Humoral and cellular immune responses to SARS CoV-2 vaccination in People with Multiple Sclerosis and NMOSD patients receiving immunomodulatory treatments.

BACKGROUND: Vaccination against SARS CoV-2 results in excellent personal protection against a severe course of COVID19. In People with Multiple Sclerosis (PwMS) vaccination efficacy may be reduced by immunomodulatory medications. OBJECTIVE: To assess the vaccination induced cellular and humoral immune response in PwMS receiving disease modifying therapies. METHODS: In a monocentric observational study on PwMS and patients with Neuromyelitis optica we quantified the cellular and humoral immune responses to SARS CoV-2. RESULTS: PwMS receiving glatiramer acetate, Interferon-ß, Dimethylfumarate, Cladribine or Natalizumab had intact humoral and cellular immune responses following vaccination against SARS CoV-2. B-cell depleting therapies reduced B-cell responses but did not affect T cell responses. Sphingosin-1-Phospate (S1P) inhibitors strongly reduced humoral and cellular immune responses. There was a good agreement between the Interferon gamma release assay and the T-SPOT assay used to measure viral antigen induced T-cell responses. CONCLUSION: This study demonstrates that S1P inhibitors impair the cellular and humoral immune response in SARS CoV-2 vaccination, whereas patients receiving B-cell depleting therapies mount an intact cellular immune response. These data can support clinicians in counselling their PwMS and NMOSD patients during the COVID 19 pandemic.

Patients' preimplantation genetic testing decision-making experience: an opinion on related psychological frameworks.

The process of deciding whether to pursue preimplantation genetic testing (PGT) of an embryo is highly stressful for individuals and couples and has adverse emotional consequences (e.g. distress and uncertainty). PGT influences patients' lives in both positive and negative ways and is experienced at an individual level, as a dyadic unit, as a family member and as part of the society. Here, we argue that providing a conceptual framework with which to understand the `experience of decision making' about PGT for monogenic disease (PGT-M) testing specifically, as well as the factors contributing to `decisional distress' and `uncertainty' that patients endure as a result-apart from what decision they make-is crucial to optimizing patient counseling, satisfaction and outcomes in the field of ART. Derived from psychological theory, the framework proposed here identifies three categories of contributing factors to decisional distress and uncertainty in considering PGT-M; namely, 'intraindividual', 'interpersonal' and 'situational' factors. We reviewed evidence from the PGT literature to inform our framework. Well-accepted theories of stress and health decision making were also reviewed for their relevance to PGT-M decision making, focusing on potential distress and uncertainty. Our novel conceptual framework can be used to inform clinical practice, to advance research and to aid the development of interventions for individuals and couples who are deciding whether or not to use PGT-M. Alleviating emotional distress and uncertainty can improve patients' well-being during their reproductive journey.

Review of patient decision-making factors and attitudes regarding preimplantation genetic diagnosis.

The increasing technical complexity and evolving options for repro-genetic testing have direct implications for information processing and decision making, yet the research among patients considering preimplantation genetic diagnosis (PGD) is narrowly focused. This review synthesizes the literature regarding patient PGD decision-making factors, and illuminates gaps for future research and clinical translation. Twenty-five articles met the inclusion criteria for evaluating experiences and attitudes of patients directly involved in PGD as an intervention or considering using PGD. Thirteen reports were focused exclusively on a specific disease or condition. Five themes emerged: (1) patients motivated by prospects of a healthy, genetic-variant-free child, (2) PGD requires a commitment of time, money, energy and emotions, (3) patients concerned about logistics and ethics of discarding embryos, (4) some patients feel sense of responsibility to use available technologies, and (5) PGD decisions are complex for individuals and couples. Patient research on PGD decision-making processes has very infrequently used validated instruments, and the data collected through both quantitative and qualitative designs have been inconsistent. Future research for improving clinical counseling is needed to fill many gaps remaining in the literature regarding this decision-making process, and suggestions are offered.

Adiponectin promotes coxsackievirus B3 myocarditis by suppression of acute anti-viral immune responses.

