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Surgery and medical treatment in persistent somatizing patients.

This study describes the utilization of surgical operations, frequency and outcome of medical and surgical treatment in a group of persistent somatizers compared with a control group of non-somatizers. The study was carried out using the Danish national medical register to identify persons in the general population (age range 17-49 yr) with at least 10 general admissions during an 8-yr period. Persistent somatizers were defined as persons with more than six medically unexplained general hospital admissions in their lifetimes before 1985. Conversely, non-somatizers were patients whose admissions could mainly be ascribed to well-defined somatic disorders. The findings show that persistent somatizers had been exposed to extensive surgery, outnumbering the non-somatizers. Surgical operations were of several categories, with gastrointestinal and gynaecological operations being the most frequent. The physicians used medical and surgical treatment nearly as often for treating persistent somatizers as in the treatment of the non-somatizers. Surgical or medical treatment was used in nearly half of the medically unexplained admissions. The outcome of the surgical treatment of the persistent somatizers was, however, generally unsuccessful in that the effect was unsatisfactory in three quarters of cases. Similarly, two thirds of the medical treatments were judged to be unsuccessful in persistent somatizers. The findings suggest that the costs of somatic diagnostic procedures and fruitless surgical and medical treatment attempts on persistent somatizers are enormous, and only exceeded by the risk of iatrogenic harm. This emphasizes the need for an early diagnosis of somatization and of treating it properly.

Adolescent↗

The use of somatic embryogenesis for plant propagation in cassava.

In cassava, somatic embryogenesis starts with the culture of leaf explants on solid Murashige and Skoog-based medium supplemented with auxins. Mature somatic embryos are formed within 6 wk. The cotyledons of the primary somatic embryos are used as explants for a new cycle of somatic embryogenesis. The cotyledons undergo secondary somatic embryogenesis on both liquid and solid Murashige and Skoog-based medium supplemented with auxins. Depending on the auxin, new somatic embryos are formed after 14-30 d after which they can be used for a new cycle of somatic embryogenesis. In liquid medium, more than 20 secondary somatic embryos are formed per initial cultured embryo. In both primary and secondary somatic embryogenesis, the somatic embryos originate directly from the explants. Transfer of clumps of somatic embryos to a Gresshoff and Doy-based medium supplemented with auxins results in indirect somatic embryogenesis. The direct form of somatic embryogenesis has a high potential for use in plant propagation, whereas the indirect has a high potential for use in genetic modification of cassava. Mature somatic embryos germinate into plants after desiccation and culture on a Murashige and Skoog-based medium supplemented with benzylaminopurine (BA). Depending on the used BA concentration, plants can either be transferred either directly to the greenhouse or after using standard multiplication protocols.

Culture Media↗

Chronic functional somatic symptoms: a single syndrome?

BACKGROUND: Reliable longitudinal data of patients with functional somatic symptoms in general practice are lacking. AIMS: To identify distinctive features in patients with chronic functional somatic symptoms, and to determine whether these symptoms support the hypothesis of the existence of specific somatic syndromes. DESIGN OF STUDY: Observational study, with a comparison control group. SETTING: Four primary care practices affiliated with the University of Nijmegen in the Netherlands. METHOD: One hundred and eighty-two patients diagnosed between 1998 and 2002 as having chronic functional somatic symptoms and 182 controls matched by age, sex, socioeconomic status, and practice were included. Data on comorbidity, referrals, diagnostic tests, and hospital admissions over a period of 10 years prior to the diagnosis were collected. Medication use and number of visits to the general practitioner (GP) were extracted from the moment computerised registration was started. RESULTS: In the 10 years before the diagnosis of chronic functional somatic symptoms, significantly more patients than controls presented functional somatic symptoms in at least two body systems, and used more somatic and psychotropic drugs. They visited the GP twice as much, statistically had significantly more psychiatric morbidity, and were referred more often to mental health workers and somatic specialists. The number of patients undergoing diagnostic tests was higher for patients with chronic functional somatic symptoms than for controls, but hospital admissions rates were equal. CONCLUSION: Patients with chronic functional somatic symptoms have a great diversity of functional somatic symptoms. They use more somatic and psychotropic drugs than controls in the years before diagnosis. Moreover, they show high rates of referrals and psychiatric morbidity. The diversity of symptoms of patients with chronic functional somatic symptoms supports the concept that symptoms do not cluster in well defined distinct syndromes. Therefore, patients with chronic functional somatic symptoms should preferably not be classified into medical subspecialty syndromes.

