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Objective: We aimed to conduct a systematic review to identify curricular and educational interventions to build research competency among Canadian psychiatry residents and fellows transitioning to the competency-by-design framework., Methods: The PRISMA guidelines were followed, searching five databases from their inception to February 2023 for relevant evaluation-type studies exploring research competency among psychiatry residents and fellows. We appraised thestudy's quality using the Joanna Briggs Institute's risk of bias tool for observational designs., Results: Overall, 36 original articles met our inclusion criteria. Surveys ( n  = 10) showed that participation in scholarly research, quality improvement, or educational projects relevant to psychiatry is needed in most residency programs. However, these vary significantly across programs; few need direct research experience for residency completion. The interventions spanned four categories: externally funded comprehensive research training programs ( n  = 5); resident research tracks ( n  = 11); workshops and seminars ( n  = 7); and specific modules ( n  = 3). Reported outcomes included overall program ratings, research output, and career trajectory. The quality of most studies was low because of the lack of controls or validated metrics for evaluating outcomes., Conclusions: While many studies have explored best practices in research curricula, the current literature does not inform competency-based models for Canadian psychiatry residency programs incorporating research training requirements. Further description is needed from Canadian psychiatric training bodies regarding appropriate curricula, milestones, and metrics for evaluating research competencies., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Anees Bahji receives a small honorarium for teaching undergraduate and postgraduate medical trainees in the Cumming School of Medicine at the University of Calgary. In addition, Anees Bahji is an unpaid member of the Canadian Network for Mood and Anxiety Treatments (CANMAT) editorial committee, the International Society of Addiction Journal Editors (ISAJE), the Canadian Society of Addiction Medicine (CSAM) policy committee, and the Addiction Psychiatry section of the Canadian Psychiatric Association (CPA). Anees Bahji is also an unpaid associate editor of the Canadian Journal of Addiction (CJA) and a mental health educator for TED-Ed, where he receives a small honorarium for supporting online educational content. Finally, Anees Bahji does not report royalties, licenses, consulting fees, payment, or honoraria for lectures or presentations, speaker’s bureaus, article writing, expert testimony, patents, or participation on other boards. Marlon Danilewitz reports personal fees from Eisai Ltd and Winterlight Labs outside the submitted work. The remaining coauthors have no relevant disclosures., (© The Author(s) 2023.)

No studies have looked at the effects of cumulative sleep restriction (CSR) on sleep architecture or the power spectrum of sleep EEG (electroencephalogram) in school-age children, as recorded by PSG (polysomnography). This is true for both typically developing (TD) children and children with ADHD (attention deficit/hyperactivity disorder), who are known to have more sleep difficulties. Participants were children (ages 6-12 years), including 18 TD and 18 ADHD, who were age- and sex-matched. The CSR protocol included a two-week baseline and two randomized conditions: Typical (six nights of sleep based on baseline sleep schedules) and Restricted (one-hour reduction of baseline time in bed). This resulted in an average of 28 min per night difference in sleep. Based on ANOVAs (analysis of variance), children with ADHD took longer to reach N3 (non-rapid eye movement), had more WASO (wake after sleep onset) (within the first 5.1 h of the night), and had more REM (rapid eye movement) sleep than TD children regardless of condition. During CSR, ADHD participants had less REM and a trend toward longer durations of N1 and N2 compared to the TD group. No significant differences in the power spectrum were found between groups or conditions. In conclusion, this CSR protocol impacted some physiological aspects of sleep but may not be sufficient to cause changes in the power spectrum of sleep EEG. Although preliminary, group-by-condition interactions suggest that the homeostatic processes in children with ADHD may be impaired during CSR.

Patients feel more vulnerable when accessing community mental health programs for the first time or after being discharged from psychiatric inpatient units. Long wait times for follow-up appointments, shortage of mental health professionals, lack of service integration, and scarcity of tailored support can weaken their connection to the health care system. As a result, patients can present low adherence, dissatisfaction with treatment, and recurrent hospitalizations. Finding solutions to avoid unnecessary high-cost services and providing tailored and cost-effective mental health interventions may reduce the health system burden and augment patient support. We propose implementing an add-on, supportive text messaging service (Text4Support), developed using cognitive-behavioural therapy (CBT) principles to augment mental health support for patients attending to or being discharged from psychiatric care in Nova Scotia, Canada. This randomized controlled trial aims to investigate the effectiveness of Text4Support in improving mental health outcomes and overall mental well-being compared with usual care. We also will examine the intervention's impact on health services utilization and patient satisfaction. The results from this study will provide evidence on stepped and technology-based mental health care, which will contribute to generating new knowledge about mental health innovations in various clinical contexts, which is not only helpful for the local context but to other jurisdictions in Canada and abroad that are seeking to improve their health care.

