Subsequent irradiation of this volume with the very same laser at higher pulse energies in the low-density-plasma regime was used for metaphase plate ablation. We show that functional fs laser-based enucleation of porcine oocytes completely inhibited further embryonic development while maintaining intact oocyte morphology. In contrast, non-irradiated oocytes were able to develop to the blastocyst stage without significant differences to control oocytes. Our results indicate that fs laser systems offer great potential for oocyte imaging and enucleation as a fast, easy to use and reliable tool which may improve the efficiency of somatic cell clone production.

DSM-IV hypochondriasis in primary care.

PubMed

Escobar, J I; Gara, M; Waitzkin, H; Silver, R C; Holman, A; Compton, W

1998-05-01

The object of this study was to assess the prevalence and correlates of the DSM-IV diagnosis of hypochondriasis in a primary care setting. A large sample (N = 1456) of primary care users was given a structured interview to make diagnoses of mood, anxiety, and somatoform disorders and estimate levels of disability. The prevalence of hypochondriasis (DSM-IV) was about 3%. Patients with this disorder had higher levels of medically unexplained symptoms (abridged somatization) and were more impaired in their physical functioning than patients without the disorder. Of the various psychopathologies examined, major depressive syndromes were the most frequent among patients with hypochondriasis. Interestingly, unlike somatization disorder, hypochondriasis was not related to any demographic factor. Hypochondriasis is a relatively rare condition in primary care that is largely separable from somatization disorder but seems closely intertwined with the more severe depressive syndromes.

Subtypes of depressive symptoms and inflammatory biomarkers: An exploratory study on a sample of HIV-positive patients

PubMed Central

Pala, A. Norcini; Steca, P.; Bagrodia, R.; Helpman, L.; Colangeli, V.; Viale, P.; Wainberg, M.L.

2017-01-01

Depressive symptoms cause major impairment and may accelerate HIV progression despite the use of antiretroviral medication. The somatic symptoms criteria for HIV infection and depression partially overlap, which can make differential diagnosis challenging. Because of chronic inflammation caused by HIV infection, HIV-positive patients may develop somatic and affective-cognitive symptoms of depression. Inflammation-related depression is primarily characterized with severe somatic symptoms such as fatigue and sleep disturbance. This study sought to explore the patterns of somatic and cognitive-affective depressive symptoms that characterize HIV-positive patients. Our specific aims were (1) to identify subtypes of depressive symptoms in a sample of HIV-positive patients; and (2) to test the subtypes’ difference on inflammatory and HIV disease progression biomarkers. HIV-positive men and women (N = 102) with and without depressive symptoms were randomly selected from an Italian HIV clinic. Depressive symptoms (PHQ-9), viral load (VL), CD4+, Il-6, TNF-α, and monocytes were assessed. The three subtypes formed using Latent Class Analysis (LCA) identified patients with (1) severe cognitive-affective and somatic depressive symptoms; (2) severe/moderate somatic symptoms; and (3) absent or low depressive symptoms. The subtype with severe/moderate somatic symptoms was characterized with elevated levels of Il-6 and monocytes. No difference on HIV progression biomarkers was found. The subtypes of depressive symptoms might help differentiating depressive symptoms from HIV- and inflammatory-related somatic symptoms. When present, cognitive-affective and/or somatic symptoms cause significant impairment to patients’ lives and thus warrant further assessment and treatment. PMID:26883521

Subtypes of depressive symptoms and inflammatory biomarkers: An exploratory study on a sample of HIV-positive patients.

PubMed

Norcini Pala, A; Steca, P; Bagrodia, R; Helpman, L; Colangeli, V; Viale, P; Wainberg, M L

2016-08-01

Depressive symptoms cause major impairment and may accelerate HIV progression despite the use of antiretroviral medication. The somatic symptoms criteria for HIV infection and depression partially overlap, which can make differential diagnosis challenging. Because of chronic inflammation caused by HIV infection, HIV-positive patients may develop somatic and affective-cognitive symptoms of depression. Inflammation-related depression is primarily characterized with severe somatic symptoms such as fatigue and sleep disturbance. This study sought to explore the patterns of somatic and cognitive-affective depressive symptoms that characterize HIV-positive patients. Our specific aims were (1) to identify subtypes of depressive symptoms in a sample of HIV-positive patients; and (2) to test the subtypes' difference on inflammatory and HIV disease progression biomarkers. HIV-positive men and women (N=102) with and without depressive symptoms were randomly selected from an Italian HIV clinic. Depressive symptoms (PHQ-9), viral load (VL), CD4+, Il-6, TNF-α, and monocytes were assessed. The three subtypes formed using Latent Class Analysis (LCA) identified patients with (1) severe cognitive-affective and somatic depressive symptoms; (2) severe/moderate somatic symptoms; and (3) absent or low depressive symptoms. The subtype with severe/moderate somatic symptoms was characterized with elevated levels of Il-6 and monocytes. No difference on HIV progression biomarkers was found. The subtypes of depressive symptoms might help differentiating depressive symptoms from HIV- and inflammatory-related somatic symptoms. When present, cognitive-affective and/or somatic symptoms cause significant impairment to patients' lives and thus warrant further assessment and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Saliva amylase as a measure of sympathetic change elicited by autogenic training in patients with functional somatic syndromes.

PubMed

Kiba, Tadashi; Kanbara, Kenji; Ban, Ikumi; Kato, Fumie; Kawashima, Sadanobu; Saka, Yukie; Yamamoto, Kazumi; Nishiyama, Junji; Mizuno, Yasuyuki; Abe, Tetsuya; Fukunaga, Mikihiko

2015-12-01

The aim of this study was to discuss the effect of autogenic training (AT) on patients with functional somatic syndrome (FSS) using salivary amylase, the skin temperature of the finger, subjective severity of symptoms, and psychological characteristics as measures. We assessed 20 patients with FSS and 23 healthy controls before and after AT. Baseline levels of salivary amylase prior to an AT session were significantly higher in the FSS group than in the control group. However, this difference was not significant after AT. The skin temperature of the finger increased after AT in both the FSS and control groups. AT contributed to the improvement of somatic symptoms in patients with FSS. Our results regarding psychological characteristics suggest that mood disturbances are deeply involved in the pathology of FSS. Individuals with FSS exhibited elevated levels of sympathetic activity compared with healthy controls. Our data indicates that AT eased dysregulation of the autonomic nervous system in patients with FSS. Thus, salivary amylase may be a useful index of change induced by AT in patients with FSS.

Somatic symptoms and psychological concerns in a general adolescent population: Exploring the relevance of DSM-5 somatic symptom disorder.

PubMed

van Geelen, Stefan M; Rydelius, Per-Anders; Hagquist, Curt

2015-10-01

DSM-5 somatic symptom disorder (SSD) constitutes a major change for psychosomatic medicine and psychiatry, as well as for epidemiological research in these fields. This study investigates somatic symptoms and psychological concerns among adolescents in order to systematically explore the relevance of SSD for general adolescent populations. A cross-sectional population-based design, with a symptoms-based strategy and a symptom-and-psychological-concern-based strategy, was used to estimate the prevalence of somatic symptoms and psychological concerns in a general adolescent population (n=2476, mean age=16years, 49% boys, 51% girls). Somatic symptoms and psychological concerns in relation to gender, and self-reported medical and psychiatric conditions were investigated. The association between somatic symptoms, psychological concerns, and functional impairment in school-, family-, peer- and physical activities was studied. Reporting 3+ persistent distressing somatic symptoms was significantly more common than reporting one or more persistent distressing somatic symptom(s) combined with serious psychological concern. The prevalence of such complaints was significantly higher in girls. The proportion of medical and psychiatric conditions was highest in the group reporting 3+ persistent distressing somatic symptoms combined with serious psychological concern. Belonging to this group most significantly increased odds ratios for functional impairment. For large-scale studies on SSD, results suggest the use of measures based on multiple somatic items in combination with psychological concerns, and a methodologically sound standardized measure of functional impairment. To further enhance clinical decision-making, the relation of symptoms to functional impairment, and the substantial overlap of SSD with medical and psychiatric conditions during adolescence should be addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

Continuity of Functional-Somatic Symptoms from Late Childhood to Young Adulthood in a Community Sample

ERIC Educational Resources Information Center

Steinhausen, Hans-Christoph; Metzke, Christa Winkler

2007-01-01

Background: The goal of this study was to assess the course of functional-somatic symptoms from late childhood to young adulthood and the associations of these symptoms with young adult psychopathology. Methods: Data were collected in a large community sample at three different points in time (1994, 1997, and 2001). Functional-somatic symptoms…

Can agonistic striving lead to unexplained illness? Implicit goals, pain tolerance, and somatic symptoms in adolescents and adults.

PubMed

Ewart, Craig K; Elder, Gavin J; Laird, Kelsey T; Shelby, Grace D; Walker, Lynn S

2014-09-01

We tested the social action theory hypotheses that (a) psychological stress induced by struggling to control others (agonistic striving) is associated with higher levels of subjective somatic symptoms than stress induced by struggling to control the self (transcendence striving); (b) the association between agonistic striving and symptoms is moderated by the ability to tolerate pain; and (c) associations among agonistic goals, pain tolerance, and subjective symptoms are not explained by personality and affective traits or negative emotional responses to personal stressors. Implicit motives and negative emotional reactivity to recurring personal stressors were assessed by Social Competence Interview in 333 adolescents and adults who participated in longitudinal research on functional abdominal pain at a university medical center. Pain tolerance was assessed by graduated thermal pain protocol; subjective somatic symptoms, and personality/affective traits assessed by questionnaires. The primary outcome measure was the self-reported severity of 35 somatic symptoms often experienced in the absence of diagnosable disease. All hypotheses were supported. Nonconscious agonistic strivings may increase the perceived frequency and severity of subjective somatic symptoms; this tendency is greatly magnified by difficulty in self-regulating responses to painful stimuli. Implicit agonistic motives and their associations with symptoms are not explained by individual differences in trait neuroticism, anxiety, depression, anger, or low self-esteem or by negative emotional reactivity to a personal stressor. These findings may afford fruitful insights into mechanisms by which stressful social environments undermine health and suggest promising directions for clinical intervention. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

[Somatization disorders of the urogenital tract].

PubMed

Günthert, E A

2002-11-01

Diffuse symptoms in the urogenital region can frequently be explained by somatization disorders. Since they cannot be proven either by laboratory tests or with common technical diagnostic methods, somatization disorders should always be taken into consideration. Somatization disorders are to be considered functional disorders. Since somatization disorders due to muscular tension prevail in the urogenital region, the functional disturbance can be explained by the muscular tension. Subsequently, muscular tension causes the pathophysiological development of symptoms. As a rule they appear as myofascial pain or disorder. Muscular tension can have a psychic origin. The absence of urological findings is typical. Males and females between the ages of 16 and 75 can be affected by somatization disorders in the urogenital region. Somatization disorders due to muscular tension belong to the large group of symptoms due to tension. Diagnostic and therapeutic procedures as well as the pathophysiology of somatization disorders due to muscular tension are illustrated by two detailed case-reports.

Somatic Pairing of Chromosome 19 in Renal Oncocytoma Is Associated with Deregulated ELGN2-Mediated Oxygen-Sensing Response

PubMed Central

Petillo, David; Westphal, Michael; Koelzer, Katherine; Metcalf, Julie L.; Zhang, Zhongfa; Matsuda, Daisuke; Dykema, Karl J.; Houseman, Heather L.; Kort, Eric J.; Furge, Laura L.; Kahnoski, Richard J.; Richard, Stéphane; Vieillefond, Annick; Swiatek, Pamela J.; Teh, Bin Tean; Ohh, Michael; Furge, Kyle A.

2008-01-01

Chromosomal abnormalities, such as structural and numerical abnormalities, are a common occurrence in cancer. The close association of homologous chromosomes during interphase, a phenomenon termed somatic chromosome pairing, has been observed in cancerous cells, but the functional consequences of somatic pairing have not been established. Gene expression profiling studies revealed that somatic pairing of chromosome 19 is a recurrent chromosomal abnormality in renal oncocytoma, a neoplasia of the adult kidney. Somatic pairing was associated with significant disruption of gene expression within the paired regions and resulted in the deregulation of the prolyl-hydroxylase ELGN2, a key protein that regulates the oxygen-dependent degradation of hypoxia-inducible factor (HIF). Overexpression of ELGN2 in renal oncocytoma increased ubiquitin-mediated destruction of HIF and concomitantly suppressed the expression of several HIF-target genes, including the pro-death BNIP3L gene. The transcriptional changes that are associated with somatic pairing of chromosome 19 mimic the transcriptional changes that occur following DNA amplification. Therefore, in addition to numerical and structural chromosomal abnormalities, alterations in chromosomal spatial dynamics should be considered as genomic events that are associated with tumorigenesis. The identification of EGLN2 as a significantly deregulated gene that maps within the paired chromosome region directly implicates defects in the oxygen-sensing network to the biology of renal oncocytoma. PMID:18773095

Proteome analysis during pod, zygotic and somatic embryo maturation of Theobroma cacao.

PubMed

Niemenak, Nicolas; Kaiser, Edward; Maximova, Siela N; Laremore, Tatiana; Guiltinan, Mark J

2015-05-15

Two dimensional electrophoresis and nano-LC-MS were performed in order to identify alterations in protein abundance that correlate with maturation of cacao zygotic and somatic embryos. The cacao pod proteome was also characterized during development. The recently published cacao genome sequence was used to create a predicted proteolytic fragment database. Several hundred protein spots were resolved on each tissue analysis, of which 72 variable spots were subjected to MS analysis, resulting in 49 identifications. The identified proteins represent an array of functional categories, including seed storage, stress response, photosynthesis and translation factors. The seed storage protein was strongly accumulated in cacao zygotic embryos compared to their somatic counterpart. However, sucrose treatment (60 g L(-1)) allows up-regulation of storage protein in SE. A high similarity in the profiles of acidic proteins was observed in mature zygotic and somatic embryos. Differential expression in both tissues was observed in proteins having high pI. Several proteins were detected exclusively in fruit tissues, including a chitinase and a 14-3-3 protein. We also identified a novel cacao protein related to known mabinlin type sweet storage proteins. Moreover, the specific presence of thaumatin-like protein, another sweet protein, was also detected in fruit tissue. We discuss our observed correlations between protein expression profiles, developmental stage and stress responses. Copyright © 2015 Elsevier GmbH. All rights reserved.

Gender similarities in somatic depression and in DSM depression secondary symptom profiles within the context of severity and bereavement.

PubMed

Thompson, Angus H; Bland, Roger C

2018-02-01

Most population studies report higher rates of depression among women than men, and some researchers have observed gender differences in depression symptoms overall, or in sub-groupings (e.g. somatic depression). However, gender symptom differences have been inconsistent, prompting this investigation of gender differences in secondary DSM symptom profiles in the context of bereavement status, age, and depression severity. Individuals with symptoms of core depression (flat affect or anhedonia) were selected from a large survey of adults in the Alberta, Canada workforce. Analyses involved the comparison of gender profiles across the seven DSM-IV secondary depressive symptoms plus a MANOVA of sex, bereavement, and age, with secondary symptoms comprising the dependent variable. Gender profiles were very similar, irrespective of depression severity or bereavement. Secondary symptoms were marginally more common among women and more frequent among bereaved young adults, but there was no evidence for a gender-related somatic factor. First, data were gathered only for persons in the workforce and thus may not be generalizable to, for example, stay-at-home parents or those with employment issues. Second, the focus here is restricted to DSM symptoms, leaving risk factors, social roles, and brain functioning for separate investigation. Third, inferences were drawn from associations between groups of persons, rather than between individuals, requiring caution when speculating about individual attributes. Gender differences in depression represent a difference in amount, not kind, suggesting that the range of depressive experiences is similar for men and women. There was no gender difference ascribable to somatic depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Should general psychiatry ignore somatization and hypochondriasis?

PubMed

Creed, Francis

2006-10-01

This paper examines the tendency for general psychiatry to ignore somatization and hypochondriasis. These disorders are rarely included in national surveys of mental health and are not usually regarded as a concern of general psychiatrists; yet primary care doctors and other physicians often feel let down by psychiatry's failure to offer help in this area of medical practice. Many psychiatrists are unaware of the suffering, impaired function and high costs that can result from these disorders, because these occur mainly within primary care and secondary medical services. Difficulties in diagnosis and a tendency to regard them as purely secondary phenomena of depression, anxiety and related disorders mean that general psychiatry may continue to ignore somatization and hypochondriasis. If general psychiatry embraced these disorders more fully, however, it might lead to better prevention and treatment of depression as well as helping to prevent the severe disability that may arise in association with these disorders.

Should general psychiatry ignore somatization and hypochondriasis?

PubMed Central

CREED, FRANCIS

2006-01-01

This paper examines the tendency for general psychiatry to ignore somatization and hypochondriasis. These disorders are rarely included in national surveys of mental health and are not usually regarded as a concern of general psychiatrists; yet primary care doctors and other physicians often feel let down by psychiatry's failure to offer help in this area of medical practice. Many psychiatrists are unaware of the suffering, impaired function and high costs that can result from these disorders, because these occur mainly within primary care and secondary medical services. Difficulties in diagnosis and a tendency to regard them as purely secondary phenomena of depression, anxiety and related disorders mean that general psychiatry may continue to ignore somatization and hypochondriasis. If general psychiatry embraced these disorders more fully, however, it might lead to better prevention and treatment of depression as well as helping to prevent the severe disability that may arise in association with these disorders. PMID:17139341

The somatic symptom scale-8 (SSS-8): a brief measure of somatic symptom burden.

PubMed

Gierk, Benjamin; Kohlmann, Sebastian; Kroenke, Kurt; Spangenberg, Lena; Zenger, Markus; Brähler, Elmar; Löwe, Bernd

2014-03-01

Somatic symptoms are the core features of many medical diseases, and they are used to evaluate the severity and course of illness. The 8-item Somatic Symptom Scale (SSS-8) was recently developed as a brief, patient-reported outcome measure of somatic symptom burden, but its reliability, validity, and usefulness have not yet been tested. To investigate the reliability, validity, and severity categories as well as the reference scores of the SSS-8. A national, representative general-population survey was performed between June 15, 2012, and July 15, 2012, in Germany, including 2510 individuals older than 13 years. The SSS-8 mean (SD), item-total correlations, Cronbach α, factor structure, associations with measures of construct validity (Patient Health Questionnaire-2 depression scale, Generalized Anxiety Disorder-2 scale, visual analog scale for general health status, 12-month health care use), severity categories, and percentile rank reference scores. The SSS-8 had excellent item characteristics and good reliability (Cronbach α = 0.81). The factor structure reflects gastrointestinal, pain, fatigue, and cardiopulmonary aspects of the general somatic symptom burden. Somatic symptom burden as measured by the SSS-8 was significantly associated with depression (r = 0.57 [95% CI, 0.54 to 0.60]), anxiety (r = 0.55 [95% CI, 0.52 to 0.58]), general health status (r = -0.24 [95% CI, -0.28 to -0.20]), and health care use (incidence rate ratio, 1.12 [95% CI, 1.10 to 1.14]). The SSS-8 severity categories were calculated in accordance with percentile ranks: no to minimal (0-3 points), low (4-7 points), medium (8-11 points), high (12-15 points), and very high (16-32 points) somatic symptom burden. For every SSS-8 severity category increase, there was a 53% (95% CI, 44% to 63%) increase in health care visits. The SSS-8 is a reliable and valid self-report measure of somatic symptom burden. Cutoff scores identify individuals with low, medium, high, and very high somatic symptom burden.

The Association Between Headaches and Temporomandibular Disorders is Confounded by Bruxism and Somatic Symptoms.

PubMed

van der Meer, Hedwig A; Speksnijder, Caroline M; Engelbert, Raoul H H; Lobbezoo, Frank; Nijhuis-van der Sanden, Maria W G; Visscher, Corine M

2017-09-01

The objective of this observational study was to establish the possible presence of confounders on the association between temporomandibular disorders (TMD) and headaches in a patient population from a TMD and Orofacial Pain Clinic. Several subtypes of headaches have been diagnosed: self-reported headache, (probable) migraine, (probable) tension-type headache, and secondary headache attributed to TMD. The presence of TMD was subdivided into 2 subtypes: painful TMD and function-related TMD. The associations between the subtypes of TMD and headaches were evaluated by single regression models. To study the influence of possible confounding factors on this association, the regression models were extended with age, sex, bruxism, stress, depression, and somatic symptoms. Of the included patients (n=203), 67.5% experienced headaches. In the subsample of patients with a painful TMD (n=58), the prevalence of self-reported headaches increased to 82.8%. The associations found between self-reported headache and (1) painful TMD and (2) function-related TMD were confounded by the presence of somatic symptoms. For probable migraine, both somatic symptoms and bruxism confounded the initial association found with painful TMD. The findings of this study imply that there is a central working mechanism overlapping TMD and headache. Health care providers should not regard these disorders separately, but rather look at the bigger picture to appreciate the complex nature of the diagnostic and therapeutic process.

Impact of perinatal somatic and common mental disorder symptoms on functioning in Ethiopian women: The P-MaMiE population-based cohort study

PubMed Central

Senturk, Vesile; Hanlon, Charlotte; Medhin, Girmay; Dewey, Michael; Araya, Mesfin; Alem, Atalay; Prince, Martin; Stewart, Robert

2012-01-01

Background Little is known of the relationship between perinatal somatic and common mental disorder (CMD) symptoms and impaired functioning in women from settings where the burden of undernutrition and infectious disease morbidity is high. Methods A population-based sample of 1065 women from Butajira, Ethiopia, was recruited in pregnancy (86.4% of those eligible) and reassessed two months postnatal (954 with singleton, live infants). At both time-points, women were administered a modified version of the Patient Health Questionnaire-15 and the Self-Reporting Questionnaire (locally-validated) to assess somatic and CMD symptoms, respectively. Negative binomial regression was used to investigate associations of CMD and somatic symptoms with functional impairment (World Health Organisation Disability Assessment Scale, version-II), after adjusting for maternal anthropometric measures, physical ill-health and sociodemographic factors. Results In pregnancy, somatic and CMD symptoms were independently associated with worse maternal functional impairment after adjustment for confounders (WHODAS-II score multiplied by 1.09 (95%CI 1.06, 1.13) and 1.11 (95%CI 1.08, 1.14) respectively for each additional symptom). In the postnatal period, the size of association between somatic symptoms and functional impairment was diminished, but the association with CMD symptoms was virtually unchanged (multiplier value 1.04 (95%CI 1.00, 1.09) and 1.11 (95%CI 1.07, 1.16) respectively). Limitations Use of largely self-report measures. Conclusions Somatic and CMD symptoms were independently associated with functional impairment in both pregnancy and the postnatal period, with CMD symptoms showing a stronger and more consistent association. This emphasises the public health relevance of both CMD and somatic symptoms in the perinatal period. PMID:22196052

Preinjury somatization symptoms contribute to clinical recovery after sport-related concussion.

PubMed

Nelson, Lindsay D; Tarima, Sergey; LaRoche, Ashley A; Hammeke, Thomas A; Barr, William B; Guskiewicz, Kevin; Randolph, Christopher; McCrea, Michael A

2016-05-17

To determine the degree to which preinjury and acute postinjury psychosocial and injury-related variables predict symptom duration following sport-related concussion. A total of 2,055 high school and collegiate athletes completed preseason evaluations. Concussed athletes (n = 127) repeated assessments serially (<24 hours and days 8, 15, and 45) postinjury. Cox proportional hazard modeling was used to predict concussive symptom duration (in days). Predictors considered included demographic and history variables; baseline psychological, neurocognitive, and balance functioning; acute injury characteristics; and postinjury clinical measures. Preinjury somatic symptom score (Brief Symptom Inventory-18 somatization scale) was the strongest premorbid predictor of symptom duration. Acute (24-hour) postconcussive symptom burden (Sport Concussion Assessment Tool-3 symptom severity) was the best injury-related predictor of recovery. These 2 predictors were moderately correlated (r = 0.51). Path analyses indicated that the relationship between preinjury somatization symptoms and symptom recovery was mediated by postinjury concussive symptoms. Preinjury somatization symptoms contribute to reported postconcussive symptom recovery via their influence on acute postconcussive symptoms. The findings highlight the relevance of premorbid psychological factors in postconcussive recovery, even in a healthy athlete sample relatively free of psychopathology or medical comorbidities. Future research should elucidate the neurobiopsychosocial mechanisms that explain the role of this individual difference variable in outcome following concussive injury. © 2016 American Academy of Neurology.

Embryogenic competence acquisition in sugarcane callus is associated with differential H+ pump abundance and activity.

PubMed

Passamani, Lucas Z; Bertolazi, Amanda A; Ramos, Alessandro C; Santa-Catarina, Claudete; Thelen, Jay J; Silveira, Vanildo

2018-06-22

Somatic embryogenesis is an important biological process in several plant species, including sugarcane. Proteomics approaches have shown that H + pumps are differentially regulated during somatic embryogenesis; however, the relationship between H + flux and embryogenic competence is still unclear. This work aimed to elucidate the association between extracellular H + flux and somatic embryo maturation in sugarcane. We performed a microsomal proteomics analysis and analyzed changes in extracellular H + flux and H + pump (P-H + -ATPase, V-H + -ATPase and H + -PPase) activity in embryogenic and non-embryogenic callus. A total of 657 proteins were identified, 16 of which were H + pumps. We observed that P-H + -ATPase and H + -PPase were more abundant in embryogenic callus. Compared with non-embryogenic callus, embryogenic callus showed higher H + influx, especially on maturation day 14, as well as higher H+ pump activity (mainly P-H+-ATPase and H+-PPase activity). H+-PPase appears to be the major H + pump in embryogenic callus during somatic embryo formation, functioning in both vacuole acidification and PPi homeostasis. These results provide evidence for an association between higher H + pump protein abundance and, consequently, higher H + flux and embryogenic competence acquisition in the callus of sugarcane, allowing for optimization of the somatic embryo conversion process by modulating the activities of these H + pumps.

Linking Anger Trait with Somatization in Low-Grade College Students: Moderating Roles of Family Cohesion and Adaptability.

PubMed

Liu, Liang; Liu, Cuilian; Zhao, Xudong

2017-02-25

Between 22% and 58% of patients in primary care settings complain of somatic symptoms. Previous research has found that somatization was associated with anger traits and family functions. However, studies that specifically assess the moderating effect of family function in how anger traits become somatic complaints are lacking. This study was designed to examine whether the variances in family cohesion and family adaptability moderated the strength of the relationship between anger traits and somatization. A cross-section design was conducted and 2008 college students were recruited from a comprehensive university in Shanghai. All participants finished questionnaires including Symptom Check List- 90 (SCL-90), State-Trait Anger Expression Inventory 2 (STAXI-2, Chinese version) and Family Adaptability and Cohesion Scale, second edition (FACES II, Chinese Version) to assess their degree of current somatization, anger trait and family function. Hierarchical linear regression analysis (Enter) was conducted respectively for men and women to examine the moderation effect of family cohesion and family adaptability in the association between anger and somatization. Somatic symptoms were significantly linked in the expected directions with depression and anger trait for both genders. Family cohesion and family adaptability were negatively associated with somatic symptoms. For female college students family cohesion was found to moderate the link between anger trait and somatization, but for male college students the moderation effect of family cohesion was marginally significant. The moderating role of family adaptability was significant for neither male nor female after current depressive symptoms were accounted for. Proneness to anger is an independent predictor of somatization. For women, a high level of family cohesion was a protective factor which could reduce the influence of anger trait on somatic symptoms. Without comorbidity of current depression, family adaptability to some degree exempted individuals with anger proneness from developing somatic complaints. Interventions that integrate family cohesion cultivation, family flexibility fostering and depression treatment might be more effective for somatic patients high in anger trait.

Relationship between somatization and remission with ECT.

PubMed

Rasmussen, Keith G; Snyder, Karen A; Knapp, Rebecca G; Mueller, Martina; Yim, Eunsil; Husain, Mustafa M; Rummans, Teresa A; Sampson, Shirlene M; O'Connor, M Kevin; Bernstein, Hilary J; Kellner, Charles H

2004-12-30

Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe depression and those with more severe depression. In the less severely depressed group, high somatic anxiety and hypochondriasis predicted a low likelihood of sustained remission with ECT. In the more severely depressed group, these traits were not predictive of ECT outcome.

A School Nurse-Delivered Intervention for Anxious Children: An Open Trial

ERIC Educational Resources Information Center

Muggeo, Michela A.; Stewart, Catherine E.; Drake, Kelly L.; Ginsburg, Golda S.

2017-01-01

Anxiety disorders are common in children and severely impair their functioning. Because a hallmark symptom of anxiety is somatic complaints, anxious youth often seek help from their school nurse. Thus, school nurses are in an ideal position to identify anxious children and intervene early. This study assessed the feasibility of a brief…

Update on Research and Treatment of Premenstrual Dysphoric Disorder

PubMed Central

Cunningham, Joanne; Yonkers, Kimberly Ann; O'Brien, Shaughn; Eriksson, Elias

2011-01-01

Many women in their reproductive years experience some mood, behavioral. or physical symptoms in the week prior to menses. Variability exists in the level of symptom burden in that some women experience mild symptoms, whereas a small minority experience severe and debilitating symptoms. For an estimated 5%–8% of premenopausal women, work or social functioning are affected by severe premenstrual syndrome. Many women in this group meet diagnostic criteria for premenstrual dysphoric disorder (PMDD). Among women who suffer from PMDD, mood and behavioral symptoms such as irritability, depressed mood, tension, and labile mood dominate. Somatic complaints, including breast tenderness and bloating, also can prove disruptive to women's overall functioning and quality of life. Recent evidence suggests that individual sensitivity to cyclical variations in levels of gonadal hormones may predispose certain women to experience these mood, behavioral, and somatic symptoms. Treatments include: antidepressants of the serotonin reuptake inhibitor class, taken intermittently or throughout the menstrual cycle; medications that suppress ovarian cyclicity; and newer oral contraceptives with novel progestins. (Harv Rev Psychiatry 2009;17:120–137.) PMID:19373620

An Examination of a Yoga Intervention With Pediatric Burn Survivors.

PubMed

Conn, Amy S; Hall, Morgan S; Quinn, Kristen; Wiggins, Bradley; Memmott, Carolyn; Brusseau, Timothy A

Burn injuries have a major influence on the survivors' physical and psychological functioning. In pediatric burns, the consequences persist long after the injury. The objective of this study is to evaluate an existing yoga kids program to gain better understanding of the physical and psychosocial effects of a yoga practice among children with burn injuries. Thirty campers participated in a series of four (1 hour) yoga sessions during the summer of 2014. Nationally trained Instructors had taught children's yoga in the Southwestern United States for at least 10 years. A Yoga Evaluation Questionnaire, designed for children, was used to evaluate perceptions of somatic and cognitive anxiety before and after each Yoga session. Camper's age ranged from 6 to 12 years old with burn severities ranging from 5 to 75%. A dependent samples t-test was used to test for differences between composite pre- and postintervention scores for both somatic and cognitive anxiety. Significant effects emerged for somatic anxiety t(29) = -4.24, P < .001, d = 0.77, and cognitive anxiety t(29) = -4.188, P < .001, d = 0.76. For both cognitive and somatic anxiety, the postintervention composite mean scores were significantly higher, indicating a decrease in somatic and cognitive anxiety. This study suggests that participation in a Yoga program may lower perceptions of cognitive and somatic anxiety in pediatric burn survivors. Further, Yoga is one technique that may compliment the short- and long-term treatment of burn injuries.

Combined multiphoton imaging and automated functional enucleation of porcine oocytes using femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Kuetemeyer, Kai; Lucas-Hahn, Andrea; Petersen, Bjoern; Lemme, Erika; Hassel, Petra; Niemann, Heiner; Heisterkamp, Alexander

2010-07-01

Since the birth of ``Dolly'' as the first mammal cloned from a differentiated cell, somatic cell cloning has been successful in several mammalian species, albeit at low success rates. The highly invasive mechanical enucleation step of a cloning protocol requires sophisticated, expensive equipment and considerable micromanipulation skill. We present a novel noninvasive method for combined oocyte imaging and automated functional enucleation using femtosecond (fs) laser pulses. After three-dimensional imaging of Hoechst-labeled porcine oocytes by multiphoton microscopy, our self-developed software automatically identified the metaphase plate. Subsequent irradiation of the metaphase chromosomes with the very same laser at higher pulse energies in the low-density-plasma regime was used for metaphase plate ablation (functional enucleation). We show that fs laser-based functional enucleation of porcine oocytes completely inhibited the parthenogenetic development without affecting the oocyte morphology. In contrast, nonirradiated oocytes were able to develop parthenogenetically to the blastocyst stage without significant differences to controls. Our results indicate that fs laser systems have great potential for oocyte imaging and functional enucleation and may improve the efficiency of somatic cell cloning.

Research on Somatization and Somatic Symptom Disorders: Ars longa, vita brevis.

PubMed

Dimsdale, Joel E

The new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition defines somatic symptom and related disorders as long-standing somatic symptoms that are associated with disproportionate thoughts, feelings, and behaviors, irrespective of whether or not a medical cause for these symptoms can be determined. In this Special Section of Psychosomatic Medicine, several articles address diagnostic issues and the central nervous system correlates of somatic symptom and related disorder and document new developments in its treatment.

Alexithymia and Somatization in Depressed Patients: The Role of the Type of Somatic Symptom Attribution

PubMed Central

TAYCAN, Okan; ÖZDEMİR, Armağan; ERDOĞAN TAYCAN, Serap

2017-01-01

Introduction This study aimed to establish the association between alexithymia and various factors, mainly somatization, and to determine the predictors of alexithymia in depressed patients. Methods A total of 90 patients with major depressive disorder who met The Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnostic criteria were administered the Toronto Alexithymia Scale (TAS), Beck Depression Inventory, Symptom Checklist-90 (SCL-90), Somatosensory Amplification Scale, and Symptom Interpretation Questionnaire. The patients were classified into two groups as alexithymic and non-alexithymic with respect to the TAS cut-off points (≥59=alexithymic). Predictors of alexithymia were tested by multiple linear regression analysis. Results Of all patients, 36 (40%) were in the alexithymic group. The percentage of women, depression severity, level of general psychopathology and distress, and somatic symptom reporting (SCL-90), as well as the tendency to somatosensory amplification and three forms of somatic symptom attributions, were significantly higher in alexithymic patients than in non-alexithymic patients. Furthermore, age, depression severity, somatic symptom reporting, and the tendency to attribute physical symptoms to somatic causes were predictors of alexithymia. Conclusion The results indicated an intimate association between alexithymia and somatization in depressed patients. Therefore, when evaluating depressed patients with alexithymia, their tendency for somatization should be considered, and alexithymic individuals should be assessed with particular attention, considering that somatization can mask the underlying depressive condition. PMID:28680305

Gender Differences in Somatic Symptoms and Current Suicidal Risk in Outpatients with Major Depressive Disorder.

PubMed

Jeon, Hong Jin; Woo, Jong-Min; Kim, Hyo-Jin; Fava, Maurizio; Mischoulon, David; Cho, Seong Jin; Chang, Sung Man; Park, Doo-Heum; Kim, Jong Woo; Yoo, Ikki; Heo, Jung-Yoon; Hong, Jin Pyo

2016-11-01

Although somatic symptoms are common complaints of patients with major depressive disorder (MDD), their associations with suicide are still unclear. A total of 811 MDD outpatients of aged between 18 to 64 years were enrolled nationwide in Korea with the suicidality module of the Mini-International Neuropsychiatric Interview (MINI) and the Depression and Somatic Symptom Scale (DSSS). On stepwise regression analysis, current suicidality scores were most strongly associated with chest pain in men, and neck or shoulder pain in women. Severe chest pain was associated with higher current suicidality scores in men than in women, whereas severe neck or shoulder pain showed no significant differences between the genders. In conclusion, MDD patients of both sexes with suicidal ideation showed significantly more frequent and severe somatic symptoms than those without. Current suicidal risk was associated with chest pain in men, and neck or shoulder pain in women. We suggest that clinicians pay attention to patients' somatic symptoms in real world practice.

The Theobroma cacao B3 domain transcription factor TcLEC2 plays a duel role in control of embryo development and maturation.

PubMed

Zhang, Yufan; Clemens, Adam; Maximova, Siela N; Guiltinan, Mark J

2014-04-24

The Arabidopsis thaliana LEC2 gene encodes a B3 domain transcription factor, which plays critical roles during both zygotic and somatic embryogenesis. LEC2 exerts significant impacts on determining embryogenic potential and various metabolic processes through a complicated genetic regulatory network. An ortholog of the Arabidopsis Leafy Cotyledon 2 gene (AtLEC2) was characterized in Theobroma cacao (TcLEC2). TcLEC2 encodes a B3 domain transcription factor preferentially expressed during early and late zygotic embryo development. The expression of TcLEC2 was higher in dedifferentiated cells competent for somatic embryogenesis (embryogenic calli), compared to non-embryogenic calli. Transient overexpression of TcLEC2 in immature zygotic embryos resulted in changes in gene expression profiles and fatty acid composition. Ectopic expression of TcLEC2 in cacao leaves changed the expression levels of several seed related genes. The overexpression of TcLEC2 in cacao explants greatly increased the frequency of regeneration of stably transformed somatic embryos. TcLEC2 overexpressing cotyledon explants exhibited a very high level of embryogenic competency and when cultured on hormone free medium, exhibited an iterative embryogenic chain-reaction. Our study revealed essential roles of TcLEC2 during both zygotic and somatic embryo development. Collectively, our evidence supports the conclusion that TcLEC2 is a functional ortholog of AtLEC2 and that it is involved in similar genetic regulatory networks during cacao somatic embryogenesis. To our knowledge, this is the first detailed report of the functional analysis of a LEC2 ortholog in a species other then Arabidopsis. TcLEC2 could potentially be used as a biomarker for the improvement of the SE process and screen for elite varieties in cacao germplasm.

Linking Anger Trait with Somatization in Low-Grade College Students: Moderating Roles of Family Cohesion and Adaptability

PubMed Central

LIU, Liang; LIU, Cuilian; ZHAO, Xudong

2017-01-01

Background Between 22% and 58% of patients in primary care settings complain of somatic symptoms. Previous research has found that somatization was associated with anger traits and family functions. However, studies that specifically assess the moderating effect of family function in how anger traits become somatic complaints are lacking. Aim This study was designed to examine whether the variances in family cohesion and family adaptability moderated the strength of the relationship between anger traits and somatization. Methods A cross-section design was conducted and 2008 college students were recruited from a comprehensive university in Shanghai. All participants finished questionnaires including Symptom Check List- 90 (SCL-90), State-Trait Anger Expression Inventory 2 (STAXI-2, Chinese version) and Family Adaptability and Cohesion Scale, second edition (FACES II, Chinese Version) to assess their degree of current somatization, anger trait and family function. Hierarchical linear regression analysis (Enter) was conducted respectively for men and women to examine the moderation effect of family cohesion and family adaptability in the association between anger and somatization. Results Somatic symptoms were significantly linked in the expected directions with depression and anger trait for both genders. Family cohesion and family adaptability were negatively associated with somatic symptoms. For female college students family cohesion was found to moderate the link between anger trait and somatization, but for male college students the moderation effect of family cohesion was marginally significant. The moderating role of family adaptability was significant for neither male nor female after current depressive symptoms were accounted for. Conclusion Proneness to anger is an independent predictor of somatization. For women, a high level of family cohesion was a protective factor which could reduce the influence of anger trait on somatic symptoms. Without comorbidity of current depression, family adaptability to some degree exempted individuals with anger proneness from developing somatic complaints. Interventions that integrate family cohesion cultivation, family flexibility fostering and depression treatment might be more effective for somatic patients high in anger trait. PMID:28769543

Aerobic Exercise Reduces Symptoms of Posttraumatic Stress Disorder: A Randomized Controlled Trial.

PubMed

Fetzner, Mathew G; Asmundson, Gordon J G

2015-01-01

Evidence suggests aerobic exercise has anxiolytic effects; yet, the treatment potential for posttraumatic stress disorder (PTSD) and responsible anxiolytic mechanisms have received little attention. Emerging evidence indicates that attentional focus during exercise may dictate the extent of therapeutic benefit. Whether benefits are a function of attentional focus toward or away from somatic arousal during exercise remains untested. Thirty-three PTSD-affected participants completed two weeks of stationary biking aerobic exercise (six sessions). To assess the effect of attentional focus, participants were randomized into three exercise groups: group 1 (attention to somatic arousal) received prompts directing their attention to the interoceptive effects of exercise, group 2 (distraction from somatic arousal) watched a nature documentary, and group 3 exercised with no distractions or interoceptive prompts. Hierarchal linear modeling showed all groups reported reduced PTSD and anxiety sensitivity (AS; i.e., fear of arousal-related somatic sensations) during treatment. Interaction effects between group and time were found for PTSD hyperarousal and AS physical and social scores, wherein group 1, receiving interoceptive prompts, experienced significantly less symptom reduction than other groups. Most participants (89%) reported clinically significant reductions in PTSD severity after the two-week intervention. Findings suggest, regardless of attentional focus, aerobic exercise reduces PTSD symptoms.

When somatization is not the only thing you suffer from: Examining comorbid syndromes using latent profile analysis, parenting practices and adolescent functioning.

PubMed

Scharf, Miri; Mayseless, Ofra; Rousseau, Sofie

2016-10-30

Understanding somatization presents a challenge to clinicians because it is often associated with other syndromes. We addressed somatization's comorbidity with other internalizing syndromes (anxiety, depression, withdrawal) using latent profile analysis. A representative sample of 3496 Israeli middle and high-school youths reported their internalizing symptoms, perceived parenting practices, psychosocial functioning, and health behaviors. Four profiles, similar across age and gender, were identified: overall-low (65.4%), moderately-high anxiety/depression/withdrawal (24.4%), high somatization (4.8%), and overall-high (5.4%). MANOVAs and follow-up ANOVAs revealed that for the most part the overall-high profile evinced the worst parenting, psychosocial functioning, and health behaviors (smoking and drinking), while the overall-low group evinced the best. For most variables the high somatization and moderately high profiles displayed midway results. However, the moderately-high profile reported higher levels of harsh parenting than the high somatization profile. The high somatization profile reported similar or higher levels of smoking, risk taking, vandalism, and rule violation than the overall-high group. High somatization, either alone or alongside anxiety, depression, and withdrawal, was associated with disruptive and risk-taking behaviors. This link might reflect problems in emotion and anger regulation and become stronger in adolescence because of dysregulation processes characterizing this period. Implications for practice are discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pathological narcissism and somatic symptoms among men and women attending an outpatient mental health clinic.

PubMed

Kealy, David; Tsai, Michelle; Ogrodniczuk, John S

2016-09-01

To explore the relationship between types of pathological narcissism and somatic symptoms among psychiatric outpatients. Patients (N = 95) completed measures of somatic symptoms, narcissistic grandiosity and vulnerability, and psychiatric symptoms. Relationships among variables were analysed using t-tests and correlations, controlling for psychiatric distress. Somatic symptoms were positively associated with two types of narcissistic dysfunction. Among women there was a positive association between somatic symptoms and narcissistic vulnerability, but not grandiosity. Among men, somatic symptoms were positively associated with narcissistic grandiosity, but not vulnerability. The connection between narcissistic pathology and somatic symptom severity appears to differ based on gender. Further research is needed to confirm and extend this preliminary finding.

The Effects of Prior Combat Experience on the Expression of Somatic and Affective Symptoms in Deploying Soldiers

DTIC Science & Technology

2006-01-01

Journal of Psychosomatic ResThe effects of prior combat experience on the expression of somatic and affective symptoms in deploying soldiers William...rates of somatic complaints compared with combat-naive soldiers. Methods: Self-reports of posttraumatic stress disorder (PTSD) and affective and somatic ...identical for the experienced and inexperienced groups, scores on the Affective and Somatic scales differed as a function of prior combat history. Previous

Somatic-Affective, But Not Cognitive-Depressive Symptoms are Associated With Reduced Health-Related Quality of Life in Patients With Congestive Heart Failure.

PubMed

Patron, Elisabetta; Messerotti Benvenuti, Simone; Lopriore, Vincenzo; Aratari, Jenny; Palomba, Daniela

Depression has been associated with poor health-related quality of life (HRQoL) in patients with congestive heart failure (CHF). However, to date, whether somatic-affective and cognitive-depressive symptoms differently contribute to poor HRQoL and behavioral functional capacity in patients with CHF has yet to be investigated. To examine the differential influence of somatic-affective vs cognitive-depressive symptoms on HRQoL and behavioral functional capacity in CHF patients. Overall, 55 patients with CHF completed a psychologic evaluation, including the Minnesota Living with Heart Failure Questionnaire, the Beck Depression Inventory-II, and the Beck Anxiety Inventory for HRQoL, depressive, and anxiety symptoms, respectively. The patients completed the Instrumental Activities of Daily Living Questionnaire and the 6-minute walk test for behavioral functional capacity. Hierarchical regression analyses were used to predict HRQoL and behavioral functional capacity from Beck Depression Inventory-II and Beck Anxiety Inventory scores. Somatic-affective depressive symptoms were associated with physical (β = 0.37, p = 0.005) and emotional (β = 0.39, p = 0.008) Minnesota Living with Heart Failure Questionnaire subscale scores. Likewise, somatic-affective depressive symptoms predicted Instrumental Activities of Daily Livings Scores (β = 0.43, p = 0.004) and distance ambulated during the 6-minute walk test (β = -0.36, p = 0.029). By contrast, cognitive-depressive symptoms and anxiety were unrelated to HRQoL and behavioral functional capacity (all p > 0.05). These findings showed that somatic-affective depressive symptoms, but not cognitive-depressive symptoms and anxiety, are associated with poor HRQoL and behavioral functional capacity independent of age, clinical functional status, and medical comorbidities. This study suggests that patients with CHF with somatic-affective rather than cognitive-depressive symptoms or anxiety may be at greater risk of poor HRQoL and behavioral functional capacity. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Youth unemployment and functional somatic symptoms in adulthood: results from the Northern Swedish cohort.

PubMed

Brydsten, Anna; Hammarström, Anne; Strandh, Mattias; Johansson, Klara

2015-10-01

Little is known about the possible long-term health consequences of youth unemployment. Research indicates that unemployment may lead to socioeconomic downward mobility and mental health problems, but we still lack knowledge of the long-term health consequences of youth unemployment. This article examines the potential long-term association between youth unemployment and functional somatic symptoms in adulthood. The 'Northern Swedish cohort' was used with data from five data collections, from 1981 (age 16) until 2007 (age 42). Youth unemployment was measured as months in unemployment between age 16 and 21, and health outcome as functional somatic symptoms (an index of 10 items of self-reported symptoms). Linear regression was used to analyse the relationship between months in youth unemployment and functional somatic symptoms at age 21 and age 42, stratified for women and men and adjusted for potential confounders, such as time spent in education at age 21 and later unemployment between age 21 and 42. Youth unemployment was significantly related to functional somatic symptoms at age 21 for men after controlling for confounders, but not for women. Among men, the association remained for functional somatic symptoms at age 42, after controlling for confounders. Adolescence seems to be a sensitive period during which unemployment could have remaining health effects in adulthood, at least for men, though assumptions of causality are tentative and more research is needed. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Further evidence for a broader concept of somatization disorder using the somatic symptom index.

PubMed

Hiller, W; Rief, W; Fichter, M M

1995-01-01

Somatization syndromes were defined in a sample of 102 psychosomatic inpatients according to the restrictive criteria of DSM-III-R somatization disorder and the broader diagnostic concept of the Somatic Symptom Index (SSI). Both groups showed a qualitatively similar pattern of psychopathological comorbidity and had elevated scores on measures of depression, hypochondriasis, and anxiety. A good discrimination between mild and severe forms of somatization was found by using the SSI criterion. SSI use accounted for a substantial amount of comorbidity variance, with rates of 15%-20% for depression, 16% for hypochondriasis, and 13% for anxiety. The results provide further evidence for the validity of the SSI concept, which reflects the clinical relevance of somatization in addition to the narrow definition of somatization disorder.

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer.

PubMed

Bailey, Swneke D; Desai, Kinjal; Kron, Ken J; Mazrooei, Parisa; Sinnott-Armstrong, Nicholas A; Treloar, Aislinn E; Dowar, Mark; Thu, Kelsie L; Cescon, David W; Silvester, Jennifer; Yang, S Y Cindy; Wu, Xue; Pezo, Rossanna C; Haibe-Kains, Benjamin; Mak, Tak W; Bedard, Philippe L; Pugh, Trevor J; Sallari, Richard C; Lupien, Mathieu

2016-10-01

Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers, suggesting that other mechanisms underlie the persistent expression of ESR1. We report significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer risk-associated loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer.

Are child anxiety and somatization associated with pain in pain-related functional gastrointestinal disorders?

USDA-ARS?s Scientific Manuscript database

This study investigated individual and incremental contributions of somatization and trait anxiety to pain report in children with pain-related functional gastrointestinal disorders. Eighty children (7-10 years) with pain-related functional gastrointestinal disorders completed the State-Trait Anxiet...

Intragenerational social mobility and functional somatic symptoms in a northern Swedish context: analyses of diagonal reference models.

PubMed

Jonsson, Frida; Sebastian, Miguel San; Hammarström, Anne; Gustafsson, Per E

2017-01-03

Research indicate that social class mobility could be potentially important for health, but whether this is due to the movement itself or a result of people having been integrated in different class contexts is, to date, difficult to infer. In addition, although several theories suggest that transitions between classes in the social hierarchy can be stressful experiences, few studies have empirically examined whether such movements may have health effects, over and above the implications of "being" in these classes. In an attempt to investigate whether intragenerational social mobility is associated with functional somatic symptoms in mid-adulthood, the current study tests three partially contrasting theories. The dissociative theory suggests that mobility in general and upward mobility in particular may be linked to psychological distress, while the falling from grace theory indicates that downward mobility is especially stressful. In contrast, the acculturation theory holds that the health implications of social mobility is not due to the movement itself but attributed to the class contexts in which people find themselves. Diagonal Reference Models were used on a sample of 924 individuals who in 1981 graduated from 9 th grade in the municipality of Luleå, Sweden. Social mobility was operationalized as change in occupational class between age 30 and 42 (measured in 1995 and 2007). The health outcome was functional somatic symptoms at age 42, defined as a clustering self-reported physical symptoms, palpitation and sleeping difficulties during the last 12 months. Overall mobility was not associated with higher levels of functional somatic symptoms compared to being immobile (p = 0.653). After controlling for prior and current class, sex, parental social position, general health, civil status, education and unemployment, the association between downward mobility was borderline significant (p = 0.055) while upward mobility was associated with lower levels of functional somatic symptoms (p = 0.03). The current study did not find unanimous support for any of the theories. Nevertheless, it sheds light on the possibility that upward mobility may be beneficial to reduce stress-related health problems in mid-life over and above the exposure to prior and current class, while downward mobility can be of less importance for middle-age health complaints.

Is the replication of somatic coliphages in water environments significant?

PubMed

Jofre, J

2009-04-01

Somatic coliphages are amid several groups of bacteriophages that have been suggested as indicators in water quality assessment. One of the limitations frequently endorsed to somatic coliphages as indicators is that they can replicate in the water environment. This review intends to evaluate the significance of this potential replication. In view of: the threshold densities of somatic coliphages and host bacteria needed for productive infection to occur, the densities of both host cells supporting somatic coliphages replication and these phages in water environments, and the poor contribution of lysogenic induction to the free somatic coliphage numbers in water, it can be concluded that replication of somatic coliphages in waters is very unlikely. Consequently, the contribution of replication in the environment of somatic coliphages is expected to have a non-noticeable influence on the numbers of somatic coliphages detected in water environments. Thus, the replication in the environment should not be argued as a limitation to the use of somatic coliphages as indicators.

Cellular Mechanisms of Somatic Stem Cell Aging

PubMed Central

Jung, Yunjoon

2014-01-01

Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

Differential relationships of somatic and cognitive anxiety with measures of processing speed in older adults.

PubMed

Schoen, Chelsea B; Holtzer, Roee

2017-09-01

Research suggests a reciprocal relationship between late-life anxiety and cognition, particularly attention and executive functions. Whereas evidence supports a conceptual distinction between cognitive and somatic dimensions of anxiety, their differential relationship with cognitive outcomes has not been examined, particularly on tests of attention/executive functions that rely on processing speed. Study goals were threefold: (a) to describe levels of overall, cognitive, and somatic anxiety in a sample of older adults without dementia, (b) to determine if overall anxiety is associated with performance on select measures of attention/executive functions that rely on processing speed, and (c) to determine if a differential relationship exists between cognitive and somatic anxiety and cognitive performance. Participants were 368 community-dwelling older adults. Results showed that elevated levels of somatic, but not cognitive anxiety were associated with poorer performance across measures. Findings suggest that the nature of anxiety symptoms may have important implications for cognitive performance in older adults.

Are we Genomic Mosaics? Variations of the Genome of Somatic Cells can Contribute to Diversify our Phenotypes.

PubMed

Astolfi, P A; Salamini, F; Sgaramella, V

2010-09-01

Theoretical and experimental evidences support the hypothesis that the genomes and the epigenomes may be different in the somatic cells of complex organisms. In the genome, the differences range from single base substitutions to chromosome number; in the epigenome, they entail multiple postsynthetic modifications of the chromatin. Somatic genome variations (SGV) may accumulate during development in response both to genetic programs, which may differ from tissue to tissue, and to environmental stimuli, which are often undetected and generally irreproducible. SGV may jeopardize physiological cellular functions, but also create novel coding and regulatory sequences, to be exposed to intraorganismal Darwinian selection. Genomes acknowledged as comparatively poor in genes, such as humans', could thus increase their pristine informational endowment. A better understanding of SGV will contribute to basic issues such as the "nature vs nurture" dualism and the inheritance of acquired characters. On the applied side, they may explain the low yield of cloning via somatic cell nuclear transfer, provide clues to some of the problems associated with transdifferentiation, and interfere with individual DNA analysis. SGV may be unique in the different cells types and in the different developmental stages, and thus explain the several hundred gaps persisting in the human genomes "completed" so far. They may compound the variations associated to our epigenomes and make of each of us an "(epi)genomic" mosaic. An ensuing paradigm is the possibility that a single genome (the ephemeral one assembled at fertilization) has the capacity to generate several different brains in response to different environments.

Functional Somatic Symptoms Across Cultures: Perceptual and Health Care Issues.

PubMed

Löwe, Bernd; Gerloff, Christian

2018-06-01

Functional neurological disorders are conceptualized as patterns of neurological symptoms that cannot be attributed to a clear organic etiology. The study by Wilkins et al. in this issue of Psychosomatic Medicine reveals that 8.2% of patients who were initially presented with suspected stroke were later diagnosed with functional disorders, i.e., "functional stroke mimics." However, the percentage of functional stroke mimics varied substantially with patients' nationality, age, and sex. In this editorial comment, we discuss potential reasons for the intercultural variation of the frequency of functional stroke mimics.The current models of symptom perception, in which symptom perception is guided by top-down processes of the central nervous system, are helpful in explaining the intercultural variation of functional symptoms. According to these models, cultural beliefs, previous illnesses, and stressful life situations influence patients' expectations, sensory input, and finally the perception of somatic symptoms. In addition, differences in insurance status, health literacy, and health care experiences are strong predictors of health care use in patients who experience somatic symptoms.This article provides a conceptual model that integrates sociocultural factors with symptom perception and health care use relevant to the different rates of functional somatic symptoms in emergency departments across nationalities. Considering these factors, future attempts to improve care for patients with functional disorders should enhance access to effective treatment for all patient groups, empower patients through education and early participation in the treatment process, and foster interdisciplinary collaboration among specialists from somatic and mental health disciplines.

Somatic symptoms beyond those generally associated with a whiplash injury are increased in self-reported chronic whiplash. A population-based cross sectional study: the Hordaland Health Study (HUSK)

PubMed Central

2012-01-01

Background Chronic whiplash leads to considerable patient suffering and substantial societal costs. There are two competing hypothesis on the etiology of chronic whiplash. The traditional organic hypothesis considers chronic whiplash and related symptoms a result of a specific injury. In opposition is the hypothesis that chronic whiplash is a functional somatic syndrome, and related symptoms a result of society-induced expectations and amplification of symptoms. According to both hypotheses, patients reporting chronic whiplash are expected to have more neck pain, headache and symptoms of anxiety and depression than the general population. Increased prevalence of somatic symptoms beyond those directly related to a whiplash neck injury is less investigated. The aim of this study was to test an implication derived from the functional hypothesis: Is the prevalence of somatic symptoms as seen in somatization disorder, beyond symptoms related to a whiplash neck injury, increased in individuals self-reporting chronic whiplash? We further aimed to explore recall bias by comparing the symptom profile displayed by individuals self-reporting chronic whiplash to that among those self-reporting a non-functional injury: fractures of the hand or wrist. We explored symptom load, etiologic origin could not be investigated in this study. Methods Data from the Norwegian population-based “Hordaland Health Study” (HUSK, 1997–99); N = 13,986 was employed. Chronic whiplash was self-reported by 403 individuals and fractures by 1,746. Somatization tendency was measured using a list of 17 somatic symptoms arising from different body parts and organ systems, derived from the research criteria for somatization disorder (ICD-10, F45). Results Chronic whiplash was associated with an increased level of all 17 somatic symptoms investigated (p<0.05). The association was moderately strong (group difference of 0.60 standard deviation), only partly accounted for by confounding. For self-reported fractures symptoms were only slightly elevated. Recent whiplash was more commonly reported than whiplash-injury a long time ago, and the association of interest weakly increased with time since whiplash (r = 0.016, p = 0.032). Conclusions The increased prevalence of somatic symptoms beyond symptoms expected according to the organic injury model for chronic whiplash, challenges the standard injury model for whiplash, and is indicative evidence of chronic whiplash being a functional somatic syndrome. PMID:22935146

Electronic Support Groups: An Open Line of Communication in Contested Illness

PubMed Central

Murphy, Michael; Kontos, Nicholas; Freudenreich, Oliver

2017-01-01

Background Patients with functional somatic syndromes are often difficult to treat. The relationship between doctors and patients can be strained, which limits communication. Instead, patients often communicate with each other over the Internet in electronic support groups. Objective This perspective summarizes studies of patient-to-patient communication over the Internet and uses the concept of contested illness to provide insights into the experiences of patients with functional somatic disorders. Discussion Conflict between a patient and their physician is a key feature of functional somatic syndromes. Physicians and patients do not have a shared understanding or appreciation of the patient’s experiences. Patients with functional somatic syndromes often value their own embodied experience over medical knowledge. At the same time, they remain deeply invested in finding a “good doctor” who believes that the patient is suffering, agrees with their conception of the cause, and assents to the treatment as directed by the patient. Electronic support groups reinforce these beliefs. Conclusion Patients may benefit from a compromising, collaborative approach that is realistic about the limitations of medical knowledge. However, physicians should not engage in unsafe treatment practices. Electronic support groups exist for a wide range of illnesses and the issues that rise to the surface in functional somatic syndromes likely occur to some extent with almost every patient. PMID:27421707

Review of somatic symptoms in post-traumatic stress disorder.

PubMed

Gupta, Madhulika A

2013-02-01

Post-traumatic stress disorder (PTSD) is associated with both (1) 'ill-defined' or 'medically unexplained' somatic syndromes, e.g. unexplained dizziness, tinnitus and blurry vision, and syndromes that can be classified as somatoform disorders (DSM-IV-TR); and (2) a range of medical conditions, with a preponderance of cardiovascular, respiratory, musculoskeletal, neurological, and gastrointestinal disorders, diabetes, chronic pain, sleep disorders and other immune-mediated disorders in various studies. Frequently reported medical co-morbidities with PTSD across various studies include cardiovascular disease, especially hypertension, and immune-mediated disorders. PTSD is associated with limbic instability and alterations in both the hypothalamic- pituitary-adrenal and sympatho-adrenal medullary axes, which affect neuroendocrine and immune functions, have central nervous system effects resulting in pseudo-neurological symptoms and disorders of sleep-wake regulation, and result in autonomic nervous system dysregulation. Hypervigilance, a central feature of PTSD, can lead to 'local sleep' or regional arousal states, when the patient is partially asleep and partially awake, and manifests as complex motor and/or verbal behaviours in a partially conscious state. The few studies of the effects of standard PTSD treatments (medications, CBT) on PTSD-associated somatic syndromes report a reduction in the severity of ill-defined and autonomically mediated somatic symptoms, self-reported physical health problems, and some chronic pain syndromes.

'I'm more sick than my doctors think': ethical issues in managing somatization in developing countries.

PubMed

Chandra, Prabha S; Satyanarayana, Veena A

2013-02-01

Several ethical issues confront the healthcare professional who is managing somatization in developing countries where cost constraints, low literacy, poverty, poor nutrition and infections and inadequate access to healthcare are common. The paper discusses these in the context of the ethical principles of autonomy, beneficence, non-maleficence and justice. Some of the ethical issues in managing somatization include being influenced by patient distress rather than rational medical decision-making, inadequate attention to the cultural meaning of symptoms, psychologizing versus medicalizing, the ethics of nomenclature and labels, communicating ethically with patients, and managing them adequately given lack of evidence and training. An ethical approach to managing somatization in this context would include using an integrated and simultaneous medical and psychiatric approach. To ensure patient beneficence, the medical, psychological and social assessment should be undertaken side-by-side as much as possible and should be cost effective. Respecting patient autonomy by using adequate communication methods and the patient's cultural model of the illness as part of management is also integral to ethical practice. In the developing world, issues of equity are also an important ethical concern. When more serious illnesses are the health priority, functional syndromes may not get equal importance or resources.

Mitochondrial DNA transmission and confounding mitochondrial influences in cloned cattle and pigs.

PubMed

Takeda, Kumiko

2013-04-01

Although somatic cell nuclear transfer (SCNT) is a powerful tool for production of cloned animals, SCNT embryos generally have low developmental competency and many abnormalities. The interaction between the donor nucleus and the enucleated ooplasm plays an important role in early embryonic development, but the underlying mechanisms that negatively impact developmental competency remain unclear. Mitochondria have a broad range of critical functions in cellular energy supply, cell signaling, and programmed cell death; thus, affect embryonic and fetal development. This review focuses on mitochondrial considerations influencing SCNT techniques in farm animals. Donor somatic cell mitochondrial DNA (mtDNA) can be transmitted through what has been considered a "bottleneck" in mitochondrial genetics via the SCNT maternal lineage. This indicates that donor somatic cell mitochondria have a role in the reconstructed cytoplasm. However, foreign somatic cell mitochondria may affect the early development of SCNT embryos. Nuclear-mitochondrial interactions in interspecies/intergeneric SCNT (iSCNT) result in severe problems. A major biological selective pressure exists against survival of exogenous mtDNA in iSCNT. Yet, mtDNA differences in SCNT animals did not reflect transfer of proteomic components following proteomic analysis. Further study of nuclear-cytoplasmic interactions is needed to illuminate key developmental characteristics of SCNT animals associated with mitochondrial biology.

The visceromotor and somatic afferent nerves of the penis.

PubMed

Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

2015-05-01

Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

Empirical Testing of an Algorithm for Defining Somatization in Children

PubMed Central

Eisman, Howard D.; Fogel, Joshua; Lazarovich, Regina; Pustilnik, Inna

2007-01-01

Introduction A previous article proposed an algorithm for defining somatization in children by classifying them into three categories: well, medically ill, and somatizer; the authors suggested further empirical validation of the algorithm (Postilnik et al., 2006). We use the Child Behavior Checklist (CBCL) to provide this empirical validation. Method Parents of children seen in pediatric clinics completed the CBCL (n=126). The physicians of these children completed specially-designed questionnaires. The sample comprised of 62 boys and 64 girls (age range 2 to 15 years). Classification categories included: well (n=53), medically ill (n=55), and somatizer (n=18). Analysis of variance (ANOVA) was used for statistical comparisons. Discriminant function analysis was conducted with the CBCL subscales. Results There were significant differences between the classification categories for the somatic complaints (p=<0.001), social problems (p=0.004), thought problems (p=0.01), attention problems (0.006), and internalizing (p=0.003) subscales and also total (p=0.001), and total-t (p=0.001) scales of the CBCL. Discriminant function analysis showed that 78% of somatizers and 66% of well were accurately classified, while only 35% of medically ill were accurately classified. Conclusion The somatization classification algorithm proposed by Postilnik et al. (2006) shows promise for classification of children and adolescents with somatic symptoms. PMID:18421368

Correlations between sexual dysfunction, depression, anxiety, and somatic symptoms among patients with major depressive disorder.

PubMed

Lin, Chiao-Fan; Juang, Yeong-Yuh; Wen, Jung-Kwang; Liu, Chia-Yih; Hung, Ching-I

2012-01-01

The purpose of this study was to investigate the degree of correlation between sexual dysfunction and depression, anxiety, and somatic symptoms among patients with major depressive disorder (MDD) and to identify the dimension most predictive of sexual dysfunction. One-hundred and thirty-five outpatients with MDD were enrolled and were treated with open-label venlafaxine 75 mg daily for one month. The Arizona Sexual Experience Scale-Chinese Version (ASEX-CV), Depression and Somatic Symptoms Scale (DSSS), Hamilton Depression Rating Scale, and Hospital Anxiety and Depression Scale (HADS) were administered at baseline and at one-month follow-up and the improvement percentage (IP) of each scale posttreatment was calculated. Multiple linear regression was used to determine the dimension most predictive of the total ASEX-CV score. Seventy subjects (20 men, 50 women) completed the one-month pharmacotherapy and the four scales. The depression subscale of the HADS was most strongly correlated with the ASEX-CV scale and was the only subscale to independently predict the total ASEX-CV score at the two points. However, the somatic subscale of the DSSS was not correlated with any ASEX-CV item. At the endpoint, depression, anxiety, and somatic symptoms were significantly improved (IP 48.5% to 26.0%); however, very little improvement was observed in the total ASEX-CV score (IP -1.6%). The severity of sexual dysfunction among patients with MDD was most correlated with the severity of the depressive dimension, but not the severity of the somatic dimension. Further studies are indicated to explore the relationships between sexual dysfunction, depression, anxiety, and somatic symptoms.

The Theobroma cacao B3 domain transcription factor TcLEC2 plays a duel role in control of embryo development and maturation

PubMed Central

2014-01-01

Background The Arabidopsis thaliana LEC2 gene encodes a B3 domain transcription factor, which plays critical roles during both zygotic and somatic embryogenesis. LEC2 exerts significant impacts on determining embryogenic potential and various metabolic processes through a complicated genetic regulatory network. Results An ortholog of the Arabidopsis Leafy Cotyledon 2 gene (AtLEC2) was characterized in Theobroma cacao (TcLEC2). TcLEC2 encodes a B3 domain transcription factor preferentially expressed during early and late zygotic embryo development. The expression of TcLEC2 was higher in dedifferentiated cells competent for somatic embryogenesis (embryogenic calli), compared to non-embryogenic calli. Transient overexpression of TcLEC2 in immature zygotic embryos resulted in changes in gene expression profiles and fatty acid composition. Ectopic expression of TcLEC2 in cacao leaves changed the expression levels of several seed related genes. The overexpression of TcLEC2 in cacao explants greatly increased the frequency of regeneration of stably transformed somatic embryos. TcLEC2 overexpressing cotyledon explants exhibited a very high level of embryogenic competency and when cultured on hormone free medium, exhibited an iterative embryogenic chain-reaction. Conclusions Our study revealed essential roles of TcLEC2 during both zygotic and somatic embryo development. Collectively, our evidence supports the conclusion that TcLEC2 is a functional ortholog of AtLEC2 and that it is involved in similar genetic regulatory networks during cacao somatic embryogenesis. To our knowledge, this is the first detailed report of the functional analysis of a LEC2 ortholog in a species other then Arabidopsis. TcLEC2 could potentially be used as a biomarker for the improvement of the SE process and screen for elite varieties in cacao germplasm. PMID:24758406

Hypochondriasis and somatization.

PubMed

Kellner, R

1987-11-20

Between 60% and 80% of healthy individuals experience somatic symptoms in any one week. About 10% to 20% of a random sample of people worry intermittently about illness. A substantial proportion of patients present physicians with somatic complaints for which no organic cause can be found. Patients who are hypochondriacal do not understand the benign nature of functional somatic symptoms and interpret these as evidence of disease. Hypochondriacal concerns range from common short-lived worries to persistent and distressing fears or convictions of having a disease. Hypochondriasis can be secondary to other psychiatric disorders (eg, melancholia or panic disorder), and hypochondriacal attitudes remit when the primary disorder is successfully treated. Patients with primary hypochondriasis are also anxious or depressed, but the fear of disease, or the false belief of having a disease, persists and is the most important feature of their psychopathology. There are substantial differences among hypochondriacal patients in their personalities and psychopathologies. Psychotherapy as well as psychotropic drugs are effective in the treatment of functional somatic symptoms. There are no adequate controlled studies on the value of psychotherapy in hypochondriasis; the recommended guidelines are based on uncontrolled studies of hypochondriasis and on controlled studies of the psychotherapy in similar disorders. The prognosis of functional somatic symptoms as well as that of hypochondriasis is good in a substantial proportion of patients.

Cancer treatment in childhood and testicular function: the importance of the somatic environment.

PubMed

Stukenborg, Jan-Bernd; Jahnukainen, Kirsi; Hutka, Marsida; Mitchell, Rod T

2018-02-01

Testicular function and future fertility may be affected by cancer treatment during childhood. Whilst survival of the germ (stem) cells is critical for ensuring the potential for fertility in these patients, the somatic cell populations also play a crucial role in providing a suitable environment to support germ cell maintenance and subsequent development. Regulation of the spermatogonial germ-stem cell niche involves many signalling pathways with hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review, we describe the somatic cell populations that comprise the testicular germ-stem cell niche in humans and how they may be affected by cancer treatment during childhood. We also discuss the experimental models that may be utilized to manipulate the somatic environment and report the results of studies that investigate the potential role of somatic cells in the protection of the germ cells in the testis from cancer treatment. © 2018 The authors.

Cancer treatment in childhood and testicular function: the importance of the somatic environment

PubMed Central

Stukenborg, Jan-Bernd; Jahnukainen, Kirsi; Hutka, Marsida

2018-01-01

Testicular function and future fertility may be affected by cancer treatment during childhood. Whilst survival of the germ (stem) cells is critical for ensuring the potential for fertility in these patients, the somatic cell populations also play a crucial role in providing a suitable environment to support germ cell maintenance and subsequent development. Regulation of the spermatogonial germ-stem cell niche involves many signalling pathways with hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review, we describe the somatic cell populations that comprise the testicular germ-stem cell niche in humans and how they may be affected by cancer treatment during childhood. We also discuss the experimental models that may be utilized to manipulate the somatic environment and report the results of studies that investigate the potential role of somatic cells in the protection of the germ cells in the testis from cancer treatment. PMID:29351905

Three forms of somatization in primary care: prevalence, co-occurrence, and sociodemographic characteristics.

PubMed

Kirmayer, L J; Robbins, J M

1991-11-01

Three definitions of somatization were operationalized: (a) high levels of functional somatic distress, measured by the Somatic Symptom Index (SSI) of the Diagnostic Interview Schedule; (b) hypochondriasis measured by high scores on a measure of illness worry in the absence of evidence for serious illness; and (c) exclusively somatic clinical presentations among patients with current major depression or anxiety. Of 685 patients attending two family medicine clinics, 26.3% met criteria for one or more forms of somatization. While DSM-III somatization disorder had a prevalence of only 1% in this population, 16.6% of the patients met abridged criteria for subsyndromal somatization disorder (SSI 4,6). Hypochondriacal worry had a prevalence of 7.7% in the clinic sample. Somatized presentations of current major depression or anxiety disorder had a prevalence of 8%. The three forms of somatization were associated with different sociodemographic and illness behavior characteristics. A majority of patients met criteria for only one type of somatization, suggesting that distinct pathogenic processes may be involved in each of the three types.

Somatic mutations contribute to genotypic diversity in sterile and fertile populations of the threatened shrub, Grevillea rhizomatosa (Proteaceae).

PubMed

Gross, C L; Nelson, Penelope A; Haddadchi, Azadeh; Fatemi, Mohammad

2012-02-01

Grevillea rhizomatosa is a spreading shrub which exhibits multiple breeding strategies within a narrow area in the fire-prone heathlands of eastern Australia. Reproductive strategies include self-compatibility, self-incompatibility and clonality (with and without sterility). The close proximity of contrasting breeding systems provides an opportunity to explore the evolution of sterility and to compare and contrast the origins of genotypic diversity (recombinant or somatic) against degrees of sexual expression. ISSR markers for 120 band positions (putative loci) were used to compare genetic diversity among five populations at a macro-scale of 5 m between samples (n = 244 shrubs), and at a micro-scale of nearest neighbours for all plants in five 25-m(2) quadrats with contrasting fertilities (n = 162 shrubs). Nearest-neighbour sampling included several clusters of connected ramets. Matrix incompatibility (MIC) analyses were used to evaluate the relative contribution of recombination and somatic mutation to genotype diversity. High levels of genotypic diversity were found in all populations regardless of fertilities (fertile populations, G/N ≥ 0·94; sterile populations, G/N ≥ 0·97) and most sterile populations had a unique genetic profile. Somatic mutations were detected along connected ramets in ten out of 42 ramet clusters. MIC analyses showed that somatic mutations have contributed to diversity in all populations and particularly so in sterile populations. Somatic mutations contribute significantly to gene diversity in sterile populations of Grevillea rhizomatosa, the accumulation of which is the likely cause of male and female sterility. High levels of genetic diversity therefore may not always be synonymous with sexual fitness and genetic health. We hypothesize that frequent fires drive selection for clonal reproduction, at the cost of flowering such that sexual functions are not maintained through selection, and the build-up of somatic mutations in meristems results in high genotype diversity at the cost of pollen and ovule fertilities.

Posttraumatic headache: biopsychosocial comparisons with multiple control groups.

PubMed

Tatrow, Kristin; Blanchard, Edward B; Hickling, Edward J; Silverman, Daniel J

2003-01-01

This study examined somatic, psychological, and cognitive functioning of subjects with posttraumatic headache in comparison with multiple control groups. Posttraumatic headache is not as widely studied as other forms of headache (eg, tension-type, migraine). Previous research has suggested poor psychological functioning in patients with posttraumatic headache in comparison with other groups of patients with pain; however, this group has yet to be compared with a group of persons who have experienced trauma but are headache-free. Nineteen subjects with posttraumatic headache were studied, with full assessments available for 14 participants. Comparison groups, containing 16 participants each, included another headache group, a nonheadache group, and a trauma (motor vehicle accident) survivor nonheadache group. Participants completed several measures assessing somatic, psychological, and cognitive functioning. Findings revealed that the posttraumatic headache group exhibited significantly poorer functioning than the comparison groups on several measures including the Psychosomatic Symptom Checklist, Postconcussion Syndrome Checklist, axis II psychiatric diagnoses, Minnesota Multiphasic Personality Inventory, and the Daily Hassles Scale (frequency and total). Additionally, they scored higher on the following: number of axis I psychiatric diagnoses, the Daily Hassles Scale (intensity), Beck Depression Inventory, State-Trait Anxiety Inventory, and State-Trait Anger Expression Inventory. The posttraumatic headache group was similar to the other trauma group on the Posttraumatic Stress Disorder Symptom Checklist and the Life-Trauma Checklist. This study confirmed the distress seen in this understudied population of persons with headache and highlights areas of focus for proper assessment and treatment of those with headache and who have had an accident.

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer

PubMed Central

Bailey, Swneke D.; Desai, Kinjal; Kron, Ken J.; Mazrooei, Parisa; Sinnott-Armstrong, Nicholas A.; Treloar, Aislinn E.; Dowar, Mark; Thu, Kelsie L.; Cescon, David W.; Silvester, Jennifer; Yang, S. Y. Cindy; Wu, Xue; Pezo, Rossanna C.; Haibe-Kains, Benjamin; Mak, Tak W.; Bedard, Philippe L.; Pugh, Trevor J.; Sallari, Richard C.; Lupien, Mathieu

2016-01-01

Sustained expression of the oestrogen receptor alpha (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon oestrogen stimulation to establish an oncogenic expression program1. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers2–5, implying that other mechanisms underlie the persistent expression of ESR1. We report the significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by a functional inherited single nucleotide variant (SNV) rs9383590 that accounts for several breast cancer risk-loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer. PMID:27571262

Electronic Support Groups: An Open Line of Communication in Contested Illness.

PubMed

Murphy, Michael; Kontos, Nicholas; Freudenreich, Oliver

Patients with functional somatic syndromes are often difficult to treat. The relationship between doctors and patients can be strained, which limits communication. Instead, patients often communicate with each other over the Internet in electronic support groups. This perspective summarizes studies of patient-to-patient communication over the Internet and uses the concept of contested illness to provide insights into the experiences of patients with functional somatic disorders. Conflict between a patient and their physician is a key feature of functional somatic syndromes. Physicians and patients do not have a shared understanding or appreciation of the patient's experiences. Patients with functional somatic syndromes often value their own embodied experience over medical knowledge. At the same time, they remain deeply invested in finding a "good doctor" who believes that the patient is suffering, agrees with their conception of the cause, and assents to the treatment as directed by the patient. Electronic support groups reinforce these beliefs. Patients may benefit from a compromising, collaborative approach that is realistic about the limitations of medical knowledge. However, physicians should not engage in unsafe treatment practices. Electronic support groups exist for a wide range of illnesses and the issues that rise to the surface in functional somatic syndromes likely occur to some extent with almost every patient. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Psychosocial functioning in consultation-liaison psychiatry patients: influence of psychosomatic syndromes, psychopathology and somatization.

