Exploring perceptions of vulnerability among women facing psychosocial adversity before, during and after pregnancy: A qualitative interview-study using thematic analysis.

OBJECTIVE: The term 'vulnerable' is often used to describe women facing psychosocial adversity during pregnancy, implying a heightened risk of experiencing suboptimal pregnancy outcomes. While this label might facilitate the pathway to appropriate care, it can be perceived as stigmatizing by the women it intends to help, which could deter their interaction with healthcare services. This study explores how women facing psychosocial adversity before, during and after pregnancy perceive the concept of vulnerability and experience being labeled as such. METHODS: We conducted a thematic analysis of semi-structured, in-depth interviews. Through purposive sampling targeting maximum variation, ten women of diverse backgrounds were included. RESULTS: Three central themes emerged: defining vulnerability, embracing vulnerability and the feeling of being stigmatized. Women perceived vulnerability as an inability to adequately care for themselves or their children, necessitating additional support alongside routine antenatal care. Acceptance of the 'vulnerable' label came when it also acknowledged their proactive efforts and strengths to improve their situation. Conversely, if discussions surrounding vulnerability failed to recognize women's agency - specifically, their personal journeys and the courage needed to seek support - the label was perceived as stigmatizing. CONCLUSIONS: Addressing vulnerability effectively in maternity care requires a nuanced, patient-centered approach, acknowledging both the challenges and strengths of women facing psychosocial adversities. Emphasizing personal narratives and their courage in seeking support can mitigate the stigmatizing effects of the 'vulnerable' label. Integrating these narratives into maternal healthcare practices can foster deeper connections with the women involved, enhancing the overall quality of care.

Antipsychotics and Identity: The Adverse Effect No One is Talking About.

People who take antipsychotics, and people who are prescribed antipsychotics without taking them, experience effects which are not frequently discussed: effects on their identity and sense of self. Qualitative research indicates the relationship between taking APs and identity is multilayered, and changeable. Taking APs can restore people to their earlier, pre-symptom sense of self. Being prescribed and taking APs can also, on the other hand, be experienced as damaging, erasing and dulling people's sense of who they are. This complexity deserves exploration in clinical practice, which we believe is currently not done routinely. More work is needed to understand whether, and how, the relationship between identity and APs is being addressed. We outline the importance of having discussions in a clinical space around identity, and a sense of agency, on the grounds that true recovery-oriented care, which enacts shared decision-making principles, demands it. Further, we argue that it will allow for better therapeutic alliance and trust to be forged between clinician and client, ultimately leading to better care.

Defining vulnerability subgroups among pregnant women using pre-pregnancy information: a latent class analysis.

BACKGROUND: Early detection of vulnerability during or before pregnancy can contribute to optimizing the first 1000 days, a crucial period for children's development and health. We aimed to identify classes of vulnerability among pregnant women in the Netherlands using pre-pregnancy data on a wide range of social risk and protective factors, and validate these classes against the risk of adverse outcomes. METHODS: We conducted a latent class analysis based on 42 variables derived from nationwide observational data sources and self-reported data. Variables included individual, socioeconomic, lifestyle, psychosocial and household characteristics, self-reported health, healthcare utilization, life-events and living conditions. We compared classes in relation to adverse outcomes using logistic regression analyses. RESULTS: In the study population of 4172 women, we identified five latent classes. The largest 'healthy and socioeconomically stable'-class [n = 2040 (48.9%)] mostly shared protective factors, such as paid work and positively perceived health. The classes 'high care utilization' [n = 485 (11.6%)], 'socioeconomic vulnerability' [n = 395 (9.5%)] and 'psychosocial vulnerability' [n = 1005 (24.0%)] were characterized by risk factors limited to one specific domain and protective factors in others. Women classified into the 'multidimensional vulnerability'-class [n = 250 (6.0%)] shared multiple risk factors in different domains (psychosocial, medical and socioeconomic risk factors). Multidimensional vulnerability was associated with adverse outcomes, such as premature birth and caesarean section. CONCLUSIONS: Co-existence of multiple risk factors in various domains is associated with adverse outcomes for mother and child. Early detection of vulnerability and strategies to improve parental health and well-being might benefit from focussing on different domains and combining medical and social care and support.

[Are conspiracy theorists psychotic? A comparison between conspiracy theories and paranoid delusions]. / Zijn complotdenkers psychotisch? Een vergelijking tussen complottheorieën en paranoïde wanen.

