Optimisation of scan duration and image quality in oncological 89Zr immunoPET imaging using the Biograph Vision PET/CT.

PURPOSE: Monoclonal antibody (mAb)-based PET (immunoPET) imaging can characterise tumour lesions non-invasively. It may be a valuable tool to determine which patients may benefit from treatment with a specific monoclonal antibody (mAb) and evaluate treatment response. For 89Zr immunoPET imaging, higher sensitivity of state-of-the art PET/CT systems equipped with silicon photomultiplier (SiPM)-based detector elements may be beneficial as the low positron abundance of 89Zr causes a low signal-to-noise level. Moreover, the long physical half-life limits the amount of activity that can be administered to the patients leading to poor image quality even when using long scan durations. Here, we investigated the difference in semiquantitative performance between the PMT-based Biograph mCT, our clinical reference system, and the SiPM-based Biograph Vision PET/CT in 89Zr immunoPET imaging. Furthermore, the effects of scan duration reduction using the Vision on semiquantitative imaging parameters and its influence on image quality assessment were evaluated. METHODS: Data were acquired on day 4 post 37 MBq 89Zr-labelled mAb injection. Five patients underwent a double scan protocol on both systems. Ten patients were scanned only on the Vision. For PET image reconstruction, three protocols were used, i.e. one camera-dependent protocol and European Association of Nuclear Medicine Research Limited (EARL) standards 1 and 2 compliant protocols. Vision data were acquired in listmode and were reprocessed to obtain images at shorter scan durations. Semiquantitative PET image parameters were derived from tumour lesions and healthy tissues to assess differences between systems and scan durations. Differently reconstructed images obtained using the Vision were visually scored regarding image quality by two nuclear medicine physicians. RESULTS: When images were reconstructed using 100% acquisition time on both systems following EARL standard 1 compliant reconstruction protocols, results regarding semiquantification were comparable. For Vision data, reconstructed images that conform to EARL1 standards still resulted in comparable semiquantification at shorter scan durations (75% and 50%) regarding 100% acquisition time. CONCLUSION: Scan duration of 89Zr immunoPET imaging using the Vision can be decreased up to 50% compared with using the mCT while maintaining image quality using the EARL1 compliant reconstruction protocol.

Deciphering the immunopeptidome in vivo reveals new tumour antigens.

Immunosurveillance of cancer requires the presentation of peptide antigens on major histocompatibility complex class I (MHC-I) molecules1-5. Current approaches to profiling of MHC-I-associated peptides, collectively known as the immunopeptidome, are limited to in vitro investigation or bulk tumour lysates, which limits our understanding of cancer-specific patterns of antigen presentation in vivo6. To overcome these limitations, we engineered an inducible affinity tag into the mouse MHC-I gene (H2-K1) and targeted this allele to the KrasLSL-G12D/+Trp53fl/fl mouse model (KP/KbStrep)7. This approach enabled us to precisely isolate MHC-I peptides from autochthonous pancreatic ductal adenocarcinoma and from lung adenocarcinoma (LUAD) in vivo. In addition, we profiled the LUAD immunopeptidome from the alveolar type 2 cell of origin up to late-stage disease. Differential peptide presentation in LUAD was not predictable by mRNA expression or translation efficiency and is probably driven by post-translational mechanisms. Vaccination with peptides presented by LUAD in vivo induced CD8+ T cell responses in naive mice and tumour-bearing mice. Many peptides specific to LUAD, including immunogenic peptides, exhibited minimal expression of the cognate mRNA, which prompts the reconsideration of antigen prediction pipelines that triage peptides according to transcript abundance8. Beyond cancer, the KbStrep allele is compatible with other Cre-driver lines to explore antigen presentation in vivo in the pursuit of understanding basic immunology, infectious disease and autoimmunity.

Notch3 is involved in adipogenesis of human adipose-derived stromal/stem cells.

