Genetic counseling and testing for females at elevated risk for breast cancer: Protocol for the randomized controlled trial of the Know Your Risk intervention.

BACKGROUND: Genetic counseling and testing have an important role in the care of patients at elevated risk for breast cancer. However, conventional pre- and post-test genetic counseling is labor and time intensive, less accessible for patients living outside major urban centers, and impractical on a large scale. A patient-driven approach to genetic counseling and testing may increase access, improve patients' experiences, affect efficiency of clinical practice, and help meet workforce demand. The objective of this 2-arm randomized controlled trial is to determine the efficacy of Know Your Risk (KYR), a genetic counseling patient preference intervention. METHODS: Females (n = 1000) at elevated risk (>20% lifetime) for breast cancer will be randomized to the KYR intervention or conventional genetic counseling. The study will provide comprehensive assessment of breast cancer risk by multigene panel testing and validated polygenic risk score. Primary outcome is adherence to National Comprehensive Cancer Network guidelines for a clinical encounter every 6-12 months and an annual mammogram (breast MRI if recommended) determined by medical record review. Secondary outcomes include adherence to other recommended cancer screening tests determined by medical record review and changes in breast cancer knowledge, perception of risk, post-test/counseling distress, and satisfaction with counseling by completion of three surveys during the study. Study aims will be evaluated for non-inferiority of the KYR intervention compared to conventional genetic counseling. CONCLUSION: If efficacious, the KYR intervention has the potential to improve patients' experience and may change how genetic counseling is delivered, inform best practices, and reduce workforce burden. TRIAL REGISTRATION: ClinicalTrials.govNCT05325151.

A Randomized Trial Comparing the Effectiveness of Pre-test Genetic Counseling Using an Artificial Intelligence Automated Chatbot and Traditional In-person Genetic Counseling in Women Newly Diagnosed with Breast Cancer.

BACKGROUND: Alternative service delivery models are critically needed to address the increasing demand for genetics services and limited supply of genetics experts available to provide pre-test counseling. METHODS: We conducted a prospective randomized controlled trial of women with stage 0-III breast cancer not meeting National Comprehensive Cancer Network (NCCN) criteria for genetic testing. Patients were randomized to pre-test counseling with a Chatbot or a certified genetic counselor (GC). Participants completed a questionnaire assessing their knowledge of breast cancer genetics and a survey assessing satisfaction with their decision regarding pre-test counseling. RESULTS: A total of 39 patients were enrolled and 37 were randomized to genetic counseling with an automated Chatbot or a GC; 19 were randomized to Chatbot and 18 to traditional genetic counseling, and 13 (38.2%) had a family member with breast cancer but did not meet NCCN criteria. All patients opted to undergo genetic testing. Testing revealed six pathogenic variants in five patients (13.5%): CHEK2 (n = 2), MSH3 (n = 1), MUTYH (n = 1), and BRCA1 and HOXB13 (n = 1). No patients had a delay in time-to-treatment due to genetic testing turnaround time, nor did any patients undergo additional risk reducing surgery. There was no significant difference in median knowledge score between Chatbot and traditional counseling (11 vs. 12, p = 0.09) or in median patient satisfaction score (30 vs. 30, p = 0.19). CONCLUSION: Satisfaction and comprehension in patients with breast cancer undergoing pre-test genetic counseling using an automated Chatbot is comparable to in-person genetic testing. Utilization of this technology can offer improved access to care and a much-needed alternative for pre-test counseling.

Factors influencing genetic counseling and testing for hereditary breast and ovarian cancer syndrome in a large US health care system.

