Genomic profiling of pediatric hematologic malignancies and diagnosis of cancer predisposition syndromes: tumor-only versus paired tumor-normal sequencing.

Not available.

Diversity of Group Memberships Predicts Well-Being: Cross-Sectional and Longitudinal Evidence.

Groups have their health and well-being impacted by satisfying their members' needs and providing resources to help cope with threats. Multiple group memberships serve to accumulate these benefits and also provide resilience to the effects of group loss. However, the additional well-being benefits of belonging to multiple different types of group remain to be determined. In a preregistered cross-sectional survey in Nottingham, England (Study 1, N = 328), we found that group-type diversity predicted well-being and that this effect was fully serially mediated by increased creative self-efficacy, then reduced loneliness. To confirm our hypothesis in a more robust sample we conducted longitudinal analyses on the English Longitudinal Study of Aging (ELSA) dataset (Study 2, N = 5,838) finding that group-type diversity at time one (T1) predicted well-being at T2 (4 years later), even when accounting for wellbeing and loneliness at T1. We discuss the implications for enhancing group-based health interventions.

Comprehensive Gene Panel Testing for Hearing Loss in Children: Understanding Factors Influencing Diagnostic Yield.

OBJECTIVE: To evaluate factors influencing the diagnostic yield of comprehensive gene panel testing (CGPT) for hearing loss (HL) in children and to understand the characteristics of undiagnosed probands. STUDY DESIGN: This was a retrospective cohort study of 474 probands with childhood-onset HL who underwent CGPT between 2016 and 2020 at a single center. Main outcomes and measures included the association between clinical variables and diagnostic yield and the genetic and clinical characteristics of undiagnosed probands. RESULTS: The overall diagnostic yield was 44% (209/474) with causative variants involving 41 genes. While the diagnostic yield was high in the probands with congenital, bilateral, and severe HL, it was low in those with unilateral, noncongenital, or mild HL; cochlear nerve deficiency; preterm birth; neonatal intensive care unit admittance; certain ancestry; and developmental delay. Follow-up studies on 49 probands with initially inconclusive CGPT results changed the diagnostic status to likely positive or negative outcomes in 39 of them (80%). Reflex to exome sequencing on 128 undiagnosed probands by CGPT revealed diagnostic findings in 8 individuals, 5 of whom had developmental delays. The remaining 255 probands were undiagnosed, with 173 (173/255) having only a single variant in the gene(s) associated with autosomal recessive HL and 28% (48/173) having a matched phenotype. CONCLUSION: CGPT efficiently identifies the genetic etiologies of HL in children. CGPT-undiagnosed probands may benefit from follow-up studies or expanded testing.

United on Sunday: The effects of secular rituals on social bonding and affect.

Religious rituals are associated with health benefits, potentially produced via social bonding. It is unknown whether secular rituals similarly increase social bonding. We conducted a field study with individuals who celebrate secular rituals at Sunday Assemblies and compared them with participants attending Christian rituals. We assessed levels of social bonding and affect before and after the rituals. Results showed the increase in social bonding taking place in secular rituals is comparable to religious rituals. We also found that both sets of rituals increased positive affect and decreased negative affect, and that the change in positive affect predicted the change in social bonding observed. Together these results suggest that secular rituals might play a similar role to religious ones in fostering feelings of social connection and boosting positive affect.

The aetiology of social deficits within mental health disorders: The role of the immune system and endogenous opioids.

The American National Institute for Mental Health (NIMH) has put out a set of research goals that include a long-term plan to identify more reliable endogenous explanations for a wide variety of mental health disorders (Insel, 2013). In response to this, we have identified a major symptom that underlies multiple mental health disorders - social bonding dysfunction. We suggest that endogenous opioid abnormalities can lead to altered social bonding, which is a symptom of various mental health disorders, including depression, schizophrenia and ASD. This article first outlines how endogenous opioids play a role in social bonding. Then we show their association with the body's inflammation immune function, and review recent literature linking inflammation to mental health 'immunophenotypes'. We finish by explaining how these immunophenotypes may be caused by alterations in the endogenous opioid system. This is the first overview of the role of inflammation across multiple disorders where we provide a biochemical explanation for why immunophenotypes might exist across diagnoses. We propose a novel mechanism of how the immune system may be causing 'sickness-type' behaviours (fatigue, appetite change, social withdrawal and inhibited motivation) in those who have these immunophenotypes. We hope that this novel aetiology can be used as a basis for future research in mental health.

Ureteroscopic management of upper tract urothelial carcinoma (UTUC) in patients with Lynch Syndrome (hereditary nonpolyposis colorectal cancer syndrome).