Parkinson's disease (PD) is a neurodegenerative disorder that is typified by motor signs and symptoms but can also lead to significant cognitive impairment and dementia Parkinson's Disease Dementia (PDD). While dementia is considered a nonmotor feature of PD that typically occurs later, individuals with PD may experience mild cognitive impairment (PD-MCI) earlier in the disease course. Olfactory deficit (OD) is considered another nonmotor symptom of PD and often presents even before the motor signs and diagnosis of PD. We examined potential links among cognitive impairment, olfactory functioning, and white matter integrity of olfactory brain regions in persons with early-stage PD. Cognitive tests were used to establish groups with PD-MCI and with normal cognition (PD-NC). Olfactory functioning was examined using the University of Pennsylvania Smell Identification Test (UPSIT) while the white matter integrity of the anterior olfactory structures (AOS) was examined using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) analysis. Those with PD-MCI demonstrated poorer olfactory functioning and abnormalities based on all DTI parameters in the AOS, relative to PD-NC individuals. OD and microstructural changes in the AOS of individuals with PD may serve as additional biological markers of PD-MCI.

Introduction: Parkinson's disease (PD) is typically diagnosed when motor symptoms first occur. However, PD-related non-motor symptoms may appear several years before diagnosis. REM sleep behaviour disorder (RBD) and olfactory deficits (hyposmia) are risk factors, but they are not specific for predicting progression towards PD. Other PD-related markers, for example brain imaging markers, may help to identify preclinical PD in hyposmic RBD patients. Studies have reported abnormal structural characteristics in the corticospinal tract (CST) of PD patients, but it is unclear whether hyposmic RBD patients have similar abnormalities that may help to predict PD in these individuals. This study examined whether CST abnormalities may be a potential marker of PD risk by using diffusion tensor imaging (DTI) measures., Methods: Twenty hyposmic RBD patients, 31 PD patients, and 29 healthy controls (HCs) were studied. DTI data were collected on a 1.5 T MRI scanner and CST characteristics (FA, MD, AD, and RD) were evaluated using probabilistic tractography (with seed regions in the bilateral primary motor cortex and mediolateral cerebral peduncles). Olfactory function was assessed with the University of Pennsylvania Smell Identification Test (UPSIT)., Results: Hyposmic RBD patients showed significantly higher mean diffusivity (MD) values of the right CST compared to HCs but did not differ from PD patients. PD patients showed a trend of higher MD values compared to HCs., Conclusions: Altered diffusivity in the CST seems to be associated with RBD. The combination of RBD, hyposmia, and CST alterations may be related to later development of PD with comorbid RBD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

Purpose: The BRCA2 p.K3326* variant is considered a low-penetrance variant for breast cancer. Aldehydes that accumulate in cells under insufficient aldehyde oxidation were most recently shown to trigger carcinogenesis by promoting depletion of BRCA2 protein. Allele T of the common variant rs10744777 in the ALDH2 gene was associated with reduced expression of aldehyde dehydrogenase, the main enzyme in aldehyde oxidation. We hypothesized that this allele could modify breast cancer risk in women with the BRCA2 p.K3326* low-penetrance variant through reduced function of ALDH2, increased accumulation of cellular aldehydes, and depletion of BRCA2 protein., Materials and Methods: We genotyped 11,873 Polish women diagnosed with breast cancer and 7,615 ethnically matched controls for these two variants. Next, we extended our analysis of rs10744777 to 231 carriers of pathogenic BRCA2 mutations., Results: BRCA2 p.K3326* variant was associated with significant increase in breast cancer risk only in those who were homozygous for the T allele of the ALDH2 rs10744777 variant (odds ratio = 1.72; 95% CI, 1.19 to 2.48; P = .003). The BRCA2 p.K3326* variant did not increase the risk of breast cancer among those who were heterozygous or homozygous for the C allele of the ALDH2 rs10744777 variant (odds ratio = 1.05; 95% CI, 0.73 to 1.51; P = .81). In the carriers of high-risk BRCA2 mutations, the TT genotype of rs10744777 conferred a modest (18%) and not significant increase in breast cancer risk., Conclusion: Our results suggest that BRCA2 p.K3326* variant, which is low-penetrance by itself, confers increased breast cancer risk on the background of the TT genotype of the ALDH2 rs10744777 variant in the Polish population., Competing Interests: Mohammad R. AkbariStock and Other Ownership Interests: GenewisePatents, Royalties, Other Intellectual Property: Breast Cancer Biomarkers (RECQL) and Methods of Diagnosis, Patent No. US 10,131,957 B2 (Inst), Breast Cancer Biomarkers (RECQL) and Methods of Treatment, Patent No. US 9,926,607 B2 (Inst)No other potential conflicts of interest were reported.