Human adipose-derived stromal/stem cells (hASCs) have tremendous therapeutic potential and the ability to offer insight into human development and disease. Here we subject human ASCs to siRNA-mediated knockdown of Notch3 cultured under both self-renewing and adipogenic differentiation conditions. Self-renewal was monitored by assessing viability and proliferation rates through staining and alamarBlue assays, respectively. Adipogenesis was measured through Oil-Red O staining, western blot, and quantitative real-time RT-PCR that determined expression levels of multipotency and adipogenic markers over time. Notch3 was expressed in self-renewing hASCs but knockdown, as validated by qRT-PCR and western blot, showed no impact on cell viability, as measured through live-dead staining, or cell proliferation rates, as measured through alamarBlue assays. However, although Notch3 expression was observed to increase during adipogenesis, in the absence of Notch3 there was a significant increase in hASC adipogenesis as demonstrated through an increased number of lipid vesicles, and increased expression of adipogenic markers ppar-γ, adiponectin, fabp4, and plin2. Although Notch3 is only one of four Notch receptors expressed on the surface of hASCs, this receptor appears important for proper regulation of adipogenic differentiation, possibly serving as a negative regulator to prevent inappropriate adipogenesis or promote other lineage commitments of ASCs.

[Emerging problems in enforcement of safe maternity and feeding protection at work: a public prevention service experience]. / Problematiche emerse nell'applicazione della tutela della lavoratrice in gravidanza, puerperio e allattamento: esperienza di un servizio pubblico di prevenzione.

We have examined the claims for advance maternity leave or prolonged benefits for breastfeeding addressed to Occupational Health Unity of Local Health Service 11 by women at harmful works in the period 2002-2005. The most frequent occupations were: shoemaker (29%), service company's employee (7%), tanners (7%), leather industry's employee (6%) and food industry's employee (6%). The most important risk factors were: bound postures, manual load handling, chemical hazards and biological agents. The numbers of claims increased during the period of interest. In the work place often risks for pregnancy and breastfeeding are not correctly assessed and women workers are not informed on their rights. The Occupational Health Unity of Local Health Service 11 tried to correct the lack of information for workers, employers, workers' representatives in health and safety and enterprise's occupational health physician.

Depressive symptoms among African American women with HIV disease.

Depressive symptoms are a common response to HIV disease and evidence suggests that women may be at particular risk. Very little of the research on depressive symptoms within the context of HIV disease has included women, however, and even fewer studies have targeted African American women. In a beginning effort to address this gap, the authors performed a secondary analysis of data collected from 1992-1995 in a sample of 264 HIV+ women. The purpose of the secondary analysis was to describe the levels of depressive symptoms for a subsample of 152 African American subjects and to identify significant covariates. The original analysis was based on a stress and coping framework and was designed to provide a description of stressors, resistance factors, and adaptational outcomes of HIV+ women. It included various measures of psychological distress and quality of life. Depressive symptoms were not examined in the original analysis as an outcome of HIV disease, however. In the secondary analysis, depressive symptoms were operationalized using a depression subscale of the Brief Symptom Inventory (BSI) (Deragotis, 1993). Major categories of correlates examined included person resources, environmental resources, coping responses, and disease-related stressors. The data used in the analysis were collected during the fourth and fifth interviews of the longitudinal study, with 152 of the African American women having completed both interviews. Variance in depressive symptoms was analyzed using ANOVA, zero-order correlations, and multiple regression analysis. The mean depressive symptoms score for the subsample of African American women was considerably higher than published means for female and male normative samples, respectively. The regression model accounted for over half of the variance in depressive symptoms (R2 = .515). Significant correlates included self-esteem, family cohesion, HIV symptoms and quality of life. The findings support personal and social resources and disease-related factors as important correlates of HIV+ African American women's depressive symptoms and suggest the need for interventions to address such factors.

Sources of occupational stress and coping strategies among nurses working in AIDS care.

Nurses working in AIDS care experience high rates of occupational stress and therefore are vulnerable to emotional exhaustion and occupational burnout. This study surveyed 499 members of the Association of Nurses in AIDS Care regarding their work-related stress experiences and coping strategies for managing stress. Qualitative analyses identified a hierarchical structure of occupational stress, with two supraclusters representing workplace and patient care-related stress and eight specific subclusters of stressors: institutions, personnel, biohazards, death, informing patients, challenging patients, families, and treatment dilemmas. Analyses showed that nurses experiencing stress from their workplace were significantly more likely to use wishful thinking, planful problem solving, and avoidance as coping strategies, whereas stress originating from patient care was more likely to be dealt with using positive appraisal and acceptance. Interventions designed to assist nurses in managing occupational stress and to prevent occupational burnout must include the sources of work-related stress among nurses in AIDS care.