Adolescent↗

Symptom patterns and causes of somatization in men: I. Differentiation of two discrete disorders.

Two distinct patterns of somatization were identified in 807 Swedish adopted men, using comprehensive lifetime psychiatric and sick-leave records. "Diversiform" somatizers had a high frequency of brief sickness occasions for a wide diversity of complaints, particularly pain in the head, joints, and abdomen. "Asthenic" somatizers had a lower frequency and diversity of complaints. They recuperate more slowly, however, and were more often disabled by fatigue, weakness, and minor illnesses such as upper respiratory infections. Both types of somatizers had associated psychosocial maladjustment, but they had discrete clinical patterns, with infrequent overlap. Diversiform somatizers had a higher risk of alcohol abuse, psychiatric hospitalization, and substandard income than either asthenic somatizers or non-somatizers. Asthenic somatizers had a higher risk of divorce than either diversiform somatizers or non-somatizers. Men with prominent somatization had an excess of psychiatric treatment for alcoholism or anxiety disorders, but, unlike female somatizers, no excess of criminality. These clinical differences suggest that the psychiatric processes associated with somatization may be qualitatively different in men and women. The method used here is generally applicable in genetic epidemiology to identify natural clinical subtypes within a heterogeneous phenotype.

Absenteeism↗

Somatization, somatosensory amplification, attribution styles and illness behaviour: a review.

Somatic symptoms have been conceptualized in many different ways in literature. Current classifications mainly focus on the numbers of symptoms, with relative neglect of the underlying psychopathology. Researchers have emphasized the importance of a number of experiential, perceptual and cognitive-behavioural aspects of somatization. This review focuses on existing literature on the role of somatosensory amplification, attribution styles, and illness behaviour in somatization. Evidence suggests that somatosensory amplification is neither sensitive nor specific to somatizing states, and that other factors like anxiety, depression, neuroticism, alexithymia may also have an influence. Attribution research supports the existence of multiple causal attributions, which are related to the numbers of somatic symptoms. While somatizing patients have more organic attributions, depressed patients have more psychological attributions. A global somatic attribution style is associated with the number of obscure somatic symptoms, while a psychological attribution style is associated with both--psychological and somatic-- symptoms of depression and anxiety. There are conflicting findings with respect to the role of normalizing attributions in reducing physician recognition of anxiety and depression. Specific symptom attributions appear to explain physician recognition of psychological distress, but global attribution styles do not appear to explain any further variance in physician recognition beyond that explained by specific causal attributions. Illness behaviour has been studied in two distinct ways in literature. Research focusing on attendance rates as a form of illness behaviour suggests that somatization is associated with high levels of health care utilization. There is also some evidence that health care utilization, amplification and attributions styles may be interrelated among somatizing patients. More structured ways to assess illness behaviour have found high levels of abnormal illness behaviour in this population. Overall, research appears to suggest a complex (and as yet unclear) relationship between somatic symptoms and underlying cognitions/illness behaviours. While it is clear that somatization is closely related to a number of perceptual and cognitive-behavioural factors, the precise nature of these relationships are yet to be elucidated.

Affective Symptoms↗

The impact of somatization on the use of gastrointestinal health-care resources in patients with irritable bowel syndrome.

BACKGROUND: It is unclear why patients with irritable bowel syndrome (IBS) consume a disproportionate amount of health-care resources versus matched controls. One possibility is the presence of comorbid somatization-a process marked by multiple unexplained somatic complaints that is highly prevalent in IBS. We sought to determine whether higher levels of somatization are associated with higher levels of gastrointestinal (GI) resource utilization in IBS. METHODS: A total of 1,410 patients >18 yr with IBS were evaluated at a university-based clinic. Subjects completed a symptom questionnaire, the SCL-90R psychometric checklist, and the SF-36 Health Survey. We measured two outcomes: (1) a 1-yr direct GI health-care costs and (2) a 1-yr number of GI physician visits. Our primary regressor was somatization as measured by the somatization subscale of the SCL-90R. We performed regression analyses to measure the adjusted influence of somatization on GI resource utilization. RESULTS: In the full sample of patients, there were no differences in the likelihood of expending versus not expending previous GI health-care costs among groups with varying levels of somatization. Similarly, there were no differences in either the likelihood of visiting a GI physician or the number of overall physician visits among patients with varying levels of somatization. However, in the subset of patients expending at least $1.00 in GI costs in the previous year (53% of cohort), there was a significantly higher cost of care for subjects with high versus low levels of somatization. CONCLUSIONS: IBS patients with high levels of somatization are not more likely to seek GI care compared to patients with low levels of somatization. However, once they are evaluated for care, patients with high somatization expend significantly more GI health-care costs. This suggests that somatization is positively associated with health-care costs in IBS, and that the association may be driven more by physicians than patients.