PubMed

Porcelli, Piero; Bellomo, Antonello; Quartesan, Roberto; Altamura, Mario; Iuso, Salvatore; Ciannameo, Ida; Piselli, Massimiliano; Elisei, Sandro

2009-01-01

This study investigated whether the Diagnostic Criteria for Psychosomatic Research (DCPR) were able to predict psychosocial functioning in addition to psychiatric diagnoses and somatization in consultation-liaison psychiatry (CLP) patients. A consecutive sample of 208 CLP patients were recruited and assessed for sociodemographic and medical data, psychopathology (SCID), psychosomatic syndromes (DCPR structured interview) and somatization (SCL-90-R SOM scale and multisomatoform disorder, MSD). The main endpoints were the mental and physical components of psychosocial functioning (SF-36). A total of 185 (89%) patients had any psychiatric diagnosis, 51 (25%) had MSD positive criteria, 176 (85%) had any DCPR syndrome, and 105 (51%) had multiple DCPR syndromes. Although psychiatric and psychosomatic syndromes were variously associated with psychosocial functioning, hierarchical regression and effect size analyses showed that only DCPR syndromes, particularly demoralization and health anxiety, with somatization but not DSM-IV psychopathology independently predicted poor psychosocial functioning. The presence of psychosomatic syndromes, assessed with DCPR criteria, and high levels of somatization had larger effect size and were independent predictors of the mental and physical components of psychosocial dysfunction, over and above psychopathology. The DCPR classification can provide CLP professionals with a set of sensitive diagnostic criteria for a comprehensive clinical evaluation of psychosomatic syndromes that might play a significant mediating role in the course and the outcome of medical patients referred for psychiatric consultation. Copyright 2009 S. Karger AG, Basel.

Cytoplasmic RNA Granules in Somatic Maintenance.

PubMed

Moujaber, Ossama; Stochaj, Ursula

2018-05-30

Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent eukaryotes, including yeast, mammals, and plants. The functions of cytoplasmic RNA granules differ widely. They are dictated by the cell type and physiological state, which in turn is determined by intrinsic cell properties and environmental factors. RNA granules provide diverse cellular functions. However, all of the granules contribute to aspects of RNA metabolism. This is exemplified by transcription, RNA storage, silencing, and degradation, as well as mRNP remodeling and regulated translation. Several forms of cytoplasmic mRNA granules are linked to normal physiological processes. For instance, they may coordinate protein synthesis and thereby serve as posttranscriptional "operons". RNA granules also participate in cytoplasmic mRNA trafficking, a process particularly well understood for neurons. Many forms of RNA granules support the preservation of somatic cell performance under normal and stress conditions. On the other hand, severe insults or disease can cause the formation and persistence of RNA granules that contribute to cellular dysfunction, especially in the nervous system. Neurodegeneration and many other diseases linked to RNA granules are associated with aging. Nevertheless, information related to the impact of aging on the various types of RNA granules is presently very limited. This review concentrates on cytoplasmic RNA granules and their role in somatic cell maintenance. We summarize the current knowledge on different types of RNA granules in the cytoplasm, their assembly and function under normal, stress, or disease conditions. Specifically, we discuss processing bodies, neuronal granules, stress granules, and other less characterized cytoplasmic RNA granules. Our focus is primarily on mammalian and yeast models, because they have been critical to unravel the physiological role of various RNA granules. RNA granules in plants and pathogens are briefly described. We conclude our viewpoint by summarizing the emerging concepts for RNA granule biology and the open questions that need to be addressed in future studies. © 2018 S. Karger AG, Basel.

Emotion, Decision-Making and Substance Dependence: A Somatic-Marker Model of Addiction

PubMed Central

Verdejo-García, A; Pérez-García, M; Bechara, A

2006-01-01

Similar to patients with orbitofrontal cortex lesions, substance dependent individuals (SDI) show signs of impairments in decision-making, characterised by a tendency to choose the immediate reward at the expense of severe negative future consequences. The somatic-marker hypothesis proposes that decision-making depends in many important ways on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between abnormalities in experiencing emotions in SDI, and their severe impairments in decision-making in real-life. Growing evidence from neuroscientific studies suggests that core aspects of substance addiction may be explained in terms of abnormal emotional guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in SDI. Combined neuropsychological and physiological assessment has demonstrated that the poorer decision-making of SDI is associated with altered reactions to reward and punishing events. Imaging studies have shown that impaired decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, including the ventromedial cortex, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker model of addiction. PMID:18615136

Associations between low back pain and depression and somatization in a Canadian emerging adult population

PubMed Central

Robertson, David; Kumbhare, Dinesh; Nolet, Paul; Srbely, John; Newton, Genevieve

2017-01-01

Introduction The association between depression, somatization and low back pain has been minimally investigated in a Canadian emerging adult population. Methods 1013 first year Canadian university students completed the Modified Zung Depression Index, the Modified Somatic Perception Questionnaire, and a survey about low back pain frequency and intensity. Multinomial logistic regression was used to measure associations between low back pain and depression and somatization, both independently and co-occurring. Results Over 50% of subjects reported low back pain across grades, and both depression and somatization were significantly positively associated with low back pain. Several positive associations between the cooccurrence of somatization and depression with various grades of low back pain were observed. Discussion These results suggest that low back pain, depression and somatization are relatively common at the onset of adulthood, and should be considered an important focus of public health. PMID:28928493

Elevated levels of psychophysiological arousal and cortisol in patients with somatization syndrome.

PubMed

Rief, W; Shaw, R; Fichter, M M

1998-01-01

This study investigates psychological and psychobiological processes in patients with somatization syndrome. We compared physiological measures (heart rate, finger pulse volume, electrodermal activity, electromyography), cortisol levels, and subjective well-being during rest and during a mental stress task as well as selective attention and memory for illness-related words in 58 patients with somatization syndrome and 21 healthy controls. The somatization group had higher morning salivary cortisol concentrations, higher heart rates, and lower levels of finger pulse volume. During the mental stress task, patients with somatization syndrome felt more distressed and had higher heart rates, whereas controls showed habituation to the experimental situation. We were unable to demonstrate an attention or memory bias specific for somatization. The results point to several psychological, psychophysiological, and psychobiological mechanisms that might be involved in the maintenance of somatization syndrome. These results are discussed from a cognitive-psychobiological perspective.

Predictive factors for somatization in a trauma sample

PubMed Central

2009-01-01

Background Unexplained somatic symptoms are common among trauma survivors. The relationship between trauma and somatization appears to be mediated by posttraumatic stress disorder (PTSD). However, only few studies have focused on what other psychological risk factors may predispose a trauma victim towards developing somatoform symptoms. Methods The present paper examines the predictive value of PTSD severity, dissociation, negative affectivity, depression, anxiety, and feeling incompetent on somatization in a Danish sample of 169 adult men and women who were affected by a series of explosions in a firework factory settled in a residential area. Results Negative affectivity and feelings of incompetence significantly predicted somatization, explaining 42% of the variance. PTSD was significant until negative affectivity was controlled for. Conclusion Negative affectivity and feelings of incompetence significantly predicted somatization in the trauma sample whereas dissociation, depression, and anxiety were not associated with degree of somatization. PTSD as a risk factor was mediated by negative affectivity. PMID:19126224

The Effectiveness of Somatization in Communicating Distress in Korean and American Cultural Contexts

PubMed Central

Choi, Eunsoo; Chentsova-Dutton, Yulia; Parrott, W. Gerrod

2016-01-01

Previous research has documented that Asians tend to somatize negative experiences to a greater degree than Westerners. It is posited that somatization may be a more functional communication strategy in Korean than American context. We examined the effects of somatization in communications of distress among participants from the US and Korea. We predicted that the communicative benefits of somatic words used in distress narratives would depend on the cultural contexts. In Study 1, we found that Korean participants used more somatic words to communicate distress than US participants. Among Korean participants, but not US participants, use of somatic words predicted perceived effectiveness of the communication and expectations of positive reactions (e.g., empathy) from others. In Study 2, we found that when presented with distress narratives of others, Koreans (but not Americans) showed more sympathy in response to narratives using somatic words than narratives using emotional words. These findings suggest that cultural differences in use of somatization may reflect differential effectiveness of somatization in communicating distress across cultural contexts. PMID:27047414

Emotional distress and dysfunctional illness perception are associated with low mental and physical quality of life in Chinese breast cancer patients.

PubMed

Tang, Lili; Fritzsche, Kurt; Leonhart, Rainer; Pang, Ying; Li, Jinjiang; Song, Lili; Fischer, Irmela; Koch, Maike; Wuensch, Alexander; Mewes, Ricarda; Schaefert, Rainer

2017-12-01

To evaluate the relationship between quality of life (QOL) and physical as well as psychological variables in Chinese breast cancer patients. This multicenter cross-sectional study enrolled 254 Chinese breast cancer patients in different stages and treatment phases. They answered standard instruments assessing QOL (EORTC), somatic symptom severity (PHQ-15), depression (PHQ-9), anxiety (GAD-7), health-related anxiety (WI-7), illness perception (BIPQ), and sense of coherence (SOC-9). Canonical correlation was applied to identify the strongest correlates between the physical, emotional and social QOL scales and the physical and psychological variables. In our sample, a low global QOL was significantly associated with the following physical and psychological variables: symptom-related disability (Karnofsky Index) (r = .211, p < .01), somatic symptom severity (r = -.391, p < .001), depression (r = -.488, p < .001), anxiety (r = -.439, p < .001), health-related anxiety (r = -.398, p < .001), dysfunctional illness perception (r = -.411, p < .001), and sense of coherence (r = .371, p < .001). In the canonical correlation analysis, high somatic symptom severity, depression, anxiety, dysfunctional illness perception, and low sense of coherence showed the strongest correlations with low physical, emotional and social functioning. The first three significant canonical correlations between these two sets of variables were .78, .56, and .45. QOL in Chinese breast cancer patients is strongly associated with psychological factors. Our results suggest that Chinese physicians and nurses should incorporate these factors into their care for women with breast cancer to improve patients' QOL.

Somatic tinnitus prevalence and treatment with tinnitus retraining therapy.

PubMed

Ostermann, K; Lurquin, P; Horoi, M; Cotton, P; Hervé, V; Thill, M P

2016-01-01

Somatic tinnitus originates from increased activity of the dorsal cochlear nucleus, a cross-point between the somatic and auditory systems. Its activity can be modified by auditory stimulation or somatic system manipulation. Thus, sound enrichment and white noise stimulation might decrease tinnitus and associated somatic symptoms. The present uncontrolled study sought to determine somatic tinnitus prevalence among tinnitus sufferers, and to investigate whether sound therapy with counselling (tinnitus retraining therapy; TRT) may decrease tinnitus-associated somatic symptoms. To determine somatic tinnitus prevalence, 70 patients following the TRT protocol completed the Jastreboff Structured Interview (JSI) with additional questions regarding the presence and type of somatic symptoms. Among 21 somatic tinnitus patients, we further investigated the effects of TRT on tinnitus-associated facial dysesthesia. Before and after three months of TRT, tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI), and facial dysesthesia was assessed with an extended JSI-based questionnaire. Among the evaluated tinnitus patients, 56% presented somatic tinnitus-including 51% with facial dysesthesia, 36% who could modulate tinnitus by head and neck movements, and 13% with both conditions. Self-evaluation indicated that TRT significantly improved tinnitus and facial dysesthesia in 76% of patients. Three months of TRT led to a 50% decrease in mean THI and JSI scores regarding facial dysesthesia. Somatic tinnitus is a frequent and underestimated condition. We suggest an extension of the JSI, including specific questions regarding somatic tinnitus. TRT significantly improved tinnitus and accompanying facial dysesthesia, and could be a useful somatic tinnitus treatment.

Somatic Mutation Patterns in Hemizygous Genomic Regions Unveil Purifying Selection during Tumor Evolution

PubMed Central

Basu, Swaraj; Larsson, Erik

2016-01-01

Identification of cancer driver genes using somatic mutation patterns indicative of positive selection has become a major goal in cancer genomics. However, cancer cells additionally depend on a large number of genes involved in basic cellular processes. While such genes should in theory be subject to strong purifying (negative) selection against damaging somatic mutations, these patterns have been elusive and purifying selection remains inadequately explored in cancer. Here, we hypothesized that purifying selection should be evident in hemizygous genomic regions, where damaging mutations cannot be compensated for by healthy alleles. Using a 7,781-sample pan-cancer dataset, we first confirmed this in POLR2A, an essential gene where hemizygous deletions are known to confer elevated sensitivity to pharmacological suppression. We next used this principle to identify several genes and pathways that show patterns indicative of purifying selection to avoid deleterious mutations. These include the POLR2A interacting protein INTS10 as well as genes involved in mRNA splicing, nonsense-mediated mRNA decay and other RNA processing pathways. Many of these genes belong to large protein complexes, and strong overlaps were observed with recent functional screens for gene essentiality in human cells. Our analysis supports that purifying selection acts to preserve the remaining function of many hemizygously deleted essential genes in tumors, indicating vulnerabilities that might be exploited by future therapeutic strategies. PMID:28027311

Disability and health-related quality-of-life 4 years after a severe traumatic brain injury: A structural equation modelling analysis.

PubMed

Azouvi, Philippe; Ghout, Idir; Bayen, Eleonore; Darnoux, Emmanuelle; Azerad, Sylvie; Ruet, Alexis; Vallat-Azouvi, Claire; Pradat-Diehl, Pascale; Aegerter, Philippe; Charanton, James; Jourdan, Claire

2016-01-01

To assess predictors and indicators of disability and quality-of-life 4 years after severe traumatic brain injury (TBI), using structural equation modelling (SEM). The PariS-TBI study is a longitudinal multi-centre inception cohort study of 504 patients with severe TBI. Among 245 survivors, 147 patients were evaluated upon 4-year follow-up, and 85 completed the full assessment. Two outcome measures were analysed separately using SEM: the Glasgow Outcome Scale-extended (GOS-E), to measure disability, and the QOLIBRI, to assess quality-of-life. Four groups of variables were entered in the model: demographics; injury severity; mood and cognitive impairments; somatic impairments. The GOS-E was directly significantly related to mood and cognition, injury severity, and somatic impairments. Age and education had an indirect effect, mediated by mood/cognition or somatic deficiencies. In contrast, the only direct predictor of QOLIBRI was mood and cognition. Age and somatic impairments had an indirect influence on the QOLIBRI. Although this study should be considered as explorative, it suggests that disability and quality-of-life were directly influenced by different factors. While disability appeared to result from an interaction of a wide range of factors, quality-of-life was solely directly related to psycho-cognitive factors.

Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples

PubMed Central

Peterson, Thomas A.; Park, Junyong

2017-01-01

The fight against cancer is hindered by its highly heterogeneous nature. Genome-wide sequencing studies have shown that individual malignancies contain many mutations that range from those commonly found in tumor genomes to rare somatic variants present only in a small fraction of lesions. Such rare somatic variants dominate the landscape of genomic mutations in cancer, yet efforts to correlate somatic mutations found in one or few individuals with functional roles have been largely unsuccessful. Traditional methods for identifying somatic variants that drive cancer are ‘gene-centric’ in that they consider only somatic variants within a particular gene and make no comparison to other similar genes in the same family that may play a similar role in cancer. In this work, we present oncodomain hotspots, a new ‘domain-centric’ method for identifying clusters of somatic mutations across entire gene families using protein domain models. Our analysis confirms that our approach creates a framework for leveraging structural and functional information encapsulated by protein domains into the analysis of somatic variants in cancer, enabling the assessment of even rare somatic variants by comparison to similar genes. Our results reveal a vast landscape of somatic variants that act at the level of domain families altering pathways known to be involved with cancer such as protein phosphorylation, signaling, gene regulation, and cell metabolism. Due to oncodomain hotspots’ unique ability to assess rare variants, we expect our method to become an important tool for the analysis of sequenced tumor genomes, complementing existing methods. PMID:28426665

Advances in computational approaches for prioritizing driver mutations and significantly mutated genes in cancer genomes.

PubMed

Cheng, Feixiong; Zhao, Junfei; Zhao, Zhongming

2016-07-01

Cancer is often driven by the accumulation of genetic alterations, including single nucleotide variants, small insertions or deletions, gene fusions, copy-number variations, and large chromosomal rearrangements. Recent advances in next-generation sequencing technologies have helped investigators generate massive amounts of cancer genomic data and catalog somatic mutations in both common and rare cancer types. So far, the somatic mutation landscapes and signatures of >10 major cancer types have been reported; however, pinpointing driver mutations and cancer genes from millions of available cancer somatic mutations remains a monumental challenge. To tackle this important task, many methods and computational tools have been developed during the past several years and, thus, a review of its advances is urgently needed. Here, we first summarize the main features of these methods and tools for whole-exome, whole-genome and whole-transcriptome sequencing data. Then, we discuss major challenges like tumor intra-heterogeneity, tumor sample saturation and functionality of synonymous mutations in cancer, all of which may result in false-positive discoveries. Finally, we highlight new directions in studying regulatory roles of noncoding somatic mutations and quantitatively measuring circulating tumor DNA in cancer. This review may help investigators find an appropriate tool for detecting potential driver or actionable mutations in rapidly emerging precision cancer medicine. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Clonal hematopoiesis as determined by the HUMARA assay is a marker for acquired mutations in epigenetic regulators in older women.

PubMed

Wiedmeier, Julia Erin; Kato, Catherine; Zhang, Zhenzhen; Lee, Hyunjung; Dunlap, Jennifer; Nutt, Eric; Rattray, Rogan; McKay, Sarah; Eide, Christopher; Press, Richard; Mori, Motomi; Druker, Brian; Dao, Kim-Hien

2016-09-01

Recent large cohort studies revealed that healthy older individuals harbor somatic mutations that increase their risk for hematologic malignancy and all-cause cardiovascular deaths. The majority of these mutations are in chromatin and epigenetic regulatory genes (CERGs). CERGs play a key role in regulation of DNA methylation (DNMT3A and TET2) and histone function (ASXL1) and in clonal proliferation of hematopoietic stem cells. We hypothesize that older women manifesting clonal hematopoiesis, defined here as a functional phenomenon in which a hematopoietic stem cell has acquired a survival and proliferative advantage, harbor a higher frequency of somatic mutations in CERGs. The human androgen receptor gene (HUMARA) assay was used in our study to detect the presence of nonrandom X inactivation in women, a marker for clonal hematopoiesis. In our pilot study, we tested 127 blood samples from women ≥65 years old without a history of invasive cancer or hematologic malignancies. Applying stringent qualitative criteria, we found that 26% displayed clonal hematopoiesis; 52.8% displayed polyclonal hematopoiesis; and 21.3% had indeterminate patterns (too close to call by qualitative assessment). Using Illumina MiSeq next-generation sequencing, we identified somatic mutations in CERGs in 15.2% of subjects displaying clonal hematopoiesis (three ASXL1 and two DNMT3A mutations with an average variant allele frequency of 15.7%, range: 6.3%-23.3%). In a more limited sequencing analysis, we evaluated the frequency of ASXL1 mutations by Sanger sequencing and found mutations in 9.7% of the clonal samples and 0% of the polyclonal samples. By comparing several recent studies (with some caveats as described), we determined the fold enrichment of detecting CERG mutations by using the HUMARA assay as a functional screen for clonal hematopoiesis. We conclude that a functional assay of clonal hematopoiesis is enriching for older women with somatic mutations in CERGs, particularly for ASXL1 and TET2 mutations and less so for DNMT3A mutations. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Trauma-informed schools: Child disaster exposure, community violence and somatic symptoms.

PubMed

Lai, Betty S; Osborne, Melissa C; Lee, NaeHyung; Self-Brown, Shannon; Esnard, Ann-Margaret; Kelley, Mary Lou

2018-06-15

Given the increasing prevalence of natural disasters, trauma-informed school settings should include efficient methods for assessing child health and mental health in post-disaster environments. To develop such methods, factors that contribute to children's vulnerability and key signs of distress reactions after disasters need to be understood. To address these issues, we evaluated pre-disaster community violence exposure as a vulnerability factor for children's post-disaster reactions and somatic symptoms as a key post-disaster outcome. We evaluated 426 children exposed to Hurricane Katrina at two timepoints (3-7 months and 13-17 months post-disaster). Structural equation models evaluated community violence exposure, hurricane exposure, and posttraumatic stress and somatic symptoms. Community violence exposure was associated with increased levels of posttraumatic stress symptoms among disaster-impacted youth, and did not moderate the relationship between disaster exposure and posttraumatic stress symptoms. Posttraumatic stress symptoms were associated with somatic symptoms in the short-term recovery period (3-7 months), but not associated with somatic symptoms during the longer-term recovery period (13-17 months). This study did not include school-level factors, and somatic symptoms were based on parent reports. The study did not include parent functioning information or distinguish between whether somatic symptoms were medical or functional in nature. Post-disaster school-based screeners may need to incorporate questions related to children's past exposure to community violence and their somatic symptoms to provide trauma-informed care for children. Copyright © 2018. Published by Elsevier B.V.

Oral health-related quality of life and somatization in the elderly.

PubMed

Hassel, Alexander J; Rolko, Claudia; Leisen, Joachim; Schmitter, Marc; Rexroth, Walter; Leckel, Michael

2007-03-01

Somatization disorders are frequent in the elderly, and previous studies have revealed that psychological factors affect the outcome of measurement of oral health-related quality of life (OHRQoL). The objective of this study was, therefore, to investigate the correlation between OHRQoL and somatization. One-hundred and twenty-five participants aged 60 years or older (mean age 76.6 years; 40 males) from a primary geriatric medical hospital participated in this cross-sectional study. OHRQoL was assessed by using the Oral Health Impact Profile (OHIP), somatization by using the somatization subscale of the Symptom Check List (SCL-90-R). To obtain dental data we performed a clinical dental examination. In bivariate analyses the most consistent correlation with somatization was found for overall OHIP sum score and the subscales physical pain and functional limitation (r > 0.4). Participants with high somatization scores had high OHIP sum scores. In multivariate analysis somatization led to additional explanation of the variance of the OHIP sum score and of all OHIP subscales. There is consistent correlation between OHRQoL and somatization. When evaluating OHRQoL in the elderly (using the OHIP) further evaluation of somatization should be considered for thorough interpretation of the results.

People with alcohol use disorders in specialized care in eight different European countries.

PubMed

Rehm, Jürgen; Allamani, Allaman; Aubin, Henri-Jean; Della Vedova, Roberto; Elekes, Zsuzsanna; Frick, Ulrich; Jakubczyk, Andrzej; Kostogianni, Nikoleta; Landsmane, Inga; Manthey, Jakob; Miquel, Laia; Paille, François; Pieper, Lars; Probst, Charlotte; Scafuri, Francesca; Shield, Kevin D; Snikere, Sigita; Struzzo, Pierluigi; Trapencieris, Marcis; Voller, Fabio; Wittchen, Hans-Ulrich; Gual, Antoni; Wojnar, Marcin

2015-05-01

To provide a description of patients receiving alcohol treatment in eight different European countries, including the level of comorbidities and functional limitations. Drinking behaviours, DSM-IV alcohol use disorder (AUD), mental and somatic comorbidities, disability and health services utilization of 1767 patients from various specialized treatment settings were assessed as representative for regions of eight European countries. Severity of alcohol dependence (AD) in terms of drinking level was compared with a large representative US sample. Patients in specialized care for AUDs showed high levels of consumption [average level of daily ethanol intake: 141.1 g, standard deviation (SD): 116.0 g], comorbidity [e.g. liver problems: 19.6%, 95% confidence interval (CI): 17.5-21.6%; depression: 43.2%, 95% CI: 40.7-45.8%; anxiety: 50.3%, 95% CI: 47.8-52.9%], disability and health services utilization (average number of nights spent in hospital(s) during the last 6 months: 8.8, SD: 19.5 nights). Severity of AD was similar to the US sample, but European men consumed on average more alcohol daily. High levels of consumption, somatic and mental comorbidities, disability and functional losses were found in this representative treatment sample, indicating that treatment was initiated only at severe stages of AUDs. Earlier initiation of treatment could help avoid some of the health and social burden. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

What is the role of "nonorganic somatic components" in functional capacity evaluations in patients with chronic nonspecific low back pain undergoing fitness for work evaluation?

PubMed

Oesch, Peter; Meyer, Kathrin; Jansen, Beatrice; Mowinckel, Petter; Bachmann, Stefan; Hagen, Kare Birger

2012-02-15

Analytical cross-sectional study. To assess the association of "nonorganic somatic components" together with physical and other psychosocial factors on functional capacity evaluation (FCE) in patients with chronic nonspecific low back pain (NSLBP) undergoing fitness-for-work evaluation. Functional capacity evaluation is increasingly used for physical fitness-for-work evaluation in patients with chronic NSLBP, but results seem to be influenced by physical as well as psychosocial factors. The influence of nonorganic somatic components together with physical and other psychosocial factors on FCE performance has not yet been investigated. One hundred twenty-six patients with chronic NSLBP referred for physical fitness-for-work evaluation were included. The 4 FCE tests were lifting from floor to waist, forward bend standing, grip strength, and 6-minute walking. Nonorganic somatic components were assessed with the 8 nonorganic somatic signs as defined by Waddell and were adjusted for age, sex, days off work, salary in the previous occupation, pain intensity, fear avoidance belief, and perceived functional ability in multivariate regression analyses. Between 42% and 58% of the variation in the FCE tests was explained in the final multivariate regression models. Nonorganic somatic components were consistent independent predictors for all tests. Their influence was most important on forward bend standing and walking distance, and less on grip strength and lifting performance. The physical factors of age and/or sex were strongly associated with grip strength and lifting, less with walking distance, and not at all with forward bend standing. The influence of at least 1 other psychosocial factor was observed in all FCE tests, having the highest proportion in the 6-minute walking test. Nonorganic somatic components seem to be consistent independent predictors in FCE testing and should be considered for interpretation of test results.

The Role of Somatic Symptoms in Sexual Medicine: Somatization as Important Contextual Factor in Male Sexual Dysfunction.

PubMed

Fanni, Egidia; Castellini, Giovanni; Corona, Giovanni; Boddi, Valentina; Ricca, Valdo; Rastrelli, Giulia; Fisher, Alessandra Daphne; Cipriani, Sarah; Maggi, Mario

2016-09-01

An important feature of somatic symptom disorder is the subjective perception of the physical symptoms and its maladaptive interpretation. Considering that psychological distress is often expressed through somatic symptoms, it is possible that they underlie at least a part of the symptoms in subjects complaining of sexual dysfunction. Nevertheless, studies on the impact of somatoform disorders in sexual dysfunction are scanty. To define the psychological, relational, and organic correlates of somatic symptoms in a large sample of patients complaining of sexual problems. A consecutive series of 2833 men (mean age 50.2 ± 13.5 years) was retrospectively studied. Somatic symptoms were assessed using the "somatized anxiety symptoms" subscale of the Middlesex Hospital Questionnaire (MHQ-S). Several clinical, biochemical, psychological, and relational parameters were studied. Patients were interviewed with the previously validated Structured Interview on Erectile Dysfunction (SIEDY), and ANDROTEST (a structured interview for the screening of hypogonadism in patients with sexual dysfunction). Among the 2833 patients studied, subjects scoring higher on somatic symptoms were older, more obese, reporting unhealthy lifestyle (current smoking, alcohol consumption), and a lower education (all P < .05). Moreover, they reported a general impairment of their sexuality more often, including erectile problems (spontaneous or sexual-related), low sexual desire, decreased frequency of intercourse, and perceived reduction of ejaculate volume (all P < .005). Interestingly, we observed a significant association between MHQ-S scoring with a reduced testosterone level and hypogonadism symptoms (both P < .05). Finally, we found a significant association between somatic symptoms and both SIEDY Scales 1 (organic domain of ED) and 3 (intrapsychic domain of ED) (both P < .0001). The present study demonstrates that the presence of somatic symptoms can represent an important contextual factor in the determination of or in the exacerbation of male sexual dysfunction. High levels of somatic symptoms in subjects with sexual dysfunction can be related to the sexual symptom itself. The consequences of this pattern have great clinical relevance in a sexual medicine setting, considering their severe impact on sexuality. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Dual functions of Macpiwi1 in transposon silencing and stem cell maintenance in the flatworm Macrostomum lignano

PubMed Central

Zhou, Xin; Battistoni, Giorgia; El Demerdash, Osama; Gurtowski, James; Wunderer, Julia; Falciatori, Ilaria; Ladurner, Peter; Schatz, Michael C.; Hannon, Gregory J.; Wasik, Kaja A.

2015-01-01

PIWI proteins and piRNA pathways are essential for transposon silencing and some aspects of gene regulation during animal germline development. In contrast to most animal species, some flatworms also express PIWIs and piRNAs in somatic stem cells, where they are required for tissue renewal and regeneration. Here, we have identified and characterized piRNAs and PIWI proteins in the emerging model flatworm Macrostomum lignano. We found that M. lignano encodes at least three PIWI proteins. One of these, Macpiwi1, acts as a key component of the canonical piRNA pathway in the germline and in somatic stem cells. Knockdown of Macpiwi1 dramatically reduces piRNA levels, derepresses transposons, and severely impacts stem cell maintenance. Knockdown of the piRNA biogenesis factor Macvasa caused an even greater reduction in piRNA levels with a corresponding increase in transposons. Yet, in Macvasa knockdown animals, we detected no major impact on stem cell self-renewal. These results may suggest stem cell maintenance functions of PIWI proteins in flatworms that are distinguishable from their impact on transposons and that might function independently of what are considered canonical piRNA populations. PMID:26323280

Annual Research Review: Functional Somatic Symptoms and Associated Anxiety and Depression--Developmental Psychopathology in Pediatric Practice

ERIC Educational Resources Information Center

Campo, John V.

2012-01-01

Background: Medically unexplained physical symptoms, commonly referred to as functional somatic symptoms (FSS), are common in pediatric medical settings and associated with suffering, impairment, and medical help seeking. The association of pediatric FSS with anxiety and depressive symptoms and disorders across the life span is reviewed.Method:…

Retinoic acid signaling is dispensable for somatic development and function in the mammalian ovary.

PubMed

Minkina, Anna; Lindeman, Robin E; Gearhart, Micah D; Chassot, Anne-Amandine; Chaboissier, Marie-Christine; Ghyselinck, Norbert B; Bardwell, Vivian J; Zarkower, David

2017-04-15

Retinoic acid (RA) is a potent inducer of cell differentiation and plays an essential role in sex-specific germ cell development in the mammalian gonad. RA is essential for male gametogenesis and hence fertility. However, RA can also disrupt sexual cell fate in somatic cells of the testis, promoting transdifferentiation of male Sertoli cells to female granulosa-like cells when the male sexual regulator Dmrt1 is absent. The feminizing ability of RA in the Dmrt1 mutant somatic testis suggests that RA might normally play a role in somatic cell differentiation or cell fate maintenance in the ovary. To test for this possibility we disrupted RA signaling in somatic cells of the early fetal ovary using three genetic strategies and one pharmaceutical approach. We found that deleting all three RA receptors (RARs) in the XX somatic gonad at the time of sex determination did not significantly affect ovarian differentiation, follicle development, or female fertility. Transcriptome analysis of adult triple mutant ovaries revealed remarkably little effect on gene expression in the absence of somatic RAR function. Likewise, deletion of three RA synthesis enzymes (Aldh1a1-3) at the time of sex determination did not masculinize the ovary. A dominant-negative RAR transgene altered granulosa cell proliferation, likely due to interference with a non-RA signaling pathway, but did not prevent granulosa cell specification and oogenesis or abolish fertility. Finally, culture of fetal XX gonads with an RAR antagonist blocked germ cell meiotic initiation but did not disrupt sex-biased gene expression. We conclude that RA signaling, although crucial in the ovary for meiotic initiation, is not required for granulosa cell specification, differentiation, or reproductive function. Copyright © 2017 Elsevier Inc. All rights reserved.

Some ethylene biosynthesis and AP2/ERF genes reveal a specific pattern of expression during somatic embryogenesis in Hevea brasiliensis

PubMed Central

2012-01-01

Background Ethylene production and signalling play an important role in somatic embryogenesis, especially for species that are recalcitrant in in vitro culture. The AP2/ERF superfamily has been identified and classified in Hevea brasiliensis. This superfamily includes the ERFs involved in response to ethylene. The relative transcript abundance of ethylene biosynthesis genes and of AP2/ERF genes was analysed during somatic embryogenesis for callus lines with different regeneration potential, in order to identify genes regulated during that process. Results The analysis of relative transcript abundance was carried out by real-time RT-PCR for 142 genes. The transcripts of ERFs from group I, VII and VIII were abundant at all stages of the somatic embryogenesis process. Forty genetic expression markers for callus regeneration capacity were identified. Fourteen markers were found for proliferating calli and 35 markers for calli at the end of the embryogenesis induction phase. Sixteen markers discriminated between normal and abnormal embryos and, lastly, there were 36 markers of conversion into plantlets. A phylogenetic analysis comparing the sequences of the AP2 domains of Hevea and Arabidopsis genes enabled us to predict the function of 13 expression marker genes. Conclusions This first characterization of the AP2/ERF superfamily in Hevea revealed dramatic regulation of the expression of AP2/ERF genes during the somatic embryogenesis process. The gene expression markers of proliferating callus capacity to regenerate plants by somatic embryogenesis should make it possible to predict callus lines suitable to be used for multiplication. Further functional characterization of these markers opens up prospects for discovering specific AP2/ERF functions in the Hevea species for which somatic embryogenesis is difficult. PMID:23268714

E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer.

PubMed

Lopes-Ramos, Camila M; Barros, Bruna P; Koyama, Fernanda C; Carpinetti, Paola A; Pezuk, Julia; Doimo, Nayara T S; Habr-Gama, Angelita; Perez, Rodrigo O; Parmigiani, Raphael B

2017-01-01

Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. We demonstrated that somatic mutation within E2F1:MIR136-5p target site impairs miRNA-mediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.

The BABY BOOM Transcription Factor Activates the LEC1-ABI3-FUS3-LEC2 Network to Induce Somatic Embryogenesis1[OPEN

PubMed Central

Weemen, Mieke

2017-01-01

Somatic embryogenesis is an example of induced cellular totipotency, where embryos develop from vegetative cells rather than from gamete fusion. Somatic embryogenesis can be induced in vitro by exposing explants to growth regulators and/or stress treatments. The BABY BOOM (BBM) and LEAFY COTYLEDON1 (LEC1) and LEC2 transcription factors are key regulators of plant cell totipotency, as ectopic overexpression of either transcription factor induces somatic embryo formation from Arabidopsis (Arabidopsis thaliana) seedlings without exogenous growth regulators or stress treatments. Although LEC and BBM proteins regulate the same developmental process, it is not known whether they function in the same molecular pathway. We show that BBM transcriptionally regulates LEC1 and LEC2, as well as the two other LAFL genes, FUSCA3 (FUS3) and ABSCISIC ACID INSENSITIVE3 (ABI3). LEC2 and ABI3 quantitatively regulate BBM-mediated somatic embryogenesis, while FUS3 and LEC1 are essential for this process. BBM-mediated somatic embryogenesis is dose and context dependent, and the context-dependent phenotypes are associated with differential LAFL expression. We also uncover functional redundancy for somatic embryogenesis among other Arabidopsis BBM-like proteins and show that one of these proteins, PLETHORA2, also regulates LAFL gene expression. Our data place BBM upstream of other major regulators of plant embryo identity and totipotency. PMID:28830937

[The possibility of using music therapy in neurology on the example of multiple sclerosis].

PubMed

Boiko, E A; Ivanchuk, E V; Gunchenko, M M; Batysheva, T T

2016-01-01

Currently music therapy plays an important role in the drug-free treatment and rehabilitation of children and adults with acute and chronic neurological and somatic diseases including demyelinating diseases. Existing studies show the effectiveness of music therapy in the improvement of social skills, cognitive function and sleep as well as in the reduction in the severity of depression, anxiety and pain in patients with multiple sclerosis.

Hematopoietic stem cells are acutely sensitive to Acd shelterin gene inactivation

PubMed Central

Jones, Morgan; Osawa, Gail; Regal, Joshua A.; Weinberg, Daniel N.; Taggart, James; Kocak, Hande; Friedman, Ann; Ferguson, David O.; Keegan, Catherine E.; Maillard, Ivan

2013-01-01

The shelterin complex plays dual functions in telomere homeostasis by recruiting telomerase and preventing the activation of a DNA damage response at telomeric ends. Somatic stem cells require telomerase activity, as evidenced by progressive stem cell loss leading to bone marrow failure in hereditary dyskeratosis congenita. Recent work demonstrates that dyskeratosis congenita can also arise from mutations in specific shelterin genes, although little is known about shelterin functions in somatic stem cells. We found that mouse hematopoietic stem cells (HSCs) are acutely sensitive to inactivation of the shelterin gene Acd, encoding TPP1. Homozygosity for a hypomorphic acd allele preserved the emergence and expansion of fetal HSCs but led to profoundly defective function in transplantation assays. Upon complete Acd inactivation, HSCs expressed p53 target genes, underwent cell cycle arrest, and were severely depleted within days, leading to hematopoietic failure. TPP1 loss induced increased telomeric fusion events in bone marrow progenitors. However, unlike in epidermal stem cells, p53 deficiency did not rescue TPP1-deficient HSCs, indicating that shelterin dysfunction has unique effects in different stem cell populations. Because the consequences of telomere shortening are progressive and unsynchronized, acute loss of shelterin function represents an attractive alternative for studying telomere crisis in hematopoietic progenitors. PMID:24316971

Parent-child Communication-centered Rehabilitative Approach for Pediatric Functional Somatic Symptoms.

PubMed

Gerner, Maya; Barak, Sharon; Landa, Jana; Eisenstein, Etzyona

2016-01-01

Functional somatic symptoms (FSS) are a type of somatization phenomenon. Integrative rehabilitation approaches are the preferred treatment for pediatric FSS. Parental roles in the treatment process have not been established. to present 1) a parent-focused treatment (PFT) for pediatric FSS and 2) the approach's preliminary results. The sample included 50 children with physical disabilities due to FSS. All children received PFT including physical and psychological therapy. A detailed description of the program's course and guiding principles is provided. FSS extinction and age-appropriate functioning. Post-program, 84% of participants did not exhibit FSS and 94% returned to age-appropriate functioning. At one-year follow-up, only 5% of participants experienced symptom recurrence. No associations were found between pre-admission symptoms and intervention duration. PFT is beneficial in treating pediatric FSS. Therefore, intensive parental involvement in rehabilitation may be cardinal.

Tinnitus: Distinguishing between Subjectively Perceived Loudness and Tinnitus-Related Distress

PubMed Central

Wallhäusser-Franke, Elisabeth; Brade, Joachim; Balkenhol, Tobias; D'Amelio, Roberto; Seegmüller, Andrea; Delb, Wolfgang

2012-01-01

Objectives Overall success of current tinnitus therapies is low, which may be due to the heterogeneity of tinnitus patients. Therefore, subclassification of tinnitus patients is expected to improve therapeutic allocation, which, in turn, is hoped to improve therapeutic success for the individual patient. The present study aims to define factors that differentially influence subjectively perceived tinnitus loudness and tinnitus-related distress. Methods In a questionnaire-based cross-sectional survey, the data of 4705 individuals with tinnitus were analyzed. The self-report questionnaire contained items about subjective tinnitus loudness, type of onset, awareness and localization of the tinnitus, hearing impairment, chronic comorbidities, sleep quality, and psychometrically validated questionnaires addressing tinnitus-related distress, depressivity, anxiety, and somatic symptom severity. In a binary step-wise logistic regression model, we tested the predictive power of these variables on subjective tinnitus loudness and tinnitus-related distress. Results The present data contribute to the distinction between subjective tinnitus loudness and tinnitus-related distress. Whereas subjective loudness was associated with permanent awareness and binaural localization of the tinnitus, tinnitus-related distress was associated with depressivity, anxiety, and somatic symptom severity. Conclusions Subjective tinnitus loudness and the potential presence of severe depressivity, anxiety, and somatic symptom severity should be assessed separately from tinnitus-related distress. If loud tinnitus is the major complaint together with mild or moderate tinnitus-related distress, therapies should focus on auditory perception. If levels of depressivity, anxiety or somatic symptom severity are severe, therapies and further diagnosis should focus on these symptoms at first. PMID:22529921

Fibroblast growth factor signaling is required for early somatic gonad development in zebrafish.

PubMed

Leerberg, Dena M; Sano, Kaori; Draper, Bruce W

2017-09-01

The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.

A review of somatoform disorders in DSM-IV and somatic symptom disorders in proposed DSM-V.

PubMed

Ghanizadeh, Ahmad; Firoozabadi, Ali

2012-12-01

Psychiatric care providers should be trained to use current changes in the somatoform disorders criteria. New diagnostic criteria for Somatic Symptom disorders in the proposed DSM-V is discussed and compared with its older counterpart in DSM-IV. A new category called Somatic Syndrome Disorders is suggested. It includes new subcategories such as "Complex Somatic Symptom Disorder" (CSSD) and "Simple Somatic Symptom Disorder" (SSSD). Some of the subcategories of DSM-IV derived disorders are included in CSSD. While there are some changes in diagnostic criteria, there are concerns and limitations about the new classification needed to be more discussed before implementation. Functional somatic disturbance, the counterpart of converion disorder in DSM-IV, can be highly dependet on the developmental level of children. However, the role of developmental level needs to be considered.

On the role of germ cells in mammalian gonad development: quiet passengers or back-seat drivers?

PubMed

Rios-Rojas, Clarissa; Bowles, Josephine; Koopman, Peter

2015-04-01

In addition to their role as endocrine organs, the gonads nurture and protect germ cells, and regulate the formation of gametes competent to convey the genome to the following generation. After sex determination, gonadal somatic cells use several known signalling pathways to direct germ cell development. However, the extent to which germ cells communicate back to the soma, the molecular signals they use to do so and the significance of any such signalling remain as open questions. Herein, we review findings arising from the study of gonadal development and function in the absence of germ cells in a range of organisms. Most published studies support the view that germ cells are unimportant for foetal gonadal development in mammals, but later become critical for stabilisation of gonadal function and somatic cell phenotype. However, the lack of consistency in the data, and clear differences between mammals and other vertebrates and invertebrates, suggests that the story may not be so simple and would benefit from more careful analysis using contemporary molecular, cell biology and imaging tools. © 2015 Society for Reproduction and Fertility.

Which psychological factors exacerbate irritable bowel syndrome? Development of a comprehensive model.

PubMed

van Tilburg, Miranda A L; Palsson, Olafur S; Whitehead, William E

2013-06-01

There is evidence that psychological factors affect the onset, severity and duration of irritable bowel syndrome (IBS). However, it is not clear which psychological factors are the most important and how they interact. The aims of the current study are to identify the most important psychological factors predicting IBS symptom severity and to investigate how these psychological variables are related to each other. Study participants were 286 IBS patients who completed a battery of psychological questionnaires including neuroticism, abuse history, life events, anxiety, somatization and catastrophizing. IBS severity measured by the IBS Severity Scale was the dependent variable. Path analysis was performed to determine the associations among the psychological variables, and IBS severity. Although the hypothesized model showed adequate fit, post hoc model modifications were performed to increase prediction. The final model was significant (Chi(2)=2.2; p=0.82; RMSEA<.05) predicting 36% of variance in IBS severity. Catastrophizing (standardized coefficient (β)=0.33; p<.001) and somatization (β=0.20; p<.001) were the only two psychological variables directly associated with IBS severity. Anxiety had an indirect effect on IBS symptoms through catastrophizing (β=0.80; p<.001); as well as somatization (β=0.37; p<.001). Anxiety, in turn, was predicted by neuroticism (β=0.66; p<.001) and stressful life events (β=0.31; p<.001). While cause-and-effect cannot be determined from these cross-sectional data, the outcomes suggest that the most fruitful approach to curb negative effects of psychological factors on IBS is to reduce catastrophizing and somatization. Copyright © 2013 Elsevier Inc. All rights reserved.

The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells

PubMed Central

Keam, Simon P.; Young, Paul E.; McCorkindale, Alexandra L.; Dang, Thurston H.Y.; Clancy, Jennifer L.; Humphreys, David T.; Preiss, Thomas; Hutvagner, Gyorgy; Martin, David I.K.; Cropley, Jennifer E.; Suter, Catherine M.

2014-01-01

The Piwi-piRNA pathway is active in animal germ cells where its functions are required for germ cell maintenance and gamete differentiation. Piwi proteins and piRNAs have been detected outside germline tissue in multiple phyla, but activity of the pathway in mammalian somatic cells has been little explored. In particular, Piwi expression has been observed in cancer cells, but nothing is known about the piRNA partners or the function of the system in these cells. We have surveyed the expression of the three human Piwi genes, Hiwi, Hili and Hiwi2, in multiple normal tissues and cancer cell lines. We find that Hiwi2 is ubiquitously expressed; in cancer cells the protein is largely restricted to the cytoplasm and is associated with translating ribosomes. Immunoprecipitation of Hiwi2 from MDAMB231 cancer cells enriches for piRNAs that are predominantly derived from processed tRNAs and expressed genes, species which can also be found in adult human testis. Our studies indicate that a Piwi-piRNA pathway is present in human somatic cells, with an uncharacterised function linked to translation. Taking this evidence together with evidence from primitive organisms, we propose that this somatic function of the pathway predates the germline functions of the pathway in modern animals. PMID:25038252

Integrated analysis of germline and somatic variants in ovarian cancer.

PubMed

Kanchi, Krishna L; Johnson, Kimberly J; Lu, Charles; McLellan, Michael D; Leiserson, Mark D M; Wendl, Michael C; Zhang, Qunyuan; Koboldt, Daniel C; Xie, Mingchao; Kandoth, Cyriac; McMichael, Joshua F; Wyczalkowski, Matthew A; Larson, David E; Schmidt, Heather K; Miller, Christopher A; Fulton, Robert S; Spellman, Paul T; Mardis, Elaine R; Druley, Todd E; Graubert, Timothy A; Goodfellow, Paul J; Raphael, Benjamin J; Wilson, Richard K; Ding, Li

2014-01-01

We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyse germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2 and PALB2. In addition, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B and MLL3). Evidence for loss of heterozygosity was found in 100 and 76% of cases with germline BRCA1 and BRCA2 truncations, respectively. Germline-somatic interaction analysis combined with extensive bioinformatics annotation identifies 222 candidate functional germline truncation and missense variants, including two pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK and MLL pathways.

Unexplained somatic symptoms during major depression: prevalence and clinical impact in a national sample of Italian psychiatric outpatients.

PubMed

Perugi, Giulio; Canonico, Pier Luigi; Carbonato, Paolo; Mencacci, Claudio; Muscettola, Giovanni; Pani, Luca; Torta, Riccardo; Vampini, Claudio; Fornaro, Michele; Parazzini, Fabio; Dumitriu, Arina

2011-01-01

The aim of this study was to explore the prevalence and impact of unexplained somatic symptoms during major depression. A total of 560 consecutive outpatients with a major depressive episode according to the DSM-IV (text revision) were evaluated in 30 psychiatric facilities throughout Italy. 'Unexplained' somatic symptoms were evaluated using the 30-item Somatic Symptoms Checklist (SSCL-30). Somatic symptoms were considered explained if they were best accounted for as coming from a concomitant physical illness or side effects. Patients evaluated their own mood symptomatology using the Zung questionnaires for depression and anxiety and the Hypomania Checklist-32. According to the SSCL-30, only 90 subjects (16.1%) had no unexplained somatic symptoms, while 231 (41.3%) had 1-5 unexplained symptoms and 239 (42.7%) had more than 5. Asthenia was the most commonly observed unexplained somatic symptom (53% of patients). Unexplained somatic symptoms were more common in females and among those suffering from major depression and depression not otherwise specified rather than in patients with recurrent major depression and bipolar disorders. No relationship between unexplained somatic symptoms and hypomanic features was observed. The presence of a large number of unexplained somatic symptoms is associated with more severe depression and higher rates of misdiagnosis and inappropriate treatment. Copyright © 2011 S. Karger AG, Basel.

Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder.

PubMed

Silverstein, Brett; Angst, Jules

2015-01-01

Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3) Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4) Most probands who report atypical depression meet criteria for "somatic depression," defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as "reactive" appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression.

Severe Mental Illness, Somatic Delusions, and Attempted Mass Murder.

PubMed

Sarteschi, Christine M

2016-01-01

A case of an attempted mass shooting at a large psychiatric hospital in the United States by a 30-year-old male with severe mental illness, somatic delusions, and exceptional access to healthcare professionals is reported. Six persons were shot, one died at the scene, and the shooter was then killed by the police. Data were gathered from court documents and media accounts. An analysis of the shooter's psychiatric history, his interactions with healthcare professionals, and communications prior to the shooting suggest a rare form of mass murder, a random attack by a documented psychotic and delusional individual suffering with somatic delusions. Despite his being psychotic, the killer planned the attack and made a direct threat 1 month prior to the shootings. This case highlights problems with the healthcare system, indicating that it might be ill equipped to appropriately deal with severe mental illness. © 2015 American Academy of Forensic Sciences.

RNA-Mediated Epigenetic Programming of Genome Rearrangements

PubMed Central

Nowacki, Mariusz; Shetty, Keerthi; Landweber, Laura F.

2012-01-01

RNA, normally thought of as a conduit in gene expression, has a novel mode of action in ciliated protozoa. Maternal RNA templates provide both an organizing guide for DNA rearrangements and a template that can transport somatic mutations to the next generation. This opportunity for RNA-mediated genome rearrangement and DNA repair is profound in the ciliate Oxytricha, which deletes 95% of its germline genome during development in a process that severely fragments its chromosomes and then sorts and reorders the hundreds of thousands of pieces remaining. Oxytricha’s somatic nuclear genome is therefore an epigenome formed through RNA templates and signals arising from the previous generation. Furthermore, this mechanism of RNA-mediated epigenetic inheritance can function across multiple generations, and the discovery of maternal template RNA molecules has revealed new biological roles for RNA and has hinted at the power of RNA molecules to sculpt genomic information in cells. PMID:21801022

Clinical Presentation of Acute Gastroenteritis in Children With Functional Abdominal Pain Disorders.

PubMed

Saps, Miguel; Mintjens, Stijn; Pusatcioglu, Cenk K; Cohen, Daniel M; Sternberg, Petra

2017-08-01

Visceral hypersensitivity and abnormal coping are common in children with functional abdominal pain disorders (FAPDs). Thus, it would be expected that children with visceral hypersensitivity would report more pain if their gut is acutely inflamed. The aim of the study was to compare clinical symptoms and somatization of children with and without FAPDs at time of an episode of acute gastroenteritis. Seventy children with acute gastroenteritis and their parents completed the Rome III Diagnostic Questionnaire for Pediatric Functional GI Disorders and the Children's Somatization Inventory. Twenty-one percent of children were diagnosed with an FAPD. Children with FAPDs showed significantly more nongastrointestinal somatic symptoms than children without FAPDs. There were no significant differences in abdominal pain, nausea, vomiting, or school absenteeism between both groups at time of consultation.

Does contextual unemployment matter for health status across the life course? A longitudinal multilevel study exploring the link between neighbourhood unemployment and functional somatic symptoms.

PubMed

Brydsten, Anna; Gustafsson, Per E; Hammarström, Anne; San Sebastian, Miguel

2017-01-01

This study examines whether neighbourhood unemployment is related to functional somatic symptoms, independently of the individual employment, across the life course and at four specific life course periods (age 16, 21, 30 and 42). Self-reported questioner data was used from a 26-year prospective Swedish cohort (n=1010) with complementary neighbourhood register data. A longitudinal and a set of age-specific cross-sectional hierarchal linear regressions was carried out. The results suggest that living in a neighbourhood with high unemployment has implications for residents' level of functional somatic symptoms, regardless of their own unemployment across time, particularly at age 30. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cloning mice and ES cells by nuclear transfer from somatic stem cells and fully differentiated cells.

PubMed

Wang, Zhongde

2011-01-01

Cloning animals by nuclear transfer (NT) has been successful in several mammalian species. In addition to cloning live animals (reproductive cloning), this technique has also been used in several species to establish cloned embryonic stem (ntES) cell lines from somatic cells. It is the latter application of this technique that has been heralded as being the potential means to produce isogenic embryonic stem cells from patients for cell therapy (therapeutic cloning). These two types of cloning differ only in the steps after cloned embryos are produced: for reproductive cloning the cloned embryos are transferred to surrogate mothers to allow them to develop to full term and for therapeutic cloning the cloned embryos are used to derive ntES cells. In this chapter, a detailed NT protocol in mouse by using somatic stem cells (neuron and skin stem cells) and fully differentiated somatic cells (cumulus cells and fibroblast cells) as nuclear donors is described.

Psychological Factors Associated with Development of TMD: the OPPERA Prospective Cohort Study

PubMed Central

Fillingim, Roger B.; Ohrbach, Richard; Greenspan, Joel D.; Knott, Charles; Diatchenko, Luda; Dubner, Ronald; Bair, Eric; Baraian, Cristina; Mack, Nicole; Slade, Gary D.; Maixner, William

2013-01-01

Case-control studies have consistently associated psychological factors with chronic pain in general and with temporomandibular disorders (TMD) specifically. However, only a handful of prospective studies has explored whether pre-existing psychological characteristics represent risk factors for first-onset TMD. The current findings derive from the prospective cohort study of the Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) cooperative agreement. For this study, 3,263 TMD-free participants completed a battery of psychological instruments assessing general psychological adjustment and personality, affective distress, psychosocial stress, somatic symptoms, and pain coping and catastrophizing. Study participants were then followed prospectively for an average of 2.8 years to ascertain cases of first-onset of TMD, and 2,737 provided follow-up data and were considered in the analyses of TMD onset. In bivariate and demographically-adjusted analyses, several psychological variables predicted increased risk of first-onset TMD, including reported somatic symptoms, psychosocial stress, and affective distress. Principal component analysis of 26 psychological scores was used to identify latent constructs, revealing four components: stress and negative affectivity, global psychological and somatic symptoms, passive pain coping, and active pain coping. In multivariable analyses, global psychological and somatic symptoms emerged as the most robust risk factor for incident TMD. These findings provide evidence that measures of psychological functioning can predict first-onset of TMD. Future analyses in the OPPERA cohort will determine whether these psychological factors interact with other variables to increase risk for TMD onset and persistence. PMID:24275225

Activating HER2 mutations in HER2 gene amplification negative breast cancer.

PubMed

Bose, Ron; Kavuri, Shyam M; Searleman, Adam C; Shen, Wei; Shen, Dong; Koboldt, Daniel C; Monsey, John; Goel, Nicholas; Aronson, Adam B; Li, Shunqiang; Ma, Cynthia X; Ding, Li; Mardis, Elaine R; Ellis, Matthew J

2013-02-01

Data from 8 breast cancer genome-sequencing projects identified 25 patients with HER2 somatic mutations in cancers lacking HER2 gene amplification. To determine the phenotype of these mutations, we functionally characterized 13 HER2 mutations using in vitro kinase assays, protein structure analysis, cell culture, and xenograft experiments. Seven of these mutations are activating mutations, including G309A, D769H, D769Y, V777L, P780ins, V842I, and R896C. HER2 in-frame deletion 755-759, which is homologous to EGF receptor (EGFR) exon 19 in-frame deletions, had a neomorphic phenotype with increased phosphorylation of EGFR or HER3. L755S produced lapatinib resistance, but was not an activating mutation in our experimental systems. All of these mutations were sensitive to the irreversible kinase inhibitor, neratinib. These findings show that HER2 somatic mutation is an alternative mechanism to activate HER2 in breast cancer and they validate HER2 somatic mutations as drug targets for breast cancer treatment. We show that the majority of HER2 somatic mutations in breast cancer patients are activating mutations that likely drive tumorigenesis. Several patients had mutations that are resistant to the reversible HER2 inhibitor lapatinib, but are sensitive to the irreversible HER2 inhibitor, neratinib. Our results suggest that patients with HER2 mutation–positive breast cancers could benefit from existing HER2-targeted drugs.

Paternal Somatic Mosaicism of a Novel Frameshift Mutation in ELANE Causing Severe Congenital Neutropenia.

PubMed

Kim, Hee-Jung; Song, Min-Jung; Lee, Ki-O; Kim, Sun-Hee; Kim, Hee-Jin

2015-12-01

Severe congenital neutropenia (SCN) is a bone marrow failure disease with an autosomal dominant inheritance from mutations in ELANE. Here, we report a 7-week-old Korean male with SCN. His elder sister died from pneumonia at 2 years. Direct sequencing of ELANE in the proband identified a heterozygous novel frameshift mutation: c.658delC (p.Arg220Glyfs20*). Family study involving his asymptomatic parents with normal cell counts revealed that his father had the same mutation, but at a lower burden than expected in a typical heterozygous state. Further molecular investigation demonstrated somatic mosaicism with ~18% mutant alleles. We concluded the proband inherited the mutation from his somatic mosaic father. © 2015 Wiley Periodicals, Inc.

The impact of somatic symptoms on the course of major depressive disorder.

PubMed

Bekhuis, Ella; Boschloo, Lynn; Rosmalen, Judith G M; de Boer, Marrit K; Schoevers, Robert A

2016-11-15

Somatic symptoms have been suggested to negatively affect the course of major depressive disorder (MDD). Mechanisms behind this association, however, remain elusive. This study examines the impact of somatic symptoms on MDD prognosis and aims to determine whether this effect can be explained by psychiatric characteristics, somatic diseases, lifestyle factors, and disability. In 463 MDD patients (mean age=44.9 years, 69.8% female) from the Netherlands Study of Depression and Anxiety (NESDA), we examined whether the type and number of somatic symptom clusters predicted the two-year persistence of MDD. Diagnoses of MDD were established with the Composite International Diagnostic Interview (CIDI) and somatic symptom clusters were assessed with the Four-Dimensional Symptom Questionnaire (4DSQ) somatization scale. Psychiatric characteristics, somatic diseases, lifestyle factors, and disability were taken into account as factors potentially underlying the association. The cardiopulmonary, gastrointestinal, and general cluster significantly predicted the two-year persistence of MDD, but only when two or more of these clusters were present (OR=2.32, 95% CI=1.51-3.57, p=<0.001). Although the association was partly explained by MDD severity, the presence of multiple somatic symptom clusters remained a significant predictor after considering all potentially underlying factors (OR=1.69, 95%CI=1.07-2.68, p=0.03). Somatic symptoms are predictors of a worse prognosis of MDD independent of psychiatric characteristics, somatic diseases, lifestyle factors, and disability. These results stress the importance of considering somatic symptoms in the diagnostic and treatment trajectory of patients with MDD. Future research should focus on identifying treatment modalities targeting depressive as well as somatic symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

Perceived social support and life satisfaction in persons with somatization disorder

PubMed Central

Ali, Arif; Deuri, S. P.; Deuri, S. K.; Jahan, Masroor; Singh, Amool R.; Verma, A. N.

2010-01-01

Background: Life satisfaction and perceived social support been shown to improve the well-being of a person and also affect the outcome of treatment in somatization disorder. The phenomenon of somatization was explored in relation to the perceived social support and life satisfaction. Aim: This study aimed at investigating perceived social support and life satisfaction in people with somatization disorder. Materials and Methods: The study was conducted on persons having somatization disorder attending the outpatient unit of LGB Regional Institute of Mental Health, Tezpur, Assam. Satisfaction with life scale and multidimensional scale of perceived social support were used to assess life satisfaction and perceived social support respectively. Results: Women reported more somatic symptoms than men. Family perceived social support was high in the patient in comparison to significant others’ perceived social support and friends’ perceived social support. Perceived social support showed that a significant positive correlation was found with life satisfaction. Conclusion: Poor social support and low life satisfaction might be a stress response with regard to increased distress severity and psychosocial stressors rather than a cultural response to express psychological problems in somatic terms. PMID:22174534

Resolving rates of mutation in the brain using single-neuron genomics

PubMed Central

Evrony, Gilad D; Lee, Eunjung; Park, Peter J; Walsh, Christopher A

2016-01-01

Whether somatic mutations contribute functional diversity to brain cells is a long-standing question. Single-neuron genomics enables direct measurement of somatic mutation rates in human brain and promises to answer this question. A recent study (Upton et al., 2015) reported high rates of somatic LINE-1 element (L1) retrotransposition in the hippocampus and cerebral cortex that would have major implications for normal brain function, and suggested that these events preferentially impact genes important for neuronal function. We identify aspects of the single-cell sequencing approach, bioinformatic analysis, and validation methods that led to thousands of artifacts being interpreted as somatic mutation events. Our reanalysis supports a mutation frequency of approximately 0.2 events per cell, which is about fifty-fold lower than reported, confirming that L1 elements mobilize in some human neurons but indicating that L1 mosaicism is not ubiquitous. Through consideration of the challenges identified, we provide a foundation and framework for designing single-cell genomics studies. DOI: http://dx.doi.org/10.7554/eLife.12966.001 PMID:26901440

Novel Somatic Mutation in LEMD3 Splice Site Results in Buschke-Ollendorff Syndrome with Polyostotic Melorheostosis and Osteopoikilosis.

PubMed

Gutierrez, Daniel; Cooper, Kevin D; Mitchell, Anna L; Cohn, Heather I

2015-01-01

Buschke-Ollendorff syndrome is a rare autosomal dominant disorder caused by loss of function in LEMD3, resulting in connective tissue nevi and varying bone dysplasia. Although typically benign, we describe a novel LEMD3 splice site mutation (IVS12 + 1delG) in a 13-year-old boy with Buschke-Ollendorff syndrome presenting with severe skeletal deformities, polyostotic melorheostosis, and osteopoikilosis. © 2015 Wiley Periodicals, Inc.

Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults.

PubMed

Aziz, Imran; Palsson, Olafur S; Whitehead, William E; Sperber, Ami D; Simrén, Magnus; Törnblom, Hans

2018-05-29

Functional nausea and vomiting disorders (FNVDs) are classified as chronic nausea and vomiting syndrome (CNVS) or cyclic vomiting syndrome (CVS) - CVS includes cannabinoid hyperemesis syndrome. We investigated the population prevalence of FNVDs, their characteristics, and associated factors. In the year 2015, an Internet cross-sectional health survey was completed by 5931 adults in the general populations of 3 English-speaking countries; 2100 participants were in the United States, Canada, or the United Kingdom. Quota-based sampling was used to generate demographically balanced and population-representative samples. The survey collected data on demographics, healthcare visits, medications, somatic symptom severity, quality of life, and symptom-based diagnostic criteria for Rome IV FNVDs as well as for irritable bowel syndrome and functional dyspepsia. Subsequent comparisons were made between Rome IV FNVD subjects and individuals without FNVDs (controls). Overall, 2.2% of the population (n=131) fulfilled symptom-based diagnostic criteria for Rome IV FNVDs - the United States (3%) had a greater prevalence than Canada (1.9%) or the United Kingdom (1.8%) (P=.02). The prevalence of CNVS was similar among the countries, ranging from 0.8% to 1.2%. However, the prevalence of CVS was higher in the United States (2%) than in Canada (0.7%) or the United Kingdom (1%) (P=.03). The proportion of subjects with CVS taking cannabis did not differ significantly among countries (P=.31), although the 7 cases of cannabinoid hyperemesis syndrome were in the United States. A significantly higher proportion of subjects with CVS reported a compulsive need for hot water bathing to alleviate emetic symptoms than subjects with CNVS (44% vs. 19%, P=.03); this behaviour was independent of cannabis but augmented by its use. Subjects with FNVDs had significantly greater health impairment and health care utilization than controls. On multivariate analysis, independent factors associated with FNVDs were younger age, increasing somatic symptom severity, lower quality of life, presence of irritable bowel syndrome, and functional dyspepsia. However, on subgroup analysis, somatic symptom severity was associated with CVS but not CNVS, whereas poor quality of life was associated with CNVS but not CVS. Based on a cross-sectional health survey of adults in the general populations of 3 English-speaking countries, approximately 2% of subjects meet symptom-based criteria for Rome IV FNVDs and have considerable health impairments. Hot water bathing to alleviate emetic symptoms is reported for all FNVDs, and is perpetuated by cannabis use. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Anxiety and Depression Are Risk Factors Rather than Consequences of Functional Somatic Symptoms in a General Population of Adolescents: The Trails Study

ERIC Educational Resources Information Center

Janssens, Karin A. M.; Rosmalen, Judith G. M.; Ormel, Johan; van Oort, Floor V. A.; Oldehinkel, Albertine J.

2010-01-01

Background: It is well known that functional somatic symptoms (FSS) are associated with anxiety and depression. However, evidence is lacking about how they are related to FSS. The aim of this study was to clarify these relationships and examine whether anxiety and depression are distinctly related to FSS. We hypothesized that anxiety contributes…

Stress and Arousal Symptoms in Individuals and Groups - Persian Gulf War Symptoms as a Paradigm.

DTIC Science & Technology

1999-09-01

Symptoms." Psychological Medicine, 1991:21: 1029-1045, quotation from pp. 1040-1041. 18Kellner R., "Functional Somatic Symptoms and Hypochondriasis ...quasi-specific for future patterns of research into the somatic and other consequences of combat stress, deployment stress and other stresses of...psychiatric folklore. Much of the earlier research into the somatic consequences of stress and indeed into medicine as a whole, was correlational in

The modulation of visceral functions by somatic afferent activity.

PubMed

Sato, A; Schmidt, R F

1987-01-01

We began by briefly reviewing the historical background of neurophysiological studies of the somato-autonomic reflexes and then discussed recent studies on somatic-visceral reflexes in combination with autonomic efferent nerve activity and effector organ responses. Most of the studies that have advanced our knowledge in this area have been carried out on anesthetized animals, thus eliminating emotional factors. We would like to emphasize again that the functions of many, or perhaps all visceral organs can be modulated by somato-sympathetic or somato-parasympathetic reflex activity induced by a appropriate somatic afferent stimulation in anesthetized animals. As mentioned previously, some autonomic nervous outflow, e.g. the adrenal sympathetic nerve activity, is involved in the control of hormonal secretion. John F. Fulton wrote in his famous textbook "Physiology of the Nervous System" (1949) that the posterior pituitary neurosecretion system (i.e. for oxytocin and vasopressin) could be considered a part of the parasympathetic nervous system. In the study of body homeostasis and environmental adaptation it would seem very important to further analyze the contribution of somatic afferent input to the autonomic nervous and hormonal regulation of visceral organ activity. Also, some immunological functions have been found to be influenced by autonomic nerves or hormones (e.g. adrenal cortical hormone and catecholamines). Finally, we must take into account, as we have briefly discussed, that visceral functions can be modulated by somatic afferent input via various degrees of integration of autonomic nerves, hormones, and immunological processes. We trust that such research will be expanded to higher species of mammals, and that ultimately this knowledge of somato-visceral reflexes obtained in the physiological laboratory will become clinically useful in influencing visceral functions.

Expression of M6 and M7 lysin in Mytilus edulis is not restricted to sperm, but occurs also in oocytes and somatic tissue of males and females.

PubMed

Heß, Anne-Katrin; Bartel, Manuela; Roth, Karina; Messerschmidt, Katrin; Heilmann, Katja; Kenchington, Ellen; Micheel, Burkhard; Stuckas, Heiko

2012-08-01

Sperm proteins of marine sessile invertebrates have been extensively studied to understand the molecular basis of reproductive isolation. Apart from molecules such as bindin of sea urchins or lysin of abalone species, the acrosomal protein M7 lysin of Mytilus edulis has been analyzed. M7 lysin was found to be under positive selection, but mechanisms driving the evolution of this protein are not fully understood. To explore functional aspects, this study investigated the protein expression pattern of M7 and M6 lysin in gametes and somatic tissue of male and female M. edulis. The study employs a previously published monoclonal antibody (G26-AG8) to investigate M6 and M7 lysin protein expression, and explores expression of both genes. It is shown that these proteins and their encoding genes are expressed in gametes and somatic tissue of both sexes. This is in contrast to sea urchin bindin and abalone lysin, in which gene expression is strictly limited to males. Although future studies need to clarify the functional importance of both acrosomal proteins in male and female somatic tissue, new insights into the evolution of sperm proteins in marine sessile invertebrates are possible. This is because proteins with male-specific expression (bindin, lysin) might evolve differently than proteins with expression in both sexes (M6/M7 lysin), and the putative function of both proteins in females opens the possibility that the evolution of M6/M7 lysin is under sexual antagonistic selection, for example, mutations beneficial to the acrosomal function that are less beneficial the function in somatic tissue of females. Copyright © 2012 Wiley Periodicals, Inc.

Parent and Child Psychological Factors in Pediatric Syncope and Other Somatic Symptoms

ERIC Educational Resources Information Center

Blount, Ronald L.; Morris, Julie A. B.; Cheng, Patricia S.; Campbell, Robert M.; Brown, Ronald T.

2004-01-01

The authors examined associations among parental and child adjustment, child syncope, somatic, and school problems. Participants were children (N = 56) ages 7-18 years with syncope. Measures included syncope severity, parental distress, and children's internalizing symptoms. For children diagnosed negative for neurocardiogenic syncope (NCS), their…

Pathological spirit possession as a cultural interpretation of trauma-related symptoms.

PubMed

Hecker, Tobias; Barnewitz, Eva; Stenmark, Hakon; Iversen, Valentina

2016-07-01

Spirit possession is a phenomenon frequently occurring in war-torn countries. It has been shown to be an idiom of distress entailing dissociative symptoms. However, its association with trauma exposure and trauma-related disorders remains unclear. This study aimed to explore subjective disease models and the relationship between pathological spirit possession and trauma-related disorders in the Eastern Democratic Republic of the Congo. Seventy-three (formerly) possessed persons (74% female, mean age = 34 years), referred by traditional and spiritual healers, were interviewed about their experiences of pathological spirit possession, trauma exposure, posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, shame and guilt, psychotic symptoms, somatic complaints, and the impairment of psychosocial functioning. The most common disease model for pathological spirit possession was another person having sent the spirit, mostly a family member or a neighbor, out of jealousy or conflict over resources. Significant correlations were found between spirit possession over lifetime and PTSD symptom severity, feelings of shame and guilt, depressive symptoms, somatic complaints, and psychotic symptoms. Spirit possession during the preceding 4 weeks was associated with PTSD symptom severity, impairment of psychosocial functioning, and psychotic symptom severity. The results of this study indicate that pathological spirit possession is a broad explanatory framework for various subjectively unexplainable mental and physical health problems, including but not limited to trauma-related disorders. Understanding pathological spirit possession as a subjective disease model for various mental and physical health problems may help researchers and clinicians to develop culturally sensitive treatment approaches for affected individuals. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Effects of copper and arsenic stress on the development of Norway spruce somatic embryos and their visualization with the environmental scanning electron microscope.

PubMed

Đorđević, Biljana; Neděla, Vilém; Tihlaříková, Eva; Trojan, Václav; Havel, Ladislav

2018-05-18

Somatic embryogenesis is an important biotechnological technique which can be used in studies associated with environmental stress. Four embryogenic cell lines of Norway spruce were grown on media enriched with copper and arsenic in concentration ranges 50-500 μM and 10-50 μM, respectively. The effects were observed during subsequent stages of somatic embryogenesis, the characteristics evaluated being proliferation potential, average number of somatic embryos obtained per g/fresh weight, morphology of developed somatic embryos, metal uptake, and microanalysis of macro- and micronutrients uptake. Copper and arsenic at higher concentrations significantly reduced the growth of early somatic embryos. In almost all treatments, the cell line V-1-3 showed the best performance compared with the other lines tested. Environmental scanning electron microscopy was used to visualize and identify morphological abnormalities in the development of somatic embryos. Abnormalities observed were classified into several categories: meristemless somatic embryos, somatic embryos with disrupted meristem, reduced number of cotyledons, single cotyledon and fused cotyledons. With the application of a low temperature method for the environmental scanning electron microscope, samples were stabilized and whole meristems could be investigated in their native state. As far as we are aware, this is the first report of the effect of copper and arsenic during the process of somatic embryogenesis and the first to evaluate the content of macro and micronutrients uptake in Norway spruce. Copyright © 2018 Elsevier B.V. All rights reserved.

[Somatic disorders in outpatient psychiatry: the added value of a standard physical examination during the intake of outpatients].

PubMed

van den Berg, K E M; Rijnders, C A Th; van Dam, A; van de Ven, A L M; van der Feltz-Cornelis, C M; Graafsma, S J

2014-01-01

It is well-known that psychiatric patients often suffer from severe somatic problems, such as diabetes mellitus and cardiovascular disease. Up till now, research has concentrated almost exclusively on the inpatient setting, but there is strong evidence that the correlation also exists in psychiatric patients who are outpatients. In the Netherlands there are, as yet, no clear recommendations regarding a standard form of somatic screening for the outpatient population. A pilot study performed by GGz Breburg has shown that somatic screening (without a physical examination) gave substantial additional value to treatment planning. To investigate the added value that a physical examination can provide when new psychiatric patients are screened for aspects of somatic concern (ASC). Newly referred outpatients (n = 70) were screened somatically by means of a questionnaire and supplementary medical interview, and by laboratory tests and physical examination. If a somatic problem was found which had not been detected previously, the patient was referred back to to the general practitioner. At least one ASC was found in 81,4% of all patients. In 45,7% of all patients the asc had not been detected. 12% of all the newly discovered somatic problems were found exclusively via the physical examination. A physical examination provides substantial information and adds value to the somatic screening of psychiatric outpatients.

The black box in somatization: unexplained physical symptoms, culture, and narratives of trauma.

PubMed

Waitzkin, H; Magaña, H

1997-09-01

Stimulated by our clinical work with patients who manifest unexplained "somatoform" symptoms in the primary care setting, this article addresses a theoretical black box in our understanding of somatization: how does culture mediate severe stress to produce symptoms that cannot be explained by the presence of physical illness? Despite various problems in his explanation of hysteria, Freud broke new ground by emphasizing narratives of traumatic experiences in the development and treatment of unexplained physical symptoms. Except in anthropologically oriented cultural psychiatry, contemporary psychiatry has traveled away from a focus on narrative in the study of somatization. On the other hand, recent interest in narrative has spread across many intellectual disciplines, including the humanities and literary criticism, psychology, history, anthropology, and sociology. We operationally define narratives as attempts at storytelling that portray the interrelationships among physical symptoms and the psychologic, social, or cultural context of these symptoms. Regarding somatization and trauma, we focus on the ways that narrative integrates the cultural context with traumatic life events. In explaining the black box, we postulate that extreme stress (torture, rape, witnessing deaths of relatives, forced migration, etc.) is processed psychologically as a terrible, largely incoherent narrative of events too awful to hold in consciousness. Culture patterns the psychologic and somatic expression of the terrible narrative. Methodologically, we have developed some techniques for eliciting narratives of severe stress and somatic symptoms, which we illustrate with observations from an ongoing research project. In designing interventions to improve the care of somatizing patients, we are focusing on the creation of social situations where patients may feel empowered to express more coherent narratives of their prior traumatic experiences.

The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells.

PubMed

Keam, Simon P; Young, Paul E; McCorkindale, Alexandra L; Dang, Thurston H Y; Clancy, Jennifer L; Humphreys, David T; Preiss, Thomas; Hutvagner, Gyorgy; Martin, David I K; Cropley, Jennifer E; Suter, Catherine M

2014-08-01

The Piwi-piRNA pathway is active in animal germ cells where its functions are required for germ cell maintenance and gamete differentiation. Piwi proteins and piRNAs have been detected outside germline tissue in multiple phyla, but activity of the pathway in mammalian somatic cells has been little explored. In particular, Piwi expression has been observed in cancer cells, but nothing is known about the piRNA partners or the function of the system in these cells. We have surveyed the expression of the three human Piwi genes, Hiwi, Hili and Hiwi2, in multiple normal tissues and cancer cell lines. We find that Hiwi2 is ubiquitously expressed; in cancer cells the protein is largely restricted to the cytoplasm and is associated with translating ribosomes. Immunoprecipitation of Hiwi2 from MDAMB231 cancer cells enriches for piRNAs that are predominantly derived from processed tRNAs and expressed genes, species which can also be found in adult human testis. Our studies indicate that a Piwi-piRNA pathway is present in human somatic cells, with an uncharacterised function linked to translation. Taking this evidence together with evidence from primitive organisms, we propose that this somatic function of the pathway predates the germline functions of the pathway in modern animals. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Targeting mitochondrial function and proteostasis to mitigate dynapenia.