Work-related stress and occupational burnout in AIDS caregivers: test of a coping model with nurses providing AIDS care.

Occupational stress and burnout are potential threats to quality of care for people living with HIV/AIDS. A total of 445 nurses who provide care to people living with HIV/AIDS responded to an anonymous postal survey that consisted of: demographic and work history questions, the Maslach Burnout Inventory, Rotter's Internal-External Locus of Control scale, and internal and external coping styles as measured by the Ways of Coping scale. Path analyses showed that both external (13.6% of the variance) and internal (3.1% of the variance) coping styles significantly predicted levels of burnout among AIDS caregivers, over and above participants' age, perceived workload and locus of control. Mediation analyses further showed that external coping mediates the effect of locus of control on burnout, but internal coping styles do not exhibit mediation. Results therefore replicate and extend previous research demonstrating the important roles of cognitive and behavioural coping styles in understanding burnout among providers of AIDS care.

Coping and psychosocial adjustment of women with diabetes.

PURPOSE: The purpose of this study was to investigate relationships between coping styles and psychosocial adjustment for women with diabetes. METHODS: The sample consisted of 115 community-residing women with diabetes. Coping was measured by the Revised Jalowiec Coping Scale and psychosocial adjustment by the Psychosocial Adjustment to Illness Scale. Pearson's product moment correlation was used to assess relationships between coping and adjustment. RESULTS: The most frequently and effectively used coping styles were optimistic, confrontive, self-reliant, and supportant. The psychological, social, and health care domains showed the most problems; the fewest were in the extended family, sexual, and vocational domains. Relationships were found between women's coping styles and psychosocial adjustment, with better adjustment associated with effective use of confrontive, supportant, optimistic, self-reliant, and palliative coping styles. CONCLUSIONS: Important relationships exist between the ways women cope with diabetes and their level of psychosocial adjustment to the illness. Knowledge of these relationships can help diabetes educators assist clients in making lifestyle changes.

Spiritual activities as a resistance resource for women with human immunodeficiency virus.

BACKGROUND: Few studies have investigated the role that spiritual activities play in the adaptational outcomes of women with human immunodeficiency virus (HIV) disease. OBJECTIVE: To examine the role of spiritual activities as a resource that may reduce the negative effects of disease-related stressors on the adaptational outcomes in HIV-infected women. METHODS: A theoretically based causal model was tested to examine the role of spiritual activities as a moderator of the impact of HIV-related stressors (functional impairment, work impairment, and HIV-related symptoms) on two stress-related adaptational outcomes (emotional distress and quality of life), using a clinic-based sample of 184 HIV-positive women. RESULTS: Findings indicated that as spiritual activities increased, emotional distress decreased even when adjustments were made for HIV-related stressors. A positive relationship between spiritual activities and quality of life was found, which approached significance. Findings showed that HIV-related stressors have a significant negative effect on both emotional distress and quality of life. CONCLUSIONS: The findings support the hypothesis that spiritual activities are an important psychological resource accounting for individual variability in adjustment to the stressors associated with HIV disease.

Women's psychosocial adjustment to diabetes.

Successful adjustment to a chronic illness such as diabetes mellitus is influenced by a variety of psychosocial factors. The purpose of this study was to examine the extent to which social support, personal resources, coping styles, and psychosocial adjustment to illness differ among women with diabetes living in different types of household structure and to explore the influence of social support, personal resources, coping styles, and household structure on the psychosocial adjustment of women with diabetes. Data were collected in 1995. The convenience sample included 115 diabetic women with an average age of 48 years. Mean length of time from diagnosis was 10 years. Instruments included a demographic data form, a measure of social support, a personal resource scale, the Jalowiec Coping Scale, the Psychosocial Adjustment to Illness Scale-Self-Report, and a self-report item for assessing household structure. Multiple analysis of variance showed that women in various types of households differed in personal resources and coping. Higher levels of social support and more adequate personal resources were associated with more effective coping and better psychosocial adjustment. The effective use of confrontive, optimistic, supportant and self-reliant coping was associated with better psychosocial adjustment, while evasive and emotive coping styles were associated with more adjustment problems. Multiple regression showed that 47% of the variance in adjustment was explained by personal resources and social support. Findings indicated that women in various types of households differed in the adequacy of their resources and in the ways that they cope with diabetes. Findings further indicated that greater social support, more adequate personal resources, and more effective coping are associated with better adjustment.