Age-friendly cities are crucial to achieve the WHO goal of healthy aging. Such cities promote opportunities for health, participation, and security, thus enhancing quality of life as people age. Older people commonly experience psychosocial challenges such as anxiety, depression, substance abuse, loss of autonomy, grief, fear, and loneliness. Australian and Canadian cities continue to seek innovation to improve healthy urban aging and create more age-friendly environments for older adults. There is increasing evidence on the effectiveness and feasibility of mobile technology in health promotion and closing psychological treatment gaps. Older adults have been demonstrated to engage frequently with mobile devices, particularly text messaging. In this article, we conceptualize the Text4HealthyAging, an evidence-based text messaging innovation to support healthy urban aging in Canadian and Australian cities., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: VIOA and EE are board members of the GPEF, a not-for-profit organization involved with the design of Text4HealthyAging program. All other authors declare no conflicting interests., (© The Author(s) 2022.)

Objectives/background: Correlational studies show that short sleep is associated with negative daytime outcomes in school-aged children, but there are few experimental sleep manipulation studies to assess whether this is a causal relation. The aim of this study was to determine the impact of mild, cumulative sleep restriction on daytime functioning of typically developing (TD) children and children with attention-deficit/hyperactivity disorder (ADHD)., Participants: A total of 36 school-aged children (n = 18 TD; n = 18 ADHD), aged 6-11 years participated., Methods: Children participated in two sleep conditions (order counter-balanced). The Restricted condition required a 1 h reduction of time in bed for one week, and the Controlled Typical condition was based on participant's average baseline sleep. At the end of each condition, participants attended the sleep lab for overnight polysomnography and daytime functioning assessments., Results: Children successfully reduced time in bed by ~1 h. Due to compensatory changes, total sleep time (TST) was reduced by only ~20 min, as children fell asleep faster and spent less time awake after sleep onset during the Restricted compared to Controlled Typical condition. Many daytime functions were not affected by this very mild sleep restriction, however, both groups showed significant changes in performance on an objective attention task and on a parent-rated emotional lability measure after six nights of minimal reductions in TST. There were no significant differences between groups., Conclusions: Results suggest that a very mild sleep restriction can affect children's attention and emotional regulation, even with evidence of compensatory sleep mechanisms.

Objective: Accumulating evidence has suggested bidirectionality between sleep problems and depression, but the underlying mechanism is unclear. We assessed the role of sleep in inhibitory control ability with emotional stimuli, which has been shown to be suboptimal among individuals with depression and proposed to perpetuate depressive symptoms., Methods: Emerging adults (aged 18-25 years, 64.6% female) were screened for depressive and other mental disorders by structured clinical interview and questionnaire. Individuals with depressive disorders were assigned to have a polysomnography-monitored daytime sleep opportunity (Sleep-Dep, n = 20), whereas nondepressed individuals were randomized to either have daytime sleep (Sleep-Ctrl, n = 27) or stay awake (Wake-Ctrl, n = 18). Participants completed the Affective Go/No-Go Task two times, separated by experimental conditions., Results: A factorial model with a between-subject factor (Sleep-Dep/Sleep-Ctrl/Wake-Ctrl) and a within-subject factor (test 1/test 2) was used to assess if the groups differed in inhibitory control across test sessions, as inferred by changes in d-prime and false alarm rates (FA). Results from mixed factorial models showed a significant interaction effect between time and group on FA in the block with neutral faces as the target and happy faces as the nontarget (F(2,61) = 5.15, pfdr = .045). Although Sleep-Dep had decreased FA after sleep (t(19) = 2.94, pfdr = .050), Sleep-Ctrl and Wake-Ctrl had no significant between-session changes (p values > .05). Postsleep improvement in FA in Sleep-Dep correlated with longer stage 2 sleep (r(20) = 0.788, pfdr < .001) and stage 2 fast spindle number at O1 (r(18) = 0.692, pfdr = .015)., Conclusions: Sleep gain, particularly stage 2 sleep and related physiology, potentially enhances inhibitory control ability responding to emotional information among individuals with depressive disorders., (Copyright © 2021 by the American Psychosomatic Society.)