PubMed

Musci, Robert V; Hamilton, Karyn L; Miller, Benjamin F

2018-01-01

Traditionally, interventions to treat skeletal muscle aging have largely targeted sarcopenia-the age-related loss of skeletal muscle mass. Dynapenia refers to the age-related loss in skeletal muscle function due to factors outside of muscle mass, which helps to inform treatment strategies for aging skeletal muscle. There is evidence that mechanisms to maintain protein homeostasis and proteostasis, deteriorate with age. One key mechanism to maintain proteostasis is protein turnover, which is an energetically costly process. When there is a mismatch between cellular energy demands and energy provision, inelastic processes related to metabolism are maintained, but there is competition for the remaining energy between the elastic processes of somatic maintenance and growth. With aging, mitochondrial dysfunction reduces ATP generation capacity, constraining the instantaneous supply of energy, thus compromising growth and somatic maintenance processes. Further, with age the need for somatic maintenance increases because of the accumulation of protein damage. In this review, we highlight the significant role mitochondria have in maintaining skeletal muscle proteostasis through increased energy provision, protein turnover, and substrate flux. In addition, we provide evidence that improving mitochondrial function could promote a cellular environment that is conducive to somatic maintenance, and consequently for mitigating dynapenia. Finally, we highlight interventions, such as aerobic exercise, that could be used to improve mitochondrial function and improve outcomes related to dynapenia.

When does hardship matter for health? Neighborhood and individual disadvantages and functional somatic symptoms from adolescence to mid-life in The Northern Swedish Cohort.

PubMed

Gustafsson, Per E; San Sebastian, Miguel

2014-01-01

A large body of research has shown that health is influenced by disadvantaged living conditions, including both personal and neighborhood conditions. Little is however known to what degree the health impact of different forms of disadvantage differ along the life course. The present study aims to examine when, during the life course, neighborhood and individual disadvantages relate to functional somatic symptoms. Participants (n = 992) came from The Northern Swedish Cohort and followed from age 16, 21, 30 until 42 years. Functional somatic symptoms, socioeconomic disadvantage, and social and material adversity were measured through questionnaires and linked to register data on neighborhood disadvantage. Data was analyzed with longitudinal and cross-sectional multilevel models. Results showed that neighborhood disadvantage, social and material adversity and gender all contributed independently to overall levels of symptoms across the life course. Cross-sectional analyses also suggested that the impact of disadvantage differed between life course periods; neighborhood disadvantage was most important in young adulthood, and the relative importance of material versus social adversity increased as participants grew older. In summary, the study suggests that disadvantages from different contextual sources may affect functional somatic health across the life course, but also through life course specific patterns.

Somatization among persons with Turkish origin: Results of the pretest of the German National Cohort Study.

PubMed

Morawa, Eva; Dragano, Nico; Jöckel, Karl-Heinz; Moebus, Susanne; Brand, Tilman; Erim, Yesim

2017-05-01

Despite the emerging need to examine mental health of immigrants, there are no investigations designed to analyze representative samples in Germany. The aim of the present study was to explore the severity of somatic symptoms/somatization among a sample of considerable size consisting of persons with Turkish origin. We studied whether somatization was associated with sociodemographic and migration-related characteristics. This examination was part of a pretest for a large national epidemiological cohort study in Germany. We applied the somatization (PHQ-15) and the depression module (PHQ-9) from the Patient Health Questionnaire in a subsample of 335 Turkish immigrants. We analyzed the distribution of the sum score. Differences in degree of somatization in relation to relevant socio-demographic (gender) and migrant-related characteristics (generation of immigration) were tested with analysis of covariance (ANCOVA), controlling for age. A multiple linear regression analysis was also conducted. Women had significantly higher age-adjusted mean scores than men (M=10.4, SD=6.3 vs. M=8.1, SD=6.3; F=10.467, p=0.001), a significant effect of age was also found (F=4.853, p=0.028). First generation immigrants had a higher age-adjusted mean number of symptoms in relation to the second generation immigrants (M=10.0, SD=6.5 vs. M=7.4, SD=7.0; F=6.042, p=0.014), the effect of age was not significant (F=0.466, p=0.495). Multiple regression analysis revealed that lower severity of somatization was associated with lower numbers of diagnosed physical illnesses (β=0.271, p<0.001) and better language proficiency (β=0.197, p=0.003, explained variance: 15.6%). The degree of somatization among Turkish immigrants in Germany is associated with gender and generation of immigration. Copyright © 2017 Elsevier Inc. All rights reserved.

Dual functions of Macpiwi1 in transposon silencing and stem cell maintenance in the flatworm Macrostomum lignano.

PubMed

Zhou, Xin; Battistoni, Giorgia; El Demerdash, Osama; Gurtowski, James; Wunderer, Julia; Falciatori, Ilaria; Ladurner, Peter; Schatz, Michael C; Hannon, Gregory J; Wasik, Kaja A

2015-11-01

PIWI proteins and piRNA pathways are essential for transposon silencing and some aspects of gene regulation during animal germline development. In contrast to most animal species, some flatworms also express PIWIs and piRNAs in somatic stem cells, where they are required for tissue renewal and regeneration. Here, we have identified and characterized piRNAs and PIWI proteins in the emerging model flatworm Macrostomum lignano. We found that M. lignano encodes at least three PIWI proteins. One of these, Macpiwi1, acts as a key component of the canonical piRNA pathway in the germline and in somatic stem cells. Knockdown of Macpiwi1 dramatically reduces piRNA levels, derepresses transposons, and severely impacts stem cell maintenance. Knockdown of the piRNA biogenesis factor Macvasa caused an even greater reduction in piRNA levels with a corresponding increase in transposons. Yet, in Macvasa knockdown animals, we detected no major impact on stem cell self-renewal. These results may suggest stem cell maintenance functions of PIWI proteins in flatworms that are distinguishable from their impact on transposons and that might function independently of what are considered canonical piRNA populations. © 2015 Zhou et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

PTSD and Trauma-Related Difficulties in Sexual Minority Women: The Impact of Perceived Social Support.

PubMed

Weiss, Brandon J; Garvert, Donn W; Cloitre, Marylène

2015-12-01

This study examined posttraumatic stress disorder (PTSD) and related symptoms among sexual minority (SM) and heterosexual women and the influence of social support on the relationship between SM status and symptoms. We hypothesized that SM women would endorse higher symptoms of PTSD and related difficulties and that social support would moderate the relationship between SM status and symptoms. The sample, women seeking treatment for PTSD related to interpersonal violence (n = 477; mean age = 36.07 years; 22.9% SM) completed clinician-administered measures of PTSD and self-report measures of trauma-related difficulties and social support. The rate of PTSD diagnosis was higher for SM women. Social support and SM status were significantly associated with suicidality, self-perceptions, depression, somatic complaints, and functional impairment. The interaction between social support and SM status was significant for both functional impairment (β = -.26) and somatic complaints (β = -.39). High social support had an equal, positive effect among SM and nonminority women, whereas low social support had a greater negative impact among SM women. Results suggested the particular salience of social support on functioning and symptom severity among SM women and the potential importance of including interventions addressing social support into PTSD treatments for SM women. Copyright © 2015 International Society for Traumatic Stress Studies.

Maximizing mutagenesis with solubilized CRISPR-Cas9 ribonucleoprotein complexes.

PubMed

Burger, Alexa; Lindsay, Helen; Felker, Anastasia; Hess, Christopher; Anders, Carolin; Chiavacci, Elena; Zaugg, Jonas; Weber, Lukas M; Catena, Raul; Jinek, Martin; Robinson, Mark D; Mosimann, Christian

2016-06-01

CRISPR-Cas9 enables efficient sequence-specific mutagenesis for creating somatic or germline mutants of model organisms. Key constraints in vivo remain the expression and delivery of active Cas9-sgRNA ribonucleoprotein complexes (RNPs) with minimal toxicity, variable mutagenesis efficiencies depending on targeting sequence, and high mutation mosaicism. Here, we apply in vitro assembled, fluorescent Cas9-sgRNA RNPs in solubilizing salt solution to achieve maximal mutagenesis efficiency in zebrafish embryos. MiSeq-based sequence analysis of targeted loci in individual embryos using CrispRVariants, a customized software tool for mutagenesis quantification and visualization, reveals efficient bi-allelic mutagenesis that reaches saturation at several tested gene loci. Such virtually complete mutagenesis exposes loss-of-function phenotypes for candidate genes in somatic mutant embryos for subsequent generation of stable germline mutants. We further show that targeting of non-coding elements in gene regulatory regions using saturating mutagenesis uncovers functional control elements in transgenic reporters and endogenous genes in injected embryos. Our results establish that optimally solubilized, in vitro assembled fluorescent Cas9-sgRNA RNPs provide a reproducible reagent for direct and scalable loss-of-function studies and applications beyond zebrafish experiments that require maximal DNA cutting efficiency in vivo. © 2016. Published by The Company of Biologists Ltd.

The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila.

PubMed

Li, Michelle A; Alls, Jeffrey D; Avancini, Rita M; Koo, Karen; Godt, Dorothea

2003-11-01

Interactions between somatic and germline cells are critical for the normal development of egg and sperm. Here we show that the gene traffic jam (tj) produces a soma-specific factor that controls gonad morphogenesis and is required for female and male fertility. tj encodes the only large Maf factor in Drosophila melanogaster, an orthologue of the atypical basic Leu zipper transcription factors c-Maf and MafB/Kreisler in vertebrates. Expression of tj occurs in somatic gonadal cells that are in direct contact with germline cells throughout development. In tj mutant gonads, somatic cells fail to inter-mingle and properly envelop germline cells, causing an early block in germ cell differentiation. In addition, tj mutant somatic cells show an increase in the level of expression for several adhesion molecules. We propose that tj is a critical modulator of the adhesive properties of somatic cells, facilitating germline-soma interactions that are essential for germ cell differentiation.

Magical thinking in somatoform disorders: an exploratory study among patients with suspected allergies.

PubMed

Hausteiner-Wiehle, C; Sokollu, F

2011-01-01

In order to reconceptualize somatoform disorders (SFDs), the psychological characteristics of SFD patients are increasingly investigated. The cognitive style of magical thinking (MT) has not been studied so far in patients with SFDs. In a cross-sectional study, 201 allergy workup patients were interviewed using the Structured Clinical Interview for DSM-IV; they answered a set of self-report questionnaires including the Schizotypal Personality Questionnaire subscale for MT and the Patient Health Questionnaire (PHQ). The expression of MT was explored in 61 patients with SFDs compared to 140 patients without SFDs. Patients with SFDs reached higher scores of MT, also when controlled for gender, depression, and anxiety. In particular, they stated more frequently that they were believers in telepathy (64 vs. 44%) and clairvoyance (43 vs. 16%). MT correlated only weakly with somatization/somatic symptom severity, depression, and anxiety. Among allergy workup patients with SFDs we found considerable MT. This indicates that SFD patients may tend to mistake correlation for causality in a more general way, and not just in an illness-related context. The relation to indicators of illness severity (somatic symptom severity/somatization, depression, and anxiety) was relatively weak. Possible implications for research, diagnostics, and therapy are discussed. Copyright © 2011 S. Karger AG, Basel.

Mental disorder and long-term risk of mortality: 41 years of follow-up of a population sample in Stockholm, Sweden.

PubMed

Lundin, A; Modig, K; Halldin, J; Carlsson, A C; Wändell, P; Theobald, H

2016-08-01

An increased mortality risk associated with mental disorder has been reported for patients, but there are few studies are based on random samples with interview-based psychiatric diagnoses. Part of the increased mortality for those with mental disorder may be attributable to worse somatic health or hazardous health behaviour - consequences of the disorder - but somatic health information is commonly lacking in psychiatric samples. This study aims to examine long-term mortality risk for psychiatric diagnoses in a general population sample and to assess mediation by somatic ill health and hazardous health behaviour. We used a double-phase stratified random sample of individuals aged 18-65 in Stockholm County 1970-1971 linked to vital records. First phase sample was 32 186 individuals screened with postal questionnaire and second phase was 1896 individuals (920 men and 976 women) that participated in a full-day examination (participation rate 88%). Baseline examination included both a semi-structured interview with a psychiatrist, with mental disorders set according to the 8th version of the International Classification of Disease (ICD-8), and clinical somatic examination, including measures of body composition (BMI), hypertension, fasting blood glucose, pulmonary function and self-reported tobacco smoking. Information on vital status was obtained from the Total Population Register for the years 1970-2011. Associations with mortality were studied with Cox proportional hazard analyses. A total of 883 deaths occurred among the participants during the 41-year follow-up. Increased mortality rates were found for ICD-8 functional psychoses (hazard ratio, HR = 2.22, 95% confidence interval (95% CI): 1.15-4.30); psycho-organic symptoms (HR = 1.94, 95% CI: 1.31-2.87); depressive neuroses (HR = 1.71, 95% CI: 1.23-2.39); alcohol use disorder (HR = 1.91, 95% CI: 1.40-2.61); drug dependence (HR = 3.71, 95% CI: 1.80-7.65) and psychopathy (HR = 2.88, 95% CI: 1.02-8.16). Non-participants (n = 349) had mortality rates similar to participants (HR = 0.98, 95% CI: 0.81-1.18). In subgroup analyses of those with psychoses, depression or alcohol use disorder, adjusting for the potential mediators smoking and pulmonary function, showed only slight changes in the HRs. This study confirms the increased risk of mortality for several psychiatric diagnoses in follow-up studies on American, Finnish and Swedish population-based samples. Only a small part of the increased mortality hazard was attributable to differences in somatic health or hazardous health behaviour measured at baseline.

Somatic focus/awareness: Relationship to negative affect and pain in chronic pain patients

PubMed Central

O’Brien, Erin M.; Atchison, James W.; Gremillion, Henry A.; Waxenberg, Lori B.; Robinson, Michael E.

2009-01-01

Somatic focus refers to the tendency to notice and report physical symptoms, and has been investigated in relation to chronically painful conditions. This study investigated the relationship between somatic focus, as measured by the Pennebaker Inventory of Limbic Languidness (PILL), negative affect and pain. A secondary purpose of the present study was to examine sex differences in these relationships. Participants included 280 chronic pain patients (69.6% females, 88.9% Caucasian), who completed a battery of self-report measures on somatic focus, pain, negative affect, coping, and dysfunction. Results for the overall sample revealed that the PILL shares considerable variance with measures of negative affect, particularly with the physiological components of anxiety and depression. When the results were analyzed separately for male and female patients, it was found that several components of negative affect and cognitive factors play a stronger role in predicting somatic focus among men compared to women. Additional analyses then examined whether somatic focus was predictive of male and female patients’ pain reports. Results indicated that somatic focus explained a small, but unique amount of variance in female patients’ pain reports, which differed from the relationship observed among male patients. PMID:17524684

Psychosocial Risk Factors for Upper Respiratory Infections: Assessment of Upper Respiratory Illness during Basic Training

DTIC Science & Technology

1988-05-23

association was low enough to ensure that the URI composite was not merely an index of somatic stress reactions or hypochondriasis . The eight-item...report somatic symptoms in response to stress. Adjusted URI Severity also is consistent with the clinical practice of ruling out other possible types

[Treatment of functional somatic syndrome with abdominal pain].

PubMed

Abe, Tetsuya; Kanbara, Kenji; Mizuno, Yasuyuki; Fukunaga, Mikihiko

2009-09-01

Functional somatic syndrome (FSS) with abdominal pain include functional gastrointestinal disorder, chronic pancreatitis, chronic pelvic pain syndrome, which generally contain autonomic dysfunction. Regarding the treatment of FSS, it is important to know about FSS for a therapist at first. Secondly, the therapist should find out physical dysfunction of patients positively, and confirm objectively the hypotheses about both peripheral and central pathophysiological mechanisms as much as possible. Heart rate variability is an easy method, and useful to assess autonomic function. After grasping the patient's explanatory model about the illness, the therapist showes the most acceptable treatment for the patient at last.

Landscape of somatic mutations in 560 breast cancer whole-genome sequences

DOE PAGES

Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; ...

2016-05-02

Here, we analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, anothermore » with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.« less

Landscape of somatic mutations in 560 breast cancer whole-genome sequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nik-Zainal, Serena; Davies, Helen; Staaf, Johan

Here, we analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, anothermore » with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.« less

Comorbidity in Migraine with Functional Somatic Syndromes, Psychiatric Disorders and Inflammatory Diseases: A Matter of Central Sensitization?

PubMed

Grassini, Simone; Nordin, Steven

2017-01-01

To approach the questions as to why migraine appears to be associated with functional somatic syndromes (FSSs) and whether central sensitization may be an underlying mechanism, the present study investigated (a) comorbidity with diagnoses of three FSSs, three psychiatric disorders, and three inflammatory diseases, (b) degree of mental health problems (stress, burnout, anxiety, depression and somatization), and (c) prevalence of ten cognitive/affective and nine airway symptoms in persons with migraine in the general population. From a randomized and stratified Swedish adult sample, questionnaire data were analyzed from 151 individuals with a diagnosis of migraine and 3,255 without migraine. The results showed (a) significant comorbidity in migraine with all FSSs, psychiatric disorders and inflammatory diseases, (b) significantly elevated scores on stress, burnout, anxiety, depression, and somatization, and (c) relatively high prevalence rates on almost all symptoms. Taken together, the results motivate future study of central sensitization as a mechanism underlying migraine.

Landscape of somatic mutations in 560 breast cancer whole genome sequences

PubMed Central

Nik-Zainal, Serena; Davies, Helen; Staaf, Johan; Ramakrishna, Manasa; Glodzik, Dominik; Zou, Xueqing; Martincorena, Inigo; Alexandrov, Ludmil B.; Martin, Sancha; Wedge, David C.; Van Loo, Peter; Ju, Young Seok; Smid, Marcel; Brinkman, Arie B; Morganella, Sandro; Aure, Miriam R.; Lingjærde, Ole Christian; Langerød, Anita; Ringnér, Markus; Ahn, Sung-Min; Boyault, Sandrine; Brock, Jane E.; Broeks, Annegien; Butler, Adam; Desmedt, Christine; Dirix, Luc; Dronov, Serge; Fatima, Aquila; Foekens, John A.; Gerstung, Moritz; Hooijer, Gerrit KJ; Jang, Se Jin; Jones, David R.; Kim, Hyung-Yong; King, Tari A.; Krishnamurthy, Savitri; Lee, Hee Jin; Lee, Jeong-Yeon; Li, Yilong; McLaren, Stuart; Menzies, Andrew; Mustonen, Ville; O’Meara, Sarah; Pauporté, Iris; Pivot, Xavier; Purdie, Colin A.; Raine, Keiran; Ramakrishnan, Kamna; Rodríguez-González, F. Germán; Romieu, Gilles; Sieuwerts, Anieta M.; Simpson, Peter T; Shepherd, Rebecca; Stebbings, Lucy; Stefansson, Olafur A; Teague, Jon; Tommasi, Stefania; Treilleux, Isabelle; Van den Eynden, Gert G.; Vermeulen, Peter; Vincent-Salomon, Anne; Yates, Lucy; Caldas, Carlos; van’t Veer, Laura; Tutt, Andrew; Knappskog, Stian; Tan, Benita Kiat Tee; Jonkers, Jos; Borg, Åke; Ueno, Naoto T; Sotiriou, Christos; Viari, Alain; Futreal, P. Andrew; Campbell, Peter J; Span, Paul N.; Van Laere, Steven; Lakhani, Sunil R; Eyfjord, Jorunn E.; Thompson, Alastair M.; Birney, Ewan; Stunnenberg, Hendrik G; van de Vijver, Marc J; Martens, John W.M.; Børresen-Dale, Anne-Lise; Richardson, Andrea L.; Kong, Gu; Thomas, Gilles; Stratton, Michael R.

2016-01-01

We analysed whole genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. 93 protein-coding cancer genes carried likely driver mutations. Some non-coding regions exhibited high mutation frequencies but most have distinctive structural features probably causing elevated mutation rates and do not harbour driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed 12 base substitution and six rearrangement signatures. Three rearrangement signatures, characterised by tandem duplications or deletions, appear associated with defective homologous recombination based DNA repair: one with deficient BRCA1 function; another with deficient BRCA1 or BRCA2 function; the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operative, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer. PMID:27135926

Quality of life and neurotic disorders in general healthcare.

PubMed

Herrman, Helen; Chopra, Prem

2009-01-01

To review recent findings on the relationship between neurotic disorders (specifically depression, anxiety and somatization) and function and quality of life (QoL) in patients with complex clinical presentations, and to consider the clinical and public health implications. The high prevalence of comorbid depression and anxiety among patients with general medical disorders is well known. The impact of the comorbidity on function in these patients is documented extensively. The study of their QoL is an emerging area of work, though its interpretation is controversial. The impact of somatization on function and QoL is less well studied. Recent findings emphasize the value of a common measure for QoL across health conditions. Depression, anxiety and somatization are a significant burden in the general population and failure to recognize and manage these problems in general healthcare contributes to delayed recovery. A holistic approach to symptom, disability and QoL assessment, done in awareness of possible measurement redundancy, is likely to assist better recognition and management of these conditions. Further research is needed on the effects on QoL of depression and anxiety in patients with general medical disorders and early detection and treatment of somatization.

Integration of Genomic, Biologic, and Chemical Approaches to Target p53 Loss and Gain-of-Function in Triple Negative Breast Cancer

DTIC Science & Technology

2014-09-01

in this renewal: p53 triple negative breast cancer subtypes gene expression somatic cell genetics CRISPR /Cas 3. OVERALL PROJECT SUMMARY...to the efficacy of the synthetic lethality screen. In addition, we have optimized the use of CRISPR /Cas, a novel somatic cell recombination...completing this stage of the research within the upcoming Year 2 of the award period. Figure 1. CRISPR /Cas-mediated in vitro somatic cell

Substance-related disorders and somatic symptoms: how should clinicians understand the associations?

PubMed

Yoshimasu, Kouichi

2012-12-01

There are five major patterns which explain the associations between somatic symptoms and substance-related disorders (SRD) in patients without organic disorders. They are withdrawal somatic symptoms, somatic symptoms related to co-morbid mental disorders, those related to co-morbid infectious diseases, functional intractable somatic symptoms (including somatoform disorders), and symptoms associated with intoxication. Those somatic symptoms that occur according to those five patterns might overlap each other, making it difficult for physicians to precisely grasp the associations between somatic symptoms and SRD. This results in a very complicated formation of various kinds of symptoms (syndrome). Furthermore, the clinical and social features of those patterns of associations differ between legal and illicit substances users. It should also be noted that such somatic symptoms associated with SRD may be affected by social factors such as cultural backgrounds or legal restrictions on such substances. Those factors differ according to each country, area, or community whose cultural backgrounds are somewhat specific. In those areas, psychosocial factors such as stigmas, prejudices, or feeling ashamed of one's mental disorder (including SRD) also differ. Thus, it is important to take into account the effects of social or psychosocial backgrounds when evaluating and studying the associations between somatic symptoms and SRD. When clinicians confront patients with somatic symptoms and suspected SRD, they should presume which association pattern is the most significant problem for the patients, based on those psychosocial and biological information obtained from the patients themselves and their surroundings. This procedure might give an opportunity to clinicians for elucidating complicated associations between somatic complaints and SRD.

A cross-sectional study of growth, nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland.

PubMed

Sands, Dorota; Umławska, Wioleta; Zielińska, Anna

2015-03-16

Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis. The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group. The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = -0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = -0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = -0.75 and Z-score = -0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure. The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters.

Coping Skills Are Associated With Gastrointestinal Symptom Severity and Somatization in Patients With Irritable Bowel Syndrome.

PubMed

Wilpart, Katarina; Törnblom, Hans; Svedlund, Jan; Tack, Jan F; Simrén, Magnus; Van Oudenhove, Lukas

2017-10-01

Coping resources and processes are altered in patients with irritable bowel syndrome (IBS). We investigated the relationship between coping resources and gastrointestinal (GI) and extraintestinal symptom severity in patients with IBS and potential mediators of this relationship. We performed a cross-sectional study of 216 patients with IBS attending a secondary/tertiary care specialized outpatient center in Sweden from 2003 through 2007. We collected data on coping resources, levels of anxiety (general and GI specific), depressive symptoms, levels of GI symptoms, and extraintestinal somatic symptoms (somatization) by administering validated self-report questionnaires. General Linear Models were used to assess associations and mediation. GI symptoms: low levels of physical coping resources (practice of activities that are beneficial for health; P = .0016), high levels of general anxiety symptoms (P = .033), and GI-specific anxiety symptoms (P < .0001), but not depressive symptoms (P = .89), were independently associated with GI symptom levels (R 2  = 0.31). Anxiety and GI-specific anxiety partially mediated the effect of physical coping. Somatization: low levels of physical coping resources (P = .003), high levels of anxiety (P = .0147), depressive (P = .0005), and GI-specific anxiety symptoms (P = .06) were associated with somatization levels (R 2  = 0.35). Levels of general and GI-specific anxiety and depressive symptoms partially mediated this physical coping effect. The effect of psychological coping resources (including optimism, social support, and accepting/expressing emotions) on somatization levels was not significant (P = .98), but was fully mediated by levels of anxiety and depressive symptoms, and partially by levels of GI-specific anxiety symptoms. In a cross-sectional study of patients with IBS in Sweden, we found associations of levels of coping resources with GI and extraintestinal symptom severity; these associations were mediated by levels of anxiety and depressive symptoms. Although confirmation in longitudinal studies is needed, this identifies coping as a potential psychological treatment target in IBS. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Ca2+-stores in sperm: their identities and functions

PubMed Central

Costello, Sarah; Michelangeli, Francesco; Nash, Kate; Lefievre, Linda; Morris, Jennifer; Machado-Oliveira, Gisela; Barratt, Christopher; Kirkman-Brown, Jackson; Publicover, Stephen

2013-01-01

Intracellular Ca2+ stores play a central role in the regulation of cellular [Ca2+]i and the generation of complex [Ca2+] signals such as oscillations and waves. Ca2+ signalling is of particular significance in sperm cells, where it is a central regulator in many key activities (including capacitation, hyperactivation, chemotaxis and acrosome reaction) yet mature sperm lack endoplasmic reticulum and several other organelles which serve as Ca2+ stores in somatic cells. Here we review (i) the evidence for the expression in sperm of the molecular components (pumps and channels) which are functionally significant in the activity of Ca2+ stores of somatic cells and (ii) the evidence for the existence of functional Ca2+ stores in sperm. This evidence supports the existence of at least two storage organelles in mammalian sperm, one in the acrosomal region and another in the region of the sperm neck and midpiece. We then go on to discuss the likely identity of these organelles and their discrete functions: regulation by the acrosome of its own secretion and regulation by membranous organelles at the sperm neck (and possibly by the mitochondria) of flagellar activity and hyperactivation. Finally we consider the ability of the sperm discretely to control mobilisation of these stores and the functional interaction of stored Ca2+ at the sperm neck/midpiece with CatSper channels in the principal piece in regulation of the activities of mammalian sperm. PMID:19542252

Survival of ovarian somatic cells during sex change in the protogynous wrasse, Halichoeres trimaculatus.

PubMed

Nozu, Ryo; Horiguchi, Ryo; Murata, Ryosuke; Kobayashi, Yasuhisa; Nakamura, Masaru

2013-02-01

The three-spot wrasse (Halichoeres trimaculatus), which inhabits the coral reefs of Okinawa, changes sex from female to male. Sex change in this species is controlled by a social system. Oocytes disappear completely from the ovary, and male germ cells and somatic cells comprising testicular tissue arise a new during the sex change process. However, little is known of the fate and origin of the gonadal tissue-forming cells during sex change. In particular, the fate of ovarian somatic cells has not been determined, although the ovarian tissue regresses histologically. To approach this question, we analyzed apoptosis and cell proliferation in the sex-changing gonads. Unexpectedly, we found that few apoptotic somatic cells were present during sex change, suggesting that ovarian somatic cells might survive during the regression of the ovarian tissue. On the other hand, cell proliferation was detected in many granulosa cells surrounding the degenerating oocytes, a few epithelial cells covering ovigerous lamella and a few somatic cells associated with gonial germ cells at an early stage of sex change. Then, we found that proliferative ovarian somatic cells remained in the gonads late in the sex change process. Based on these results, we concluded that some functional somatic cells of the ovary are reused as testicular somatic cells during the gonadal sex change in the three-spot wrasse.

Symptom correlates of cerebral blood flow following acute concussion.

PubMed

Churchill, Nathan W; Hutchison, Michael G; Graham, Simon J; Schweizer, Tom A

2017-01-01

Concussion is associated with significant symptoms within hours to days post-injury, including disturbances in physical function, cognition, sleep and emotion. However, little is known about how subjective impairments correlate with objective measures of cerebrovascular function following brain injury. This study examined the relationship between symptoms and cerebral blood flow (CBF) in individuals following sport-related concussion. Seventy university level athletes had CBF measured using Arterial Spin Labelling (ASL), including 35 with acute concussion and 35 matched controls and their symptoms were assessed using the Sport Concussion Assessment Tool 3 (SCAT3). For concussed athletes, greater total symptom severity was associated with elevated posterior cortical CBF, although mean CBF was not significantly different from matched controls ( p  = 0.46). Examining symptom clusters, athletes reporting greater cognitive symptoms also had lower frontal and subcortical CBF, relative to athletes with greater somatic symptoms. The "cognitive" and "somatic" subgroups also exhibited significant differences in CBF relative to controls ( p  ≤ 0.026). This study demonstrates objective CBF correlates of symptoms in recently concussed athletes and shows that specific symptom clusters may have distinct patterns of altered CBF, significantly extending our understanding of the neurobiology of concussion and traumatic brain injury.

[Tips for taking history of pain].

PubMed

Noda, Kazutaka; Ikusaka, Masatomi

2012-11-01

Pain is physiologically classified as nociceptive pain, neuropathic pain, and psychogenic pain. Nociceptive pain is further divided into visceral pain, somatic pain, and referred pain. Visceral pain is dull, and it is difficult to locate the origin of such pain. Somatic pain is sharp, severe, and well localized. On receiving visceral input for pain, it affects somatic nerve inputting to the same spinal segments, then referred pain is felt in the skin and muscles supplied by it. Referred pain is felt in an area that is located at a distance from its cause. History taking is the most important factor for determining the cause of pain. Generally, all the necessary information regarding pain can be acquired if pain-related history is obtained using the "OPQRST" mnemonic, that is, onset, provocation/palliative factor, quality, region/radiation/related symptoms, severity, and time characteristics.

Somatic INK4a-ARF locus mutations: a significant mechanism of gene inactivation in squamous cell carcinomas of the head and neck.

PubMed

Poi, M J; Yen, T; Li, J; Song, H; Lang, J C; Schuller, D E; Pearl, D K; Casto, B C; Tsai, M D; Weghorst, C M

2001-01-01

The INK4a-ARF locus is located on human chromosome 9p21 and is known to encode two functionally distinct tumor-suppressor genes. The p16(INK4a) (p16) tumor-suppressor gene product is a negative regulator of cyclin-dependent kinases 4 and 6, which in turn positively regulate progression of mammalian cells through the cell cycle. The p14(ARF) tumor-suppressor gene product specifically interacts with human double minute 2, leading to the subsequent stabilization of p53 and G(1) arrest. Previous investigations analyzing the p16 gene in squamous cell carcinomas of the head and neck (SCCHNs) have suggested the predominate inactivating events to be homozygous gene deletions and hypermethylation of the p16 promoter. Somatic mutational inactivation of p16 has been reported to be low (0-10%, with a combined incidence of 25 of 279, or 9%) and to play only a minor role in the development of SCCHN. The present study examined whether this particular mechanism of INK4a/ARF inactivation, specifically somatic mutation, has been underestimated in SCCHN by determining the mutational status of the p16 and p14(ARF) genes in 100 primary SCCHNs with the use of polymerase chain reaction technology and a highly sensitive, nonradioactive modification of single-stranded conformational polymorphism (SSCP) analysis termed "cold" SSCP. Exons 1alpha, 1beta, and 2 of INK4a/ARF were amplified using intron-based primers or a combination of intron- and exon-based primers. A total of 27 SCCHNs (27%) exhibited sequence alterations in this locus, 22 (22%) of which were somatic sequence alterations and five (5%) of which were a single polymorphism in codon 148. Of the 22 somatic alterations, 20 (91%) directly or indirectly involved exon 2, and two (9%) were located within exon 1alpha. No mutations were found in exon 1beta. All 22 somatic mutations would be expected to yield altered p16 proteins, but only 15 of them should affect p14(ARF) proteins. Specific somatic alterations included microdeletions or insertions (nine of 22, 41%), a microrearrangement (one of 22, 5%), and single nucleotide substitutions (12 of 22, 56%). In addition, we analyzed the functional characteristics of seven unique mutant p16 proteins identified in this study by assessing their ability to inhibit cyclin-dependent kinase 4 activity. Six of the seven mutant proteins tested exhibited reduced function compared with wild-type p16, ranging from minor decreases of function (twofold to eightfold) in four samples to total loss of function (29- to 38-fold decrease) in two other samples. Overall, somatic mutation of the INK4a/ARF tumor suppressor locus, resulting in functionally deficient p16 and possibly p14(ARF) proteins, seems to be a prevalent event in the development of SCCHN. Mol. Carcinog. 30:26-36, 2001. Copyright 2001 Wiley-Liss, Inc.

Independent validation of the MMPI-2-RF Somatic/Cognitive and Validity scales in TBI Litigants tested for effort.

PubMed

Youngjohn, James R; Wershba, Rebecca; Stevenson, Matthew; Sturgeon, John; Thomas, Michael L

2011-04-01

The MMPI-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) is replacing the MMPI-2 as the most widely used personality test in neuropsychological assessment, but additional validation studies are needed. Our study examines MMPI-2-RF Validity scales and the newly created Somatic/Cognitive scales in a recently reported sample of 82 traumatic brain injury (TBI) litigants who either passed or failed effort tests (Thomas & Youngjohn, 2009). The restructured Validity scales FBS-r (restructured symptom validity), F-r (restructured infrequent responses), and the newly created Fs (infrequent somatic responses) were not significant predictors of TBI severity. FBS-r was significantly related to passing or failing effort tests, and Fs and F-r showed non-significant trends in the same direction. Elevations on the Somatic/Cognitive scales profile (MLS-malaise, GIC-gastrointestinal complaints, HPC-head pain complaints, NUC-neurological complaints, and COG-cognitive complaints) were significant predictors of effort test failure. Additionally, HPC had the anticipated paradoxical inverse relationship with head injury severity. The Somatic/Cognitive scales as a group were better predictors of effort test failure than the RF Validity scales, which was an unexpected finding. MLS arose as the single best predictor of effort test failure of all RF Validity and Somatic/Cognitive scales. Item overlap analysis revealed that all MLS items are included in the original MMPI-2 Hy scale, making MLS essentially a subscale of Hy. This study validates the MMPI-2-RF as an effective tool for use in neuropsychological assessment of TBI litigants.

Mammalian nuclear transplantation to Germinal Vesicle stage Xenopus oocytes – A method for quantitative transcriptional reprogramming

PubMed Central

Halley-Stott, R.P.; Pasque, V.; Astrand, C.; Miyamoto, K.; Simeoni, I.; Jullien, J.; Gurdon, J.B.

2010-01-01

Full-grown Xenopus oocytes in first meiotic prophase contain an immensely enlarged nucleus, the Germinal Vesicle (GV), that can be injected with several hundred somatic cell nuclei. When the nuclei of mammalian somatic cells or cultured cell lines are injected into a GV, a wide range of genes that are not transcribed in the donor cells, including pluripotency genes, start to be transcriptionally activated, and synthesize primary transcripts continuously for several days. Because of the large size and abundance of Xenopus laevis oocytes, this experimental system offers an opportunity to understand the mechanisms by which somatic cell nuclei can be reprogrammed to transcribe genes characteristic of oocytes and early embryos. The use of mammalian nuclei ensures that there is no background of endogenous maternal transcripts of the kind that are induced. The induced gene transcription takes place in the absence of cell division or DNA synthesis and does not require protein synthesis. Here we summarize new as well as established results that characterize this experimental system. In particular, we describe optimal conditions for transplanting somatic nuclei to oocytes and for the efficient activation of transcription by transplanted nuclei. We make a quantitative determination of transcript numbers for pluripotency and housekeeping genes, comparing cultured somatic cell nuclei with those of embryonic stem cells. Surprisingly we find that the transcriptional activation of somatic nuclei differs substantially from one donor cell-type to another and in respect of different pluripotency genes. We also determine the efficiency of an injected mRNA translation into protein. PMID:20123126

The level of recognition of physical symptoms in patients with a major depression episode in the outpatient psychiatric practice in Puerto Rico: An observational study

PubMed Central

Tamayo, Jorge M; Román, Karis; Fumero, Juan J; Rivas, María

2005-01-01

Background This study was designed to evaluate the psychiatrists' level of recognition of somatic symptoms associated to a major depressive episode (MDE) (DSM-IV-TR criteria) and the impact of those somatic symptoms on the treatment effectiveness. Methods This non-interventional study was conducted in 25 medical offices in Puerto Rico from February to December 2003. It had 2 visits separated by 8 weeks. The level of recognition was determined by: the correlation between the physician clinical evaluation and their patients' self-evaluations through different validated instruments using kappa statistics. Chi-square test was used to evaluate the impact of somatic symptoms on treatment antidepressants' effectiveness. Results All the 145 recruited patients reported the presence of at least one somatic symptom associated with their current MDE. In the two visits covered by the study, a fair agreement between the psychiatrists' and the patients' reports was noted for headache, abdominal pain and upper limb pains (0.4003 ≤ κ ≥ 0.6594). For other painful symptoms and painless somatic symptoms, the Kappa values obtained were non-significant. Slight but significant reductions in depression and painful symptoms severity were observed after 8 weeks of treatment. A proportional relationship between the pain and depression severity was observed (p < 0.0001). Conclusion The study results show that somatic symptoms: are very common in depressed Puerto Rican patients; are significant under-reported by psychiatrists; and have a significant impact on the antidepressant effectiveness. PMID:15967039

Somatic syndromes and chronic pain in women with overactive bladder

PubMed Central

Reynolds, W. Stuart; Mock, Stephen; Zhang, Xuechao; Kaufman, Melissa; Wein, Alan; Bruehl, Stephen; Dmochowski, Roger

2016-01-01

Aims Mechanisms underlying pain perception and afferent hypersensitivity, such as central sensitization, may impact overactive bladder (OAB) symptoms. However, little is known about associations between OAB symptom severity, pain experience, and presence of comorbid chronic pain syndromes. This study examined relationships between OAB symptoms, somatic symptoms, and specific chronic pain conditions in which central sensitization is believed to play a primary role, in a community-based sample of adult women with OAB Methods We recruited adult women with OAB to complete questionnaires assessing urinary symptoms, pain and somatic symptoms, and preexisting diagnoses of central sensitivity syndromes. We analyzed the effects of overall bodily pain intensity, general somatic symptoms, and diagnoses of central sensitivity syndromes on OAB symptom bother and health-related quality of life. Results Of the 116 women in this study, over half (54%) stated their urge to urinate was associated with pain, pressure, or discomfort. Participants reported a wide range of OAB symptoms and health-related quality of life. There was a significant, positive correlation between OAB symptoms and somatic symptoms as well as overall pain intensity. Only 7% of women met diagnostic criteria for fibromyalgia; yet these women demonstrated significantly increased OAB symptom burden and decreased OAB quality of life compared to those without fibromyalgia. Conclusion Women with more severe OAB symptoms reported increased general somatic symptom burden and increased overall body pain intensity, especially women with fibromyalgia. These findings suggest that attributes of pain and co-morbidity with chronic pain conditions may impact the experience of OAB symptoms for many women. PMID:27367486

Somatic comorbidity in anorexia nervosa: First results of a 21-year follow-up study on female inpatients

PubMed Central

2012-01-01

Background Anorexia nervosa is a severe psychosomatic disease with somatic complications in the long-term course and a high mortality rate. Somatic comorbidities independent of anorexia nervosa have rarely been studied, but pose a challenge to clinical practitioners. We investigated somatic comorbidities in an inpatient cohort and compared somatically ill anorexic patients and patients without a somatic comorbidity. In order to evaluate the impact of somatic comorbidity for the long-term course of anorexia nervosa, we monitored survival in a long-term follow-up. Method One hundred and sixty-nine female inpatients with anorexia nervosa were treated at the Charité University Medical Centre, Campus Benjamin Franklin, Berlin, between 1979 and 2011. We conducted retrospective analyses using patient's medical and psychological records. Information on survival and mortality were required through the local registration office and was available for one hundred patients. The mean follow-up interval for this subgroup was m = 20.9 years (sd = 4.7, min = 13.3, max = 31.6, range = 18.3). We conducted survival analysis using cox regression and included somatic comorbidity in a multivariate model. Results N = 41 patients (24.3%) showed a somatic comorbidity, n = 13 patients (7.7%) showed somatic comorbidities related to anorexia nervosa and n = 26 patients (15.4%) showed somatic comorbidities independent of anorexia nervosa, n = 2 patients showed somatic complications related to other psychiatric disorders. Patients with a somatic comorbidity were significantly older (m = 29.5, sd = 10.3 vs m = 25.0, sd = 8.7; p = .006), showed a later anorexia nervosa onset (m = 24.8, sd = 9.9 vs. m = 18.6, sd = 5.1; p < .000) and a longer duration of treatment in our clinic (m = 66.6, sd = 50.3 vs. m = 50.0, sd = 47; p = .05) than inpatients without somatic comorbidity. Out of 100 patients, 9 patients (9%) had died, on average at age of m = 37 years (sd = 9.5). Mortality was more common among inpatients with somatic comorbidity (n = 6, 66.7%) than among inpatients without a somatic disease (n = 3, 33.3%; p = .03). Somatic comorbidity was a significant coefficient in a multivariate survival model (B = 2.32, p = .04). Conclusion Somatic comorbidity seems to be an important factor for anorexia nervosa outcome and should be included in multivariate analyses on the long-term course of anorexia nervosa as an independent variable. Further investigations are needed in order to understand in which way anorexia nervosa and a somatic disease can interact. PMID:22300749

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

PubMed Central

Merrill, Liana; Malley, Susan

2013-01-01

Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P ≤ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P ≤ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P ≤ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P ≤ 0.01) increased at all monofilament forces tested (0.1–4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P ≤ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity. PMID:23657640

Proteomic analysis of stipe explants reveals differentially expressed proteins involved in early direct somatic embryogenesis of the tree fern Cyathea delgadii Sternb.

PubMed

Domżalska, Lucyna; Kędracka-Krok, Sylwia; Jankowska, Urszula; Grzyb, Małgorzata; Sobczak, Mirosław; Rybczyński, Jan J; Mikuła, Anna

2017-05-01

Using cyto-morphological analysis of somatic embryogenesis (SE) in the tree fern Cyathea delgadii as a guide, we performed a comparative proteomic analysis in stipe explants undergoing direct SE. Plant material was cultured on hormone-free medium supplemented with 2% sucrose. Phenol extracted proteins were separated using two-dimensional gel electrophoresis (2-DE) and mass spectrometry was performed for protein identification. A total number of 114 differentially regulated proteins was identified during early SE, i.e. when the first cell divisions started and several-cell pro-embryos were formed. Proteins were assigned to seven functional categories: carbohydrate metabolism, protein metabolism, cell organization, defense and stress responses, amino acid metabolism, purine metabolism, and fatty acid metabolism. Carbohydrate and protein metabolism were found to be the most sensitive SE functions with the greatest number of alterations in the intensity of spots in gel. Differences, especially in non-enzymatic and structural protein abundance, are indicative for cell organization, including cytoskeleton rearrangement and changes in cell wall components. The highest induced changes concern those enzymes related to fatty acid metabolism. Global analysis of the proteome reveals several proteins that can represent markers for the first 16days of SE induction and expression in fern. The findings of this research improve the understanding of molecular processes involved in direct SE in C. delgadii. Copyright © 2017 Elsevier B.V. All rights reserved.

Somatic Symptoms in Traumatized Children and Adolescents

ERIC Educational Resources Information Center

Kugler, Brittany B.; Bloom, Marlene; Kaercher, Lauren B.; Truax, Tatyana V.; Storch, Eric A.

2012-01-01

Childhood exposure to trauma has been associated with increased rates of somatic symptoms (SS), which may contribute to diminished daily functioning. One hundred and sixty-one children residing at a residential treatment home who had experienced neglect and/or abuse were administered the Trauma Symptom Checklist for Children (TSCC), the…

Long-Term Hyperphagia and Caloric Restriction Caused by Low- or High-Density Husbandry Have Differential Effects on Zebrafish Postembryonic Development, Somatic Growth, Fat Accumulation and Reproduction

PubMed Central

Leibold, Sandra; Hammerschmidt, Matthias

2015-01-01

In recent years, the zebrafish (Danio rerio) has emerged as an alternative vertebrate model for energy homeostasis and metabolic diseases, including obesity and anorexia. It has been shown that diet-induced obesity (DIO) in zebrafish shares multiple pathophysiological features with obesity in mammals. However, a systematic and comprehensive analysis of the different pathways of energy expenditure in obese and starved fish had been missing thus far. Here, we carry out long-term ad libitum feeding (hyperphagia) and caloric restriction studies induced by low- or high-density husbandry, respectively, to investigate the impact of caloric intake on the timing of scale formation, a crucial step of postembryonic development and metamorphosis, and on somatic growth, body weight, fat storage and female reproduction. We show that all of them are positively affected by increased caloric intake, that middle-aged fish develop severe DIO, and that the body mass index (BMI) displays a strict linear correlation with whole-body triglyceride levels in adult zebrafish. Interestingly, juvenile fish are largely resistant to DIO, while BMI and triglyceride values drop in aged fish, pointing to aging-associated anorexic effects. Histological analyses further indicate that increased fat storage in white adipose tissue involves both hyperplasia and hypertrophy of adipocytes. Furthermore, in ovaries, caloric intake primarily affects the rate of oocyte growth, rather than total oocyte numbers. Finally, comparing the different pathways of energy expenditure with each other, we demonstrate that they are differentially affected by caloric restriction / high-density husbandry. In juvenile fish, scale formation is prioritized over somatic growth, while in sexually mature adults, female reproduction is prioritized over somatic growth, and somatic growth over fat storage. Our data will serve as a template for future functional studies to dissect the neuroendocrine regulators of energy homeostasis mediating differential energy allocation. PMID:25799180

Long-term hyperphagia and caloric restriction caused by low- or high-density husbandry have differential effects on zebrafish postembryonic development, somatic growth, fat accumulation and reproduction.

PubMed

Leibold, Sandra; Hammerschmidt, Matthias

2015-01-01

In recent years, the zebrafish (Danio rerio) has emerged as an alternative vertebrate model for energy homeostasis and metabolic diseases, including obesity and anorexia. It has been shown that diet-induced obesity (DIO) in zebrafish shares multiple pathophysiological features with obesity in mammals. However, a systematic and comprehensive analysis of the different pathways of energy expenditure in obese and starved fish had been missing thus far. Here, we carry out long-term ad libitum feeding (hyperphagia) and caloric restriction studies induced by low- or high-density husbandry, respectively, to investigate the impact of caloric intake on the timing of scale formation, a crucial step of postembryonic development and metamorphosis, and on somatic growth, body weight, fat storage and female reproduction. We show that all of them are positively affected by increased caloric intake, that middle-aged fish develop severe DIO, and that the body mass index (BMI) displays a strict linear correlation with whole-body triglyceride levels in adult zebrafish. Interestingly, juvenile fish are largely resistant to DIO, while BMI and triglyceride values drop in aged fish, pointing to aging-associated anorexic effects. Histological analyses further indicate that increased fat storage in white adipose tissue involves both hyperplasia and hypertrophy of adipocytes. Furthermore, in ovaries, caloric intake primarily affects the rate of oocyte growth, rather than total oocyte numbers. Finally, comparing the different pathways of energy expenditure with each other, we demonstrate that they are differentially affected by caloric restriction / high-density husbandry. In juvenile fish, scale formation is prioritized over somatic growth, while in sexually mature adults, female reproduction is prioritized over somatic growth, and somatic growth over fat storage. Our data will serve as a template for future functional studies to dissect the neuroendocrine regulators of energy homeostasis mediating differential energy allocation.

[New possibilities will open up in human gene therapy].

PubMed

Portin, Petter

2016-01-01

Gene therapy is divided into somatic and germ line therapy. The latter involves reproductive cells or their stem cells, and its results are heritable. The effects of somatic gene therapy are generally restricted to a single tissue of the patient in question. Until now, all gene therapies in the world have belonged to the regime of somatic therapy, germ line therapy having been a theoretical possibility only. Very recently, however, a method has been developed which is applicable to germ line therapy as well. In addition to technical challenges, severe ethical problems are associated with germ line therapy, demanding opinion statement.

Assessing somatic symptom burden: a psychometric comparison of the patient health questionnaire-15 (PHQ-15) and the somatic symptom scale-8 (SSS-8).

PubMed

Gierk, Benjamin; Kohlmann, Sebastian; Toussaint, Anne; Wahl, Inka; Brünahl, Christian A; Murray, Alexandra M; Löwe, Bernd

2015-04-01

The Patient Health Questionnaire-15 (PHQ-15) is a frequently used questionnaire to assess somatic symptom burden. Recently, the Somatic Symptom Scale-8 (SSS-8) has been published as a short version of the PHQ-15. This study examines whether the instruments' psychometric properties and estimates of symptom burden are comparable. Psychosomatic outpatients (N=131) completed the PHQ-15, the SSS-8 and other questionnaires (PHQ-9, GAD-7, WI-7, SF-12). Item characteristics and measures of reliability, validity, and symptom severity were determined and compared. The reliabilities of the PHQ-15 and SSS-8 were α=0.80 and α=0.76, respectively and both scales were highly correlated (r=0.83). The item characteristics were comparable. Both instruments showed the same pattern of correlations with measures of depression, anxiety, health anxiety and health-related quality of life (r=0.32 to 0.61). On both scales a 1-point increase was associated with a 3% increase in health care use. The percentile distributions of the PHQ-15 and the SSS-8 were similar. Using the same thresholds for somatic symptom severity (5, 10, and 15 points), both instruments identified nearly identical subgroups of patients with respect to health related quality of life. The PHQ-15 and the SSS-8 showed similar reliability and validity but the comparability of severity classifications needs further evaluation in other populations. Until then we recommend the use of the previously established thresholds. Overall, the SSS-8 performed well as a short version of the PHQ-15 which makes it preferable for assessment in time restricted settings. Copyright © 2014 Elsevier Inc. All rights reserved.

The relationship between somatic symptoms and depression.

PubMed

Han, Hyeseung; Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Pae, Chi-Un

2014-01-01

We investigated the influence of somatic symptoms on the severity and clinical outcomes in female Korean patients with major depressive disorder (MDD) in routine practice. Two hundred and seven female patients with MDD were prospectively recruited. Patients with somatic symptoms (PSS) was defined as a total score ≥ 10 on the Patient Health Questionnaire-15 (PHQ-15), others were classified as non PSS (NPSS). The PHQ-9 for de-pression, the Generalized Anxiety Disorder Scale (GAD-7) for anxiety, the Clinical Global Impression-Severity (CGI-S) for clinical status, and the Visual Analogue Scale (VAS) for health status were utilised. Of 207 participants, 126 (60.9%) were PSS and 81 (39.1%) were classified as NPSS. The proportion of patients showing severe symptoms (65.1% vs. 24.7%) and recurrence of depression (74.6% vs. 49.4%), the CGI-S (4.6 vs. 4.1), the PHQ-9 (16.8 vs. 11.1), and the GAD-7 (8.3 vs 6.7) scores were significantly higher in PSS than in NPSS, while the VAS (39.4 vs. 51.2) was significantly lower in PSS than in NPSS. The improvement of depressive symptoms (-1.3 vs. -2.0) measured by the changes in CGI-S was also significantly less in PSS than in NPSS after 6 months treatment. Our findings have shown the significant impact of somatic symptoms on the symptomatology as well as treatment outcomes in Korean female patients with MDD, indicating that clinicians should carefully evaluate somatic symptoms in patients with MDD in routine clinical practice. Due to the methodological shortcomings of the present study, further adequately powered and well-designed investigations are necessary.

Somatic Symptoms and Diseases are more Common in Women Exposed to Violence

PubMed Central

Schei, Berit; Eskild, Anne

2007-01-01

BACKGROUND Exposure to violence has been shown to have an impact on somatic health. However, our knowledge about the possible dose–response relationship between frequency of violence exposure and health is still limited. OBJECTIVE To study the associations between recent and repetitive exposure to violence and presence of somatic symptoms and diseases in women. DESIGN Cross-sectional, community-based, self-reporting survey. PARTICIPANTS Two thousand seven hundred thirty women aged 18–40 years (mean age 30.5 years). MEASUREMENTS The somatic symptom scale derived from the Primary Care Evaluation of Mental Disorders was used to obtain information on the presence of somatization. In addition, we asked about the presence of 11 diseases or organ-specific diseases. Exposure to violence was measured by the Abuse Assessment Screen. RESULTS Eighteen percent (486/2,730) of women surveyed reported exposure to physical violence. Three percent (94/2,730) had been forced into sexual intercourse as an adult. All somatic symptoms, and several diseases, were significantly more common in women exposed to physical and/or sexual violence as compared to nonexposed women. Women exposed to 3 or more violent episodes in the past 12 months reported a presence of 4.8 somatic symptoms and 1.2 diseases (mean) as compared to 1.8 symptoms and 0.5 diseases in nonexposed women. Women with exposure to both physical and sexual violence reported 6.0 symptoms and 1.5 diseases. The impact of violence on somatic symptoms and diseases remained after controlling for depression and sociodemographic factors. CONCLUSIONS Violence was associated with the presence of somatic symptoms and diseases. The more a woman is exposed to violence, the higher the number of somatic symptoms and diseases reported is. PMID:17922169

Factors accounting for the association between anxiety and depression, and eczema: the Hordaland health study (HUSK)

PubMed Central

2010-01-01

Background The association between anxiety and depression, and eczema is well known in the literature, but factors underlying this association remain unclear. Low levels of omega-3 fatty acids and female gender have been found to be associated with both depression and eczema. Somatization and health anxiety are known to be associated with anxiety and depression, further, somatization symptoms and health anxiety have also been found in several dermatological conditions. Accordingly, omega-3 fatty acid supplement, female gender, somatization and health anxiety are possible contributing factors in the association between anxiety and depression, and eczema. The aim of the study is to examine the relevance of proposed contributing factors for the association between anxiety and depression, and eczema, including, omega-3 fatty acid supplement, female gender, health anxiety and somatization. Methods Anxiety and depression was measured in the general population (n = 15715) employing the Hospital Anxiety and Depression Scale (HADS). Information on eczema, female gender, omega-3 fatty acid supplement, health anxiety and somatization was obtained by self-report. Results Somatization and health anxiety accounted for more than half of the association between anxiety/depression, and eczema, while the other factors examined were of minor relevance for the association of interest. Conclusions We found no support for female gender and omega-3 fatty acid supplement as contributing factors in the association between anxiety/depression, and eczema. Somatization and health anxiety accounted for about half of the association between anxiety/depression, and eczema, somatization contributed most. The association between anxiety/depression, and eczema was insignificant after adjustment for somatization and health anxiety. Biological mechanisms underlying the mediating effect of somatization are yet to be revealed. PMID:20412596

TCPs, WUSs, and WINDs: families of transcription factors that regulate shoot meristem formation, stem cell maintenance, and somatic cell differentiation.

PubMed

Ikeda, Miho; Ohme-Takagi, Masaru

2014-01-01

In contrast to somatic mammalian cells, which cannot alter their fate, plant cells can dedifferentiate to form totipotent callus cells and regenerate a whole plant, following treatment with specific phytohormones. However, the regulatory mechanisms and key factors that control differentiation-dedifferentiation and cell totipotency have not been completely clarified in plants. Recently, several plant transcription factors that regulate meristem formation and dedifferentiation have been identified and include members of the TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP), WUSCHEL (WUS), and WOUND INDUCED DEDIFFERENTIATION (WIND1) families. WUS and WIND positively control plant cell totipotency, while TCP negatively controls it. Interestingly, TCP is a transcriptional activator that acts as a negative regulator of shoot meristem formation, and WUS is a transcriptional repressor that positively maintains totipotency of the stem cells of the shoot meristem. We describe here the functions of TCP, WUS, and WIND transcription factors in the regulation of differentiation-dedifferentiation by positive and negative transcriptional regulators.

Neurostimulation for bladder evacuation: is sacral root stimulation a substitute for microstimulation?

PubMed

Probst, M; Piechota, H J; Hohenfellner, M; Gleason, C A; Tanagho, E A

1997-04-01

To determine by anatomical and functional studies whether stimulation of sacral rootlets might permit selective stimulation of autonomic fibres, thus avoiding the detrusor/sphincter dyssynergia characteristic of current techniques of neurostimulation for bladder evacuation. In 10 male mongrel dogs, the S2 root was isolated and its constituent rootlets followed from their origin in the spinal cord to the point of exit from the dura. The entire root and the individual rootlets were then stimulated, including intra- and extra-dural stimulation and at proximal, mid and distal levels. Neuroanatomical and histological findings showed that rootlets of ventral S2 maintain their identity throughout their intradural course; some carry predominantly autonomic fibres, some predominantly somatic and some a mixture of the two. It appears surgically feasible to identify, isolate and sever the predominantly somatic rootlets intradurally, sparing the predominantly autonomic rootlets for inclusion in extradural electrode placement around the entire sacral root, thus eliminating sphincteric interference with detrusor contraction for voiding at low pressure.

Somatic hypermutation in MutS homologue (MSH)3-, MSH6-, and MSH3/MSH6-deficient mice reveals a role for the MSH2-MSH6 heterodimer in modulating the base substitution pattern.

PubMed

Wiesendanger, M; Kneitz, B; Edelmann, W; Scharff, M D

2000-02-07

Although the primary function of the DNA mismatch repair (MMR) system is to identify and correct base mismatches that have been erroneously introduced during DNA replication, recent studies have further implicated several MMR components in somatic hypermutation of immunoglobulin (Ig) genes. We studied the immune response in mice deficient in MutS homologue (MSH)3 and MSH6, two mutually exclusive partners of MSH2 that have not been examined previously for their role in Ig hypermutation. In Msh6(-)/- and Msh3(-)/-/Msh6(-)/- mice, base substitutions are preferentially targeted to G and C nucleotides and to an RGYW hot spot, as has been shown previously in Msh2(-)/- mice. In contrast, Msh3(-)/- mice show no differences from their littermate controls. These findings indicate that the MSH2-MSH6 heterodimer, but not the MSH2-MSH3 complex, is responsible for modulating Ig hypermutation.

Physical "phantasies" and family functions: overcoming the mind/body dualism in somatization.

PubMed

Redekop, F; Stuart, S; Mertens, C

1999-01-01

In this article, we examine some of the ways in which family therapists have conceptualized the experience of illness of unexplained physical origin. We argue that opinions about the etiology of somatic symptoms should not be the primary focus of therapeutic work with people who share the prototypical characteristics of what has been defined as "somatization disorder." We suggest that current research in neurobiology can expand the linguistic resources of clinicians and help them avoid perpetuating unhelpful dichotomies between the mind and the body.

A systems approach defining constraints of the genome architecture on lineage selection and evolvability during somatic cancer evolution

PubMed Central

Rübben, Albert; Nordhoff, Ole

2013-01-01

Summary Most clinically distinguishable malignant tumors are characterized by specific mutations, specific patterns of chromosomal rearrangements and a predominant mechanism of genetic instability but it remains unsolved whether modifications of cancer genomes can be explained solely by mutations and selection through the cancer microenvironment. It has been suggested that internal dynamics of genomic modifications as opposed to the external evolutionary forces have a significant and complex impact on Darwinian species evolution. A similar situation can be expected for somatic cancer evolution as molecular key mechanisms encountered in species evolution also constitute prevalent mutation mechanisms in human cancers. This assumption is developed into a systems approach of carcinogenesis which focuses on possible inner constraints of the genome architecture on lineage selection during somatic cancer evolution. The proposed systems approach can be considered an analogy to the concept of evolvability in species evolution. The principal hypothesis is that permissive or restrictive effects of the genome architecture on lineage selection during somatic cancer evolution exist and have a measurable impact. The systems approach postulates three classes of lineage selection effects of the genome architecture on somatic cancer evolution: i) effects mediated by changes of fitness of cells of cancer lineage, ii) effects mediated by changes of mutation probabilities and iii) effects mediated by changes of gene designation and physical and functional genome redundancy. Physical genome redundancy is the copy number of identical genetic sequences. Functional genome redundancy of a gene or a regulatory element is defined as the number of different genetic elements, regardless of copy number, coding for the same specific biological function within a cancer cell. Complex interactions of the genome architecture on lineage selection may be expected when modifications of the genome architecture have multiple and possibly opposed effects which manifest themselves at disparate times and progression stages. Dissection of putative mechanisms mediating constraints exerted by the genome architecture on somatic cancer evolution may provide an algorithm for understanding and predicting as well as modifying somatic cancer evolution in individual patients. PMID:23336076

Somatization revisited: diagnosis and perceived causes of common mental disorders.

PubMed

Henningsen, Peter; Jakobsen, Thorsten; Schiltenwolf, Marcus; Weiss, Mitchell G

2005-02-01

The assessment of somatoform disorders is complicated by persistent theoretical and practical questions of classification and assessment. Critical rethinking of professional concepts of somatization suggests the value of complementary assessment of patients' illness explanatory models of somatoform and other common mental disorders. We undertook this prospective study to assess medically unexplained somatic symptoms and their patient-perceived causes of illness and to show how patients' explanatory models relate to professional diagnoses of common mental disorders and how they may predict the short-term course of illness. Tertiary care patients (N=186) with prominent somatoform symptoms were evaluated with the Structured Clinical Interview for DSM-IV, a locally adapted Explanatory Model Interview to elicit patients' illness experience (priority symptoms) and perceived causes, and clinical self-report questionnaires. The self-report questionnaires were administered at baseline and after 6 months. Diagnostic overlap between somatoform, depressive, and anxiety disorders occurred frequently (79.6%). Patients explained pure somatoform disorders mainly with organic causal attributions; they explained pure depressive and/or anxiety disorders mainly with psychosocial perceived causes, and patients in the diagnostic overlap group typically reported mixed causal attributions. In this last group, among patients with similar levels of symptom severity, organic perceived causes were related to a lower physical health sum score on the MOS Short Form, and psychosocial perceived causes were related to less severe depressive symptoms, assessed with the Hospital Anxiety and Depression Scale at 6 months. Among patients meeting criteria for comorbid somatoform with anxiety and/or depressive disorders, complementary assessment of patient-perceived causes, a key element of illness explanatory models, was related to levels of functional impairment and short-term prognosis. For such patients, causal attributions may be particularly useful to clarify clinically significant features of common mental disorders and thereby contribute to clinical assessment.

Sperm quality assays: How good are they? The horse perspective.

PubMed

Love, Charles C

2018-04-22

Sperm quality assays have increased in number in the last 10 years. Most of these assays are flow cytometry based in application and are modified from assays that have been developed to measure somatic cell function. The goal of any sperm quality assay should be to advance the clinicians/researchers understanding of sperm cell function and the relationship to fertility. While these assays appear to measure somatic cell-like functions in sperm there tends to be little understanding how the results of these assays relate to fertility. Copyright © 2018. Published by Elsevier B.V.

Somatic and vicarious pain are represented by dissociable multivariate brain patterns

PubMed Central

Krishnan, Anjali; Woo, Choong-Wan; Chang, Luke J; Ruzic, Luka; Gu, Xiaosi; López-Solà, Marina; Jackson, Philip L; Pujol, Jesús; Fan, Jin; Wager, Tor D

2016-01-01

Understanding how humans represent others’ pain is critical for understanding pro-social behavior. ‘Shared experience’ theories propose common brain representations for somatic and vicarious pain, but other evidence suggests that specialized circuits are required to experience others’ suffering. Combining functional neuroimaging with multivariate pattern analyses, we identified dissociable patterns that predicted somatic (high versus low: 100%) and vicarious (high versus low: 100%) pain intensity in out-of-sample individuals. Critically, each pattern was at chance in predicting the other experience, demonstrating separate modifiability of both patterns. Somatotopy (upper versus lower limb: 93% accuracy for both conditions) was also distinct, located in somatosensory versus mentalizing-related circuits for somatic and vicarious pain, respectively. Two additional studies demonstrated the generalizability of the somatic pain pattern (which was originally developed on thermal pain) to mechanical and electrical pain, and also demonstrated the replicability of the somatic/vicarious dissociation. These findings suggest possible mechanisms underlying limitations in feeling others’ pain, and present new, more specific, brain targets for studying pain empathy. DOI: http://dx.doi.org/10.7554/eLife.15166.001 PMID:27296895

Cerebral responses to innocuous somatic pressure stimulation following aerobic exercise rehabilitation in chronic pain patients: a functional magnetic resonance imaging study

PubMed Central

Micalos, Peter S; Korgaonkar, Mayuresh S; Drinkwater, Eric J; Cannon, Jack; Marino, Frank E

2014-01-01

Objective The purpose of this research was to assess the functional brain activity and perceptual rating of innocuous somatic pressure stimulation before and after exercise rehabilitation in patients with chronic pain. Materials and methods Eleven chronic pain patients and eight healthy pain-free controls completed 12 weeks of supervised aerobic exercise intervention. Perceptual rating of standardized somatic pressure stimulation (2 kg) on the right anterior mid-thigh and brain responses during functional magnetic resonance imaging (fMRI) were assessed at pre- and postexercise rehabilitation. Results There was a significant difference in the perceptual rating of innocuous somatic pressure stimulation between the chronic pain and control groups (P=0.02) but no difference following exercise rehabilitation. Whole brain voxel-wise analysis with correction for multiple comparisons revealed trends for differences in fMRI responses between the chronic pain and control groups in the superior temporal gyrus (chronic pain > control, corrected P=0.30), thalamus, and caudate (control > chronic, corrected P=0.23). Repeated measures of the regions of interest (5 mm radius) for blood oxygen level-dependent signal response revealed trend differences for superior temporal gyrus (P=0.06), thalamus (P=0.04), and caudate (P=0.21). Group-by-time interactions revealed trend differences in the caudate (P=0.10) and superior temporal gyrus (P=0.29). Conclusion Augmented perceptual and brain responses to innocuous somatic pressure stimulation were shown in the chronic pain group compared to the control group; however, 12-weeks of exercise rehabilitation did not significantly attenuate these responses. PMID:25210471

Somatic mutations affect key pathways in lung adenocarcinoma

PubMed Central

Ding, Li; Getz, Gad; Wheeler, David A.; Mardis, Elaine R.; McLellan, Michael D.; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Muzny, Donna M.; Morgan, Margaret B.; Fulton, Lucinda; Fulton, Robert S.; Zhang, Qunyuan; Wendl, Michael C.; Lawrence, Michael S.; Larson, David E.; Chen, Ken; Dooling, David J.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin; Metcalf, Ginger A.; Ng, Brian; Milosavljevic, Aleksandar; Gonzalez-Garay, Manuel L.; Osborne, John R.; Meyer, Rick; Shi, Xiaoqi; Tang, Yuzhu; Koboldt, Daniel C.; Lin, Ling; Abbott, Rachel; Miner, Tracie L.; Pohl, Craig; Fewell, Ginger; Haipek, Carrie; Schmidt, Heather; Dunford-Shore, Brian H.; Kraja, Aldi; Crosby, Seth D.; Sawyer, Christopher S.; Vickery, Tammi; Sander, Sacha; Robinson, Jody; Winckler, Wendy; Baldwin, Jennifer; Chirieac, Lucian R.; Dutt, Amit; Fennell, Tim; Hanna, Megan; Johnson, Bruce E.; Onofrio, Robert C.; Thomas, Roman K.; Tonon, Giovanni; Weir, Barbara A.; Zhao, Xiaojun; Ziaugra, Liuda; Zody, Michael C.; Giordano, Thomas; Orringer, Mark B.; Roth, Jack A.; Spitz, Margaret R.; Wistuba, Ignacio I.; Ozenberger, Bradley; Good, Peter J.; Chang, Andrew C.; Beer, David G.; Watson, Mark A.; Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William; Province, Michael A.; Weinstock, George M.; Varmus, Harold E.; Gabriel, Stacey B.; Lander, Eric S.; Gibbs, Richard A.; Meyerson, Matthew; Wilson, Richard K.

2009-01-01

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers—including NF1, APC, RB1 and ATM—and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment. PMID:18948947

Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes.

PubMed

Nakagawa, Kenji; Gonzalez-Roca, Eva; Souto, Alejandro; Kawai, Toshinao; Umebayashi, Hiroaki; Campistol, Josep María; Cañellas, Jeronima; Takei, Syuji; Kobayashi, Norimoto; Callejas-Rubio, Jose Luis; Ortego-Centeno, Norberto; Ruiz-Ortiz, Estíbaliz; Rius, Fina; Anton, Jordi; Iglesias, Estibaliz; Jimenez-Treviño, Santiago; Vargas, Carmen; Fernandez-Martin, Julian; Calvo, Inmaculada; Hernández-Rodríguez, José; Mendez, María; Dordal, María Teresa; Basagaña, Maria; Bujan, Segundo; Yashiro, Masato; Kubota, Tetsuo; Koike, Ryuji; Akuta, Naoko; Shimoyama, Kumiko; Iwata, Naomi; Saito, Megumu K; Ohara, Osamu; Kambe, Naotomo; Yasumi, Takahiro; Izawa, Kazushi; Kawai, Tomoki; Heike, Toshio; Yagüe, Jordi; Nishikomori, Ryuta; Aróstegui, Juan I

2015-03-01

: Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ≈35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes. To evaluate somatic NLRP3 mosaicism as the disease-causing mechanism in patients with clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative. NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)-dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. A variable degree (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled patients, all of them with a MWS phenotype. Six different missense variants, three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and functional analyses confirmed that they were disease-causing, gain-of-function NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long-lasting positive responses. We herein show somatic NLRP3 mosaicism underlying MWS, probably representing a shared genetic mechanism in CAPS not restricted to CINCA syndrome. The data here described allowed definitive diagnoses of these patients, which had serious implications for gaining access to anti-interleukin 1 treatments under legal indication and for genetic counselling. The detection of somatic mosaicism is difficult when using conventional methods. Potential candidates should benefit from the use of modern genetic tools. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Illness perceptions of people with long-term conditions are associated with frequent use of the emergency department independent of mental illness and somatic symptom burden.

PubMed

Ninou, Aggeliki; Guthrie, Elspeth; Paika, Vassiliki; Ntountoulaki, Elisavet; Tomenson, Barbara; Tatsioni, Athina; Karagiannopoulou, Evangelia; Carvalho, Andre F; Hyphantis, Thomas

2016-02-01

To determine whether illness perceptions of patients with long-term conditions (LTCs) are associated with urgent healthcare use and whether this association is independent from mental illness and somatic symptom burden. Illness perceptions (B-IPQ) and somatic symptom severity (PHQ-15) were assessed in 304 patients with diabetes, rheumatological disorders and COPD attending an Accident and Emergency Department (AED) in Greece over a one year period. The presence of mental illness was determined by the Mini International Neuropsychiatric Interview. A Generalized Linear Model (Negative Binomial) regression was used to determine the associations of illness perceptions with AED use after adjusting for mental illness, somatic symptom severity, disease parameters and demographics. Eighty-six patients (28.3%) reported at least one visit to the AED during the previous year and 75 (24.7%) twice or more. 124 patients (40.8%) had some form of mental disorder with 85 (28.0%) meeting criteria for major depressive disorder. The degree to which the patients had an understanding of their illness (illness comprehensibility) (p<0.01) along with younger age (p<0.05), additional comorbidities (p<0.05) and greater somatic symptom burden (p<0.001) was strongly associated with AED use; AED visits were expected to be reduced by 9.1% for each unit increase in illness comprehensibility. The way people perceive their illness influences urgent healthcare seeking behavior independent of somatic symptom burden. This finding indicates that information provision may prove effective in reducing urgent healthcare use and encourage the design of psycho-educational interventions targeting disease-related cognitions in an attempt to prevent unnecessary healthcare utilization. Copyright © 2016 Elsevier Inc. All rights reserved.

Pms2 Suppresses Large Expansions of the (GAA·TTC)n Sequence in Neuronal Tissues

PubMed Central

Bourn, Rebecka L.; De Biase, Irene; Pinto, Ricardo Mouro; Sandi, Chiranjeevi; Al-Mahdawi, Sahar; Pook, Mark A.; Bidichandani, Sanjay I.

2012-01-01

Expanded trinucleotide repeat sequences are the cause of several inherited neurodegenerative diseases. Disease pathogenesis is correlated with several features of somatic instability of these sequences, including further large expansions in postmitotic tissues. The presence of somatic expansions in postmitotic tissues is consistent with DNA repair being a major determinant of somatic instability. Indeed, proteins in the mismatch repair (MMR) pathway are required for instability of the expanded (CAG·CTG)n sequence, likely via recognition of intrastrand hairpins by MutSβ. It is not clear if or how MMR would affect instability of disease-causing expanded trinucleotide repeat sequences that adopt secondary structures other than hairpins, such as the triplex/R-loop forming (GAA·TTC)n sequence that causes Friedreich ataxia. We analyzed somatic instability in transgenic mice that carry an expanded (GAA·TTC)n sequence in the context of the human FXN locus and lack the individual MMR proteins Msh2, Msh6 or Pms2. The absence of Msh2 or Msh6 resulted in a dramatic reduction in somatic mutations, indicating that mammalian MMR promotes instability of the (GAA·TTC)n sequence via MutSα. The absence of Pms2 resulted in increased accumulation of large expansions in the nervous system (cerebellum, cerebrum, and dorsal root ganglia) but not in non-neuronal tissues (heart and kidney), without affecting the prevalence of contractions. Pms2 suppressed large expansions specifically in tissues showing MutSα-dependent somatic instability, suggesting that they may act on the same lesion or structure associated with the expanded (GAA·TTC)n sequence. We conclude that Pms2 specifically suppresses large expansions of a pathogenic trinucleotide repeat sequence in neuronal tissues, possibly acting independently of the canonical MMR pathway. PMID:23071719

Pms2 suppresses large expansions of the (GAA·TTC)n sequence in neuronal tissues.

PubMed

Bourn, Rebecka L; De Biase, Irene; Pinto, Ricardo Mouro; Sandi, Chiranjeevi; Al-Mahdawi, Sahar; Pook, Mark A; Bidichandani, Sanjay I

2012-01-01

Expanded trinucleotide repeat sequences are the cause of several inherited neurodegenerative diseases. Disease pathogenesis is correlated with several features of somatic instability of these sequences, including further large expansions in postmitotic tissues. The presence of somatic expansions in postmitotic tissues is consistent with DNA repair being a major determinant of somatic instability. Indeed, proteins in the mismatch repair (MMR) pathway are required for instability of the expanded (CAG·CTG)(n) sequence, likely via recognition of intrastrand hairpins by MutSβ. It is not clear if or how MMR would affect instability of disease-causing expanded trinucleotide repeat sequences that adopt secondary structures other than hairpins, such as the triplex/R-loop forming (GAA·TTC)(n) sequence that causes Friedreich ataxia. We analyzed somatic instability in transgenic mice that carry an expanded (GAA·TTC)(n) sequence in the context of the human FXN locus and lack the individual MMR proteins Msh2, Msh6 or Pms2. The absence of Msh2 or Msh6 resulted in a dramatic reduction in somatic mutations, indicating that mammalian MMR promotes instability of the (GAA·TTC)(n) sequence via MutSα. The absence of Pms2 resulted in increased accumulation of large expansions in the nervous system (cerebellum, cerebrum, and dorsal root ganglia) but not in non-neuronal tissues (heart and kidney), without affecting the prevalence of contractions. Pms2 suppressed large expansions specifically in tissues showing MutSα-dependent somatic instability, suggesting that they may act on the same lesion or structure associated with the expanded (GAA·TTC)(n) sequence. We conclude that Pms2 specifically suppresses large expansions of a pathogenic trinucleotide repeat sequence in neuronal tissues, possibly acting independently of the canonical MMR pathway.

Functional Abdominal Pain: "Get" the Function, Loose the Pain.

PubMed

Draeger-Muenke, Reinhild

2015-07-01

Functional abdominal pain is a mind-body, psychosocial, and self-reinforcing experience with significant consequences for the sufferer and the surrounding support network. The occurrence of unpredictable symptoms and their severity add an element of dread and feeling out-of-control to daily life and often reduce overall functioning in a downward spiral. Two clinical presentations of functional abdominal pain are offered in this article (composites to protect confidentiality) dealing with abdominal pain syndrome and abdominal migraines. The treatment demonstrates the use of hypnotic principles for self-regulation, exploration, and meaning-making. Hypnosis treatment is conducted in combination with mindfulness-based interventions and Traditional Chinese Medicine's (TCM) teachings regarding abdominal health and illness. The clinical examples illustrate medical findings that suggest children with early life stress and an early onset of gastrointestinal somatization may not simply outgrow their functional abdominal pain but may suffer into adulthood.

Effects of nanotopography on stem cell phenotypes.