BACKGROUND: Conspiracy theories are popular during the COVID-19 pandemic. Conspiratorial thinking is characterised by the strong conviction that a certain situation that one sees as unjust is the result of a deliberate conspiracy of a group of people with bad intentions. Conspiratorial thinking appears to have many similarities with paranoid delusions. AIM: To explore the nature, consequences, and social-psychological dimensions of conspiratorial thinking, and describe similarities and differences with paranoid delusions. METHOD: Critically assessing relevant literature about conspiratorial thinking and paranoid delusions. RESULTS: Conspiratorial thinking meets epistemic, existential, and social needs. It provides clarity in uncertain times and connection with an in-group of like-minded people. Both conspiratorial thinking and paranoid delusions involve an unjust, persistent, and sometimes bizarre conviction. Unlike conspiracy theorists, people with a paranoid delusion are almost always the only target of the presumed conspiracy, and they usually stand alone in their conviction. Furthermore, conspiracy theories are not based as much on unusual experiences of their inner self, reality, or interpersonal contacts. CONCLUSIONS Conspirational thinking is common in uncertain circumstances. It gives grip, certainty, moral superiority and social support. Extreme conspirational thinking seems to fit current psychiatric definitions of paranoid delusions, but there are also important differences. To make a distinction with regard to conspiratorial thinking, deepening of conventional definitions of delusions is required. Instead of the strong focus on the erroneous content of delusions, more attention should be given to the underlying idiosyncratic, changed way of experiencing reality.

Brain areas associated with clinical and cognitive insight in psychotic disorders: A systematic review and meta-analysis.

In the past years, ample interest in brain abnormalities related to clinical and cognitive insight in psychosis has contributed several neuroimaging studies to the literature. In the current study, published findings on the neural substrates of clinical and cognitive insight in psychosis are integrated by performing a systematic review and meta-analysis. Coordinate-based meta-analyses were performed with the parametric coordinate-based meta-analysis approach, non-coordinate based meta-analyses were conducted with the metafor package in R. Papers that could not be included in the meta-analyses were systematically reviewed. Thirty-seven studies were retrieved, of which 21 studies were included in meta-analyses. Poorer clinical insight was related to smaller whole brain gray and white matter volume and gray matter volume of the frontal gyri. Cognitive insight was predominantly positively associated with structure and function of the hippocampus and ventrolateral prefrontal cortex. Impaired clinical insight is not associated with abnormalities of isolated brain regions, but with spatially diffuse global and frontal abnormalities suggesting it might rely on a range of cognitive and self-evaluative processes. Cognitive insight is associated with specific areas and appears to rely more on retrieving and integrating self-related information.

Social cognitive group treatment for impaired insight in psychosis: A multicenter randomized controlled trial.

PURPOSE: The majority of people with schizophrenia has impaired insight, which is related to a poorer outcome. In this study, we evaluate a new psychosocial intervention 'REFLEX' aimed at improving insight in people with schizophrenia. REFLEX focuses on targeting stigma-sensitivity, perspective taking and self-reflection in people with schizophrenia and low insight. Primary objective is to improve insight and subsequently to improve functional outcome and symptoms. METHOD: A total of 121 people diagnosed with schizophrenia according to DSM IV criteria with impaired insight was included in 2012-2015 from seven sites in a multicenter randomized controlled trial. REFLEX was compared to an active control condition consisting of group-wise simplified cognitive remediation training. Primary outcome of the study were the preconditions of insight: internalized stigma, self-reflection, mental flexibility and perspective taking. Clinical insight and cognitive insight were secondary outcomes. RESULTS: Although perspective taking, self-reflection, mental flexibility and stigma sensitivity remained unchanged after the intervention, results showed a significant improvement of clinical insight in both conditions directly after treatment (SAI-E Rater, p < .001, PANSS G12, p < .005) and at follow-up (SAI-E Rater, p < .01, SAI-E interview, p < .001, PANSS G12, p < .0001). Improvement of clinical insight directly after treatment was larger in the REFLEX condition (SAI-E Rater, p < .05). Other outcomes (self-esteem, quality of life and depression) remained unchanged. CONCLUSION: Though insight improved in both conditions, REFLEX was not superior to simplified drill-and-practice cognitive remediation training. Nevertheless, this study indicates that structured interventions can significantly improve insight. Further research on the underlying mechanisms of both conditions is needed, as insight is unlikely to improve spontaneously in chronic patients.

Contemporary approaches in mental health rehabilitation.