Background: The objective of this study was to establish the contribution of PALB2 mutations to prostate cancer risk and to estimate survival among PALB2 carriers., Methods: We genotyped 5472 unselected men with prostate cancer and 8016 controls for two Polish founder variants of PALB2 (c.509&#95;510delGA and c.172&#95;175delTTGT). In patients with prostate cancer, the survival of carriers of a PALB2 mutation was compared to that of non-carriers., Results: A PALB2 mutation was found in 0.29% of cases and 0.21% of controls (odds ratio (OR) = 1.38; 95% confidence interval (CI) 0.70-2.73; p = 0.45). PALB2 mutation carriers were more commonly diagnosed with aggressive cancers of high (8-10) Gleason score than non-carriers (64.3 vs 18.1%, p < 0.0001). The OR for high-grade prostate cancer was 8.05 (95% CI 3.57-18.15, p < 0.0001). After a median follow-up of 102 months, the age-adjusted hazard ratio for all-cause mortality associated with a PALB2 mutation was 2.52 (95% CI 1.40-4.54; p = 0.0023). The actuarial 5-year survival was 42% for PALB2 carriers and was 72% for non-carriers (p = 0.006)., Conclusion: In Poland, PALB2 mutations predispose to an aggressive and lethal form of prostate cancer., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Sleep and circadian rhythm disruptions commonly occur in individuals with schizophrenia. Stable tubule only polypeptide (STOP) knockout (KO) mice show behavioral impairments resembling symptoms of schizophrenia. We previously reported that STOP KO mice slept less and had more fragmented sleep and waking than wild-type littermates under a light/dark (LD) cycle. Here, we assessed the circadian phenotype of male STOP KO mice by examining wheel-running activity rhythms and EEG/EMG-defined sleep/wake states under both LD and constant darkness (DD) conditions. Wheel-running activity rhythms in KO and wild-type mice were similarly entrained in LD, and had similar free-running periods in DD. The phase delay shift in response to a light pulse given early in the active phase under DD was preserved in KO mice. KO mice had markedly lower activity levels, lower amplitude activity rhythms, less stable activity onsets, and more fragmented activity than wild-type mice in both lighting conditions. KO mice also spent more time awake and less time in rapid eye movement sleep (REMS) and non-REMS (NREMS) in both LD and DD conditions, with the decrease in NREMS concentrated in the active phase. KO mice also showed altered EEG features and higher amplitude rhythms in wake and NREMS (but not REMS) amounts in both lighting conditions, with a longer free-running period in DD, compared to wild-type mice. These results indicate that the STOP null mutation in mice altered the regulation of sleep/wake physiology and activity rhythm expression, but did not grossly disrupt circadian mechanisms., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objective: There is a growing body of research on the impact of stimulant medication on sleep in children with attention-deficit/hyperactivity disorder (ADHD). Negative sleep side effects are a common reason for nonadherence or for discontinuing a course of treatment. However, there is no published evidence as to whether pretreatment sleep can predict responses to treatment and the emergence of side effects., Method: In this study, baseline sleep variables were used to predict therapeutic effect (i.e., reduction of ADHD symptoms) and side effects (both sleep and global side effects) in a sample of newly diagnosed, medication-naive children (n = 50)., Results: The results of hierarchical regression analysis showed that parent-reported shorter sleep duration before medication treatment significantly predicted better response to treatment, independent of pretreatment ADHD symptoms. Baseline sleep features did not significantly predict global (nonsleep) side effects but did predict increased sleep side effects during treatment., Conclusion: These results indicate that baseline sleep variables may be helpful in predicting therapeutic response to medication and sleep disturbance as a side effect of stimulant medication., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