PubMed

Ravichandran, Rajeswari; Liao, Susan; Ng, Clarisse Ch; Chan, Casey K; Raghunath, Michael; Ramakrishna, Seeram

2009-12-31

Stem cells are unspecialized cells that can self renew indefinitely and differentiate into several somatic cells given the correct environmental cues. In the stem cell niche, stem cell-extracellular matrix (ECM) interactions are crucial for different cellular functions, such as adhesion, proliferation, and differentiation. Recently, in addition to chemical surface modifications, the importance of nanometric scale surface topography and roughness of biomaterials has increasingly becoming recognized as a crucial factor for cell survival and host tissue acceptance in synthetic ECMs. This review describes the influence of nanotopography on stem cell phenotypes.

Growth, Nutritional Status, and Pulmonary Function in Children with Chronic Recurrent Bronchitis.

PubMed

Umławska, Wioleta; Lipowicz, Anna

2016-01-01

Bronchitis is a common health problem in children. Frequent bronchitis in infancy increases the risk of developing chronic respiratory diseases. The aim of the study was to assess the level of growth and the nutritional status in children and youths with special regard to the level of body fatness assessed by measuring skin-fold thickness. Relationships between somatic development, pulmonary function and the course of the disease were also explored. The study was carried out using anthropometric and spirometric measurements and also information on the severity and course of the disease in 141 children with chronic or recurrent bronchitis. All of the subjects were patients of the Pulmonary Medicine and Allergology Center in Karpacz, Poland. The mean body height did not differ significantly between the children examined and their healthy peers. However, the infection-prone children had excessive body fatness and muscle mass deficiency. The increased level of subcutaneous adipose tissue occurred especially in children with short duration of the disease, i.e. a maximum of 1 year. The functional lung parameters were generally normal. The presence of atopic diseases such as allergic rhinitis or atopic dermatitis did not impair the course of the children's somatic development. Also, long-term disease or the presence of additional allergic diseases did not impair lung function in the examined children. Taking appropriate preventive measures is recommended to achieve and maintain normal body weight in children who receive therapy due to bronchitis.

Flow cytometric and morphological analyses of Pinus pinaster somatic embryogenesis.

PubMed

Marum, Liliana; Loureiro, João; Rodriguez, Eleazar; Santos, Conceição; Oliveira, M Margarida; Miguel, Célia

2009-09-25

An approach combining morphological profiling and flow cytometric analysis was used to assess genetic stability during the several steps of somatic embryogenesis in Pinus pinaster. Embryogenic cell lines of P. pinaster were established from immature zygotic embryos excised from seeds obtained from open-pollinated trees. During the maturation stage, phenotype of somatic embryos was characterized as being either normal or abnormal. Based upon the prevalent morphological traits, different types of abnormal embryos underwent further classification and quantification. Nuclear DNA content of maritime pine using the zygotic embryos was estimated to be 57.04 pg/2C, using propidium iodide flow cytometry. According to the same methodology, no significant differences (P< or =0.01) in DNA ploidy were detected among the most frequently observed abnormal phenotypes, embryogenic cell lines, zygotic and normal somatic embryos, and somatic embryogenesis-derived plantlets. Although the differences in DNA ploidy level do not exclude the occurrence of a low level of aneuploidy, the results obtained point to the absence of major changes in ploidy level during the somatic embryogenesis process of this economically important species. Therefore, our primary goal of true-to-typeness was assured at this level.

Somatic deleterious mutation rate in a woody plant: estimation from phenotypic data

PubMed Central

Bobiwash, K; Schultz, S T; Schoen, D J

2013-01-01

We conducted controlled crosses in populations of the long-lived clonal shrub, Vaccinium angustifolium (lowbush blueberry) to estimate inbreeding depression and mutation parameters associated with somatic deleterious mutation. Inbreeding depression level was high, with many plants failing to set fruit after self-pollination. We also compared fruit set from autogamous pollinations (pollen collected from within the same inflorescence) with fruit set from geitonogamous pollinations (pollen collected from the same plant but from inflorescences separated by several meters of branch growth). The difference between geitonogamous versus autogamous fitness within single plants is referred to as ‘autogamy depression' (AD). AD can be caused by somatic deleterious mutation. AD was significantly different from zero for fruit set. We developed a maximum-likelihood procedure to estimate somatic mutation parameters from AD, and applied it to geitonogamous and autogamous fruit set data from this experiment. We infer that, on average, approximately three sublethal, partially dominant somatic mutations exist within the crowns of the plants studied. We conclude that somatic mutation in this woody plant results in an overall genomic deleterious mutation rate that exceeds the rate measured to date for annual plants. Some implications of this result for evolutionary biology and agriculture are discussed. PMID:23778990

Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms

PubMed Central

Milosevic Feenstra, Jelena D.; Nivarthi, Harini; Gisslinger, Heinz; Leroy, Emilie; Rumi, Elisa; Chachoua, Ilyas; Bagienski, Klaudia; Kubesova, Blanka; Pietra, Daniela; Gisslinger, Bettina; Milanesi, Chiara; Jäger, Roland; Chen, Doris; Berg, Tiina; Schalling, Martin; Schuster, Michael; Bock, Christoph; Constantinescu, Stefan N.; Cazzola, Mario

2016-01-01

Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic diseases characterized by clonal hematopoiesis and hyperproliferation of terminally differentiated myeloid cells. The disease is driven by somatic mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the remaining cases are termed “triple negative.” We aimed to identify the disease-causing mutations in the triple-negative cases of ET and PMF by applying whole-exome sequencing (WES) on paired tumor and control samples from 8 patients. We found evidence of clonal hematopoiesis in 5 of 8 studied cases based on clonality analysis and presence of somatic genetic aberrations. WES identified somatic mutations in 3 of 8 cases. We did not detect any novel recurrent somatic mutations. In 3 patients with clonal hematopoiesis analyzed by WES, we identified a somatic MPL-S204P, a germline MPL-V285E mutation, and a germline JAK2-G571S variant. We performed Sanger sequencing of the entire coding region of MPL in 62, and of JAK2 in 49 additional triple-negative cases of ET or PMF. New somatic (T119I, S204F, E230G, Y591D) and 1 germline (R321W) MPL mutation were detected. All of the identified MPL mutations were gain-of-function when analyzed in functional assays. JAK2 variants were identified in 5 of 57 triple-negative cases analyzed by WES and Sanger sequencing combined. We could demonstrate that JAK2-V625F and JAK2-F556V are gain-of-function mutations. Our results suggest that triple-negative cases of ET and PMF do not represent a homogenous disease entity. Cases with polyclonal hematopoiesis might represent hereditary disorders. PMID:26423830

Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms.

PubMed

Milosevic Feenstra, Jelena D; Nivarthi, Harini; Gisslinger, Heinz; Leroy, Emilie; Rumi, Elisa; Chachoua, Ilyas; Bagienski, Klaudia; Kubesova, Blanka; Pietra, Daniela; Gisslinger, Bettina; Milanesi, Chiara; Jäger, Roland; Chen, Doris; Berg, Tiina; Schalling, Martin; Schuster, Michael; Bock, Christoph; Constantinescu, Stefan N; Cazzola, Mario; Kralovics, Robert

2016-01-21

Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic diseases characterized by clonal hematopoiesis and hyperproliferation of terminally differentiated myeloid cells. The disease is driven by somatic mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the remaining cases are termed "triple negative." We aimed to identify the disease-causing mutations in the triple-negative cases of ET and PMF by applying whole-exome sequencing (WES) on paired tumor and control samples from 8 patients. We found evidence of clonal hematopoiesis in 5 of 8 studied cases based on clonality analysis and presence of somatic genetic aberrations. WES identified somatic mutations in 3 of 8 cases. We did not detect any novel recurrent somatic mutations. In 3 patients with clonal hematopoiesis analyzed by WES, we identified a somatic MPL-S204P, a germline MPL-V285E mutation, and a germline JAK2-G571S variant. We performed Sanger sequencing of the entire coding region of MPL in 62, and of JAK2 in 49 additional triple-negative cases of ET or PMF. New somatic (T119I, S204F, E230G, Y591D) and 1 germline (R321W) MPL mutation were detected. All of the identified MPL mutations were gain-of-function when analyzed in functional assays. JAK2 variants were identified in 5 of 57 triple-negative cases analyzed by WES and Sanger sequencing combined. We could demonstrate that JAK2-V625F and JAK2-F556V are gain-of-function mutations. Our results suggest that triple-negative cases of ET and PMF do not represent a homogenous disease entity. Cases with polyclonal hematopoiesis might represent hereditary disorders. © 2016 by The American Society of Hematology.

The English version of the four-dimensional symptom questionnaire (4DSQ) measures the same as the original Dutch questionnaire: a validation study.

PubMed

Terluin, Berend; Smits, Niels; Miedema, Baukje

2014-12-01

Translations of questionnaires need to be carefully validated to assure that the translation measures the same construct(s) as the original questionnaire. The four-dimensional symptom questionnaire (4DSQ) is a Dutch self-report questionnaire measuring distress, depression, anxiety and somatization. To evaluate the equivalence of the English version of the 4DSQ. 4DSQ data of English and Dutch speaking general practice attendees were analysed and compared. The English speaking group consisted of 205 attendees, aged 18-64 years, in general practice, in Canada whereas the Dutch group consisted of 302 general practice attendees in the Netherlands. Differential item functioning (DIF) analysis was conducted using the Mantel-Haenszel method and ordinal logistic regression. Differential test functioning (DTF; i.e., the scale impact of DIF) was evaluated using linear regression analysis. DIF was detected in 2/16 distress items, 2/6 depression items, 2/12 anxiety items, and 1/16 somatization items. With respect to mean scale scores, the impact of DIF on the scale level was negligible for all scales. On the anxiety scale DIF caused the English speaking patients with moderate to severe anxiety to score about one point lower than Dutch patients with the same anxiety level. The English 4DSQ measures the same constructs like the original Dutch 4DSQ. The distress, depression and somatization scales can employ the same cut-off points as the corresponding Dutch scales. However, cut-off points of the English 4DSQ anxiety scale should be lowered by one point to retain the same meaning as the Dutch anxiety cut-off points.

Integration of DSM-III and ICD-8 to be used in a consultation-liaison psychiatric service. Preliminary experiences.

PubMed

Poulsen, D L; Zierau, F; Eplov, L; Jepsen, P W; Kastrup, M; Kijne, B; Rasmussen, S; Stubgaard, M; Bech, P

1987-01-01

In 1983 a total of 405 patients received psychiatric supervision in somatic departments in the general hospital. At this supervision, these patients were registered by means of a five-axial diagnostic coding according to the DMS III principle, and this was combined with a quantitative global assessment of the severity of the condition. Reliability testing was undertaken by five supervising physicians with a total of 15 patients. The total number of supervisions constituted one supervision per somatic bed per annum. Women were overrepresented, and medical departments made the greatest use of psychiatric supervision. Reactive conditions dominated parallel with a high relative incidence of alcohol-related conditions. In patients with diagnoses of psychoses, only slight to moderate psychiatric symptoms were encountered. This held true also for personality deviations. 50% of the patients had experienced significant psychosocial stress, but 10% of these were diagnosed as having non-reactive psychoses, 52% of the patients had moderate to pronounced disturbances of social function. Half of the patients supervised in this manner could be investigated or treated in the referring departments. Approximately half of the patients in whom referral to private psychiatric specialists was made did not keep these appointments. Reliability testing in the material shows the employability of the diagnostic armamentarium. All in all, the investigation suggests that extension of the liaison psychiatric service in somatic departments would result in a relative increase in the number of patients who could be treated in the referring department and an increase in the number of psychiatric conditions diagnosed. Establishment of a psychiatric outpatient clinic in the somatic environment appears to be indicated.

“Caseness” for Depression and Anxiety in a Depressed Outpatient Population: Symptomatic Outcome as a Function of Baseline Diagnostic Categories

PubMed Central

Verhaeghen, Anne; Dantchev, Nicolas; Grassi, Luigi; Montejo, Angel L.; Perahia, David G. S.; Quail, Deborah; Reed, Catherine; Tylee, Andre; Bauer, Michael

2009-01-01

Objective: To examine the diagnostic status of patients enrolled in the Factors Influencing Depression Endpoints Research (FINDER) study and symptomatic outcomes and baseline characteristics associated with remission 6 months after commencing antidepressant therapy. Method: Status of clinically diagnosed depressed patients was based on self-rated Hospital Anxiety and Depression Scale (HADS) scores. Five diagnostic categories were defined: noncaseness, mixed anxiety-depression (subthreshold depressive and anxious symptomatology), caseness for depression, caseness for anxiety, and caseness for comorbid anxiety-depression. Assessments included the Somatic Symptom Inventory and health-related quality of life (HRQoL) using the Medical Outcomes Study 36-item Short-Form Health Survey. Remission rates (based on HADS noncaseness for both depression and anxiety) and their associations with baseline characteristics were investigated. Patients were enrolled between May 2004 and September 2005. Results: Of the 3,353 patients enrolled, 66.4% met the HADS criteria for probable depressive disorder and 74.1% met the HADS criteria for probable anxiety disorder. Somatic symptom severity (painful and nonpainful) was highest and HRQoL was lowest in the comorbid anxiety-depression group. After 6 months, remission rates were 50.2% for caseness for depression, 40.4% for caseness for anxiety, and 40.6% for caseness for comorbid anxiety-depression. A lower number of previous depressive episodes, shorter current episode duration, lower painful and nonpainful somatic symptom scores, being married, a higher educational level, and working for pay were most consistently associated with higher remission rates. Conclusions: Physicians do not always differentiate between anxiety and depressive symptoms when making a clinical diagnosis of depression. At baseline, most enrolled patients had significant emotional depressive and anxious symptoms, as well as significant nonpainful and painful somatic symptomatology, and these factors were associated with outcome. PMID:20098522

Somatic HLA Mutations Expose the Role of Class I-Mediated Autoimmunity in Aplastic Anemia and its Clonal Complications.

PubMed

Babushok, Daria V; Duke, Jamie L; Xie, Hongbo M; Stanley, Natasha; Atienza, Jamie; Perdigones, Nieves; Nicholas, Peter; Ferriola, Deborah; Li, Yimei; Huang, Hugh; Ye, Wenda; Morrissette, Jennifer J D; Kearns, Jane; Porter, David L; Podsakoff, Gregory M; Eisenlohr, Laurence C; Biegel, Jaclyn A; Chou, Stella T; Monos, Dimitrios S; Bessler, Monica; Olson, Timothy S

2017-10-10

Acquired aplastic anemia (aAA) is an acquired deficiency of early hematopoietic cells, characterized by inadequate blood production, and a predisposition to myelodysplastic syndrome (MDS) and leukemia. Although its exact pathogenesis is unknown, aAA is thought to be driven by Human Leukocyte Antigen (HLA)-restricted T cell immunity, with earlier studies favoring HLA class II-mediated pathways. Using whole exome sequencing (WES), we recently identified two aAA patients with somatic mutations in HLA class I genes. We hypothesized that HLA class I mutations are pathognomonic for autoimmunity in aAA, but were previously underappreciated because the Major Histocompatibility Complex (MHC) region is notoriously difficult to analyze by WES. Using a combination of targeted deep sequencing of HLA class I genes and single nucleotide polymorphism array (SNP-A) genotyping we screened 66 aAA patients for somatic HLA class I loss. We found somatic HLA loss in eleven patients (17%), with thirteen loss-of-function mutations in HLA-A *33:03, HLA-A *68:01, HLA-B *14:02 and HLA-B *40:02 alleles. Three patients had more than one mutation targeting the same HLA allele. Interestingly, HLA-B *14:02 and HLA-B *40:02 were significantly overrepresented in aAA patients, compared to ethnicity-matched controls. Patients who inherited the targeted HLA alleles, regardless of HLA mutation status, had a more severe disease course with more frequent clonal complications as assessed by WES, SNP-A, and metaphase cytogenetics, and more frequent secondary MDS. The finding of recurrent HLA class I mutations provides compelling evidence for a predominant HLA class I-driven autoimmunity in aAA, and establishes a novel link between aAA patients' immunogenetics and clonal evolution.

Somatic HLA mutations expose the role of class I–mediated autoimmunity in aplastic anemia and its clonal complications

PubMed Central

Duke, Jamie L.; Xie, Hongbo M.; Stanley, Natasha; Atienza, Jamie; Perdigones, Nieves; Nicholas, Peter; Ferriola, Deborah; Li, Yimei; Huang, Hugh; Ye, Wenda; Morrissette, Jennifer J. D.; Kearns, Jane; Porter, David L.; Podsakoff, Gregory M.; Eisenlohr, Laurence C.; Biegel, Jaclyn A.; Chou, Stella T.; Monos, Dimitrios S.; Bessler, Monica; Olson, Timothy S.

2017-01-01

Acquired aplastic anemia (aAA) is an acquired deficiency of early hematopoietic cells, characterized by inadequate blood production, and a predisposition to myelodysplastic syndrome (MDS) and leukemia. Although its exact pathogenesis is unknown, aAA is thought to be driven by human leukocyte antigen (HLA)–restricted T cell immunity, with earlier studies favoring HLA class II-mediated pathways. Using whole-exome sequencing (WES), we recently identified 2 patients with aAA with somatic mutations in HLA class I genes. We hypothesized that HLA class I mutations are pathognomonic for autoimmunity in aAA, but were previously underappreciated because the major histocompatibility complex (MHC) region is notoriously difficult to analyze by WES. Using a combination of targeted deep sequencing of HLA class I genes and single nucleotide polymorphism array (SNP-A) genotyping, we screened 66 patients with aAA for somatic HLA class I loss. We found somatic HLA loss in 11 patients (17%), with 13 loss-of-function mutations in HLA-A*33:03, HLA-A*68:01, HLA-B*14:02, and HLA-B*40:02 alleles. Three patients had more than 1 mutation targeting the same HLA allele. Interestingly, HLA-B*14:02 and HLA-B*40:02 were significantly overrepresented in patients with aAA compared with ethnicity-matched controls. Patients who inherited the targeted HLA alleles, regardless of HLA mutation status, had a more severe disease course with more frequent clonal complications as assessed by WES, SNP-A, and metaphase cytogenetics, and more frequent secondary MDS. The finding of recurrent HLA class I mutations provides compelling evidence for a predominant HLA class I-driven autoimmunity in aAA and establishes a novel link between immunogenetics and clonal evolution of patients with aAA. PMID:28971166

A cross-sectional study of growth, nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland

PubMed Central

Sands, Dorota; Zielińska, Anna

2015-01-01

Introduction Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis. Material and methods The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group. Results The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = –0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = –0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = –0.75 and Z-score = –0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure. Conclusions The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters. PMID:25861303

Relation of Psychiatric Symptoms with Epilepsy, Asthma, and Allergy in Youth with ASD vs. Psychiatry Referrals.

PubMed

Weber, Rebecca J; Gadow, Kenneth D

2017-08-01

The present study aimed to characterize the association of psychopathology with the clinical correlates of epilepsy, asthma, and allergy within and between neurobehavioral syndromes. Participants were consecutively evaluated youth (6-18 years, 75 % male) with autism spectrum disorder (ASD; n = 589) and non-ASD outpatient psychiatry referrals (n = 653). Informants completed a background questionnaire (parents) and a psychiatric symptom severity rating scale (parents, teachers). Youth with ASD had higher rates of epilepsy and allergy but not asthma than psychiatry referrals, even when analyses were limited to youth with IQ ≥ 70. Somatic conditions evidenced variable associations with medical services utilization, educational interventions, family income, and maternal education. Youth with ASD with versus without epilepsy had more severe ASD social deficits (parents' ratings) and less severe ASD repetitive behaviors (teachers' ratings). Epilepsy was associated with more severe depression, mania, and schizophrenia symptoms in youth with ASD. Youth with allergy (psychiatry referrals only) had more severe anxiety and depression symptoms (parents' ratings) but less severe aggression (teachers' ratings) thus providing evidence of both context- and diagnostic-specificity. Youth with ASD versus non-ASD psychiatry referrals evidence a variable pattern of relations between somatic conditions and a range of clinical correlates, which suggests that the biologic substrates and psychosocial concomitants of neurodevelopmental disorders and their co-occurring somatic conditions may interact to produce unique clinical phenotypes.

Innexin2 gap junctions in somatic support cells are required for cyst formation and for egg chamber formation in Drosophila.

PubMed

Mukai, Masanori; Kato, Hirotaka; Hira, Seiji; Nakamura, Katsuhiro; Kita, Hiroaki; Kobayashi, Satoru

2011-01-01

Germ cells require intimate associations with surrounding somatic cells during gametogenesis. During oogenesis, gap junctions mediate communication between germ cells and somatic support cells. However, the molecular mechanisms by which gap junctions regulate the developmental processes during oogenesis are poorly understood. We have identified a female sterile allele of innexin2 (inx2), which encodes a gap junction protein in Drosophila. In females bearing this inx2 allele, cyst formation and egg chamber formation are impaired. In wild-type germaria, Inx2 is strongly expressed in escort cells and follicle cells, both of which make close contact with germline cells. We show that inx2 function in germarial somatic cells is required for the survival of early germ cells and promotes cyst formation, probably downstream of EGFR pathway, and that inx2 function in follicle cells promotes egg chamber formation through the regulation of DE-cadherin and Bazooka (Baz) at the boundary between germ cells and follicle cells. Furthermore, genetic experiments demonstrate that inx2 interacts with the zero population growth (zpg) gene, which encodes a germline-specific gap junction protein. These results indicate a multifunctional role for Inx2 gap junctions in somatic support cells in the regulation of early germ cell survival, cyst formation and egg chamber formation. Inx2 gap junctions may mediate the transfer of nutrients and signal molecules between germ cells and somatic support cells, as well as play a role in the regulation of cell adhesion. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

PubMed Central

Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Chapuy, Bjoern; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Zou, Lihua; Gould, Joshua; Saksena, Gordon; Stransky, Nicolas; Rangel-Escareño, Claudia; Fernandez-Lopez, Juan Carlos; Hidalgo-Miranda, Alfredo; Melendez-Zajgla, Jorge; Hernández-Lemus, Enrique; Schwarz-Cruz y Celis, Angela; Imaz-Rosshandler, Ivan; Ojesina, Akinyemi I.; Jung, Joonil; Pedamallu, Chandra S.; Lander, Eric S.; Habermann, Thomas M.; Cerhan, James R.; Shipp, Margaret A.; Getz, Gad; Golub, Todd R.

2012-01-01

To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase–mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease. PMID:22343534

Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM.

PubMed

Tamada, Hiromi; Kiryu-Seo, Sumiko; Hosokawa, Hiroki; Ohta, Keisuke; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Nakamura, Kei-Ichiro; Kiyama, Hiroshi

2017-08-01

Mitochondria undergo morphological changes through fusion and fission for their quality control, which are vital for neuronal function. In this study, we examined three-dimensional morphologies of mitochondria in motor neurons under normal, nerve injured, and nerve injured plus fission-impaired conditions using the focused ion beam/scanning electron microscopy (FIB/SEM), because the FIB/SEM technology is a powerful tool to demonstrate both 3D images of whole organelle and the intra-organellar structure simultaneously. Crossing of dynamin-related protein 1 (Drp1) gene-floxed mice with neuronal injury-specific Cre driver mice, Atf3:BAC Tg mice, allowed for Drp1 ablation specifically in injured neurons. FIB/SEM analysis demonstrated that somatic mitochondrial morphologies in motor neurons were not altered before or after nerve injury. However, the fission impairment resulted in prominent somatic mitochondrial enlargement, which initially induced complex morphologies with round regions and long tubular processes, subsequently causing a decrease in the number of processes and further enlargement of the round regions, which eventually resulted in big spheroidal mitochondria without processes. The abnormal mitochondria exhibited several degradative morphologies: local or total cristae collapse, vacuolization, and mitophagy. These suggest that mitochondrial fission is crucial for maintaining mitochondrial integrity in injured motor neurons, and multiple forms of mitochondria degradation may accelerate neuronal degradation. © 2017 Wiley Periodicals, Inc.

Histological and transcript analyses of intact somatic embryos in an elite maize (Zea mays L.) inbred line Y423.

PubMed

Liu, Beibei; Su, Shengzhong; Wu, Ying; Li, Ying; Shan, Xiaohui; Li, Shipeng; Liu, Hongkui; Dong, Haixiao; Ding, Meiqi; Han, Junyou; Yuan, Yaping

2015-07-01

Intact somatic embryos were obtained from an elite maize inbred line Y423, bred in our laboratory. Using 13-day immature embryos after self-pollination as explants, and after 4-5 times subculture, a large number of somatic embryos were detected on the surface of the embryonic calli on the medium. The intact somatic embryos were transferred into the differential medium, where the plantlets regenerated with shoots and roots forming simultaneously. Histological analysis and scanning electron micrographs confirmed the different developmental stages of somatic embryogenesis, including globular-shaped embryo, pear-shaped embryo, scutiform embryo, and mature embryo. cDNA-amplified fragment length polymorphism (cDNA-AFLP) was used for comparative transcript profiling between embryogenic and non-embryogenic calli of a new elite maize inbred line Y423 during somatic embryogenesis. Differentially expressed genes were cloned and sequenced. Gene Ontology analysis of 117 candidate genes indicated their involvement in cellular component, biological process and molecular function. Nine of the candidate genes were selected. The changes in their expression levels during embryo induction and regeneration were analyzed in detail using quantitative real-time PCR. Two full-length cDNA sequences, encoding ZmSUF4 (suppressor of fir 4-like protein) and ZmDRP3A (dynamin-related protein), were cloned successfully from intact somatic embryos of the elite inbred maize line Y423. Here, a procedure for maize plant regeneration from somatic embryos is described. Additionally, the possible roles of some of these genes during the somatic embryogenesis has been discussed. This study is a systematic analysis of the cellular and molecular mechanism during the formation of intact somatic embryos in maize. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

How well do parental and peer relationships in adolescence predict health in adulthood?

PubMed

Landstedt, Evelina; Hammarström, Anne; Winefield, Helen

2015-07-01

Although health effects of social relationships are well-researched, long-term health consequences of adolescent family as well as peer relationships are poorly understood. The aim of the study was to explore the prospective importance of parental and peer social relationships in adolescence on internalising and functional somatic symptoms in adulthood. Data were drawn from four waves of the Northern Swedish Cohort Study, response rate 94.3%, N=1001. Outcome variables were internalising and functional somatic symptoms at the ages of 21, 30 and 42. Relationship variables at age 16 were poor parental contact and three indicators of poor peer relationships. Associations were assessed in multivariate ordinal logistic regressions with adjustment for confounders and baseline health. Results show that the main relationships-related predictors of adult internalising symptoms were self-rated poor peer relationships in terms of spending time alone during after-school hours and poor parental relationship. Functional somatic symptoms on the other hand were most strongly associated with poor parental contact and not being happy with classmates at age 16. The quality of parental and peer relationships in adolescence predicts adult mental and functional somatic health as much as 26 years later, even when accounting for confounders and adolescent symptomatology. This study extends past research by exploring how both adolescent parental and peer relationships (self-reported as well as teacher reported) predict adult self-reported health. © 2015 the Nordic Societies of Public Health.

Residues in the analyst of the patient's symbiotic connection at a somatic level: unrepresented states in the patient and analyst.

PubMed

Godsil, Geraldine

2018-02-01

This paper discusses the residues of a somatic countertransference that revealed its meaning several years after apparently successful analytic work had ended. Psychoanalytic and Jungian analytic ideas on primitive communication, dissociation and enactment are explored in the working through of a shared respiratory symptom between patient and analyst. Growth in the analyst was necessary so that the patient's communication at a somatic level could be understood. Bleger's concept that both the patient's and analyst's body are part of the setting was central in the working through. © 2018, The Society of Analytical Psychology.

Monozygotic twins discordant for constitutive BRCA1 promoter methylation, childhood cancer and secondary cancer.

PubMed

Galetzka, Danuta; Hansmann, Tamara; El Hajj, Nady; Weis, Eva; Irmscher, Benjamin; Ludwig, Marco; Schneider-Rätzke, Brigitte; Kohlschmidt, Nicolai; Beyer, Vera; Bartsch, Oliver; Zechner, Ulrich; Spix, Claudia; Haaf, Thomas

2012-01-01

We describe monozygotic twins discordant for childhood leukemia and secondary thyroid carcinoma. We used bisulfite pyrosequencing to compare the constitutive promoter methylation of BRCA1 and several other tumor suppressor genes in primary fibroblasts. The affected twin displayed an increased BRCA1 methylation (12%), compared with her sister (3%). Subsequent bisulfite plasmid sequencing demonstrated that 13% (6 of 47) BRCA1 alleles were fully methylated in the affected twin, whereas her sister displayed only single CpG errors without functional implications. This between-twin methylation difference was also found in irradiated fibroblasts and untreated saliva cells. The BRCA1 epimutation may have originated by an early somatic event in the affected twin: approximately 25% of her body cells derived from different embryonic cell lineages carry one epigenetically inactivated BRCA1 allele. This epimutation was associated with reduced basal protein levels and a higher induction of BRCA1 after DNA damage. In addition, we performed a genome-wide microarray analysis of both sisters and found several copy number variations, i.e., heterozygous deletion and reduced expression of the RSPO3 gene in the affected twin. This monozygotic twin pair represents an impressive example of epigenetic somatic mosaicism, suggesting a role for constitutive epimutations, maybe along with de novo genetic alterations in recurrent tumor development.

Monozygotic twins discordant for constitutive BRCA1 promoter methylation, childhood cancer and secondary cancer

PubMed Central

Galetzka, Danuta; Hansmann, Tamara; El Hajj, Nady; Weis, Eva; Irmscher, Benjamin; Ludwig, Marco; Schneider-Rätzke, Brigitte; Kohlschmidt, Nicolai; Beyer, Vera; Bartsch, Oliver; Zechner, Ulrich; Spix, Claudia; Haaf, Thomas

2012-01-01

We describe monozygotic twins discordant for childhood leukemia and secondary thyroid carcinoma. We used bisulfite pyrosequencing to compare the constitutive promoter methylation of BRCA1 and several other tumor suppressor genes in primary fibroblasts. The affected twin displayed an increased BRCA1 methylation (12%), compared with her sister (3%). Subsequent bisulfite plasmid sequencing demonstrated that 13% (6 of 47) BRCA1 alleles were fully methylated in the affected twin, whereas her sister displayed only single CpG errors without functional implications. This between-twin methylation difference was also found in irradiated fibroblasts and untreated saliva cells. The BRCA1 epimutation may have originated by an early somatic event in the affected twin: approximately 25% of her body cells derived from different embryonic cell lineages carry one epigenetically inactivated BRCA1 allele. This epimutation was associated with reduced basal protein levels and a higher induction of BRCA1 after DNA damage. In addition, we performed a genome-wide microarray analysis of both sisters and found several copy number variations, i.e., heterozygous deletion and reduced expression of the RSPO3 gene in the affected twin. This monozygotic twin pair represents an impressive example of epigenetic somatic mosaicism, suggesting a role for constitutive epimutations, maybe along with de novo genetic alterations in recurrent tumor development. PMID:22207351

Respiratory and psychiatric abnormalities in chronic symptomatic hyperventilation.

PubMed Central

Bass, C; Gardner, W N

1985-01-01

Many physicians believe that the hyperventilation syndrome is invariably associated with anxiety or undiagnosed organic disease such as asthma and pulmonary embolus, or both. Twenty one patients referred by specialist physicians with unexplained somatic symptoms and unequivocal chronic hypocapnia (resting end tidal Pco2 less than or equal to 4 kPa (30 mm Hg) on repeated occasions during prolonged measurement) were investigated. All but one complained of inability to take a satisfying breath. Standard lung function test results and chest radiographs were normal in all patients, but histamine challenge showed bronchial hyper-reactivity in two of 20 patients tested, and skin tests to common allergens were positive in three of 18. Ventilation-perfusion scanning was abnormal in a further three of 15 patients studied, with unmatched perfusion defects in two and isolated ventilation defects in one. None of the 21 had thyrotoxicosis, severe coronary heart disease, or other relevant cardiovascular abnormalities. Ten of the 21 patients were neurotic and suffered from chronic psychiatric disturbance characterised by anxiety, panic, and phobic symptoms. The remainder had no detectable psychiatric disorders but reported proportionately more somatic than anxiety symptoms. Severe hyperventilation can occur in the absence of formal psychiatric or detectable respiratory or other organic abnormalities. Asthma and pulmonary embolus must be specifically excluded. PMID:3922504

[Somatic symptoms in those hospitalized for dizziness or vertigo].

PubMed

Goto, Fumiyuki; Tsutumi, Tomoko; Arai, Motohiro; Ogawa, Kaoru

2010-09-01

Anxiety and depression greatly affect the prognosis of and burden on subjects seen for dizziness or vertigo, who usually report multiple somatic symptoms. We studied the prevalence of these symptoms in 145 subjects hospitalized for dizziness or vertigo and taking part in 4-day group vestibular rehabilitation. Questionnaires given to determine the prevalence of somatic symptoms assessed headache, insomnia, diarrhea, constipation, stomachache, chest pain, palpitations, dyspnea, general fatigue, and stress. Quantitation used aerical rating scale (NRS). Anxiety and depression were assessed using the hospital anxiety and depression scale (HADS). Disability due to dizziness was assessed using the dizziness handicap inventory (DHI). We conducted correlational analysis between dizziness and somatic symptoms. The top four average NRS scores for somatic symptoms were dizziness at 3.5 +/- 2.8, general fatigue at 2.8 +/- 2.6, insomnia at 2.4 +/- 2.6, and headache at 1.8 +/- 2.3. These symptoms resembled those reported for subjects with anxiety and depression. The correlation between headache and dizziness NRS scores was R = 0.48 (P < 0.0001). The total HADS score was 13.9 +/- 8.1 points (anxiety 7.2 +/- 4.3, depression 6.7 +/- 4.3). The average DHI score was 36.3 +/- 24.1 points. These results indicate that those with dizziness reported several somatic symptoms related to anxiety and depression attributable to dizziness. This underscores the need to treat these somatic symptoms when treating subjects seen chiefly dizziness or vertigo.

Somatic mutations in histiocytic sarcoma identified by next generation sequencing.

PubMed

Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Hornick, Jason L; Woda, Bruce; Yu, Hongbo

2016-08-01

Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.

Assertive community treatment for elderly people with severe mental illness

PubMed Central

2010-01-01

Background Adults aged 65 and older with severe mental illnesses are a growing segment of the Dutch population. Some of them have a range of serious problems and are also difficult to engage. While assertive community treatment is a common model for treating difficult to engage severe mental illnesses patients, no special form of it is available for the elderly. A special assertive community treatment team for the elderly is developed in Rotterdam, the Netherlands and tested for its effectiveness. Methods We will use a randomized controlled trial design to compare the effects of assertive community treatment for the elderly with those of care as usual. Primary outcome measures will be the number of dropouts, the number of patients engaged in care and patient's psychiatric symptoms, somatic symptoms, and social functioning. Secondary outcome measures are the number of unmet needs, the subjective quality of life and patients' satisfaction. Other secondary outcomes include the number of crisis contacts, rates of voluntary and involuntary admission, and length of stay. Inclusion criteria are aged 65 plus, the presence of a mental disorder, a lack of motivation for treatment and at least four suspected problems with functioning (addiction, somatic problems, daily living activities, housing etc.). If patients meet the inclusion criteria, they will be randomly allocated to either assertive community treatment for the elderly or care as usual. Trained assessors will use mainly observational instruments at the following time points: at baseline, after 9 and 18 months. Discussion This study will help establish whether assertive community treatment for the elderly produces better results than care as usual in elderly people with severe mental illnesses who are difficult to engage. When assertive community treatment for the elderly proves valuable in these respects, it can be tested and implemented more widely, and mechanisms for its effects investigated. Trial Registration The Netherlands National Trial Register NTR1620 PMID:20958958

Assertive community treatment for elderly people with severe mental illness.

PubMed

Stobbe, Jolanda; Mulder, Niels C L; Roosenschoon, Bert-Jan; Depla, Marja; Kroon, Hans

2010-10-19

Adults aged 65 and older with severe mental illnesses are a growing segment of the Dutch population. Some of them have a range of serious problems and are also difficult to engage. While assertive community treatment is a common model for treating difficult to engage severe mental illnesses patients, no special form of it is available for the elderly. A special assertive community treatment team for the elderly is developed in Rotterdam, the Netherlands and tested for its effectiveness. We will use a randomized controlled trial design to compare the effects of assertive community treatment for the elderly with those of care as usual. Primary outcome measures will be the number of dropouts, the number of patients engaged in care and patient's psychiatric symptoms, somatic symptoms, and social functioning. Secondary outcome measures are the number of unmet needs, the subjective quality of life and patients' satisfaction. Other secondary outcomes include the number of crisis contacts, rates of voluntary and involuntary admission, and length of stay. Inclusion criteria are aged 65 plus, the presence of a mental disorder, a lack of motivation for treatment and at least four suspected problems with functioning (addiction, somatic problems, daily living activities, housing etc.). If patients meet the inclusion criteria, they will be randomly allocated to either assertive community treatment for the elderly or care as usual. Trained assessors will use mainly observational instruments at the following time points: at baseline, after 9 and 18 months. This study will help establish whether assertive community treatment for the elderly produces better results than care as usual in elderly people with severe mental illnesses who are difficult to engage. When assertive community treatment for the elderly proves valuable in these respects, it can be tested and implemented more widely, and mechanisms for its effects investigated. The Netherlands National Trial Register NTR1620.

Metabolite profiling of somatic embryos of Cyclamen persicum in comparison to zygotic embryos, endosperm, and testa

PubMed Central

Winkelmann, Traud; Ratjens, Svenja; Bartsch, Melanie; Rode, Christina; Niehaus, Karsten; Bednarz, Hanna

2015-01-01

Somatic embryogenesis has been shown to be an efficient in vitro plant regeneration system for many crops such as the important ornamental plant Cyclamen persicum, for which this regeneration pathway of somatic embryogenesis is of interest for the vegetative propagation of parental lines as well as elite plants. However, somatic embryogenesis is not commercially used in many crops due to several unsolved problems, such as malformations, asynchronous development, deficiencies in maturation and germination of somatic embryos. In contrast, zygotic embryos in seeds develop and germinate without abnormalities in most cases. Instead of time-consuming and labor-intensive experiments involving tests of different in vitro culture conditions and plant growth regulator supplements, we follow a more directed approach. Zygotic embryos served as a reference and were compared to somatic embryos in metabolomic analyses allowing the future optimization of the in vitro system. The aims of this study were to detect differences in the metabolite profiles of torpedo stage somatic and zygotic embryos of C. persicum. Moreover, major metabolites in endosperm and testa were identified and quantified. Two sets of extracts of two to four biological replicates each were analyzed. In total 52 metabolites were identified and quantified in the different tissues. One of the most significant differences between somatic and zygotic embryos was that the proline concentration in the zygotic embryos was about 40 times higher than that found in somatic embryos. Epicatechin, a scavenger for reactive oxygen species, was found in highest abundance in the testa. Sucrose, the most abundant metabolite was detected in significantly higher concentrations in zygotic embryos. Also, a yet unknown trisaccharide, was significantly enriched in zygotic embryos. PMID:26300898

Modification by two genes of associations between general somatic health and incident depressive syndrome in older people.

PubMed

Kim, Jae-Min; Stewart, Robert; Kim, Sung-Wan; Yang, Su-Jin; Shin, Il-Seon; Yoon, Jin-Sang

2009-04-01

To investigate the modifying effects of two candidate genes (serotonin transporter gene linked promoter region (5-HTTLPR) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms) on the associations between general somatic morbidity and incidence of depression in an East Asian population with high frequencies of potential risk alleles. With a 2-year prospective study of a community sample (N = 521) of older people (aged 65+), information on baseline number of health complaints, diagnosis of moderate/severe depressive syndrome (Geriatric Mental State), and genotypes for 5-HTTLPR and MTHFR C677T polymorphisms were ascertained. Interactions between somatic morbidity and the two genotypes were investigated for incident depression. Incident depression was present in 63 (12%) and was associated with worse somatic health. Significant interactions between number of somatic complaints and both genotypes were observed. For the 5-HTTLPR genotypes, the association between the number of somatic disorders and depression was significant in s/s homozygotes (chi2 = 8.80 (1 df), p = .003) but not in heterozygotes (chi2 = 0.23, p = .634) or l/l homozygotes (chi2 = 0.04, p = .840). For the MTHFR genotypes, the association between the number of somatic disorders and depression was significant in T/T homozygotes (chi2 = 4.97, p = .026) but not in C/T heterozygotes (chi2 = 1.24, p = .265) or C/C homozygotes (chi2 = 1.04, p = .307). These findings suggest that associations between general somatic morbidity and late-life depression are modified by at least two genes, and that elders with particular genotypes are at greater risk for onset of depression in the presence of somatic ill health.

The Somatic Appraisal Model of Affect: Paradigm for Educational Neuroscience and Neuropedagogy

ERIC Educational Resources Information Center

Patten, Kathryn E.

2011-01-01

This chapter presents emotion as a function of brain-body interaction, as a vital part of a multi-tiered phylogenetic set of neural mechanisms, evoked by both instinctive processes and learned appraisal systems, and argues to establish the primacy of emotion in relation to cognition. Primarily based on Damasio's somatic marker hypothesis, but also…

Transcriptional Noise and Somatic Mutations in the Aging Pancreas.

PubMed

Swisa, Avital; Kaestner, Klaus H; Dor, Yuval

2017-12-05

The underlying mechanisms and functional significance of pancreatic β cell heterogeneity are an intensive area of investigation. In a recent Cell paper, Enge and colleagues (2017) performed single-cell RNA sequencing of human pancreatic cells and concluded that with age, pancreatic cells become transcriptionally noisy and accumulate somatic mutations. Copyright © 2017. Published by Elsevier Inc.

Interaction of angiotensin-converting enzyme (ACE) with membrane-bound carboxypeptidase M (CPM) - a new function of ACE.

PubMed

Sun, Xiaoou; Wiesner, Burkhard; Lorenz, Dorothea; Papsdorf, Gisela; Pankow, Kristin; Wang, Po; Dietrich, Nils; Siems, Wolf-Eberhard; Maul, Björn

2008-12-01

Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE.

Psychological Distress in Young Adult Males with Atopic Dermatitis: A Cross-Sectional Study.

PubMed

Kim, Si-Heon; Hur, Jae; Jang, Jae-Yeon; Park, Hae-Sim; Hong, Chang Hyung; Son, Sang Joon; Chang, Ki Jung

2015-06-01

The relationship between atopic dermatitis (AD) and psychological distress has been well established for children and adolescents. However, it is unclear whether this relationship exists in young adults. This study aimed to assess the relationship between AD and psychological distress in young male adults in South Korea. A cross-sectional study was conducted using regional conscription data from 2008 to 2012. A dermatologist diagnosed AD based on historical and clinical features, and determined severity using the eczema area and severity index. A psychiatrist used medical records, an interview, and a psychological test to examine psychological distress (depression, anxiety, and somatization). The relationship between psychological distress and AD was assessed by multivariate logistic regression analyses. Among the 120,508 conscripts, 1517 (1.2%) presented with AD. The odds of having each type of psychological distress were significantly greater for individuals with AD compared with those without AD. The adjusted odds ratios for depression, anxiety, and somatization were 1.79 (95% CI 1.40-2.29), 1.38 (95% CI 1.08-1.76), and 1.75 (95% CI 1.40-2.20), respectively. Moderate-to-severe AD was significantly related to depression and somatization to a greater extent compared with mild AD. Depression, anxiety, and somatization are strongly and independently associated with AD in young adult males. Early treatment of skin inflammation might modify the risk of psychiatric problems. Prospective cohort studies are needed to verify causal relationships.

A dimensional approach to the phantom vibration and ringing syndrome during medical internship.

PubMed

Lin, Yu-Hsuan; Chen, Ching-Yen; Li, Peng; Lin, Sheng-Hsuan

2013-09-01

Phantom vibrations and ringing of mobile phones are prevalent hallucinations in the general population. They might be considered as a "normal" brain mechanism. The aim of this study was to determine if a dimensional approach to identify individuals suffering from these hallucinations was more important than a categorical approach. A prospective longitudinal study of 74 medical interns (male: 46, mean age: 24.8 ± 1.2) was carried out using repeated investigations of the severity of phantom vibrations and ringing, as well as accompanying symptoms of anxiety and depression as measured by Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI) before, at the 3rd, 6th, and 12th month during internship, and 2 weeks after internship. We utilized the cognitive and somatic subscales of the BDI, as well as the subjective, somatic and panic subscales of the BAI. The correlation between phantom vibration and ringing was lowest before the internship but became moderate during the internship and high 2 weeks after it. Compared to interns with subclinical phantom ringing and vibrations, interns with severe phantom vibrations and ringing had higher subjective and somatic anxiety and somatic depressive scores at any time point throughout the internship. Only interns with severe phantom ringing had more cognitive/affective depression. A dimensional approach to the phantom vibration and ringing syndrome is a powerful way to identify their correlation, as well as their association with anxiety and depression. Copyright © 2013 Elsevier Ltd. All rights reserved.

Differentiated muscles are mandatory for gas-filling of the Drosophila airway system.

PubMed

Wang, Yiwen; Cruz, Tina; Irion, Uwe; Moussian, Bernard

2015-11-30

At the end of development, organs acquire functionality, thereby ensuring autonomy of an organism when it separates from its mother or a protective egg. In insects, respiratory competence starts when the tracheal system fills with gas just before hatching of the juvenile animal. Cellular and molecular mechanisms of this process are not fully understood. Analyses of the phenotype of Drosophila embryos with malformed muscles revealed that they fail to gas-fill their tracheal system. Indeed, we show that major regulators of muscle formation like Lame duck and Blown fuse are important, while factors involved in the development of subsets of muscles including cardiac and visceral muscles are dispensable for this process, suggesting that somatic muscles (or parts of them) are essential to enable tracheal terminal differentiation. Based on our phenotypic data, we assume that somatic muscle defect severity correlates with the penetrance of the gas-filling phenotype. This argues that a limiting molecular or mechanical muscle-borne signal tunes tracheal differentiation. We think that in analogy to the function of smooth muscles in vertebrate lungs, a balance of physical forces between muscles and the elasticity of tracheal walls may be decisive for tracheal terminal differentiation in Drosophila. © 2015. Published by The Company of Biologists Ltd.

Endomembrane-associated RSD-3 is important for RNAi induced by extracellular silencing RNA in both somatic and germ cells of Caenorhabditis elegans

PubMed Central

Imae, Rieko; Dejima, Katsufumi; Kage-Nakadai, Eriko; Arai, Hiroyuki; Mitani, Shohei

2016-01-01

RNA silencing signals in C. elegans spread among cells, leading to RNAi throughout the body. During systemic spread of RNAi, membrane trafficking is thought to play important roles. Here, we show that RNAi Spreading Defective-3 (rsd-3), which encodes a homolog of epsinR, a conserved ENTH (epsin N-terminal homology) domain protein, generally participates in cellular uptake of silencing RNA. RSD-3 is previously thought to be involved in systemic RNAi only in germ cells, but we isolated several deletion alleles of rsd-3, and found that these mutants are defective in the spread of silencing RNA not only into germ cells but also into somatic cells. RSD-3 is ubiquitously expressed, and intracellularly localized to the trans-Golgi network (TGN) and endosomes. Tissue-specific rescue experiments indicate that RSD-3 is required for importing silencing RNA into cells rather than exporting from cells. Structure/function analysis showed that the ENTH domain alone is sufficient, and membrane association of the ENTH domain is required, for RSD-3 function in systemic RNAi. Our results suggest that endomembrane trafficking through the TGN and endosomes generally plays an important role in cellular uptake of silencing RNA. PMID:27306325

Endomembrane-associated RSD-3 is important for RNAi induced by extracellular silencing RNA in both somatic and germ cells of Caenorhabditis elegans.

PubMed

Imae, Rieko; Dejima, Katsufumi; Kage-Nakadai, Eriko; Arai, Hiroyuki; Mitani, Shohei

2016-06-16

RNA silencing signals in C. elegans spread among cells, leading to RNAi throughout the body. During systemic spread of RNAi, membrane trafficking is thought to play important roles. Here, we show that RNAi Spreading Defective-3 (rsd-3), which encodes a homolog of epsinR, a conserved ENTH (epsin N-terminal homology) domain protein, generally participates in cellular uptake of silencing RNA. RSD-3 is previously thought to be involved in systemic RNAi only in germ cells, but we isolated several deletion alleles of rsd-3, and found that these mutants are defective in the spread of silencing RNA not only into germ cells but also into somatic cells. RSD-3 is ubiquitously expressed, and intracellularly localized to the trans-Golgi network (TGN) and endosomes. Tissue-specific rescue experiments indicate that RSD-3 is required for importing silencing RNA into cells rather than exporting from cells. Structure/function analysis showed that the ENTH domain alone is sufficient, and membrane association of the ENTH domain is required, for RSD-3 function in systemic RNAi. Our results suggest that endomembrane trafficking through the TGN and endosomes generally plays an important role in cellular uptake of silencing RNA.

Acupuncture's Cardiovascular Actions: A Mechanistic Perspective.

PubMed

Longhurst, John

2013-04-01

Over the last several decades, there has been an explosion of articles on acupuncture, including studies that have begun to explore mechanisms underlying its analgesic and cardiovascular actions. Modulation of cardiovascular function is most effective during manual and low-frequency, low-intensity electroacupuncture (EA) at a select set of acupoints situated along meridians located over deep somatic nerves on the upper and lower extremities. Stimulation at these acupoints activates underlying sensory neural pathways that project to a number of regions in the central nervous system (CNS) that ultimately regulate autonomic outflow and hence cardiovascular function. A long-loop pathway involving the hypothalamus, midbrain, and medulla underlies EA modulation of reflex increases in blood pressure (BP). Actions of excitatory and inhibitory neurotransmitters in the supraspinal CNS underlie processing of the somatic input and adjustment of autonomic outflow during EA. Acupuncture also decreases elevated blood pressure through actions in the thoracic spinal cord. Reflexes that lower BP likewise are modulated by EA through its actions on sympathetic and parasympathetic nuclei in the medulla. The autonomic influence of acupuncture is slow in onset but prolonged in duration, typically lasting beyond the period of stimulation. Clinical studies suggest that acupuncture can be used to treat cardiac diseases, such as myocardial ischemia and hypertension, associated with overactivity of the sympathetic nervous system.

Acupuncture's Cardiovascular Actions: A Mechanistic Perspective

PubMed Central

2013-01-01

Abstract Over the last several decades, there has been an explosion of articles on acupuncture, including studies that have begun to explore mechanisms underlying its analgesic and cardiovascular actions. Modulation of cardiovascular function is most effective during manual and low-frequency, low-intensity electroacupuncture (EA) at a select set of acupoints situated along meridians located over deep somatic nerves on the upper and lower extremities. Stimulation at these acupoints activates underlying sensory neural pathways that project to a number of regions in the central nervous system (CNS) that ultimately regulate autonomic outflow and hence cardiovascular function. A long-loop pathway involving the hypothalamus, midbrain, and medulla underlies EA modulation of reflex increases in blood pressure (BP). Actions of excitatory and inhibitory neurotransmitters in the supraspinal CNS underlie processing of the somatic input and adjustment of autonomic outflow during EA. Acupuncture also decreases elevated blood pressure through actions in the thoracic spinal cord. Reflexes that lower BP likewise are modulated by EA through its actions on sympathetic and parasympathetic nuclei in the medulla. The autonomic influence of acupuncture is slow in onset but prolonged in duration, typically lasting beyond the period of stimulation. Clinical studies suggest that acupuncture can be used to treat cardiac diseases, such as myocardial ischemia and hypertension, associated with overactivity of the sympathetic nervous system. PMID:24761168

Bladder pain syndrome/interstitial cystitis as a functional somatic syndrome.

PubMed

Warren, John W

2014-12-01

To determine whether bladder pain syndrome/interstitial cystitis (BPS/IC) has the characteristics of a functional somatic syndrome (FSS). There is no accepted definition of an FSS. Consequently, this paper reviewed the literature for common FSS characteristics and for reports that BPS/IC has these characteristics. Eleven articles met inclusion and exclusion criteria and yielded 18 FSS characteristics. BPS/IC patients manifest all but two: the exceptions were normal light microscopic anatomy (after hydrodistention under anesthesia, some BPS/IC bladders have Hunner's lesions and most have petechial hemorrhages) and normal laboratory tests (many BPS/IC patients have hematuria). Petechial hemorrhages and hematuria are probably related and may appear during naturally-occurring bladder distention. Without such distention, then, the 90% of BPS/IC patients without a Hunner's lesion have all the characteristics of an FSS. Comparisons in the opposite direction were consistent: several additional features of BPS/IC were found in FSSs. This systematic but untested method is consistent with but does not test the hypothesis that BPS/IC in some patients might best be understood as an FSS. Like most conditions, BPS/IC is probably heterogeneous; hence only a proportion of BPS/IC cases are likely to be manifestations of an FSS. This hypothesis has several implications. Explorations of processes that connect the FSSs might contribute to understanding the pathogenesis of BPS/IC. Patients with FSSs are at risk for BPS/IC and may benefit from future preventive strategies. Therapies that are useful in FSSs also may be useful in some cases of BPS/IC. Copyright © 2014 Elsevier Inc. All rights reserved.

[Functional somatization: a conceptual review].

PubMed

Fabião, Cristina; Fleming, Manuela; Barbosa, António

2011-01-01

The authors have brought together and analised texts about the history of the concept of hysteria. In these texts hysteria is fundamentally considered a disease of organic origin (of the womb), and, in the Middle Age, evidence of demonic possession. From the XVII century onwards, apart from the etiopathogenic concepts, also taken into consideration are aspects connected to the differential diagnosis with other similar entities and the therapy used each period. Even, in subsequent centuries, authors such as Syndenham, who consider hysteria to be a multidimensional entity, are rare. Empiricism has contributed to discoveries in biology and physiology, both general and of the nervous system itself, and given birth to the formulation of the Spinal Irritation Theory and Reflex Theory. These theories have led to strictly organic treatment of hysteria, in the same way that hysterectomies were performed to alleviate somatic symptoms connected to this disease. The introduction of hypnosis in medical practice, with Charcot in X1X century, allowed for the element of suggestion to be observed ( a non organic element) which accompanies the symptoms of hysteria. Two of his disciples, Janet and Freud, would define and isolate psychic mechanisms in the symptoms of hysteria: Dissociation of the consciousness (Janet) and Conversion (Freud). The last one developed a therapeutic method of a psychological nature for hysteria. The therapeutic implications and the pertinence of the distinction between unspecific somatization or functional (of somatic origin) somatization and somatization linked to disassociation mechanisms and conversion (psychic origin) are discussed as well as the evolution of international classification systems of somatization and the questions posed by the algorithms chosen for the cataloguing of symptoms. A revision of the relevant empirical studies about the association of somatization with depressive and anxiety disorders, within the general population, is made. The characteristics that permeate the clinical descriptions of somatoform disorders (whose validity criteria remain weak) and are not integrated within the diagnostic criteria for somatoform disorders are considered. We draw conclusions about the difficulties and consequences of the changes that some authors advocate in relation to the new classification system for somatoform syndromes.

Somatic outcome among patients hospitalised for anorexia nervosa in adolescence: disorders reported and links with global outcome.

PubMed

Roux, Hélène; Blanchet, Corinne; Stheneur, Chantal; Chapelon, Emeline; Godart, Nathalie

2013-06-01

(1) To describe the frequency of somatic pathologies and depression among former anorexia nervosa (AN) patients; (2) to study links with subjects' clinical history and global outcomes. 97 women hospitalised for AN during adolescence, 9.00 ± 1.92 years previously, were interviewed using structured questionnaires concerning somatic and psychiatric disorders that they had experienced. Iron deficiency, migraine, cystitis, upper digestive system disorders, fractures, osteoporosis, and dental problems were reported with a frequency >20 %. Depression was reported by 2/3 of the sample. Osteoporosis was 14 times more frequent in case of vitamin D deficiency. Fractures were three times more frequent in presence of osteoporosis and less frequent when the overall outcome was better. Among women who had AN in adolescence, somatic comorbidities are frequent in adulthood. They are linked to the severity and the duration of AN, and to the overall outcome of the subject.

Development and Validation of an Instrument to Predict Functional Recovery in Tibial Fracture Patients: The Somatic Pre-Occupation and Coping (SPOC) Questionnaire

PubMed Central

Busse, Jason W.; Bhandari, Mohit; Guyatt, Gordon H.; Heels-Ansdell, Diane; Kulkarni, Abhaya V.; Mandel, Scott; Sanders, David; Schemitsch, Emil; Swiontkowski, Marc; Tornetta, Paul; Wai, Eugene; Walter, Stephen D.

2011-01-01

Objective To explore the role of patients’ beliefs in their likelihood of recovery from severe physical trauma. Methods We developed and validated an instrument designed to capture the impact of patients’ beliefs on functional recovery from injury; the Somatic Pre-occupation and Coping (SPOC) questionnaire. At 6-weeks post-surgical fixation, we administered the SPOC questionnaire to 359 consecutive patients with operatively managed tibial shaft fractures. We constructed multivariable regression models to explore the association between SPOC scores and functional outcome at 1-year, as measured by return to work and short form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) scores. Results In our adjusted multivariable regression models that included pre-injury SF-36 scores, SPOC scores at 6-weeks post-surgery accounted for 18% of the variation in SF-36 PCS scores and 18% of SF-36 MCS scores at 1-year. In both models, 6-week SPOC scores were a far more powerful predictor of functional recovery than age, gender, fracture type, smoking status, or the presence of multi-trauma. Our adjusted analysis found that for each 14 point increment in SPOC score at 6-weeks (14 chosen on the basis of half a standard deviation of the mean SPOC score) the odds of returning to work at 1-year decreased by 40% (odds ratio = 0.60; 95% CI = 0.50 to 0.73). Conclusion The SPOC questionnaire is a valid measurement of illness beliefs in tibial fracture patients and is highly predictive of their long-term functional recovery. Future research should explore if these results extend to other trauma populations and if modification of unhelpful illness beliefs is feasible and would result in improved functional outcomes. PMID:22011635

Relationship between Chronic Non-Urological Associated Somatic Syndromes (NUAS) and Symptom Severity in Urological Chronic Pelvic Pain Syndromes: Baseline Evaluation of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Study

PubMed Central

Krieger, John N.; Stephens, Alisa J.; Landis, J. Richard; Clemens, J. Quentin; Kreder, Karl; Lai, H. Henry; Afari, Niloofar; Rodriguez, Larissa; Schaeffer, Anthony; Mackey, Sean; Andriole, Gerald L.; Williams, David A.

2015-01-01

Purpose We report data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) network to: (1) identify participants having either (a) urologic chronic pelvic pain syndromes (UCPPS) only or (b) chronic functional non-urological associated somatic syndromes (NUAS) in addition to UCPPS, (2) characterize these two subgroups, and (3) explore these two subgroups using three criteria: (a) the MAPP eligibility criteria, (b) self-reported medical history, or (c) RAND interstitial cystitis epidemiologic (RICE) criteria. Materials and Methods Self-reported cross-sectional data were collected from men and women with UCPPS including: predominant symptoms, symptom duration and severity, NUAS symptoms, and psychosocial factors. Results Of 424 UCPPS participants, 162 (38%) had NUAS: 93 (22%) irritable bowel syndrome, 15 (4%) fibromyalgia, 13 (3%) chronic fatigue syndrome, and 41 (10%) with multiple syndromes. Among 233 females, 103 (44%) had NUAS compared to 59 (31%) of 191 males (p = 0.006). Participants with NUAS had more severe urological symptoms, and more frequent depression and anxiety. Of 424 participants, 228 (54%) met RICE criteria. Among 228 RICE-positive participants, 108 (47%) had NUAS compared to 54 (28%) of 203 RICE-negative patients with NUAS (p < 0.001). Conclusions NUAS represent important clinical characteristics of UCPPS. Participants with NUAS have more severe symptoms, longer duration and higher rates of depression and anxiety. RICE-positive patients are more likely to have NUAS and more severe symptoms. Because NUAS are more common in women, future studies need to account for this potential confounding factor in UCPPS. PMID:25444992

A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types.

PubMed

Cheng, Feixiong; Liu, Chuang; Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

2015-09-01

Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics.

A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

PubMed Central

Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

2015-01-01

Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

Spontaneous generation of germline characteristics in mouse fibrosarcoma cells

NASA Astrophysics Data System (ADS)

Ma, Zhan; Hu, Yao; Jiang, Guoying; Hou, Jun; Liu, Ruilai; Lu, Yuan; Liu, Chunfang

2012-10-01

Germline/embryonic-specific genes have been found to be activated in somatic tumors. In this study, we further showed that cells functioning as germline could be present in mouse fibrosarcoma cells (L929 cell line). Early germline-like cells spontaneously appeared in L929 cells and further differentiated into oocyte-like cells. These germline-like cells can, in turn, develop into blastocyst-like structures in vitro and cause teratocarcinomas in vivo, which is consistent with natural germ cells in function. Generation of germline-like cells from somatic tumors might provide a novel way to understand why somatic cancer cells have strong features of embryonic/germline development. It is thought that the germline traits of tumors are associated with the central characteristics of malignancy, such as immortalization, invasion, migration and immune evasion. Therefore, germline-like cells in tumors might provide potential targets to tumor biology, diagnosis and therapy.

Simultaneous detection of somatic and F-specific coliphages in different settings by Escherichia coli strain CB390.

PubMed

Agulló-Barceló, Miriam; Galofré, Belén; Sala, Lluís; García-Aljaro, Cristina; Lucena, Francisco; Jofre, Juan

2016-09-01

Bacteriophages are increasingly being used as water quality indicators. Two groups of phages infecting Escherichia coli, somatic and F-specific coliphages, are being considered as indicators of fecal and viral contamination for several types of water around the world. However, some uncertainties remain regarding which coliphages to assess. Recently, E. coli strain CB390 has been reported to be suitable for simultaneous detection of both groups, which seems to be more informative than determining only one of the groups. Here, a significant number of samples from different settings, mostly those where F-specific phages have been reported to outnumber somatic coliphages, are analyzed for somatic coliphages, F-specific RNA phages by standardized methods and coliphages detected by host strain CB390. The results presented here confirm that the numbers of phages counted using CB390 are equivalent to the sum of the somatic and F-specific coliphages counted independently in all settings. Hence the usefulness of this strain for simultaneous detection of somatic and F-specific coliphages is confirmed. Also, sets of data on the presence of coliphages in reclaimed and groundwater are reported. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modeling Human Neurological and Neurodegenerative Diseases: From Induced Pluripotent Stem Cells to Neuronal Differentiation and Its Applications in Neurotrauma.

PubMed

Bahmad, Hisham; Hadadeh, Ola; Chamaa, Farah; Cheaito, Katia; Darwish, Batoul; Makkawi, Ahmad-Kareem; Abou-Kheir, Wassim

2017-01-01

With the help of several inducing factors, somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) lines. The success is in obtaining iPSCs almost identical to embryonic stem cells (ESCs), therefore various approaches have been tested and ultimately several ones have succeeded. The importance of these cells is in how they serve as models to unveil the molecular pathways and mechanisms underlying several human diseases, and also in its potential roles in the development of regenerative medicine. They further aid in the development of regenerative medicine, autologous cell therapy and drug or toxicity screening. Here, we provide a comprehensive overview of the recent development in the field of iPSCs research, specifically for modeling human neurological and neurodegenerative diseases, and its applications in neurotrauma. These are mainly characterized by progressive functional or structural neuronal loss rendering them extremely challenging to manage. Many of these diseases, including Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) have been explored in vitro . The main purpose is to generate patient-specific iPS cell lines from the somatic cells that carry mutations or genetic instabilities for the aim of studying their differentiation potential and behavior. This new technology will pave the way for future development in the field of stem cell research anticipating its use in clinical settings and in regenerative medicine in order to treat various human diseases, including neurological and neurodegenerative diseases.

Global Characterization of Protein Altering Mutations in Prostate Cancer

DTIC Science & Technology

2011-08-01

prevalence of candidate cancer genes observed here in prostate cancer. (3) Perform integrative analyses of somatic mutation with gene expression and copy...analyses of somatic mutation with gene expression and copy number change data collected on the same samples. Body This is a “synergy” project between...However, to perform initial verification/validation studies, we have evaluated the mutation calls for several genes discovered initially by the

Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features

PubMed Central

Medrano, Jose V.; Martínez-Arroyo, Ana M.; Míguez, Jose M.; Moreno, Inmaculada; Martínez, Sebastián; Quiñonero, Alicia; Díaz-Gimeno, Patricia; Marqués-Marí, Ana I.; Pellicer, Antonio; Remohí, Jose; Simón, Carlos

2016-01-01

The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY), and hMSC (46, XY)) into a germ cell-like phenotype in vitro. Induced germ cell-like cells showed a marked switch in their transcriptomic profile and expressed several post-meiotic germ line related markers, showed meiotic progression, evidence of epigenetic reprogramming, and approximately 1% were able to complete meiosis as demonstrated by their haploid status and the expression of several post-meiotic markers. Furthermore, xenotransplantation assays demonstrated that a subset of induced cells properly colonize the spermatogonial niche. Knowledge obtained from this work can be used to create in vitro models to study gamete-related diseases in humans. PMID:27112843

The role of chromatin modifications in somatic embryogenesis in plants

PubMed Central

De-la-Peña, Clelia; Nic-Can, Geovanny I.; Galaz-Ávalos, Rosa M.; Avilez-Montalvo, Randy; Loyola-Vargas, Víctor M.

2015-01-01

Somatic embryogenesis (SE) is a powerful tool for plant genetic improvement when used in combination with traditional agricultural techniques, and it is also an important technique to understand the different processes that occur during the development of plant embryogenesis. SE onset depends on a complex network of interactions among plant growth regulators, mainly auxins and cytokinins, during the proembryogenic early stages, and ethylene and gibberellic and abscisic acids later in the development of the somatic embryos. These growth regulators control spatial and temporal regulation of multiple genes in order to initiate change in the genetic program of somatic cells, as well as moderating the transition between embryo developmental stages. In recent years, epigenetic mechanisms have emerged as critical factors during SE. Some early reports indicate that auxins and in vitro conditions modify the levels of DNA methylation in embryogenic cells. The changes in DNA methylation patterns are associated with the regulation of several genes involved in SE, such as WUS, BBM1, LEC, and several others. In this review, we highlight the more recent discoveries in the understanding of the role of epigenetic regulation of SE. In addition, we include a survey of different approaches to the study of SE, and new opportunities to focus SE studies. PMID:26347757

Somatic and Functional Status of Boys from Various Social and Environmental Categories

ERIC Educational Resources Information Center

Domaradzki, Jaroslaw; Ignasiak, Zofia; Slawinska, Teresa

2009-01-01

Study aim: To assess the somatic and fitness status of adolescent boys from polluted industrial areas. Material and methods: A group of 313 boys aged 11-15 years from 5 villages located in the copper mine area in South-Western Poland were classified by the degree of lead and cadmium pollution (high--very high) and by parents' education…

Hypochondriasis and somatization in college women: a personal projects analysis.

PubMed

Karoly, P; Lecci, L

1993-03-01

Although the descriptive features of hypochondriasis and somatization have been widely studied, the motivational correlates (goal representations) of individuals manifesting abnormal illness patterns have not been considered. The Personal Projects Analysis method (Little, 1983) was used to contrast the health and nonhealth goals of female undergraduates. Subjects selected 10 goals for evaluation along a series of dimensions. When health pursuits alone were examined, hypochondriasis on the Minnesota Multiphasic Personality Inventory was found to correlate directly with goal appraisal dimensions subsumed by an anxiety-absorption factor and inversely with dimensions characterizing rewardingness, thus suggesting a negativity of health goal construal. Somatizers also pursued more health-related projects than did nonsomatizers; nonhealth goal cognition did not relate as strongly to hypochondriasis. Finally, using discriminant function analysis, goal representations were shown to significantly and substantially differentiate somatizers from nonsomatizers.

Surgical anatomy of the retroperitoneal spaces, Part V: Surgical applications and complications.

PubMed

Mirilas, Petros; Skandalakis, John E

2010-04-01

Knowledge of the surgical anatomy of the retroperitoneum is crucial for surgery of the retroperitoneal organs. Surgery is essential for treatment of retroperitoneal pathologies. The list of these diseases is extensive and comprises acute and chronic inflammatory processes (abscess, injury, hematoma, idiopathic fibrosis), metastatic neoplasms, and primary neoplasms from fibroadipose tissue, connective tissue, smooth and striated muscle, vascular tissue, somatic and sympathetic nervous tissue, extraadrenal chromaffin tissue, and lymphatic tissue. The retroperitoneum can be approached and explored by several routes, including the transperitoneal route and the extraperitoneal route. The retroperitoneal approach to the iliac fossa is used for ectopic renal transplantation. Safe and reliable primary retroperitoneal access can be performed for laparoscopic exploration. The anatomic complications of retroperitoneal surgery are the complications of the organs located in several compartments of the retroperitoneal space. Complications may arise from incisions to the somatic wall, somatic nerves, blood and lymphatic vessels, lymph nodes, visceral autonomous plexuses, and neighboring splanchna.

Evaluating the impact of depression, anxiety & autonomic function on health related quality of life, vocational functioning and health care utilisation in acute coronary syndrome patients: the ADVENT study protocol

PubMed Central

2013-01-01

Background Depression and anxiety are highly prevalent and co-morbid in acute coronary syndrome patients. Somatic and cognitive subtypes of depression and anxiety in acute coronary syndrome have been shown to be associated with mortality although their association with patient outcomes is unknown, as are the mechanisms that underpin these associations. We are conducting a prospective cohort study which aims to examine in acute coronary syndrome patients: (1) the role of somatic subtypes of depression and anxiety as predictors of health related quality of life outcomes; (2) how somatic subtypes of depression and anxiety relate to long term vocational functioning and healthcare utilisation; and (3) the role of the autonomic nervous system assessed by heart rate variability as a moderator of these associations. Methods Patients are being screened after index admission for acute coronary syndrome at a single, high volume centre, MonashHeart, Monash Health, Victoria, Australia. The inclusion criterion is all patients aged > 21 years old and fluent in English admitted to MonashHeart, Monash Health with a diagnosis of acute coronary syndrome. The primary outcome is mean health related quality of life (Short Form-36) Physical and Mental Health Summary scores at 12 and 24 months in subtypes with somatic symptoms of depression and anxiety. Depressive domains are assessed by the Beck Depression Inventory II and the Cardiac Depression Scale. Anxiety is measured using the Speilberger State-Trait Anxiety Inventory and the Crown Crisp Phobic Anxiety questionnaire. Secondary outcomes include clinical variables, healthcare service utilisation and vocational functioning. Discussion This manuscript presents the protocol for a prospective cohort study which will investigate the role of somatic subtypes of depression and anxiety as predictors of health related quality of life, long-term vocational functioning and health service use, and the role of the autonomic nervous system in moderating these associations. Findings from the study have the potential to inform more effective pharmacological, psychological and behavioural interventions and better guide health policy on the use of health care resources. PMID:24237848

Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors.

PubMed

Chang, Hsun-Ming; Qiao, Jie; Leung, Peter C K

2016-12-01

Initially identified for their capability to induce heterotopic bone formation, bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor β superfamily. Using cellular and molecular genetic approaches, recent studies have implicated intra-ovarian BMPs as potent regulators of ovarian follicular function. The bi-directional communication of oocytes and the surrounding somatic cells is mandatory for normal follicle development and oocyte maturation. This review summarizes the current knowledge on the physiological role and molecular determinants of these ovarian regulatory factors within the human germline-somatic regulatory loop. The regulation of ovarian function remains poorly characterized in humans because, while the fundamental process of follicular development and oocyte maturation is highly similar across species, most information on the regulation of ovarian function is obtained from studies using rodent models. Thus, this review focuses on the studies that used human biological materials to gain knowledge about human ovarian biology and disorders and to develop strategies for preventing, diagnosing and treating these abnormalities. Relevant English-language publications describing the roles of BMPs or growth differentiation factors (GDFs) in human ovarian biology and phenotypes were comprehensively searched using PubMed and the Google Scholar database. The publications included those published since the initial identification of BMPs in the mammalian ovary in 1999 through July 2016. Studies using human biological materials have revealed the expression of BMPs, GDFs and their putative receptors as well as their molecular signaling in the fundamental cells (oocyte, cumulus/granulosa cells (GCs) and theca/stroma cells) of the ovarian follicles throughout follicle development. With the availability of recombinant human BMPs/GDFs and the development of immortalized human cell lines, functional studies have demonstrated the physiological role of intra-ovarian BMPs/GDFs in all aspects of ovarian functions, from follicle development to steroidogenesis, cell-cell communication, oocyte maturation, ovulation and luteal function. Furthermore, there is crosstalk between these potent ovarian regulators and the endocrine signaling system. Dysregulation or naturally occurring mutations within the BMP system may lead to several female reproductive diseases. The latest development of recombinant BMPs, synthetic BMP inhibitors, gene therapy and tools for BMP-ligand sequestration has made the BMP pathway a potential therapeutic target in certain human fertility disorders; however, further clinical trials are needed. Recent studies have indicated that GDF8 is an intra-ovarian factor that may play a novel role in regulating ovarian functions in the human ovary. Intra-ovarian BMPs/GDFs are critical regulators of folliculogenesis and human ovarian functions. Any dysregulation or variations in these ligands or their receptors may affect the related intracellular signaling and influence ovarian functions, which accounts for several reproductive pathologies and infertility. Understanding the normal and pathological roles of intra-ovarian BMPs/GDFs, especially as related to GC functions and follicular fluid levels, will inform innovative approaches to fertility regulation and improve the diagnosis and treatment of ovarian disorders. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Marriage and Partnership Integrity After Aneurysmal Subarachnoid Hemorrhage: Small Alterations in Neurologic Status Matter Most.

PubMed

Schöni, Daniel; Lauber, Lara; Fung, Christian; Goldberg, Johannes; Müri, René; Raabe, Andreas; Nyffeler, Thomas; Beck, Jürgen

2018-05-01

Common sequelae of subarachnoid hemorrhage (SAH) include somatic and/or cognitive impairment. This can cause emotional stress, social tensions, and difficulties in relationships. To test our hypothesis that more severe somatic and cognitive impairments increased the likelihood of disruption of a relationship after SAH, we assessed the integrity of marriage or partnership status in a well-evaluated subset of SAH patients. Our sample comprised 50 SAH patients who were discharged to a neurologic, in-house rehabilitation center between 2005 and 2010. Deficits on admission to the rehabilitation center were divided into 18 categories and grouped into minor and major somatic deficits, as well as cognitive deficits. Clinical outcome scores, marital/partnership status, and duration of partnership before ictus were recorded. A follow-up questionnaire after 4.3 (2012) and 8.8 (2017) years was used to assess changes in marital/partnership status. Possible predictor parameters were estimated and included in a stepdown regression analysis. In 2012, after a mean follow-up of 4.3 years, 8 of the 50 SAH patients were divorced or separated, whereas after 8.8 years only 1 additional relationship had ended. In our regression model analysis, a "short duration of relationship" before SAH and the presence of a "few minor somatic deficits" were associated with a higher likelihood of divorce or separation in the near future and remained unchanged at long-term follow-up. Contrary to our hypothesis, neither the presence of severe somatic or cognitive deficits nor clinical evaluation scores reliably predicted divorce or separation after SAH. Copyright © 2018 Elsevier Inc. All rights reserved.

Social support and health among elderly Kuwaitis.

PubMed

Al-Kandari, Yagoub Y; Crews, Douglas E

2014-07-01

The aim of this study was to examine differences in several aspects of health between Kuwaiti men and women aged 60 years and over across three age categories (60-69, 70-79, 80+ years). The relationships between several social support variables, somatic symptoms and systolic and diastolic blood pressures were examined. A total of 1427 adult men (472) and women (955) aged 60 years and over representing all six governorates were selected. Data were collected during 2008-2009 by interview and completion of a questionnaire by participants in their own homes, after obtaining their informed consent. The Social Support Scale (SSS), Frequency of Contact Scale (FOC), Strength of Relations (SOR), Somatic Symptoms Inventory (SSI) and self-rated scales of general health were included. Systolic and diastolic blood pressures were measured. The data show that self-rated health and health in the last year differ significantly across age groups. Glycaemia differed significantly across the three age groups for the total sample. Systolic and diastolic blood pressure were higher in older respondents than younger ones, but no significant differences were observed between men and women. No significant differences in somatic symptoms were observed across the three age groups. Strength of relationship, frequency of contact, social support and children living with an elderly adult were all associated with fewer somatic symptoms, and all, except social support, were associated with lower systolic and diastolic blood pressure. Having children, the perception of social support, frequency of contact with, and strength of, relationships with kin are important modulators of somatic symptoms and blood pressure among elderly Kuwaitis.

Cellular and molecular changes associated with somatic embryogenesis induction in Agave tequilana.