In many European countries, deinstitutionalisation has been an ongoing process over the last few decades. Mental health organisations were transformed to provide support in a more integrated and comprehensive manner, preferably in their own homes in the community. Yet, despite the welcome aspiration of community integration for all, people with complex mental health problems (also termed severe mental illness) have continued to require high levels of support, in inpatient settings and in the community. This group's needs make them highly dependent on their caregivers. The attitudes, knowledge and skills of the staff providing treatment and support is crucial to their recovery. Rehabilitation programmes provide a much-needed framework to guide practitioners and help them organise and focus their recovery-oriented approach. In this editorial, we will provide a non-exhaustive overview of such rehabilitation programmes and interventions to illuminate the wide scope and practical usability of these interventions for this group of people with complex mental health problems.

Prompted awareness and use of Eating Well with Canada's Food Guide: a population-based study.

BACKGROUND: Little is known about the awareness of Canada's Food Guide (CFG). The present study aimed to report the general and specific awareness of CFG recommendations among adults in Alberta, Canada. METHODS: For this cross-sectional study, respondents (aged >18 years) from randomly selected households completed a telephone survey. Questions pertaining to CFG, physical activity, and vegetable and fruit consumption were included. Logistic regression determined associations between demographic characteristics and awareness of CFG. RESULTS: Thousand two hundred and ten Albertans (50% female, mean age 50.5 years) responded. Most [86.5%; 95% confidence interval (CI) = 84.6-88.4] indicated being generally aware of CFG when prompted and 82.5% were aware of specific CFG recommendations. There were no differences in age between those generally aware and unaware of CFG. Female sex [odds ratio (OR) = 3.6; 95%CI = 24-5.4], Caucasian ethnicity (OR = 3.7; 95% CI = 2.3-5.8), income ≥ Canadian $100 000 per annum (OR = 1.6; 95% CI = 1.1-2.3), reporting ≥5 vegetables and fruit per day (OR = 2.1; 95% CI = 1.4-3.2), exceeding recommended levels for physical activity (OR = 2.0; 95% CI = 1.3-2.9) and perception of current weight as healthy (OR = 1.8; 95% CI = 1.2-2.8) were associated with an awareness of CFG. CONCLUSIONS: Sex, ethnicity and income were associated with general awareness of CFG. Future studies could explore the relationship between awareness and other health-related behaviours.

Insight change in psychosis: relationship with neurocognition, social cognition, clinical symptoms and phase of illness.

OBJECTIVE: Impaired insight is an important and prevalent symptom of psychosis. It remains unclear whether cognitive disturbances hamper improvements in insight. We investigated the neurocognitive, social cognitive, and clinical correlates of changes in insight. METHOD: One hundred and fifty-four patients with a psychotic disorder were assessed at baseline (T0 ) and after three years (T3 ) with the Birchwood Insight Scale, the Positive And Negative Syndrome Scale, measures of neurocognition and social cognition. Linear regression analyses were conducted to examine to what extend neurocognition, social cognition, clinical symptoms and phase of illness could uniquely predict insight change. Subsequently, changes in these factors were related to insight change. RESULTS: Better neurocognitive performance and fewer clinical symptoms at baseline explained insight improvements. The additional effect of clinical symptoms over and above the contribution of neurocognition was significant. Together, these factors explained 10% of the variance. Social cognition and phase of illness could not predict insight change. Changes in clinical symptoms, but not changes in neurocognitive performance were associated with insight change. CONCLUSION: Neurocognitive abilities may predict, in part, the development of insight in psychosis.

Adverse childhood experiences of persons at risk for Huntington's disease or BRCA1/2 hereditary breast/ovarian cancer.

Huntington's disease (HD) is known to have a negative impact on family life. Offspring of HD patients may be exposed to adversity in childhood because of the parent's disease and its psychological consequences. BRCA1/2 hereditary breast and ovarian cancer (BRCA1/2) increases the risk for offspring of being exposed to parental disease or loss. Childhood adversity is associated with psychopathology and various other problems in later life. Adverse childhood experiences (ACEs) before age 16 were assessed in adults at 50% risk for HD (n = 74) or BRCA1/2 (n = 82) and in controls (n = 101), using the Negative Life Events Scale. Mean number and occurrence of ACEs were compared between groups. The odds of having experienced adversity in childhood were higher in HD offspring and BRCA1/2 offspring than in controls. HD offspring reported a higher mean number of ACEs than controls or BRCA1/2 offspring. In HD offspring, the prevalence of parental disease and parental dysfunction experienced before age 16 was higher than in controls. In BRCA1/2 offspring, the prevalence of parental loss before age 16 was higher than in controls. This study indicates that 53% of HD offspring and 45% of BRCA1/2 offspring are exposed to adversity in childhood or adolescence. The relevance of these findings for counseling in predictive testing programs, reproductive decision-making, and child rearing matters is discussed.

Gfi1 and Gfi1b: key regulators of hematopoiesis.