Adolescent↗

Differences in polyadenylation site choice between somatic and male germ cells.

BACKGROUND: We have previously noted that there were differences in somatic and male germ cell polyadenylation site choices. First, male germ cells showed a lower incidence of the sequence AAUAAA (an important element for somatic polyadenylation site choice) near the polyadenylation site choice. Second, the polyadenylation sites chosen in male germ cells tended to be nearer the 5' end of the mRNA than those chosen in somatic cells. Finally, a number of mRNAs used a different polyadenylation site in male germ cells than in somatic cells. These differences suggested that male germ cell-specific polyadenylation sites may be poor substrates for polyadenylation in somatic cells. We therefore hypothesized that male germ cell-specific polyadenylation sites would be inefficiently used in somatic cells. RESULTS: We tested whether pre-mRNA sequences surrounding male germ cell-specific polyadenylation sites (polyadenylation cassettes) could be used to direct polyadenylation efficiently in somatic cells. To do this, we developed a luciferase reporter system in which luciferase activity correlated with polyadenylation efficiency. We showed that in somatic cells, somatic polyadenylation cassettes were efficiently polyadenylated, while male germ cell-specific polyadenylation cassettes were not. We also developed a sensitive, 3' RACE-based assay to analyze polyadenylation site choice. Using this assay, we demonstrated that male germ cell-specific polyadenylation cassettes were not polyadenylated at the expected site in somatic cells, but rather at aberrant sites upstream of the sites used in male germ cells. Finally, mutation of the male germ cell-specific poly(A) signal to a somatic poly(A) signal resulted in more efficient polyadenylation in somatic cells. CONCLUSION: These data suggest that regulated polyadenylation site choice of male germ cell-specific polyadenylation sites requires one or more factors that are absent from somatic cells.

3T3 Cells↗

The attribution of somatization in schizophrenia patients: a naturalistic follow-up study.

BACKGROUND: Knowledge is limited concerning somatic symptoms that cannot be accounted for by detectable somatic illness among schizophrenia patients. This study aimed to explore the prevalence, correlates, and predictors of somatization among schizophrenia patients. METHOD: Initial data on all consecutively admitted adult patients with DSM-IV schizophrenia, schizoaffective disorder, major depressive disorder, or bipolar disorder were collected between August 1998 and August 2000. Standardized measures of psychopathology, somatization, emotional distress, adverse effects, insight, and stress process-related (psychosocial) variables were administered to 237 schizophrenia patients at admission and at least 12 months thereafter (N = 148). Partial correlation and multiple regression analyses were performed. RESULTS: The frequency of somatization, defined as the presentation of 5 or more medically unexplained somatic symptoms (Somatic Symptom Index-5), among the inpatient population (27%) did not change significantly after at least 12 months (30%; p =.61). Regression analysis showed that somatization scores were best predicted by the combination of scores for emotional distress attributed to psychopathology and side effects, expressed emotion, and insight. This combined model explains at least 40% of the variance in somatization scores. Self-esteem and social support showed negative association with somatization scores. Somatization scores were not associated with gender, age, education, age at onset, observed severity of psychopathology, subtype and duration of illness, number of admissions and treatment settings, or type and dose of antipsychotic agents. CONCLUSIONS: Somatization is a prevalent problem among schizophrenia patients and is associated with emotional distress attributed to psychopathology, side effects of antipsychotic agents, and family members' attitudes toward schizophrenia patients. This study suggests that insight, self-esteem, and social support may protect against somatization in schizophrenia patients.

