Circular Concatemers of Ultra-Short DNA Segments Produce Regulatory RNAs.

In the ciliated protozoan Paramecium tetraurelia, Piwi-associated small RNAs are generated upon the elimination of tens of thousands of short transposon-derived DNA segments as part of development. These RNAs then target complementary DNA for elimination in a positive feedback process, contributing to germline defense and genome stability. In this work, we investigate the formation of these RNAs, which we show to be transcribed directly from the short (length mode 27 bp) excised DNA segments. Our data support a mechanism whereby the concatenation and circularization of excised DNA segments provides a template for RNA production. This process allows the generation of a double-stranded RNA for Dicer-like protein cleavage to give rise to a population of small regulatory RNAs that precisely match the excised DNA sequences. VIDEO ABSTRACT.

A programmable dual-targeting siRNA scaffold supports potent two-gene modulation in the central nervous system.

Divalent short-interfering RNA (siRNA) holds promise as a therapeutic approach allowing for the sequence-specific modulation of a target gene within the central nervous system (CNS). However, an siRNA modality capable of simultaneously modulating gene pairs would be invaluable for treating complex neurodegenerative disorders, where more than one pathway contributes to pathogenesis. Currently, the parameters and scaffold considerations for multi-targeting nucleic acid modalities in the CNS are undefined. Here, we propose a framework for designing unimolecular 'dual-targeting' divalent siRNAs capable of co-silencing two genes in the CNS. We systematically adjusted the original CNS-active divalent siRNA and identified that connecting two sense strands 3' and 5' through an intra-strand linker enabled a functional dual-targeting scaffold, greatly simplifying the synthetic process. Our findings demonstrate that the dual-targeting siRNA supports at least two months of maximal distribution and target silencing in the mouse CNS. The dual-targeting divalent siRNA is highly programmable, enabling simultaneous modulation of two different disease-relevant gene pairs (e.g. Huntington's disease: MSH3 and HTT; Alzheimer's disease: APOE and JAK1) with similar potency to a mixture of single-targeting divalent siRNAs against each gene. This work enhances the potential for CNS modulation of disease-related gene pairs using a unimolecular siRNA.

Versatile CRISPR/Cas9-mediated mosaic analysis by gRNA-induced crossing-over for unmodified genomes.

Mosaic animals have provided the platform for many fundamental discoveries in developmental biology, cell biology, and other fields. Techniques to produce mosaic animals by mitotic recombination have been extensively developed in Drosophila melanogaster but are less common for other laboratory organisms. Here, we report mosaic analysis by gRNA-induced crossing-over (MAGIC), a new technique for generating mosaic animals based on DNA double-strand breaks produced by CRISPR/Cas9. MAGIC efficiently produces mosaic clones in both somatic tissues and the germline of Drosophila. Further, by developing a MAGIC toolkit for 1 chromosome arm, we demonstrate the method's application in characterizing gene function in neural development and in generating fluorescently marked clones in wild-derived Drosophila strains. Eliminating the need to introduce recombinase-recognition sites into the genome, this simple and versatile system simplifies mosaic analysis in Drosophila and can in principle be applied in any organism that is compatible with CRISPR/Cas9.

Alternative treatments of adenomyosis - an update in procedural management and clinical outcomes.

PURPOSE OF REVIEW: Adenomyosis is a common cause of abnormal uterine bleeding (AUB), dysmenorrhea, and pelvic pain. Definitive diagnosis and treatment have historically been by uterine histopathology at time of hysterectomy; however, advances in imaging have supported earlier diagnosis and subsequent conservative treatment. This review aims to update the evidence supporting the uterine-sparing, procedural management options with a focus on clinical outcomes. RECENT FINDINGS: Uterine artery embolization (UAE), radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), percutaneous microwave ablation (PMWA), and adenomyomectomy are minimally invasive interventions proven to be effective in reducing AUB and dysmenorrhea due to adenomyosis. Symptom improvement is associated with a decrease in uterine volume. Studies support the use of alternative treatment options given the overall low rates of symptom recurrence and reintervention. Combination therapy may be more effective than monotherapy. SUMMARY: This review provides the current evidence for use of alternative treatment options for adenomyosis. Access to ablative therapies in the USA is limited and primarily off label, given lack of FDA approval. High-quality prospective and randomized controlled trials are needed in order to further delineate treatment comparisons, efficacy, safety, and ideal patient selection for these treatments. More data are needed to assess safety and utility in those desiring future fertility.