In designing national strategies for genetic testing, it is important to define the full spectrum of pathogenic mutations in prostate cancer (PCa) susceptibility genes. To investigate the frequency of mutations in PCa susceptibility genes in Polish familial PCa cases and to estimate gene-related PCa risks and probability of aggressive disease, we analyzed the coding regions of 14 genes by exome sequencing in 390 men with familial prostate cancer and 308 cancer-free controls. We compared the mutation frequencies between PCa cases and controls. We also compared clinical characteristics of prostate cancers between mutation carriers and noncarriers. Of the 390 PCa cases, 76 men (19.5%) carried a mutation in BRCA1, BRCA2, NBN, ATM, CHEK2, HOXB13, MSH2 or MSH6 genes. No mutations were found in BRIP1, PTEN, TP53, MLH1, PMS2 and SPOP. Significant associations with familial PCa risk were observed for CHEK2, NBN, ATM, and HOXB13. High-grade (Gleason 8-10) tumors were seen in 56% of BRCA2, NBN or ATM carriers, compared to 21% of patients who tested negative for mutations in these genes (OR = 4.7, 95% CI 2.0-10.7, P = .0003). In summary, approximately 20% of familial prostate cancer cases in Poland can be attributed to mutations in eight susceptibility genes. Carriers of mutations in BRCA2, NBN and ATM develop aggressive disease and may benefit from intensified screening and/or chemotherapy., (© 2020 Union for International Cancer Control.)

Objective: Although stimulant medications, such as methylphenidate hydrochloride (MPH), are effective at reducing the core symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), they may also disrupt children's sleep. This study aimed to investigate the acute impact of extended-release MPH on sleep using both actigraphy and polysomnography (PSG)., Method: Participants were 26 medication-naïve newly and rigorously diagnosed children with ADHD (23 males; 3 females) with a mean age of 8 years, 8 months ( SD = 24.5mos) who were enrolled in a clinically-administered crossover medication trial with 2 conditions: 2 weeks of placebo and 2 weeks of MPH treatment. The effect of condition on sleep variables as measured by actigraphy (primary outcome) and PSG (secondary outcome) was analyzed using repeated measures MANOVAs., Results: Based on actigraphy data, total sleep time was significantly reduced by 30 minutes and sleep onset latency was significantly increased by 30 minutes in the MPH condition compared to the placebo condition (p<0.001). No differences were found in sleep efficiency. No statistically significant differences were found for the same variables assessed by PSG; however, the means were in the same direction as the actigraphy data. There was a significant increase in the relative percentage of stage N3 sleep by 3.2% during MPH treatment (p<0.05)., Conclusions: Increased sleep onset latency resulting in reduced total sleep time, which has been linked to poorer daytime functioning, is a potential adverse effect of stimulant medication which may require management to optimize outcome., (Copyright © 2020 Canadian Academy of Child and Adolescent Psychiatry.)

To optimize genetic testing, it is necessary to establish the spectrum of breast cancer-predisposing mutations in particular ethnic groups. We studied 1,018 women with a strong family history for breast cancer (families with hereditary breast cancer; HBC) from genetically homogenous population of Poland, which is populated by ethnic Slavs, for mutations in 14 cancer susceptibility genes. Additionally, we compared the frequency of candidate pathogenic variants in breast cancer cases and controls. Germline mutations were detected in 512 of 1,018 probands with breast cancer (50.3%), including BRCA1/2 mutations detected in 420 families and non-BRCA mutations seen in 92 families. Thirteen BRCA1/2 founder mutations represented 84% of all BRCA1/2-positive cases. Seven founder mutations of CHEK2, PALB2, NBN and RECQL represented 73% of all non-BRCA-positive cases. Odds ratios for hereditary breast cancer were 87.6 for BRCA1, 15.4 for PALB2, 7.2 for CHEK2, 2.8 for NBN and 15.8 for RECQL. Odds ratios for XRCC2, BLM and BARD1 were below 1.3. In summary, we found that 20 founder mutations in six genes (BRCA1/2, CHEK2, PALB2, NBN and RECQL) are responsible for 82% of Polish hereditary breast cancer families. A simple test for these 20 mutations will facilitate genetic testing for breast cancer susceptibility in Poland. It may also facilitate genetic testing for breast cancer susceptibility in other Slavic populations and women of Slavic descent worldwide., (© 2019 UICC.)