Investigate whether disparities and other factors influence referral to genetic counseling and testing for hereditary breast and ovarian cancer syndrome (HBOC) in a large health care system. Examination of clinical, demographic, and socioeconomic factors from electronic health records associated with genetic referral and testing within 12 months after a new cancer diagnosed between August 1, 2013 and December 31, 2018. For patients meeting institutional criteria for HBOC testing, 60.6% were referred for genetic counseling, 88% of whom underwent germline testing; at least one pathogenic variant was found in 15.3%. Referral rates for patients with breast (69%) or ovarian cancer (65.7%) were much higher than for metastatic prostate (11.1%, p < 0.0001) or pancreatic cancer (22.3%, p < 0.0001); referral criteria were implemented more recently for the latter two cancers. Younger age, family history, and chemotherapy were associated with referral. Higher Elixhauser comorbidity score and prior cancer were associated with non-referral. No other factors were associated with genetic referral for all eligible cancers combined, although differences were seen in specific cancers. Race was a significant factor only for breast cancer, with fewer Asians than Whites referred. Health disparities in referral to genetics for HBOC cancers are mitigated in a comprehensive integrated health care system.

Genetic counseling students' and recent graduates' attitudes toward psychiatric illness.

Due to the high prevalence of mental illness in the general population, genetic counselors are likely to encounter patients with mental illness in practice, regardless of specialty. However, previous studies have shown that recent graduates of genetic counseling programs do not feel comfortable discussing mental illness in clinical encounters. One possible explanation for this discomfort is stigma toward mental illness, a well-documented phenomenon both in society and in the healthcare field. Previous studies of this phenomenon in genetic counselors and trainees have relied on self-report measures and are vulnerable to social desirability bias. We sought to gain a holistic understanding of attitudes toward mental illness held by genetic counseling trainees by measuring implicit and explicit biases. This study assessed 141 responses from genetic counseling students and recent graduates from master's graduate programs across North America. They were asked to complete a survey, which included a demographic questionnaire, a scale that has been validated for use for a variety of healthcare professionals (Nordt et al. 2006, Schizophrenia Bulletin, 32, 709), measuring explicit attitudes toward those with depression and schizophrenia (i.e., social distance and stereotype endorsement), and an implicit association test. Mean scores on the social distance and stereotype endorsement scales were higher for schizophrenia than depression, indicating higher levels of explicit bias toward the former than the latter. Participants held slightly significant implicit bias toward individuals with either physical or mental illness. These data suggest that unconscious or implicit bias may not contribute to unpreparedness to address psychiatric disorders in clinical practice that has been previously reported by new graduates. Therefore, genetic counseling trainees may be receptive to clinically relevant education pertaining to mental illness. These results could inform the curriculum of genetic counseling programs and facilitate provision of services to this population.

Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants.

Genotype-first approach allows to systematically identify carriers of pathogenic variants in BRCA1/2 genes conferring a high risk of familial breast and ovarian cancer. Participants of the Estonian biobank have expressed support for the disclosure of clinically significant findings. With an Estonian biobank cohort, we applied a genotype-first approach, contacted carriers, and offered return of results with genetic counseling. We evaluated participants' responses to and the clinical utility of the reporting of actionable genetic findings. Twenty-two of 40 contacted carriers of 17 pathogenic BRCA1/2 variants responded and chose to receive results. Eight of these 22 participants qualified for high-risk assessment based on National Comprehensive Cancer Network criteria. Twenty of 21 counseled participants appreciated being contacted. Relatives of 10 participants underwent cascade screening. Five of 16 eligible female BRCA1/2 variant carriers chose to undergo risk-reducing surgery, and 10 adhered to surveillance recommendations over the 30-month follow-up period. We recommend the return of results to population-based biobank participants; this approach could be viewed as a model for population-wide genetic testing. The genotype-first approach permits the identification of individuals at high risk who would not be identified by application of an approach based on personal and family histories only.

Role play for genetic counseling learning: Value and students perceptions.

BACKGROUND: Performing genetic counseling is one of the tasks of every paediatrician. This assumes prior training during the residency. AIM: To assess the impact of role-play (RP) for training of paediatric residents in genetic counseling and participants' perception. METHODS: Repetitive cross-sectional evaluation study. During two RP sessions, two residents played the role of the parents of a patient with cystic fibrosis, and another the role of the doctor. Residents had an evaluation by standardized patient exercises immediately before and after the session. Test scores were compared by the Wilcoxon rank test for associated samples. A satisfaction questionnaire was completed by the participants anonymously. RESULTS: Post-test scores were better than pre-test scores overall (p = 0.002) and for items in the cognitive domain (p = 0.002). Of the 12 participants, only one had had previous training in genetic counseling. All participants were satisfied with the learning and felt that it would change the way they practice. All participants thought they could do genetic counseling autonomously, but nine of them wanted to have other RP sessions on the same theme. Only one participant found the session stressful and all wanted to multiply this type of sessions for other learning. CONCLUSION: RP is an effective and well-accepted means for genetic counseling training. It should be integrated with paediatric resident training.