OBJECTIVES: To report our experience with ureteroscopic laser ablation of upper tract urothelial carcinoma (UTUC) in patients with Lynch Syndrome (LS), as defined by a documented germline mutation in the MSH-2 gene. To increase awareness among urologists about UTUC in this unique patient population and refer to genetic counselling when appropriate. PATIENTS AND METHODS: Demographic, clinical and pathological data on 13 consecutive patients with UTUC and documented MSH-2 mutation comprising 15 involved renal units were retrospectively collected. Ureteroscopic evaluations involved biopsy and laser treatment with combination holmium/neodymium yttrium aluminum garnet (YAG) lasers. Tumours were graded from 1 to 3 according to the 1973 World Health Organisation classification by a single pathologist evaluating cell block preparations. RESULTS: The mean patient age at initial presentation was 56.5 years, with six of 13 patients having metachronous bilateral UT disease. The mean follow-up was 59 months with a mean number of surveillances of 12. Of 15 affected renal units, 10/15 (67%) of initial tumours involved the ureter with mean lesion size of 17.5 mm, while five of 15 (33%) involved the intrarenal collecting system with mean lesion size of 25 mm. Ureteroscopy cleared 13/15 (87%) lesions and four of those 13 (31%) needed staged procedures. Renal preservation rate was 14/15 (93%) with one nephroureterectomy and one segmental ureterectomy performed. One patient developed metastatic UTUC after 40 months surveillance. No patient presented with bladder tumours but seven of the 13 (54%) developed them within 10 months of the initial ureteroscopy. CONCLUSIONS: Patients with LS who develop UTUC present at younger ages and appear to be more likely to have bilateral UT disease over their lifetimes vs sporadic UTUC patients. Ureteroscopic laser ablation offers a good renal preservation rate with reasonable cancer control in patients willing to undergo endoscopic surveillance. Development of new bladder tumours is common.

A case of endometrial cancer in the context of a BRCA2 mutation and double heterozygosity for Lynch syndrome.

► Endometrial cancer with BRCA2 mutation and double heterozygosity for Lynch syndrome. ► Loss of MLH1 and PMS2 by immunohistochemical stain. ► MSH1 and MSH6 gene mutations by genomic sequencing.

Identifying pancreatic cancer patients for targeted treatment: the challenges and limitations of the current selection process and vision for the future.

Recent preclinical data have demonstrated that pancreatic adenocarcinoma (PDA) cells with defects in the Fanconi anemia/BRCA2 pathway are hypersensitive to interstrand crosslinking agents. The challenge is to efficiently identify patients who will benefit from these therapies. Patients were chosen for this study by evaluating personal history, ethnic background and family history of pancreatic malignancy. Molecular assays were performed on tissue samples. Patient A developed PDA in the context of a known BRCA2 frameshift mutation (2157delG), suspected because of her personal and multigenerational family history of breast cancer. She was treated with surgical resection, and targeted chemotherapy. Patient A continues to be disease free 32 months after her diagnosis and treatment. Patient B developed PDA in the context of a strong family history of PDA and Ashkenazi Jewish heritage. Genetic analysis on critical DNA repair genes revealed no alterations. This patient did not receive a tailored treatment regimen. This study highlights the challenge of treating PDA patients and selecting those eligible for targeted therapy. The current targeted treatment options for PDA are reviewed. A new multidisciplinary approach for stratifying PDA patients for promising targeted adjuvant therapy and familial risk counseling is proposed.

Publishing a master's thesis: a guide for novice authors.

Publication of original research, clinical experiences, and critical reviews of literature are vital to the growth of the genetic counseling field, delivery of genetic counseling services, and professional development of genetic counselors. Busy clinical schedules, lack of time and funding, and training that emphasizes clinical skills over research skills may make it difficult for new genetic counselors to turn their thesis projects into publications. This paper summarizes and elaborates upon a presentation aimed at de-mystifying the publishing process given at the 2008 National Society of Genetic Counselors Annual Education Conference. Specific topics include familiarizing prospective authors, particularly genetic counseling students, with the basics of the publication process and related ethical considerations. Former students' experiences with publishing master's theses also are described in hopes of encouraging new genetic counselors to submit for publication papers based on their thesis projects.

Satisfaction with genetic counseling for BRCA1 and BRCA2 mutations among African American women.

OBJECTIVE: The objective of this study was to evaluate satisfaction with genetic counseling for BRCA1 and BRCA2 (BRCA1/2) mutations among African American women. METHODS: Participants were 54 African American women at moderate and high risk for BRCA1/2 mutations who were offered genetic testing as part of a randomized clinical trial designed to compare the effects of culturally tailored genetic counseling (CTGC) and standard genetic counseling (SGC). Satisfaction with genetic counseling was evaluated using a self-administered questionnaire following culturally tailored or standard pre-test education and counseling. RESULTS: Overall, the majority of women (96%) were very satisfied with genetic counseling; however, only 26% reported that their worries were lessened and 22% reported that they were able to cope better. Women who received CTGC were significantly more likely than women who received SGC to report that their worries were lessened (p<0.05). In addition, women with household incomes less than US$ 35,000 were significantly more likely to report that the counselor lessened their worries compared to women with higher incomes (p<0.05). CONCLUSIONS: Most African American women were satisfied with genetic counseling; however, women who received culturally tailored genetic counseling were significantly more likely to strongly agree that their worries were lessened compared to women who received standard genetic counseling. PRACTICE IMPLICATIONS: Discussion of cultural beliefs and values during genetic counseling may be beneficial to African American women, especially those with low incomes.