The effectiveness of coping strategies used by HIV-seropositive women.

The effectiveness of active and passive coping strategies was examined in a sample of 264 women infected with HIV. Coping was measured concurrent with, and 3 months prior to, measurement of physical symptoms and emotional distress. Two causal models were tested: one for active coping and one for passive coping. Active coping strategies examined included seeking social support, managing the illness, and spiritual activities. Avoidance was used as an indicator of passive coping. In both models, physical symptoms and emotional distress were positively and significantly related. The findings indicated that, whereas current avoidance coping was not related to emotional distress, current active coping was positively related to physical symptoms and negatively related to emotional distress. The immediate effects of active coping appeared to serve a protective function in that emotional distress decreased with greater use of active coping, even as physical symptoms increased. Avoidance coping had no such protective effect for emotional distress. In addition, the use of avoidance coping decreased and active coping increased as physical symptoms increased, suggesting that active coping is more likely to be used with increasing levels of physical symptoms. The findings suggest that interventions that support attempts to use active coping strategies as physical symptoms increase may be effective in promoting positive adaptation to HIV disease.

Maternal drug use during pregnancy: are preterm and full-term infants affected differently?

This study examined whether preterm infants are more vulnerable to the effects of prenatal drug exposure than are full-term infants. The sample of 235 low-income African American mothers and their infants included 119 cocaine-polydrug users, 19 alcohol-only users, and 97 nonusers; 148 infants were full term and 87 were preterm. Direct effects of exposure on birth weight, birth length, ponderal index, and irritability were moderated by length of gestation: Fetal growth deficits were more extreme in later-born infants, whereas increases in irritability were more extreme in earlier born infants. Effects of exposure on cardiorespiratory reactivity to a neonatal exam were not moderated by length of gestation. In general, effects of exposure occurred for both cocaine-polydrug and alcohol only users and so could not be unambiguously attributed to either of these drugs alone.

Quality of life in HIV-infected women in the south-eastern United States.

The purpose of this study was to evaluate the relative importance of social (social support, material resources, disclosure, and family functioning) and psychological factors (stigma, emotional distress, intrusion, avoidance, and fatalism) as predictors of the quality of life of women infected with HIV. The cross-sectional data were drawn from interviews of a sample of 264 women recruited from 8 HIV/AIDS treatment sites in a south-eastern state. Variance in quality of life variables, included limited daily functioning, general anxiety, and HIV symptoms was analyzed using ANOVA, correlations, and hierarchical multiple regression analysis. Limited daily functioning was predicted by stigma, fatalism, employment status, and stage of disease (R2 = 0.179). General anxiety was predicted by emotional distress, intrusion, and marital status (R2 = 0.503). Reported HIV symptoms were predicted by material resources, disclosure, intrusion, age, employment status, and race (R2 = 0.294). The results of this study support that social and, particularly, psychological factors are important in their influence on quality of life in women with HIV infection and suggest the need for interventions which address such factors.

Resources, stigma, and patterns of disclosure in rural women with HIV infection.

A growing number of cases of HIV infection are being diagnosed in rural communities especially among women. Although HIV-specific education and care delivery programs have been focused on rural areas in recent years, limited data are available on the impact of such initiatives on the lives of women with HIV infection. The purpose of this study was to examine characteristics of women with HIV disease living in rural communities. The study used a cross-sectional sample of rural women in Georgia. Data analysis indicated that although a majority of the women reported adequate resources, there was a group of women for whom resources for basic needs were not always adequate. Additionally, women with HIV who had not progressed to AIDS had greater difficulty in obtaining a number of resources. Almost half of the women felt stigmatized due to having HIV. Yet, a high percentage of these women had disclosed their HIV status to health care workers, sexual partners, and family. Study results provide insight into the needs of HIV-infected rural women from their perspective. This information can be important to nurses working in public health and community settings as they face the challenge of developing effective health care services for this population.

The impact of HIV on emotional distress of infected women: cognitive appraisal and coping as mediators.