Genomic Essentialism: Its Provenance and Trajectory as an Anticipatory Ethical Concern.

Since the inception of large-scale human genome research, there has been much caution about the risks of exacerbating a number of socially dangerous attitudes linked to human genetics. These attitudes are usually labeled with one of a family of genetic or genomic "isms" or "ations" such as "genetic essentialism," "genetic determinism," "genetic reductionism," "geneticization," "genetic stigmatization," and "genetic discrimination." The psychosocial processes these terms refer to are taken to exacerbate several ills that are similarly labeled, from medical racism and psychological fatalism to economic exploitation and social exclusion. But as genomic information becomes more familiar in clinical and research settings as well as other life activities, do we need to continue to worry so much about this family of attitudes and their impact on existing problems? In genomics, the underlying anxiety has been that disclosure of genomic information will trigger a series of (seemingly unavoidable) negative responses that will affect individuals, their families, and their communities at large. The fundamental social challenges that hyperbolic genomic messaging, low genomic literacy, and "folk biology" help sustain remain to be addressed. If we hope to break the cycle of genomic isms and ations, we will have to get better at resisting overinterpretations of the relevance that genomics has for people's future potentials, ancestral vulnerabilities, community memberships, and ethnic affiliations.

Efeito a curto prazo da laser acupuntura na dor, ansiedade e depressão de pacientes com disfunção temporomandibular: ensaio clínico randomizado / Short-term effect of laser acupuncture on pain, anxiety and depression in patients with temporomandibular disorders: randomized clinical trial

Objetivo: Avaliar o efeito a curto prazo da laser acupuntura na dor, ansiedade e depressão em pacientes com DTM. Métodos: Foi realizado um ensaio clínico randomizado cego com portadores de DTM, diagnosticados pelo Critério de Diagnóstico de DTM (RDC/TMD). 60 pacientes foram alocados de forma aleatória em quatro grupos distintos: aconselhamento (AC), placa Oclusal (PO), fisioterapia (FP) e laser acupuntura (LA) e foram avaliados no baseline, e com 1 mês após a terapia. Para avaliação da ansiedade foram utilizados HADS, BAI, e o IDATE. Para a depressão foi BDI e HADS. Para dor foi utilizada a EVA. Foi utilizado o teste Kruskal-Wallis com nível de confiança de 95% para análise entre grupos. O pós teste de Mann-Whitney, para verificar onde estava a diferença encontrada entre os grupos. E o teste de classificações assinadas por Wilcoxon, para análise entre os tempos analisados. Resultados: Ao longo do tempo houve redução na sintomatologia dolorosa nos grupos PL (p=0,001), FP (p= 0,014) e grupo LA ficou no limiar de significância (p= 0,08). Após 30 dias de terapia houve redução significativa entre os grupos FP versus AC (p=0,004) e FP versus LA (p=0,006). O grupo FP foi o único grupo que reduziu os sintomas de ansiedade pelo BAI (p=0,09) e pelo IDATE-E (p=0,042). Nos parâmetros depressivos houve diferença estatisticamente significativa ao longo do tempo pelo BDI nos grupos PO (p=0,044) e LA (p=0,009). Entre os grupos houve diferença estatisticamente significativa pelo BDI, entre PO versus LA (p=0,004), e FP versus LA (p=0,005). E pelo HADS, entre FP versus LA (p=0,012). Conclusão: Para pacientes com ansiedade e depressão, a laser acupuntura não é a terapia mais indicada para diminuição da sintomatologia dolorosa a curto prazo (AU).