Adult↗

Detection of Salmonella enterica somatic groups C1 and E1 by PCR-enzyme-linked immunosorbent assay.

Objectives of this study were to develop a PCR-based enzyme-linked immunosorbent assay (PCR-ELISA) for identification of Salmonella enterica somatic groups C1 and E1 and to evaluate this procedure along with a PCR-ELISA procedure for S. enterica somatic groups B, C2, and D in a masked study. Primers were selected from the rfb gene cluster, which is responsible for biosynthesis of O antigens of Salmonella lipopolysaccharide. Previously serogrouped Salmonella isolates (n = 169) were used to determine the sensitivity and specificity of the PCR-ELISA procedure. DNA from all isolates was amplified using the PCR procedure for selected somatic groups and amplified products were visualized on agarose gels, as well as subjected to the ELISA procedure. The PCR-ELISA technique correctly identified 97% of somatic group C1 and 87% of somatic group E1. The sensitivity of this procedure to correctly identify S. enterica somatic group C1 was 97% and 88% for somatic group E1. The specificity was 98% for both somatic groups C1 and E1. The PCR-ELISA techniques correctly identified 93% of Salmonella isolates belonging to somatic groups B, C1, C2, D, and E1. The overall sensitivity of this procedure to correctly identify S. enterica somatic groups was 96% and the specificity was 98%. Ninety-one percent of somatic group D, 92% of somatic group B, and 97% of somatic group C2 were identified correctly with this procedure. Results of this study indicate that the PCR-ELISA procedure is a rapid and accurate method for serogrouping Salmonella isolates. Utilization of the PCR-ELISA procedure for Salmonella serogrouping would aide in identification, surveillance, prevention, and control of Salmonella.

Base Sequence↗

Pooled analysis of venlafaxine XR efficacy on somatic and psychic symptoms of anxiety in patients with generalized anxiety disorder.

We evaluated the relative efficacy of venlafaxine XR on the psychic versus somatic symptoms of anxiety in patients with generalized anxiety disorder as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Data were pooled and analyzed from 1,841 patients with generalized anxiety disorder who participated in five short-term (8-week) double-blind, multicenter, placebo-controlled studies, two of which had long-term (6-month) extensions. Somatic and psychic anxieties were studied using the Hamilton rating scale for anxiety (HAM-A) factor scores. We examined response rates (> or =50% improvement over baseline severity score) in the overall population and in patients with mainly somatic symptomatology at baseline (somatizers). Venlafaxine XR significantly reduced factor scores for both psychic and somatic HAM-A factors compared with placebo, from the first and second weeks of treatment, respectively. Patients treated with venlafaxine XR had significantly higher rates of response than patients receiving placebo on the psychic (58% vs. 38%, P<.001 at week 8; 66% vs. 35% at week 24, P<.001) and somatic (56% vs. 43%, P<.001 at week 8; 67% vs. 47% at week 24, P<.001) factors of the HAM-A. There was a TreatmentxFactor interaction (P<.027) in response rates: Patients treated with venlafaxine showed similar somatic and psychic anxiety response rates, whereas placebo-treated patients showed higher somatic compared with psychic response rates. Somatizers showed similar rates of response to the total population for the somatic factor of the HAM-A in either treatment group. Patients with generalized anxiety disorder treated with venlafaxine XR showed similar absolute rates of response on somatic and psychic symptoms, but relative to patients treated with placebo, more improvement in psychic than somatic symptoms.

Adult↗

Patients who somatize in primary care: a longitudinal study of cognitive and social characteristics.

We examined the cognitive and sociodemographic characteristics of patients making somatic presentations of depression and anxiety in primary care. Only 15% of patients with depressive symptomatology on self-report, and only 21% of patients with current major depression or anxiety disorders on diagnostic interview, presented psychosocial symptoms to their GP. The remainder of patients with psychiatric distress presented exclusively somatic symptoms and were divided into three groups-initial, facultative and true somatizers-based on their willingness to offer or endorse a psychosocial cause for their symptoms. Somatizers did not differ markedly from psychologizers in sociodemographic characteristics except for a greater proportion of men among the true somatizers. Compared to psychologizers, somatizers reported lower levels of psychological distress, less introspectiveness and less worry about having an emotional problem. Somatizers were also less likely to attribute common somatic symptoms to psychological causes and more likely to endorse normalizing causes. In the 12 months following their initial visit, somatizers made less use of speciality mental health care and were less likely to present emotional problems to their GP. Somatizers were markedly less likely to talk about personal problems to their GP and reported themselves less likely to seek help for anxiety or sadness. Somatization represents a persistent pattern of illness behaviour in which mental health care is not sought despite easily elicited evidence of emotional distress. Somatization is not, however, associated with higher levels of medical health care utilization than that found among patients with frank depression or anxiety.