PubMed

Portillo, L; Olmedilla, A; Santacruz-Ruvalcaba, F

2012-10-01

In spite of the importance of somatic embryogenesis for basic research in plant embryology as well as for crop improvement and plant propagation, it is still unclear which mechanisms and cell signals are involved in acquiring embryogenic competence by a somatic cell. The aim of this work was to study cellular and molecular changes involved in the induction stage in calli of Agave tequilana Weber cultivar azul in order to gain more information on the initial stages of somatic embryogenesis in this species. Cytochemical and immunocytochemical techniques were used to identify differences between embryogenic and non-embryogenic cells from several genotypes. Presence of granular structures was detected after somatic embryogenesis induction in embryogenic cells; composition of these structures as well as changes in protein and polysaccharide distribution was studied using Coomassie brilliant blue and Periodic Acid-Schiff stains. Distribution of arabinogalactan proteins (AGPs) and pectins was investigated in embryogenic and non-embryogenic cells by immunolabelling using anti-AGP monoclonal antibodies (JIM4, JIM8 and JIM13) as well as an anti-methyl-esterified pectin-antibody (JIM7), in order to evaluate major modifications in cell wall composition in the initial stages of somatic embryogenesis. Our observations pointed out that induction of somatic embryogenesis produced accumulation of proteins and polysaccharides in embryogenic cells. Presence of JIM8, JIM13 and JIM7 epitopes were detected exclusively in embryogenic cells, which supports the idea that specific changes in cell wall are involved in the acquisition of embryogenic competence of A. tequilana.

The contribution of mammary infections by coagulase-negative staphylococci to the herd bulk milk somatic cell count.

PubMed

Rainard, P; Ducelliez, M; Poutrel, B

1990-01-01

Quarter foremilk samples were taken at 2-3 weekly intervals for several years in an experimental herd comprising about 45 cows. The samples were submitted to bacteriological analysis and somatic cell counting. The most prevalent quarter infections from 1982 to 1988 were by coagulase-negative staphylococci (15-20% of all the quarters sampled). Most of these (75.6%) persisted until drying-off. Dry cow therapy eliminated 86.5% of these infections. Comparison of udder quarters within cows, involving 775 samples from pairs of non-infected quarters and quarters infected by coagulase-negative staphylococci, yielded geometric means of somatic cell counts of 210,000 and 420,000 cells/ml, respectively. The correlation (r = 0.87) between the herd bulk milk somatic cell count (SCC) and its estimation from the quarter milk somatic cell count performed on the same day allowed us to evaluate the contribution of the different categories of quarters, according to their infection status, to the herd bulk milk SCC. Quarters infected by a major pathogen (8.5% of samples) gave rise to 46.6% of the total number of cells, while quarters infected by coagulase-negative staphylococci (17.8% of samples) gave rise to 18.1%. Although coagulase-negative staphylococci represented only a secondary source of somatic cells as compared to major pathogens, they were not a negligible source considering the threshold of 300,000 somatic cells advocated for herd milk of good quality.

Posttraumatic stress disorder and somatic symptoms among child and adolescent survivors following the Lushan earthquake in China: A six-month longitudinal study.

PubMed

Zhang, Jun; Zhu, Shenyue; Du, Changhui; Zhang, Ye

2015-08-01

To explore somatic conditions in a sample of 2299 child and adolescent survivors of an earthquake and their relationship to posttraumatic stress disorder (PTSD) symptoms. The Children's Revised Impact of Event Scale, the Patient Health Questionnaire (PHQ)-13 scale, a short version of PHQ-15 scale that omits two items involving sexual pain/problems and menstrual problems, and a project-developed questionnaire were administered to participants three and six months after the earthquake. Among child and adolescent survivors, the prevalence rates of probable PTSD were 37.4 and 24.2% three and six months, respectively, after the earthquake. The most common somatic symptoms were trouble sleeping (58.4 and 48.4%), feeling tired or having low energy (52.0 and 46.1%), and stomach pain (45.8 and 45.4%) after three and six months, respectively. Several specific somatic symptoms evaluated three months after the earthquake including trouble sleeping, headache, and shortness of breath were predictors of the overall PTSD symptoms evaluated six months after the earthquake. Additionally, the symptom of hyperarousal evaluated after three months could predict the overall somatic symptoms evaluated after six months. PTSD and somatic symptoms were common after the earthquake, and a longitudinal association between PTSD and somatic symptoms was detected among child and adolescent survivors. These findings have implications in China and possibly elsewhere. Copyright © 2015 Elsevier Inc. All rights reserved.

Somatization is associated with worse outcome in a chiropractic patient population with neck pain and low back pain.

PubMed

Ailliet, L; Rubinstein, S M; Knol, D; van Tulder, M W; de Vet, H C W

2016-02-01

To determine if psychosocial factors are associated with outcome in patients with neck pain or low back pain. In a prospective, multi-center chiropractic practice-based cohort study in Belgium and The Netherlands, 917 patients, of which 326 with neck pain and 591 with low back pain, completed self-administered questionnaires at baseline, following the second visit, and at 1, 3, 6 and 12 months. Psychosocial factors assessed at baseline were: distress, depression, anxiety and somatization via the Four Dimensional Symptom Questionnaire, patient's beliefs regarding the effect of physical activity and work on their complaint via the Fear Avoidance Beliefs Questionnaire, and social support via the Feij social support scale. Primary outcome measures were perceived recovery, pain intensity, and functional status which was measured with the Neck Disability Index and Oswestry Disability Index. A univariable regression analysis to estimate the relation between each psychological variable and outcome was followed by a multivariable multilevel regression analysis. There were no differences in baseline patient characteristics between the patient population from Belgium and the Netherlands. Somatization scores are consistently associated with perceived recovery, functional status and pain for both neck pain and low-back pain. Depression was associated with poorer functioning in patients with LBP. There was a small association between fear and function and pain for patients with neck pain or low-back pain. Somatization was the only variable consistently found to be associated with diminished perceived recovery, higher degree of neck or low back disability, and increased neck or low back pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fecal Incontinence in Adolescents Is Associated With Child Abuse, Somatization, and Poor Health-related Quality of Life.

PubMed

Rajindrajith, Shaman; Devanarayana, Niranga Manjuri; Benninga, Marc Alexander

2016-05-01

The aim of this study was to evaluate the association between fecal incontinence (FI), child abuse, somatization, and health-related quality of life (HRQoL) in adolescents. Adolescents (ages 13-18 years) were selected from 4 semi-urban schools in the Gampaha district, Sri Lanka. A validated, self-administered questionnaire was used for data collection. FI was defined as at least 1 episode of leakage of feces per month. A total of 1807 adolescents were analyzed (boys 973 [53.8%], mean age 14.4 years, standard deviation [SD] 1.4 years). A total of 47 (2.6%) had FI. Prevalence of sexual abuse (17% vs 2.3% in controls, P < 0.0001), emotional abuse (40.4% vs 22.7%, P < 0.0001), and physical abuse (51% vs 24.3%, P < 0.0001) was significantly higher in children with FI. Adolescents with FI had higher mean somatization scores [mean 20.1, (SD 14.5) vs mean 9.3, (SD 9.2)] compared with those without FI (P < 0.0001). Those with FI also had lower HRQoL scores for physical functioning, social functioning, emotional functioning domains, and performances at school, together with a lower overall HRQoL score compared with those without FI (74.6 vs 87.1, P < 0.0001). There is a significant association between FI and physical, sexual, and emotional abuse. They also have a higher somatization score and a poor HRQoL score in physical, emotional, social, and school functioning domains compared with those without FI.

Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder.

PubMed

Laursen, Thomas Munk; Munk-Olsen, Trine; Agerbo, Esben; Gasse, Christiane; Mortensen, Preben Bo

2009-07-01

Excess mortality from heart disease is observed in patients with severe mental disorder. This excess mortality may be rooted in adverse effects of pharmacological or psychotropic treatment, lifestyle factors, or inadequate somatic care. To examine whether persons with severe mental disorder, defined as persons admitted to a psychiatric hospital with bipolar affective disorder, schizoaffective disorder, or schizophrenia, are in contact with hospitals and undergoing invasive procedures for heart disease to the same degree as the nonpsychiatric general population, and to determine whether they have higher mortality rates of heart disease. A population-based cohort of 4.6 million persons born in Denmark was followed up from 1994 to 2007. Rates of mortality, somatic contacts, and invasive procedures were estimated by survival analysis. Incidence rate ratios of heart disease admissions and heart disease mortality as well as probability of invasive cardiac procedures. The incidence rate ratio of heart disease contacts in persons with severe mental disorder compared with the rate for the nonpsychiatric general population was only slightly increased, at 1.11 (95% confidence interval, 1.08-1.14). In contrast, their excess mortality rate ratio from heart disease was 2.90 (95% confidence interval, 2.71-3.10). Five years after the first contact for somatic heart disease, the risk of dying of heart disease was 8.26% for persons with severe mental disorder (aged <70 years) but only 2.86% in patients with heart disease who had never been admitted to a psychiatric hospital. The fraction undergoing invasive procedures within 5 years was reduced among patients with severe mental disorder as compared with the nonpsychiatric general population (7.04% vs 12.27%, respectively). Individuals with severe mental disorder had only negligible excess rates of contact for heart disease. Given their excess mortality from heart disease and lower rates of invasive procedures after first contact, it would seem that the treatment for heart disease offered to these individuals in Denmark is neither sufficiently efficient nor sufficiently intensive. This undertreatment may explain part of their excess mortality.

Embodying analysis: the body and the therapeutic process.

PubMed

Martini, Salvatore

2016-02-01

This paper considers the transfer of somatic effects from patient to analyst, which gives rise to embodied countertransference, functioning as an organ of primitive communication. By means of processes of projective identification, the analyst experiences somatic disturbances within himself or herself that are connected to the split-off complexes of the analysand. The analysty's own attempt at mind-body integration ushers the patient towards a progressive understanding and acceptance of his or her inner suffering. Such experiences of psychic contagion between patient and analyst are related to Jung's 'psychology of the transference' and the idea of the 'subtle body' as an unconscious shared area. The re-attribution of meaning to pre-verbal psychic experiences within the 'embodied reverie' of the analyst enables the analytic dyad to reach the archetypal energies and structuring power of the collective unconscious. A detailed case example is presented of how the emergence of the vitalizing connection between the psyche and the soma, severed through traumatic early relations with parents or carers, allows the instinctual impulse of the Self to manifest, thereby reactivating the process of individuation. © 2016, The Society of Analytical Psychology.

Coordination of m6A mRNA methylation and gene transcription by ZFP217 regulates pluripotency and reprogramming

PubMed Central

Aguilo, Francesca; Zhang, Fan; Sancho, Ana; Fidalgo, Miguel; Di Cecilia, Serena; Vashisht, Ajay; Lee, Dung-Fang; Chen, Chih-Hung; Rengasamy, Madhumitha; Andino, Blanca; Jahouh, Farid; Roman, Angel; Krig, Sheryl R.; Wang, Rong; Zhang, Weijia; Wohlschlegel, James A.; Wang, Jianlong; Walsh, Martin J.

2015-01-01

SUMMARY Epigenetic and epitranscriptomic networks have important functions in maintaining pluripotency of embryonic stem cells (ESCs) and somatic cell reprogramming. However the mechanisms integrating the actions of these distinct networks are only partially understood. Here, we show that the chromatin-associated zinc finger protein 217 (ZFP217) coordinates epigenetic and epitranscriptomic regulation. ZFP217 interacts with several epigenetic regulators, activates transcription of key pluripotency genes, and modulates N6-methyladenosine (m6A) deposition on their transcripts by sequestering the enzyme m6A methyltransferase-like 3 (METTL3). Consistently, Zfp217 depletion compromises ESC self-renewal and somatic cell reprogramming, globally increases m6A RNA levels, and enhances m6A modification of Nanog, Sox2, Klf4, and c-Myc mRNAs, promoting their degradation. ZFP217 binds its own target gene mRNAs, which are also METTL3-associated, and is enriched at promoters of m6A-modified transcripts. Collectively, these findings shed light on how a transcription factor can tightly couple gene transcription to m6A RNA modification to insure ESC identity. PMID:26526723

Engagement in multidisciplinary interventions for pediatric chronic pain: parental expectations, barriers, and child outcomes.

PubMed

Simons, Laura E; Logan, Deirdre E; Chastain, Laura; Cerullo, Madelin

2010-05-01

To examine the adherence to the recommendations of pain treatment among children and adolescents evaluated for a variety of chronic and recurrent pain conditions. Several measures during initial evaluation and after 3 months were collected to assess satisfaction with initial evaluation, adherence to multidisciplinary recommendations, pain ratings, somatic symptoms, functional limitations, and school attendance. Of the 120 patients who initially enrolled in the study, 70 parents and 57 children participated in 3-month follow-up interviews and reported significantly fewer doctor visits, decreased somatic symptoms, fewer functional limitations, and decreased pain compared with their initial evaluation. Adherence to multidisciplinary recommendations ranged from 46.7% to 100% with the highest level of overall adherence to physical therapy. Factors associated with adherence varied across type of recommendation. For medical recommendations, higher parent-reported patient satisfaction and expectations that medical tests would be beneficial were associated with engagement in medical treatment, whereas parent reports of negative attitude-type barriers and experience with surgery were associated with less frequent engagement in recommended treatment. With regard to physical therapy recommendations, only earlier experience with exercise was associated with better adherence. For psychologic recommendations, familiarity with hypnosis and biofeedback in addition to positive expectations regarding psychologic treatment and biofeedback were all associated with subsequent engagement in psychologic treatment. Lastly, we identified modest associations between functional improvements and adherence to specific recommendations. Results of this study support the importance of examining adherence to multidisciplinary interventions among children and adolescents with chronic pain.

Pathogen Trojan Horse Delivers Bioactive Host Protein to Alter Maize Anther Cell Behavior in Situ.

PubMed

van der Linde, Karina; Timofejeva, Ljudmilla; Egger, Rachel L; Ilau, Birger; Hammond, Reza; Teng, Chong; Meyers, Blake C; Doehlemann, Gunther; Walbot, Virginia

2018-03-01

Small proteins are crucial signals during development, host defense, and physiology. The highly spatiotemporal restricted functions of signaling proteins remain challenging to study in planta. The several month span required to assess transgene expression, particularly in flowers, combined with the uncertainties from transgene position effects and ubiquitous or overexpression, makes monitoring of spatiotemporally restricted signaling proteins lengthy and difficult. This situation could be rectified with a transient assay in which protein deployment is tightly controlled spatially and temporally in planta to assess protein functions, timing, and cellular targets as well as to facilitate rapid mutagenesis to define functional protein domains. In maize ( Zea mays ), secreted ZmMAC1 (MULTIPLE ARCHESPORIAL CELLS1) was proposed to trigger somatic niche formation during anther development by participating in a ligand-receptor module. Inspired by Homer's Trojan horse myth, we engineered a protein delivery system that exploits the secretory capabilities of the maize smut fungus Ustilago maydis , to allow protein delivery to individual cells in certain cell layers at precise time points. Pathogen-supplied ZmMAC1 cell-autonomously corrected both somatic cell division and differentiation defects in mutant Zm mac1-1 anthers. These results suggest that exploiting host-pathogen interactions may become a generally useful method for targeting host proteins to cell and tissue types to clarify cellular autonomy and to analyze steps in cell responses. © 2018 American Society of Plant Biologists. All rights reserved.

Systematic review of measurement properties of questionnaires measuring somatization in primary care patients.

PubMed

Sitnikova, Kate; Dijkstra-Kersten, Sandra M A; Mokkink, Lidwine B; Terluin, Berend; van Marwijk, Harm W J; Leone, Stephanie S; van der Horst, Henriëtte E; van der Wouden, Johannes C

2017-12-01

The aim of this review is to critically appraise the evidence on measurement properties of self-report questionnaires measuring somatization in adult primary care patients and to provide recommendations about which questionnaires are most useful for this purpose. We assessed the methodological quality of included studies using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. To draw overall conclusions about the quality of the questionnaires, we conducted an evidence synthesis using predefined criteria for judging the measurement properties. We found 24 articles on 9 questionnaires. Studies on the Patient Health Questionnaire-15 (PHQ-15) and the Four-Dimensional Symptom Questionnaire (4DSQ) somatization subscale prevailed and covered the broadest range of measurement properties. These questionnaires had the best internal consistency, test-retest reliability, structural validity, and construct validity. The PHQ-15 also had good criterion validity, whereas the 4DSQ somatization subscale was validated in several languages. The Bodily Distress Syndrome (BDS) checklist had good internal consistency and structural validity. Some evidence was found for good construct validity and criterion validity of the Physical Symptom Checklist (PSC-51) and good construct validity of the Symptom Check-List (SCL-90-R) somatization subscale. However, these three questionnaires were only studied in a small number of primary care studies. Based on our findings, we recommend the use of either the PHQ-15 or 4DSQ somatization subscale for somatization in primary care. Other questionnaires, such as the BDS checklist, PSC-51 and the SCL-90-R somatization subscale show promising results but have not been studied extensively in primary care. Copyright © 2017 Elsevier Inc. All rights reserved.

Health Effects Associated With Geographical Area of Residence During the 1991 Gulf War: A Comparative Health Study of Iraqi Soldiers and Civilians

PubMed Central

Jamil, Hikmet; Hamdan, Thamer A.; Grzybowski, Mary; Arnetz, Bengt B.

2011-01-01

Context Although Iraqis sustained the gravest exposure conditions during the 1991 Gulf War (GW), little is known about the possible relationship between environmental exposures during the GW and long-term health in Iraqis. Objective To study the relationship between distance from Kuwait during the GW and somatic health among Iraqi Soldiers vs civilians. Methods A survey questionnaire was distributed to a sample of 742 GW veterans and 413 civilians in Iraq. The odds ratios were calculated for somatic disorders as a function of distance from Kuwait during the GW, as well as a self-reported environmental exposure index. Results Soldiers reported a significantly higher prevalence of somatic disorders as compared to civilians. Soldiers closest to Kuwait reported significantly more somatic disorders as compared to Soldiers deployed further away from Kuwait. Conclusion Iraqi GW veterans are at an increased risk of numerous somatic disorders. Soldiers are at an increased risk compared to civilians, suggesting that war-associated exposures are of etiologic relevance. PMID:21805460

Clonal evolution models of tumor heterogeneity.

PubMed

Shlush, Liran I; Hershkovitz, Dov

2015-01-01

Somatic/clonal evolution is the process of sequential acquisition of vertically transmittable genetic/epigenetic elements in multicellular organisms. Cancer is the result of somatic evolution. Understanding the processes that shape the evolution of individual tumors might help us to treat cancer more efficiently. The initiating genetic/epigenetic events occur in functional cells and provide the cell of origin a selective advantage under a changing environment. The initiating genetic events tend to be enriched in specific tissues (and are sometimes specific for those tissues), as different tissues undergo different changes in the environment that will activate selective forces on different cells of origin. For the initial clonal expansion to occur premalignant clones need to have a relative fitness advantage over their competitors. It is estimated that the premalignant phase can take several years. Once the premalignant clonal expansion is established, the premalignant cells will contribute to the changing environment and will start competing among themselves. In late stages of cancer evolution the environmental changes might be similar across different tissues, including a lack of physical space, a shortage of energy, and activation of the immune system, and more and more of the hallmarks of cancer will evolve. In this review we will explore the possible clinical relevance of the heterogeneity that evolves during this long somatic evolution. Above all, it should be stressed that the earlier the clonal expansion is recognized, the less diverse and less fit for survival the cells in the population are.

Combined mismatch repair and POLE/POLD1 defects explain unresolved suspected Lynch syndrome cancers

PubMed Central

Jansen, Anne ML; van Wezel, Tom; van den Akker, Brendy EWM; Ventayol Garcia, Marina; Ruano, Dina; Tops, Carli MJ; Wagner, Anja; Letteboer, Tom GW; Gómez-García, Encarna B; Devilee, Peter; Wijnen, Juul T; Hes, Frederik J; Morreau, Hans

2016-01-01

Many suspected Lynch Syndrome (sLS) patients who lack mismatch repair (MMR) germline gene variants and MLH1 or MSH2 hypermethylation are currently explained by somatic MMR gene variants or, occasionally, by germline POLE variants. To further investigate unexplained sLS patients, we analyzed leukocyte and tumor DNA of 62 sLS patients using gene panel sequencing including the POLE, POLD1 and MMR genes. Forty tumors showed either one, two or more somatic MMR variants predicted to affect function. Nine sLS tumors showed a likely ultramutated phenotype and were found to carry germline (n=2) or somatic variants (n=7) in the POLE/POLD1 exonuclease domain (EDM). Six of these POLE/POLD1-EDM mutated tumors also carried somatic MMR variants. Our findings suggest that faulty proofreading may result in loss of MMR and thereby in microsatellite instability. PMID:26648449

Functional and structural microanatomy of the fetal sciatic nerve.

PubMed

Creze, Maud; Zaitouna, Mazen; Krystel, Nyangoh Timoh; Diallo, Djibril; Lebacle, Cédric; Bellin, Marie-France; Ducreux, Denis; Benoit, Gérard; Bessede, Thomas

2017-10-01

The ultrastructure of a nerve has implications for surgical nerve repair. The aim of our study was to characterize the fascicular versus fibrillar anatomy and the autonomic versus somatic nature of the fetal sciatic nerve (SN). Immunohistochemistry for vesicular acetylcholine transporter, tyrosine hydroxylase, and peripheral myelin protein 22 was performed to identify cholinergic, adrenergic, and somatic axons, respectively, in the human fetal SN. Two-dimensional (2D) analysis and 3D reconstructions were performed. The fetal SN is composed of one-third stromal tissue and two-thirds neural tissue. Autonomic fibers are predominant over somatic fibers within the neural tissue. The distribution of somatic fibers is initially random, but then become topographically organized after intra- and interfascicular rearrangements have occurred within the nerve. The fetal model presents limitations but enables illustration of the nature of the nerve fibers and the 3D fascicular anatomy of the SN. Muscle Nerve 56: 787-796, 2017. © 2017 Wiley Periodicals, Inc.

Stochastic modeling indicates that aging and somatic evolution in the hematopoetic system are driven by non-cell-autonomous processes.

PubMed

Rozhok, Andrii I; Salstrom, Jennifer L; DeGregori, James

2014-12-01

Age-dependent tissue decline and increased cancer incidence are widely accepted to be rate-limited by the accumulation of somatic mutations over time. Current models of carcinogenesis are dominated by the assumption that oncogenic mutations have defined advantageous fitness effects on recipient stem and progenitor cells, promoting and rate-limiting somatic evolution. However, this assumption is markedly discrepant with evolutionary theory, whereby fitness is a dynamic property of a phenotype imposed upon and widely modulated by environment. We computationally modeled dynamic microenvironment-dependent fitness alterations in hematopoietic stem cells (HSC) within the Sprengel-Liebig system known to govern evolution at the population level. Our model for the first time integrates real data on age-dependent dynamics of HSC division rates, pool size, and accumulation of genetic changes and demonstrates that somatic evolution is not rate-limited by the occurrence of mutations, but instead results from aged microenvironment-driven alterations in the selective/fitness value of previously accumulated genetic changes. Our results are also consistent with evolutionary models of aging and thus oppose both somatic mutation-centric paradigms of carcinogenesis and tissue functional decline. In total, we demonstrate that aging directly promotes HSC fitness decline and somatic evolution via non-cell-autonomous mechanisms.

Pituitary Volumes Are Reduced in Patients with Somatization Disorder

PubMed Central

Yildirim, Hanefi; Sirlier, Burcu; Kayali, Alperen

2012-01-01

Objective Despite of the suggested physiological relationship between somatoform disorder and disturbances in HPA axis function no volumetric study of pituitary volumes in somatization disorder has been carried out. Therefore, we aimed to use structural MRI to evaluate the pituitary volumes of the patients with somatization disorder. Methods Eighteen female patients with somatization disorder according to DSM-IV and same number of healthy controls were included into the study. All subjects were scanned using a 1.5-T General Electric (GE; Milwaukee, USA) scanner. Pituitary volume measurements were determined by using manuallly tracings according to standard antomical atlases. Results It was found significantly smaller pituitary volumes of the whole group of somatization patients compared to healthy (t=-3.604, p=0.001). ANCOVA predicting pituitary volumes demonstrated a significant main effect of diagnostic group (F=13.530, p<0.001) but TBV (F=1.924, p>0.05) or age (F=1.159, p>0.05). It was determined that there was no significant correlation between smaller pituitary volumes and the duration of illness (r=0.16, p>0.05) in the patient group. Conclusion In conclusion, we suggest that the patients with somatization disorder might have significantly smaller pituitary volumes compared to healthy control subjects. PMID:22993528

Three forms of somatization presenting in primary care settings in Spain.

PubMed

García-Campayo, J; Lobo, A; Pérez-Echeverría, M J; Campos, R

1998-09-01

The objective of this paper is to study the prevalence and clinical characteristics of functional, hypochondriacal, and presenting somatization (FSTS, HSTS, and PSTS, respectively) defined by standardized criteria, as well as the validity of their distinction in primary care in Spain. A two-stage epidemiological study of a representative sample (N = 1559) of primary care patients was carried out. In the first phase, the validated Spanish versions of General Health Questionnaire, Mini-Mental State Examination, and CAGE were used. In the second phase, the Standardized Polyvalent Psychiatric Interview, an interview for the multiaxial assessment of medical patients, was employed. The prevalence of any form of somatization in Spain was 21.3% (FSTS: 16.2%, PSTS: 9.4%, HSTS: 6.7%). Overlap of any of the three clinical forms was very frequent (42.7%). FSTS patients tended to be more chronic and showed higher scores in fatigue but lower scores in both depression and anxiety. Chronicity was frequent among somatizers, particularly in those who fulfilled more than one kind of somatization. Differences in diagnostic distribution among the three groups were also observed. In conclusion, this is the first study giving support to the validity of the distinction among three types of somatization in Spain, but overlap was more frequent than reported in North American studies.

CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline

PubMed Central

Campbell, Anne C.; Updike, Dustin L.

2015-01-01

Germ granules (P granules) in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the misexpression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcripts do not increase in the young adult germline when P granules are impaired. Instead, we found that impairing P granules causes sperm-specific mRNAs to become highly overexpressed. This includes the accumulation of major sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by feminization of the germline. A core component of P granules, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to license transcripts for germline expression. However, impairing CSR-1 has very little effect on the accumulation of its mRNA targets. Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm-specific mRNAs from being transcribed in the hermaphrodite germline. These findings suggest that P granules protect germline integrity through two different mechanisms, by (1) preventing the inappropriate expression of somatic proteins at the level of translational regulation, and by (2) functioning with CSR-1 to limit the domain of sperm-specific expression at the level of transcription. PMID:25968310

Profile Analyses of the Personality Assessment Inventory Following Military-Related Traumatic Brain Injury

PubMed Central

Kennedy, Jan E.; Cooper, Douglas B.; Reid, Matthew W.; Tate, David F.; Lange, Rael T.

2015-01-01

Personality Assessment Inventory (PAI) profiles were examined in 160 U.S. service members (SMs) following mild–severe traumatic brain injury (TBI). Participants who sustained a mild TBI had significantly higher PAI scores than those with moderate–severe TBI on eight of the nine clinical scales examined. A two-step cluster analysis identified four PAI profiles, heuristically labeled “High Distress”, “Moderate Distress”, “Somatic Distress,” and “No Distress”. Postconcussive and posttraumatic stress symptom severity was highest for the High Distress group, followed by the Somatic and Moderate Distress groups, and the No Distress group. Profile groups differed in age, ethnicity, rank, and TBI severity. Findings indicate that meaningful patterns of behavioral and personality characteristics can be detected in active duty military SMs following TBI, which may prove useful in selecting the most efficacious rehabilitation strategies. PMID:25857403

Profile analyses of the Personality Assessment Inventory following military-related traumatic brain injury.

PubMed

Kennedy, Jan E; Cooper, Douglas B; Reid, Matthew W; Tate, David F; Lange, Rael T

2015-05-01

Personality Assessment Inventory (PAI) profiles were examined in 160 U.S. service members (SMs) following mild-severe traumatic brain injury (TBI). Participants who sustained a mild TBI had significantly higher PAI scores than those with moderate-severe TBI on eight of the nine clinical scales examined. A two-step cluster analysis identified four PAI profiles, heuristically labeled "High Distress", "Moderate Distress", "Somatic Distress," and "No Distress". Postconcussive and posttraumatic stress symptom severity was highest for the High Distress group, followed by the Somatic and Moderate Distress groups, and the No Distress group. Profile groups differed in age, ethnicity, rank, and TBI severity. Findings indicate that meaningful patterns of behavioral and personality characteristics can be detected in active duty military SMs following TBI, which may prove useful in selecting the most efficacious rehabilitation strategies. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Somatization symptoms and hypochondriacal features in the general population.

PubMed

Rief, W; Hessel, A; Braehler, E

2001-01-01

The principal goal of this study is to examine the base rates of somatoform symptoms and of hypochondriacal features in the general population. A representative sample of 2050 persons in Germany was examined by use of screening for somatoform symptoms and the Whiteley Index. The most frequent somatoform symptoms were back pain, joint pain, pain in extremities, and headache, as well as abdominal symptoms (bloating or intolerance of several foods) and cardiovascular symptoms (palpitation). People reported a mean of two somatization symptoms of DSM-IV somatization disorder (SD) during the prior 2 years. Strong age and medium gender effects were found for most somatoform symptoms, as well as for composite indices. However, the sex ratio suggested in DSM-IV for SD seems to be an overestimation. Hypochondriacal features showed only small sex differences but, again, pronounced age effects. In contrast to low rates for SD, the base rates for somatization and hypochondriacal features were high and represented the health care relevance of subthreshold syndromes. We present base rates of hypochondriacal and somatization features that may be important facets in the development of classification criteria and in the interpretation of health care expenditure.

HSP90 Shapes the Consequences of Human Genetic Variation.

PubMed

Karras, Georgios I; Yi, Song; Sahni, Nidhi; Fischer, Máté; Xie, Jenny; Vidal, Marc; D'Andrea, Alan D; Whitesell, Luke; Lindquist, Susan

2017-02-23

HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of genetic stability at SSR loci during somatic embryogenesis in maritime pine (Pinus pinaster).

PubMed

Marum, Liliana; Rocheta, Margarida; Maroco, João; Oliveira, M Margarida; Miguel, Célia

2009-04-01

Somatic embryogenesis (SE) is a propagation tool of particular interest for accelerating the deployment of new high-performance planting stock in multivarietal forestry. However, genetic conformity in in vitro propagated plants should be assessed as early as possible, especially in long-living trees such as conifers. The main objective of this work was to study such conformity based on genetic stability at simple sequence repeat (SSR) loci during somatic embryogenesis in maritime pine (Pinus pinaster Ait.). Embryogenic cell lines (ECLs) subjected to tissue proliferation during 6, 14 or 22 months, as well as emblings regenerated from several ECLs, were analyzed. Genetic variation at seven SSR loci was detected in ECLs under proliferation conditions for all time points, and in 5 out of 52 emblings recovered from somatic embryos. Three of these five emblings showed an abnormal phenotype consisting mainly of plagiotropism and loss of apical dominance. Despite the variation found in somatic embryogenesis-derived plant material, no correlation was established between genetic stability at the analyzed loci and abnormal embling phenotype, present in 64% of the emblings. The use of microsatellites in this work was efficient for monitoring mutation events during the somatic embryogenesis in P. pinaster. These molecular markers should be useful in the implementation of new breeding and deployment strategies for improved trees using SE.

Dogs cloned from adult somatic cells.

PubMed

Lee, Byeong Chun; Kim, Min Kyu; Jang, Goo; Oh, Hyun Ju; Yuda, Fibrianto; Kim, Hye Jin; Hossein, M Shamim; Shamim, M Hossein; Kim, Jung Ju; Kang, Sung Keun; Schatten, Gerald; Hwang, Woo Suk

2005-08-04

Several mammals--including sheep, mice, cows, goats, pigs, rabbits, cats, a mule, a horse and a litter of three rats--have been cloned by transfer of a nucleus from a somatic cell into an egg cell (oocyte) that has had its nucleus removed. This technology has not so far been successful in dogs because of the difficulty of maturing canine oocytes in vitro. Here we describe the cloning of two Afghan hounds by nuclear transfer from adult skin cells into oocytes that had matured in vivo. Together with detailed sequence information generated by the canine-genome project, the ability to clone dogs by somatic-cell nuclear transfer should help to determine genetic and environmental contributions to the diverse biological and behavioural traits associated with the many different canine breeds.

PHF6 Degrees of Separation: The Multifaceted Roles of a Chromatin Adaptor Protein.

PubMed

Todd, Matthew A M; Ivanochko, Danton; Picketts, David J

2015-06-19

The importance of chromatin regulation to human disease is highlighted by the growing number of mutations identified in genes encoding chromatin remodeling proteins. While such mutations were first identified in severe developmental disorders, or in specific cancers, several genes have been implicated in both, including the plant homeodomain finger protein 6 (PHF6) gene. Indeed, germline mutations in PHF6 are the cause of the Börjeson-Forssman-Lehmann X-linked intellectual disability syndrome (BFLS), while somatic PHF6 mutations have been identified in T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Studies from different groups over the last few years have made a significant impact towards a functional understanding of PHF6 protein function. In this review, we summarize the current knowledge of PHF6 with particular emphasis on how it interfaces with a distinct set of interacting partners and its functional roles in the nucleoplasm and nucleolus. Overall, PHF6 is emerging as a key chromatin adaptor protein critical to the regulation of neurogenesis and hematopoiesis.

Coherent Somatic Mutation in Autoimmune Disease

PubMed Central

Ross, Kenneth Andrew

2014-01-01

Background Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation. Results Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed. Conclusions The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases. PMID:24988487

The association of work stress with somatic symptoms in Chinese working women: a large cross-sectional survey.

PubMed

Li, Jian; Ding, Hui; Han, Wei; Jin, Lei; Kong, Ling-Na; Mao, Kang-Na; Wang, Hong; Wu, Jiang-Ping; Wu, Ying; Yang, Liu; Zhou, Yu; Wang, You-Xin; Wang, Wei; Loerbroks, Adrian; Angerer, Peter

2016-10-01

It has been suggested that the relationship between work stress and somatic symptoms (e.g., cardiopulmonary, gastrointestinal complaints, general pain, and fatigue) is particularly pronounced in women. As evidence from China is sparse, we used a large sample of Chinese working women to test those potential associations. Data were obtained from a cross-sectional study of 6826 working women in five urban areas in China who were free from major clinical disease. The sample was drawn from five occupations (physicians, nurses, school teachers, bank employees, and industrial workers). The Effort-Reward Imbalance Questionnaire and Patient Health Questionnaire-15 were used to measure work stress and somatic symptoms, respectively. Multivariate ordinal logistic regression was performed to analyze the associations. 52.6% participants reported high work stress in terms of concurrent high effort and low reward. The distribution of severity of somatic symptoms covered the full range from minimal (37.3%) and low (30.6%), to medium (19.7%) and high (12.4%). The adjusted odds ratio of somatic symptoms by high work stress was 2.45 (95% confidence interval=2.24-2.68), and all single psychosocial work factors (effort, reward, and over-commitment) exerted substantial effects on somatic symptoms (odds ratios>2.00). Work stress is strongly associated with somatic symptoms in Chinese working women. Future longitudinal studies and intervention studies are needed to understand and improve women's psychosocial work environment and their psychosomatic health in China and elsewhere. Copyright © 2016 Elsevier Inc. All rights reserved.

The Relationship between Depression, Anxiety, Somatization, Personality and Symptoms of Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia.

PubMed

Koh, Jun Sung; Ko, Hyo Jung; Wang, Sheng-Min; Cho, Kang Joon; Kim, Joon Chul; Lee, Soo-Jung; Pae, Chi-Un

2015-04-01

This study investigated the relationship of personality, depression, somatization, anxiety with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). The LUTS/BPH patients were evaluated with the International Prostate Symptom Score (IPSS), 44-item Big Five Inventory (BFI), the Patient Health Questionnaire-9 (PHQ-9), the PHQ-15, and 7-item Generalized Anxiety Disorder Scale (GAD-7). The LUTS/BPH symptoms were more severe in patients with depression (p=0.046) and somatization (p=0.024), respectively. Neurotic patients were associated with greater levels of depression, anxiety and somatisation (p=0.0059, p=0.004 and p=0.0095, respectively). Patients with high extraversion showed significantly low depression (p=0.00481) and anxiety (p=0.035) than those with low extraversion. Our exploratory results suggest patients with LUTS/BPH may need careful evaluation of psychiatric problem including depression, anxiety and somatization. Additional studies with adequate power and improved designs are necessary to support the present exploratory findings.

Children of people with somatization disorder.

PubMed

Livingston, R

1993-05-01

The author investigated psychopathology, suicidal behavior, child abuse, somatization, and health care utilization in 34 children with a parent who has somatization disorder (SD-P) and two comparison groups: 41 children with a somatizing parent (SOM) (fewer symptoms than required for diagnosis of SD-P), and 30 pediatrically ill controls (CON). Child and parent versions of the Diagnostic Interview for Children and Adolescents were scored for diagnosis and symptom counts in specified categories. Medical records were obtained and abstracted. Children of SD-P had significantly more psychiatric disorders and suicide attempts than did children of SOM or the CON. SD-P and CON had significantly more unexplained physical symptoms than SOM. SD-P showed a trend toward more hospitalizations and experienced significantly more maltreatment. Children of SD-P are at significant risk in several respects. Clinical implications of these findings include a need for awareness and cooperation among general psychiatrists, primary care physicians, and child and adolescent psychiatrists to facilitate detection and treatment of these children's problems.

Association of internet use and depression among the spinal cord injury population.

PubMed

Tsai, I-Hsuan; Graves, Daniel E; Lai, Ching-Huang; Hwang, Lu-Yu; Pompeii, Lisa A

2014-02-01

To examine the relation between the frequency of Internet use and depression among people with spinal cord injury (SCI). Cross-sectional survey. SCI Model Systems. People with SCI (N=4618) who were interviewed between 2004 and 2010. Not applicable. The frequency of Internet use and the severity of depressive symptoms were measured simultaneously by interview. Internet use was reported as daily, weekly, monthly, or none. The depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ-9), with 2 published criteria being used to screen for depressive disorder. The diagnostic method places more weight on nonsomatic items (ie, items 1, 2, and 9), and the cut-off method that determines depression by a (PHQ-9) score ≥10 places more weight on somatic factors. The average scores of somatic and nonsomatic items represented the severity of somatic and nonsomatic symptoms, respectively. Our multivariate logistic regression model indicated that daily Internet users were less likely to have depressive symptoms (odds ratio=.77; 95% confidence interval, .64-.93), if the diagnostic method was used. The linear multivariate regression analysis indicated that daily and weekly Internet usage were associated with fewer nonsomatic symptoms; no significant association was observed between daily or weekly Internet usage and somatic symptoms. People with SCI who used the Internet daily were less likely to have depressive symptoms. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2

PubMed Central

Bayne, Rosemary A.; Donnachie, Douglas J.; Kinnell, Hazel L.; Childs, Andrew J.; Anderson, Richard A.

2016-01-01

STUDY QUESTION Do changes in the expression of bone morphogenetic proteins (BMPs) 2 and 4, and their antagonists Gremlin1 (GREM1) and Gremlin2 (GREM2) during human fetal ovarian development impact on BMP pathway activity and lead to changes in gene expression that may influence the fate and/or function of ovarian somatic cells? STUDY FINDING BMPs 2 and 4 differentially regulate gene expression in cultured human fetal ovarian somatic cells. Expression of some, but not all BMP target genes is antagonised by GREM1 and GREM2, indicating the existence of a mechanism to fine-tune BMP signal intensity in the ovary. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker of immature ovarian somatic cells, is identified as a novel transcriptional target of BMP4. WHAT IS KNOWN ALREADY Extensive re-organisation of the germ and somatic cell populations in the feto-neonatal ovary culminates in the formation of primordial follicles, which provide the basis for a female's future fertility. BMP growth factors play important roles at many stages of ovarian development and function. GREM1, an extracellular antagonist of BMP signalling, regulates the timing of primordial follicle formation in the mouse ovary, and mRNA levels of BMP4 decrease while those of BMP2 increase prior to follicle formation in the human fetal ovary. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Expression of genes encoding BMP pathway components, BMP antagonists and markers of ovarian somatic cells were determined by quantitative (q)RT-PCR in human fetal ovaries (from 8 to 21 weeks gestation) and fetal ovary-derived somatic cell cultures. Ovarian expression of GREM1 protein was confirmed by immunoblotting. Primary human fetal ovarian somatic cell cultures were derived from disaggregated ovaries by differential adhesion and cultured in the presence of recombinant human BMP2 or BMP4, with or without the addition of GREM1 or GREM2. MAIN RESULTS AND THE ROLE OF CHANCE We demonstrate that the expression of BMP antagonists GREM1, GREM2 and CHRD  increases in the lead-up to primordial follicle formation in the human fetal ovary, and that the BMP pathway is active in cultured ovarian somatic cells. This leads to differential changes in the expression of a number of genes, some of which are further modulated by GREM1 and/or GREM2. The positive transcriptional regulation of LGR5 (a marker of less differentiated somatic cells) by BMP4 in vitro suggests that increasing levels of GREM1 and reduced levels of BMP4 as the ovary develops in vivo may act to reduce LGR5 levels and allow pre-granulosa cell differentiation. LIMITATIONS, REASONS FOR CAUTION While we have demonstrated that markers of different somatic cell types are expressed in the cultured ovarian somatic cells, their proportions may not represent the same cells in the intact ovary which also contains germ cells. WIDER IMPLICATIONS OF THE FINDINGS This study extends previous work identifying germ cells as targets of ovarian BMP signalling, and suggests BMPs may regulate the development of both germ and somatic cells in the developing ovary around the time of follicle formation. LARGE SCALE DATA Not applicable. STUDY FUNDING/COMPETING INTERESTS This work was supported by The UK Medical Research Council (Grant No.: G1100357 to RAA), and Medical Research Scotland (Grant No. 345FRG to AJC). The authors have no competing interests to declare. PMID:27385727

BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2.

PubMed

Bayne, Rosemary A; Donnachie, Douglas J; Kinnell, Hazel L; Childs, Andrew J; Anderson, Richard A

2016-09-01

Do changes in the expression of bone morphogenetic proteins (BMPs) 2 and 4, and their antagonists Gremlin1 (GREM1) and Gremlin2 (GREM2) during human fetal ovarian development impact on BMP pathway activity and lead to changes in gene expression that may influence the fate and/or function of ovarian somatic cells? BMPs 2 and 4 differentially regulate gene expression in cultured human fetal ovarian somatic cells. Expression of some, but not all BMP target genes is antagonised by GREM1 and GREM2, indicating the existence of a mechanism to fine-tune BMP signal intensity in the ovary. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker of immature ovarian somatic cells, is identified as a novel transcriptional target of BMP4. Extensive re-organisation of the germ and somatic cell populations in the feto-neonatal ovary culminates in the formation of primordial follicles, which provide the basis for a female's future fertility. BMP growth factors play important roles at many stages of ovarian development and function. GREM1, an extracellular antagonist of BMP signalling, regulates the timing of primordial follicle formation in the mouse ovary, and mRNA levels of BMP4 decrease while those of BMP2 increase prior to follicle formation in the human fetal ovary. Expression of genes encoding BMP pathway components, BMP antagonists and markers of ovarian somatic cells were determined by quantitative (q)RT-PCR in human fetal ovaries (from 8 to 21 weeks gestation) and fetal ovary-derived somatic cell cultures. Ovarian expression of GREM1 protein was confirmed by immunoblotting. Primary human fetal ovarian somatic cell cultures were derived from disaggregated ovaries by differential adhesion and cultured in the presence of recombinant human BMP2 or BMP4, with or without the addition of GREM1 or GREM2. We demonstrate that the expression of BMP antagonists GREM1, GREM2 and CHRD  increases in the lead-up to primordial follicle formation in the human fetal ovary, and that the BMP pathway is active in cultured ovarian somatic cells. This leads to differential changes in the expression of a number of genes, some of which are further modulated by GREM1 and/or GREM2. The positive transcriptional regulation of LGR5 (a marker of less differentiated somatic cells) by BMP4 in vitro suggests that increasing levels of GREM1 and reduced levels of BMP4 as the ovary develops in vivo may act to reduce LGR5 levels and allow pre-granulosa cell differentiation. While we have demonstrated that markers of different somatic cell types are expressed in the cultured ovarian somatic cells, their proportions may not represent the same cells in the intact ovary which also contains germ cells. This study extends previous work identifying germ cells as targets of ovarian BMP signalling, and suggests BMPs may regulate the development of both germ and somatic cells in the developing ovary around the time of follicle formation. Not applicable. This work was supported by The UK Medical Research Council (Grant No.: G1100357 to RAA), and Medical Research Scotland (Grant No. 345FRG to AJC). The authors have no competing interests to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Local anesthesia selection algorithm in patients with concomitant somatic diseases.

PubMed

Anisimova, E N; Sokhov, S T; Letunova, N Y; Orekhova, I V; Gromovik, M V; Erilin, E A; Ryazantsev, N A

2016-01-01

The paper presents basic principles of local anesthesia selection in patients with concomitant somatic diseases. These principles are history taking; analysis of drugs interaction with local anesthetic and sedation agents; determination of the functional status of the patient; patient anxiety correction; dental care with monitoring of hemodynamics parameters. It was found that adhering to this algorithm promotes prevention of urgent conditions in patients in outpatient dentistry.

Central sensitivity syndromes: a new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness.

PubMed

Yunus, Muhammad B

2008-06-01

To discuss the current terminologies used for fibromyalgia syndrome (FMS) and related overlapping conditions, to examine if central sensitivity syndromes (CSS) is the appropriate nosology for these disorders, and to explore the issue of disease versus illness. A literature search was performed through PubMed, Web of Science, and ScienceDirect using a number of keywords, eg, functional somatic syndromes, somatoform disorders, medically unexplained symptoms, organic and nonorganic, and diseases and illness. Relevant articles were then reviewed and representative ones cited. Terminologies currently used for CSS conditions predominantly represent a psychosocial construct and are inappropriate. On the other hand, CSS seems to be the logical nosology based on a biopsychosocial model. Such terms as "medically unexplained symptoms," "somatization," "somatization disorder," and "functional somatic syndromes" in the context of CSS should be abandoned. Given current scientific knowledge, the concept of disease-illness dualism has no rational basis and impedes proper patient-physician communication, resulting in poor patient care. The concept of CSS is likely to promote research, education, and proper patient management. CSS seems to be a useful paradigm and an appropriate terminology for FMS and related conditions. The disease-illness, as well as organic/non-organic dichotomy, should be rejected.

[PIWI protein as a nucleolus visitor in Drosophila melanogaster].

PubMed

Mikhaleva, E A; Iakushev, E Iu; Stoliarenko, A D; Klenov, M S; Pozovskiĭ, Ia M; Gvozdev, V A

2015-01-01

The evolutionarily conserved nuclear Piwi protein of Drosophila melanogaster is a representative of the Argonaute small RNA binding protein family. Guided by small piRNAs, Piwi functions in transposon silencing in somatic and germ cells of the gonad. We found that in ovarian somatic and germ cells, as well as in the established ovarian somatic cell line, Piwi is concentrated predominantly in the nucleolus--the main nuclear compartment, participating not only in rRNA synthesis, but also in various cell stress responses. We demonstrated the colocalization of Piwi with nucleolar marker proteins--fibrillarin and Nopp140. A mutation preventing Piwi transport to the nucleus and disturbing transposon silencing (piwi(Nt)) leads to 6-8-fold upregulation of rRNA genes expression, as evaluated by the level of transcripts of transposon insertions in 28S rRNA genes. RNase treatment of live cultured ovarian somatic cells depletes Piwi from the nucleolus. The same effect is observed upon inhibiting RNA polymerase I which transcribes rRNA, but not RNA polymerase II. In contrast, upon heat shock Piwi is concentrated in the nucleolus and is depleted from the nucleoplasm. These results implicate Piwi in RNA polymerase activity modulation and stress response in the nucleolus. We discuss possible noncanonical Piwi functions along with its canonical role in transposon silencing by piRNAs.

A model of the generation of ataque de nervios: the role of fear of negative affect and fear of arousal symptoms.

PubMed

Hinton, Devon E; Lewis-Fernández, Roberto; Pollack, Mark H

2009-01-01

This article examines a model of the generation of ataque de nervios, according to which both fear of negative affectivity and fear of arousal symptoms are associated with the emergence of ataques. We examine the relationship of fear of negative affectivity and fear of arousal to the severity of ataque de nervios during the last month and the last 6 months among Caribbean Latinos residing in the United States. The measures include a Fear of Anger Scale and the Anxiety Sensitivity Index (ASI), the ASI augmented with two items that assess fear of arousal symptoms common in ataques: chest tightness and a sense of inner heat. In keeping with the model of ataque generation, one-way analysis of variances (ANOVAs) and discriminant function analyses illustrated that items assessing "fear of negative affect" and "fear of somatic and psychological symptoms of arousal" both differentiated well among the levels of ataque severity. In addition, key ataque symptoms-mental incapacitation fears, shakiness, chest tightness, palpitations, and a sense of inner heat-were the best discriminators among levels of ataque severity. In patients with severe ataques, the scores of "fear of negative affect" and "fear of ataque-de-nervios-type somatic and psychological symptoms" were extremely elevated. This further suggests that both these types of fears are associated with this idiom of distress and that the specific content of the fears is linked to the symptom picture of the idiom. This suggests specific therapeutic targets for the treatment of ataque, namely, the reduction of anxiety sensitivity (and more generally negative-emotion and arousal sensitivity) using cognitive behavioral therapy (CBT), relaxation, and mindfulness techniques.

Depression is a major determinant of quality of life in patients with chronic systolic heart failure in general practice.

PubMed

Müller-Tasch, Thomas; Peters-Klimm, Frank; Schellberg, Dieter; Holzapfel, Nicole; Barth, Annika; Jünger, Jana; Szecsenyi, Joachim; Herzog, Wolfgang

2007-12-01

Quality of life (QoL) is severely restricted in patients with chronic heart failure (CHF). Patients frequently suffer from depressive comorbidity. It is not clear, to what extent sociodemographic variables, heart failure severity, somatic comorbidities and depression determine QoL of patients with CHF in primary care. In a cross-sectional analysis, 167 patients, 68.2 +/- 10.1 years old, 68.9% male, New York Heart Association (NYHA) functional class II-IV, Left ventricular ejection fraction (LVEF) < or = 40%, were recruited in their general practitioner's practices. Heart failure severity was assessed with echocardiography and N-terminal brain natriuretic peptide (NT-proBNP); multimorbidity was assessed with the Cumulative Illness Rating Scale (CIRS-G). QoL was measured with the Short Form 36 Health Survey (SF-36) and depression with the depression module of the Patient Health Questionnaire (PHQ-9). Significant correlations with all SF-36 subscales were only found for the CIRS-G (r = -0.18 to -0.36; P < .05) and the PHQ-9 (r = -0.26 to -0.75; P < .01). In multivariate forward regression analyses, the PHQ-9 summary score explained the most part of QoL variance in all of the SF-36 subscales (r2 = 0.17-0.56). LVEF and NT-proBNP did not have significant influence on QoL. Depression is a major determinant of quality of life in patients with chronic systolic heart failure, whereas somatic measures of heart failure severity such as NT-proBNP and LVEF do not contribute to quality of life. Correct diagnosis and treatment of depressive comorbidity in heart failure patients is essential.

Somatic cells initiate primordial follicle activation and govern the development of dormant oocytes in mice.

PubMed

Zhang, Hua; Risal, Sanjiv; Gorre, Nagaraju; Busayavalasa, Kiran; Li, Xin; Shen, Yan; Bosbach, Benedikt; Brännström, Mats; Liu, Kui

2014-11-03

The majority of oocytes in the mammalian ovary are dormant oocytes that are enclosed in primordial follicles by several somatic cells, which we refer to as primordial follicle granulosa cells (pfGCs). Very little is known, however, about how the pfGCs control the activation of primordial follicles and the developmental fates of dormant oocytes. By targeting molecules in pfGCs with several mutant mouse models, we demonstrate that the somatic pfGCs initiate the activation of primordial follicles and govern the quiescence or awakening of dormant oocytes. Inhibition of mTORC1 signaling in pfGCs prevents the differentiation of pfGCs into granulosa cells, and this arrests the dormant oocytes in their quiescent states, leading to oocyte death. Overactivation of mTORC1 signaling in pfGCs accelerates the differentiation of pfGCs into granulosa cells and causes premature activation of all dormant oocytes and primordial follicles. We further show that pfGCs trigger the awakening of dormant oocytes through KIT ligand (KITL), and we present an essential communication network between the somatic cells and germ cells that is based on signaling between the mTORC1-KITL cascade in pfGCs and KIT-PI3K signaling in oocytes. Our findings provide a relatively complete picture of how mammalian primordial follicles are activated. The microenvironment surrounding primordial follicles can activate mTORC1-KITL signaling in pfGCs, and these cells trigger the awakening of dormant oocytes and complete the process of follicular activation. Such communication between the microenvironment, somatic cells, and germ cells is essential to maintaining the proper reproductive lifespan in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Post Hoc Analyses of Anxiety Measures in Adult Patients With Generalized Anxiety Disorder Treated With Vilazodone

PubMed Central

Khan, Arif; Durgam, Suresh; Tang, Xiongwen; Ruth, Adam; Mathews, Maju; Gommoll, Carl P.

2016-01-01

Objective To investigate vilazodone, currently approved for major depressive disorder in adults, for generalized anxiety disorder (GAD). Method Three randomized, double-blind, placebo-controlled studies showing positive results for vilazodone (2,040 mg/d) in adult patients with GAD (DSM-IV-TR) were pooled for analyses; data were collected from June 2012 to March 2014. Post hoc outcomes in the pooled intent-to-treat population (n = 1,462) included mean change from baseline to week 8 in Hamilton Anxiety Rating Scale (HARS) total score, psychic and somatic anxiety subscale scores, and individual item scores; HARS response (≥ 50% total score improvement) and remission (total score ≤ 7) at week 8; and category shifts, defined as HARS item score ≥ 2 at baseline (moderate to very severe symptoms) and score of 0 at week 8 (no symptoms). Results The least squares mean difference was statistically significant for vilazodone versus placebo in change from baseline to week 8 in HARS total score (−1.83, P < .0001) and in psychic anxiety (−1.21, P < .0001) and somatic anxiety (−0.63, P < .01) subscale scores; differences from placebo were significant on 11 of 14 HARS items (P < .05). Response rates were higher with vilazodone than placebo (48% vs 39%, P < .001), as were remission rates (27% vs 21%, P < .01). The percentage of patients who shifted to no symptoms was significant for vilazodone on several items: anxious mood, tension, intellectual, depressed mood, somatic-muscular, somatic-sensory, cardiovascular, respiratory, and autonomic symptoms (P < .05). Conclusions Treatment with vilazodone versus placebo was effective in adult GAD patients, with significant differences between treatment groups found on both psychic and somatic HARS items. Trial Registration ClinicalTrials.gov identifiers: NCT01629966, NCT01766401, NCT01844115. PMID:27486544

Post Hoc Analyses of Anxiety Measures in Adult Patients With Generalized Anxiety Disorder Treated With Vilazodone.

PubMed

Khan, Arif; Durgam, Suresh; Tang, Xiongwen; Ruth, Adam; Mathews, Maju; Gommoll, Carl P

2016-01-01

To investigate vilazodone, currently approved for major depressive disorder in adults, for generalized anxiety disorder (GAD). Three randomized, double-blind, placebo-controlled studies showing positive results for vilazodone (2,040 mg/d) in adult patients with GAD (DSM-IV-TR) were pooled for analyses; data were collected from June 2012 to March 2014. Post hoc outcomes in the pooled intent-to-treat population (n = 1,462) included mean change from baseline to week 8 in Hamilton Anxiety Rating Scale (HARS) total score, psychic and somatic anxiety subscale scores, and individual item scores; HARS response (≥ 50% total score improvement) and remission (total score ≤ 7) at week 8; and category shifts, defined as HARS item score ≥ 2 at baseline (moderate to very severe symptoms) and score of 0 at week 8 (no symptoms). The least squares mean difference was statistically significant for vilazodone versus placebo in change from baseline to week 8 in HARS total score (-1.83, P < .0001) and in psychic anxiety (-1.21, P < .0001) and somatic anxiety (-0.63, P < .01) subscale scores; differences from placebo were significant on 11 of 14 HARS items (P < .05). Response rates were higher with vilazodone than placebo (48% vs 39%, P < .001), as were remission rates (27% vs 21%, P < .01). The percentage of patients who shifted to no symptoms was significant for vilazodone on several items: anxious mood, tension, intellectual, depressed mood, somatic-muscular, somatic-sensory, cardiovascular, respiratory, and autonomic symptoms (P < .05). Treatment with vilazodone versus placebo was effective in adult GAD patients, with significant differences between treatment groups found on both psychic and somatic HARS items. ClinicalTrials.gov identifiers: NCT01629966, NCT01766401, NCT01844115.

Expression and function of CCL2/CCR2 in rat micturition reflexes and somatic sensitivity with urinary bladder inflammation

PubMed Central

Arms, Lauren; Girard, Beatrice M.; Malley, Susan E.

2013-01-01

Chemokines are proinflammatory mediators of the immune response, and there is growing evidence for chemokine/receptor signaling involvement in pronociception. Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder-related with at least one urinary symptom. We have explored the expression and functional roles of CCL2 (monocyte chemoattractant protein-1) and its high-affinity receptor, CCR2, in micturition reflex function and somatic sensitivity in rats with urinary bladder inflammation induced by cyclophosphamide (CYP) treatment of varying duration (4 h, 48 h, chronic). Real-time quantitative RT-PCR, ELISAs, and immunohistochemistry demonstrated significant (P ≤ 0.01) increases in CCL2 and CCR2 expression in the urothelium and in Fast Blue-labeled bladder afferent neurons in lumbosacral dorsal root ganglia with CYP-induced cystitis. Intravesical infusion of RS504393 (5 μM), a specific CCR2 antagonist, reduced voiding frequency and increased bladder capacity and void volume in rats with CYP-induced cystitis (4 h), as determined with open outlet, conscious cystometry. In addition, CCR2 blockade, at the level of the urinary bladder, reduced referred somatic sensitivity of the hindpaw and pelvic region in rats with CYP treatment, as determined with von Frey filament testing. We provide evidence of functional roles for CCL2/CCR2 signaling at the level of the urinary bladder in reducing voiding frequency and somatic sensitivity following CYP-induced cystitis (4 h). These studies suggest that chemokines/receptors may be novel targets with therapeutic potential in the context of urinary bladder inflammation. PMID:23594826

[Personality and somatic disorders].

PubMed

Darves-Bornoz, J-M

2018-06-08

In the title of this text, by somatic disorders we mean those physical illnesses clearly related to a non-psychiatric medical field, frequently termed psychosomatic illnesses and somatoform disorders. For forty years, a trend of thought has focused with pertinence on the psychological peculiarities in patients with severe somatic diseases. Moreover, causality was often supposed in the regularly mentioned association between personality features and somatoform disorders. However, the revival of the study of the earlier field of relationships between mind and body by Briquet, Charcot, Janet and Freud in his first period has led to the reassessment of the meaning of these observations. This reexamination is marked out by several assertions. Two of them work as preliminaries to argumentation: 1. existential wounds may produce long-lasting personality alterations; 2. existential wounds may produce somatoform disorders. These phenomena have been rediscovered over the last few years among assaulted subjects as well as war veterans in whom a frequent occurrence of somatizations has been, in addition, closely linked to the incidence of behavior or personality disorders. Two theses then emerge: 1. somatic diseases may produce long-lasting personality alterations; 2. until now no premorbid personality univocally predisposing to somatic diseases could be found. Indeed, during the 1980s a growing body of negative results coming from retrospective and prospective studies as well as anatomical comparisons have accumulated upon the potential role of certain personality factors in the incidence of somatic illnesses. This dialectic leads to the connection of two corollary assertions: 1. "pensée opératoire" and "alexithymia" in patients with somatic diseases may represent only an effect of the announcement or chronicity of the organic disease; 2. the old "dissociative hysteria" with somatic manifestations finds its substratum in existential wounds and not in pre-trauma personality. Indeed, on the one hand, recent publications do not allow the assertion to be confirmed that alexithymia and "pensée opératoire" predispose to somatizations. On the other hand, personality disorders in subjects with "dissociative hysteria" as well as their somatoform symptoms appear mainly as an effect of an existential wound and express in fact the Janetian concept of "a drop in Psychological Tension". Then, in spite of their differences, conversion and psychosomatic symptoms share the property of being a primitive response to existential wounds in which the subject cannot produce any appropriate psychic or behavioral response to his distress. Light is shed on these phenomena when put alongside the field of "fixed ideas" thought of by Pierre Janet as the recourse to archaic automatisms. Indeed, the experience which contradicts the vision of existence provokes an "unspeakable terror". It is mentally unrepresented or represented in too slight a way. In such cases, no previous personality prevails, but the resulting personality often appears modified, including when the breakdown of vision of the existence results from the diagnosis of an illness or its protracted course. Copyright © 2018 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

[Health-related long-term effects of adverse childhood experiences - an update].

PubMed

Egle, Ulrich T; Franz, Matthias; Joraschky, Peter; Lampe, Astrid; Seiffge-Krenke, Inge; Cierpka, Manfred

2016-10-01

In the last decade strong empirical evidence from several long-term studies supports the conclusion that physical and sexual abuse as well as emotional deprivation in childhood make people significantly more vulnerable to mental and functional disorders across their lifetime. Additionally, an increased vulnerability to several somatic disorders (cardiovascular disorders, type-2-diabetes, hepatitis, chronic obstructive pulmonary disease (COPD), immunological and pain disorders, pharynx and lung cancer) was demonstrated - most of them with a reduced life expectancy. A review of the current research will be presented that outlines the underlying developmental neurobiological and psychological mechanisms mediating these long-term effects. There is now sufficient evidence about familial risk constellations that demonstrates the well-documented impact of specific prevention strategies by several model projects. Only by establishing these strategies, future enormous health-related burdens and high economic costs (unfitness to work, early retirement) can presumably be limited.

Compartmentalized beta subunit distribution determines characteristics and ethanol sensitivity of somatic, dendritic, and terminal large-conductance calcium-activated potassium channels in the rat central nervous system.

PubMed

Wynne, P M; Puig, S I; Martin, G E; Treistman, S N

2009-06-01

Neurons are highly differentiated and polarized cells, whose various functions depend upon the compartmentalization of ion channels. The rat hypothalamic-neurohypophysial system (HNS), in which cell bodies and dendrites reside in the hypothalamus, physically separated from their nerve terminals in the neurohypophysis, provides a particularly powerful preparation in which to study the distribution and regional properties of ion channel proteins. Using electrophysiological and immunohistochemical techniques, we characterized the large-conductance calcium-activated potassium (BK) channel in each of the three primary compartments (soma, dendrite, and terminal) of HNS neurons. We found that dendritic BK channels, in common with somatic channels but in contrast to nerve terminal channels, are insensitive to iberiotoxin. Furthermore, analysis of dendritic BK channel gating kinetics indicates that they, like somatic channels, have fast activation kinetics, in contrast to the slow gating of terminal channels. Dendritic and somatic channels are also more sensitive to calcium and have a greater conductance than terminal channels. Finally, although terminal BK channels are highly potentiated by ethanol, somatic and dendritic channels are insensitive to the drug. The biophysical and pharmacological properties of somatic and dendritic versus nerve terminal channels are consistent with the characteristics of exogenously expressed alphabeta1 versus alphabeta4 channels, respectively. Therefore, one possible explanation for our findings is a selective distribution of auxiliary beta1 subunits to the somatic and dendritic compartments and beta4 to the terminal compartment. This hypothesis is supported immunohistochemically by the appearance of distinct punctate beta1 or beta4 channel clusters in the membrane of somatic and dendritic or nerve terminal compartments, respectively.

SMART precision cancer medicine: a FHIR-based app to provide genomic information at the point of care.

PubMed

Warner, Jeremy L; Rioth, Matthew J; Mandl, Kenneth D; Mandel, Joshua C; Kreda, David A; Kohane, Isaac S; Carbone, Daniel; Oreto, Ross; Wang, Lucy; Zhu, Shilin; Yao, Heming; Alterovitz, Gil

2016-07-01

Precision cancer medicine (PCM) will require ready access to genomic data within the clinical workflow and tools to assist clinical interpretation and enable decisions. Since most electronic health record (EHR) systems do not yet provide such functionality, we developed an EHR-agnostic, clinico-genomic mobile app to demonstrate several features that will be needed for point-of-care conversations. Our prototype, called Substitutable Medical Applications and Reusable Technology (SMART)® PCM, visualizes genomic information in real time, comparing a patient's diagnosis-specific somatic gene mutations detected by PCR-based hotspot testing to a population-level set of comparable data. The initial prototype works for patient specimens with 0 or 1 detected mutation. Genomics extensions were created for the Health Level Seven® Fast Healthcare Interoperability Resources (FHIR)® standard; otherwise, the prototype is a normal SMART on FHIR app. The PCM prototype can rapidly present a visualization that compares a patient's somatic genomic alterations against a distribution built from more than 3000 patients, along with context-specific links to external knowledge bases. Initial evaluation by oncologists provided important feedback about the prototype's strengths and weaknesses. We added several requested enhancements and successfully demonstrated the app at the inaugural American Society of Clinical Oncology Interoperability Demonstration; we have also begun to expand visualization capabilities to include cancer specimens with multiple mutations. PCM is open-source software for clinicians to present the individual patient within the population-level spectrum of cancer somatic mutations. The app can be implemented on any SMART on FHIR-enabled EHRs, and future versions of PCM should be able to evolve in parallel with external knowledge bases. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Role of the body self and self-esteem in experiencing the intensity of menopausal symptoms.

PubMed

Włodarczyk, Małgorzata; Dolińska-Zygmunt, Grażyna

2017-10-29

The aim of the study was to test differences in self-esteem and strength of the body self, body image, comfort with closeness with others and body protection among women reporting high and low intensity of psychological, vasomotor and somatic symptoms of menopause. The sample included 201 women aged 45-55 years. The Menopause Symptom List was used to test the intensity of menopausal symptoms, the Body Self Questionnaire was used to diagnose the body self, and the Rosenberg Self-Esteem Scale was used to examine participants'levels of self-esteem. Differences between women experiencing high and low intensity of symptoms were analyzed using Student's t-test for independent samples. Women experiencing high-intensity psychological, vasomotor and somatic symptoms of menopause showed significantly lower self-esteem and poorer body-self functioning in all its dimensions except for body protection. Women experiencing high-intensity psychological, vasomotor and somatic symptoms of menopause demonstrated poorer functioning of the body self and lower self-esteem.

Germline mutations and somatic inactivation of TRIM28 in Wilms tumour

PubMed Central

Halliday, Benjamin J.; Markie, David M.; Grundy, Richard G.; Ludgate, Jackie L.; Black, Michael A.; Weeks, Robert J.; Catchpoole, Daniel R.; Reeve, Anthony E.

2018-01-01

Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer. Inactivation of TRIM28, either germline or somatic, occurred through inactivating mutations, loss of heterozygosity or epigenetic silencing. TRIM28-mutated tumours had a monomorphic epithelial histology that is uncommon for Wilms tumour. Critically, these tumours were negative for TRIM28 immunohistochemical staining whereas the epithelial component in normal tissue and other Wilms tumours stained positively. These data, together with a characteristic gene expression profile, suggest that inactivation of TRIM28 provides the molecular basis for defining a previously described subtype of Wilms tumour, that has early age of onset and excellent prognosis. PMID:29912901

Fanca deficiency reduces A/T transitions in somatic hypermutation and alters class switch recombination junctions in mouse B cells

PubMed Central

Nguyen, Thuy Vy; Riou, Lydia

2014-01-01

Fanconi anemia is a rare genetic disorder that can lead to bone marrow failure, congenital abnormalities, and increased risk for leukemia and cancer. Cells with loss-of-function mutations in the FANC pathway are characterized by chromosome fragility, altered mutability, and abnormal regulation of the nonhomologous end-joining (NHEJ) pathway. Somatic hypermutation (SHM) and immunoglobulin (Ig) class switch recombination (CSR) enable B cells to produce high-affinity antibodies of various isotypes. Both processes are initiated after the generation of dG:dU mismatches by activation-induced cytidine deaminase. Whereas SHM involves an error-prone repair process that introduces novel point mutations into the Ig gene, the mismatches generated during CSR are processed to create double-stranded breaks (DSBs) in DNA, which are then repaired by the NHEJ pathway. As several lines of evidence suggest a possible role for the FANC pathway in SHM and CSR, we analyzed both processes in B cells derived from Fanca−/− mice. Here we show that Fanca is required for the induction of transition mutations at A/T residues during SHM and that despite globally normal CSR function in splenic B cells, Fanca is required during CSR to stabilize duplexes between pairs of short microhomology regions, thereby impeding short-range recombination downstream of DSB formation. PMID:24799500

Fanca deficiency reduces A/T transitions in somatic hypermutation and alters class switch recombination junctions in mouse B cells.

PubMed

Nguyen, Thuy Vy; Riou, Lydia; Aoufouchi, Saïd; Rosselli, Filippo

2014-06-02

Fanconi anemia is a rare genetic disorder that can lead to bone marrow failure, congenital abnormalities, and increased risk for leukemia and cancer. Cells with loss-of-function mutations in the FANC pathway are characterized by chromosome fragility, altered mutability, and abnormal regulation of the nonhomologous end-joining (NHEJ) pathway. Somatic hypermutation (SHM) and immunoglobulin (Ig) class switch recombination (CSR) enable B cells to produce high-affinity antibodies of various isotypes. Both processes are initiated after the generation of dG:dU mismatches by activation-induced cytidine deaminase. Whereas SHM involves an error-prone repair process that introduces novel point mutations into the Ig gene, the mismatches generated during CSR are processed to create double-stranded breaks (DSBs) in DNA, which are then repaired by the NHEJ pathway. As several lines of evidence suggest a possible role for the FANC pathway in SHM and CSR, we analyzed both processes in B cells derived from Fanca(-/-) mice. Here we show that Fanca is required for the induction of transition mutations at A/T residues during SHM and that despite globally normal CSR function in splenic B cells, Fanca is required during CSR to stabilize duplexes between pairs of short microhomology regions, thereby impeding short-range recombination downstream of DSB formation. © 2014 Nguyen et al.

Dissecting the Function and Assembly of Acentriolar Microtubule Organizing Centers in Drosophila Cells In Vivo

PubMed Central

Baumbach, Janina; Novak, Zsofia Anna; Raff, Jordan W.; Wainman, Alan

2015-01-01

Acentriolar microtubule organizing centers (aMTOCs) are formed during meiosis and mitosis in several cell types, but their function and assembly mechanism is unclear. Importantly, aMTOCs can be overactive in cancer cells, enhancing multipolar spindle formation, merotelic kinetochore attachment and aneuploidy. Here we show that aMTOCs can form in acentriolar Drosophila somatic cells in vivo via an assembly pathway that depends on Asl, Cnn and, to a lesser extent, Spd-2—the same proteins that appear to drive mitotic centrosome assembly in flies. This finding enabled us to ablate aMTOC formation in acentriolar cells, and so perform a detailed genetic analysis of the contribution of aMTOCs to acentriolar mitotic spindle formation. Here we show that although aMTOCs can nucleate microtubules, they do not detectably increase the efficiency of acentriolar spindle assembly in somatic fly cells. We find that they are required, however, for robust microtubule array assembly in cells without centrioles that also lack microtubule nucleation from around the chromatin. Importantly, aMTOCs are also essential for dynein-dependent acentriolar spindle pole focusing and for robust cell proliferation in the absence of centrioles and HSET/Ncd (a kinesin essential for acentriolar spindle pole focusing in many systems). We propose an updated model for acentriolar spindle pole coalescence by the molecular motors Ncd/HSET and dynein in conjunction with aMTOCs. PMID:26020779

Depression, Help-Seeking and Self-Recognition of Depression among Dominican, Ecuadorian and Colombian Immigrant Primary Care Patients in the Northeastern United States

PubMed Central

Caplan, Susan; Buyske, Steven

2015-01-01

Latinos, the largest minority group in the United States, experience mental health disparities, which include decreased access to care, lower quality of care and diminished treatment engagement. The purpose of this cross-sectional study of 177 Latino immigrants in primary care is to identify demographic factors, attitudes and beliefs, such as stigma, perceived stress, and ethnic identity that are associated with depression, help-seeking and self-recognition of depression. Results indicated that 45 participants (25%) had depression by Patient Health Questionnaire (PHQ-9) criteria. Factors most likely to be associated with depression were: poverty; difficulty in functioning; greater somatic symptoms, perceived stress and stigma; number of chronic illnesses; and poor or fair self-rated mental health. Fifty-four people endorsed help-seeking. Factors associated with help-seeking were: female gender, difficulty in functioning, greater somatic symptoms, severity of depression, having someone else tell you that you have an emotional problem, and poor or fair self-rated mental health. Factors most likely to be associated with self-recognition were the same, but also included greater perceived stress. This manuscript contributes to the literature by examining attitudinal factors that may be associated with depression, help-seeking and self-recognition among subethnic groups of Latinos that are underrepresented in research studies. PMID:26343691

Big Five personality characteristics are associated with depression subtypes and symptom dimensions of depression in older adults.

PubMed

Koorevaar, A M L; Hegeman, J M; Lamers, F; Dhondt, A D F; van der Mast, R C; Stek, M L; Comijs, H C

2017-12-01

This study examined the associations of personality characteristics with both subtypes and symptom dimensions of depression in older adults. Three hundred and seventy-eight depressed older adults participated in the Netherlands Study of Depression in Older Persons. Personality characteristics were assessed by the NEO-Five Factor Inventory. Subtypes and symptom dimensions of depression were determined using the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology (IDS). Multinomial logistic regression analyses were performed to examine the associations between personality and atypical, melancholic, and unspecified subtypes of major depression. Linear regression analyses examined the associations between personality and the IDS mood, somatic, and motivation symptom dimensions. The analyses were adjusted for confounders and additionally adjusted for depression severity. Neuroticism, Extraversion, Conscientiousness, and Agreeableness were associated with specified (atypical or melancholic) major depression compared with unspecified major depression in the bivariate analyses but lost their significance after adjustments for functional limitations and severity of depression. Neuroticism was positively associated with the IDS mood and motivation symptom dimensions, also in the adjusted models. Further, Extraversion and Agreeableness were negatively associated with the IDS mood symptom dimension, and Extraversion and Conscientiousness were negatively associated with the IDS motivation symptom dimension. None was associated with the IDS somatic symptom dimension. This study demonstrated the association of personality characteristics with mood and motivational symptoms of late-life depression. The lacking ability of personality to differentiate between melancholic and atypical depression seems to be largely explained by severity of depressive symptoms. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome.

PubMed

Boztug, K; Germeshausen, M; Avedillo Díez, I; Gulacsy, V; Diestelhorst, J; Ballmaier, M; Welte, K; Maródi, L; Chernyshova, Li; Klein, C

2008-07-01

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disorder associated with microthrombocytopenia, eczema, autoimmunity and predisposition to malignant lymphoma. Although rare, few cases of somatic mosaicism have been published in WAS patients to date. We here report on two Ukrainian siblings who were referred to us at the age of 3 and 4 years, respectively. Both patients suffered from severe WAS caused by a nonsense mutation in exon 1 of the WAS gene. In both siblings, flow cytometric analysis revealed the presence of Wiskott-Aldrich syndrome protein (WASp)-positive and WASp-negative cell populations among T and B lymphocytes as well as natural killer (NK) cells. In contrast to previously described cases of revertant mosaicism in WAS, molecular analyses in both children showed that the WASp-positive T cells, B cells, and NK cells carried multiple different second-site mutations, resulting in different missense mutations. To our knowledge, this is the first report describing somatic mosaicism in WAS patients caused by several independent second-site mutations in the WAS gene.