Objective: To evaluate the short-term effect of laser acupuncture compared with counseling, occlusal plaque, and physiotherapy treatments on pain, anxiety, and depression in TMD patients. Methods: A randomized clinical trial was performed with patients with TMD, diagnosed by the TMD (RDC / TMD). 60 patients were randomly allocated to four distinct groups: counseling (AC), Occlusal Plaque (PO), physical therapy (PF) and laser acupuncture (LA) and were evaluated at baseline, and at 1 month after therapy. To evaluate anxiety, HADS, BAI, and STAI were used. For depression was BDI and HADS. For pain, VAS was used. The Kruskal-Wallis test with a 95% confidence level was used for intergroup analysis. The Mann-Whitney post-test, to verify where was the difference found between the groups. And the Wilcoxon signed rank test for analysis between the times analyzed. Results: Over time there was a reduction in pain symptoms in the PL (p = 0.001), PF (p = 0.014) and LA groups were at the significance threshold (p = 0.08). After 30 days of therapy there was a significant reduction between the PF versus AC (p = 0.004) and FP versus LA (p = 0.006) groups. The FP group was the only group that reduced anxiety symptoms by BAI (p = 0.09) and by STAI-E (p = 0.042). In depressive parameters there was a statistically significant difference over time by BDI in the PO (p = 0.044) and LA (p = 0.009) groups. Between groups there was a statistically significant difference by BDI, between PO versus LA (p = 0.004), and PF versus LA (p = 0.005). And by HADS, between FP versus LA (p = 0.012). Conclusion: For patients with anxiety and depression, laser acupuncture is not the most appropriate therapy to reduce pain symptoms in the short term (AU).

The influence of Malay cultural beliefs on breast cancer screening and genetic testing: A focus group study.

OBJECTIVE: Malays comprise an Asian cultural group reported to have low breast cancer screening uptake rates and poor cancer outcomes. Little is known about Malay cultural factors influencing beliefs and practice of cancer screening and genetic testing. Our study aims to explore health beliefs of Malay women around breast cancer screening and genetic testing. METHODS: We conducted focus groups among healthy English-speaking Malay women in Singapore, aged 40 to 69 years, using a structured guide developed through literature review, expertise input and participant refinement. Thematic analysis was conducted to extract dominant themes representing key motivators and barriers to screening and genetic testing. We used grounded theory to interpret results and derive a framework of understanding, with implications for improving uptake of services. RESULTS: Five focus groups (four to six participants per group) comprising 27 women were conducted to theme saturation. Major themes were (a) spiritual and religious beliefs act as barriers towards uptake of screening and genetic testing; (b) preference for traditional medicine competes with Western medicine recommendations; (c) family and community influence health-related decisions, complexed by differences in intergenerational beliefs creating contrasting attitudes towards screening and prevention. CONCLUSIONS: Decisions to participate in breast cancer screening and genetic testing are influenced by cultural, traditional, spiritual/religious, and intergenerational beliefs. Strategies to increase uptake should include acknowledgement and integration of these beliefs into counseling and education and collaboration with key influential Malay stakeholders and leaders.

Mindfulness Among Genetic Counselors Is Associated with Increased Empathy and Work Engagement and Decreased Burnout and Compassion Fatigue.

Genetic counselors experience high rates of compassion fatigue and an elevated risk for burnout, both of which can negatively impact patient care and retention in the profession. In other healthcare professions, mindfulness training has been successfully used to address similar negative psychological sequelae and to bolster empathy, which is the foundation of our counseling work. We aimed to assess associations between mindfulness and key professional variables, including burnout, compassion fatigue, work engagement, and empathy. Data were collected via an anonymous, online survey that included validated measures of mindfulness and these key professional variables. The survey was completed by 441 genetic counselors involved in direct patient care. Half of the respondents (50.1%) reported engaging in yoga, meditation, and/or breathing exercises. Mindfulness was positively correlated with work engagement (r = 0.24, p < 0.001) and empathy (as measured through four subscales: perspective taking (r = 0.15, p = 0.002), empathic concern (r = 0.11, p = 0.03), fantasy (r = - 0.11, p = 0.03) and personal distress (r = - 0.15, p = 0.001)). Mindfulness was negatively correlated with compassion fatigue (r = - 0.48, p < 0.001) and burnout (r = - 0.50, p < 0.001). Given these findings, mindfulness training may be a valuable addition to graduate and continuing education for genetic counselors. The integration of mindfulness into the genetic counseling field will likely improve professional morale and well-being, while promoting workforce retention and bolstering the relational and counseling aspects of our clinical work.