Background: XRCC2 participates in homologous recombination and in DNA repair. XRCC2 has been reported to be a breast cancer susceptibility gene and is now included in several breast cancer susceptibility gene panels., Methods: We sequenced XRCC2 in 617 Polish women with familial breast cancer and found a founder mutation. We then genotyped 12,617 women with breast cancer and 4599 controls for the XRCC2 founder mutation., Results: We identified a recurrent truncating mutation of XRCC2 (c.96delT, p.Phe32fs) in 3 of 617 patients with familial breast cancer who were sequenced. The c.96delT mutation was then detected in 29 of 12,617 unselected breast cancer cases (0.23%) compared to 11 of 4599 cancer-free women (0.24%) (OR = 0.96; 95% CI 0.48-1.93). The mutation frequency in 1988 women with familial breast cancer was 0.2% (OR = 0.84, 95% CI 0.27-2.65). Breast cancers in XRCC2 mutation carriers and non-carriers were similar with respect to age of diagnosis and clinical characteristics. Loss of the wild-type XRCC2 allele was observed only in one of the eight breast cancers from patients who carried the XRCC2 mutation. No cancer type was more common in first- or second-degree relatives of XRCC2 mutation carriers than in relatives of the non-carriers., Conclusion: XRCC2 c.96delT is a protein-truncating founder variant in Poland. There is no evidence that this mutation predisposes to breast cancer (and other cancers). It is premature to consider XRCC2 as a breast cancer-predisposing gene.

Background: NBN 657del5 founder mutation predisposes to breast and prostate cancer. Recently, it has been reported that the pathogenicity of this mutation with regard to prostate cancer risk is modified by a missense variant of the same gene (E185Q)., Methods: To evaluate the interaction of the 657del5 and E185Q founder alleles of NBN on breast cancer risk in Poland, 4964 women with breast cancer and 6152 controls were genotyped for these two recurrent variants of NBN (657del5 truncating variant and E185Q missense variant)., Results: The NBN 657del5 mutation was detected in 57 of 4964 unselected cases and in 35 of 6152 controls (OR = 2.0, p = 0.001). The E185Q GG genotype was detected in 2167 of 4964 unselected cases and in 2617 of 6152 controls (OR = 1.04, p = 0.3). In carriers of the 657del5 deletion, the elevated cancer risk was restricted to women with the GG genotype of the E185Q variant (OR = 3.6, 95% CI 1.9-6.6; p < 0.0001). Among women with other E185Q genotypes, the OR associated with 657del5 was 1.0 (95% CI 0.5-1.8; p = 0.9). The interaction between the two alleles was statistically significant (homogeneity p = 0.003)., Conclusion: In Poland, the pathogenicity of the NBN 657del5 mutation is restricted to women with a homozygous GG genotype of missense variant of the same gene (E185Q). This is the first clear example whereby a moderate penetrance breast cancer gene is impacted by a genetic modifier.

Bloom Syndrome is a rare recessive disease which includes a susceptibility to various cancers. It is caused by homozygous mutations of the BLM gene. To investigate whether heterozygous carriers of a BLM mutation are predisposed to breast cancer, we sequenced BLM in 617 patients from Polish families with a strong family history of breast cancer. We detected a founder mutation (c.1642C>T, p.Gln548Ter) in 3 of the 617 breast cancer patients (0.49%) who were sequenced. Then, we genotyped 14,804 unselected breast cancer cases and 4698 cancer-free women for the founder mutation. It was identified in 82 of 14,804 (0.55%) unselected cases and in 26 of 4698 (0.55%) controls (OR = 1.0; 95%CI 0.6-1.6). Clinical characteristics of breast cancers in the BLM mutation carriers and non-carriers were similar. Loss of the wild-type BLM allele was not detected in cancers from the BLM mutation carriers. No cancer type was more common in the relatives of mutation carriers compared to relatives of non-carriers. The BLM founder mutation p.Gln548Ter, which in a homozygous state is a cause of Bloom syndrome, does not appear to predispose to breast cancer in a heterozygous state. The finding casts doubt on the designation of BLM as an autosomal dominant breast cancer susceptibility gene.