Adiponectin (APN) is an immunomodulatory adipocytokine that improves outcome in patients with virus-negative inflammatory cardiomyopathy and mice with autoimmune myocarditis. Here, we investigated whether APN modulates cardiac inflammation and injury in coxsackievirus B3 (CVB3) myocarditis. Myocarditis was induced by CVB3 infection of APN-KO and WT mice. APN reconstitution was performed by adenoviral gene transfer. Expression analyses were performed by qRT-PCR and immunoblot. Cardiac histology was analyzed by H&E-stain and immunohistochemistry. APN-KO mice exhibited diminished subacute myocarditis with reduced viral load, attenuated inflammatory infiltrates determined by NKp46, F4/80 and CD3/CD4/CD8 expression and reduced IFNß, IFNγ, TNFα, IL-1ß and IL-12 levels. Moreover, myocardial injury assessed by necrotic lesions and troponin I release was attenuated resulting in preserved left ventricular function. Those changes were reversed by APN reconstitution. APN had no influence on adhesion, uptake or replication of CVB3 in cardiac myocytes. In acute CVB3 myocarditis, cardiac viral load did not differ between APN-KO and WT mice. However, APN-KO mice displayed an enhanced acute immune response, i.e. increased expression of myocardial CD14, IFNß, IFNγ, IL-12, and TNFα resulting in increased cardiac infiltration with pro-inflammatory M1 macrophages and activated NK cells. Up-regulation of cardiac CD14 expression, type I and II IFNs and inflammatory cell accumulation in APN-KO mice was inhibited by APN reconstitution. Our observations indicate that APN promotes CVB3 myocarditis by suppression of toll-like receptor-dependent innate immune responses, polarization of anti-inflammatory M2 macrophages and reduction of number and activation of NK cells resulting in attenuated acute anti-viral immune responses.

The impact of prenatal maternal stress and optimistic disposition on birth outcomes in medically high-risk women.

A sizable body of evidence indicates that prenatal maternal stress (PNMS) has an adverse impact on birth outcomes, including birth weight and gestational age at delivery. The authors hypothesized that effects of PNMS are attributable in part to dispositions such as pessimism that lead women to view their lives as stressful and that effects of PNMS and disposition on birth outcome are mediated by prenatal health behaviors. Using structural equations modeling procedures, the authors examined prospective impact of PNMS and dispositional optimism on birth weight and gestational age in a medically high-risk sample (N = 129), controlling for effects of risk and ethnicity. After its strong inverse association with optimism was accounted for, PNMS had no impact on birth outcomes. Women who were least optimistic delivered infants who weighed significantly less, controlling for gestational age. Optimists were more likely to exercise, and exercise was associated with lower risk of preterm delivery. Results suggest that chronic stress in pregnancy may be a reflection of underlying dispositions that contribute to adverse birth outcomes.

The perils of outperformance: sensitivity about being the target of a threatening upward comparison.

Outperforming others, although privately satisfying, can be a source of interpersonal strain. This article presents the framework of a major form of outperformance-related distress, which we label sensitivity about being the target of a threatening upward comparison (STTUC). To become STTUC, an individual must believe that another person is making an upward comparison against the self and feels threatened by the contrast in status. The outperformer must also experience concern about some facet of the other's response, and this concern may be focused on the other, the self, or the relationship. In addition to offering new predictions about outperformance-related distress, the STTUC framework unites many previously disconnected findings on topics such as fear of success, envy, self-presentation, and self-evaluation maintenance.

Coping and distress in pregnancy: an investigation of medically high risk women.

The association between coping and pregnancy-specific distress was examined in 167 pregnant women at high medical risk. A population-appropriate coping inventory and prenatal distress measure were administered in mid-pregnancy (mean of 24 weeks gestation). Subjects experienced moderately high levels of distress about preterm delivery, physical symptoms, labor and delivery, weight gain, and having an unhealthy baby. They most frequently coped with the demands and challenges of pregnancy through prayer and positive appraisal. Sociodemographic variables including age, income, education, and parity were significantly associated with ways of coping. Coping by avoidance, preparation for motherhood, and substance use were associated with greater distress, whereas coping by positive appraisal was associated with less distress. These effects differed somewhat when levels of global, non-specific distress were controlled. Findings underscore the unique nature of high-risk pregnancy as a stressful life event.