Upgraded CRISPR/Cas9 tools for tissue-specific mutagenesis in Drosophila.

CRISPR/Cas9 has emerged as a powerful technology for tissue-specific mutagenesis. However, tissue-specific CRISPR/Cas9 tools currently available in Drosophila remain deficient in three significant ways. First, many existing gRNAs are inefficient, such that further improvements of gRNA expression constructs are needed for more efficient and predictable mutagenesis in both somatic and germline tissues. Second, it has been difficult to label mutant cells in target tissues with current methods. Lastly, application of tissue-specific mutagenesis at present often relies on Gal4-driven Cas9, which hampers the flexibility and effectiveness of the system. Here, we tackle these deficiencies by building upon our previous CRISPR-mediated tissue-restricted mutagenesis (CRISPR-TRiM) tools. First, we significantly improved gRNA efficiency in somatic tissues by optimizing multiplexed gRNA design. Similarly, we also designed efficient dual-gRNA vectors for the germline. Second, we developed methods to positively and negatively label mutant cells in tissue-specific mutagenesis by incorporating co-CRISPR reporters into gRNA expression vectors. Lastly, we generated genetic reagents for convenient conversion of existing Gal4 drivers into tissue-specific Cas9 lines based on homology-assisted CRISPR knock-in. In this way, we expand the choices of Cas9 for CRISPR-TRiM analysis to broader tissues and developmental stages. Overall, our upgraded CRISPR/Cas9 tools make tissue-specific mutagenesis more versatile, reliable, and effective in Drosophila These improvements may be also applied to other model systems.

Personality and insomnia: A systematic review and narrative synthesis.

The inherent nature of personality serves as a predisposing, and possible maintaining, factor of insomnia. However, methodological differences limit the ability to draw causal conclusions regarding the specific traits involved in the aetiology of the disorder. This systematic review of the relationship between insomnia and personality provides a narrative synthesis of the literature to date. Here, we identified N = 76 studies meeting the inclusion/exclusion criteria. The outcomes reliably evidenced the experience of insomnia to be associated with personality traits that are typically considered to be negative or maladaptive in nature. More specifically, insomnia was related to neuroticism, introversion, perfectionistic doubts and concerns, elevated personal standards, negative affect, social inhibition and avoidance, hysteria, hypochondriasis, psychasthenia, impulsive behaviour, anger, hostility, and psychopathic tendencies, schizotypal and borderline traits, reduced conscientiousness and self-directedness, and negatively perceived perception of the self. Several studies examined the role that personality plays in predicting the treatment efficacy and adherence of CBTi. Moving forward, longitudinal research, methodological consistency, the mediating role of treatment outcomes and adherence, and clinical and population representative samples should be prioritised. Methodological strengths and limitations of the literature are discussed alongside the next steps that should be taken to advance our understanding of the literature.

Outcomes associated with once-daily versus multiple-daily dosing of buprenorphine/naloxone for opioid use disorder.