Adolescent↗

Gender and cross-cultural differences in somatic symptoms associated with emotional distress. An international study in primary care.

BACKGROUND: Gender and cross-cultural differences in the association between somatic symptoms and emotional distress were investigated, using data from the World Health Organization Collaborative Project on Psychological Problems in General Health Care. METHODS: Data were collected at 15 centres in 14 countries around the world. At each centre, a stratified random sample of primary care attenders aged 15-65 years was assessed using, among other instruments, the 28-item General Health Questionnaire and the Composite International Diagnostic Interview-Primary Health Care Version. RESULTS: Females reported higher levels of somatic symptoms and emotional distress than males. A strong correlation between somatic symptoms and emotional distress was found in both sexes, with females reporting more somatic symptoms at each level of emotional distress. However, linear regression analysis showed that gender had no significant effect on level of somatic symptoms, when the effects of centre and emotional distress were controlled for. In both sexes, no specific pattern of association emerged between somatic symptom clusters and either anxiety or depression. Primary care attenders from less developed centres reported more somatic symptoms and showed greater gender differences than individuals from more developed centres, but inter-centre differences were small. Finally, gender was not a significant predictor of reason for consultation (somatic versus mental/behavioural symptoms), after controlling for levels of somatic symptoms and emotional distress as well as for centre effect. CONCLUSIONS: These data do not support the common belief that females somatize more than males or the traditional view that somatization is a basic orientation prevailing in developing countries. Instead, somatic symptoms and emotional distress are strongly associated in primary care attenders, with few differences between the two sexes and across cultures.

Adolescent↗

Developmental pathway of somatic embryogenesis in Picea abies as revealed by time-lapse tracking.

Several coniferous species can be propagated via somatic embryogenesis. This is a useful method for clonal propagation, but it can also be used for studying how embryo development is regulated in conifers. However, in conifers it is not known to what extent somatic and zygotic embryos develop similarly, because there has been little research on the origin and development of somatic embryos. A time-lapse tracking technique has been set up, and the development of more than 2000 single cells and few-celled aggregates isolated from embryogenic suspension cultures of Norway spruce (Picea abies L. Karst.) and embedded in thin layers of agarose has been traced. Experiments have shown that somatic embryos develop from proembryogenic masses which pass through a series of three characteristic stages distinguished by cellular organization and cell number (stages I, II and III) to transdifferentiate to somatic embryos. Microscopic inspection of different types of structures has revealed that proembryogenic masses are characterized by high interclonal variation of shape and cellular constitution. In contrast, somatic embryos are morphologically conservative structures, possessing a distinct protoderm-like cell layer as well as embryonal tube cells and suspensor. The lack of staining of the arabinogalactan protein epitope recognized by the monoclonal antibody JIM13 was shown to be an efficient marker for distinguishing proembryogenic masses from somatic embryos. The vast majority of cells in proembryogenic masses expressed this epitope and none of cells in the early somatic embryos. The conditions that promote cell proliferation (i.e. the presence of exogenous auxin and cytokinin), inhibit somatic embryo formation; instead, continuous multiplication of stage I proembryogenic masses by unequal division of embryogenic cells with dense cytoplasm is the prevailing process. Once somatic embryos have formed, their further development to mature forms requires abscisic acid and shares a common histodifferentiation pattern with zygotic embryos. Although the earliest stages of somatic embryo development comparable to proembryogeny could not be characterized, the subsequent developmental processes correspond closely to what occurs in the course of early and late zygotic embryogeny. A model for somatic embryogenesis pathways in Picea abies is presented.

Models, Biological↗

Somatization: a spectrum of severity.