When god disappoints: difficulty forgiving god and its role in negative emotion.

In light of growing empirical interest in the links between forgiveness, religious belief, and well-being, a study was designed to examine the emotional impact of a specific problem with forgiveness: difficulty forgiving God. Difficulty forgiving God was found to predict anxious and depressed mood within a college student sample (N 5 200), and its contribution was independent of difficulties forgiving the self and others. Two psychological factors emerged as central in explaining the link between difficulty forgiving God and negative emotion: an angry disposition and feelings of alienation from God. Also, among those who currently believed in God, forgiving God for a specific, powerful incident predicted lower levels of anxious and depressed mood. These findings suggest that an unforgiving attitude toward God is a distinct type of problem with forgiveness, one that serves as a potent predictor of negative emotion.

Single-mode operation of a laser-diode array with frequency-selective phase-conjugate feedback.

A new technique for single-mode operation of laser-diode arrays is presented. A gain-guided GaAlAs laser diode array is coupled to an external frequency-selective phase-conjugate feedback system that contains a photorefractive barium titanate crystal, a Fabry-Perot etalon, and a spatial filter. The etalon is the key component, and it forces the array, which has low spatial and spectral coherence when it runs freely, to oscillate in a single spatial and a single longitudinal mode. At a drive current of two times the threshold current, the far-field pattern is reduced to only 1.4 times the diffraction limit, the spectral bandwidth is less than 0.02 nm, and the coherence length is increased by a factor of 70. The technique has general validity and can be applied to various other multimode laser systems.

Conception, commitment, and health behavior practices in medically high-risk pregnant women.

Based on cognitive dissonance and related theories of commitment, this study tested hypotheses that planning pregnancy and number of months spent trying to conceive would be associated with better prenatal health behaviors and that commitment to pregnancy and motherhood would mediate these associations. Participants (N = 96) were pregnant women at high medical risk for an adverse birth outcome. As predicted, planning pregnancy predicted better prenatal health care practices, and this effect was mediated by commitment level. Among women who planned their pregnancy, longer time to conceive predicted higher commitment but did not influence prenatal health behaviors directly. Women who had given birth previously practiced fewer prenatal health behaviors. Commitment, however, remained the strongest predictor of prenatal health care practices. Results are consistent with theories of commitment and with prominent approaches to the study of health behavior.

Psychosocial predictors of postpartum depressed mood in socioeconomically disadvantaged women.

The effects of stress, social support, and labor and delivery experiences on postpartum depressed mood were examined in an ethnically diverse sample of low-income women (N = 108). Women were interviewed on multiple occasions throughout pregnancy and then once approximately 2 months postpartum. Information on labor and delivery outcomes was abstracted from medical charts. Results indicated that women who were more satisfied with the prenatal social support they received were less likely to experience postpartum depressed mood, after controlling for prenatal depressive symptomatology. In addition, women who experienced more distressing life events during pregnancy and who reported higher levels of prenatal anxiety were also more likely to feel depressed, after controlling for all other factors in the model. Finally, women who were more satisfied with their labor and delivery experience tended to be less depressed in the early months following childbirth. Together, these variables accounted for 45% of the variance in postpartum depressed mood.

Conceptualizations, measurement, and effects of prenatal maternal stress on birth outcomes.

This article analyzes the conceptual and methodological approaches which have been used to investigate effects of prenatal maternal stress on birth outcomes and highlights the major findings of this research. By viewing the most widely used operational definitions of prenatal stress in a broader theoretical framework, it can be seen that most studies have failed to conceptualize stress reliably. This, in addition to common methodological and design flaws which are described in the article, has produced equivocal findings about the role of stress in adverse birth outcomes such as preterm delivery and low birth weight. Recent studies using more powerful, multidimensional approaches to stress definition and measurement provide more definitive evidence and suggest some precise effects. Implications and strategies for future research are presented.

Effects of environmental demands, stress, and mood on health practices.