BACKGROUND AND OBJECTIVES: Clinical studies examining once-daily versus multiple-daily dosing of buprenorphine/naloxone in patients with opioid use disorder (OUD) in the absence of comorbid pain are lacking. METHODS: This retrospective chart review aimed to compare 100 patients prescribed single-daily buprenorphine/naloxone (n = 50) to those prescribed multiple-daily buprenorphine/naloxone (n = 50) to elucidate the impact that dosing frequency has on negative urine drug screens (UDS) and the number of relapses in OUD. RESULTS: The once-daily cohort produced 84% negative UDSs compared with 74% in the multiple-daily cohort which was statistically significant (p = .034). There were a total of 43 relapses reported in the once-daily cohort, compared with 141 relapses in the multiple-daily cohort (p < .001). The average number of relapses per patient in the single-daily cohort was 0.68 compared with the multiple-daily cohort average of 2.16 (p < .001). In the once-daily cohort, 14% of patients experienced at least one relapse throughout the study, compared with 31% in the multiple-daily cohort (p < .002). There were no significant differences between time to relapse, adherence to treatment, or treatment retention. Statistically significantly more patients in the multiple-daily cohort were using methamphetamines (p = .005); there were no significant differences between groups with the use of any other illicit or non-prescribed substances. DISCUSSION AND CONCLUSIONS: Once-daily dosing was associated with more negative UDSs and fewer opioid relapses compared with multiple-daily dosing. SCIENTIFIC SIGNIFICANCE: This was the first study to evaluate buprenorphine/naloxone dosing frequency for opioid use disorder, in the absence of chronic pain. Additional studies evaluating optimal dosing schedules for relapse prevention are warranted.

Facilitators and barriers to social distancing for young people during the COVID-19 pandemic.

BACKGROUND: Social (or physical) distancing is an important transmission-prevention behaviour that has been endorsed to minimize COVID-19 transmission. This qualitative study explores the facilitators of and barriers to social distancing for young people during the COVID-19 pandemic, with recognition that young people represent a unique demographic group, with differing psychosocial needs and experiences to other age cohorts. METHODS: Qualitative data was collected as part of a larger Qualtrics survey between July 28th 2020 and August 24th 2020. Eligible participants were young people living on the Island of Ireland, aged 16-25 years. The survey design was underpinned by the Capability, Opportunity, and Motivation model of behaviour change (COM-B). Semi-inductive thematic analysis was used to analyse comments collected via three free-text survey items. The COM-B model provided a thematic framework to organise subthemes extracted. RESULTS: A total of N = 477 young people completed the survey, of which N = 347 provided comments for at least one of three free-text survey items. The majority of respondents lived in Northern Ireland (96%), the average age was 21 years, and most respondents were female (73%) and were students (81%). Key barriers identified included lack of environmental support for social distancing (lack of physical Opportunity to social distance), observing other people not social distancing (lack of social Opportunities supporting social distancing), and missing physical interaction from others (relating to the dissuading influence of automatic Motivational factors i.e. the influence of loneliness). Key facilitators included presence of clear and consistent environmental cues and availability of space to support social distancing (increasing physical Opportunity to social distance), increasing awareness and perceived consequences of risk of transmission (enhancing reflective Motivational factors i.e. perceived benefits (versus costs) of social distancing), and increasing opportunities to observe others' adhering to guidelines (increasing social Opportunities supporting social distancing). CONCLUSIONS: These findings suggest that the actions and endorsement of peers and the physical design of environments have a key role in influencing social distancing behaviour among young people living in NI. The COM-B factors identified in this study can inform the development of tailored interventions using models such as the Behaviour Change Wheel. The findings of this study suggest that intervention functions based on peer modelling and physical environmental restructuring and enablement should be priortitised, however it is imperative that interventions are co-designed with young people to foster collaboration and empowerment.

Opioid Use After Laparoscopic Surgery for Endometriosis and Pelvic Pain.