Objective: To examine how risk-related decision making might be associated with habitual sleep variables, including sleep variability, sleep duration and perceived sleep need in young adults cross-sectionally and longitudinally. Design: 166 participants completed a 7-day protocol with sleep and risk-related decision-making measures at baseline (T1) and 12 months later (T2). Results: Habitual short sleep duration (averaging < 6 h nightly) was identified in 11.0% in our sample. After controlling for baseline demographic factors and risk-taking measures, self-reported sleep need at T1 interacted with habitual short sleep in predicting risk taking at follow-up ( F 8,139 =9.575, adjusted R 2 =.431, p <.001). T1 greater perceived sleep need predicted more risk taking among short sleepers, but decreased risk taking among normal sleepers at T2. Variable sleep timing was cross-sectionally correlated with making more Risky choices at baseline and fewer Safe choices after loss at follow up. Conclusions: Young adults with variable sleep timing and those with short sleep duration coupled with high perceived sleep need were more likely to take risks. The moderating effects of perceived sleep need suggest that individual differences may alter the impact of sleep loss and hence should be measured and accounted for in future studies.

Purpose: To establish the contribution of four founder alleles of NBN to prostate cancer risk and cancer survival., Materials and Methods: Five thousand one hundred eighty-nine men with prostate cancer and 6,152 controls were genotyped for four recurrent variants of NBN (657del5, R215W, I171V, and E185Q)., Results: The NBN 657del5 mutation was detected in 74 of 5,189 unselected cases and in 35 of 6,152 controls (odds ratio [OR], 2.5; p < 0.001). In carriers of 657del5 deletion, the cancer risk was restricted to men with the GG genotype of the E185Q variant of the same gene. Among men with the GG genotype, the OR associated with 657del5 was 4.4 (95% confidence interval [CI], 2.4 to 8.0). Among men with other E185Q genotypes, the OR associated with 657del5 was 1.4 (95% CI, 0.8 to 2.4) and the interaction was significant (homogeneity p=0.006). After a median follow-up of 109 months, mortality was worse for 657del5 mutation carriers than for non-carriers (hazard ratio [HR], 1.6; p=0.001). The adverse effect of 657del5 on survival was only seen on the background of the GG genotype of E185Q (HR, 1.9; p=0.0004)., Conclusion: The NBN 657del5 mutation predisposes to poor prognosis prostate cancer. The pathogenicity of this mutation, with regards to both prostate cancer risk and survival, is modified by a missense variant of the same gene (E185Q).

Background: Sleep problems in childhood are an early predictor of mood disorders among individuals at high familial risk. However, the majority of the research has focused on sleep disturbances in already diagnosed individuals and has largely neglected investigating potential differences between weeknight and weekend sleep in high-risk offspring. This study examined sleep parameters in offspring of parents with major depressive disorder or bipolar disorder during both weeknights and weekends. Methods: We used actigraphy, sleep diaries, and questionnaires to measure several sleep characteristics in 73 offspring aged 4-19 years: 23 offspring of a parent with major depressive disorder, 22 offspring of a parent with bipolar disorder, and 28 control offspring. Results: Offspring of parents with major depressive disorder slept, on average, 26 min more than control offspring on weeknights (95% confidence interval, 3 to 49 min, p = 0.027). Offspring of parents with bipolar disorder slept, on average, 27 min more on weekends than on weeknights compared to controls, resulting in a significant family history × weekend interaction (95% confidence interval, 7 to 47 min, p = 0.008). Conclusions: Sleep patterns in children and adolescents were related to the psychiatric diagnosis of their parent(s). Future follow-up of these results may clarify the relations between early sleep differences and the risk of developing mood disorders in individuals at high familial risk.