The present study examined how environmental demands, stress, and positive and negative affect were related to health practices. College undergraduates (N = 79) completed measures of stress, mood, and health practices during periods of low and high academic demands. Positive affect was positively related to exercise, nutrition, self-care practices, and overall health practices at two measurement points. Levels of stress (daily hassles, perceived stress, academic stress) increased over time, but increases in daily hassles and perceived stress were unrelated to health practices. Increases in academic demands completed in the previous week were associated with improvements in nutrition and self-care practices, greater drug avoidance, and greater overall health practices. This pattern indicates that a "rebound effect" may occur after high demand periods, during which individuals engage in more health-promoting activities. The results also suggest that the determinants of positive health practices may differ from those of negative health practices.

Social support in pregnancy: psychosocial correlates of birth outcomes and postpartum depression.

This prospective study examined the effects of prenatal social support on maternal and infant health and well-being in a sample of low-income pregnant women (N = 129). Three aspects of support (amount received, quality of support received, and network resources) and four outcomes (birth weight, Apgar scores, labor progress, and postpartum depression) were studied. Results indicated that women who received more support had better labor progress and babies with higher Apgar scores. Women with higher quality support had babies with higher Apgar scores and experienced less postpartum depression. Also, women with larger networks had babies of higher birth weight. Further analyses indicated that the outcomes as a whole were more consistently predicted by instrumental rather than emotional forms of support. Finally, although there was some evidence for stress-buffering effects of support, the overall findings were more consistent with a main effect model.

Prenatal maternal stress and prematurity: a prospective study of socioeconomically disadvantaged women.

Developed and tested a biopsychosocial model of birthweight and gestational age at delivery using structural equation modeling procedures. The model tested the effects of medical risk and prenatal stress on these indicators of prematurity after controlling for whether a woman had ever given birth (parity). Subjects were 130 women of low socioeconomic status interviewed throughout pregnancy in conjunction with prenatal care visits to a public clinic. The majority of women were Latino or African-American. Half were interviewed in Spanish. Lower birthweight was predicted by earlier delivery and by prenatal stress. Earlier delivery was predicted by medical risk and by prenatal stress. Parity was not related to time of delivery or to birthweight. Implications of results for the development of biopsychosocial research on pregnancy and on stress are discussed.

Social comparison activity under threat: downward evaluation and upward contacts.

Social comparison processes include the desire to affiliate with others, the desire for information about others, and explicit self-evaluation against others. Previously these types of comparison activity and their corresponding measures have been treated as interchangeable. We present evidence that in certain groups under threat, these comparison activities diverge, with explicit self-evaluation made against a less fortunate target (downward evaluation), but information and affiliation sought out from more fortunate others (upward contacts). These effects occur because downward evaluation and upward contacts appear to serve different needs, the former ameliorating self-esteem and the latter enabling a person to improve his or her situation and simultaneously increase motivation and hope. Implications for the concept, measurement, and theory of social comparison are discussed.

[The nuclear surface area as a malignancy parameter in breast cancer]. / Die Kernflächengrösse als Malignitätsparameter beim Mammakarzinom.

For better characterisation of the degree of malignancy of breast cancers, we have attempted to establish a correlation between nuclear size and prognosis in breast cancer. Karyometric investigations were carried out on biopsies from 200 primary breast cancers. On the basis of the nuclear areas determined, we were able to distinguish three groups of carcinomas: group I: carcinomas with small nuclear areas (n = 33), mean value 97.76 microns 2, group II: carcinomas with intermediate nuclear areas (n = 98), mean value of the nuclear areas 146.5 microns 2, group III: carcinomas with large nuclear areas (n = 69), mean value 190.8 microns 2. After five years, 6% of the patients in group I had died, as compared to 35% in group II and 48% in group III. The median survival time was 45 to 48 months in group I, as compared to 37 months in group II and 28 months in group III. There was a direct correlation between axillary lymph node status and nuclear size: the carcinomas with the small nuclear sizes showed the least involvement. A comparison of the prognostic relevance of nodal status and nuclear area size, reveals a good relevance for the nuclear area similar to that of the nodal status. The results of the biopsy cytology are already available to the surgeon before the operation.