STUDY OBJECTIVE: The primary objective was to quantify postoperative opioid use after laparoscopic surgery for endometriosis or pelvic pain. The secondary objective was to identify patient characteristics associated with greater postoperative opioid requirements. DESIGN: Prospective, survey-based study in which subjects completed 1 preoperative and 7 postoperative surveys within 28 days of surgery regarding medication usage and pain control. SETTING: Tertiary care, academic center. PATIENTS: A total of 100 women with endometriosis or pelvic pain. INTERVENTIONS: Laparoscopic same-day discharge surgery by fellowship-trained minimally invasive gynecologists. MEASUREMENTS AND MAIN RESULTS: A total of 100 patients were recruited and 8 excluded, for a final sample size of 92 patients. All patients completed the preoperative survey. Postoperative response rates ranged from 70.7% to 80%. The mean number of pills (5 mg oxycodone tablets) taken by day 28 was 6.8. The average number of pills prescribed was 10.2, with a minimum of 4 (n = 1) and maximum of 20 (n = 3). Previous laparoscopy for pelvic pain was associated with a significant increase in postoperative narcotic use (8.2 vs 5.6; p = .044). Hysterectomy was the only surgical procedure associated with a significant increase in postoperative narcotic use (9.7 vs 5.4; p = .013). There were no difference in number of pills taken by presence of deep endometriosis or pathology-confirmed endometriosis (all p >.36). There was a trend of greater opioid use in patients with diagnoses of self-reported chronic pelvic pain, anxiety, and depression (7.9 vs 5.7, p = .051; 7.7 vs 5.2, p = .155; 8.1 vs 5.6, p = .118). CONCLUSION: Most patients undergoing laparoscopic surgery for endometriosis and pelvic pain had a lower postoperative opioid requirement than prescribed, suggesting surgeons can prescribe fewer postoperative narcotics in this population. Patients with a previous surgery for pelvic pain, self-reported chronic pelvic pain syndrome, anxiety, and depression may represent a subset of patients with increased postoperative opioid requirements.

The role of the COVID-19 pandemic in altered psychological well-being, mental health and sleep: an online cross-sectional study.

Coronavirus disease 2019 (COVID-19) is a global pandemic. Measures to reduce transmission of the virus have altered usual activities, routines, and livelihoods, and have had a significant impact on mental health. The current study aims to examine the potential alterations in psychological wellbeing, mental health, sleep and diurnal preference due to the COVID-19 pandemic. A cross sectional online questionnaire-based study with n = 200 participants (aged 18-62; 7.86.0% female, 93.0% white, 92.5% UK-based, 73.5% students). Data were collected between 15th April and 8 June 2020. Participants answered questions on lifestyle changes and their concerns and worries about COVID-19, and completed the SCI, PHQ9, GAD7, PWB18, UCLA3 and MEQ. Results showed self-isolation was linked to lower psychological well-being, and increased loneliness, anxiety and depression. Home-working was related to a shift in diurnal preference. Reduced work/income was related to decreased psychological well-being and sleep quality and increased anxiety, depression, loneliness and. Intensity of worried thoughts and concerns about COVID-19 were positively correlated with anxiety, depression and negatively with sleep quality. In conclusion, the social, occupational and economic disruption due to COVID19 has had a negative impact on psychological well-being. However, the transition to home-working may have been somewhat beneficial for some individuals in terms of sleep. These findings should be taken into account by policy makers during the transition to the 'new normal' post-pandemic.

Community sharing: Contextualizing Western research notions of contamination within an Indigenous research paradigm.

Báa nnilah is a chronic illness self-management program designed by and for the Apsáalooke (Crow) community. Arising from a collaboration between an Indigenous nonprofit organization and a university-based research team, Báa nnilah's development, implementation, and evaluation have been influenced by both Indigenous and Western research paradigms (WRPs). Báa nnilah was evaluated using a randomized wait-list control group design. In a WRP, contamination, or intervention information shared by the intervention group with the control group, is actively discouraged as it makes ascertaining causality difficult, if not impossible. This approach is not consonant with Apsáalooke cultural values that include the encouragement of sharing helpful information with others, supporting an Indigenous research paradigm's (IRP) goal of benefiting the community. The purpose of this paper is to address contamination and sharing as an area of tension between WRP and IRP. We describe how the concepts of contamination and sharing within Báa nnilah's implementation and evaluation are interpreted differently when viewed from these contrasting paradigms, and set forth a call for greater exploration of Indigenous research approaches for developing, implementing, and evaluating intervention programs in Indigenous communities. (Improving Chronic Illness Management with the Apsáalooke Nation: The Báa nnilah Project.: NCT03036189), ClinicalTrials. gov: NCT03036189).

Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for regional control.

Approximately half the mammalian genome is composed of repetitive sequences, and accumulating evidence suggests that some may have an impact on genome function. Here, we characterized a large array class of repeats of long-interspersed elements (LINE-1). Although widely distributed in mammals, locations of such arrays are species specific. Using targeted deletion, we asked whether a 170-kb LINE-1 array located at a mouse imprinted domain might function as a modulator of local transcriptional control. The LINE-1 array is lamina associated in differentiated ES cells consistent with its AT-richness, and although imprinting occurs both proximally and distally to the array, active LINE-1 transcripts within the tract are biallelically expressed. Upon deletion of the array, no perturbation of imprinting was observed, and abnormal phenotypes were not detected in maternal or paternal heterozygous or homozygous mutant mice. The array does not shield nonimprinted genes in the vicinity from local imprinting control. Reduced neural expression of protein-coding genes observed upon paternal transmission of the deletion is likely due to the removal of a brain-specific enhancer embedded within the LINE array. Our findings suggest that presence of a 170-kb LINE-1 array reflects the tolerance of the site for repeat insertion rather than an important genomic function in normal development.

Abdominal wall endometriosis: an update in diagnosis, perioperative considerations and management.

PURPOSE OF REVIEW: Abdominal wall endometriosis (AWE) is rare with limited evidence guiding diagnosis and treatment. The purpose of this review is to provide an update of the diagnosis, perioperative considerations, and treatment of AWE. RECENT FINDINGS: Recent studies further characterize presenting symptoms and locations of AWE. Prior abdominal surgery remains the greatest risk factor for the development of AWE. Newer evidence suggests that increasing BMI may also be a risk factor. Ultrasound is first-line imaging for diagnosis. Magnetic resonance image is preferred for surgical planning for deep or extensive lesions. Laparotomy with wide local excision is considered standard treatment for AWE with great success. Novel techniques in minimally invasive surgery have been described as effective for the treatment of AWE. A multidisciplinary surgical approach is often warranted for successful excision and reapproximation of skin and/or fascial defects. Noninvasive therapies including ultrasonic ablation or cryotherapy are also emerging as promising treatment strategies in select patients. SUMMARY: Recent studies provide further evidence to guide diagnosis through physical exam and imaging as well as pretreatment planning. Treatment options for AWE are rapidly expanding with novel approaches in minimally invasive and noninvasive therapies now available.

What are the underlying reasons behind socioeconomic differences in doctor-patient communication in head and neck oncology review clinics?

OBJECTIVE: To explore socioeconomic status (SES) differences in patterns of doctor-patient communication within head and neck cancer clinics and why such differences exist. METHODS: Thirty-six head and neck cancer review appointments with five Physicians were observed and audio-taped, along with follow-up interviews involving 32 patients. Data were analysed using Thematic Analysis, and compared by patient SES (education, occupation and Indices of Multiple Deprivation). RESULTS: Three main themes were identified: (a) Physicians used more humour and small talk in their consultations with high SES patients; (b) Low SES patients were more passive in their participation, engaged in less agenda setting and information-seeking, and framed their clinical experience differently; (c) Low SES patients had different preferences for involvement, defining involvement differently to high SES patients and were seen to take a more stoical approach. CONCLUSION: Low SES patients take a more passive role in medical consultations, engage in less relational talk and are less likely to raise concerns, but were satisfied with this. Physicians may adapt their communication behaviour in response to low SES patients' expectations and preferences. PRACTICE IMPLICATIONS: A question prompt list may help low SES patients to raise concerns during their consultations. This may reduce inequalities in communication and health.