Issues Arising in Psychological Consultations to Help Parents Talk to Minor and Young Adult Children about their Cancer Genetic Test Result: a Guide to Providers.

The defining difference between genetic and traditional medicine is that genetic findings have implications not just for the patient, but also for their relatives. Discussion of a test result between parent and child is both a transformative and a translational moment in the life of a family. Parents report wanting help in talking to their children. The challenge for genetic counselors and other providers is to be able to recognize which issues are at the core of parental distress and be able to offer recommendations to empower and support parents. The complexity of potential genetic findings, including variants of uncertain significance (VUS) and incidental findings have vastly increased, requiring considerable explanation and leaving less time for discussion of emotional issues. While the nature of the testing (single gene to multigene panel and genomic testing) is dramatically changing, the nature of parent concerns remains remarkably constant. Families differ in many respects, so no "recipe" suffices to answer parents' questions about how this important task should be approached in each family. Successful consultation to parents requires true counseling, matching parents' fears and questions with information, exploration and advice specific to their concerns, their circumstances and strengths.

Dying at life׳s beginning: Experiences of parents and health professionals in Switzerland when an 'in utero ' diagnosis incompatible with life is made.

OBJECTIVE: The disclosure of a diagnosis during pregnancy of a fetal malformation, which is incompatible with life, normally comes completely unexpectedly to the parents. Although a body of international literature has considered the topic, most of it comes from the United States and little has been generated from Europe. This study aims to illuminate the contemporary treatment associated with such diagnoses, regardless of whether parents decide to terminate or continue the pregnancy. DESIGN: a qualitative design was used with data collected by semi-structured interviews and subjected to a thematic analysis. SETTING: the research was conducted in the German speaking areas of Switzerland with data collected from participants in places of their choice. PARTICIPANTS: 61 interviews were conducted with 32 parents and 29 health professionals. FINDINGS: the theme of 'temporality' identified four main time points from the professionals: diagnosis, decision, birth/death, and afterwards. However, in contrast to these, six major themes in this study, primarily generated from parents and extended from receiving the diagnosis until the interview, were identified: shock, choices and dilemmas, taking responsibility, still being pregnant, forming a relationship with the baby, letting go. Although there was concurrence on many aspects of care at the point of contact, parents expressed major issues as gaps between the points of contact. CONCLUSIONS: care varied regionally but was as sensitive as possible, attempting to give parents the space to accept their loss but fulfil legal requirements. A gap exists between diagnosis and decision with parents feeling pressured to make decisions regarding continuing or terminating their pregnancies although health professionals' testimonies indicated otherwise. A major gap manifested following the decision with no palliative care packages offered. During the birth/death of the baby, care was sensitive but another gap manifested following discharge from hospital.

"Be Prepared if I Bring It Up:" Patients' Perceptions of the Utility of Religious and Spiritual Discussion During Genetic Counseling.

As debates continue about the relevance of religion to health care, research is needed to guide decisions about whether genetic counselors (GCs) should routinely address religious and/or spiritual (R/S) issues with their patients. We conducted an online survey to gauge patient perspectives on this issue. Among the 70 respondents, frequencies of closed-ended responses and thematic analyses of open-ended responses revealed multiple patient concerns related to R/S discussions with GCs. Although 60 respondents reported being R/S, only a small minority would want to discuss R/S issues if it meant less time discussing medical information. Most respondents also expressed opinions that: 1) genetic counseling should be about science; 2) GCs are not qualified to discuss R/S issues; 3) other outlets are available to meet the needs of patients who want R/S counseling; and/or 4) R/S discussions are more likely to be acceptable if patients broach the topic or in specific circumstances (e.g., when patients are facing end-of life issues). Overall, responses suggest routine or comprehensive R/S assessments or discussions are not necessary and that GCs would be best equipped to help all their patients if they were prepared to listen, be supportive, and make referrals when R/S issues arise in clinic.