Transcription factor Growth factor independence 1 (Gfi1) is required for multilineage blood cell development, from stem and progenitor cells to differentiated lymphoid and myeloid cells. Gfi1 expression is rapidly induced by cytokines that control both the adaptive and innate immune systems. Gfi1 itself represses the expression of genes implicated in cell survival, proliferation and differentiation. Changes in Gfi1 expression and function have not only been implicated in neutropenia, allergy, autoimmunity and hyperinflammatory responses, but also in lymphoma and more recently in the development of leukemia. In this study, we review how Gfi1 and its paralogue Gfi1b control the development of blood cells, discuss how changes in Gfi1 and Gfi1b function contribute to hematological disease and report on the molecular function of these proteins.

The ubiquitin ligase Triad1 inhibits myelopoiesis through UbcH7 and Ubc13 interacting domains.

Ubiquitination plays a major role in many aspects of hematopoiesis. Alterations in ubiquitination have been implicated in hematological cancer. The ubiquitin ligase Triad1 controls the proliferation of myeloid cells. Here, we show that two RING (really interesting new gene) domains in Triad1 differentially bind ubiquitin-conjugating enzymes, UbcH7 and Ubc13. UbcH7 and Ubc13 are known to catalyze the formation of different poly-ubiquitin chains. These chains mark proteins for proteasomal degradation or serve crucial non-proteolytic functions, respectively. In line with the dual Ubc interactions, we observed that Triad1 catalyzes the formation of both types of ubiquitin chains. The biological relevance of this finding was studied by testing Triad1 mutants in myeloid clonogenic assays. Full-length Triad1 and three mutants lacking conserved domains inhibited myeloid colony formation by over 50%. Strikingly, deletion of either RING finger completely abrogated the inhibitory effect of Triad1 in clonogenic growth. We conclude that Triad1 exhibits dual ubiquitin ligase activity and that both of its RING domains are crucial to inhibit myeloid cell proliferation. The differential interaction of the RINGs with Ubcs strongly suggests that the ubiquitination mediated through UbcH7 as well as Ubc13 plays a major role in myelopoiesis.

Excited-state lifetimes of far-infrared collective modes in proteins.

Vibrational excitations of low frequency collective modes are essential for functionally important conformational transitions in proteins. Here we report the first direct measurement on the lifetime of vibrational excitations of the collective modes at 87 pm (115 cm(-1)) in bacteriorhodopsin, a transmembrane protein. The data show that these modes have extremely long lifetime of vibrational excitations, over 500 picoseconds, accommodating 1500vibrations. We suggest that there is a connection between this relativelyslow anharmonic relaxation rate of approximately 10 g sec(-1) and thesimilar observed rate of conformational transitions in proteins, which require require multi-level vibrational excitations and energy exchanges with othervibrational modes and collisional motions of solvent molecules.

Long-lived amide I vibrational modes in myoglobin.

Pump-probe experiments in the infrared measure vibrational relaxation rates. Myoglobin, which is almost entirely alpha helix in secondary structure, has an unusually long, nonexponential excited state relaxation generated by optically pumping at the blue side ( 5. 85 microm) of the amide I band. The amino acid alanine and the predominantly beta sheet protein photoactive yellow protein do not have such a long-lived state, suggesting that the alpha helix in proteins can support nonlinear states of 15 ps characteristic times.

The outcome of pregnancy in Kell alloimmunisation.

OBJECTIVE: To assess management and outcome of pregnancies with anti-Kell in the West Midlands in the UK over 13 years. DESIGN: A retrospective review of casenotes. SETTING: A regional referral clinic for red cell alloimmune disease and fetal medicine unit at a university hospital. POPULATION: Sixty-five pregnancies were identified in 52 Kell-sensitised women with Kell positive partners from the records of the Birmingham Blood Transfusion Centre. METHODS: Information from the casenotes was entered on a database and comparisons were made using the SPSS for Windows statistics package. MAIN OUTCOME MEASURES: Mode of sensitisation, degree of fetal or neonatal anaemia, need for transfusion, gestation at delivery, birthweight and pregnancy outcome. RESULTS: Alloimmunisation was transfusion-related in 29 pregnancies and pregnancy-induced in 33. The cause could not be identified in three cases. There were 22 proven Kell positive fetuses, of which 18 were affected, in which alloimmunisation was pregnancy-related in 12 cases and transfusion-related in five. Antibody titres and amniotic fluid OD450 were not helpful in management. Severe or very severe disease occurred in 50% of the affected pregnancies (9/18). There was no difference in pregnancy outcome between transfusion or pregnancy induced sensitisation. CONCLUSIONS: Anti-Kell alloimmunisation is an uncommon cause of serious anaemia in a significant proportion of affected pregnancies. There appears to be no difference between that caused by pregnancy or transfusion. Estimation of fetal haemoglobin concentration by cordocentesis is recommended, as antibody titres and amniocentesis are not helpful.