Progress toward generating a ferret model of cystic fibrosis by somatic cell nuclear transfer

PubMed Central

Li, Ziyi; Engelhardt, John F

2003-01-01

Mammalian cloning by nuclear transfer from somatic cells has created new opportunities to generate animal models of genetic diseases in species other than mice. Although genetic mouse models play a critical role in basic and applied research for numerous diseases, often mouse models do not adequately reproduce the human disease phenotype. Cystic fibrosis (CF) is one such disease. Targeted ablation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in mice does not adequately replicate spontaneous bacterial infections observed in the human CF lung. Hence, several laboratories are pursuing alternative animal models of CF in larger species such as the pig, sheep, rabbits, and ferrets. Our laboratory has focused on developing the ferret as a CF animal model. Over the past few years, we have investigated several experimental parameters required for gene targeting and nuclear transfer (NT) cloning in the ferret using somatic cells. In this review, we will discuss our progress and the hurdles to NT cloning and gene-targeting that accompany efforts to generate animal models of genetic diseases in species such as the ferret. PMID:14613541

Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC

PubMed Central

Marcó, Sara; Pujol, Anna; Roca, Carles; Motas, Sandra; Ribera, Albert; Garcia, Miguel; Molas, Maria; Villacampa, Pilar; Melia, Cristian S.; Sánchez, Víctor; Sánchez, Xavier; Bertolin, Joan; Ruberte, Jesús; Haurigot, Virginia

2016-01-01

ABSTRACT Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT) that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches. PMID:27491071

Employment status and perceived health in the Hordaland Health Study (HUSK)

PubMed Central

Overland, Simon; Glozier, Nicholas; Mæland, John Gunnar; Aarø, Leif Edvard; Mykletun, Arnstein

2006-01-01

Background Most western countries have disability benefit schemes ostensibly based upon requiring (1) a work inhibiting functional limitation that (2) can be attributed to a diagnosable condition, injury or disease. The present paper examines to what extent current practice matches the core premises of this model by examining how much poorer the perceived health of disability benefit recipients is, compared to the employed and the unemployed, and further to examine to what extent any poorer perceived health among benefit recipients can be attributed to mental or somatic illness and symptoms. Methods Information on disability benefit recipiency was obtained from Norwegian registry data, and merged with health information from the Hordaland Health Study (HUSK) in Western Norway, 1997–99. Participants (N = 14 946) aged 40–47 were assessed for perceived physical and mental health (Short Form-12), somatic symptoms, mental health, and self reported somatic conditions and diseases treated with medication. Differences associated with employment status were tested in chi-square and t-tests, as well as multivariate and univariate regression models to adjust for potential confounders. Results Recipients of disability benefits (n = 1 351) had poorer perceived physical and mental health than employees (n = 13 156); group differences were 1.86 and 0.74 pooled standard deviations respectively. Self reported somatic diagnoses, mental health and symptoms accounted for very little of this difference in perceived health. The unemployed (n = 439) were comparable to the employed rather than the recipients of disability benefits. Conclusion Recipients of disability benefits have poor perceived health compared to both the employed and the unemployed. Surprisingly little of this difference can be ascribed to respondents' descriptions of their illnesses and symptoms. Even allowing for potential underascertainment of condition severity, this finding supports the increasing focus on non-disease oriented contributing factors. Rehabilitation efforts aiming at return to work should have a strong focus on the patients' perceptions of their health in addition to symptom relief and social factors. PMID:16939642

Three sides to a story: Child, parent, and nurse perspectives on the child's experience during hematopoietic stem cell transplantation.

PubMed

Ullrich, Christina K; Rodday, Angie Mae; Bingen, Kristin M; Kupst, Mary Jo; Patel, Sunita K; Syrjala, Karen L; Harris, Lynnette L; Recklitis, Christopher J; Chang, Grace; Guinan, Eva C; Terrin, Norma; Tighiouart, Hocine; Phipps, Sean; Parsons, Susan K

2017-08-15

The experience of children undergoing hematopoietic stem cell transplantation (HSCT), including the ways in which different participants (ie, children, parents, and nurses) contribute to the overall picture of a child's experience, is poorly characterized. This study evaluated parent, child, and nurse perspectives on the experience of children during HSCT and factors contributing to interrater differences. Participants were enrolled in a multicenter, prospective study evaluating child and parent health-related quality of life over the year after HSCT. Children (n = 165) and their parents and nurses completed the Behavioral, Affective, and Somatic Experiences Scale (BASES) at baseline (before/during conditioning), 7 days after the stem cell infusion (day+7), and 21 days after the stem cell infusion (day+21). The BASES domains included Somatic Distress, Mood Disturbance, Cooperation, and Getting Along. Higher scores indicated more distress/impairment. Repeated measures models by domain assessed differences by raters and changes over time and identified other factors associated with raters' scores. Completion rates were high (≥73% across times and raters). Multivariate models revealed significant time-rater interactions, which varied by domain. For example, parent-rated Somatic Distress scores increased from baseline to day+7 and remained elevated at day+21 (P < .001); children's scores were lower than parents' scores across time points. Nurses' baseline scores were lower than parents' baseline scores, although by day+21 they were similar. Older child age was associated with higher Somatic Distress and Mood Disturbance scores. Worse parent emotional functioning was associated with lower scores across raters and domains except for Cooperation. Multirater assessments are highly feasible during HSCT. Ratings differ by several factors; considering ratings in light of such factors may deepen our understanding of the child's experience. Cancer 2017;123:3159-66. © 2017 American Cancer Society. © 2017 American Cancer Society.

Life events and difficulties and their association with antenatal distress in White and South Asian women in the UK.

PubMed

Traviss, Gemma D; Meer, Shaista; West, Robert M; House, Allan O

2013-05-01

Symptoms of distress during pregnancy are common and often go unnoticed. There is a well-established relation between life events and depression. The current study aims to explore the association between life events and difficulties, and symptoms of emotional and somatic distress during pregnancy in White and South Asian women in the UK. 100 pregnant women attending routine antenatal appointments were interviewed using the Life Events and Difficulties Schedule (LEDS). We investigated the frequency and type of events experienced in the year prior to conception and during pregnancy, as predictors for somatic and emotional distress, measured using the GHQ-28. Non-severe stressors accounted for over 90 % of those reported, half of which (43-53 %) were health and reproduction-related. Somatic symptoms were associated with the number of non-severe events, and number of children and emotional symptoms were associated with non-marked difficulties. There was little evidence of an association between severe events and distress. Ethnicity had little effect on any associations although South Asian women were at slightly higher odds of experiencing emotional symptoms, which appear to be buffered by social support. In routine antenatal care it is important to assess both emotional and somatic symptoms. Health professionals need to be sensitive to the health, social, cultural and environmental circumstances of women during pregnancy and ensure appropriate support is in place, particularly for multi-parous women. Regression models explained a small but significant amount of the variance in distress symptoms. Further work is necessary to explore other contributory factors and also the mechanisms through which stressors have their effect.

The function of Xenopus Bloom's syndrome protein homolog (xBLM) in DNA replication

PubMed Central

Liao, Shuren; Graham, Jeanine; Yan, Hong

2000-01-01

The Bloom's syndrome gene (BLM) plays a pivotal role in the maintenance of genomic stability in somatic cells. It encodes a DNA helicase (BLM) of the RecQ family, but the exact function of BLM remains elusive. To study this question, we have cloned the BLM homolog of the frog Xenopus laevis (xBLM) and have raised antibodies to it. Immunodepletion of xBLM from a Xenopus egg extract severely inhibits the replication of DNA in reconstituted nuclei. Moreover, the inhibition can be rescued by the addition of the recombinant xBLM protein. These results provide the first direct evidence that BLM plays an important role in DNA replication, suggesting that Bloom's syndrome may be the consequence of defective DNA replication. PMID:11040210

Functional consequences of inadequate sleep in adolescents: a systematic review.

PubMed

Shochat, Tamar; Cohen-Zion, Mairav; Tzischinsky, Orna

2014-02-01

During adolescence, changes in sleep patterns due to biological and environmental factors are well documented. Later bedtimes and inadequate sleep, i.e., short and disrupted sleep patterns, insomnia and daytime sleepiness, have become increasingly common. Accumulating evidence suggests that sleep plays a crucial role in healthy adolescent development. This review systematically explores descriptive evidence, based on prospective and cross sectional investigations, indicating that inadequate sleep is associated with negative outcomes in several areas of health and functioning, including somatic and psychosocial health, school performance and risk taking behavior. Findings highlight the need for longitudinal investigations aimed at establishing the underpinnings of these associations and for developing and implementing interventions designed to achieve healthier and more balanced sleep patterns in the adolescent population. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Functional somatic syndromes from the view of cultural anthropology].

PubMed

Nakagami, Ayako; Tsujiuchi, Takuya

2009-09-01

The functional somatic syndromes have acquired major socio-cultural and political dimensions. Socio-cultural factors clearly affect symptoms, suffering, and disability perception and reporting. And knowledge of explanatory models of bodily distress for patients from different cultural backgrounds is useful in the establishment of a stable doctor -patient relationship. FSS may be an operational category to bridge between medical explanatory model and patient's model. According to medical anthropology, sickness has two faces; illness and disease. "Disease" is the problem from the practitioner's perspective, and "illness" is the human experience of symptoms and suffering. In this paper, the anthropological research on chronic fatigue syndrome as "not real" illness experience was described.

PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells

PubMed Central

Juliano, Celina E.; Reich, Adrian; Liu, Na; Götzfried, Jessica; Zhong, Mei; Uman, Selen; Reenan, Robert A.; Wessel, Gary M.; Steele, Robert E.; Lin, Haifan

2014-01-01

PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) are found in animal germlines and are essential for fertility, but their functions outside of the gonad are not well understood. The cnidarian Hydra is a simple metazoan with well-characterized stem/progenitor cells that provides a unique model for analysis of PIWI function. Here we report that Hydra has two PIWI proteins, Hydra PIWI (Hywi) and Hydra PIWI-like (Hyli), both of which are expressed in all Hydra stem/progenitor cells, but not in terminally differentiated cells. We identified ∼15 million piRNAs associated with Hywi and/or Hyli and found that they exhibit the ping-pong signature of piRNA biogenesis. Hydra PIWI proteins are strictly cytoplasmic and thus likely act as posttranscriptional regulators. To explore this function, we generated a Hydra transcriptome for piRNA mapping. piRNAs map to transposons with a 25- to 35-fold enrichment compared with the abundance of transposon transcripts. By sequencing the small RNAs specific to the interstitial, ectodermal, and endodermal lineages, we found that the targeting of transposons appears to be largely restricted to the interstitial lineage. We also identified putative nontransposon targets of the pathway unique to each lineage. Finally we demonstrate that hywi function is essential in the somatic epithelial lineages. This comprehensive analysis of the PIWI–piRNA pathway in the somatic stem/progenitor cells of a nonbilaterian animal suggests that this pathway originated with broader stem cell functionality. PMID:24367095

PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells.

PubMed

Juliano, Celina E; Reich, Adrian; Liu, Na; Götzfried, Jessica; Zhong, Mei; Uman, Selen; Reenan, Robert A; Wessel, Gary M; Steele, Robert E; Lin, Haifan

2014-01-07

PIWI proteins and their bound PIWI-interacting RNAs (piRNAs) are found in animal germlines and are essential for fertility, but their functions outside of the gonad are not well understood. The cnidarian Hydra is a simple metazoan with well-characterized stem/progenitor cells that provides a unique model for analysis of PIWI function. Here we report that Hydra has two PIWI proteins, Hydra PIWI (Hywi) and Hydra PIWI-like (Hyli), both of which are expressed in all Hydra stem/progenitor cells, but not in terminally differentiated cells. We identified ∼15 million piRNAs associated with Hywi and/or Hyli and found that they exhibit the ping-pong signature of piRNA biogenesis. Hydra PIWI proteins are strictly cytoplasmic and thus likely act as posttranscriptional regulators. To explore this function, we generated a Hydra transcriptome for piRNA mapping. piRNAs map to transposons with a 25- to 35-fold enrichment compared with the abundance of transposon transcripts. By sequencing the small RNAs specific to the interstitial, ectodermal, and endodermal lineages, we found that the targeting of transposons appears to be largely restricted to the interstitial lineage. We also identified putative nontransposon targets of the pathway unique to each lineage. Finally we demonstrate that hywi function is essential in the somatic epithelial lineages. This comprehensive analysis of the PIWI-piRNA pathway in the somatic stem/progenitor cells of a nonbilaterian animal suggests that this pathway originated with broader stem cell functionality.

Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

PubMed Central

Steehouwer, Marloes; Gilissen, Christian; Graham, Sarah A.; Hoover-Fong, Julie; Telegrafi, Aida B.; Destree, Anne; Smigiel, Robert; Lambie, Lindsday A.; Kayserili, Hülya; Altunoglu, Umut; Lapi, Elisabetta; Uzielli, Maria Luisa; Aracena, Mariana; Nur, Banu G.; Mihci, Ercan; Moreira, Lilia M. A.; Borges Ferreira, Viviane; Horovitz, Dafne D. G.; da Rocha, Katia M.; Jezela-Stanek, Aleksandra; Brooks, Alice S.; Reutter, Heiko; Cohen, Julie S.; Fatemi, Ali; Smitka, Martin; Grebe, Theresa A.; Di Donato, Nataliya; Deshpande, Charu; Vandersteen, Anthony; Marques Lourenço, Charles; Dufke, Andreas; Rossier, Eva; Andre, Gwenaelle; Baumer, Alessandra; Spencer, Careni; McGaughran, Julie; Franke, Lude; Veltman, Joris A.; De Vries, Bert B. A.; Schinzel, Albert; Fisher, Simon E.; Hoischen, Alexander

2017-01-01

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype. PMID:28346496

Effect of ethanolic Neem (Azadirachta indica) leaf extract as an herb contraceptive on Hepato-somatic Index of the male mice (Mus musculus)

NASA Astrophysics Data System (ADS)

Janika Sitasiwi, Agung; Isdadiyanto, Sri; Muflichatun Mardiati, Siti

2018-05-01

Neem has been known as herb contraceptive plant which shows an antifertility effect both in male and female rats. The anti-fertility compound of Neem has the same potencies to interfere with or affect the function of several organs. The Hepato-somatic index (HSI) reflects the value of toxic compounds that enter the animal body also. HSI values can also be used to assess animal health levels. A study to examine the effect of ethanolic extract of Neem as an herb contraceptive to the hepato-somatic index of male mice has been done. Neem leaf was collected from the campus area, dried, mashed then extracted with ethanol 70%. Mature male Swiss Webster mice with 25-30 grams in weight were used as laboratory animals. Mice were divided into 4 groups: P0 (given distilled water), P1, P2, and P3 were given Neem leaf extract with 8.4, 11.2 and 14 mg/KgBW/day respectively. Each treatment group had six replications. Treatment was given orally for 21 days. The body weight was measured every week until the end of treatment. The mice were anesthetized with chloroform at the end of treatment, continued by dissecting and isolating liver isolation. The isolated liver is then weighed to determine the HSI value. Data were analyzed with ANOVA followed by DMRT test. The results showed that the body weight of control group showed a significant difference (p<0.05) to the treatment group. The hepatic weights and HSI values of the control group showed nonsignificant differences (p>0.05) with the P1 and P2 treatment groups but showed a significant difference (p<0.05) with the P3 treatment group. It can be concluded that the exposure of ethanolic Neem leaves extract as herb contraceptive affects liver function which causes the increase of hepatic weight and HSI value.

University of Texas MD Anderson Cancer Center: High-Throughput Screening Identifying Driving Mutations in Endometrial Cancer | Office of Cancer Genomics

Cancer.gov

Recent advances in next-generation sequencing technology have enabled the unprecedented characterization of a full spectrum of somatic alterations in cancer genomes. Given the large numbers of somatic mutations typically detected by this approach, a key challenge in the downstream analysis is to distinguish “drivers” that functionally contribute to tumorigenesis from “passengers” that occur as the consequence of genomic instability.

How to make spinal motor neurons.

PubMed

Davis-Dusenbery, Brandi N; Williams, Luis A; Klim, Joseph R; Eggan, Kevin

2014-02-01

All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanistic studies or drug screens. Progress towards overcoming this challenge has been achieved through the synthesis of developmental biology paradigms and advances in stem cell and reprogramming technology, which allow the production of motor neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron development has been applied to allow generation of motor neurons either from pluripotent stem cells by directed differentiation and transcriptional programming, or from somatic cells by direct lineage conversion. Finally, we discuss methods to evaluate the molecular and functional properties of motor neurons generated through each of these techniques.

Impaired conditioned pain modulation in youth with functional abdominal pain

PubMed Central

Morris, Matthew C.; Walker, Lynn S.; Bruehl, Stephen; Stone, Amanda L.; Mielock, Alyssa S.; Rao, Uma

2016-01-01

Functional abdominal pain (FAP) is associated with enhanced pain responsiveness. Although impaired conditioned pain modulation (CPM) characterizes adults with a variety of chronic pain conditions, relatively little is known about CPM in youth with FAP. The present study assessed CPM to evoked thermal pain in 140 youth (ages 10 to 17), 63 of whom had FAP and 77 of whom were healthy controls. Multilevel models demonstrated weaker CPM effects in FAP than healthy youth, as evident in slower within-person decreases in pain ratings during the conditioning phase. Weaker CPM effects were associated with greater somatic symptom severity and functional disability. Pain responses in FAP youth were heterogeneous, with 43% of youth showing an unexpected increase in pain ratings during the conditioning phase, suggesting sensitization rather than CPM-related pain inhibition. These findings highlight directions for future research on the emergence and maintenance of FAP in youth. PMID:27389918

Impaired conditioned pain modulation in youth with functional abdominal pain.

PubMed

Morris, Matthew C; Walker, Lynn S; Bruehl, Stephen; Stone, Amanda L; Mielock, Alyssa S; Rao, Uma

2016-10-01

Functional abdominal pain (FAP) is associated with enhanced pain responsiveness. Although impaired conditioned pain modulation (CPM) characterizes adults with a variety of chronic pain conditions, relatively little is known about CPM in youth with FAP. This study assessed CPM to evoked thermal pain in 140 youth (ages 10-17), 63 of whom had FAP and 77 of whom were healthy controls. Multilevel models demonstrated weaker CPM effects in youth with FAP than in healthy youth, as evident in slower within-person decreases in pain ratings during the conditioning phase. Weaker CPM effects were associated with greater somatic symptom severity and functional disability. Pain responses in youth with FAP were heterogeneous, with 43% of youth showing an unexpected increase in pain ratings during the conditioning phase, suggesting sensitization rather than CPM-related pain inhibition. These findings highlight directions for future research on the emergence and maintenance of FAP in youth.

Identification and characterization of bZIP-type transcription factors involved in carrot (Daucus carota L.) somatic embryogenesis.

PubMed

Guan, Yucheng; Ren, Haibo; Xie, He; Ma, Zeyang; Chen, Fan

2009-10-01

Seed dormancy is an important adaptive trait that enables seeds of many species to remain quiescent until conditions become favorable for germination. Abscisic acid (ABA) plays an important role in these developmental processes. Like dormancy and germination, the elongation of carrot somatic embryo radicles is retarded by sucrose concentrations at or above 6%, and normal growth resumes at sucrose concentrations below 3%. Using a yeast one-hybrid screening system, we isolated two bZIP-type transcription factors, CAREB1 and CAREB2, from a cDNA library prepared from carrot somatic embryos cultured in a high-sucrose medium. Both CAREB1 and CAREB2 were localized to the nucleus, and specifically bound to the ABA response element (ABRE) in the Dc3 promoter. Expression of CAREB2 was induced in seedlings by drought and exogenous ABA application; whereas expression of CAREB1 increased during late embryogenesis, and reduced dramatically when somatic embryos were treated with fluridone, an inhibitor of ABA synthesis. Overexpression of CAREB1 caused somatic embryos to develop slowly when cultured in low-sucrose medium, and retarded the elongation of the radicles. These results indicate that CAREB1 and CAREB2 have similar DNA-binding activities, but play different roles during carrot development. Our results indicate that CAREB1 functions as an important trans-acting factor in the ABA signal transduction pathway during carrot somatic embryogenesis.

Evolutionary origins of germline segregation in Metazoa: evidence for a germ stem cell lineage in the coral Orbicella faveolata (Cnidaria, Anthozoa).

PubMed

Barfield, Sarah; Aglyamova, Galina V; Matz, Mikhail V

2016-01-13

The ability to segregate a committed germ stem cell (GSC) lineage distinct from somatic cell lineages is a characteristic of bilaterian Metazoans. However, the occurrence of GSC lineage specification in basally branching Metazoan phyla, such as Cnidaria, is uncertain. Without an independently segregated GSC lineage, germ cells and their precursors must be specified throughout adulthood from continuously dividing somatic stem cells, generating the risk of propagating somatic mutations within the individual and its gametes. To address the potential for existence of a GSC lineage in Anthozoa, the sister-group to all remaining Cnidaria, we identified moderate- to high-frequency somatic mutations and their potential for gametic transfer in the long-lived coral Orbicella faveolata (Anthozoa, Cnidaria) using a 2b-RAD sequencing approach. Our results demonstrate that somatic mutations can drift to high frequencies (up to 50%) and can also generate substantial intracolonial genetic diversity. However, these somatic mutations are not transferable to gametes, signifying the potential for an independently segregated GSC lineage in O. faveolata. In conjunction with previous research on germ cell development in other basally branching Metazoan species, our results suggest that the GSC system may be a Eumetazoan characteristic that evolved in association with the emergence of greater complexity in animal body plan organization and greater specificity of stem cell functions. © 2016 The Author(s).

Evolutionary origins of germline segregation in Metazoa: evidence for a germ stem cell lineage in the coral Orbicella faveolata (Cnidaria, Anthozoa)

PubMed Central

Barfield, Sarah; Aglyamova, Galina V.; Matz, Mikhail V.

2016-01-01

The ability to segregate a committed germ stem cell (GSC) lineage distinct from somatic cell lineages is a characteristic of bilaterian Metazoans. However, the occurrence of GSC lineage specification in basally branching Metazoan phyla, such as Cnidaria, is uncertain. Without an independently segregated GSC lineage, germ cells and their precursors must be specified throughout adulthood from continuously dividing somatic stem cells, generating the risk of propagating somatic mutations within the individual and its gametes. To address the potential for existence of a GSC lineage in Anthozoa, the sister-group to all remaining Cnidaria, we identified moderate- to high-frequency somatic mutations and their potential for gametic transfer in the long-lived coral Orbicella faveolata (Anthozoa, Cnidaria) using a 2b-RAD sequencing approach. Our results demonstrate that somatic mutations can drift to high frequencies (up to 50%) and can also generate substantial intracolonial genetic diversity. However, these somatic mutations are not transferable to gametes, signifying the potential for an independently segregated GSC lineage in O. faveolata. In conjunction with previous research on germ cell development in other basally branching Metazoan species, our results suggest that the GSC system may be a Eumetazoan characteristic that evolved in association with the emergence of greater complexity in animal body plan organization and greater specificity of stem cell functions. PMID:26763699

CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline.

PubMed

Campbell, Anne C; Updike, Dustin L

2015-05-15

Germ granules (P granules) in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the misexpression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcripts do not increase in the young adult germline when P granules are impaired. Instead, we found that impairing P granules causes sperm-specific mRNAs to become highly overexpressed. This includes the accumulation of major sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by feminization of the germline. A core component of P granules, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to license transcripts for germline expression. However, impairing CSR-1 has very little effect on the accumulation of its mRNA targets. Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm-specific mRNAs from being transcribed in the hermaphrodite germline. These findings suggest that P granules protect germline integrity through two different mechanisms, by (1) preventing the inappropriate expression of somatic proteins at the level of translational regulation, and by (2) functioning with CSR-1 to limit the domain of sperm-specific expression at the level of transcription. © 2015. Published by The Company of Biologists Ltd.

Axonal propagation of simple and complex spikes in cerebellar Purkinje neurons.

PubMed

Khaliq, Zayd M; Raman, Indira M

2005-01-12

In cerebellar Purkinje neurons, the reliability of propagation of high-frequency simple spikes and spikelets of complex spikes is likely to regulate inhibition of Purkinje target neurons. To test the extent to which a one-to-one correspondence exists between somatic and axonal spikes, we made dual somatic and axonal recordings from Purkinje neurons in mouse cerebellar slices. Somatic action potentials were recorded with a whole-cell pipette, and the corresponding axonal signals were recorded extracellularly with a loose-patch pipette. Propagation of spontaneous and evoked simple spikes was highly reliable. At somatic firing rates of approximately 200 spikes/sec, <10% of spikes failed to propagate, with failures becoming more frequent only at maximal somatic firing rates (approximately 260 spikes/sec). Complex spikes were elicited by climbing fiber stimulation, and their somatic waveforms were modulated by tonic current injection, as well as by paired stimulation to depress the underlying EPSCs. Across conditions, the mean number of propagating action potentials remained just above two spikes per climbing fiber stimulation, but the instantaneous frequency of the propagating spikes changed, from approximately 375 Hz during somatic hyperpolarizations that silenced spontaneous firing to approximately 150 Hz during spontaneous activity. The probability of propagation of individual spikelets could be described quantitatively as a saturating function of spikelet amplitude, rate of rise, or preceding interspike interval. The results suggest that ion channels of Purkinje axons are adapted to produce extremely short refractory periods and that brief bursts of forward-propagating action potentials generated by complex spikes may contribute transiently to inhibition of postsynaptic neurons.

Anhedonia is associated with poor health status and more somatic and cognitive symptoms in patients with coronary artery disease.

PubMed

Pelle, Aline J; Pedersen, Susanne S; Erdman, Ruud A M; Kazemier, Marten; Spiering, Marquita; van Domburg, Ron T; Denollet, Johan

2011-06-01

The effectiveness of cardiac rehabilitation (CR) in patients with coronary artery disease (CAD) is moderated by negative emotions and clinical factors, but no studies evaluated the role of positive emotions. This study examined whether anhedonia (i.e. the lack of positive affect) moderated the effectiveness of CR on health status and somatic and cognitive symptoms. CAD patients (n = 368) filled out the Hospital Anxiety and Depression Scale (HADS) to assess anhedonia at the start of CR, and the Short-Form Health Survey (SF-36) and the Health Complaints Scale (HCS) at the start of CR and at 3 months to assess health status and somatic and cognitive symptoms, respectively. Adjusting for clinical and demographic factors, health status improved significantly during the follow-up (F(1,357) = 10.84, P = .001). Anhedonic patients reported poorer health status compared with non-anhedonic patients, with anhedonia exerting a stable effect over time (F(1,358) = 34.80, P < .001). Somatic and cognitive symptoms decreased over time (F(1,358) = 3.85, P = .05). Anhedonics experienced more benefits in terms of somatic and cognitive symptoms over time (F(1,358) = 13.00, P < .001). Anhedonic patients reported poorer health status and higher levels of somatic and cognitive symptoms prior to and after CR. Somatic and cognitive symptoms differed as a function of anhedonia over time, but health status did not. Anhedonia might provide a new avenue for secondary prevention in CAD.

De novo assembly and characterization of global transcriptome of coconut palm (Cocos nucifera L.) embryogenic calli using Illumina paired-end sequencing.

PubMed

Rajesh, M K; Fayas, T P; Naganeeswaran, S; Rachana, K E; Bhavyashree, U; Sajini, K K; Karun, Anitha

2016-05-01

Production and supply of quality planting material is significant to coconut cultivation but is one of the major constraints in coconut productivity. Rapid multiplication of coconut through in vitro techniques, therefore, is of paramount importance. Although somatic embryogenesis in coconut is a promising technique that will allow for the mass production of high quality palms, coconut is highly recalcitrant to in vitro culture. In order to overcome the bottlenecks in coconut somatic embryogenesis and to develop a repeatable protocol, it is imperative to understand, identify, and characterize molecular events involved in coconut somatic embryogenesis pathway. Transcriptome analysis (RNA-Seq) of coconut embryogenic calli, derived from plumular explants of West Coast Tall cultivar, was undertaken on an Illumina HiSeq 2000 platform. After de novo transcriptome assembly and functional annotation, we have obtained 40,367 transcripts which showed significant BLASTx matches with similarity greater than 40 % and E value of ≤10(-5). Fourteen genes known to be involved in somatic embryogenesis were identified. Quantitative real-time PCR (qRT-PCR) analyses of these 14 genes were carried in six developmental stages. The result showed that CLV was upregulated in the initial stage of callogenesis. Transcripts GLP, GST, PKL, WUS, and WRKY were expressed more in somatic embryo stage. The expression of SERK, MAPK, AP2, SAUR, ECP, AGP, LEA, and ANT were higher in the embryogenic callus stage compared to initial culture and somatic embryo stages. This study provides the first insights into the gene expression patterns during somatic embryogenesis in coconut.

Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link

PubMed Central

Gupta, Anindya; Silman, Alan J

2004-01-01

The present review attempts to reconcile the dichotomy that exists in the literature in relation to fibromyalgia, in that it is considered either a somatic response to psychological stress or a distinct organically based syndrome. Specifically, the hypothesis explored is that the link between chronic stress and the subsequent development of fibromyalgia can be explained by one or more abnormalities in neuroendocrine function. There are several such abnormalities recognised that both occur as a result of chronic stress and are observed in fibromyalgia. Whether such abnormalities have an aetiologic role remains uncertain but should be testable by well-designed prospective studies. PMID:15142258

The pathway to femaleness: current knowledge on embryonic development of the ovary

PubMed Central

Yao, Humphrey Hung-Chang

2014-01-01

Increasing evidence indicates that organogenesis of the ovary is not a passive process arising by default in the absence of the testis pathway. A coordinated interaction is actually in force between somatic cells and female germ cells in embryonic ovaries, thus creating a unique microenvironment that facilitates the formation of follicles. Identification of the functional roles of several novel regulatory elements such as Figα, Foxl2, follistatin, and Wnt4 reveals the complexity of early ovarian organization. Challenges await us to establish the molecular connections of these molecules as well as to discover new candidates in the pathway of early ovarian development. PMID:15664455

[Psychosomatics and psychotraumatology of refugees and migrants : A Challenge for the Internist].

PubMed

Schellong, J; Epple, F; Weidner, K

2016-05-01

Many refugees experience severely stressful events in their home countries, during migration and occasionally even after arrival in the country of destination. The individual reactions not only influence the mental health but also somatic well being. Traumatic events may have an essential impact on psychosocial functioning; moreover, the social circumstances during the integration process influence mental stability. Physicians play an important role in identifying possible traumatization and subsequently guiding towards adequate treatment; hence, the healthcare of refugees should regularly include psychosomatic and psychotraumatological aspects. Knowledge of screening instruments, trauma-informed care and interpreter-assisted communication are necessary to meet required standards.

Psychodynamic psychotherapy for complex trauma: targets, focus, applications, and outcomes

PubMed Central

Spermon, Deborah; Darlington, Yvonne; Gibney, Paul

2010-01-01

Complex trauma describes that category of severe, chronic interpersonal trauma usually originating in the formative years of a child. In the adult, this can result in global dissociative difficulties across areas of cognitive, affective, somatic, and behavioral functions. Targeting this field of traumatic pathology, this article reviews the contributions and developments within one broad approach: psychodynamic theory and practice. Brief descriptions of aspects of analytical, Jungian, relational, object relations, and attachment therapeutic approaches are given, along with understandings of pathology and the formulation of therapeutic goals. Major practices within client sessions are canvassed and the issues of researching treatment outcomes are discussed. PMID:22110335

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

PubMed Central

Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

2014-01-01

Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

Androgen receptor polyglutamine repeat length (AR-CAGn) modulates the effect of testosterone on androgen-associated somatic traits in Filipino young adult men.

PubMed

Ryan, Calen P; Georgiev, Alexander V; McDade, Thomas W; Gettler, Lee T; Eisenberg, Dan T A; Rzhetskaya, Margarita; Agustin, Sonny S; Hayes, M Geoffrey; Kuzawa, Christopher W

2017-06-01

The androgen receptor (AR) mediates expression of androgen-associated somatic traits such as muscle mass and strength. Within the human AR is a highly variable glutamine short-tandem repeat (AR-CAGn), and CAG repeat number has been inversely correlated to AR transcriptional activity in vitro. However, evidence for an attenuating effect of long AR-CAGn on androgen-associated somatic traits has been inconsistent in human populations. One possible explanation for this lack of consistency is that the effect of AR-CAGn on AR bioactivity in target tissues likely varies in relation to circulating androgen levels. We tested whether relationships between AR-CAGn and several androgen-associated somatic traits (waist circumference, lean mass, arm muscle area, and grip strength) were modified by salivary (waking and pre-bed) and circulating (total) testosterone (T) levels in young adult males living in metropolitan Cebu, Philippines (n = 675). When men's waking T was low, they had a reduction in three out of four androgen-associated somatic traits with lengthening AR-CAGn (p < .1), consistent with in vitro research. However, when waking T was high, we observed the opposite effect-lengthening AR-CAGn was associated with an increase in these same somatic traits. Our finding that longer AR-CAGn predicts greater androgen-associated trait expression among high-T men runs counter to in vitro work, but is generally consistent with the few prior studies to evaluate similar interactions in human populations. Collectively, these results raise questions about the applicability of findings derived from in vitro AR-CAGn studies to the receptor's role in maintaining androgen-associated somatic traits in human populations. © 2017 Wiley Periodicals, Inc.

Discordance of somatic mutations between Asian and Caucasian patient populations with gastric cancer

PubMed Central

Jia, Feifei; Teer, Jamie K.; Knepper, Todd C.; Lee, Jae K.; Zhou, Hong-Hao; He, Yi-Jing; McLeod, Howard L.

2017-01-01

Background Differences in response to cancer treatments have been observed among racially and ethnically diverse gastric cancer patient populations. In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. Mapping driver gene mutations for the gastric cancer patient population as a whole has significant potential to advance precision therapy. Methods Gastric cancer patient cases with sequencing data (total n=473) were obtained from The Cancer Genome Atlas (TCGA; n=295), Moffitt Cancer Center Total Cancer Care™ (TCC; n=33), and three published studies (n=145). Relevant somatic mutation frequency data were obtained from cBioPortal, TCC database and in-house analysis tool, and relevant publication Results We have found somatic mutation rates of several driver genes significantly vary between gastric cancer patients of Asian and Caucasian descent, with substantial variation across different geographic regions. Non-parametric statistical tests were performed to examine significant differences in protein-altering somatic mutations between Asian and Caucasian gastric cancer patient groups. Frequencies of somatic mutations of 5 genes were APC(Asian: Caucasian 6.06% vs. 14.40%, p=0.0076) ARIDIA(20.7% vs. 32.1%, p=0.01) KMT2A(4.04% vs. 12.35%, p=0.003) PIK3CA(9.6% vs. 18.52%, p=0.01) PTEN(2.52% vs. 9.05%, p=0.008), showing significant differences between Asian and Caucasian gastric cancer patients. Conclusions Our study has found significant differences in protein-altering somatic mutation frequencies in diverse geographic populations. In particular, we found that the somatic patterns may offer better insight and important opportunities for both targeted drug development and precision therapeutic strategies between Asian and Caucasian gastric cancer patients. PMID:28039579

Discordance of Somatic Mutations Between Asian and Caucasian Patient Populations with Gastric Cancer.

PubMed

Jia, Feifei; Teer, Jamie K; Knepper, Todd C; Lee, Jae K; Zhou, Hong-Hao; He, Yi-Jing; McLeod, Howard L

2017-04-01

Differences in response to cancer treatments have been observed among racially and ethnically diverse gastric cancer (GC) patient populations. In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. Mapping driver gene mutations for the GC patient population as a whole has significant potential to advance precision therapy. GC patients with sequencing data (N = 473) were obtained from The Cancer Genome Atlas (TCGA; n = 295), Moffitt Cancer Center Total Cancer Care™ (TCC; n = 33), and three published studies (n = 145). In addition, relevant somatic mutation frequency data were obtained from cBioPortal, the TCC database, and an in-house analysis tool, as well as relevant publications. We found that the somatic mutation rates of several driver genes vary significantly between GC patients of Asian and Caucasian descent, with substantial variation across different geographic regions. Non-parametric statistical tests were performed to examine the significant differences in protein-altering somatic mutations between Asian and Caucasian GC patient groups. The frequencies of somatic mutations of five genes were: APC (Asian: Caucasian 6.06 vs. 14.40%, p = 0.0076), ARIDIA (20.7 vs. 32.1%, p = 0.01), KMT2A (4.04 vs. 12.35%, p = 0.003), PIK3CA (9.6 vs. 18.52%, p = 0.01), and PTEN (2.52 vs. 9.05%, p = 0.008), showing significant differences between Asian and Caucasian GC patients. Our study found significant differences in protein-altering somatic mutation frequencies in diverse geographic populations. In particular, we found that the somatic patterns may offer better insight and important opportunities for both targeted drug development and precision therapeutic strategies between Asian and Caucasian GC patients.

Economic weights of somatic cell score in dairy sheep.

PubMed

Legarra, A; Ramón, M; Ugarte, E; Pérez-Guzmán, M D; Arranz, J

2007-03-01

The economic weights for somatic cell score (SCS) have been calculated using profit functions. Economic data were collected in the Latxa breed. Three aspects have been considered: bulk tank milk payment, veterinary treatments due to high SCS, and culling. All of them are non-linear profit functions. Milk payment is based on the sum of the log-normal distributions of somatic cell count, and veterinary treatments on the probability of subclinical mastitis, which is inferred when individual SCS surpass some threshold. Both functions lead to non-standard distributions. The derivatives of the profit function were computed numerically. Culling was computed by assuming that a conceptual trait culled by mastitis (CBM) is genetically correlated to SCS. The economic weight considers the increase in the breeding value of CBM correlated to an increase in the breeding value of SCS, assuming genetic correlations ranging from 0 to 0.9. The relevance of the economic weights for selection purposes was checked by the estimation of genetic gains for milk yield and SCS under several scenarios of genetic parameters and economic weights. The overall economic weights for SCS range from - 2.6 to - 9.5 € per point of SCS, with an average of - 4 € per point of SCS, depending on the expected average SCS of the flock. The economic weight is higher around the thresholds for payment policies. Economic weights did not change greatly with other assumptions. The estimated genetic gains with economic weights of 0.83 € per l of milk yield and - 4 € per point of SCS, assuming a genetic correlation of - 0.30, were 3.85 l and - 0.031 SCS per year, with an associated increase in profit of 3.32 €. This represents a very small increase in profit (about 1%) relative to selecting only for milk yield. Other situations (increased economic weights, different genetic correlations) produced similar genetic gains and changes in profit. A desired-gains index reduced the increase in profit by 3%, although it could be greater depending on the genetic parameters. It is concluded that the inclusion of SCS in dairy sheep breeding programs is of low economic relevance and recommended only if recording is inexpensive or for animal welfare concerns.

Evolution and expression analysis reveal the potential role of the HD-Zip gene family in regulation of embryo abortion in grapes (Vitis vinifera L.).

PubMed

Li, Zhiqian; Zhang, Chen; Guo, Yurui; Niu, Weili; Wang, Yuejin; Xu, Yan

2017-09-21

The HD-Zip family has a diversity of functions during plant development. In this study, we identify 33 HD-Zip transcription factors in grape and detect their expressions in ovules and somatic embryos, as well as in various vegetative organs. A genome-wide survey for HD-Zip transcription factors in Vitis was conducted based on the 12 X grape genome (V. vinifera L.). A total of 33 members were identified and classified into four subfamilies (I-IV) based on phylogeny analysis with Arabidopsis, rice and maize. VvHDZs in the same subfamily have similar protein motifs and intron/exon structures. An evaluation of duplication events suggests several HD-Zip genes arose before the divergence of the grape and Arabidopsis lineages. The 33 members of HD-Zip were differentially expressed in ovules of the stenospermic grape, Thompson Seedless and of the seeded grape, Pinot noir. Most have higher expressions during ovule abortion in Thompson Seedless. In addition, transcripts of the HD-Zip family were also detected in somatic embryogenesis of Thompson Seedless and in different vegetative organs of Thompson Seedless at varying levels. Additionally, VvHDZ28 is located in the nucleus and had transcriptional activity consistent with the typical features of the HD-Zip family. Our results provide a foundation for future grape HD-Zip gene function research. The identification and expression profiles of the HD-Zip transcription factors in grape, reveal their diverse roles during ovule abortion and organ development. Our results lay a foundation for functional analysis of grape HDZ genes.

The relationship between ataque de nervios and unexplained neurological symptoms: a preliminary analysis.

PubMed

Interian, Alejandro; Guarnaccia, Peter J; Vega, William A; Gara, Michael A; Like, Robert C; Escobar, Javier I; Díaz-Martínez, Angélica M

2005-01-01

Within somatization, unexplained neurological symptoms (UNSs) have been shown to mark a distinct subgroup with greater clinical severity. However, some UNSs resemble ataque de nervios somatic symptoms. This raises questions about cultural factors related to Hispanics with somatization characterized by UNSs. To examine cultural factors, preliminary analyses examined the relationship between Hispanic ethnicity, UNSs, and ataque de nervios. Data were obtained from 127 primary care patients (95 Hispanic, 32 European American) with somatization. The Composite International Diagnostic Interview provided somatization data, whereas the Primary Care Evaluation of Mental Disorders was used for data on Axis I disorders. Ataque de nervios was assessed via a proxy measure. Within each ethnic group, cross-tabs examined the relationship between ataque de nervios and multiple UNSs, and ataque de nervios and selected Axis I disorders. Only among Hispanics, a significant overlap was found between ataque de nervios and having four or more UNSs (p < .001), and ataque de nervios and a diagnosis of panic disorder (p = .05). Although equal percentages of European Americans and Hispanics experience multiple UNSs, these results show that the presentation of UNSs among some Hispanics may be qualitatively different, because it may involve features related to ataque de nervios. A diagnosis of panic disorder also appears to interact with cultural factors.

Decreased Plasma BDNF Levels of Patients with Somatization Disorder

PubMed Central

Kang, Nam-In; Park, Jong-Il

2016-01-01

Objective Brain-derived neurotrophic factor (BDNF), one of the most abundant and important neurotrophins, is known to be involved in the development, survival, maintenance, and plasticity of neurons in the nervous system. Some studies have suggested that BDNF may play a role in the pathophysiology of several psychiatric illnesses such as depression and schizophrenia. Similarly, it is likely that the alteration of BDNF may be associated with the neuro-modulation that contributes to the development of somatization disorder. Methods The purpose of this study was to determine whether there is an abnormality of plasma BDNF levels in patients with somatization disorder, and to analyze the nature of the alteration after pharmacotherapy using an enzyme-linked immunosorbent assay (ELISA). Results The plasma BDNF levels of the patients with a somatization disorder were significantly lower compared with those of the control volunteers (83.61±89.97 pg/mL vs. 771.36±562.14 pg/mL); moreover, the plasma BDNF levels of those patients who received an antidepressant were significantly increased after the treatment (118.13±91.45 pg/mL vs. 72.92±88.21 pg/mL). Conclusion These results suggest that BDNF may play a role in the pathophysiology of somatization disorder. PMID:27757131

Ecstasy (MDMA) and high prevalence psychiatric symptomatology: somatic anxiety symptoms are associated with polydrug, not ecstasy, use.

PubMed

Bedi, G; Van Dam, N T; Redman, J

2010-02-01

Although previous studies have examined anxiety and depression in ecstasy (+/-3,4-methylenedioxymethamphetamine; MDMA) users, it remains unclear whether symptoms are associated specifically with ecstasy or with polydrug use in general. We compared mean symptomatology and clinically significant symptoms in 45 ecstasy polydrug, 48 cannabis polydrug and 40 legal drug users, who completed standardised self-report anxiety and depression symptom measures. We further examined whether group differences were secondary to increased somatic symptom reporting, which may reflect acute/subacute drug effects. Anxiety and depression scores were higher in polydrug than legal drug users, with no difference between ecstasy and cannabis groups. There was no difference in numbers meeting criteria for clinically significant depression or 'moderate' or 'severe' anxiety, but the polydrug group contained more individuals reporting at least 'mild' anxiety symptoms than the legal drug control. Multivariate analyses indicated that anxiety alone was sufficient to discriminate groups. Polydrug users reported more somatic anxiety symptoms than legal drug users, but endorsed equivalent numbers of non-somatic symptoms. High prevalence psychiatric symptomatology in ecstasy polydrug users may be associated with polydrug rather than ecstasy use. Higher ratings in polydrug users appear to be secondary to increased somatic symptom reporting, suggesting possible impacts of drug effects on symptom endorsement.

Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements.

PubMed

Lewis, Samuel H; Quarles, Kaycee A; Yang, Yujing; Tanguy, Melanie; Frézal, Lise; Smith, Stephen A; Sharma, Prashant P; Cordaux, Richard; Gilbert, Clément; Giraud, Isabelle; Collins, David H; Zamore, Phillip D; Miska, Eric A; Sarkies, Peter; Jiggins, Francis M

2018-01-01

In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were probably present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and messenger RNAs are common among arthropods. The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs, spiders and scorpions) suggests that arthropods originally used a plant-like RNA interference mechanism to silence TEs. Our results call into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrate that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropod evolution.

Remembrance of things past retrieved from the Paramecium genome.

PubMed

Sperling, Linda

2011-01-01

Paramecium and other ciliates are the only unicellular eukaryotes that separate germinal and somatic functions. A germline micronucleus transmits the genetic information to sexual progeny, while a somatic macronucleus expresses the genetic information during vegetative growth to determine the phenotype. At each sexual generation, a new macronucleus develops from the zygotic nucleus through programmed rearrangements of the germline genome. Paramecium tetraurelia somatic genome sequencing, reviewed here, has provided insight into the organization and evolution of the genome. A series of at least 3 whole genome duplications was detected in the Paramecium lineage and selective pressures that determine the fate of the gene duplicates analyzed. Variability in the somatic DNA was characterized and could be attributed to the genome rearrangement processes. Since, in Paramecium, alternative genome rearrangement patterns can be inherited across sexual generations by homology-dependent epigenetic mechanisms and can affect phenotype, I discuss the possibility that ciliate nuclear dimorphism buffers genetic variation hidden in the germline. Copyright © 2011 Institut Pasteur. Published by Elsevier SAS. All rights reserved.

Psychosomatics: a current overview.

PubMed

Fischbein, José Eduardo

2011-02-01

The term 'psychosomatic' has typically defined a series of illnesses in which somatic injury breaks out from psychic conflict not recognized as such. Currently, health is considered the only psychosomatic state of integration of mind and soma: an ideal state of integration. Somatic pathology is an effect of mind/body splitting. In the heterogeneous 'field of psychosomatics' interaction between psyche and soma ranges from classical psychosomatic illness to sporadic episodes in which the body has responded to an inability to process mental conflict. The author briefly reviews the development of psychoanalytic thought on psychosomatics in Argentina. He suggests the need to find appropriate conceptual tools to approach the mental structure underlying this pathology. He presents his ideas about the mental functioning of patients with somatization disorders. He introduces the concept of somatic event as a restitution phenomenon through which the subject attempts to re-establish self-integration and links with reality. He also offers some reflections on temporality and on changes in psychoanalytic technique with these patients. A clinical case illustrates his ideas. Copyright © 2011 Institute of Psychoanalysis.

Comorbid thyroid disease in patients with major depressive disorder - results from the European Group for the Study of Resistant Depression (GSRD).

PubMed

Fugger, Gernot; Dold, Markus; Bartova, Lucie; Kautzky, Alexander; Souery, Daniel; Mendlewicz, Julien; Serretti, Alessandro; Zohar, Joseph; Montgomery, Stuart; Frey, Richard; Kasper, Siegfried

2018-06-01

This multicenter study of the European Group for the Study of Resistant Depression (GSRD) aimed to explore the association between major depressive disorder (MDD) and comorbid thyroid disease. A total number of 1410 patients` characteristics in terms of demographic and clinical information were compared between MDD subjects with and without concurrent thyroid disease using descriptive statistics, analyses of covariance (ANCOVA) and binary logistic regression analyses. We determined a point prevalence rate for comorbid hypothyroidism of 13.2% and 1.6% for comorbid hyperthyroidism respectively. Patients with MDD+comorbid hypothyroidism were significantly older, more likely to be female, inpatient and suffering from other comorbid chronic somatic conditions. Furthermore, MADRS score at onset of the current depressive episode was significantly higher, psychotic features of depression were more likely pronounced. Overall, patients in the MDD+comorbid hypothyroidism group were rather treated with a combination of drugs, for example, pregabalin, antipsychotic drugs and mood stabilizers. In the MDD+comorbid hyperthyroidism group patients were significantly older, of Caucasian origin and diagnosed with other somatic comorbidities. In conclusion, our analyses suggest that abnormal thyroid function, especially hypothyroidism, is linked to depression severity and associated with distinct psychopathologic features of depression. However, comorbid thyroid disease has no influence on treatment response. A combination or augmentation of psychopharmacological drugs, especially with antipsychotics, mood stabilizers and pregabalin is more likely in patients with hypothyroid conditions. Thyroid disorder is frequently found in combination with other chronic somatic diseases including hypertension and heart disease. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

The personality trait of neuroticism is strongly associated with long-term morbidity in testicular cancer survivors.

PubMed

Grov, Ellen Karine; Fosså, Sophie D; Bremnes, Roy M; Dahl, Olav; Klepp, Olbjørn; Wist, Erik; Dahl, Alv A

2009-01-01

Neuroticism is a personality trait expressing nervousness and insecurity. Associations between neuroticism and morbidity in long-term cancer survivors have hardly been explored. The aim of this study was to explore associations between neuroticism and somatic and mental morbidity and lifestyle issues in long-term survivors of testicular cancer (TCSs). All Norwegian TCSs treated between 1980 and 1994 (n = 1 814) were invited to this cross-sectional study. Among them 1 428 (79% response rate) delivered valid data. Neuroticism was self-rated on an abridged version of the Eysenck Personality Inventory. Information was collected by mailed questionnaires. The associations of neuroticism and self-reported variables were tested with multivariate logistic regression analyses. Neuroticism was significantly associated with presence of somatic complaints, reduced physical function, neurotoxic side-effects (tinnitus, hearing impairment, peripheral neuropathy, and Raynaud's Phenomenon), self-esteem, concerns about not being able to father children, sexual problems, hazardous alcohol use, daily use of medication, use of sedatives and hypnotics, recent visits to a general practitioner, and seeing a psychologist/ psychiatrist after ended cancer treatment. Poor self-rated health, higher number of negative life events, economical problems and problems getting loans granted showed significant associations with neuroticism. Neuroticism in TCSs at long-term follow-up is significantly associated with somatic and mental morbidities, and several aspects of unhealthy lifestyle. High levels of neuroticism should be considered in TCSs expressing multiple complaints and concerns at follow-up consultations. Assessment of neuroticism may be clinically important in order to offer appropriate interventions to prevent and manage morbidity in TCSs.

Mindfulness-Based Therapies in the Treatment of Functional Gastrointestinal Disorders: A Meta-Analysis

PubMed Central

2014-01-01

Background. Functional gastrointestinal disorders are highly prevalent and standard treatments are often unsatisfactory. Mindfulness-based therapy has shown benefit in conditions including chronic pain, mood, and somatization disorders. Objectives. To assess the quality and effectiveness reported in existing literature, we conducted a meta-analysis of mindfulness-based therapy in functional gastrointestinal disorders. Methods. Pubmed, EBSCO, and Cochrane databases were searched from inception to May 2014. Study inclusion criteria included randomized, controlled studies of adults using mindfulness-based therapy in the treatment of functional gastrointestinal disorders. Study quality was evaluated using the Cochrane risk of bias. Effect sizes were calculated and pooled to achieve a summary effect for the intervention on symptom severity and quality of life. Results. Of 119 records, eight articles, describing seven studies, met inclusion criteria. In six studies, significant improvements were achieved or maintained at the end of intervention or follow-up time points. The studies had an unclear or high risk of bias. Pooled effects were statistically significant for IBS severity (0.59, 95% CI 0.33 to 0.86) and quality of life (0.56, 95% CI 0.47 to 0.79). Conclusion. Studies suggest that mindfulness based interventions may provide benefit in functional gastrointestinal disorders; however, substantial improvements in methodological quality and reporting are needed. PMID:25295066

Culture of East Indian sandalwood tree somatic embryos in air-lift bioreactors for production of santalols, phenolics and arabinogalactan proteins

PubMed Central

Misra, Biswapriya B.; Dey, Satyahari

2013-01-01

The East Indian sandalwood tree, Santalum album, yields one of the costliest heartwoods and precious essential oil. Unsurprisingly, this endangered forest species is severely affected due to unmet global demands, illegal trade and harvesting, overharvesting and an epidemic mycoplasmal spike disease. In vitro micropropagation endeavours have resulted in defined in vitro stages such as somatic embryos that are amenable to mass production in bioreactors. We report on somatic embryo production in a 10-L air-lift-type bioreactor, and compare the growth and biochemical parameters with those of a 2-L air-lift-type bioreactor. For the 10-L bioreactor with biomass (475.7 ± 18 g fresh weight; P < 0.01), concomitantly santalols (5.2 ± 0.15 mg L−1; P < 0.05), phenolics (31 ± 1.6 mg L−1) and arabinogalactan proteins (AGPs) (39 ± 3.1 mg L−1; P < 0.05) are produced in 28 days. In addition, we identified and quantified several santalols and phenolics by means of high-performance thin-layer chromatography and reverse-phase high-pressure liquid chromatography analyses, respectively. Results indicate that 10-L-capacity air-lift bioreactors are capable of supporting somatic embryo cultures, while the extracellular medium provides opportunities for production of industrial raw materials such as santalols, phenolics and AGPs. This will prove useful for further optimization and scale-up studies of plant-produced metabolites.

Cognitive-behavioral therapy for somatization and symptom syndromes: a critical review of controlled clinical trials.

PubMed

Kroenke, K; Swindle, R

2000-01-01

Few treatments for somatization have been proven effective. In the past decade, however, clinical trials of cognitive-behavioral therapy (CBT) have been promising. Our aim was to critically review and synthesize the evidence from these trials. A search of the Medline database from 1966 through July 1999 was conducted to identify controlled trials designed to evaluate the efficacy of CBT in patients with somatization or symptom syndromes. A total of 31 controlled trials (29 randomized and 2 nonrandomized) were identified. Twenty-five studies targeted a specific syndrome (e.g. chronic fatigue, irritable bowel, pain) while 6 focused on more general somatization or hypochondriasis. Primary outcome assessment included physical symptoms, psychological distress and functional status in 28, 26 and 19 studies, respectively. Physical symptoms appeared the most responsive: CBT-treated patients improved more than control subjects in 71% of the studies and showed possibly greater improvement (i.e., a trend) in another 11% of the studies. A definite or possible advantage of CBT for reducing psychological distress was demonstrated in only 38 and 8% of studies, and for improving functional status in 47 and 26%. Group therapy and interventions as brief as 5 sessions proved efficacious. Benefits were sustained for up to 12 months. CBT can be an effective treatment for patients with somatization or symptom syndromes. Benefits can occur whether or not psychological distress is ameliorated. Since chronic symptoms are exceptionally common and most studies were conducted in referral populations, the optimal sequencing of CBT in treating primary care patients and the identification of those most likely to accept and respond to therapy should be further evaluated. Copyright 2000 S. Karger AG, Basel.

Effect of nutritional rehabilitation on gastric motility and somatization in adolescents with anorexia.

PubMed

Perez, Maria E; Coley, Brian; Crandall, Wallace; Di Lorenzo, Carlo; Bravender, Terrill

2013-09-01

To examine gastric function, as well as the presence of somatic complaints, anxiety symptoms, and functional gastrointestinal disorders (FGIDs), in adolescents with anorexia nervosa (AN) before and after nutritional rehabilitation. Sixteen females with AN and 22 healthy controls with similar demographic profiles were included. Gastric emptying (measured as residual gastric volume) and gastric accommodation (measured as postprandial antral diameter) were assessed with abdominal ultrasonography. Participants completed the Children's Somatization Inventory (CSI), the Screen for Child Anxiety-Related Emotional Disorders, and the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III version. All testing was repeated 3-4 months later. Body mass index in the AN group improved over time (P = .012). Fasting gastric parameters were similar in the 2 groups. Maximum postprandial antral diameter was significantly greater in controls compared with the AN group (P = .008). Only adolescents with AN demonstrated a significant increase in maximum postprandial diameter at repeat testing (P = .009). There was no difference in residual gastric volume between the 2 groups. Initial CSI scores were higher in adolescents with AN (P < .0001), including higher scores for nausea and abdominal pain. CSI scores were significantly lower in adolescents with AN (P = .035). Initial scores on the Screen for Child Anxiety-Related Emotional Disorders were significantly higher in adolescents with AN (P = .0005), but did not change over time. Adolescents with AN met significantly more criteria for FGIDs (P = .003). Adolescents with AN have impaired gastric accommodation that improves after nutritional rehabilitation, have significantly more somatic complaints, and meet more criteria for anxiety disorders and FGIDs. After nutritional rehabilitation, somatization improves and FGIDs become less common, but symptoms of anxiety persist. Copyright © 2013 Mosby, Inc. All rights reserved.

University of Texas MD Anderson Cancer Center (UT-MDACC): High-Throughput Screening Identifying Driving Mutations in Endometrial Cancer | Office of Cancer Genomics

Cancer.gov

Recent advances in next-generation sequencing technology have enabled the unprecedented characterization of a full spectrum of somatic alterations in cancer genomes. Given the large numbers of somatic mutations typically detected by this approach, a key challenge in the downstream analysis is to distinguish “drivers” that functionally contribute to tumorigenesis from “passengers” that occur as the consequence of genomic instability.

Somatic Mutations in NEK9 Cause Nevus Comedonicus

PubMed Central

Levinsohn, Jonathan L.; Sugarman, Jeffrey L.; McNiff, Jennifer M.; Antaya, Richard J.; Choate, Keith A.

2016-01-01

Acne vulgaris (AV) affects most adolescents, and of those affected, moderate to severe disease occurs in 20%. Comedones, follicular plugs consisting of desquamated keratinocytes and sebum, are central to its pathogenesis. Despite high heritability in first-degree relatives, AV genetic determinants remain incompletely understood. We therefore employed whole-exome sequencing (WES) in nevus comedonicus (NC), a rare disorder that features comedones and inflammatory acne cysts in localized, linear configurations. WES identified somatic NEK9 mutations, each affecting highly conserved residues within its kinase or RCC1 domains, in affected tissue of three out of three NC-affected subjects. All mutations are gain of function, resulting in increased phosphorylation at Thr210, a hallmark of NEK9 kinase activation. We found that comedo formation in NC is marked by loss of follicular differentiation markers, expansion of keratin-15-positive cells from localization within the bulge to the entire sub-bulge follicle and cyst, and ectopic expression of keratin 10, a marker of interfollicular differentiation not present in normal follicles. These findings suggest that NEK9 mutations in NC disrupt normal follicular differentiation and identify NEK9 as a potential regulator of follicular homeostasis. PMID:27153399

Chemical strategies for pancreatic β cell differentiation, reprogramming, and regeneration.

PubMed

Ma, Xiaojie; Zhu, Saiyong

2017-04-01

Generation of unlimited functional pancreatic β cells is critical for the study of pancreatic biology and treatment of diabetes mellitus. Recent advances have suggested several promising directions, including directed differentiation of pancreatic β cells from pluripotent stem cells, reprogramming of pancreatic β cells from other types of somatic cells, and stimulated proliferation and enhanced functions of existing pancreatic β cells. Small molecules are useful in generating unlimited numbers of functional pancreatic cells in vitro and could be further developed as drugs to stimulate endogenous pancreatic regeneration. Here, we provide an updated summary of recent major achievements in pancreatic β cell differentiation, reprogramming, proliferation, and function. These studies will eventually lead to significant advances in the field of pancreatic biology and regeneration. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A randomized trial of treatments for high-utilizing somatizing patients.

PubMed

Barsky, Arthur J; Ahern, David K; Bauer, Mark R; Nolido, Nyryan; Orav, E John

2013-11-01

Somatization and hypochondriacal health anxiety are common sources of distress, impairment, and costly medical utilization in primary care practice. A range of interventions is needed to improve the care of these patients. To determine the effectiveness of two cognitive behavioral interventions for high-utilizing, somatizing patients, using the resources found in a routine care setting. Patients were randomly assigned to a two-step cognitive behavioral treatment program accompanied by a training seminar for their primary care physicians, or to relaxation training. Providers routinely working in these patients' primary care practices delivered the cognitive behavior therapy and relaxation training. A follow-up assessment was completed immediately prior to treatment and 6 and 12 months later. Eighty-nine medical outpatients with elevated levels of somatization, hypochondriacal health anxiety, and medical care utilization. Somatization and hypochondriasis, overall psychiatric distress, and role impairment were assessed with well-validated, self-report questionnaires. Outpatient visits and medical care costs before and after the intervention were obtained from the encounter claims database. At 6 month and 12 month follow-up, both intervention groups showed significant improvements in somatization (p < 0.01), hypochondriacal symptoms (p < 0.01), overall psychiatric distress (p < 0.01), and role impairment (p < 0.01). Outcomes did not differ significantly between the two groups. When both groups were combined, ambulatory visits declined from 10.3 to 8.8 (p = 0.036), and mean ambulatory costs decreased from $3,574 to $2,991 (pp = 0.028) in the year preceding versus the year following the interventions. Psychiatric visits and costs were unchanged. Two similar cognitive behavioral interventions, delivered with the resources available in routine primary care, improved somatization, hypochondriacal symptoms, overall psychiatric distress, and role function. They also reduced the ambulatory visits and costs of these high utilizing outpatients.

Beyond "somatization" and "psychologization": symptom-level variation in depressed Han Chinese and Euro-Canadian outpatients.

PubMed

Dere, Jessica; Sun, Jiahong; Zhao, Yue; Persson, Tonje J; Zhu, Xiongzhao; Yao, Shuqiao; Bagby, R Michael; Ryder, Andrew G

2013-01-01

The finding that people of Chinese heritage tend to emphasize somatic rather than psychological symptoms of depression has frequently been discussed in the culture and mental health literature since the 1970s. Recent studies have confirmed that Chinese samples report more somatic and fewer psychological depression symptoms compared to "Western" samples. The question remains, however, as to whether or not these effects are attributable to variation in all the constituent symptoms or to a subset. If the latter, there is the additional possibility that some symptoms might show a divergent pattern. Such findings would have implications for how cultural variations in symptom presentation are interpreted, and would also inform the cultural study of affective experiences more broadly. The current study addressed these issues in Chinese (n = 175) and Euro-Canadian (n = 107) psychiatric outpatients originally described by Ryder et al. (2008). Differential item functioning (DIF) was used to examine whether specific somatic and psychological symptoms diverged from the overall patterns of cultural variation. Chi-square analyses were used to examine atypical somatic symptoms (e.g., hypersomnia), previously neglected in this literature. No DIF was observed for the typical somatic symptoms, but Euro-Canadians reported greater levels of atypical somatic symptoms, and showed higher rates of atypical depression. DIF was observed for psychological symptoms-the Chinese reported high levels of "suppressed emotions" and "depressed mood," relative to their overall psychological symptom reporting. Chinese outpatients also spontaneously reported "depressed mood" at similar levels as the Euro-Canadians, contrary to prevailing ideas about Chinese unwillingness to discuss depression. Overall, the findings provide a more nuanced picture of how culture shapes symptom presentation and point toward future studies designed to unpack cultural variation in narrower subsets of depressive symptoms.

Germ cell regeneration-mediated, enhanced mutagenesis in the ascidian Ciona intestinalis reveals flexible germ cell formation from different somatic cells.

PubMed

Yoshida, Keita; Hozumi, Akiko; Treen, Nicholas; Sakuma, Tetsushi; Yamamoto, Takashi; Shirae-Kurabayashi, Maki; Sasakura, Yasunori

2017-03-15

The ascidian Ciona intestinalis has a high regeneration capacity that enables the regeneration of artificially removed primordial germ cells (PGCs) from somatic cells. We utilized PGC regeneration to establish efficient methods of germ line mutagenesis with transcription activator-like effector nucleases (TALENs). When PGCs were artificially removed from animals in which a TALEN pair was expressed, somatic cells harboring mutations in the target gene were converted into germ cells, this germ cell population exhibited higher mutation rates than animals not subjected to PGC removal. PGC regeneration enables us to use TALEN expression vectors of specific somatic tissues for germ cell mutagenesis. Unexpectedly, cis elements for epidermis, neural tissue and muscle could be used for germ cell mutagenesis, indicating there are multiple sources of regenerated PGCs, suggesting a flexibility of differentiated Ciona somatic cells to regain totipotency. Sperm and eggs of a single hermaphroditic, PGC regenerated animal typically have different mutations, suggesting they arise from different cells. PGCs can be generated from somatic cells even though the maternal PGCs are not removed, suggesting that the PGC regeneration is not solely an artificial event but could have an endogenous function in Ciona. This study provides a technical innovation in the genome-editing methods, including easy establishment of mutant lines. Moreover, this study suggests cellular mechanisms and the potential evolutionary significance of PGC regeneration in Ciona. Copyright © 2017 Elsevier Inc. All rights reserved.

Divergent functions of the left and right central amygdala in visceral nociception

PubMed Central

Sadler, Katelyn E.; McQuaid, Neal A.; Cox, Abigail C.; Behun, Marissa N.; Trouten, Allison M.; Kolber, Benedict J.

2017-01-01

The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2–mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase–activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2–mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain–like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries. PMID:28225716

Divergent functions of the left and right central amygdala in visceral nociception.

PubMed

Sadler, Katelyn E; McQuaid, Neal A; Cox, Abigail C; Behun, Marissa N; Trouten, Allison M; Kolber, Benedict J

2017-04-01

The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2-mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase-activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2-mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain-like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.

Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC.

PubMed

Marcó, Sara; Pujol, Anna; Roca, Carles; Motas, Sandra; Ribera, Albert; Garcia, Miguel; Molas, Maria; Villacampa, Pilar; Melia, Cristian S; Sánchez, Víctor; Sánchez, Xavier; Bertolin, Joan; Ruberte, Jesús; Haurigot, Virginia; Bosch, Fatima

2016-09-01

Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT) that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches. © 2016. Published by The Company of Biologists Ltd.

Association between the Center for Epidemiologic Studies Depression Scale (CES-D) and mortality in a community sample: An artifact of the somatic complaints factor?1

PubMed Central

Pettit, Jeremy W.; Lewinsohn, Peter M.; Seeley, John R.; Roberts, Robert E.; Hibbard, Judith H.; Hurtado, Arnold V.

2009-01-01

Most previous studies of the depression-mortality association have not examined distinct depressive symptom clusters. This ex post facto study examined which aspects of depression may account for its association with mortality. The Center for Epidemiologic Studies Depression Scale (CES-D) was administered to 3,867 community dwelling adults. Cox proportional hazards procedures estimated the risk of mortality as a function of depression status and each of 4 CES-D factor scores. Depressed participants (CES-D ≥ 16) had a 1.23-fold higher risk of mortality (95% CI 1.03-1.49), adjusting for sociodemographics. Somatic Complaints (SC) was the only factor to predict mortality (HR 1.19, 95% CI 1.03-1.38). After excluding SC, CES-D scores no longer predicted mortality (HR .98, 95% CI .79-1.21). The association between CES-D depressive symptoms and mortality appears to be a function of the SC factor. The association between non-somatic depressive symptoms and mortality may not be as robust as past findings suggest. PMID:19936326

Association between the Center for Epidemiologic Studies Depression Scale (CES-D) and mortality in a community sample: An artifact of the somatic complaints factor?

PubMed

Pettit, Jeremy W; Lewinsohn, Peter M; Seeley, John R; Roberts, Robert E; Hibbard, Judith H; Hurtado, Arnold V

2008-05-01

Most previous studies of the depression-mortality association have not examined distinct depressive symptom clusters. This ex post facto study examined which aspects of depression may account for its association with mortality. The Center for Epidemiologic Studies Depression Scale (CES-D) was administered to 3,867 community dwelling adults. Cox proportional hazards procedures estimated the risk of mortality as a function of depression status and each of 4 CES-D factor scores. Depressed participants (CES-D ≥ 16) had a 1.23-fold higher risk of mortality (95% CI 1.03-1.49), adjusting for sociodemographics. Somatic Complaints (SC) was the only factor to predict mortality (HR 1.19, 95% CI 1.03-1.38). After excluding SC, CES-D scores no longer predicted mortality (HR .98, 95% CI .79-1.21). The association between CES-D depressive symptoms and mortality appears to be a function of the SC factor. The association between non-somatic depressive symptoms and mortality may not be as robust as past findings suggest.

Subtle persistent working memory and selective attention deficits in women with premenstrual syndrome.

PubMed

Slyepchenko, Anastasiya; Lokuge, Sonali; Nicholls, Brianne; Steiner, Meir; Hall, Geoffrey B C; Soares, Claudio N; Frey, Benicio N

2017-03-01

As a recurrent, cyclical phenomenon, premenstrual syndrome (PMS) affects a significant proportion of women of the reproductive age, and leads to regular monthly days of functional impairment. Symptoms of PMS include somatic and psychological symptoms, such as headaches, sleep disturbances, social withdrawal and mood changes, during the late luteal phase of the menstrual cycle, which alleviate during the follicular phase. This study investigated neurocognitive functioning in women with moderate to severe PMS symptoms (n=13) compared to women with mild/no PMS (n=27) through administration of a battery of neuropsychological tests during the asymptomatic follicular phase of the menstrual cycle. Relative to women with mild/no PMS symptoms, women with moderate to severe PMS showed significantly poorer accuracy and more errors of omission on the N-0-back, as well as more errors of omission on the N-2-back task, indicating the presence of impairment in selective attention and working memory. This study provides evidence of persistent, subtle working memory and selective attention difficulties in those with moderate to severe PMS during the follicular phase of the menstrual cycle. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Computational approaches to identify functional genetic variants in cancer genomes

PubMed Central

Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris; Ritchie, Graham R.S.; Creixell, Pau; Karchin, Rachel; Vazquez, Miguel; Fink, J. Lynn; Kassahn, Karin S.; Pearson, John V.; Bader, Gary; Boutros, Paul C.; Muthuswamy, Lakshmi; Ouellette, B.F. Francis; Reimand, Jüri; Linding, Rune; Shibata, Tatsuhiro; Valencia, Alfonso; Butler, Adam; Dronov, Serge; Flicek, Paul; Shannon, Nick B.; Carter, Hannah; Ding, Li; Sander, Chris; Stuart, Josh M.; Stein, Lincoln D.; Lopez-Bigas, Nuria

2014-01-01

The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor, but only a minority drive tumor progression. We present the result of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype. PMID:23900255

Epilepsy as a systemic condition: Link with somatic comorbidities.

PubMed

Novy, J; Bell, G S; Peacock, J L; Sisodiya, S M; Sander, J W

2017-10-01

People with epilepsy have more concomitant medical conditions than the general population; these comorbidities play an important role in premature mortality. We sought to generate explanatory hypotheses about the co-occurrence of somatic comorbidities and epilepsy, avoiding causal and treatment-resultant biases. We collected clinical, demographic and somatic comorbidity data for 2016 consecutive adults with epilepsy undergoing assessment at a tertiary centre and in 1278 people with epilepsy in the community. Underlying causes of epilepsy were not classed as comorbidities. Somatic comorbidities were more frequent in the referral centre (49%) where people more frequently had active epilepsy than in the community (36%). Consistent risk factors for comorbidities were found in both cohorts. Using multivariable ordinal regression adjusted for age, longer epilepsy duration and an underlying brain lesion were independently associated with a smaller burden of somatic conditions. The treatment burden, measured by the number of drugs to which people were exposed, was not an independent predictor. Shorter epilepsy duration was a predictor for conditions that conceivably harbour significant mortality risks. Somatic comorbidities do not occur randomly in relation to epilepsy; having more severe epilepsy seems to be a risk factor. Independently from age, the early period after epilepsy onset appears to be at particular risk, although it is not clear whether this relates to an early mortality or to a later decrease in the burden of comorbidities. These results suggest that, for some people, epilepsy should be considered a systemic condition not limited to the CNS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Linking maternal and somatic 5S rRNA types with different sequence-specific non-LTR retrotransposons

PubMed Central

Pagano, Johanna F.B.; Ensink, Wim A.; van Olst, Marina; van Leeuwen, Selina; Nehrdich, Ulrike; Zhu, Kongju; Spaink, Herman P.; Girard, Geneviève; Rauwerda, Han; Jonker, Martijs J.; Dekker, Rob J.

2017-01-01

5S rRNA is a ribosomal core component, transcribed from many gene copies organized in genomic repeats. Some eukaryotic species have two 5S rRNA types defined by their predominant expression in oogenesis or adult tissue. Our next-generation sequencing study on zebrafish egg, embryo, and adult tissue identified maternal-type 5S rRNA that is exclusively accumulated during oogenesis, replaced throughout the embryogenesis by a somatic-type, and thus virtually absent in adult somatic tissue. The maternal-type 5S rDNA contains several thousands of gene copies on chromosome 4 in tandem repeats with small intergenic regions, whereas the somatic-type is present in only 12 gene copies on chromosome 18 with large intergenic regions. The nine-nucleotide variation between the two 5S rRNA types likely affects TFIII binding and riboprotein L5 binding, probably leading to storage of maternal-type rRNA. Remarkably, these sequence differences are located exactly at the sequence-specific target site for genome integration by the 5S rRNA-specific Mutsu retrotransposon family. Thus, we could define maternal- and somatic-type MutsuDr subfamilies. Furthermore, we identified four additional maternal-type and two new somatic-type MutsuDr subfamilies, each with their own target sequence. This target-site specificity, frequently intact maternal-type retrotransposon elements, plus specific presence of Mutsu retrotransposon RNA and piRNA in egg and adult tissue, suggest an involvement of retrotransposons in achieving the differential copy number of the two types of 5S rDNA loci. PMID:28003516

Polycythemia and paraganglioma with a novel somatic HIF2A mutation in a male.

PubMed

Toyoda, Hidemi; Hirayama, Jyunya; Sugimoto, Yuka; Uchida, Keiichi; Ohishi, Kohshi; Hirayama, Masahiro; Komada, Yoshihiro

2014-06-01

Recently, a new syndrome of paraganglioma, somatostatinoma, and polycythemia has been discovered (known as Pacak-Zhuang syndrome). This new syndrome, with somatic HIF2A gain-of-function mutations, has never been reported in male patients. We describe a male patient with Pacak-Zhuang syndrome who carries a newly discovered HIF2A mutation. Congenital polycythemias have diverse etiologies, including germline mutations in the oxygen-sensing pathway. These include von Hippel-Lindau (Chuvash polycythemia), prolyl hydroxylase domain-containing protein-2, and hypoxia-inducible factor-2α (HIF-2α). Somatic gain-of-function mutations in the gene encoding HIF-2α were reported in patients with paraganglioma and polycythemia and have been found exclusively in female patients. Through sequencing of the HIF2A using DNA from paraganglioma in 15-year-old male patient, we identified a novel mutation of HIF2A: a heterozygous C to A substitution at base 1589 in exon 12 of HIF2A. The mutation was not found in germline DNA from leukocytes. The C1589A mutations resulted in substitution of alanine 530 in the HIF-2α protein with glutamic acid. This mutation is undoubtedly associated with increased HIF-2α activity and increased protein half-life, because it affects the vicinity of the prolyl hydroxylase target residue, proline 531. To our knowledge, this is the first report describing Pacak-Zhuang syndrome with somatic gain-of-function mutation in HIF2A in a male patient. Congenital polycythemia of unknown origin should raise suspicion for the novel disorder Pacak-Zhuang syndrome, even in male patients. Copyright © 2014 by the American Academy of Pediatrics.

A polymorphism in the MSH3 mismatch repair gene is associated with the levels of somatic instability of the expanded CTG repeat in the blood DNA of myotonic dystrophy type 1 patients.

PubMed

Morales, Fernando; Vásquez, Melissa; Santamaría, Carolina; Cuenca, Patricia; Corrales, Eyleen; Monckton, Darren G

2016-04-01

Somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 is age-dependent, tissue-specific and expansion-biased, contributing toward the tissue-specificity and progressive nature of the symptoms. Previously, using regression modelling of repeat instability we showed that variation in the rate of somatic expansion in blood DNA contributes toward variation in age of onset, directly implicating somatic expansion in the disease pathway. Here, we confirm these results using a larger more genetically homogenous Costa Rican DM1 cohort (p<0.001). Interestingly, we also provide evidence that supports subtle sex-dependent differences in repeat length-dependent age at onset and somatic mutational dynamics. Previously, we demonstrated that variation in the rate of somatic expansion was a heritable quantitative trait. Given the important role that DNA mismatch repair genes play in mediating expansions in mouse models, we tested for modifier gene effects with 13 DNA mismatch gene polymorphisms (one each in MSH2, PMS2, MSH6 and MLH1; and nine in MSH3). After correcting for allele length and age effects, we identified three polymorphisms in MSH3 that were associated with variation in somatic instability: Rs26279 (p=0.003); Rs1677658 (p=0.009); and Rs10168 (p=0.031). However, only the association with Rs26279 remained significant after multiple testing correction. Although we revealed a statistically significant association between Rs26279 and somatic instability, we did not detect an association with the age at onset. Individuals with the A/A genotype for Rs26279 tended to show a greater propensity to expand the CTG repeat than other genotypes. Interestingly, this SNP results in an amino acid change in the critical ATPase domain of MSH3 and is potentially functionally dimorphic. These data suggest that MSH3 is a key player in generating somatic variation in DM1 patients and further highlight MSH3 as a potential therapeutic target. Copyright © 2016 Elsevier B.V. All rights reserved.

Cryopyrin-associated Periodic Syndromes in Italian Patients: Evaluation of the Rate of Somatic NLRP3 Mosaicism and Phenotypic Characterization.