Inadequate nightly sleep duration can impair daytime functioning, including interfering with attentional and other cognitive processes. Current models posit that attention is a complex function regulated by several separate, but interacting, neural systems responsible for vigilance, orienting, and executive control. However, it is not clear to what extent each of these underlying component processes is affected by sleep loss. The purpose of this study was to evaluate the effects of acute sleep restriction on these attentional components using the Dalhousie Computerized Attention Battery (DalCAB). DalCAB tasks were administered to healthy women (aged 19-25 years) on two consecutive mornings: once after a night with 9 h time in bed (TIB), and once again after either another night with 9 h TIB (control condition, n = 19) or after a night with 3 h TIB (sleep restriction condition, n = 20). Self-ratings of sleepiness and mood were also obtained following each sleep condition. Participants showed increases in self-reported sleepiness and fatigue after the second night only in the sleep restriction group. Sleep restriction primarily affected processing speed on tasks measuring vigilance; however, performance deficits were also observed on some measures of executive function (e.g., go/no-go task, flanker task, working memory). Tasks assessing orienting of attention were largely unaffected. These results indicate that acute sleep restriction has differential effects on distinct components of attention, which should be considered in modeling the impacts of sleep loss on the underlying attentional networks.

APOBEC3B , in addition to other members of the APOBEC3 gene family, has recently been intensively studied due to its identification as a gene whose activation in cancer is responsible for a specific pattern of massively occurring somatic mutations. It was recently shown that a common large deletion in the APOBEC3 cluster (the APOBEC3B deletion) may increase the risk of breast cancer. However, conflicting evidence regarding this association was also reported. In the first step of our study, using different approaches, including an in-house designed multiplex ligation-dependent probe amplification assay, we analyzed the structure of the deletion and showed that although the breakpoints are located in highly homologous regions, which may generate recurrent occurrence of similar but not identical deletions, there is no sign of deletion heterogeneity. This knowledge allowed us to distinguish transcripts of all affected genes, including the highly homologous canonical APOBEC3A and APOBEC3B , and the hybrid APOBEC3A/APOBEC3B gene. We unambiguously confirmed the presence of the hybrid transcript and showed that the APOBEC3B deletion negatively correlates with APOBEC3A and APOBEC3B expression and positively correlates with APOBEC3A/APOBEC3B expression, whose mRNA level is >10-fold and >1500-fold lower than the level of APOBEC3A and APOBEC3B , respectively. In the next step, we performed a large-scale association study in three different cohorts (2972 cases and 3682 controls) and showed no association of the deletion with breast cancer, familial breast cancer or ovarian cancer. Further, we conducted a meta-analysis that confirmed the lack of the association of the deletion with breast cancer in non-Asian populations., Competing Interests: CONFLICTS OF INTEREST All authors declare no conflicts of interest.

This study sought to: (1) compare actigraphy-derived estimated sleep variables to the same variables based on the gold-standard of sleep assessment, polysomnography; (2) examine whether the correlations between the measures differ between children with attention-deficit/hyperactivity disorder and typically developing children; and (3) determine whether these correlations are altered when children with attention-deficit/hyperactivity disorder are treated with medication. Participants (24 attention-deficit/hyperactivity disorder; 24 typically developing), aged 6-12 years, completed a 1-week baseline assessment of typical sleep and daytime functioning. Following the baseline week, participants in the attention-deficit/hyperactivity disorder group completed a 4-week blinded randomized control trial of methylphenidate hydrochloride, including a 2-week placebo and 2-week methylphenidate hydrochloride treatment period. At the end of each observation (typically developing: baseline; attention-deficit/hyperactivity disorder: baseline, placebo and methylphenidate hydrochloride treatment), all participants were invited to a sleep research laboratory, where overnight polysomnography and actigraphy were recorded concurrently. Findings from intra-class correlations and Bland-Altman plots were consistent. Actigraphy was found to provide good estimates (e.g. intra-class correlations >0.61) of polysomnography results for sleep duration for all groups and conditions, as well as for sleep-onset latency and sleep efficiency for the typically developing group and attention-deficit/hyperactivity disorder group while on medication, but not for the attention-deficit/hyperactivity disorder group during baseline or placebo. Based on the Bland-Altman plots, actigraphy tended to underestimate for sleep duration (8.6-18.5 min), sleep efficiency (5.6-9.3%) and sleep-onset latency, except for attention-deficit/hyperactivity disorder during placebo in which actigraphy overestimated (-2.1 to 6.3 min). The results of the current study highlight the importance of utilizing a multimodal approach to sleep assessment in children with attention-deficit/hyperactivity disorder., (© 2016 European Sleep Research Society.)