This study examined the role of psychological factors as mediators of the impact of HIV-related stressors on emotional distress of a clinic-based sample of 264 HIV+ women. Based upon Lazarus and colleagues' cognitively oriented theory of stress and coping, causal modeling was used to test for mediating effects of cognitive appraisal (intrusive thoughts and perceived stigma) and coping variables (avoidance and fatalism) on emotional distress within the context of HIV-related stressors (functional impairment and work performance impairment). The findings supported the mediating effects of cognitive appraisal but not of the coping variables. Consistent with theory, the effect of HIV-related stressors on emotional distress was indirect through cognitive appraisal; however, there were no significant direct effects of HIV-related stressors, fatalism or avoidance on emotional distress. The causal model accounted for significant portions of variance in emotional distress (R2 = .49) and the model fit, as a whole, was more than adequate. The findings indicate that how HIV+ women think about HIV-related stressors is an important factor that may account for individual variability in the ability to maintain a sense of subjective well-being in the face of a devastating fatal disease.

Older adults' attitudes toward suicide: are there race and gender differences?

Suicide among older persons in the United States is a major problem that has increased dramatically during the past decade. Little is known about older nonsuicidal adults' attitudes toward suicide. The purpose of this study was to identify attitudes of older persons toward suicide and to explore the relationship of race and gender to attitudes toward suicide. The Suicide Attitude Vignette Experiences for the Elderly (SAVE-L) scale, which consists of 16 vignettes, was used to measure empathy toward suicidal people and agreement with suicidal actions as portrayed in 16 vignettes. The sample consisted of 54 low-income, inner city residents, aged 65 or older. Participants reported a moderate level of empathy with suicidal behavior (M = 2.82 on a 5-point scale) and a low level of agreement with suicidal actions (M = 1.31 on a 5-point scale). There were no differences in empathy toward suicidal people nor in agreement with suicidal people's actions based on race (African American or White) or gender; nor was there a significant interactional effect of race and gender on attitudes toward suicide.

The health status of elderly persons in the last year of life: a comparison of deaths by suicide, injury, and natural causes.

OBJECTIVES: This study identified health status variables related to suicide by elderly persons and compared the health status of suicide decedents with natural death and injury decedents. METHODS: Data were obtained from the 1986 National Mortality Followback Survey. RESULTS: When other variables were controlled for, suicide decedents were significantly more likely than injury decedents to have a history of cancer (odds ratio [OR] = 51.94), moderate (OR = 29.37) or heavy (OR = 22.87) alcohol use, and mental or emotional disorder (OR = 10.91) and to be White (OR = 18.54) and male (OR = 9.12). CONCLUSIONS: The findings indicate that a history of cancer should be considered as a risk for suicide in the elderly.

Self-care activities of women infected with human immunodeficiency virus.

The article describes a qualitative focus group study exploring the self-care activities undertaken by women testing positive for human immunodeficiency virus (HIV) to promote and maintain their health. The sample included 27 women who participated in one of four focus group sessions. Participants represented women from both rural and urban settings in the South. Subjects talked about and described the ways in which they took care of themselves. Content analysis was used to code the data and to determine major categories of activities. Seven categories were identified: special dietary and nutrition practices, choosing not to use medically prescribed therapies, spiritual reliance and rituals, staying active, cognitive strategies, self-education, and adopting healthy life styles. These findings support the value of developing a holistic approach to health care of women infected with HIV.

Barriers to health-seeking behaviors for women infected with HIV.

There is a growing need to develop services for women with human immunodeficiency virus (HIV) infection, despite the reluctance of many to seek help. Yet, there is limited knowledge of the forces that act as barriers to health-seeking behaviors among these women. In the analysis of this focus group study of 46 women with HIV, eight distinct categories of perceived barriers to care were identified. These were: Lack of knowledge on the part of health care providers, fear of negative treatment, insensitivity of health care providers, fear by providers, lack of patient education, lack of confidentiality, lack of honesty, and blaming the victim. The women's descriptions of their experiences with health care providers are presented and discussed in the context of the potential impact of such behaviors on women's willingness to accept or continue treatment for HIV infection.

Perceptions of stigma in women infected with HIV.

This qualitative focus group study explored perceptions of stigma in HIV-seropositive women. The sample included 19 HIV-positive women who participated in one of four focus group sessions. Participants were asked to talk about and describe their perceptions of how others think about and respond to them and other HIV-infected individuals. Content analysis was used to code the data and identify participant perceptions. Four themes representing distinctly different perceptions of stigma were identified: distancing, overgeneralizing stereotypes, social discomfort, and pity. The implications of the findings for intervention and future research are discussed.