OBJECTIVE: The DSM-III-R diagnosis of somatization disorder requires that a patient have a specific number of medically unexplained somatic symptoms. This number of symptoms was developed by committee consensus, and it is not clear whether patients with this specific number of symptoms can be differentiated from patients with lower but still substantial numbers of somatic symptoms. METHOD: Fifty-one percent of 767 high utilizers of two primary care clinics were identified as distressed by an elevated SCL anxiety, depression, or somatization scale score or by their primary care physician. The Diagnostic Interview Schedule (DIS) was completed on 119 distressed high utilizers who were randomly assigned to an intervention group in a controlled trial of psychiatric consultation. The 119 distressed high utilizers were separated into four categories according to the number of unexplained somatic symptoms found on the DIS and were compared on demographic, psychiatric distress, disability, medical, and health utilization variables. RESULTS: The data suggest that many clinical and behavioral features of somatization are significantly more common in patients with four to 12 medically unexplained somatic symptoms rather than changing dramatically at the diagnostic threshold for somatization disorder. The data also showed that patients who meet the DSM-III-R criteria for somatization disorder are severely ill and have a high burden of psychiatric illness and disability. CONCLUSIONS: The results suggest that the DSM-IV somatoform disorders section should include somatization disorder, an abridged definition of somatization disorder often associated with anxiety and depression, as well as a type of somatization associated with an adjustment disorder.

Activities of Daily Living↗

Cerebellar projections to the somatic pretectum in the cat.

Neurons in the somatic pretectum receive input from the dorsal column nuclei (DCN) and project to a comparable "somatic" portion of the dorsal accessory nucleus of the inferior olive (DAO). This somatic DAO is reciprocally connected with the anterior interpositus nucleus of the cerebellum. One question that arises is whether this circuitry is further controlled by an output specifically from the anterior interpositus nucleus to the somatic pretectum. Wheatgerm agglutinin conjugated to horseradish peroxidase was injected into various parts of the cat pretectum. Injection sites were interpreted as including the somatic pretectum if neurons in the DCN were retrogradely labeled and if anterograde terminal labeling occurred in somatic DAO. The locations of retrogradely labeled neurons within the deep cerebellar nuclei were then compared in cases in which the injection sites included or excluded the somatic pretectum. In all cases in which the injection site included the somatic pretectum, retrogradely labeled neurons were observed in the anterior interpositus nucleus as well as in the lateral cerebellar nuclei. In some of these cases, neurons in the posterior interpositus and medial nuclei were also labeled. In contrast, in cases in which the pretectal injection site was located outside or at the border of the somatic pretectum, retrogradely labeled neurons were observed only in the lateral, posterior interpositus, and medial nuclei. Thus, the somatic pretectum appears to receive input primarily from neurons in the anterior interpositus nucleus, along with some input from neurons in the lateral nucleus. These results provide additional evidence for a pathway through the DCN in which sequentially processed somatic information has access to and is modulated by cerebellar circuitry. The existence of such a pathway supports the conclusion that neurons in the DCN convey somatic information important not only for cutaneous, kinesthestic, and other bodily sensations, but also for the control of movement.

Afferent Pathways↗

The relation between anger expression, depression, and somatic symptoms in depressive disorders and somatoform disorders.

BACKGROUND: In previous studies, the relationship between either anger suppression and depression or anger suppression and somatic symptoms was examined. However, the relationship between anger expression, depression, and somatic symptoms was not examined in depressive disorders and somatoform disorders. METHOD: The DSM-IV-diagnosed subjects included 73 patients with depressive disorders and 47 patients with somatoform disorders. The Anger Expression Scale was used to assess the level of anger expression or suppression. The severity of depression was assessed using the Symptom Checklist-90-Revised (SCL-90-R). The Somatization Rating Scale and the SCL-90-R somatization subscale were used to assess the severity of somatic symptoms. Data were collected from March 2000 to March 2001. RESULTS: The results of the path analyses showed that in depressive disorder patients, anger expression had a stronger effect on somatic symptoms through depression than did anger suppression, although both anger expression and anger suppression had a significant indirect effect on somatic symptoms. The depressive disorder group also showed a significant but negative direct effect of anger suppression on anger expression in the path from anger suppression to anger expression to depression to somatic symptoms. However, only anger suppression had an indirect effect on somatic symptoms through depression in somatoform disorder patients. CONCLUSIONS: The results suggest that anger expression might play a more predominant role in depression and somatic symptoms of depressive disorder patients than anger suppression, but only anger suppression might be associated with depression and somatic symptoms of somatoform disorder patients. In addition, incomplete anger suppression followed by anger expression is likely to be associated with depression and somatic symptoms in depressive disorders.