Respecting autonomous decision making among Filipinos: a re-emphasis in genetic counseling.

Family cohesiveness provides a unique cultural influence in the observance and expression of autonomy in terms of Filipino patients' decision making. With genetic counseling yet in its dawning practice in the Philippines, healthcare professionals (i.e., geneticists, practitioners) practicing genetic counseling and students in the pioneering genetic counseling program face the challenge of how to provide culturally appropriate measures in respecting Filipinos' autonomy. There is much deliberation with respect to identifying autonomous decision making among Filipino patients as counselees in genetic counseling. Cultural values influence how autonomy and bioethical principles are upheld. In a culturally-appropriate manner of identifying who makes health care and genetic counseling decisions, the sole focus on an individualistic perspective may be too western-based and may render genetic counseling less effective. The uniquely important cultural feature of family cohesiveness necessitates its incorporation into the practice of genetic counseling in the Philippines.

Midwives' views on appropriate antenatal counselling for congenital anomaly tests: do they match clients' preferences?

OBJECTIVE: this study aims to provide insight into: (a) midwives' views on appropriate antenatal counselling for congenital anomaly tests, and (b) whether these views match clients' preferences regarding antenatal counselling. DESIGN: a comparative (midwives versus clients) questionnaire survey. Cognitive interviews (n=8) were used to validate the internal validity of the midwifery questionnaire results. PARTICIPANTS AND SETTING: 1416 Dutch midwives (response 62%) completed a questionnaire measuring their views on appropriate antenatal counselling for congenital anomaly tests. MEASUREMENTS: we used the 58-item midwives' version of the QUOTE (prenatal), an instrument to assess clients' counselling preferences. Descriptive statistics were used to explore midwives' views on appropriate counselling and how these relate to client preferences as measured previously with the clients' version of the QUOTE (prenatal). FINDINGS: almost all midwives consider the client-midwife relation (100%) and health education (95%) to be (very) important for appropriate antenatal counselling for congenital anomaly tests. Almost half of the midwives consider decision-making support (47%) to be (very) important. These findings are practically congruent with client preferences. Still, clinically relevant differences were found regarding 13 individual items, e.g. more clients than midwives value 'medical information about congenital anomalies' and 'getting advice whether to take prenatal tests or not'. KEY CONCLUSION: like clients, most midwives value a good client-midwife relation and health education as (very) important for antenatal counselling for congenital anomaly tests. Less than half of them value decision-making support. These findings are in contrast with the literature in which decision-making support is seen as the most important part of antenatal counselling for congenital anomaly tests. IMPLICATION FOR PRACTICE: preferably, antenatal counselling for congenital anomaly tests should be consistent with the three-function model of antenatal counselling i.e. maintaining a client-midwife relation, providing health education as well as decision-making support, and tailored to clients' individual preferences. As not all midwives subscribe to these functions, reflection on their views is important. Furthermore, midwives need to bridge their views on appropriate antenatal counselling and client preferences. To do so, midwives may benefit from the Shared Decision Making approach.

Avaliação do impacto do suporte familiar e da espiritualidade no aconselhamento genético de portadores da Síndrome de Li-Fraumeni e Li-Fraumeni Like / Evaluation of the impact of family support and spirituality in genetic counseling of patients with Li-Fraumeni and Li-Fraumeni Like Syndromes