The prognostic importance of the volume of traumatic epidural and subdural haematomas revisited.

The size of a traumatic intracranial haematoma at the moment of diagnosis can be impressive. Haematoma thickness is an inaccurate estimator of haematoma volume, and association with patient outcome is controversial. In this study computerized volumetry of offline digitized CT scans was used to relate haematoma volume with both patient characteristics on admission and at the six months outcome. This retrospective study covered the time period 1981/1990. Ninety eight patients operated upon for an epidural haematoma and 91 patients operated upon for an acute subdural haematoma were analyzed. The relative importance of clinical data, CT scan parameters, and calculated haematoma volumes was determined by multivariate analysis. Volume of the haematoma did not correlate with preoperative neurological condition or the six months outcome in either group, and consequently is not of additional prognostic value.

Inhibition of the hepatic O6-alkylguanine-DNA alkyltransferase in vivo by pretreatment with antineoplastic agents.

The mammalian DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AT) is inactivated during the repair process and its activity can only be restored by de novo synthesis. We have made use of this property to determine whether and to what extent various chemotherapeutic agents alkylate DNA in the O6-position of guanine, ie. produce lesions susceptible to AT repair. Adult female Fischer rats received a single i.p. injection of a high dose (LD50) of the respective agent and, 5 hr later, a chasing dose of N-nitroso-[14C]dimethylamine (0.2 mg/kg; 4 hr survival). The amount of 7-[14C]methylguanine formed was approximately 95 mumol/mol guanine and not significantly altered by pretreatment with any of the drugs. The ratio of O6-[14C]methylguanine/7-[14C]methylguanine was 0.019 for control animals, indicating that during the observation period of 4 hr, 83% of the O6-[14C]methylguanine produced had been removed by the hepatic AT. Little or no effect was found in rats that received spirohydantoin mustard, hexamethylmelamine, cis-platinum or mitomycin C. A significant increase in the O6-/7-[14C]methylguanine ratio was found after pretreatment with AZQ (0.026) and cyclophosphamide (0.028), agents for which lesions involving the O6-position of guanine have not yet been identified. N-(2-Hydroxyethyl)-N-nitrosourea and the cytostatic haloethylinitrosoureas, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU), and N-chloroethyl-N-hydroxyethylnitrosourea (HECNU) inhibited the hepatic AT, producing a ratio of 0.025-0.035. Considerably higher ratios of 0.059 and 0.101 were observed after administration of the methylating agents procarbazine and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC), respectively. Complete saturation of the repair system (O6-/7-[14C]methylguanine ratio, 0.11) was only achieved with N-methyl-N-nitrosourea.

In vivo metabolism and reaction with DNA of the cytostatic agent, 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC).

The cytostatic drug dacarbazine [DTIC, 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide] is strongly carcinogenic in rats. Bioactivation of DTIC yields a methylating intermediate but the extent of interaction with cellular macromolecules has not previously been reported. Following a single i.p. injection of [14C-methyl]DTIC, exhalation of 14CO2 occurred with a t1/2 max of approximately 2 hr (0.95 mg/kg) and 2.5 hr (95 mg/kg). Of the total radioactivity administered, 8.5% was exhaled as 14CO2; 54% was excreted via the urine, predominantly as unchanged DTIC. In liver, kidney and lung, formation of 7-[14C]methylguanine in DNA and RNA was directly proportional with dose. DNA methylation by a single dose of DTIC (9.8 mg/kg; 5 hr survival time) was highest in liver (35 mumoles 7-methylguanine/mole guanine), followed by kidney (25 mumoles) and lung (20 mumoles). The remainder tissues showed 7-methylguanine concentrations approximately 50% of those in liver DNA, with the exception of the brain which had a very low extent of DNA modification (approximately 1 mumole/mole guanine). At the specific radioactivity used (48 mCi/mmole), the promutagenic base O6-methylguanine was only detectable in liver, kidney, lung, and stomach DNA (0.6-0.8 mumoles/mole guanine). Autoradiographic studies revealed a diffuse distribution of reaction products in rat liver. In contrast, N-nitrosodimethylamine and related carcinogens known to be bioactivated by the hepatic cytochrome P-450 system show a predominantly centrilobular distribution. This difference may be due to the greater stability of proximate carcinogens generated by alpha-C hydroxylation at one of the methyl groups of DTIC.