Adult↗

Distinct mutational landscapes for germline and somatic cancer variants in forty tumor suppressor genes.

Germline and somatic cancer variants in tumor suppressor genes (TSGs) share loss-of-function mechanisms, but studies of a few genes (DICER1 and CEBPA) have demonstrated differences in variant consequence and location. To systematically assess whether TSGs display distinct mutational patterns, we leveraged large public genetic databases and compared 32,941 high-quality pathogenic/likely pathogenic (P/LP) germline variants in ClinVar, with 12,907 oncogenic/likely oncogenic (O/LO) somatic tumor variants from cBioPortal across 40 TSGs. Only 3,863 (9.2%) variants were shared. Eighteen TSGs showed significantly different distributions of variant occurrences by molecular consequence, replicated with non-overlapping somatic data from the COSMIC database (chi-squared tests, false discovery rate = 5%). DICER1, TP53, and SMAD4 displayed excess somatic missense events, while nine TSGs (e.g., RB1 and APC) contained excess somatic stop-gain events throughout the coding sequence. Analysis by tumor type revealed excess stop-gain events in tissues exposed to environmental mutagens with corresponding mutation signatures. For several TSGs (WT1), germline variants predispose to tumors (Wilms' tumor) distinct from the majority source of somatic data (myeloid leukemia). Germline and somatic events are also distributed unevenly across cDNA locations, with 103 regions of preferential clustering in 39 TSGs (78 somatic and 25 germline). Twenty somatic clusters contained recurring frameshifts in homopolymer runs, many in tumors with microsatellite instability. Germline clusters contain more germline-exclusive variants, some driving non-cancer phenotypes reflecting genetic pleiotropy. Altogether, germline and somatic variants of TSGs represent unique sets with substantially different patterns shaped by selection pressures from gene-specific and somatic mutational mechanisms. Characterizing these distinctions enables more accurate clinical interpretation of TSG variants.

Humans↗

A key developmental switch during Norway spruce somatic embryogenesis is induced by withdrawal of growth regulators and is associated with cell death and extracellular acidification.

The biotechnology of somatic embryogenesis holds considerable promise for clonal propagation and breeding programs in forestry. To efficiently regulate the whole process of plant regeneration through somatic embryogenesis, it is of outmost importance to understand early developmental events when somatic embryos are just formed. In Norway spruce, somatic embryos transdifferentiate from proembryogenic masses (PEMs). This work describes the developmental dynamics (frequency distribution of PEMs and early somatic embryos) of the whole embryogenic suspension culture growing in the presence and absence of plant growth regulators (PGRs), auxin and cytokinin. The experiments have shown that PEM-to-somatic embryo transition is a key developmental switch that determines the yield and quality of mature somatic embryos and ultimately plant production. This switch was induced by the withdrawal of PGRs in cell suspension leading to a rapid accumulation of early somatic embryos (to a maximum of 75% of the entire population of suspension culture) and concomitant degradation of PEMs. The latter was evident from increased level of cell death measured through spectrophotometric Evans blue staining assay. Proembryogenic mass-to-embryo transition and concomitant activation of cell death were mediated by strong extracellular acidification. Therefore, buffering PGR-free culture medium at high (pH 5.8) or low (pH 4.5) levels of pH inhibited both PEM-to-embryo transition and cell death. The yield of mature somatic embryos on abscisic acid (ABA)-containing medium was increased up to 10-fold if the suspension culture had been pretreated for 1 to 9 days in unbuffered PGR-free medium. In this case a large proportion (75%) of the total number of mature embryos was formed within a short, 5-week, contact with ABA. The latter is practically important because prolonged contact with ABA suppresses the growth of somatic embryo plants. Based on these results, an improved method for regulating somatic embryogenesis was set up and tested for nine genotypes of Norway spruce. Over 800 plants regenerated from all tested genotypes demonstrated a good performance in the greenhouse and they were transferred to the field.

Apoptosis↗