PubMed

Lasigliè, Denise; Mensa-Vilaro, Anna; Ferrera, Denise; Caorsi, Roberta; Penco, Federica; Santamaria, Giuseppe; Di Duca, Marco; Amico, Giulia; Nakagawa, Kenji; Antonini, Francesca; Tommasini, Alberto; Consolini, Rita; Insalaco, Antonella; Cattalini, Marco; Obici, Laura; Gallizzi, Romina; Santarelli, Francesca; Del Zotto, Genny; Severino, Mariasavina; Rubartelli, Anna; Ravazzolo, Roberto; Martini, Alberto; Ceccherini, Isabella; Nishikomori, Ryuta; Gattorno, Marco; Arostegui, Juan I; Borghini, Silvia

2017-11-01

To evaluate the rate of somatic NLRP3 mosaicism in an Italian cohort of mutation-negative patients with cryopyrin-associated periodic syndrome (CAPS). The study enrolled 14 patients with a clinical phenotype consistent with CAPS in whom Sanger sequencing of the NLRP3 gene yielded negative results. Patients' DNA were subjected to amplicon-based NLRP3 deep sequencing. Low-level somatic NLRP3 mosaicism has been detected in 4 patients, 3 affected with chronic infantile neurological cutaneous and articular syndrome and 1 with Muckle-Wells syndrome. Identified nucleotide substitutions encode for 4 different amino acid exchanges, with 2 of them being novel (p.Y563C and p.G564S). In vitro functional studies confirmed the deleterious behavior of the 4 somatic NLRP3 mutations. Among the different neurological manifestations detected, 1 patient displayed mild loss of white matter volume on brain magnetic resonance imaging. The allele frequency of somatic NLRP3 mutations occurs generally under 15%, considered the threshold of detectability using the Sanger method of DNA sequencing. Consequently, routine genetic diagnostic of CAPS should be currently performed by next-generation techniques ensuring high coverage to identify also low-level mosaicism, whose actual frequency is yet unknown and probably underestimated.

Retrotransposon Capture Sequencing (RC-Seq): A Targeted, High-Throughput Approach to Resolve Somatic L1 Retrotransposition in Humans.

PubMed

Sanchez-Luque, Francisco J; Richardson, Sandra R; Faulkner, Geoffrey J

2016-01-01

Mobile genetic elements (MGEs) are of critical importance in genomics and developmental biology. Polymorphic and somatic MGE insertions have the potential to impact the phenotype of an individual, depending on their genomic locations and functional consequences. However, the identification of polymorphic and somatic insertions among the plethora of copies residing in the genome presents a formidable technical challenge. Whole genome sequencing has the potential to address this problem; however, its efficacy depends on the abundance of cells carrying the new insertion. Robust detection of somatic insertions present in only a subset of cells within a given sample can also be prohibitively expensive due to a requirement for high sequencing depth. Here, we describe retrotransposon capture sequencing (RC-seq), a sequence capture approach in which Illumina libraries are enriched for fragments containing the 5' and 3' termini of specific MGEs. RC-seq allows the detection of known polymorphic insertions present in an individual, as well as the identification of rare or private germline insertions not previously described. Furthermore, RC-seq can be used to detect and characterize somatic insertions, providing a valuable tool to elucidate the extent and characteristics of MGE activity in healthy tissues and in various disease states.

A medical record review for functional somatic symptoms in children.

PubMed

Rask, Charlotte Ulrikka; Borg, Carsten; Søndergaard, Charlotte; Schulz-Pedersen, Søren; Thomsen, Per Hove; Fink, Per

2010-04-01

The objectives of this study were to develop and test a systematic medical record review for functional somatic symptoms (FSSs) in paediatric patients and to estimate the inter-rater reliability of paediatricians' recognition of FSSs and their associated impairments while using this method. We developed the Medical Record Review for Functional Somatic Symptoms in Children (MRFC) for retrospective medical record review. Described symptoms were categorised as probably, definitely, or not FSSs. FSS-associated impairment was also determined. Three paediatricians performed the MRFC on the medical records of 54 children with a diagnosed, well-defined physical disease and 59 with 'symptom' diagnoses. The inter-rater reliabilities of the recognition and associated impairment of FSSs were tested on 20 of these records. The MRFC allowed identification of subgroups of children with multisymptomatic FSSs, long-term FSSs, and/or impairing FSSs. The FSS inter-rater reliability was good (combined kappa=0.69) but only fair as far as associated impairment was concerned (combined kappa=0.29). In the hands of skilled paediatricians, the MRFC is a reliable method for identifying paediatric patients with diverse types of FSSs for clinical research. However, additional information is needed for reliable judgement of impairment. The method may also prove useful in clinical practice. Copyright 2010 Elsevier Inc. All rights reserved.

Frequency and outcomes of painful physical symptoms in a naturalistic population with major depressive disorder: an analysis of pooled observational studies focusing on subjects aged 65 years and over.

PubMed

Brnabic, A; Raskin, J; Alev, L; Serap Monkul, E; Lowry, A

2012-12-01

To estimate the frequency of painful physical symptoms (PPS) in elderly subjects (≥ 65 years) with major depressive disorder (MDD) in real-world clinical conditions and to establish whether PPS are associated with poor depression outcomes, including more severe depression and worse health-related quality of life (HRQoL). Observational studies of MDD that included assessment of PPS and elderly subjects were screened. Measures of PPS were based on the Somatic Symptom Inventory (SSI) or Visual Analogue Scale (VAS). Data from a variety of depressive symptom severity and HRQoL scales were used. Analysis cohorts were based on age [aged ≥ 65 years (elderly) or < 65 years (younger)] and/or PPS status (presence or absence); five subsets were used to examine specific outcomes in matched elderly subjects. Data from seven studies (representing 26 countries) were collated. Of the 11,477 subjects, 14% were aged ≥ 65 years and 71% were classified as having PPS (PPS+). PPS were more frequent in elderly subjects (74% vs. 70% of younger subjects) and were positively associated with being female and Hispanic, and negatively associated with being East Asian in the elderly. The presence of PPS was associated with more severe clinical symptomatology and comparatively poorer HRQoL in elderly subjects. PPS, although frequent in younger MDD patients, were slightly more frequent in elderly MDD patients and associated with comparatively poorer clinical and functional outcomes. As elderly patients report somatic symptoms more readily than emotional symptoms, physicians should consider depression in addition to physical causes when PPS are present. © 2012 Blackwell Publishing Ltd.

Genetic errors of the human CARD-BCL10-MALT1 (CBM) complex: molecular, immunological, and clinical heterogeneity

PubMed Central

de Diego, Rebeca Pérez; Sánchez-Ramón, Silvia; López-Collazo, Eduardo; Martínez-Barricarte, Rubén; Cubillos-Zapata, Carolina; Cerdán, Antonio Ferreira; Casanova, Jean-Laurent; Puel, Anne

2016-01-01

Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These three CARD-BCL10-MALT1 (CBM) complexes activate NF-κB in both the innate and adaptive arms of immunity. Human inherited defects of the three components of the CBM complex, including the two adaptors CARD9 and CARD11 and the two core components BCL10 and MALT1, have recently been reported. Bi-allelic loss-of-function (LOF) mutant alleles underlie several different immunological and clinical phenotypes, which can be assigned to two distinct categories. Isolated invasive fungal infections, of unclear cellular basis, are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1 and BCL10 deficiencies. Interestingly, humans with these mutations have some features in common with the corresponding knockout mice, but other features are different between humans and mice. Moreover, germline and somatic gain-of-function (GOF) mutations of MALT1, BCL10 and CARD11 have also been found in other patients with lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including LOF and GOF mutations, highlights the contribution of each of the components of the CBM to human immunity. PMID:26277595

Bacteriophage ecology in a small community sewer system related to their indicative role in sewage pollution of drinking water.

PubMed

Gino, Efrat; Starosvetsky, Jeana; Armon, Robert

2007-10-01

In view of various studies looking for the merit of coliphages as indicators of water pollution with viruses originating from faecal material, a small agricultural community (population of approximately 1500 inhabitants of all ages, 2-3 km from Haifa) was selected in order to understand these bacteriophage ecology (F-RNA and somatic coliphages) in its sewer and oxidation pond system. Along the sewer lines, it was possible to isolate constantly both bacteriophage types (F-RNA and somatic coliphages) at 10(2)-10(4) plaque-forming units (pfu) ml(-1). The average numbers of somatic and F-RNA phages isolated from oxidation pond were 10(3)-10(4) pfu ml(-1); however, somatic coliphages were undetectable for several months (April-August). Significant high correlation (0.944 < R(2) < 0.99) was found between increased anionic detergent concentrations and F-RNA coliphage numbers. Infants less than 1 year old excreted both phage types and few only F-RNA coliphages (at high numbers > 10(5) pfu g(-1)) for up to 1 year. The excretion of F-RNA coliphages was highly linked to Escherichia coli F(+) harborage in the intestinal track as found in their faecal content. Finally, three bacterial hosts E. coli F(+), F(-) and CN(13) tested for survivability in sewage filtrate revealed that E. coli F(+) had the highest survivability under these conditions. Presence of somatic and F male-specific phages in sewer lines of a small community are influenced by several factors such as: anionic detergents, nutrients, temperature, source (mainly infants), shedding and survival capability of the host strain. Better understanding of coliphages ecology in sewer systems can enhance our evaluation of these proposed indicator/index microorganisms used in tracking environmental pollution of water, soil and crop contamination with faecal material containing enteric viruses.

Age-related variability in the presentation of symptoms of major depressive disorder.

PubMed

Schaakxs, R; Comijs, H C; Lamers, F; Beekman, A T F; Penninx, B W J H

2017-02-01

The heterogeneous aetiology of major depressive disorder (MDD) might affect the presentation of depressive symptoms across the lifespan. We examined to what extent a range of mood, cognitive, and somatic/vegetative depressive symptoms were differentially present depending on patient's age. Data came from 1404 participants with current MDD (aged 18-88 years) from two cohort studies: the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Study of Depression in Older Persons (NESDO). Associations between age (per 10 years) and 30 depressive symptoms as well as three symptom clusters (mood, cognitive, somatic/vegetative) were assessed using logistic and linear regression analyses. Depression severity was found to be stable with increasing age. Nevertheless, 20 (67%) out of 30 symptoms were associated with age. Most clearly, with ageing there was more often early morning awakening [odds ratio (OR) 1.47, 95% confidence interval (CI) 1.36-1.60], reduced interest in sex (OR 1.42, 95% CI 1.31-1.53), and problems sleeping during the night (OR 1.33, 95% CI 1.24-1.43), whereas symptoms most strongly associated with younger age were interpersonal sensitivity (OR 0.72, 95% CI 0.66-0.79), feeling irritable (OR 0.73, 95% CI 0.67-0.79), and sleeping too much (OR 0.75, 95% CI 0.68-0.83). The sum score of somatic/vegetative symptoms was associated with older age (B = 0.23, p < 0.001), whereas the mood and cognitive sum scores were associated with younger age (B = -0.20, p < 0.001; B = -0.04, p = 0.004). Depression severity was found to be stable across the lifespan, yet depressive symptoms tend to shift with age from being predominantly mood-related to being more somatic/vegetative. Due to the increasing somatic presentation of depression with age, diagnoses may be missed.

Life Course Pathways of Adversities Linking Adolescent Socioeconomic Circumstances and Functional Somatic Symptoms in Mid-Adulthood: A Path Analysis Study

PubMed Central

Jonsson, Frida; San Sebastian, Miguel; Strömsten, Lotta M. J.; Hammarström, Anne; Gustafsson, Per E.

2016-01-01

While research examining the health impact of early socioeconomic conditions suggests that effects may exist independently of or jointly with adult socioeconomic position, studies exploring other potential pathways are few. Following a chain of risk life course model, this prospective study seeks to examine whether pathways of occupational class as well as material and social adversities across the life course link socioeconomic disadvantage in adolescent to functional somatic symptoms in mid-adulthood. Applying path analysis, a multiple mediator model was assessed using prospective data collected during 26 years through the Northern Swedish Cohort. The sample contained 987 individuals residing in the municipality of Luleå, Sweden, who participated in questionnaire surveys at age 16, 21, 30 and 42. Socioeconomic conditions (high/low) in adolescence (age 16) were operationalized using the occupation of the parents, while occupational class in adulthood (manual/non-manual) was measured using the participant’s own occupation at age 21 and 30. The adversity measurements were constructed as separate age specific parcels at age 21 and 30. Social adversity included items pertaining to stressful life events that could potentially harm salient relationships, while material adversity was operationalized using items concerning unfavorable financial and material circumstances. Functional somatic symptoms at age 42 was a summary measure of self-reported physical symptoms, palpitation and sleeping difficulties that had occurred during the last 12 months. An association between socioeconomic conditions at age 16 and functional somatic symptoms at age 42 (r = 0.068) which was partially explained by people’s own occupational class at age 21 and then material as well as social adversity at age 30 was revealed. Rather than proposing a direct and independent health effect of the socioeconomic conditions of the family, the present study suggests that growing up in an unfavorable socioeconomic environment might be a source for a chain of adverse material and social living situations, which in turn affects adult health. PMID:27214206

Neither self-reported atopy nor IgE-mediated allergy are linked to gastrointestinal symptoms in patients with irritable bowel syndrome.

PubMed

Nybacka, S; Öhman, L; Störsrud, S; Mybeck, M; Böhn, L; Wilpart, K; Winkvist, A; Bengtsson, U; Törnblom, H; Simrén, M

2018-06-01

Among patients with irritable bowel syndrome (IBS), atopic disease has been proposed as a common comorbidity increasing the IBS symptom burden. We therefore assessed the prevalence of self-reported atopy among patients with IBS as compared to non-IBS controls, and whether atopy and higher serum IgE levels were associated with increased IBS symptom severity. Levels of total and specific IgE in serum were measured and questionnaires assessing the presence of atopic disease (ie, eczema, asthma, rhinoconjunctivitis, and pollen allergy), gastrointestinal symptom burden, food intolerance, somatic, and psychological symptoms were completed. In total, 223 patients with IBS and 47 controls participated. Presence of atopic disease was reported in 55% of patients with IBS compared to 40% of controls (P = .07). IBS patients with atopic manifestations (N = 123) had higher total serum IgE levels (median 31 vs 16 kU A /L, P < .001) and higher prevalence of self-reported food intolerance (28% vs 9%, P = .002) than non-atopic IBS patients (N = 100), respectively, but no major difference in gastrointestinal or psychological symptom burden was noted. However, severe somatic symptoms were more common among atopic than non-atopic patients with IBS (38% vs 27%, P = .028). We found no associations between self-reported atopy and IBS symptom severity using linear regression models. Atopic disease is common in patients with IBS, but that is also true for subjects without IBS. The presence of atopic disease in IBS is associated with self-reported food intolerance and somatic symptom severity, but unrelated to IBS symptom severity. © 2018 John Wiley & Sons Ltd.

The Chinese version of the cognitive, affective, and somatic empathy scale for children: Validation, gender invariance and associated factors.

PubMed

Liu, Jianghong; Qiao, Xin; Dong, Fanghong; Raine, Adrian

2018-01-01

Empathy is hypothesized to have several components, including affective, cognitive, and somatic contributors. The only validated, self-report measure to date that assesses all three forms of empathy is the Cognitive, Affective, and Somatic Empathy Scale (CASES), but no current study has reported the psychometric properties of this scale outside of the initial U.S. sample. This study reports the first psychometric analysis of a non-English translation of the CASES. Confirmatory factor analysis was used to assess the factor structure of CASES as well as its associations with callous-unemotional traits in 860 male and female children (mean age 11.54± .64 years) from the China Jintan Child Cohort Study. Analyses supported a three-factor model of cognitive, affective, and somatic empathy, with satisfactory fit indices consistent with the psychometric properties of the English version of CASES. Construct validity was established by three findings. First, females scored significantly higher in empathy than males. Second, lower scores of empathy were associated with lower IQ. Third, children with lower empathy also showed more callous-unemotional attributes. We established for the first time cross-cultural validity for Cognitive, Affective, and Somatic Empathy Scale (CASES). Our Chinese data supports the use of this new instrument in non-Western samples, and affirms the utility of this instrument for a comprehensive assessment of empathy in children.

Bovine somatic cell nuclear transfer.

PubMed

Ross, Pablo J; Cibelli, Jose B

2010-01-01

Somatic cell nuclear transfer (SCNT) is a technique by which the nucleus of a differentiated cell is introduced into an oocyte from which its genetic material has been removed by a process called enucleation. In mammals, the reconstructed embryo is artificially induced to initiate embryonic development (activation). The oocyte turns the somatic cell nucleus into an embryonic nucleus. This process is called nuclear reprogramming and involves an important change of cell fate, by which the somatic cell nucleus becomes capable of generating all the cell types required for the formation of a new individual, including extraembryonic tissues. Therefore, after transfer of a cloned embryo to a surrogate mother, an offspring genetically identical to the animal from which the somatic cells where isolated, is born. Cloning by nuclear transfer has potential applications in agriculture and biomedicine, but is limited by low efficiency. Cattle were the second mammalian species to be cloned after Dolly the sheep, and it is probably the most widely used species for SCNT experiments. This is, in part due to the high availability of bovine oocytes and the relatively higher efficiency levels usually obtained in cattle. Given the wide utilization of this species for cloning, several alternatives to this basic protocol can be found in the literature. Here we describe a basic protocol for bovine SCNT currently being used in our laboratory, which is amenable for the use of the nuclear transplantation technique for research or commercial purposes.

Functional impact of the human mobilome.

PubMed

Babatz, Timothy D; Burns, Kathleen H

2013-06-01

The human genome is replete with interspersed repetitive sequences derived from the propagation of mobile DNA elements. Three families of human retrotransposons remain active today: LINE1, Alu, and SVA elements. Since 1988, de novo insertions at previously recognized disease loci have been shown to generate highly penetrant alleles in Mendelian disorders. Only recently has the extent of germline-transmitted retrotransposon insertion polymorphism (RIP) in human populations been fully realized. Also exciting are recent studies of somatic retrotransposition in human tissues and reports of tumor-specific insertions, suggesting roles in tissue heterogeneity and tumorigenesis. Here we discuss mobile elements in human disease with an emphasis on exciting developments from the last several years. Copyright © 2013 Elsevier Ltd. All rights reserved.

Aging and reprogramming: a two-way street

PubMed Central

Mahmoudi, Salah; Brunet, Anne

2012-01-01

Aging is accompanied by the functional decline of cells, tissues, and organs, as well as a striking increase in a wide range of diseases. The reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) opens new avenues for the aging field and has important applications for therapeutic treatments of age-related diseases. Here we review emerging studies on how aging and age-related pathways influence iPSC generation and property. We discuss the exciting possibility that reverting to a pluripotent stem cell stage erases several deficits associated with aging and will provide new strategies for rejuvenation. Finally, we argue that reprogramming provides a unique opportunity to model aging and perhaps exceptional longevity. PMID:23146768

Characterization of embryo-specific genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sung, Z.R.

1988-01-01

The objective of the proposed research is to characterize the structure and function of a set of genes whose expression is regulated in embryo development, and that are not expressed in mature tissues -- the embryogenic genes. In order to isolate these genes, we immunized a rabbit with total extracts of somatic embryos of carrot, and enriched the anti-embryo antiserum for antibodies reacting with extracts of carrot somatic embryos. Using this enriched antiserum, we screened a lambda gt11 cDNA library constructed from embryo poly A{sup +} RNA, and isolated 10 cDNA clones that detect embryogenic mRNAs. Monospecific antibodies have beenmore » purified for proteins corresponding to each cDNA sequence. Four cDNA clones were further characterized in terms of the expression of their corresponding mRNA and protein in somatic embryos of carrot. In some cases, comparable gene sequences or products have been detected in somatic and zygotic embryos of other plant species. The characteristics of these 4 cDNA clones -- clone Nos. 8, 59, and 66 -- are described in this report. 3 figs.« less

DNMT1 maintains progenitor function in self-renewing somatic tissue.

PubMed

Sen, George L; Reuter, Jason A; Webster, Daniel E; Zhu, Lilly; Khavari, Paul A

2010-01-28

Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1) maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintenance, the role for DNMT1 in maintaining the progenitor state in constantly replenished somatic tissues, such as mammalian epidermis, is unclear. Here we show that DNMT1 is essential for epidermal progenitor cell function. DNMT1 protein was found enriched in undifferentiated cells, where it was required to retain proliferative stamina and suppress differentiation. In tissue, DNMT1 depletion led to exit from the progenitor cell compartment, premature differentiation and eventual tissue loss. Genome-wide analysis showed that a significant portion of epidermal differentiation gene promoters were methylated in self-renewing conditions but were subsequently demethylated during differentiation. Furthermore, UHRF1 (refs 9, 10), a component of the DNA methylation machinery that targets DNMT1 to hemi-methylated DNA, is also necessary to suppress premature differentiation and sustain proliferation. In contrast, Gadd45A and B, which promote active DNA demethylation, are required for full epidermal differentiation gene induction. These data demonstrate that proteins involved in the dynamic regulation of DNA methylation patterns are required for progenitor maintenance and self-renewal in mammalian somatic tissue.

Somatic experiencing: using interoception and proprioception as core elements of trauma therapy

PubMed Central

Payne, Peter; Levine, Peter A.; Crane-Godreau, Mardi A.

2015-01-01

Here we present a theory of human trauma and chronic stress, based on the practice of Somatic Experiencing® (SE), a form of trauma therapy that emphasizes guiding the client's attention to interoceptive, kinesthetic, and proprioceptive experience. SE™ claims that this style of inner attention, in addition to the use of kinesthetic and interoceptive imagery, can lead to the resolution of symptoms resulting from chronic and traumatic stress. This is accomplished through the completion of thwarted, biologically based, self-protective and defensive responses, and the discharge and regulation of excess autonomic arousal. We present this theory through a composite case study of SE treatment; based on this example, we offer a possible neurophysiological rationale for the mechanisms involved, including a theory of trauma and chronic stress as a functional dysregulation of the complex dynamical system formed by the subcortical autonomic, limbic, motor and arousal systems, which we term the core response network (CRN). We demonstrate how the methods of SE help restore functionality to the CRN, and we emphasize the importance of taking into account the instinctive, bodily based protective reactions when dealing with stress and trauma, as well as the effectiveness of using attention to interoceptive, proprioceptive and kinesthetic sensation as a therapeutic tool. Finally, we point out that SE and similar somatic approaches offer a supplement to cognitive and exposure therapies, and that mechanisms similar to those discussed in the paper may also be involved in the benefits of meditation and other somatic practices. PMID:25699005

Fibromyalgia: A Critical and Comprehensive Review.

PubMed

Borchers, Andrea T; Gershwin, M Eric

2015-10-01

Fibromyalgia is a disorder that is part of a spectrum of syndromes that lack precise classification. It is often considered as part of the global overview of functional somatic syndromes that are otherwise medically unexplained or part of a somatization disorder. Patients with fibromyalgia share symptoms with other functional somatic problems, including issues of myalgias, arthralgias, fatigue and sleep disturbances. Indeed, there is often diagnostic and classification overlap for the case definitions of a variety of somatization disorders. Fibromyalgia, however, is a critically important syndrome for physicians and scientists to be aware of. Patients should be taken very seriously and provided optimal care. Although inflammatory, infectious, and autoimmune disorders have all been ascribed to be etiological events in the development of fibromyalgia, there is very little data to support such a thesis. Many of these disorders are associated with depression and anxiety and may even be part of what has been sometimes called affected spectrum disorders. There is no evidence that physical trauma, i.e., automobile accidents, is associated with the development or exacerbation of fibromyalgia. Treatment should be placed on education, patient support, physical therapy, nutrition, and exercise, including the use of drugs that are approved for the treatment of fibromyalgia. Treatment should not include opiates and patients should not become poly pharmacies in which the treatment itself can lead to significant morbidities. Patients with fibromyalgia are living and not dying of this disorder and positive outlooks and family support are key elements in the management of patients.

Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues.

PubMed

De Cecco, Marco; Criscione, Steven W; Peterson, Abigail L; Neretti, Nicola; Sedivy, John M; Kreiling, Jill A

2013-12-01

Transposable elements (TEs) were discovered by Barbara McClintock in maize and have since been found to be ubiquitous in all living organisms. Transposition is mutagenic and organisms have evolved mechanisms to repress the activity of their endogenous TEs. Transposition in somatic cells is very low, but recent evidence suggests that it may be derepressed in some cases, such as cancer development. We have found that during normal aging several families of retrotransposable elements (RTEs) start being transcribed in mouse tissues. In advanced age the expression culminates in active transposition. These processes are counteracted by calorie restriction (CR), an intervention that slows down aging. Retrotransposition is also activated in age-associated, naturally occurring cancers in the mouse. We suggest that somatic retrotransposition is a hitherto unappreciated aging process. Mobilization of RTEs is likely to be an important contributor to the progressive dysfunction of aging cells.

Somatic Embryogenesis in Peach Palm Using the Thin Cell Layer Technique: Induction, Morpho-histological Aspects and AFLP Analysis of Somaclonal Variation

PubMed Central

Steinmacher, D. A.; Krohn, N. G.; Dantas, A. C. M.; Stefenon, V. M.; Clement, C. R.; Guerra, M. P.

2007-01-01

Background and Aims The thin cell layer (TCL) technique is based on the use of very small explants and has allowed enhanced in vitro morphogenesis in several plant species. The present study evaluated the TCL technique as a procedure for somatic embryo production and plantlet regeneration of peach palm. Methods TCL explants from different positions in the shoot apex and leaf sheath of peach palm were cultivated in MS culture medium supplemented with 0–600 µm Picloram in the presence of activated charcoal. The production of primary calli and embryogenic calli was evaluated in these different conditions. Histological and amplified fragment length polymorphism (AFLP) analyses were conducted to study in vitro morphogenetic responses and genetic stability, respectively, of the regenerated plantlets. Key Results Abundant primary callus induction was observed from TCLs of the shoot meristem in culture media supplemented with 150–600 µm Picloram (83–97 %, respectively). The production of embryogenic calli depends on Picloram concentration and explant position. The best response observed was 43 % embryogenic callus production from shoot meristem TCL on 300 µm Picloram. In maturation conditions, 34 ± 4 somatic embryos per embryogenic callus were obtained, and 45·0 ± 3·4 % of these fully developed somatic embryos were converted, resulting in plantlets ready for acclimatization, of which 80 % survived. Histological studies revealed that the first cellular division events occurred in cells adjacent to vascular tissue, resulting in primary calli, whose growth was ensured by a meristematic zone. A multicellular origin of the resulting somatic embryos arising from the meristematic zone is suggested. During maturation, histological analyses revealed bipolarization of the somatic embryos, as well as the development of new somatic embryos. AFLP analyses revealed that 92 % of the regenerated plantlets were true to type. The use of TCL explants considerably improves the number of calli and somatic embryos produced in comparison with previously described protocols for in vitro regeneration of peach palm. Conclusions The present study suggests that the TCL somatic embryogenesis protocol developed is feasible, although it still requires further optimization for in vitro multiplication of peach palm, especially the use of similar explants obtained from adult palm trees. PMID:17670751

Differential symptomatology and functioning in borderline personality disorder across age groups.

PubMed

Frías, Álvaro; Palma, Carol; Solves, Laia; Martínez, Bárbara; Salvador, Ana

2017-12-01

There is increasing research aimed at addressing whether patients with borderline personality disorder (BPD) may exhibit variations in symptomatology and functioning according to their chronological age. The current study consisted of 169 outpatients diagnosed with BPD, who were divided into four age groups as follows: 16-25 years (n = 41), 26-35 years (n = 43), 36-45 years (n = 45), and 46 and more years (n = 40). Age groups were compared for symptomatology, normal personality traits, psychiatric comorbidities, functioning, and treatment-related features. The younger group had significantly higher levels of physical/verbal aggression and suicide attempts relative to the older group. Conversely, the older group had significantly greater severity of somatization, depression, and anxiety symptoms. In addition, the older group showed significantly greater functional impairment overall and across physical/psychological domains, specifically when compared to the younger group. Overall, these findings may suggest that age-related symptoms should be considered when diagnosing BPD. Also, functional impairments should be the target interventions for older BPD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced GABAergic Inputs Contribute to Functional Alterations of Cholinergic Interneurons in the R6/2 Mouse Model of Huntington's Disease.

PubMed

Holley, Sandra M; Joshi, Prasad R; Parievsky, Anna; Galvan, Laurie; Chen, Jane Y; Fisher, Yvette E; Huynh, My N; Cepeda, Carlos; Levine, Michael S

2015-01-01

In Huntington's disease (HD), a hereditary neurodegenerative disorder, striatal medium-sized spiny neurons undergo degenerative changes. In contrast, large cholinergic interneurons (LCIs) are relatively spared. However, their ability to release acetylcholine (ACh) is impaired. The present experiments examined morphological and electrophysiological properties of LCIs in the R6/2 mouse model of HD. R6/2 mice show a severe, rapidly progressing phenotype. Immunocytochemical analysis of choline acetyltransferase-positive striatal neurons showed that, although the total number of cells was not changed, somatic areas were significantly smaller in symptomatic R6/2 mice compared to wildtype (WT) littermates, For electrophysiology, brain slices were obtained from presymptomatic (3-4 weeks) and symptomatic (>8 weeks) R6/2 mice and their WT littermates. Striatal LCIs were identified by somatic size and spontaneous action potential firing in the cell-attached mode. Passive and active membrane properties of LCIs were similar in presymptomatic R6/2 and WT mice. In contrast, LCIs from symptomatic R6/2 animals displayed smaller membrane capacitance and higher input resistance, consistent with reduced somatic size. In addition, more LCIs from symptomatic mice displayed irregular firing patterns and bursts of action potentials. They also displayed a higher frequency of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) and larger amplitude of electrically evoked IPSCs. Selective optogenetic stimulation of somatostatin- but not parvalbumin-containing interneurons also evoked larger amplitude IPSCs in LCIs from R6/2 mice. In contrast, glutamatergic spontaneous or evoked postsynaptic currents were not affected. Morphological and electrophysiological alterations, in conjunction with the presence of mutant huntingtin in LCIs, could explain impaired ACh release in HD mouse models.

Depressive symptoms, functional measures and long-term outcomes of high-risk ST-elevated myocardial infarction patients treated by primary angioplasty.

PubMed

Compostella, Leonida; Lorenzi, Sonia; Russo, Nicola; Setzu, Tiziana; Compostella, Caterina; Vettore, Elia; Isabella, Giambattista; Tarantini, Giuseppe; Iliceto, Sabino; Bellotto, Fabio

2017-02-01

The presence of major depressive symptoms is usually considered a negative long-term prognostic factor after an acute myocardial infarction (AMI); however, most of the supporting research was conducted before the era of immediate reperfusion by percutaneous coronary intervention. The aims of this study are to evaluate if depression still retains long-term prognostic significance in our era of immediate coronary reperfusion, and to study possible correlations with clinical parameters of physical performance. In 184 patients with recent ST-elevated AMI (STEMI), treated by immediate reperfusion, moderate or severe depressive symptoms (evaluated by Beck Depression Inventory version I) were present in 10 % of cases. Physical performance was evaluated by two 6-min walk tests and by a symptom-limited cardiopulmonary exercise test: somatic/affective (but not cognitive/affective) symptoms of depression and perceived quality of life (evaluated by the EuroQoL questionnaire) are worse in patients with lower levels of physical performance. Follow-up was performed after a median of 29 months by means of telephone interviews; 32 major adverse cardiovascular events (MACE) occurred. The presence of three vessels disease and low left ventricle ejection fraction are correlated with a greater incidence of MACE; only somatic/affective (but not cognitive/affective) symptoms of depression correlate with long-term outcomes. In patients with recent STEMI treated by immediate reperfusion, somatic/affective but not cognitive/affective symptoms of depression show prognostic value on long-term MACE. Depression symptoms are not predictors "per se" of adverse prognosis, but seem to express an underlying worse cardiac efficiency, clinically reflected by poorer physical performance.

Efficient modification of the myostatin gene in porcine somatic cells and generation of knockout piglets.

PubMed

Rao, Shengbin; Fujimura, Tatsuya; Matsunari, Hitomi; Sakuma, Tetsushi; Nakano, Kazuaki; Watanabe, Masahito; Asano, Yoshinori; Kitagawa, Eri; Yamamoto, Takashi; Nagashima, Hiroshi

2016-01-01

Myostatin (MSTN) is a negative regulator of myogenesis, and disruption of its function causes increased muscle mass in various species. Here, we report the generation of MSTN-knockout (KO) pigs using genome editing technology combined with somatic-cell nuclear transfer (SCNT). Transcription activator-like effector nuclease (TALEN) with non-repeat-variable di-residue variations, called Platinum TALEN, was highly efficient in modifying genes in porcine somatic cells, which were then used for SCNT to create MSTN KO piglets. These piglets exhibited a double-muscled phenotype, possessing a higher body weight and longissimus muscle mass measuring 170% that of wild-type piglets, with double the number of muscle fibers. These results demonstrate that loss of MSTN increases muscle mass in pigs, which may help increase pork production for consumption in the future. © 2015 Wiley Periodicals, Inc.

The effects of congenital hypothyroidism using the hyt/hyt mouse on locomotor activity and learned behavior.

PubMed

Anthony, A; Adams, P M; Stein, S A

1993-09-01

The offspring of matings between hyt/hyt male mice and hyt/+ females were examined for somatic and behavioral differences. The hyt/hyt offspring displayed delayed somatic development for eye opening and ear extension relative to their euthyroid littermates. Behavioral measurement of locomotor activity indicated hyperactivity at 14 days of age and hypoactivity at 21 and 40 days relative to the euthyroid mice. Impaired swimming escape behavior and Morris maze spatial learning were observed in the hyt/hyt animals. Comparative evaluation of +/+ progenitor strain offspring having no hypothyroidism in their genetic background indicated significant differences in somatic and behavioral endpoints between the hyt/hyt and euthyroid (hyt/+, +/+) animals. These results confirm the utility of the hyt/hyt mouse for studies of the impact of congenital hypothyroidism on the functional development of the offspring.

Somatization as a predictor of suicidal ideation in dissociative disorders.

PubMed

Oztürk, Erdinç; Sar, Vedat

2008-12-01

This study was concerned with correlates of suicidal ideation among patients with chronic complex dissociative disorders. Participants were 40 patients diagnosed as having either dissociative identity disorder or dissociative disorder not otherwise specified according to the DSM-IV. The Dissociative Disorders Interview Schedule, the Dissociative Experiences Scale, the Somatoform Dissociation and the Childhood Trauma Questionnaires, the Spielberger Trait Anger Inventory, the Beck Suicidal Ideation Scale, and the Borderline Personality Disorder section of the Structured Clinical Interview for DSM-IV Personality Disorders were administered to all patients. Patients with suicidal ideas (n = 15) had concurrent somatization disorder more frequently than the remaining patients. Having significantly high scores on both trait and state dissociation measures, their dissociative disorder was more severe than that of the patients with no suicidal ideation. They had elevated scores for childhood emotional abuse, physical abuse and emotional neglect. Concurrent somatization disorder diagnosis was the only predictor of suicidal ideation when childhood trauma scores and borderline personality disorder diagnosis were controlled. Among dissociative patients, there is an association between somatization and suicidal ideation. A trauma-related insecure attachment pattern is considered as a common basis of this symptom cluster.

Do patients with unexplained physical symptoms pressurise general practitioners for somatic treatment? A qualitative study.

PubMed

Ring, Adele; Dowrick, Christopher; Humphris, Gerry; Salmon, Peter

2004-05-01

To identify the ways in which patients with medically unexplained symptoms present their problems and needs to general practitioners and to identify the forms of presentation that might lead general practitioners to feel pressurised to deliver somatic interventions. Qualitative analysis of audiorecorded consultations between patients and general practitioners. 7 general practices in Merseyside, England. 36 patients selected consecutively from 21 general practices, in whom doctors considered that patients' symptoms were medically unexplained. Inductive qualitative analysis of ways in which patients presented their symptoms to general practitioners. Although 34 patients received somatic interventions (27 received drug prescriptions, 12 underwent investigations, and four were referred), only 10 requested them. However, patients presented in other ways that had the potential to pressurise general practitioners, including: graphic and emotional language; complex patterns of symptoms that resisted explanation; description of emotional and social effects of symptoms; reference to other individuals as authority for the severity of symptoms; and biomedical explanations. Most patients with unexplained symptoms received somatic interventions from their general practitioners but had not requested them. Though such patients apparently seek to engage the general practitioner by conveying the reality of their suffering, general practitioners respond symptomatically.

The relationship between somatic and cognitive-affective depression symptoms and error-related ERP’s

PubMed Central

Bridwell, David A.; Steele, Vaughn R.; Maurer, J. Michael; Kiehl, Kent A.; Calhoun, Vince D.

2014-01-01

Background The symptoms that contribute to the clinical diagnosis of depression likely emerge from, or are related to, underlying cognitive deficits. To understand this relationship further, we examined the relationship between self-reported somatic and cognitive-affective Beck’s Depression Inventory-II (BDI-II) symptoms and aspects of cognitive control reflected in error event-related potential (ERP) responses. Methods Task and assessment data were analyzed within 51 individuals. The group contained a broad distribution of depressive symptoms, as assessed by BDI-II scores. ERP’s were collected following error responses within a go/no-go task. Individual error ERP amplitudes were estimated by conducting group independent component analysis (ICA) on the electroencephalographic (EEG) time series and analyzing the individual reconstructed source epochs. Source error amplitudes were correlated with the subset of BDI-II scores representing somatic and cognitive-affective symptoms. Results We demonstrate a negative relationship between somatic depression symptoms (i.e. fatigue or loss of energy) (after regressing out cognitive-affective scores, age and IQ) and the central-parietal ERP response that peaks at 359 ms. The peak amplitudes within this ERP response were not significantly related to cognitive-affective symptom severity (after regressing out the somatic symptom scores, age, and IQ). Limitations These findings were obtained within a population of female adults from a maximum-security correctional facility. Thus, additional research is required to verify that they generalize to the broad population. Conclusions These results suggest that individuals with greater somatic depression symptoms demonstrate a reduced awareness of behavioral errors, and help clarify the relationship between clinical measures of self-reported depression symptoms and cognitive control. PMID:25451400

The relationship between somatic and cognitive-affective depression symptoms and error-related ERPs.

PubMed

Bridwell, David A; Steele, Vaughn R; Maurer, J Michael; Kiehl, Kent A; Calhoun, Vince D

2015-02-01

The symptoms that contribute to the clinical diagnosis of depression likely emerge from, or are related to, underlying cognitive deficits. To understand this relationship further, we examined the relationship between self-reported somatic and cognitive-affective Beck'sDepression Inventory-II (BDI-II) symptoms and aspects of cognitive control reflected in error event-related potential (ERP) responses. Task and assessment data were analyzed within 51 individuals. The group contained a broad distribution of depressive symptoms, as assessed by BDI-II scores. ERPs were collected following error responses within a go/no-go task. Individual error ERP amplitudes were estimated by conducting group independent component analysis (ICA) on the electroencephalographic (EEG) time series and analyzing the individual reconstructed source epochs. Source error amplitudes were correlated with the subset of BDI-II scores representing somatic and cognitive-affective symptoms. We demonstrate a negative relationship between somatic depression symptoms (i.e. fatigue or loss of energy) (after regressing out cognitive-affective scores, age and IQ) and the central-parietal ERP response that peaks at 359 ms. The peak amplitudes within this ERP response were not significantly related to cognitive-affective symptom severity (after regressing out the somatic symptom scores, age, and IQ). These findings were obtained within a population of female adults from a maximum-security correctional facility. Thus, additional research is required to verify that they generalize to the broad population. These results suggest that individuals with greater somatic depression symptoms demonstrate a reduced awareness of behavioral errors, and help clarify the relationship between clinical measures of self-reported depression symptoms and cognitive control. Copyright © 2014 Elsevier B.V. All rights reserved.

DSM-IV-TR “pain disorder associated with psychological factors” as a nonhysterical form of somatization

PubMed Central

Aragona, Massimiliano; Tarsitani, Lorenzo; De Nitto, Serena; Inghilleri, Maurizio

2008-01-01

BACKGROUND: Elevated Minnesota Multiphasic Personality Inventory (MMPI) scores on the hysteria (Hy) scale are reported in several forms of pain. Previous results were possibly biased by diagnostic heterogeneity (psychogenic, somatic and mixed pain syndromes included in the same index sample) or Hy heterogeneity (failure to differentiate Hy scores into clinically meaningful sub-scales, such as admission of symptoms [Ad] and denial of symptoms [Dn]). METHODS: To overcome this drawback, 48 patients diagnosed as having a Diagnostic and Statistical Manual of Mental Disorders, 4th edn, Text Revision (DSM-IV-TR) diagnosis of “pain disorder associated with psychological factors” were compared with 48 patients experiencing somatic pain excluding psychological factors, and 42 somatic controls without pain. RESULTS: MMPI Hy and hypochondriasis (Hs) scores were significantly higher in the pain disorder group than in control groups, who scored similarly. MMPI correction (K) scores and Dn scores were similar in the three groups, whereas Ad was significantly higher in the pain disorder group and lower and similar in the two control groups, respectively. In the pain disorder group, Ad and Dn were negatively correlated, whereas in control groups they were unrelated. CONCLUSIONS: These findings suggest that whereas a pattern of high Hs and Hy scores together with a normal K score might characterize patients with a pain disorder associated with psychological factors, elevated Hy scores per se do not indicate hysterical traits. In the pain disorder group, elevated Hy scores reflected the Ad subscale alone, indicating a strikingly high frequency of distressing somatic symptoms. They tend not to repress or deny the emotional malaise linked to symptoms, as the hysterical construct expects. The pain disorder designation should be considered a nonhysterical form of somatization. PMID:18301811

DSM-IV-TR "pain disorder associated with psychological factors" as a nonhysterical form of somatization.

PubMed

Aragona, Massimiliano; Tarsitani, Lorenzo; De Nitto, Serena; Inghilleri, Maurizio

2008-01-01

Elevated Minnesota Multiphasic Personality Inventory (MMPI) scores on the hysteria (Hy) scale are reported in several forms of pain. Previous results were possibly biased by diagnostic heterogeneity (psychogenic, somatic and mixed pain syndromes included in the same index sample) or Hy heterogeneity (failure to differentiate Hy scores into clinically meaningful subscales, such as admission of symptoms [Ad] and denial of symptoms [Dn]). To overcome this drawback, 48 patients diagnosed as having a Diagnostic and Statistical Manual of Mental Disorders, 4th edn, Text Revision (DSM-IV-TR) diagnosis of "pain disorder associated with psychological factors" were compared with 48 patients experiencing somatic pain excluding psychological factors, and 42 somatic controls without pain. MMPI Hy and hypochondriasis (Hs) scores were significantly higher in the pain disorder group than in control groups, who scored similarly. MMPI correction (K) scores and Dn scores were similar in the three groups, whereas Ad was significantly higher in the pain disorder group and lower and similar in the two control groups, respectively. In the pain disorder group, Ad and Dn were negatively correlated, whereas in control groups they were unrelated. These findings suggest that whereas a pattern of high Hs and Hy scores together with a normal K score might characterize patients with a pain disorder associated with psychological factors, elevated Hy scores per se do not indicate hysterical traits. In the pain disorder group, elevated Hy scores reflected the Ad subscale alone, indicating a strikingly high frequency of distressing somatic symptoms. They tend not to repress or deny the emotional malaise linked to symptoms, as the hysterical construct expects. The pain disorder designation should be considered a nonhysterical form of somatization.

Linking maternal and somatic 5S rRNA types with different sequence-specific non-LTR retrotransposons.

PubMed

Locati, Mauro D; Pagano, Johanna F B; Ensink, Wim A; van Olst, Marina; van Leeuwen, Selina; Nehrdich, Ulrike; Zhu, Kongju; Spaink, Herman P; Girard, Geneviève; Rauwerda, Han; Jonker, Martijs J; Dekker, Rob J; Breit, Timo M

2017-04-01

5S rRNA is a ribosomal core component, transcribed from many gene copies organized in genomic repeats. Some eukaryotic species have two 5S rRNA types defined by their predominant expression in oogenesis or adult tissue. Our next-generation sequencing study on zebrafish egg, embryo, and adult tissue identified maternal-type 5S rRNA that is exclusively accumulated during oogenesis, replaced throughout the embryogenesis by a somatic-type, and thus virtually absent in adult somatic tissue. The maternal-type 5S rDNA contains several thousands of gene copies on chromosome 4 in tandem repeats with small intergenic regions, whereas the somatic-type is present in only 12 gene copies on chromosome 18 with large intergenic regions. The nine-nucleotide variation between the two 5S rRNA types likely affects TFIII binding and riboprotein L5 binding, probably leading to storage of maternal-type rRNA. Remarkably, these sequence differences are located exactly at the sequence-specific target site for genome integration by the 5S rRNA-specific Mutsu retrotransposon family. Thus, we could define maternal- and somatic-type MutsuDr subfamilies. Furthermore, we identified four additional maternal-type and two new somatic-type MutsuDr subfamilies, each with their own target sequence. This target-site specificity, frequently intact maternal-type retrotransposon elements, plus specific presence of Mutsu retrotransposon RNA and piRNA in egg and adult tissue, suggest an involvement of retrotransposons in achieving the differential copy number of the two types of 5S rDNA loci. © 2017 Locati et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Client Predictors of Short-term Psychotherapy Outcomes among Asian and White American Outpatients

PubMed Central

Kim, Jin E.; Zane, Nolan W.; Blozis, Shelley A.

2015-01-01

Purpose To examine predictors of psychotherapy outcomes, focusing on client characteristics that are especially salient for culturally diverse clients. Method Sixty clients (31 women; 27 White Americans, 33 Asian Americans) participated in this treatment study. Client characteristics were measured at pre-treatment, and outcomes were measured post-fourth session via therapist ratings of functioning and symptomatology. Regression analyses were utilized to test for predictors of outcomes, and bootstrap analyses were utilized to test for mediators. Results Higher levels of somatic symptoms predicted lower psychosocial functioning at post-treatment. Avoidant coping style predicted more negative symptoms and more psychological discomfort. Non-English language preference predicted worse outcomes; this effect was mediated by an avoidant coping style. Conclusions Language preference, avoidant coping style, and somatic symptoms predicted treatment outcome in a culturally diverse sample. Findings suggest that race/ethnicity-related variables may function through mediating proximal variables to affect outcomes. PMID:22836681

Foxl2 function in ovarian development.

PubMed

Uhlenhaut, Nina Henriette; Treier, Mathias

2006-07-01

Foxl2 is a forkhead transcription factor essential for proper reproductive function in females. Human patients carrying mutations in the FOXL2 gene display blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), an autosomal dominant disease associated with eyelid defects and premature ovarian failure in females. Recently, animal models for BPES have been developed that in combination with a catalogue of human FOXL2 mutations provide further insight into its molecular function. Mice homozygous mutant for Foxl2 display craniofacial malformations and female infertility. The analysis of the murine phenotype has revealed that Foxl2 is required for granulosa cell function. These ovarian somatic cells surround and nourish the oocyte and play an important role in follicle formation and activation. Mutations upstream of FOXL2 in humans, not affecting the coding sequence itself, have also been shown to cause BPES, which points to the existence of a distant regulatory element necessary for proper gene expression. The same regulatory sequences may be deleted in the goat polled intersex syndrome (PIS), in which FoxL2 expression is severely reduced. Sequence comparison of FoxL2 from several vertebrate species has shown that it is a highly conserved gene involved in ovary development. Thus, the detailed understanding of Foxl2 function and regulation and the identification of its transcriptional targets may open new avenues for the treatment of female infertility in the future.

Idiopathic burning mouth syndrome: a common treatment-refractory somatoform condition responsive to ECT.

PubMed

McGirr, Alexander; Davis, Lindsay; Vila-Rodriguez, Fidel

2014-04-30

Somatic symptom disorders are common causes of disability and suffering, and can pose significant management challenges. Idiopathic burning mouth syndrome is a challenging somatic symptom disorder with relatively high prevalence, particularly among post-menopausal women. Here, we present the case of a woman with severe treatment refractory idiopathic burning mouth syndrome and comorbid major depressive disorder, who was successfully treated with bitemporal electroconvulsive therapy. This case highlights the potential effectiveness of electroconvulsive therapy in idiopathic burning mouth syndrome when other treatment options have been exhausted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The use of centrifugation to study early Drosophila embryogenesis

NASA Technical Reports Server (NTRS)

Abbott, M. K.; Spooner, B. S. (Principal Investigator)

1993-01-01

By the end of 10th nuclear cycle, the somatic nuclei of the Drosophila embryo have migrated to the periphery of the egg. Centrifugation of embryos did not result in the displacement of these nuclei, since cytoskeletal elements anchor them to the cortex. But, mild centrifugal forces displace the centrally located, nascent yolk nuclei. If this increased sensitivity to hypergravity occurs before the beginning of nuclear differentiation during cycle 8, when the nascent yolk and somatic nuclei physically separate, then it would mark the earliest functional difference between these two lineages.

Perceptions of health and somatic sensations in women reporting premenstrual syndrome and premenstrual dysphoric disorder.

PubMed

Craner, Julia; Sigmon, Sandra; Martinson, Amber; McGillicuddy, Morgan

2013-09-01

Focus on bodily sensations may be involved in the etiology of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). This study investigated the relationship between two types of somatic self-focus (i.e., health anxiety and anxiety sensitivity) and health-related quality of life (QOL) in women with provision diagnoses of PMS and PMDD. On the basis of responses to a screening measure, 731 college women were divided into three groups: PMDD, Moderate/Severe PMS, and Mild/No PMS. Measures included health-related QOL, health anxiety, anxiety sensitivity, and trait anxiety. Women with provisional diagnoses of PMDD and moderate/severe PMS reported higher levels of health anxiety and anxiety sensitivity. These relationships were not accounted for by trait anxiety. Furthermore, women in the PMDD and Moderate/Severe PMS groups reported lower health-related QOL. There is a significant health-related QOL burden for college women with PMDD and PMS. Health anxiety and anxiety sensitivity may contribute to the etiology of premenstrual disorders.

PTSD and key somatic complaints and cultural syndromes among rural Cambodians: the results of a needs assessment survey.

PubMed

Hinton, Devon E; Hinton, Alexander L; Eng, Kok-Thay; Choung, Sophearith

2012-09-01

This article describes a culturally sensitive assessment tool for traumatized Cambodians, the Cambodian "Somatic Symptom and Syndrome Inventory" (SSI), and reports the outcome of a needs assessment conducted in rural Cambodia using the instrument. Villagers locally identified (N = 139) as still suffering the effects of the Pol Pot genocide were evaluated. All 139 had post-traumatic stress disorder (PTSD) as assessed by the PTSD Checklist (PCL), and they had elevated SSI scores. The severity of the SSI items varied by level of PTSD severity, and several items--for example, dizziness, dizziness on standing, khyâl (a windlike substance) attacks, and "thinking a lot"--were extremely elevated in those participants with higher levels of PTSD. The SSI was more highly correlated to self-perceived health (Short Form Health Survey-3) and past trauma events (Harvard Trauma Questionnaire) than was the PCL. The study shows the SSI items to be a core aspect of the Cambodian trauma ontology.

Symptoms of somatization as a rapid screening tool for mitochondrial dysfunction in depression

PubMed Central

Gardner, Ann; Boles, Richard G

2008-01-01

Aims Somatic symptomatology is common in depression, and is often attributed to the Freudian-inspired concept of "somatization". While the same somatic symptoms and depression are common in mitochondrial disease, in cases with concurrent mood symptoms the diagnosis of a mitochondrial disorder and related therapy are typically delayed for many years. A short screening tool that can identify patients with depression at high risk for having underlying mitochondrial dysfunction is presented. Methods Six items of the Karolinska Scales of Personality (KSP) were found to differentiate among 21 chronically-depressed Swedish subjects with low versus normal muscle ATP production rates. A screening tool consisting of the six KSP questions was validated in the relatives of American genetics clinic patients, including in 24 matrilineal relatives in families with maternally inherited mitochondrial disease and in 30 control relatives. Results Among the depressed Swedish patients, the screening tool was positive in 13/14 with low and 1/7 with normal mitochondrial function (P = 0.0003). Applied to the American relatives of patients, the screening tool was positive in 13/24 matrilineal relatives and in 1/30 control relatives (P = 2 × 10-5). Conclusion Our preliminary data suggest that a small number of specific somatic-related questions can be constructed into a valid screening tool for cases at high risk for having a component of energy metabolism in their pathogenesis. PMID:18294386

Passive dendrites enable single neurons to compute linearly non-separable functions.

PubMed

Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

2013-01-01

Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non-separable functions.

Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions

PubMed Central

Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

2013-01-01

Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non-separable functions. PMID:23468600

Separation of somatic and germ cells is required to establish primate spermatogonial cultures.

PubMed

Langenstroth, Daniel; Kossack, Nina; Westernströer, Birgit; Wistuba, Joachim; Behr, Rüdiger; Gromoll, Jörg; Schlatt, Stefan

2014-09-01

Can primate spermatogonial cultures be optimized by application of separation steps and well defined culture conditions? We identified the cell fraction which provides the best source for primate spermatogonia when prolonged culture is desired. Man and marmoset show similar characteristics in regard to germ cell development and function. Several protocols for isolation and culture of human testis-derived germline stem cells have been described. Subsequent analysis revealed doubts on the germline origin of these cells and characterized them as mesenchymal stem cells or fibroblasts. Studies using marmosets as preclinical model confirmed that the published isolation protocols did not lead to propagation of germline cells. Testicular cells derived from nine adult marmoset monkeys (Callithrix jacchus) were cultured for 1, 3, 6 and 11 days and consecutively analyzed for the presence of spermatogonia, differentiating germ cells and testicular somatic cells. Testicular tissue of nine adult marmoset monkeys was enzymatically dissociated and subjected to two different cell culture approaches. In the first approach all cells were kept in the same dish (non-separate culture, n = 5). In the second approach the supernatant cells were transferred into a new dish 24 h after seeding and subsequently supernatant and attached cells were cultured separately (separate culture, n = 4). Real-time quantitative PCR and immunofluorescence were used to analyze the expression of reliable germ cell and somatic markers throughout the culture period. Germ cell transplantation assays and subsequent wholemount analyses were performed to functionally evaluate the colonization of spermatogonial cells. This is the first report revealing an efficient isolation and culture of putative marmoset spermatogonial stem cells with colonization ability. Our results indicate that a separation of spermatogonia from testicular somatic cells is a crucial step during cell preparation. We identified the overgrowth of more rapidly expanding somatic cells to be a major problem when establishing spermatogonial cultures. Initiating germ cell cultures from the supernatant and maintaining germ cells in suspension cultures minimized the somatic cell contamination and provided enriched germ cell fractions which displayed after 11 days of culture a significantly higher expression of germ cell markers genes (DDX-4, MAGE A-4; P < 0.05) compared with separately cultured attached cells. Additionally, germ cell transplantation experiments demonstrated a significantly higher absolute number of cells with colonization ability (P < 0.001) in supernatant cells after 11 days of separate culture. This study presents a relevant aspect for the successful setup of spermatogonial cultures but provides limited data regarding the question of whether the long-term maintenance of spermatogonia can be achieved. Transfer of these preclinical data to man may require modifications of the protocol. Spermatogonial cultures from rodents have become important and innovative tools for basic and applied research in reproductive biology and veterinary medicine. It is expected that spermatogonia-based strategies will be transformed into clinical applications for the treatment of male infertility. Our data in the marmoset monkey may be highly relevant to establish spermatogonial cultures of human testes. Funding was provided by the DFG-Research Unit FOR 1041 Germ Cell Potential (SCHL394/11-2) and by the Graduate Program Cell Dynamics and Disease (CEDAD) together with the International Max Planck Research School - Molecular Biomedicine (IMPRS-MBM). The authors declare that there is no conflict of interest. Not applicable. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mental health of residents during Obstetrics and Gynecology training in Thailand.

PubMed

Prasertsiri, K; Suntharasaj, T; Pitanupong, J

2006-03-01

To evaluate mental health of residents during Obstetrics and Gynecology training and identify the factors that affect mental health problems. During January-April 2004, one hundred and sixty Obstetrics and Gynecology residents (62% of 259) had completed a self-administered questionnaire composed of demographic data, workload, self-report of life stressors, and the Thai Mental Health Questionnaire (TMHQ-70). The prevalence of mental health problems was 29% (46/160). Somatization and social function were found in the first and second rank (18.1% and 11.9%), respectively. A resident who was younger than 25 years old, was married, cared for more than 20 patients per 8 hours in the labor room, performed more than 10 academic activities per year, or attended more than 5 examinations per year was at risk to develop social function problems. About one-third of residents training in Obstetrics and Gynecology have faced mental health problems--somatization, social function, depression and anxiety. The significant risk factors associated with social function problems were younger age, marriage and excessive workload

Use of the Central Sensitization Inventory (CSI) as a treatment outcome measure for patients with chronic spinal pain disorder in a functional restoration program.

PubMed

Neblett, Randy; Hartzell, Meredith M; Williams, Mark; Bevers, Kelley R; Mayer, Tom G; Gatchel, Robert J

2017-12-01

The Central Sensitization Inventory (CSI) is a valid and reliable patient-reported instrument designed to identify patients whose presenting symptoms may be related to central sensitization (CS). Part A of the CSI measures a full array of 25 somatic and emotional symptoms associated with CS, and Part B asks if patients have previously been diagnosed with one or more specific central sensitivity syndromes (CSSs) and related disorders. The CSI has previously been validated in a group of patients with chronic pain who were screened by a trained psychiatrist for specific CSS diagnoses. It is currently unknown if the CSI can be a useful treatment-outcome assessment tool for patients with chronic spinal pain disorder (CSPD) who are not screened for comorbid CSSs. It is known, however, that previous studies have identified CS-related symptoms, and comorbid CSSs, in subsets of patients with CSPDs. Studies have also shown that CS-related symptoms can be influenced by cognitive and psychosocial factors, including abuse history in both childhood and adulthood, sleep disturbance, catastrophic and fear-avoidant cognitions, and symptoms of depression and anxiety. This study aimed to evaluate CSI scores, and their associations with other clinically relevant psychosocial variables, in a cohort of patients with CSPD who entered and completed a functional restoration program. A retrospective study of prospectively collected data from a cohort study of patients with CSPD, who completed the CSI at admission to, and discharge from, an interdisciplinary function restoration program (FRP) was carried out. A cohort of 763 patients with CSPD comprised the study sample. Clinical interviews evaluated mood disorders and abuse history. A series of self-reported measures evaluated comorbid psychosocial symptoms, including pain intensity, pain-related anxiety, depressive symptoms, somatization symptoms, perceived disability, and sleep disturbance, at FRP admission and discharge. Patients were grouped into five severity level groups, from mild to extreme, based on total CSI scores, at FRP admission, and then again at discharge. The FRP included a quantitatively directed and medically supervised exercise process, as well as a multimodal psychosocial disability management component. The CSI severity groups were strongly associated with Major Depressive Disorder and previous abuse history (p<.01), which are known risk factors for CS-related symptoms and diagnoses. The CSI scores were also strongly associated with patient-reported CSS diagnoses on CSI Part B. The percentage of patients who reported a comorbid CSS diagnosis increased in each higher CSI-severity group, from 11% in the Subclinical group, to 56% in the Extreme group. The CSI severity groups were significantly related to other CS-related patient-reported symptoms, including pain intensity, pain-related anxiety, depressive symptoms, somatization symptoms, perceived disability, and sleep disturbance (p's<.001). The CSI scores, along with all other psychosocial measures, decreased at treatment discharge. In the present study, admission CSI scores were highly associated with previous CSS diagnoses, CS-related symptoms, and clinically relevant patient-reported psychosocial variables. All psychosocial variables, as well as scores on the CSI, were significantly improved at FRP discharge. The CSI may have important clinical utility, as a screener and as a treatment outcome measure, for patients with CSPD participating in an interdisciplinary FRP. Copyright © 2017 Elsevier Inc. All rights reserved.

Alterations in cognitive and psychological functioning after organic solvent exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrow, L.A.; Ryan, C.M.; Hodgson, M.J.

1990-05-01

Exposure to organic solvents has been linked repeatedly to alterations in both personality and cognitive functioning. To assess the nature and extent of these changes more thoroughly, 32 workers with a history of exposure to mixtures of organic solvents and 32 age- and education-matched blue-collar workers with no history of exposure were assessed with a comprehensive battery of neuropsychological tests. Although both groups were comparable on measures of general intelligence, significant differences were found in virtually all other cognitive domains tested (Learning and Memory, Visuospatial, Attention and Mental Flexibility, Psychomotor Speed). In addition, Minnesota Multiphasic Personality Inventories of exposed workersmore » indicated clinically significant levels of depression, anxiety, somatic concerns and disturbances in thinking. The reported psychological distress was unrelated to degree of cognitive deficit. Finally, several exposure-related variables were associated with poorer performance on tests of memory and visuospatial ability.« less

How to Diagnose and Treat Functional Chest Pain.

PubMed

Remes-Troche, Jose M

2016-12-01

Chest pain that is not explained by reflux disease or cardiac, musculoskeletal, mucosal, or motor esophageal abnormalities is classified as functional chest pain (FCP). Although several mechanisms are involved, esophageal hypersensitivity plays a major role and it could be considered a biomarker for FCP. Psychologic comorbidity such as anxiety, neuroticism, depression, and somatization is common. When the diagnosis of FCP is suspected, patients should undergo evaluation with esophageal motility testing, endoscopy, 24-h esophageal pH monitoring, and in some cases, sensory tests. Once the diagnosis of FCP has been established, treatment options rely on controlling patients' symptoms. Medical treatment has focused predominantly on medications that target pain, such as antidepressants and other pain neuromodulators. Non-pharmacologic interventions with complementary behavioral treatments, such as cognitive behavioral therapy, biofeedback, and hypnosis, have recently been recognized as useful in FCP patients. The latest findings on the evaluation and treatment of FCP are outlined herein.

A comparison study of psychological, family function marital and life satisfactions of polygamous and monogamous women in Jordan.

PubMed

Al-Krenawi, Alean; Graham, John R; Al Gharaibeh, Fakir

2011-10-01

This study surveyed a 2009 convenience sampling of 199 women, 93 of whom were first (or senior) wives in polygamous marriages and 106 were wives in monogamous marriages. We deployed the McMaster Family Assessment Device (FAD), ENRICH marital satisfaction questionnaire, SCL-90 mental health symptoms checklist, Rosenberg self-esteem (SE) scale, and Diener, Emmons, Larsen, and Griffin life satisfaction scale, a basic sociodemographic scale, including attitudes towards polygamy. Women from polygamous families experienced more problems in family functioning, marital relations, and reported low self-esteem, less satisfaction with life, and more somatization, interpersonal sensitivity, depression, anxiety, hostility, paranoid ideation, psychoticism and their general severity index was higher (GSI). More women in polygamous marriages agreed with the practice of polygamy, as compared to their monogamous counterparts. The conclusion considers implications for mental health practice, policy, and further research.

Dynamic regulation of nuclear architecture and mechanics—a rheostatic role for the nucleus in tailoring cellular mechanosensitivity

PubMed Central

Lee, David A.

2017-01-01

ABSTRACT Nuclear architecture, a function of both chromatin and nucleoskeleton structure, is known to change with stem cell differentiation and differs between various somatic cell types. These changes in nuclear architecture are associated with the regulation of gene expression and genome function in a cell-type specific manner. Biophysical stimuli are known effectors of differentiation and also elicit stimuli-specific changes in nuclear architecture. This occurs via the process of mechanotransduction whereby extracellular mechanical forces activate several well characterized signaling cascades of cytoplasmic origin, and potentially some recently elucidated signaling cascades originating in the nucleus. Recent work has demonstrated changes in nuclear mechanics both with pluripotency state in embryonic stem cells, and with differentiation progression in adult mesenchymal stem cells. This review explores the interplay between cytoplasmic and nuclear mechanosensitivity, highlighting a role for the nucleus as a rheostat in tuning the cellular mechano-response. PMID:28152338

Dynamic regulation of nuclear architecture and mechanics-a rheostatic role for the nucleus in tailoring cellular mechanosensitivity.

PubMed

Thorpe, Stephen D; Lee, David A

2017-05-04

Nuclear architecture, a function of both chromatin and nucleoskeleton structure, is known to change with stem cell differentiation and differs between various somatic cell types. These changes in nuclear architecture are associated with the regulation of gene expression and genome function in a cell-type specific manner. Biophysical stimuli are known effectors of differentiation and also elicit stimuli-specific changes in nuclear architecture. This occurs via the process of mechanotransduction whereby extracellular mechanical forces activate several well characterized signaling cascades of cytoplasmic origin, and potentially some recently elucidated signaling cascades originating in the nucleus. Recent work has demonstrated changes in nuclear mechanics both with pluripotency state in embryonic stem cells, and with differentiation progression in adult mesenchymal stem cells. This review explores the interplay between cytoplasmic and nuclear mechanosensitivity, highlighting a role for the nucleus as a rheostat in tuning the cellular mechano-response.

Psychological characteristics and GoNogo research of patients with functional constipation

PubMed Central

Li, Xiaoyi; Feng, Rui; Wu, Hao; Zhang, Lei; Zhao, Lan; Dai, Ning; Yu, Enyan

2016-01-01

Abstract The emotional state, psychological characteristics, cognitive function, and the relevance among above factors in patients with functional constipation (FC) are complex. This study aimed to investigate whether FC symptoms might be related to implicit processing such as psychological characteristics and emotional somatization. Thirty-five FC patients and 24 normal volunteers were recruited to collect event-related potentials (ERP) behavior and electroencephalogram data when simple digital GoNogo visual tasks were performed. Hamilton Depression Scale (HAMD-17), Hamilton Anxiety Scale (HAMA), Symptom Checklist, and Eysenck Personality Inventory (EPQ) were assessed before the ERP test. There was significant difference in average score, positive index, somatization, obsessive-compulsive disorder, anxiety, depression and psychoticism in HAMD-17, HAMA, Symptom Checklist, and extroversion or introversion and neuroticism in EPQ between the FC patients group and the normal control group (P < 0.05). There was a significant difference in the amplitude of ERP-P300 at site F4, F7, and FZ (P < 0.05). FC patients showed anxiety and depression. The asymmetric forebrain abnormal activities in the 2 hemispheres might initiate implicit automatic processing, such as somatization and obsessive-compulsive disorder, in order to cope with painful experience caused by anxiety and depression in patients with FC. Cognitive dysfunction of implicit processing might be involved in the abnormality of visual communication and information processing. PMID:28033259

Piwi Is Required in Multiple Cell Types to Control Germline Stem Cell Lineage Development in the Drosophila Ovary

PubMed Central

Ma, Xing; Wang, Su; Do, Trieu; Song, Xiaoqing; Inaba, Mayu; Nishimoto, Yoshiya; Liu, Lu-ping; Gao, Yuan; Mao, Ying; Li, Hui; McDowell, William; Park, Jungeun; Malanowski, Kate; Peak, Allison; Perera, Anoja; Li, Hua; Gaudenz, Karin; Haug, Jeff; Yamashita, Yukiko; Lin, Haifan; Ni, Jian-quan; Xie, Ting

2014-01-01

The piRNA pathway plays an important role in maintaining genome stability in the germ line by silencing transposable elements (TEs) from fly to mammals. As a highly conserved piRNA pathway component, Piwi is widely expressed in both germ cells and somatic cells in the Drosophila ovary and is required for piRNA production in both cell types. In addition to its known role in somatic cap cells to maintain germline stem cells (GSCs), this study has demonstrated that Piwi has novel functions in somatic cells and germ cells of the Drosophila ovary to promote germ cell differentiation. Piwi knockdown in escort cells causes a reduction in escort cell (EC) number and accumulation of undifferentiated germ cells, some of which show active BMP signaling, indicating that Piwi is required to maintain ECs and promote germ cell differentiation. Simultaneous knockdown of dpp, encoding a BMP, in ECs can partially rescue the germ cell differentiation defect, indicating that Piwi is required in ECs to repress dpp. Consistent with its key role in piRNA production, TE transcripts increase significantly and DNA damage is also elevated in the piwi knockdown somatic cells. Germ cell-specific knockdown of piwi surprisingly causes depletion of germ cells before adulthood, suggesting that Piwi might control primordial germ cell maintenance or GSC establishment. Finally, Piwi inactivation in the germ line of the adult ovary leads to gradual GSC loss and germ cell differentiation defects, indicating the intrinsic role of Piwi in adult GSC maintenance and differentiation. This study has revealed new germline requirement of Piwi in controlling GSC maintenance and lineage differentiation as well as its new somatic function in promoting germ cell differentiation. Therefore, Piwi is required in multiple cell types to control GSC lineage development in the Drosophila ovary. PMID:24658126

Functional Neuroimaging in Psychopathy.

PubMed

Del Casale, Antonio; Kotzalidis, Georgios D; Rapinesi, Chiara; Di Pietro, Simone; Alessi, Maria Chiara; Di Cesare, Gianluigi; Criscuolo, Silvia; De Rossi, Pietro; Tatarelli, Roberto; Girardi, Paolo; Ferracuti, Stefano

2015-01-01

Psychopathy is associated with cognitive and affective deficits causing disruptive, harmful and selfish behaviour. These have considerable societal costs due to recurrent crime and property damage. A better understanding of the neurobiological bases of psychopathy could improve therapeutic interventions, reducing the related social costs. To analyse the major functional neural correlates of psychopathy, we reviewed functional neuroimaging studies conducted on persons with this condition. We searched the PubMed database for papers dealing with functional neuroimaging and psychopathy, with a specific focus on how neural functional changes may correlate with task performances and human behaviour. Psychopathy-related behavioural disorders consistently correlated with dysfunctions in brain areas of the orbitofrontal-limbic (emotional processing and somatic reaction to emotions; behavioural planning and responsibility taking), anterior cingulate-orbitofrontal (correct assignment of emotional valence to social stimuli; violent/aggressive behaviour and challenging attitude) and prefrontal-temporal-limbic (emotional stimuli processing/response) networks. Dysfunctional areas more consistently included the inferior frontal, orbitofrontal, dorsolateral prefrontal, ventromedial prefrontal, temporal (mainly the superior temporal sulcus) and cingulated cortices, the insula, amygdala, ventral striatum and other basal ganglia. Emotional processing and learning, and several social and affective decision-making functions are impaired in psychopathy, which correlates with specific changes in neural functions. © 2015 S. Karger AG, Basel.

Attribution of somatic symptoms in hypochondriasis.

PubMed

Neng, Julia M B; Weck, Florian

2015-01-01

The misinterpretation of bodily symptoms as an indicator of a serious illness is a key feature of the criteria and the cognitive-behavioural models of hypochondriasis. Previous research suggests that individuals suffering from health anxiety endorse attributions of physical disease, whereas persons with elevated general anxiety have the tendency to attribute psychological causes to their symptoms. However, whether a somatic attribution style is specific to patients with hypochondriasis, as opposed to those with anxiety disorders, has not yet been investigated and is therefore part of the present study. Fifty patients with hypochondriasis, 50 patients with a primary anxiety disorder and 50 healthy participants were presented with nine common bodily sensations and had to spontaneously attribute possible causes to the symptoms. Patients with hypochondriasis differed from patients with anxiety disorders and healthy controls in giving significantly fewer normalizing explanations, but attributing more often in terms of moderate or serious diseases. Patients with anxiety disorders also made significantly fewer normalizing attributions and more somatic attributions to a severe illness than healthy controls. There were no differences between the groups in the frequency of psychological attributions and somatic attributions concerning mild diseases. The present study demonstrates that hypochondriasis is associated with a disorder-specific attribution style connecting somatic symptoms primarily with moderate and serious diseases. By contrast, normalizing attributions are largely omitted from consideration by patients with hypochondriasis. The findings conform with the cognitive conception of hypochondriasis and support the strategy of modifying symptom attributions, as practiced in cognitive-behavioural therapy. Copyright © 2013 John Wiley & Sons, Ltd.

The Impacts of Migraine among Outpatients with Major Depressive Disorder at a Two-Year Follow-Up

PubMed Central

Hung, Ching-I; Liu, Chia-Yih; Yang, Ching-Hui; Wang, Shuu-Jiun

2015-01-01

Background No study has investigated the impacts of migraine on depression, anxiety, and somatic symptoms and remission at the two-year follow-up point among patients with major depressive disorder (MDD). This study aimed to investigate the above issues. Methods Psychiatric outpatients with MDD recruited at baseline were investigated at a two-year follow-up (N = 106). The Hamilton Depression Rating Scale, Hospital Anxiety and Depression Scale, and Depression and Somatic Symptoms Scale were used. Migraine was diagnosed according to the International Classification of Headache Disorders, 2nd edition. The patients were divided into no migraine, inactive migraine, and active migraine subgroups. Multiple logistic regressions were used to investigate the significant factors related to full remission of depression. Results Among patients without pharmacotherapy at the follow-up, patients with active migraine had significantly greater severities of anxiety and somatic symptoms as compared with patients without migraine; moreover, patients with active migraine had the lowest improvement percentage and full remission rate. There were no significant differences in depression, anxiety, and somatic symptoms between patients with inactive migraine and those without migraine. Active headache at follow-up was a significant factor related to a lower full remission rate. Conclusions Active headache at follow-up was associated with a lower rate of full remission and more residual anxiety and somatic symptoms at follow-up among patients with migraine. Physicians should integrate a treatment plan for depression and migraine for the treatment of patients with MDD. PMID:26000962

Cultural differences in symptom representation for depression and somatization measured by the PHQ between Vietnamese and German psychiatric outpatients.

PubMed

Dreher, Annegret; Hahn, Eric; Diefenbacher, Albert; Nguyen, Main Huong; Böge, Kerem; Burian, Hannah; Dettling, Michael; Burian, Ronald; Ta, Thi Minh Tam

2017-11-01

Despite an extensive body of research on somatic symptom presentation among people of East- and Southeast-Asian descent, results are still inconclusive. Examining and comparing symptom presentation in clinically and ethnically well-characterized populations may constitute a step towards understanding symptom presentation between patients with a different cultural background. This study aims to compare Vietnamese and German patients regarding cultural dynamics of symptom presentation upon first admission to a psychiatric outpatient service. 110 Vietnamese and 109 German patients seeking psychiatric treatment at two outpatient clinics completed the Patient Health Questionnaire (PHQ). The somatic symptom subscale (PHQ-15), the depression subscale (PHQ-9) and PHQ-subscales examining anxiety and psychosocial stress levels were analyzed and compared for both groups using multivariate analysis of covariance. Regression analysis was utilized to examine the influences of sociodemographic and migration specific factors. Vietnamese and German patients showed comparable Cronbach's alpha for all subscales. Vietnamese patients endorsed significantly higher levels of somatic symptoms overall and on certain items (as pain-related items, dizziness, and fainting spells) despite similar levels of depression severity in comparison with German patients. Vietnamese patients with poor German language skills showed a significantly higher focus on somatic symptoms. Raising awareness for cultural dynamics of symptom presentation in patients with depression is indispensable. Cross-cultural symptom assessment using the PHQ seems feasible and expands our understanding of depressive and psychosomatic symptoms when assessed by clinicians. Copyright © 2017. Published by Elsevier Inc.

The Impacts of Migraine among Outpatients with Major Depressive Disorder at a Two-Year Follow-Up.

PubMed

Hung, Ching-I; Liu, Chia-Yih; Yang, Ching-Hui; Wang, Shuu-Jiun

2015-01-01

No study has investigated the impacts of migraine on depression, anxiety, and somatic symptoms and remission at the two-year follow-up point among patients with major depressive disorder (MDD). This study aimed to investigate the above issues. Psychiatric outpatients with MDD recruited at baseline were investigated at a two-year follow-up (N = 106). The Hamilton Depression Rating Scale, Hospital Anxiety and Depression Scale, and Depression and Somatic Symptoms Scale were used. Migraine was diagnosed according to the International Classification of Headache Disorders, 2nd edition. The patients were divided into no migraine, inactive migraine, and active migraine subgroups. Multiple logistic regressions were used to investigate the significant factors related to full remission of depression. Among patients without pharmacotherapy at the follow-up, patients with active migraine had significantly greater severities of anxiety and somatic symptoms as compared with patients without migraine; moreover, patients with active migraine had the lowest improvement percentage and full remission rate. There were no significant differences in depression, anxiety, and somatic symptoms between patients with inactive migraine and those without migraine. Active headache at follow-up was a significant factor related to a lower full remission rate. Active headache at follow-up was associated with a lower rate of full remission and more residual anxiety and somatic symptoms at follow-up among patients with migraine. Physicians should integrate a treatment plan for depression and migraine for the treatment of patients with MDD.

Biotechnological advances in mango (Mangifera indica L.) and their future implication in crop improvement: a review.

PubMed

Krishna, Hare; Singh, S K

2007-01-01

Biotechnology can complement conventional breeding and expedite the mango improvement programmes. Studies involving in vitro culture and selection, micropropagation, embryo rescue, genetic transformation, marker-assisted characterization and DNA fingerprinting, etc. are underway at different centers worldwide. In vitro culture and somatic embryogenesis of several different genotypes have been achieved. The nucellus excised from immature fruitlets is the appropriate explant for induction of embryogenic cultures. High frequency somatic embryogenesis has been achieved in some genotypes; however, some abnormalities can occur during somatic embryo germination. Embryo rescue from young and dropped fruitlets can improve the hybridization success in a limited flowering season. Protocols for protoplast culture and regeneration have also been developed. In vitro selections for antibiotic tolerance and fungal toxin resistance have been very promising for germplasm screening. Genetic transformation using Agrobacterium tumefaciens has been reported. Genes that are involved with fruit ripening have been cloned and there have been attempts to deliver these genes into plants. DNA fingerprinting and studies on genetic diversity of mango cultivars and Mangifera species are also being conducted at several research stations. The purpose of this review is to focus upon contemporary information on biotechnological advances made in mango. It also describes some ways of overcoming the problems encountered during in vitro propagation of mango.