Examining the Factor Structure, Reliability, and Validity of the Disturbing Dreams and Nightmare Severity Index (DDNSI) Consequences Sub-component.

Background: The Disturbing Dreams and Nightmares Severity Index (DDNSI) is commonly used when assessing the experience of nightmares. It comprises two parts examining i) chronicity and ii) nightmare consequences. The primary aim of the present study was to explore the dimensional structure of the optional and currently unvalidated nightmare consequences component using exploratory factor analysis. Internal reliability and construct validity were also examined. A secondary aim explored the relationships between nightmare chronicity and perceived consequences with measures of anxiety, depression, stress, self-efficacy, and insomnia.Methods: A cross-sectional survey was conducted with complete data from N = 757 students from six UK-based universities. Participants completed the chronicity and consequences components of the DDNSI, alongside the Sleep Condition Indicator, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Perceived Stress Scale, and General Self-Efficacy Scale.Results: Two nightmare consequences factors emerged; 'Sleep-Interference' (four items; α =.848), and 'Psychosocial Well-being' (six items; α =.946). Significantly moderate correlations were observed between the two emerging factors and the nightmare chronicity component, as well as with insomnia, anxiety, depression, perceived stress, and self-efficacy. Perceived 'Sleep-Interference' (ß =-.241) was the strongest predictor of insomnia, and 'Psychosocial wellbeing' was the strongest predictor of anxiety (ß =.688) depression (ß =.804) perceived stress and lower self-efficacy.Conclusions: The perceived nightmare consequences component of the DDSNI is a multidimensional construct comprising two internally consistent and distinct, but related dimensions. The potential importance of distinguishing between types of perceived nightmare consequences and the associations with mental health outcomes in a student population is highlighted.

Homogeneity of cognitive and behavioural processes underlying the relationship between insomnia and body image disturbance.

Specific cognitive behavioural mechanisms related to selective attention, situational avoidance and physical appearance are implicated in the development and maintenance of insomnia and negative reinforcement of body image disturbances. Therefore, we examined whether these processes potentially mediate the relationship between insomnia and body image perception. N = 728 participants completed self-reported measures of sleep-associated monitoring, insomnia symptoms, body image disturbance and coping with body image challenges. Symptoms of insomnia and sleep-associated monitoring behaviour were independently related to increased reports of body image disturbance, cognitive distortions of body image, appearance fixing (i.e. altering appearance by covering, camouflaging or correcting the perceived defect), avoidance (i.e. attempt to escape or avert stressful body image situations) and reduced levels of positive rationale acceptance (i.e. acceptance of the challenging event and positive self-care or rationale self-talk about one's appearance). More crucially, sleep-related monitoring on awakening, cognitive distortion of body image and negative coping strategies related to body image (i.e. appearance fixing, avoidance, rationale acceptance) mediated the relationship between reports of body image disturbance and insomnia symptoms. The current findings expand upon previous research demonstrating consistent relationships between poor sleep and increased dissatisfaction with cutaneous features, by providing novel evidence that body image disturbances are associated with symptoms of insomnia. More crucially, we highlight the role of particular cognitive and behavioural mechanisms pertaining to sleep (i.e. selective attention for physical signs of poor sleep) and body image (i.e. avoidance and rationale acceptance) which may be targeted as part of cognitive behavioural treatments.

Necessity Is the Mother of Invention: Ciliates, Transposons, and Transgenerational Inheritance.

Ciliates are a fascinating model system for the study of the interaction between eukaryotic germlines and somatic lines, especially with regard to the invasion and defence against transposable elements. They separate their germline and somatic line into two nuclei within the same cell, and they silence transposons and repetitive elements by way of deleting them from their somatic genome. This large-scale deletion event uses a series of intricate sequence targeting pathways involving small RNAs and transposases, part of which consists of a transnuclear comparison between maternal soma and daughter germline. We present recent progress in this dynamic field, and argue that these DNA targeting pathways provide an optimal system for the transgenerational inheritance of acquired traits. Ciliates thus also demonstrate the evolutionary value of transposable elements, both as sources of sequence diversity and also as drivers of adaptive evolution by necessitating defensive systems.