O Glioblastoma (GBM) é o tumor de células gliais mais comum e agressivo dentre os tumores cerebrais primários. Caracterizar mecanismos moleculares associados com a progressão desse tumor pode auxiliar no desenvolvimento de novas estratégias para seu tratamento e garantir a maior sobrevida de pacientes. A proteína STAT3 (Proteína transdutora de sinal e ativadora de transcrição 3) é um fator de transcrição ativado por fosforilação e conhecido por seu importante papel na gliomagênese. Com o uso de microarranjos de tecidos (TMAs) avaliamos a expressão total e a localização nuclear de STAT3 e de suas formas fosforiladas pSTAT3 (Y705) e pSTAT3(S727) em astrocitomas e tecido cerebral não tumoral. STAT3 possui uma localização nuclear aumentada em GBMs humanos, quando comparada com astrocitomas de menor grau ou tecido cerebral não tumoral. Interessantemente, o aumento da localização nuclear de STAT3 nos GBMs não está associado com o incremento de suas formas fosforiladas. Além disso, altos níveis de STAT3 nuclear em GBM estão correlacionados com o menor tempo livre de recidiva e a uma menor sobrevida nesses pacientes. Esse perfil não foi visto para as formas fosforiladas, indicando que outros mecanismos de ativação de STAT3, que não a via canônica de fosforilação, podem estar presentes nos GBMs. A identificação dessas modificações pode representar uma nova estratégia terapêutica para a abordagem desses tumores uma vez que as drogas disponíveis atualmente têm como alvo os domínios fosforilados de STAT3. Uma modificação pós-traducional que poderia contribuir para a translocação nuclear de STAT3 é a SUMOilação. A proteína PIAS1 (Proteína inibidora da atividade de STAT1) está envolvida neste mecanismo por mediar a adição de SUMO (Pequena proteína modificadora relacionada à ubiquitina) às proteínas-alvo. Nossos dados mostraram que PIAS1 apresenta maior localização nuclear em GBM quando comparado ao tecido não tumoral. Além disso, PIAS1 promove o acúmulo nuclear...

Glioblastoma is the most common and aggressive primary brain tumor. This work was conducted to characterize molecular mechanisms associated with GBM progression that could assist in developing of new strategies for its treatment and ensure better overall survival of these patients. STAT3 (Signal Transducer and Activator of Transcription 3) is a transcription factor activated by phosphorylation and known for its important role in gliomagenesis. Using tissue microarrays (TMAs) we evaluated the total expression and nuclear localization of STAT3 and its phosphorylated forms, pSTAT3 (Y705) and pSTAT3 (S727) in astrocytomas and non-tumor brain tissue. GBMs showed higher levels of nuclear STAT3 compared to lower grade astrocitomas or non-tumor brain tissue. Interestingly, increased nuclear STAT3 in GBMs is not associated with the improvement of its phosphorylated forms. Moreover, high levels of nuclear STAT3 in GBMs correlate with lower free-recurrence survival and overall survival of these patients. This profile followed by its phosphorylated forms, indicating that other activation mechanisms besides than the canonical STAT3 phosphorylation is present in GBM. The identification of these post-translation modifications may represent new therapeutic strategies for the treatment of these tumors since the currently available drugs target only the phosphorylation sites of STAT3. A posttranslational modification that could contribute to nuclear translocation of STAT3 is the SUMOylation although we were unable to see this interaction in cultured cells. On the other hand, GBMs have a higher nuclear PIAS1 compared to non-tumor brain tissue. PIAS1 protein (Protein Inhibitor of Activity of STAT1) is involved in protein SUMOylation by mediating the addition of SUMO to target proteins. Moreover, PIAS1 promotes nuclear retention of the co-chaperone STI1/Hop (Stress inducible protein 1/Hsp70- Hsp90 organizing protein) in astrocytes treated with gamma radiation, which may...

Prenatal counseling for congenital anomaly tests: parental preferences and perceptions of midwife performance.

OBJECTIVE: Evidence-based instruments to evaluate the preferences and experiences of future parents regarding prenatal counseling for congenital anomaly tests are currently lacking. We developed the quality of care through clients' eyes prenatal questionnaire (QUOTE(prenatal) ), a client-centered instrument, and assessed its components. Furthermore, the QUOTE(prenatal) was used to provide insight into (1) clients' previsit preferences and (2) clients' postvisit experience, that is, perceived care provider performance regarding the counseling they received. METHOD: In the questionnaire survey, a principal component analysis was used to gain insight into the underlying components of the questionnaire. Regression analysis was performed to examine differences between groups. RESULTS: In 17 Dutch midwifery practices, 941 pregnant women and their partners (response rate 79%) completed the 59-item QUOTE(prenatal) previsit and postvisit, measuring preferences and perceived performances, respectively. A principal component analysis revealed three counseling components: client-midwife relation, health education and decision-making support. Reponses showed that, previsit, most clients consider the client-midwife relationship and health education to be (very) important. One third of the clients consider decision-making support to be (very) important. Nulliparae had higher preferences for health education and decision-making support than multiparae. CONCLUSION: Clients perceive that their midwives perform well in building the client-midwife relationship and in giving health education. Improvement is needed in decision-making support.