Influences of Mental Illness, Current Psychological State, and Concussion History on Baseline Concussion Assessment Performance.

PubMed

Weber, Michelle L; Dean, John-Henry L; Hoffman, Nicole L; Broglio, Steven P; McCrea, Michael; McAllister, Thomas W; Schmidt, Julianne D; Hoy, April Reed; Hazzard, Joseph B; Kelly, Louise A; Ortega, Justus D; Port, Nicholas; Putukian, Margot; Langford, T Dianne; Tierney, Ryan; Campbell, Darren E; McGinty, Gerald; O'Donnell, Patrick; Svoboda, Steven J; DiFiori, John P; Giza, Christopher C; Benjamin, Holly J; Buckley, Thomas; Kaminski, Thomas W; Clugston, James R; Feigenbaum, Luis A; Eckner, James T; Guskiewicz, Kevin; Mihalik, Jason P; Miles, Jessica Dysart; Anderson, Scott; Master, Christina L; Collins, Micky; Kontos, Anthony P; Bazarian, Jeffrey J; Chrisman, Sara P D; Brooks, Allison; Duma, Stefan; Bullers, Christopher Todd; Miles, Christopher M; Dykhuizen, Brian H

2018-06-01

A student-athlete's mental state, including history of trait anxiety and depression, or current psychological state may affect baseline concussion assessment performance. (1) To determine if mental illness (anxiety, depression, anxiety with depression) influences baseline scores, (2) to determine if psychological state correlates with baseline performance, and (3) to determine if history of concussion affects Brief Symptom Inventory-18 (BSI-18) subscores of state anxiety, depression, and somatization. Cross-sectional study; Level of evidence, 3. A sample of 8652 collegiate student-athletes (54.5% males, 45.5% females) participated in the Concussion Assessment, Research and Education (CARE) Consortium. Baseline assessments included a demographic form, a symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, a psychological state assessment (BSI-18), and Immediate Post-concussion Assessment and Cognitive Test. Baseline scores were compared between individuals with a history of anxiety (n = 59), depression (n = 283), and anxiety with depression (n = 68) and individuals without a history of those conditions (n = 8242). Spearman's rho correlations were conducted to assess the relationship between baseline and psychological state subscores (anxiety, depression, somatization) (α = .05). Psychological state subscores were compared between individuals with a self-reported history of concussions (0, 1, 2, 3, 4+) using Kruskal-Wallis tests (α = .05). Student-athletes with anxiety, depression, and anxiety with depression demonstrated higher scores in number of symptoms reported (anxiety, 4.3 ± 4.2; depression, 5.2 ± 4.8; anxiety with depression, 5.4 ± 3.9; no anxiety/depression, 2.5 ± 3.4), symptom severity (anxiety, 8.1 ± 9.8; depression, 10.4 ± 12.4; anxiety with depression, 12.4 ± 10.7; no anxiety/depression, 4.1 ± 6.9), and psychological distress in state anxiety (anxiety, 3.7 ± 4.7; depression, 2.5 ± 3.6; anxiety with depression, 3.8 ± 4.2; no anxiety/depression, 0.8 ± 1.8), depression (anxiety, 2.4 ± 4.0; depression, 3.2 ± 4.5; anxiety with depression, 3.8 ± 4.8; no anxiety/depression, 0.8 ± 1.8), and somatization (anxiety, 2.3 ± 2.9; depression, 1.8 ± 2.8; anxiety with depression, 2.2 ± 2.4; no anxiety/depression, 0.9 ± 1.7). A moderate positive relationship existed between all BSI-18 subscores and total symptom number (n = 8377; anxiety: r s = 0.43, P < .001; depression: r s = 0.42, P < .001; somatization: r s = 0.45, P < .001), as well as total symptom severity (anxiety: r s = 0.43, P < .001; depression: r s = 0.41, P < .001; somatization: r s = 0.45, P < .001). Anxiety, depression, and somatization subscores were greater among student-athletes that self-reported more concussions. Clinicians should be cognizant that student-athletes with a history of trait anxiety, depression, and anxiety with depression may report higher symptom score and severity at baseline. Individuals with extensive concussion history may experience greater state anxiety, depression, and somatization.

Ovarian-Cell-Like Cells from Skin Stem Cells Restored Estradiol Production and Estrus Cycling in Ovariectomized Mice

PubMed Central

Park, Bong-Wook; Pan, Bo; Toms, Derek; Huynh, Evanna; Byun, June-Ho; Lee, Yeon-Mi; Shen, Wei

2014-01-01

Reduction of estradiol production and high serum concentrations of follicular stimulating hormone (FSH) are endocrine disorders associated with premature ovarian failure. Here, we report that transplantation of ovarian-like cells differentiated from stem cells restored endogenous serum estradiol levels. Stem cells were isolated from postnatal mouse skin and differentiated into ovarian-cell-like cells that are consistent with female germ, and ovarian follicle somatic cells. The ovarian-cell-like cells were transplanted into ovariectomized mice (Cell Trans), whereas control mice were subjected to bilateral ovariectomies without cell transplantation (OVX). Using vaginal cytology analysis, it was revealed that in 13 out of 19 Cell Trans mice, estrus cycles were restored around 8 weeks after cell transplantation and were maintained until 16 weeks post-transplantation, whereas in the OVX group, all mice were arrested at metestrus/diestrus of the estrus cycle. The uterine weight in the Cell Trans group was similar to sham operation mice (Sham OP), while severe uterine atrophy and a decreased uterine weight were observed in the OVX group. Histologically, ectopic follicle-like structures and blood vessels were found within and around the transplants. At 12–14 weeks after cell transplantation, mean serum estradiol level in Cell Trans mice (178.0±35 pg/mL) was comparable to that of the Sham OP group (188.9±29 pg/mL), whereas it was lower in the OVX group (59.0±4 pg/mL). Serum FSH concentration increased in the OVX group (1.62±0.32 ng/mL) compared with the Sham OP group (0.39±0.34 ng/mL). Cell Trans mice had a similar FSH level (0.94±0.23 ng/mL; P<0.05) to Sham OP mice. Our results suggest that ovarian somatic cells differentiated from stem cells are functional in vivo. In addition to providing insights into the function of ovarian somatic cells derived from stem cells, our study may offer potential therapeutic means for patients with hypo-estradiol levels like those encountered in premature ovarian failure. PMID:24593690

Genome editing in pluripotent stem cells: research and therapeutic applications.

PubMed

Deleidi, Michela; Yu, Cong

2016-05-06

Recent progress in human pluripotent stem cell (hPSC) and genome editing technologies has opened up new avenues for the investigation of human biology in health and disease as well as the development of therapeutic applications. Gene editing approaches with programmable nucleases have been successfully established in hPSCs and applied to study gene function, develop novel animal models and perform genetic and chemical screens. Several studies now show the successful editing of disease-linked alleles in somatic and patient-derived induced pluripotent stem cells (iPSCs) as well as in animal models. Importantly, initial clinical trials have shown the safety of programmable nucleases for ex vivo somatic gene therapy. In this context, the unlimited proliferation potential and the pluripotent properties of iPSCs may offer advantages for gene targeting approaches. However, many technical and safety issues still need to be addressed before genome-edited iPSCs are translated into the clinical setting. Here, we provide an overview of the available genome editing systems and discuss opportunities and perspectives for their application in basic research and clinical practice, with a particular focus on hPSC based research and gene therapy approaches. Finally, we discuss recent research on human germline genome editing and its social and ethical implications. Copyright © 2016 Elsevier Inc. All rights reserved.

Using sea urchin gametes and zygotes to investigate centrosome duplication.

PubMed

Sluder, Greenfield

2016-01-01

Centriole structure and function in the sea urchin zygote parallel those in mammalian somatic cells. Here, I briefly introduce the properties and attributes of the sea urchin system that make it an attractive platform for the study of centrosome and centriole duplication. These attributes apply to all echinoderms readily available from commercial suppliers: sea urchins, sand dollars, and starfish. I list some of the practical aspects of the system that make it a cost- and time-effective system for experimental work and then list properties that are a "tool kit" that can be used to conduct studies that would not be practical, or in some cases not possible, with mammalian somatic cells. Since centrioles organize and localize the pericentriolar material that nucleates the astral arrays of microtubules (Bobinnec et al. in J Cell Biol 143(6):1575-1589, 1998), the pattern of aster duplication over several cell cycles can be used as a reliable measure for centriole duplication (Sluder and Rieder in J Cell Biol 100(3):887-896, 1985). Descriptions of the methods my laboratory has used to handle and image echinoderm zygotes are reviewed in Sluder et al. (Methods Cell Biol 61:439-472, 1999). Also included is a bibliography of papers that describe additional methods.

The DSM-IV nosology of chronic pain: a comparison of pain disorder and multiple somatization syndrome.

PubMed

Hiller, W; Heuser, J; Fichter, M M

2000-01-01

This study evaluates the classification of pain from the perspective of the DSM-IV system. Of 60 in-patients with long-standing and disabling pain syndromes, 29 with pain disorder (PD) and 31 with pain as part of a multiple somatization syndrome (MSS) were compared before and after a structured cognitive-behavioral treatment. It was hypothesized that MSS patients show more psychological distress, are more severely disabled, and respond less to the treatment. Both groups were similar with respect to sociodemographic status, history of pain symptomatology and comorbidity with DSM-IV mental disorders. The results show that MSS patients had higher levels of affective and sensoric pain sensations as well as more pain-related disabilities. They were also less successful during treatment to reduce their pain-related depression and anxiety. Psychosocial functioning was improved only by PD patients, but remained almost unchanged in the MSS group. However, there were no group differences concerning general depression and hypochondriasis, dysfunctional attitudes towards body and health, and use of pain coping strategies. It is concluded that the DSM-IV distinction between 'pure' pain disorder and syndromes involving pain plus multiple somatoform symptoms cannot generally be confirmed, but further studies of validation are needed. Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain.

Somatostatin and Somatostatin Receptor Gene Expression in Dominant and Subordinate Males of an African Cichlid Fish

PubMed Central

Trainor, Brian C.; Hofmann, Hans A.

2009-01-01

Somatostatin is a neuropeptide best known for its inhibitory effects on growth hormone secretion and has recently been implicated in the control of social behavior. Several somatostatin receptor subtypes have been identified in vertebrates, but the functional basis for this diversity is still unclear. Here we investigate the expression levels of the somatostatin prepropeptide and two of its receptors, sstR2, and sstR3, in the brains of socially dominant and subordinate A. burtoni males using real-time PCR. Dominant males had higher somatostatin prepropeptide and sstR3 expression in hypothalamus compared to subordinate males. Hypothalamic sstR2 expression did not differ. There were no differences in gene expression in the telencephalon. We also observed an interesting difference between dominants and subordinates in the relationship between hypothalamic sstR2 expression and body size. As would be predicted based on the inhibitory effects of somatostatin on somatic growth, sstR2 expression was negatively correlated with body size in dominant males. In contrast sstR2 expression was positively correlated with body size in subordinate males. These results suggest that somatostatin prepropeptide and receptor gene expression in the hypothalamus are associated with the control of somatic growth in A. burtoni depending on social status. PMID:17374406

Regulatory concerns in the development of biologic-biomaterial combinations. United States Food and Drug Administration.

PubMed

Chapekar, M S

1996-01-01

Several biologic-biomaterial combinations are currently under development in an attempt to modulate tissue or organ function in patients. The FDA regulations on combination products and the intercenter agreements among the Center for Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health (CDRH), and the Center for Drugs Evaluation and Research (CDER) provide further guidance on center jurisdiction of combination products and other products where there are jurisdictional concerns. The biological component of biologic-biomaterial combinations raises a number of issues that relate to the safety and bioactivity of the final product. For example, transmission of adventitious agents to patients via somatic cells, tissue, or cell-derived products is a major safety concern as are in vivo inflammatory responses elicited by the biomaterial component. CBER has drafted a number of "Points to Consider" documents to provide further guidance in the development of biological products. The intent of this article is to provide the highlights of the FDA regulations for combination products and the intercenter agreement between CBER and CDRH delineating the responsibilities of each center for medical device activities. In addition, the article focuses on the CBER's concerns related to the development of somatic cell-biomaterial combinations for therapeutic use.

Psychometric Analysis of the Heart Failure Somatic Perception Scale as a Measure of Patient Symptom Perception.

PubMed

Jurgens, Corrine Y; Lee, Christopher S; Riegel, Barbara

Symptoms are known to predict survival among patients with heart failure (HF), but discrepancies exist between patients' and health providers' perceptions of HF symptom burden. The purpose of this study is to quantify the internal consistency, validity, and prognostic value of patient perception of a broad range of HF symptoms using an HF-specific physical symptom measure, the 18-item HF Somatic Perception Scale v. 3. Factor analysis of the HF Somatic Perception Scale was conducted in a convenience sample of 378 patients with chronic HF. Convergent validity was examined using the Physical Limitation subscale of the Kansas City Cardiomyopathy Questionnaire. Divergent validity was examined using the Self-care of HF Index self-care management score. One-year survival based on HF Somatic Perception Scale scores was quantified using Cox regression controlling for Seattle HF Model scores to account for clinical status, therapeutics, and lab values. The sample was 63% male, 85% white, 67% functionally compromised (New York Heart Association class III-IV) with a mean (SD) age of 63 (12.8) years. Internal consistency of the HF Somatic Perception Scale was α = .90. Convergent (r = -0.54, P < .0001) and divergent (r = 0.18, P > .05) validities were supported. Controlling for Seattle HF scores, HF Somatic Perception Scale was a significant predictor of 1-year survival, with those most symptomatic having worse survival (hazard ratio, 1.012; 95% confidence interval, 1.001-1.024; P = .038). Perception of HF symptom burden as measured by the HF Somatic Perception Scale is a significant predictor of survival, contributing additional prognostic value over and above objective Seattle HF Risk Model scores. This analysis suggests that assessment of a broad range of HF symptoms, or those related to dyspnea or early and subtle symptoms, may be useful in evaluating therapeutic outcomes and predicting event-free survival.

Operationalization of diagnostic criteria of DSM-5 somatic symptom disorders.

PubMed

Xiong, Nana; Zhang, Yaoyin; Wei, Jing; Leonhart, Rainer; Fritzsche, Kurt; Mewes, Ricarda; Hong, Xia; Cao, Jinya; Li, Tao; Jiang, Jing; Zhao, Xudong; Zhang, Lan; Schaefert, Rainer

2017-11-07

The aim of this study was to test the operationalization of DSM-5 somatic symptom disorder (SSD) psychological criteria among Chinese general hospital outpatients. This multicenter, cross-sectional study enrolled 491 patients from 10 general hospital outpatient departments. The structured clinical "interview about cognitive, affective, and behavioral features associated with somatic complaints" was used to operationalize the SSD criteria B. For comparison, DSM-IV somatoform disorders were assessed with the Mini International Neuropsychiatric Interview plus. Cohen's к scores were given to illustrate the agreement of the diagnoses. A three-structure model of the interview, within which items were classified as respectively assessing the cognitive (B1), affective (B2), and behavioral (B3) features, was examined. According to percentages of screening-positive persons and the receiver operator characteristic (ROC) analysis, a cut-off point of 2 was recommended for each subscale of the interview. With the operationalization, the frequency of DSM-5 SSD was estimated as 36.5% in our sample, and that of DSM-IV somatoform disorders was 8.2%. The agreement between them was small (Cohen's к = 0.152). Comparisons of sociodemographic features of SSD patients with different severity levels (mild, moderate, severe) showed that mild SSD patients were better-off in terms of financial and employment status, and that the severity subtypes were congruent with the level of depression, anxiety, quality of life impairment, and the frequency of doctor visits. The operationalization of the diagnosis and severity specifications of SSD was valid, but the diagnostic agreement between DSM-5 SSD and DSM-IV somatoform disorders was small. The interpretation the SSD criteria should be made cautiously, so that the diagnosis would not became over-inclusive.

Health-related quality of life and symptom severity in Chinese patients with major depressive disorder.

PubMed

Cao, Yuping; Li, Wen; Shen, Jingjin; Malison, Robert T; Zhang, Yalin; Luo, Xingguang

2013-12-01

Patients suffering from major depressive disorder (MDD) have been reported to have substantial long-lasting limitations in multiple domains of health-related quality of life (HRQoL). The thoughtful assessment of HRQoL and the impact of treatment response on HRQoL are emerging as important issues in the care of patients with major depressive disorder. One hundred and three patients meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for MDD took fluoxetine (20 mg/d) for 6 weeks and were assessed by the Short Form 36 Health Survey (SF-36), the 17-item Hamilton Depression Rating (HAMD-17) and the Clinical Global Impression (CGI) scales. Relationships between SF-36 scores and depressive symptom severity and early change of these symptoms were tested. SF-36 component scores at week 6 were higher than those at baseline (all P ≤ 0.0058). Scores for general health were significantly higher in responders than non-responders (P = 0.0009). The overall HAMD-17 and CGI scores at 2- and 6-week follow-up were significantly lower than those at baseline (P ≤ 0.0001). Higher scores for anxiety/somatization were significantly associated with poorer SF-36 scores at baseline (P = 0.0001); role-physical scores at week 6 were positively correlated with reduction rate of anxiety/somatization in 2-week follow-up (P = 0.0002). Depressive symptom severity was associated with HRQoL in patients with MDD. HRQoL may vary with severity of depression and/or anxiety-somatization at baseline. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype.

PubMed

Moncada-Vélez, M; Vélez-Ortega, A; Orrego, J; Santisteban, I; Jagadeesh, J; Olivares, M; Olaya, N; Hershfield, M; Candotti, F; Franco, J

2011-11-01

Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. We report a child with severe combined immunodeficiency (T-B- SCID) due to ADA deficiency diagnosed at the age of 1 month, whose lymphocyte counts including CD4+ and CD8+ T and NK cells began to improve after several months with normalization of ADA activity in Peripheral blood lymphocytes (PBL), as a result of somatic mosaicism caused by monoallelic reversion of the causative mutation in the ADA gene. He was not eligible for haematopoietic stem cell transplantation (HSCT) or gene therapy (GT); therefore he was placed on enzyme replacement therapy (ERT) with bovine PEG-ADA. The follow-up of metabolic and immunologic responses to ERT included gradual improvement in ADA activity in erythrocytes and transient expansion of most lymphocyte subsets, followed by gradual stabilization of CD4+ and CD8+ T (with naïve phenotype) and NK cells, and sustained expansion of TCRγδ+ T cells. This was accompanied by the disappearance of the revertant T cells as shown by DNA sequencing from PBL. Although the patient's clinical condition improved marginally, he later developed a germinal cell tumour and eventually died at the age of 67 months from sepsis. This case adds to our current knowledge of spontaneous reversion of mutations in ADA deficiency and shows that the effects of the ERT may vary among these patients, suggesting that it could depend on the cell and type in which the somatic mosaicism is established upon reversion. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Somatic mosaicism due to monoallelic reversion of a mutation in T cells of an ADA-SCID patient and the effects of enzyme replacement therapy on the revertant phenotype

PubMed Central

Moncada-Vélez, Marcela; Vélez-Ortega, Alejandra C.; Orrego, Julio C.; Santisteban, Inés; Jagadeesh, Jayashree; Olivares, Margarita; Olaya, Natalia; Hershfield, Michael S.; Candotti, Fabio; Franco, Jose L.

2011-01-01

Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. We report a child with severe combined immunodeficiency (T-B-NK- SCID) due to ADA deficiency diagnosed at the age of 1 month, whose lymphocyte counts including CD4+ and CD8+ T and NK cells began to improve after several months with normalization of ADA activity in PBL, as a result of somatic mosaicism due to monoallelic reversion of the causative mutation in the ADA gene. Our patient was not eligible for hematopoietic stem cell transplantation (HSCT) or gene therapy (GT); therefore enzyme replacement therapy (ERT) with bovine PEG-ADA was initiated. The follow up of metabolic and immunologic responses to ERT included gradual improvement in ADA activity in erythrocytes and transient expansion of most lymphocyte subsets, followed by gradual stabilization of CD4+ and CD8+ T (with naïve phenotype) and NK cells, with sustained expansion of TCRγδ+ T cells. This was accompanied by disappearance of the revertant T cells as shown by DNA sequencing from PBL. Although the patient’s clinical condition improved marginally, he later developed a germinal cell tumor and eventually died at the age of 67 months from sepsis. This case adds to our current knowledge of spontaneous reversion of mutations in ADA deficiency and shows that the effects of the ERT may vary among these patients, suggesting that it could depend on the cell and type in which the somatic mosaicism is established upon reversion. PMID:21671975

TMC-SNPdb: an Indian germline variant database derived from whole exome sequences.

PubMed

Upadhyay, Pawan; Gardi, Nilesh; Desai, Sanket; Sahoo, Bikram; Singh, Ankita; Togar, Trupti; Iyer, Prajish; Prasad, Ratnam; Chandrani, Pratik; Gupta, Sudeep; Dutt, Amit

2016-01-01

Cancer is predominantly a somatic disease. A mutant allele present in a cancer cell genome is considered somatic when it's absent in the paired normal genome along with public SNP databases. The current build of dbSNP, the most comprehensive public SNP database, however inadequately represents several non-European Caucasian populations, posing a limitation in cancer genomic analyses of data from these populations. We present the T: ata M: emorial C: entre-SNP D: ata B: ase (TMC-SNPdb), as the first open source, flexible, upgradable, and freely available SNP database (accessible through dbSNP build 149 and ANNOVAR)-representing 114 309 unique germline variants-generated from whole exome data of 62 normal samples derived from cancer patients of Indian origin. The TMC-SNPdb is presented with a companion subtraction tool that can be executed with command line option or using an easy-to-use graphical user interface with the ability to deplete additional Indian population specific SNPs over and above dbSNP and 1000 Genomes databases. Using an institutional generated whole exome data set of 132 samples of Indian origin, we demonstrate that TMC-SNPdb could deplete 42, 33 and 28% false positive somatic events post dbSNP depletion in Indian origin tongue, gallbladder, and cervical cancer samples, respectively. Beyond cancer somatic analyses, we anticipate utility of the TMC-SNPdb in several Mendelian germline diseases. In addition to dbSNP build 149 and ANNOVAR, the TMC-SNPdb along with the subtraction tool is available for download in the public domain at the following:Database URL: http://www.actrec.gov.in/pi-webpages/AmitDutt/TMCSNP/TMCSNPdp.html. © The Author(s) 2016. Published by Oxford University Press.

EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation

PubMed Central

Béguelin, Wendy; Popovic, Relja; Teater, Matt; Jiang, Yanwen; Bunting, Karen L.; Rosen, Monica; Shen, Hao; Yang, Shao Ning; Wang, Ling; Ezponda, Teresa; Martinez-Garcia, Eva; Zhang, Haikuo; Zhang, Yupeng; Verma, Sharad K.; McCabe, Michael T.; Ott, Heidi M.; Van Aller, Glenn S.; Kruger, Ryan G.; Liu, Yan; McHugh, Charles F.; Scott, David W.; Chung, Young Rock; Kelleher, Neil; Shaknovich, Rita; Creasy, Caretha L.; Gascoyne, Randy D.; Wong, Kwok-Kin; Cerchietti, Leandro C.; Levine, Ross L.; Abdel-Wahab, Omar; Licht, Jonathan D.; Elemento, Olivier; Melnick, Ari M.

2013-01-01

The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B-cells and targeted by somatic mutations in B-cell lymphomas. Here we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions in mice. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B-cell differentiation. Somatic mutations reinforce these physiological effects through enhanced silencing of EZH2 targets in B-cells, and in human B-cell lymphomas. Conditional expression of mutant EZH2 in mice induces GC hyperplasia and accelerated lymphomagenesis in cooperation with BCL2. GCB-type DLBCLs are mostly addicted to EZH2, regardless of mutation status, but not the more differentiated ABC-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting. PMID:23680150

The actin-binding protein profilin is required for germline stem cell maintenance and germ cell enclosure by somatic cyst cells

PubMed Central

Shields, Alicia R.; Spence, Allyson C.; Yamashita, Yukiko M.; Davies, Erin L.; Fuller, Margaret T.

2014-01-01

Specialized microenvironments, or niches, provide signaling cues that regulate stem cell behavior. In the Drosophila testis, the JAK-STAT signaling pathway regulates germline stem cell (GSC) attachment to the apical hub and somatic cyst stem cell (CySC) identity. Here, we demonstrate that chickadee, the Drosophila gene that encodes profilin, is required cell autonomously to maintain GSCs, possibly facilitating localization or maintenance of E-cadherin to the GSC-hub cell interface. Germline specific overexpression of Adenomatous Polyposis Coli 2 (APC2) rescued GSC loss in chic hypomorphs, suggesting an additive role of APC2 and F-actin in maintaining the adherens junctions that anchor GSCs to the niche. In addition, loss of chic function in the soma resulted in failure of somatic cyst cells to maintain germ cell enclosure and overproliferation of transit-amplifying spermatogonia. PMID:24346697

Neuroendocrine regulation of somatic growth in fishes.

PubMed

Dai, XiangYan; Zhang, Wei; Zhuo, ZiJian; He, JiangYan; Yin, Zhan

2015-02-01

Growth is a polygenic trait that is under the influence of multiple physiological pathways regulating energy metabolism and muscle growth. Among the possible growth-regulating pathways in vertebrates, components of the somatotropic axis are thought to have the greatest influence. There is growing body of literature focusing on the somatotropic axis and its role regulating growth in fish. This includes research into growth hormone, upstream hypothalamic hormones, insulin-like growth factors, and downstream signaling molecules. Many of these signals have both somatic effects stimulating the growth of tissues and metabolic effects that play a role in nutrient metabolism. Signals of other endocrine axes exhibit profound effects on the function of the somatotropic axis in vivo. In this review we highlight recent advances in our understanding of the teleost fish endocrine somatotropic axis, including emerging research using genetic modified models. These studies have revealed new aspects and challenges associated with regulation of the important steps of somatic growth.

The psychophysiology of crying.

PubMed

Gross, J J; Frederickson, B L; Levenson, R W

1994-09-01

Two conflicting views have emerged as to why people cry when they are sad. One suggests that crying serves homeostasis by facilitating recovery; the other suggests that crying produces an aversive high-arousal state that motivates behavior aimed at ending the tears. To test hypotheses drawn from these views, we showed a short film known to elicit sadness to 150 women. During this film, 33 subjects spontaneously cried and 117 did not. Subjects who cried exhibited more expressive behavior and reported feeling more sadness and pain than did subjects who did not cry. Crying also was associated with increases in somatic and autonomic nervous system activity. The increases in autonomic activity could not be accounted for solely by the increases in somatic activity. Crying is thus associated with an aversive state, including negative emotion and a complex mixture of sympathetic, parasympathetic, and somatic activation, and we speculate about the functional implications of these findings.

Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs

PubMed Central

Matsunari, Hitomi; Nagashima, Hiroshi; Watanabe, Masahito; Umeyama, Kazuhiro; Nakano, Kazuaki; Nagaya, Masaki; Kobayashi, Toshihiro; Yamaguchi, Tomoyuki; Sumazaki, Ryo; Herzenberg, Leonard A.; Nakauchi, Hiromitsu

2013-01-01

In the field of regenerative medicine, one of the ultimate goals is to generate functioning organs from pluripotent cells, such as ES cells or induced pluripotent stem cells (PSCs). We have recently generated functional pancreas and kidney from PSCs in pancreatogenesis- or nephrogenesis-disabled mice, providing proof of principle for organogenesis from PSCs in an embryo unable to form a specific organ. Key when applying the principles of in vivo generation to human organs is compensation for an empty developmental niche in large nonrodent mammals. Here, we show that the blastocyst complementation system can be applied in the pig using somatic cell cloning technology. Transgenic approaches permitted generation of porcine somatic cell cloned embryos with an apancreatic phenotype. Complementation of these embryos with allogenic blastomeres then created functioning pancreata in the vacant niches. These results clearly indicate that a missing organ can be generated from exogenous cells when functionally normal pluripotent cells chimerize a cloned dysorganogenetic embryo. The feasibility of blastocyst complementation using cloned porcine embryos allows experimentation toward the in vivo generation of functional organs from xenogenic PSCs in large animals. PMID:23431169

Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs.

PubMed

Matsunari, Hitomi; Nagashima, Hiroshi; Watanabe, Masahito; Umeyama, Kazuhiro; Nakano, Kazuaki; Nagaya, Masaki; Kobayashi, Toshihiro; Yamaguchi, Tomoyuki; Sumazaki, Ryo; Herzenberg, Leonard A; Nakauchi, Hiromitsu

2013-03-19

In the field of regenerative medicine, one of the ultimate goals is to generate functioning organs from pluripotent cells, such as ES cells or induced pluripotent stem cells (PSCs). We have recently generated functional pancreas and kidney from PSCs in pancreatogenesis- or nephrogenesis-disabled mice, providing proof of principle for organogenesis from PSCs in an embryo unable to form a specific organ. Key when applying the principles of in vivo generation to human organs is compensation for an empty developmental niche in large nonrodent mammals. Here, we show that the blastocyst complementation system can be applied in the pig using somatic cell cloning technology. Transgenic approaches permitted generation of porcine somatic cell cloned embryos with an apancreatic phenotype. Complementation of these embryos with allogenic blastomeres then created functioning pancreata in the vacant niches. These results clearly indicate that a missing organ can be generated from exogenous cells when functionally normal pluripotent cells chimerize a cloned dysorganogenetic embryo. The feasibility of blastocyst complementation using cloned porcine embryos allows experimentation toward the in vivo generation of functional organs from xenogenic PSCs in large animals.

Control of female gamete formation by a small RNA pathway in Arabidopsis.

PubMed

Olmedo-Monfil, Vianey; Durán-Figueroa, Noé; Arteaga-Vázquez, Mario; Demesa-Arévalo, Edgar; Autran, Daphné; Grimanelli, Daniel; Slotkin, R Keith; Martienssen, Robert A; Vielle-Calzada, Jean-Philippe

2010-03-25

In the ovules of most sexual flowering plants female gametogenesis is initiated from a single surviving gametic cell, the functional megaspore, formed after meiosis of the somatically derived megaspore mother cell (MMC). Because some mutants and certain sexual species exhibit more than one MMC, and many others are able to form gametes without meiosis (by apomixis), it has been suggested that somatic cells in the ovule are competent to respond to a local signal likely to have an important function in determination. Here we show that the Arabidopsis protein ARGONAUTE 9 (AGO9) controls female gamete formation by restricting the specification of gametophyte precursors in a dosage-dependent, non-cell-autonomous manner. Mutations in AGO9 lead to the differentiation of multiple gametic cells that are able to initiate gametogenesis. The AGO9 protein is not expressed in the gamete lineage; instead, it is expressed in cytoplasmic foci of somatic companion cells. Mutations in SUPPRESSOR OF GENE SILENCING 3 and RNA-DEPENDENT RNA POLYMERASE 6 exhibit an identical defect to ago9 mutants, indicating that the movement of small RNA (sRNAs) silencing out of somatic companion cells is necessary for controlling the specification of gametic cells. AGO9 preferentially interacts with 24-nucleotide sRNAs derived from transposable elements (TEs), and its activity is necessary to silence TEs in female gametes and their accessory cells. Our results show that AGO9-dependent sRNA silencing is crucial to specify cell fate in the Arabidopsis ovule, and that epigenetic reprogramming in companion cells is necessary for sRNA-dependent silencing in plant gametes.

DNMT1 Maintains Progenitor Function in Self-Renewing Somatic Tissue

PubMed Central

Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A.

2010-01-01

Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation1,2. DNA methylation3,4,5 provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1)6,7 maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintenance,8 a clear role for DNMT1 in maintaining the progenitor state in constantly replenished somatic tissues, such as mammalian epidermis, is unknown. Here we show that DNMT1 is essential for epidermal progenitor cell function. DNMT1 protein was found enriched in undifferentiated cells, where it was required to retain proliferative stamina and suppress differentiation. In tissue, DNMT1 depletion led to exit from the progenitor cell compartment, premature differentiation and eventual tissue loss. Genome-wide analysis revealed that a significant portion of epidermal differentiation gene promoters were methylated in self-renewing conditions but were subsequently demethylated during differentiation. Furthermore, we show that UHRF1,9,10 a component of the DNA methylation machinery that targets DNMT1 to hemi-methylated DNA, is also necessary to suppress premature differentiation and sustain proliferation. In contrast, Gadd45A11,12 and B13, which promote active DNA demethylation, are required for full epidermal differentiation gene induction. These data demonstrate that proteins involved in the dynamic regulation of DNA methylation patterns are required for progenitor maintenance and self-renewal in mammalian somatic tissue. PMID:20081831

Somatization: the under-recognized factor in nonspecific eczema. The Hordaland Health Study (HUSK).

PubMed

Klokk, M; Stansfeld, S; Overland, S; Wilhelmsen, I; Gotestam, K G; Steinshamn, S; Mykletun, A

2011-03-01

Psychodermatology has focused primarily on depression and anxiety in eczema. Skin symptoms are listed among many others for the ICD-10 diagnosis of somatization disorder. Somatization (unexplained somatic symptoms) is highly prevalent in the general population, but its association with eczema is yet to be empirically investigated. We therefore explored the association between somatization and eczema by examining the extent of somatization in eczema compared with allergic rhinitis, and by examining if eczema was more strongly associated with somatization than with anxiety and depression. Finally, we aimed to examine the relationship between the site of eczema and somatization for individual somatic symptoms and for somatic symptoms as a whole. For this population-based cross-sectional study we employed data from the Hordaland Health Study (HUSK) with 15,225 participants aged 41-48 years. Information on nonspecific eczema, allergic rhinitis, somatization, anxiety, depression and other covariates was obtained by self-report. The association between nonspecific eczema and somatization was strong and followed a dose-response pattern, as did all somatic symptoms in our index of somatization when analysed separately. The association between nonspecific eczema and somatization was stronger than that between rhinitis and somatization, and also the association between nonspecific eczema and anxiety and depression. In multivariate models, somatization accounted for most of the association between nonspecific eczema and anxiety/depression. In contrast, the association between nonspecific eczema and somatization was robust for adjustment for anxiety/depression. Somatization was strongly associated with nonspecific eczema. This applies to a whole range of somatic symptoms constituting the construct of somatization. There is hardly any mention of somatization in leading dermatological journals, in contrast to anxiety and depression which are frequently reported in eczema. We speculate that this under-recognition of somatization in the dermatological literature may correspond to under-recognition of this factor also in clinical practice. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Child behavior check list and Korean personality inventory for children with functional visual loss.

PubMed

Kyung, Sung Eun; Lee, Sang Mi; Lim, Myung Ho

2014-08-01

To investigate the clinical psychiatric characteristics of children with the main complaint of functional visual loss, their behavior and personality were evaluated by the means of the Korean child behavior check list (K-CBCL), and the Korean personality inventory for children (KPI-C). The evaluation was carried out by the K-CBCL and the KPI-C, the domestically standardized tools, with 20 child subjects suspected of functional visual loss, among the patients who visited our hospital, between August, 2005 and December, 2012. The control group included 160 children in general schools of the same region. The 20 patients whose main complaint was functional visual loss were diagnosed as having a functional visual disorder. The child patient group showed a higher score for the K-CBCL and KPI-C sub-scales of somatic complaints, social problems, aggressive behavior, internalizing problems, externalizing problems, total behavioral problems, somatization and hyperactivity, than that of the control group. The results of the K-CBCL and KPI-C tests among children with functional visual loss, were significantly different from those of the normal control group. This result suggested that psychological factors may influence children with a main complaint of functional visual loss.

Health symptoms during midlife in relation to menopausal transition: British prospective cohort study

PubMed Central

Kuh, Diana

2012-01-01

Objective To characterise symptoms experienced by women during the transition into natural menopause, to classify women into distinct symptom profiles or trajectories, and to relate these profiles to sociodemographic factors and health behaviours. Design Nationally representative cohort study. Setting England, Scotland, and Wales. Participants 695 women followed-up since birth in 1946 and annually from age 47 to 54 who experienced natural menopause and reported on 20 common health symptoms. Main outcome measure Longitudinal profiles for reported bothersome symptoms. Results Of 20 individual symptoms, 18 formed into four stable symptom groups: psychological, somatic, vasomotor, and sexual discomfort. Using latent class analyses, all except the somatic group of symptoms showed a clear relation with the timing of menopause for some women. A small proportion of women (10%, n=63) had a severe psychological symptom profile that peaked at or in the year after menopause. For vasomotor symptoms, 14% of women (n=83) had the early severe profile that also peaked around early postmenopause and then declined noticeably; 11% (n=67) had the late severe profile of bothersome symptoms that increased rapidly in perimenopause and remained high for four years or more after menopause. Women were less likely to have a profile for severe vasomotor symptoms if they were from a non-manual social class (odds ratio 0.79, 95% confidence interval 0.57 to 1.01) or had degree level qualifications (0.37, 0.18 to 0.77). The 14% of women (n=85) who had the late severe profile for sexual discomfort showed a similar increase in symptoms until menopause, with symptoms persisting after menopause. Married women were more likely to have the late severe or late moderate profile than women of other marital status (2.40, 1.30 to 4.41). Four profiles each were identified for somatic symptoms (mild, moderate, severe, and very severe), although these did not vary by chronological age or age at menopause. Conclusion Profiles for psychological, vasomotor, and sexual discomfort symptoms relative to age at menopause could help health professionals to tailor their advice for women with natural menopause. PMID:22318435

Functional decline and herpes zoster in older people: an interplay of multiple factors.

PubMed

2015-12-01

Herpes zoster is a frequent painful infectious disease whose incidence and severity increase with age. In older people, there is a strong bidirectional link between herpes zoster and functional decline, which refers to a decrement in ability to perform activities of daily living due to ageing and disabilities. However, the exact nature of such link remains poorly established. Based on the opinion from a multidisciplinary group of experts, we here propose a new model to account for the interplay between infection, somatic/psychiatric comorbidity, coping skills, polypharmacy, and age, which may account for the functional decline related to herpes zoster in older patients. This model integrates the risk of decompensation of underlying disease; the risk of pain becoming chronic (e.g. postherpetic neuralgia); the risk of herpes zoster non-pain complications; the detrimental impact of herpes zoster on quality of life, functioning, and mood; the therapeutic difficulties due to multimorbidity, polypharmacy, and ageing; and the role of stressful life events in the infection itself and comorbid depression. This model underlines the importance of early treatment, strengthening coping, and vaccine prevention.

Diagnostic criteria for psychosomatic research and somatic symptom disorders.

PubMed

Sirri, Laura; Fava, Giovanni A

2013-02-01

The Diagnostic Criteria for Psychosomatic Research (DCPR) were introduced in 1995 by an international group of investigators to expand the traditional domains of the disease model. The DCPR are a set of 12 'psychosomatic syndromes' which provide operational tools for psychosocial variables with prognostic and therapeutic implications in clinical settings. Eight syndromes concern the main manifestations of abnormal illness behaviour: somatization, hypochondriacal fears and beliefs, and illness denial. The other four syndromes (alexithymia, type A behaviour, demoralization and irritable mood) refer to the domain of psychological factors affecting medical conditions. This review describes the conceptual bases of the DCPR and the main findings concerning their application, with particular reference to the incremental information they added to the customary psychiatric classification. The DCPR were also compared with the provisional DSM-5 somatic symptom disorders. The DCPR were found to be more sensitive than DSM-IV in identifying subthreshold psychological distress and characterizing patients' psychological response to medical illness. DSM-5 somatic symptom disorders seem to neglect important clinical phenomena, such as illness denial, resulting in a narrow view of patients' functioning. The additional information provided by the DCPR may enhance the decision-making process.

The critical role of psychosomatics in promoting a new perspective upon health and disease.

PubMed

Dragoş, Dorin; Tănăsescu, Maria Daniela

2009-01-01

In an evolutionary model, health and disease are regarded as successful and respectively failed adaptation to the demands of the environment. The social factors are critical for a successful adaptation, while emotions are means of both signaling the organism's state and of adapting the physiological responses to environmental challenges. Hence the importance of a biopsychosocial model of health and disease. Psychoemotional distress generates and/or amplifies somatic symptoms. Somatization may be viewed as an altered cognitive process, inclining the individual to an augmented perception of bodily sensations and to an increased degree of complexity in reporting negative experiences (hence the greater cognitive effort allocated thereto). Somatosensory amplification and alexithymia are key elements in this process. The brain's right hemisphere is more involved in the generation of emotionally conditioned somatization symptoms. Somatic symptoms have various psychological and social functions and are strongly influenced by the particular belief system of the individual. Inappropriately perceiving the environment as an aggressor and excessively responding to it (by activating the cytokine system in correlation with the arousal of the psychic, nervous, and endocrine systems) may be a key element in the altered cognition conducive to ill health.

[The correlations of somatic, dermatoglyphic and psychological characteristics in the structure of general human constitution from the standpoint of systemic approach].

PubMed

Negasheva, M A

2008-01-01

669 young men and women aged 16-23 years were examined using a program including the measurements of 40 body, head and face parameters, fingerprinting and determination of personal psychological characteristics. On the basis of the study of the correlations between the different groups of characteristics, the evidence was obtained that supports the concept of a relative autonomy of the morpho-functional systems as an essential condition for the integrity of the organism as a whole. The coefficients of canonical correlation were calculated between the somatic and dermatoglyphic features (R=0.3), somatic sizes and psychological personality characteristics (R=0.4), psychological characteristics and the dermatoglyphic indices (R=0.4). An original model is suggested that describes the correlations of somatic, dermatoglyphic and psychological features in the structure of general human constitution on the basis of statistically significant canonical correlations (revealed by the author) and that takes in consideration the degree of the influence of genetic and social-economic complex of factors (on the basis of the literature data) on the development and formation of the investigated systems of characteristics.

The Effects of Attention Problems on Psychosocial Functioning in Childhood Brain Tumor Survivors: A 2-Year Postcraniospinal Irradiation Follow-up.

PubMed

Oh, Yunhye; Seo, Hyunjung; Sung, Ki Woong; Joung, Yoo Sook

2017-03-01

To examine the psychosocial outcomes and impact of attention problems in survivors of pediatric brain tumor. The survivors' cognitive functioning was measured using the Wechsler Intelligence Scale for Children. The Child Behavior Checklist-Attention Problems scale was used to screen for attention problems, and participants were classified as having attention problems (n=15) or normal attention (n=36). Psychosocial functioning was examined with the Korean Personality Rating scale for Children (K-PRC) at precraniospinal radiation and at 2-year follow-up. The attention problem group showed significantly higher depression and externalizing symptoms (delinquency, hyperactivity) and more significant impairment in family relationships than did the normal attention group at baseline. At follow-up, the attention problem group demonstrated significantly more delinquency and impaired family and social relationships. With the K-PRC scores, except for the somatization, social relationship subscale, there were significant differences between groups, but not in terms of treatment by time interaction or within time. At follow-up, multiple linear regressions showed that age at diagnosis significantly predicted K-PRC somatization (B=-1.7, P=0.004) and social relationships (B=-1.7, P=0.004), baseline full-scale intelligence quotient predicted K-PRC depression (B=-0.4, P=0.032) and somatization (B=-0.3, P=0.015), and attention problems at baseline predicted K-PRC depression (B=-15.2, P=0.036) and social relationships (B=-11.6, P=0.016). Pediatric brain tumor survivors, in particular, patients with attention problems, had worse psychosocial functioning at baseline and follow-up. Attention problems at baseline need to be carefully evaluated in assessing psychosocial functioning of pediatric brain tumor survivors.

Brief Report: Late-Onset Cryopyrin-Associated Periodic Syndrome Due to Myeloid-Restricted Somatic NLRP3 Mosaicism.

PubMed

Mensa-Vilaro, Anna; Teresa Bosque, María; Magri, Giuliana; Honda, Yoshitaka; Martínez-Banaclocha, Helios; Casorran-Berges, Marta; Sintes, Jordi; González-Roca, Eva; Ruiz-Ortiz, Estibaliz; Heike, Toshio; Martínez-Garcia, Juan J; Baroja-Mazo, Alberto; Cerutti, Andrea; Nishikomori, Ryuta; Yagüe, Jordi; Pelegrín, Pablo; Delgado-Beltran, Concha; Aróstegui, Juan I

2016-12-01

Gain-of-function NLRP3 mutations cause cryopyrin-associated periodic syndrome (CAPS), with gene mosaicism playing a relevant role in the pathogenesis. This study was undertaken to characterize the genetic cause underlying late-onset but otherwise typical CAPS. We studied a 64-year-old patient who presented with recurrent episodes of urticaria-like rash, fever, conjunctivitis, and oligoarthritis at age 56 years. DNA was extracted from both unfractionated blood and isolated leukocyte and CD34+ subpopulations. Genetic studies were performed using both the Sanger method of DNA sequencing and next-generation sequencing (NGS) methods. In vitro and ex vivo analyses were performed to determine the consequences that the presence of the variant have in the normal structure or function of the protein of the detected variant. NGS analyses revealed the novel p.Gln636Glu NLRP3 variant in unfractionated blood, with an allele frequency (18.4%) compatible with gene mosaicism. Sanger sequence chromatograms revealed a small peak corresponding to the variant allele. Amplicon-based deep sequencing revealed somatic NLRP3 mosaicism restricted to myeloid cells (31.8% in monocytes, 24.6% in neutrophils, and 11.2% in circulating CD34+ common myeloid progenitor cells) and its complete absence in lymphoid cells. Functional analyses confirmed the gain-of-function behavior of the gene variant and hyperactivity of the NLRP3 inflammasome in the patient. Treatment with anakinra resulted in good control of the disease. We identified the novel gain-of-function p.Gln636Glu NLRP3 mutation, which was detected as a somatic mutation restricted to myeloid cells, as the cause of late-onset but otherwise typical CAPS. Our results expand the diversity of CAPS toward milder phenotypes than previously reported, including those starting during adulthood. © 2016, American College of Rheumatology.

Is psychotherapy for functional somatic syndromes harmful? A mixed methods study on negative effects.

PubMed

Holsting, A F; Pedersen, H F; Rask, M T; Frostholm, L; Schröder, A

2017-07-01

Concern for negative effects of psychotherapy for functional somatic syndromes (FSS) has been expressed by clinicians and some patient associations, which may prevent patients from seeking treatment. Therefore, we sought to explore the occurrence and characteristics of negative effects from group-based psychotherapy as experienced by patients with severe or multiple FSS. An adapted version of the explanatory sequential mixed methods design was applied. We used data from an on-going pilot study on Acceptance and Commitment Therapy and Mindfulness-Based Stress Reduction. Negative effects were measured by Inventory for the assessment of Negative Effects of Psychotherapy (INEP). In addition, telephone interviews were conducted with randomly chosen patients and patients who reported negative effects. The latter were asked to elaborate on their INEP response. Quantitative data were analysed descriptively while interview transcripts were explored by thematic analysis. Eighty patients responded to the questionnaire (89%). Negative effects to different extent (from 'slightly agree' to 'fully agree') were reported by 25 (31%). The most frequent negative effects were dependence on the therapist (12%), feeling down after therapy (6%) and insurance problems (7%). By exploring 27 participants' experiences of negative effects 3 main themes were identified: relations in therapy, outcome and transition from therapy to everyday life. Patients with FSS reported a few specific negative effects, all with low frequency. Generally, therapy was well-received. Some patients did however express negative effects both within and outside the therapeutic context. It is important to inform patients about potential negative effects prior to psychotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional Nausea in Children: A Review of the Literature and Need for Diagnostic Criteria

PubMed Central

Russell, Alexandra C.; Stone, Amanda L.; Walker, Lynn S.

2016-01-01

Nausea is common amongst children with functional gastrointestinal disorders and is associated with a high burden of somatic and psychosocial comorbidities in both the short and long-term. Current treatments including medications, phytotherapy, stress-reduction techniques, and gastric electrical stimulation for recalcitrant cases, are reviewed. Functional nausea merits its own diagnostic criteria as a pediatric functional gastrointestinal disorder. PMID:27417243

THE MOLECULAR PATHOLOGY OF MELANOMA: AN INTEGRATED TAXONOMY OF MELANOCYTIC NEOPLASIA

PubMed Central

Bastian, Boris C.

2016-01-01

Melanomas are comprised of multiple biologically distinct categories, which differ in cell of origin, age of onset, clinical and histologic presentation, pattern of metastasis, ethnic distribution, causative role of UV radiation, predisposing germ line alterations, mutational processes, and patterns of somatic mutations. Neoplasms are initiated by gain of function mutations in one of several primary oncogenes, typically leading to benign melanocytic nevi with characteristic histologic features. The progression of nevi is restrained by multiple tumor suppressive mechanisms. Secondary genetic alterations override these barriers and promote intermediate or overtly malignant tumors along distinct progression trajectories. The current knowledge about pathogenesis, clinical, histological and genetic features of primary melanocytic neoplasms is reviewed and integrated into a taxonomic framework. PMID:24460190

Developmental characteristics of somatic cell hybrids between totipotent mouse teratocarcinoma and rat intestinal villus cells.

PubMed

van der Kamp, A W; Roza-de Jongh, E J; Houwen, R H; Magrane, G G; van Dongen, J M; Evans, M J

1984-09-01

Hybrids between mouse PCC4-azal teratocarcinoma cells and rat epithelial intestinal villus cells (PCI hybrids) are phenotypically teratocarcinoma cells. They express several teratocarcinoma-specific traits but do not express functions specific for differentiated cells. Tumour formation is partially or completely suppressed. Some of the hybrids show more extensive differentiation both in vitro and in vivo than the PCC4-azal parental line. The hybrids are capable of endoderm formation in monolayer cultures and of the formation of embryoid bodies in suspension cultures. Two of the tumour-forming hybrids generate derivatives of all three germ layers, whereas differentiation in the PCC4-azal tumours is restricted to the formation of primitive neuronal tissues.

ANXIETY AS A RISK FACTOR FOR MENOPAUSAL HOT FLASHES: EVIDENCE FROM THE PENN OVARIAN AGING COHORT

PubMed Central

Freeman, Ellen W.; Sammel, Mary D.

2016-01-01

Objective The aim of this study was to identify temporal associations of anxiety dimensions with menopausal hot flashes in women progressing through the menopause transition. We hypothesized that associations of both somatic and affective dimensions of anxiety with hot flashes increased in the menopause transition, and that somatic anxiety was an independent risk factor for menopausal hot flashes. Methods Hot flashes, anxiety symptoms, hormone levels and other psychosocial variables were assessed annually for 14 years of follow-up. The 233 women were premenopausal at baseline and continued through one year or more after the final menstrual period. Anxiety dimensions were assessed with the Zung Anxiety Scale (ZAS), a validated measure of affective anxiety and somatic anxiety. Summed item scores were divided by the number of items rated, so that ranges of the two dimensions were comparable. Results Seventy-two percent of the sample reported moderate/severe hot flashes during the 14-year interval. There was no significant interaction between anxiety dimensions and menopausal stages. However, when adjusted for menopausal stage, the magnitude of association between somatic anxiety and hot flashes dramatically increased (OR 3.03, 95% CI: 2.12, 4.32, P<0.001), while the association between affective anxiety and hot flashes increased to a lesser extent (OR 1.27, 95% CI: 1.03, 1.57, P=0.024). Women with high levels of somatic anxiety (top third of the sample) had the greatest risk of hot flashes (P<0.001). When the anxiety dimensions were considered in combination, the additive effect of high affective anxiety symptoms was minimal, with no significant difference between the group with high affective/low somatic symptoms and the low symptom group in incident hot flashes at each menopausal stage (P=0.54). In multivariable analysis, somatic anxiety increased the risk of hot flashes more than 3 times (OR 3.13, 95% CI: 2.16, 4.53, P<0.001), but affective anxiety was not significantly associated with hot flashes after adjustment for other study variables (OR 1.19, 95% CI: 0.96, 1.48, P=0.117). Time-lagged somatic anxiety scores significantly predicted hot flashes, with a 71% increase in risk (OR 1.71, 95% CI: 1.21, 2.41, P=0.002). Time-lagged affective anxiety scores did not predict hot flashes, (OR 1.06, 95% CI: 0.87, 1.31, P=0.58). Conclusions This study showed a strong predictive association of somatic anxiety with the risk of menopausal hot flashes. The temporal associations suggest that somatic anxiety is not simply a redundant measure of hot flashes but predicts the risk of menopausal hot flashes and may be a potential target in clinical management of perimenopausal women. PMID:27433864

Transposable elements at the center of the crossroads between embryogenesis, embryonic stem cells, reprogramming, and long non-coding RNAs.

PubMed

Hutchins, Andrew Paul; Pei, Duanqing

Transposable elements (TEs) are mobile genomic sequences of DNA capable of autonomous and non-autonomous duplication. TEs have been highly successful, and nearly half of the human genome now consists of various families of TEs. Originally thought to be non-functional, these elements have been co-opted by animal genomes to perform a variety of physiological functions ranging from TE-derived proteins acting directly in normal biological functions, to innovations in transcription factor logic and influence on epigenetic control of gene expression. During embryonic development, when the genome is epigenetically reprogrammed and DNA-demethylated, TEs are released from repression and show embryonic stage-specific expression, and in human and mouse embryos, intact TE-derived endogenous viral particles can even be detected. A similar process occurs during the reprogramming of somatic cells to pluripotent cells: When the somatic DNA is demethylated, TEs are released from repression. In embryonic stem cells (ESCs), where DNA is hypomethylated, an elaborate system of epigenetic control is employed to suppress TEs, a system that often overlaps with normal epigenetic control of ESC gene expression. Finally, many long non-coding RNAs (lncRNAs) involved in normal ESC function and those assisting or impairing reprogramming contain multiple TEs in their RNA. These TEs may act as regulatory units to recruit RNA-binding proteins and epigenetic modifiers. This review covers how TEs are interlinked with the epigenetic machinery and lncRNAs, and how these links influence each other to modulate aspects of ESCs, embryogenesis, and somatic cell reprogramming.

Somatic and Reinforcement-Based Plasticity in the Initial Stages of Human Motor Learning.

PubMed

Sidarta, Ananda; Vahdat, Shahabeddin; Bernardi, Nicolò F; Ostry, David J

2016-11-16

As one learns to dance or play tennis, the desired somatosensory state is typically unknown. Trial and error is important as motor behavior is shaped by successful and unsuccessful movements. As an experimental model, we designed a task in which human participants make reaching movements to a hidden target and receive positive reinforcement when successful. We identified somatic and reinforcement-based sources of plasticity on the basis of changes in functional connectivity using resting-state fMRI before and after learning. The neuroimaging data revealed reinforcement-related changes in both motor and somatosensory brain areas in which a strengthening of connectivity was related to the amount of positive reinforcement during learning. Areas of prefrontal cortex were similarly altered in relation to reinforcement, with connectivity between sensorimotor areas of putamen and the reward-related ventromedial prefrontal cortex strengthened in relation to the amount of successful feedback received. In other analyses, we assessed connectivity related to changes in movement direction between trials, a type of variability that presumably reflects exploratory strategies during learning. We found that connectivity in a network linking motor and somatosensory cortices increased with trial-to-trial changes in direction. Connectivity varied as well with the change in movement direction following incorrect movements. Here the changes were observed in a somatic memory and decision making network involving ventrolateral prefrontal cortex and second somatosensory cortex. Our results point to the idea that the initial stages of motor learning are not wholly motor but rather involve plasticity in somatic and prefrontal networks related both to reward and exploration. In the initial stages of motor learning, the placement of the limbs is learned primarily through trial and error. In an experimental analog, participants make reaching movements to a hidden target and receive positive feedback when successful. We identified sources of plasticity based on changes in functional connectivity using resting-state fMRI. The main finding is that there is a strengthening of connectivity between reward-related prefrontal areas and sensorimotor areas in the basal ganglia and frontal cortex. There is also a strengthening of connectivity related to movement exploration in sensorimotor circuits involved in somatic memory and decision making. The results indicate that initial stages of motor learning depend on plasticity in somatic and prefrontal networks related to reward and exploration. Copyright © 2016 the authors 0270-6474/16/3611682-11$15.00/0.

Somatic and Reinforcement-Based Plasticity in the Initial Stages of Human Motor Learning

PubMed Central

Sidarta, Ananda; Vahdat, Shahabeddin; Bernardi, Nicolò F.

2016-01-01

As one learns to dance or play tennis, the desired somatosensory state is typically unknown. Trial and error is important as motor behavior is shaped by successful and unsuccessful movements. As an experimental model, we designed a task in which human participants make reaching movements to a hidden target and receive positive reinforcement when successful. We identified somatic and reinforcement-based sources of plasticity on the basis of changes in functional connectivity using resting-state fMRI before and after learning. The neuroimaging data revealed reinforcement-related changes in both motor and somatosensory brain areas in which a strengthening of connectivity was related to the amount of positive reinforcement during learning. Areas of prefrontal cortex were similarly altered in relation to reinforcement, with connectivity between sensorimotor areas of putamen and the reward-related ventromedial prefrontal cortex strengthened in relation to the amount of successful feedback received. In other analyses, we assessed connectivity related to changes in movement direction between trials, a type of variability that presumably reflects exploratory strategies during learning. We found that connectivity in a network linking motor and somatosensory cortices increased with trial-to-trial changes in direction. Connectivity varied as well with the change in movement direction following incorrect movements. Here the changes were observed in a somatic memory and decision making network involving ventrolateral prefrontal cortex and second somatosensory cortex. Our results point to the idea that the initial stages of motor learning are not wholly motor but rather involve plasticity in somatic and prefrontal networks related both to reward and exploration. SIGNIFICANCE STATEMENT In the initial stages of motor learning, the placement of the limbs is learned primarily through trial and error. In an experimental analog, participants make reaching movements to a hidden target and receive positive feedback when successful. We identified sources of plasticity based on changes in functional connectivity using resting-state fMRI. The main finding is that there is a strengthening of connectivity between reward-related prefrontal areas and sensorimotor areas in the basal ganglia and frontal cortex. There is also a strengthening of connectivity related to movement exploration in sensorimotor circuits involved in somatic memory and decision making. The results indicate that initial stages of motor learning depend on plasticity in somatic and prefrontal networks related to reward and exploration. PMID:27852776

Experimental immunization of ponies with Strongylus vulgaris radiation-attenuated larvae or crude soluble somatic extracts from larval or adult stages.

PubMed

Monahan, C M; Taylor, H W; Chapman, M R; Klei, T R

1994-12-01

Protection from Strongylus vulgaris infection through immunization with radiation-attenuated third-stage larvae (L3) or crude soluble homogenates from larval or adult stages was examined. Yearling ponies raised parasite-free were divided into 3 immunization groups: radiation-attenuated L3; soluble adult somatic extracts; larval somatic extracts with excretory/secretory products (E/S) from in vitro culture; and 1 medium control group. Ponies were immunized twice; attenuated larvae were administered orally and somatic extracts or controls injected intramuscularly with adjuvant. Approximately 6 wk following the second immunization, all ponies were challenged. Necrospy examinations were performed 6 wk following challenge. Irradiated larvae recipients had the fewest postchallenge clinical signs and lesions and were 91% protected from infection determined by larval recoveries from arterial dissections. Soluble antigen recipients and controls had similar larval recoveries and thus equal susceptibility to challenge. Soluble antigen recipients had more severe clinical signs and lesions than controls, suggesting that parenteral immunization exacerbated postchallenge inflammatory responses. Protection by immunization with irradiated larvae was associated with an anamnestic eosinophilia and postimmunization antibody recognition of S. vulgaris L3 surface antigens. Histologic staining of eosinophils within tissues of this group suggested that this immunization induced a cytophilic antibody response that facilitated degranulation.

Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations

PubMed Central

Bianchi-Frias, Daniella; Basom, Ryan; Delrow, Jeffrey J; Coleman, Ilsa M; Dakhova, Olga; Qu, Xiaoyu; Fang, Min; Franco, Omar E.; Ericson, Nolan G.; Bielas, Jason H.; Hayward, Simon W.; True, Lawrence; Morrissey, Colm; Brown, Lisha; Bhowmick, Neil A.; Rowley, David; Ittmann, Michael; Nelson, Peter S.

2017-01-01

Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole genome copy number analyses, targeted sequencing of TP53, and fluorescence in situ hybridization. Comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy number aberrations (SCNAs). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, no loss of heterozygosity (LOH) or copy-neutral LOH in cultured cancer-associated fibroblasts (CAFs), which are known to promote prostate cancer progression in vivo. PMID:26753621

Quality of life related to health chronic kidney disease: Predictive importance of mood and somatic symptoms.

PubMed

Perales Montilla, Carmen M; Duschek, Stefan; Reyes Del Paso, Gustavo A

2016-01-01

To compare the predictive capacity of self-reported somatic symptoms and mood (depression and anxiety) on health-related quality of life (HRQOL) in patients with chronic renal disease. Data were obtained from 52 patients undergoing haemodialysis. Measures included a) the SF-36 health survey, b) the somatic symptoms scale revised (ESS-R) and c) the hospital anxiety and depression scale (HADS). Multiple regression was the main method of statistical analysis. Patients exhibited HRQOL levels below normative values, with anxiety and depression prevalence at 36.5% and 27%, respectively. Mood was the strongest predictor of physical (β=-.624) and mental (β=-.709) HRQOL. Somatic symptoms were also associated with physical HRQOL, but their predictive value was weaker (β=-.270). These results indicate that mood is a superior predictor of the physical and mental components of HRQOL in patients compared with the number and severity of physical symptoms. The data underline the importance of assessing negative emotional states (depression and anxiety) in kidney patients as a basis for intervention, which may facilitate reduction of the impact of chronic renal disease on HRQOL. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic symptoms: a longitudinal cohort study in the general population.

PubMed

Tak, Lineke M; Bakker, Stephan J L; Rosmalen, Judith G M

2009-07-01

In persons with functional somatic symptoms (FSS), no conventionally defined organic pathology is apparent. It has been suggested that complex interactions of psychological, physiological, and social factors are involved in the etiology of FSS. One of the physiological mechanisms that may contribute to FSS is the function of the hypothalamic-pituitary-adrenal (HPA)-axis. This study investigates the association of HPA-axis function with cross-sectional presence and prospective development of FSS in the general population. This study was performed in a population-based cohort of 741 male and female adults (mean age 53.1, S.D. 10.9). Participants completed the somatization section of the Composite International Diagnostic Interview (CIDI) in which the presence of 43 FSS is surveyed. In addition to the total number of FSS, bodily system FSS clusters with musculoskeletal, gastrointestinal, cardiorespiratory, and general symptoms were constructed. HPA-axis function was assessed by measuring 24-h urinary free cortisol (24-h UFC) excretion. Follow-up measurements were performed approximately 2 years later. All analyses were adjusted for age, gender, body mass index, smoking, alcohol use, depression, exercise frequency, and urinary volume. Regression analysis detected no cross-sectional association between 24-h UFC excretion and the number of FSS (beta=-0.021, t=-0.521, p=0.603). In addition, 24-h UFC excretion was not associated with any of the bodily system FSS clusters (all p>0.050). Furthermore, 24-h UFC excretion did not predict new-onset FSS in the 2-year follow-up period (beta=0.021, t=0.566, p=0.572). We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population. We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population.

Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins.

PubMed

van den Broek, Walther J A A; Nelen, Marcel R; Wansink, Derick G; Coerwinkel, Marga M; te Riele, Hein; Groenen, Patricia J T A; Wieringa, Bé

2002-01-15

The mechanism of expansion of the (CTG)n repeat in myotonic dystrophy (DM1) patients and the cause of its pathobiological effects are still largely unknown. Most likely, long repeats exert toxicity at the level of nuclear RNA transport or splicing. Here, we analyse cis- and trans-acting parameters that determine repeat behaviour in novel mouse models for DM1. Our mice carry 'humanized' myotonic dystrophy protein kinase (Dmpk) allele(s) with either a (CTG)84 or a (CTG)11 repeat, inserted at the correct position into the endogenous DM locus. Unlike in the human situation, the (CTG)84 repeat in the syntenic mouse environment was relatively stable during intergenerational segregation. However, somatic tissues showed substantial repeat expansions which were progressive upon aging and prominent in kidney, and in stomach and small intestine, where it was cell-type restricted. Other tissues examined showed only marginal size changes. The (CTG)11 allele was completely stable, as anticipated. Introducing the (CTG)84 allele into an Msh3-deficient background completely blocked the somatic repeat instability. In contrast, Msh6 deficiency resulted in a significant increase in the frequency of somatic expansions. Competition of Msh3 and Msh6 for binding to Msh2 in functional complexes with different DNA mismatch-recognition specificity may explain why the somatic (CTG)n expansion rate is differentially affected by ablation of Msh3 and Msh6.

Brief Cognitive-Behavioral Treatment for TMD Pain: Long-Term Outcomes and Moderators of Treatment

PubMed Central

Litt, Mark D.; Shafer, David M.; Kreutzer, Donald L.

2010-01-01

The purpose of this study was to determine whether a brief (6–8 sessions) cognitive-behavioral treatment for temporomandibular dysfunction-related pain could be efficacious in reducing pain, pain-related interference with lifestyle and depressive symptoms. The patients were 101 men and women with pain in the area of the temporomandibular joint of at least 3 months duration, randomly assigned to either Standard Treatment (STD; n=49) or to Standard Treatment + Cognitive-Behavioral skills training (STD+CBT; n=52). Patients were assessed at posttreatment (6 weeks), 12 weeks, 24 weeks, 36 weeks, and 52 weeks. Linear mixed model analyses of reported pain indicated that both treatments yielded significant decreases in pain, with the STD+CBT condition resulting in steeper decreases in pain over time compared to the STD condition. Somatization, self-efficacy and readiness for treatment emerged as significant moderators of outcome, such that those low in somatization, or higher in self-efficacy or readiness, and treated with STD+CBT reported lower pain over time. Somatization was also a significant moderator of treatment effects on pain-related interference with functioning, with those low on somatization reporting less pain interference over time when treated in the STD+CBT condition. It was concluded that brief treatments can yield significant reductions in pain, life interference and depressive symptoms in TMD sufferers, and that the addition of cognitive-behavioral coping skills will add to efficacy, especially for those low in somatization, or high in readiness or self-efficacy. PMID:20655662

Somatic symptoms of generalized anxiety disorder from the DSM-IV: associations with pathological worry and depression symptoms in a nonclinical sample.

PubMed

Joormann, J; Stöber, J

1999-01-01

The present study investigates specificity of the six somatic symptoms that are associated with generalized anxiety disorder (GAD), according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. A nonclinical sample of 183 students provided severity ratings for (a) restlessness, (b) easily fatigued, (c) difficulty concentrating, (d) irritability, (e) muscle tension, and (f) sleep disturbance. In addition, they responded to questionnaires assessing pathological worry and depression symptoms. Partial correlations and multiple regression analyses indicated that only muscle tension showed a unique relation to pathological worry. In contrast, difficulty concentrating was exclusively related to depression symptoms. Present findings corroborate psychophysiological findings that elevated muscle tension is a specific characteristic of pathological worriers. Moreover, they suggest that the problem of unclear boundaries between GAD and major depression may be reduced if future revisions of the somatic symptom list for GAD emphasize muscle tension while de-emphasizing difficulty concentrating.

An Overview of Direct Somatic Reprogramming: The Ins and Outs of iPSCs

PubMed Central

Menon, Siddharth; Shailendra, Siny; Renda, Andrea; Longaker, Michael; Quarto, Natalina

2016-01-01

Stem cells are classified into embryonic stem cells and adult stem cells. An evolving alternative to conventional stem cell therapies is induced pluripotent stem cells (iPSCs), which have a multi-lineage potential comparable to conventionally acquired embryonic stem cells with the additional benefits of being less immunoreactive and avoiding many of the ethical concerns raised with the use of embryonic material. The ability to generate iPSCs from somatic cells provides tremendous promise for regenerative medicine. The breakthrough of iPSCs has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. iPSCs are also relevant tools for modeling human diseases and drugs screening. However, there are still several hurdles to overcome before iPSCs can be used for translational purposes. Here, we review the recent advances in somatic reprogramming and the challenges that must be overcome to move this strategy closer to clinical application. PMID:26805822

Acceptance and commitment group therapy for health anxiety--results from a pilot study.

PubMed

Eilenberg, T; Kronstrand, L; Fink, P; Frostholm, L

2013-06-01

Health anxiety (or hypochondriasis) is prevalent, may be persistent and disabling for the sufferers and associated with high societal costs. Acceptance and Commitment Therapy (ACT) is a new third-wave behavioral cognitive therapy that has not yet been tested in health anxiety. 34 consecutive Danish patients with severe health anxiety were referred from general practitioners or hospital departments and received a ten-session ACT group therapy. Patients were followed up by questionnaires for 6 months. There were significant reductions in health anxiety, somatic symptoms and emotional distress at 6 months compared to baseline: a 49% reduction in health anxiety (Whiteley-7 Index), a 47% decrease in emotional distress (SCL-8), and a 40% decrease in somatic symptoms (SCL-90R Somatization Subscale). The patients' emotional representations and perception of the consequences of their illness (IPQ) improved significantly, and 87% of the patients were very or extremely satisfied with the treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bridging the divide

PubMed Central

McLean, Peter F; Cooley, Lynn

2014-01-01

Ring canals are made from arrested cleavage furrows, and provide direct cytoplasmic connections among sibling cells. They are well documented for their participation in Drosophila oogenesis, but little is known about their role in several somatic tissues in which they are also found. Using a variety of genetic tools in live and fixed tissue, we recently demonstrated that rapid intercellular exchange occurs through somatic ring canals by diffusion, and presented evidence that ring canals permit equilibration of protein among transcriptionally mosaic cells. We also used a novel combination of markers to evaluate the extent of protein movement within and across mitotic clones in follicle cells and imaginal discs, providing evidence of robust movement of GFP between the 2 sides of mitotic clones and frequently into non-recombined cells. These data suggest that, depending on the experimental setup and proteins of interest, inter-clonal diffusion of protein may alter the interpretation of clonal data in follicle cells. Here, we discuss these results and provide additional insight into the impact of ring canals in Drosophila somatic tissues. PMID:24406334

Investigating the psychological impact of bank robbery: a cohort study.

PubMed

Hansen, Maj; Armour, Cherie; Shevlin, Mark; Elklit, Ask

2014-06-01

Despite numerous annual bank robberies worldwide, research in the psychological sequelae of bank robberies is sparse and characterized by several limitations. To overcome these limitations we investigated the psychological impact of bank robbery in a cohort study by comparing general levels of traumatization and somatization in employees never exposed to robbery and employees exposed to robbery at different degrees and time-points, while controlling for selected risk factors of posttraumatic distress. Multivariate regression analyses showed that only the acute directly exposed robbery group which had a significantly higher score on general traumatization and somatization compared to the control group whilst controlling for other factors. In conclusion, bank robbery exposure appears to be especially associated with psychological distress in the acute phase and in victims present during the robbery. After the acute phase, other factors appear more important in predicting general traumatization and somatization in bank employees compared to exposure to robbery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Epitranscriptomics: A New Regulatory Mechanism of Brain Development and Function

PubMed Central

Noack, Florian; Calegari, Federico

2018-01-01

Epigenetic modifications of DNA and chromatin are long known to control stem cell differentiation and organ function but the role of similar modifications at the level or regulatory RNAs is just beginning to emerge. Over 160 RNA modifications have been identified but their abundance, distribution and functional significance are not known. The few available maps of RNA modifications indicated their dynamic regulation during somatic stem cell differentiation, brain development and function in adulthood suggesting a hitherto unsuspected layer of regulation both at the level of RNA metabolism and post-transcriptional control of gene expression. The advent of programmable, RNA-specific CRISPR-Cas editing platforms together with the identification of RNA modifying enzymes now offers the opportunity to investigate the functional role of these elusive epitranscriptome changes. Here, we discuss recent insights in studying the most abundant modifications in functional mRNAs and lncRNAs, N6-methyladenosine and 5-(hydroxy-)methylcytosine, and their role in regulating somatic stem cell differentiation with particular attention to neural stem cells during mammalian corticogenesis. An outlook on novel CRISPR-Cas based systems that allow stem cell reprogramming by epitranscriptome-editing will also be discussed. PMID:29515357

Dysfunctional illness perception and illness behaviour associated with high somatic symptom severity and low quality of life in general hospital outpatients in China.

PubMed

Zhang, Yaoyin; Fritzsche, Kurt; Leonhart, Rainer; Zhao, Xudong; Zhang, Lan; Wei, Jing; Yang, Jianzhong; Wirsching, Michael; Nater-Mewes, Ricarda; Larisch, Astrid; Schaefert, Rainer

2014-09-01

In primary care populations in Western countries, high somatic symptom severity (SSS) and low quality of life (QoL) are associated with adverse psychobehavioural characteristics. This study assessed the relationship between SSS, QoL and psychobehavioural characteristics in Chinese general hospital outpatients. This multicentre cross-sectional study enrolled 404 patients from 10 outpatient departments, including Neurology, Gastroenterology, Traditional Chinese Medicine [TCM] and Psychosomatic Medicine departments, in Beijing, Shanghai, Chengdu and Kunming. A structured interview was used to assess the cognitive, affective and behavioural features associated with somatic complaints, independent of their origin. Several standard instruments were used to assess SSS, emotional distress and health-related QoL. Patients who reported low SSS (PHQ-15<10, n=203, SOM-) were compared to patients who reported high SSS (PHQ-15≥10, n=201, SOM+). As compared to SOM- patients, SOM+ patients showed significantly more frequently adverse psychobehavioural characteristics in all questions of the interview. In hierarchical linear regression analyses adjusted for anxiety, depression, gender and medical conditions (SSS additionally for doctor visits), high SSS was significantly associated with "catastrophising" and "illness vulnerability"; low physical QoL was associated with "avoidance of physical activities" and "disuse of body parts"; low mental QoL was associated with "need for immediate medical help." In accordance with the results from Western countries, high SSS was associated with negative illness and self-perception, low physical QoL with avoidance behaviour, and low mental QoL with reassurance seeking in Chinese general hospital outpatients. Copyright © 2014 Elsevier Inc. All rights reserved.

Is somatic comorbidity associated with more somatic symptoms, mental distress, or unhealthy lifestyle in elderly cancer survivors?

PubMed

Grov, Ellen Karine; Fosså, Sophie D; Dahl, Alv A

2009-06-01

The associations of lifestyle factors, somatic symptoms, mental distress, and somatic comorbidity in elderly cancer survivors have not been well studied. This study examines these associations among elderly cancer survivors (age >or=65 years) in a population-based sample. A cross-sectional comparative study of Norwegian elderly cancer survivors. Combining information from The Norwegian Cancer Registry, and by self-reporting, 972 elderly cancer survivors were identified, of whom 632 (65%) had somatic comorbidity and 340 did not. Elderly cancer survivors with somatic comorbidity had significantly higher BMI, more performed minimal physical activity, had more somatic symptoms, used more medication, and had more frequently seen a medical doctor than survivors without somatic comorbidity. In multivariable analyses, unhealthy lifestyle and higher somatic symptoms scores were significantly associated with cancer cases with somatic comorbidity. In univariate analyses those with somatic comorbidity were significantly older, had lower levels of education, higher proportions of BMI >or= 30, less physical activity, poorer self-rated health, higher somatic symptoms score, more mental distress, had more frequently seen a medical doctor last year, and more frequently used daily medication. Our outcome measures of lifestyle, somatic symptoms and mental distress were all significantly associated with somatic comorbidity in elderly cancer survivors, however only lifestyle and somatic symptoms were significant in multivariable analyses. In elderly cancer survivors not only cancer, but also somatic comorbidity, deserve attention. Such comorbidity is associated with unhealthy lifestyles, more somatic symptoms and mental distress which should be evaluated and eventually treated.

Antecedents and mediators of physical activity in endometrial cancer survivors: Increasing physical activity through Steps to Health

PubMed Central

Cox, Matthew; Carmack, Cindy; Hughes, Daniel; Baum, George; Brown, Jubilee; Jhingran, Anuja; Lu, Karen; Basen-Engquist, Karen

2015-01-01

OBJECTIVE Research shows that physical activity (PA) has a positive effect on cancer survivors including improving quality of life, improving physical fitness, and decreasing risk for cancer recurrence in some cancer types. Theory-based intervention approaches have identified self-efficacy as a potential mediator of PA interventions. This study examines the temporal relationships at four time points (T1–T4) between several social cognitive theory constructs and PA among a group of endometrial cancer survivors receiving a PA intervention. METHOD A sample of 98 sedentary women who were at least six months post treatment for endometrial cancer were given an intervention to increase their PA. The study tested whether modeling, physiological somatic sensations, and social support at previous time points predicted self-efficacy at later time points, which in turn predicted PA at later time points. RESULTS Results indicate that as physiological somatic sensations at T2 decrease, self-efficacy at T3 increases, which leads to an increase in PA at T4. This suggests that self-efficacy is a significant mediator between physiological somatic sensations and PA. Exploratory follow up models suggest model fit can be improved with the addition of contemporaneous effects between self-efficacy and PA at T3 and T4, changing the timing of the mediational relationships. CONCLUSIONS Physiological somatic sensations appear to be an important construct to target in order to increase PA in this population. While self-efficacy appeared to mediate the relationship between physiological somatic sensations and PA, the timing of this relationship is requires further study. PMID:25642840