Examination of sleep health dimensions and their associations with perceived stress and health in a UK sample.

BACKGROUND: Sleep health is a relatively new multidimensional concept, however, there is no consensus on its underlying dimensions. A previous study examined potential indicators of sleep health using an aggregated sleep health measure. However, the psychometric properties are yet to be determined. The primary aim was to assess the factor structure, reliability and validity of this measure. A secondary aim was to explore the relationships with perceived stress, and physical and mental health. METHODS: A cross-sectional online survey was conducted with 257 adults from the UK aged 18-65 (78.4% female, mean age = 29.39 [SD = 11.37]). Participants completed 13 Sleep health items, the Pittsburgh Sleep Quality Inventory, Insomnia Severity Scale, Epworth Sleepiness Scale, Perceived Stress Scale and SF-12 Health Survey. RESULTS: The measure exhibited good internal consistency (α = 0.785) and construct validity as determined by associations with existing measures. Principle components analysis produced four factors e; sleep quality (α = 0.818), sleep adaptability (α = 0.917), sleep wellness (α = 0.621) and daytime functioning (α = 0.582). Adaptability (ß = -241) was strongest predictor of perceived stress, and daytime functioning was strongest predictor of physical (ß = 0.322) and mental health (ß = 0.312). CONCLUSIONS: Sleep health is a multidimensional construct comprising four distinct but related dimensions. The importance of sleep health in terms of perceived stress and mental and physical health is highlighted.

Dysfunctional sleep-related cognition and anxiety mediate the relationship between multidimensional perfectionism and insomnia symptoms.

Perfectionism is one of several personality traits associated with insomnia. Whilst research has examined the relationships between perfectionism and insomnia, the mediating role of dysfunctional sleep-related cognition (i.e. sleep-related worry and dysfunctional beliefs about the biological attribution of and consequences of poor sleep) has yet to be examined. This study aimed to determine whether aspects of multidimensional perfectionism were related to increased reporting of insomnia symptoms. In addition, the potential mediating role of dysfunctional sleep-related cognition and anxiety symptoms was examined. Members of the general population (N = 624) completed the Dysfunctional Beliefs and Attitudes About Sleep Scale, the Insomnia Severity Index, the Hospital Anxiety and Depression Scale, and the Multidimensional Perfectionism Scale. The results showed that perfectionism dimensions, anxiety symptoms, and dysfunctional sleep-related cognition were significantly associated with insomnia symptoms. Regression-based mediation analyses further showed that both dysfunctional sleep-related cognition and anxiety significantly mediated the associations between insomnia symptoms and three perfectionism dimensions (i.e. doubts about action, parental expectations, and parental criticism). The experience of perfectionistic tendencies, anxiety, and dysfunctional sleep-related cognition may initiate behavioural strategies (e.g. daytime napping) when faced with an acute sleep problem. However, these strategies may serve to transition insomnia from an acute to a chronic condition.

Subclinical hypothyroidism: To treat or not to treat?

Subclinical hypothyroidism affects 4.3% of the US population. Despite this prevalence, whether to treat or to observe patients with subclinical hypothyroidism remains controversial. Guidelines for overt hypothyroidism strongly favor treatment for symptomatic benefits, but the same benefits of levothyroxine treatment have not been proven for patients with subclinical hypothyroidism-most likely due to the asymptomatic nature of the condition. Additionally, a connection between subclinical hypothyroidism and cardiovascular complications has not been definitively established, although the evidence favors a relationship. This article describes the background, presentation, and diagnostics of subclinical hypothyroidism, treatment, and potential cardiovascular complications, so clinicians can decide if initiating treatment is best for their patients with subclinical hypothyroidism.