Does the diagnosis of breast or ovarian cancer trigger referral to genetic counseling?

OBJECTIVE: Kaiser Permanente Northern California is a large integrated health care delivery system in the United States that has guidelines for referring women with newly diagnosed BRCA1-and BRCA2-associated cancers for genetic counseling. This study assesses adherence to genetic counseling referral guidelines within this health system. METHODS: Chart review was performed to identify patients with cancer who met the following pathology-based Kaiser Permanente Northern California guidelines for referral for genetic counseling: invasive breast cancer, younger than age 40; nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer, younger than age 60; women with synchronous or metachronous primary cancers of the breast and ovaries; and male breast cancer. We assessed compliance with referral guidelines. An electronic notice was sent to the managing physician of patients with newly diagnosed cancer to assess the feasibility of this intervention. RESULTS: A total of 340 patients were identified with breast cancer at younger than age 40 or with ovarian, peritoneal, or tubal cancer between January and June, 2008. Upon chart review, 105 of these patients met pathology-based criteria for referral to genetic counseling, of whom 47 (45%) were referred within the 2-year study period. Of the 67 subjects with breast cancer, 40 subjects (60%) were referred. In contrast, only 7 (21%) of 33 patients with ovarian cancer were referred (P < 0.001). A pilot study was performed to test the feasibility of notifying managing oncologists with an electronic letter alerting them of eligibility for genetic referral of patients with new diagnosis (n = 21). In the 3 to 6 months after this notification, 12 of these 21 patients were referred for counseling including 5 of 7 patients with a diagnosis of ovarian cancer. CONCLUSION: There is a missed opportunity for referring patients to genetic counseling, especially among patients with ovarian cancer. A pilot study suggests that alerting treating physicians is a feasible strategy to increase appropriate referral.

Genetic counseling: a survey to explore knowledge and attitudes of Italian nurses and midwives.

In the past, genetic services were delivered to a limited number of families with rare conditions. However, genomics is now being applied to both inherited and common diseases in a range of healthcare settings, and there is a greater need for nurses to understand the basic concepts of genetic health care. The aim of this cross-sectional survey was to explore the understanding and attitudes of Italian nurses toward genetic health care. A questionnaire was completed by 102 nurses and midwives (85% response rate). Of these, 61% believed that genetic counseling was only an informative and advisory process, and 53.9% could not specify to whom the counseling was aimed. When asked to identify nurses' role in genetic health care, 62% of the respondents believed they had no role, although 28% believed that nurses could provide information, support, and counseling. These findings indicate that nurses have only partial knowledge of the issues surrounding genetic health care. To prepare nurses for the post-genomic era, improved genetic education at the undergraduate and postgraduate levels is required.

A qualitative investigation of the decision-making process of couples considering prenatal screening for Down syndrome.

OBJECTIVE: The aim of this study was to investigate how couples regard screening information and how they make subsequent decisions about undergoing prenatal screening for Down syndrome. METHODS: Twenty semi-structured interviews were conducted to explore aspects of the decision-making process. Interviews were digitally recorded and transcribed verbatim, and data were analysed using the framework approach. RESULTS: Couples reported a strong desire for a joint but ultimately private decision-making process and saw the main role of their midwife as an information provider. Considerable confusion existed over which screening tests were available via the National Health Service and which were offered privately. Provision of experiential information regarding both subsequent diagnostic tests and the experience of living with Down syndrome would have been beneficial. CONCLUSION: This study shows that couples would benefit from receiving experiential information when they are deciding about Down syndrome screening. Future research should be conducted to establish what form such information should take, the most helpful means to provide such information, and whether such information would also be useful in other contexts where people need to make decisions whether to undergo screening.