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Hilal Uygur,1 Oli Ahmed,2 Omer Faruk Uygur,3 Christopher B Miller,4,5 Onur Hursitoglu,6 Aynur Bahar,7 Dudu Demiroz,8 Christopher L Drake9,10 1Department of Psychiatry, Erzurum Training and Research Hospital, Erzurum, Turkey; 2Department of Psychology, University of Chittagong, Chattogram, Bangladesh; 3Department of Psychiatry, Ataturk University School of Medicine, Erzurum, Turkey; 4Big Health Ltd, London, UK; 5Department of Clinical Neurosciences, Sleep and Circadian Neuroscience Institute, University of Oxford, Oxford, UK; 6Department of Psychiatry, Sular Academy Hospital, Kahramanmaras, Turkey; 7Department of Psychiatric Nursing, Gaziantep University Faculty of Health Sciences, Gaziantep, Turkey; 8Department of Psychiatry, Karamanoglu Mehmetbey University, Karaman, Turkey; 9Henry Ford Hospital Sleep Disorders and Research Center, Detroit, MI, USA; 10Department of Psychiatry and Behavioral Neurosciences, Wayne State College of Medicine, Detroit, MI, USACorrespondence: Hilal Uygur, Department of Psychiatry, Erzurum Training and Research Hospital, Erzurum, Turkey, Tel +90 (442) 4321000, Email atilahilal@yahoo.comPurpose: We aimed to adapt the Turkish Sleep Condition Indicator (SCI) version and examine its psychometric properties among the general population.Methods: This study was a cross-sectional study. The item-total correlation, standard error of measurement, Cronbach’s α, and McDonald’s ω were used for internal consistency. We ran confirmatory factor analysis (CFA) and network analysis to confirm the factor structure. Multigroup CFA was run to assess the measurement invariance across gender, whether clinical insomnia or not, and poor sleep quality. We correlated SCI scores with Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) scores to evaluate construct validity. A receiver operating characteristic (ROC) curve analysis was conducted to calculate the cut-off score of the SCI. The temporal stability was examined with the intraclass correlation coefficient.Results: Eight hundred thirty-four participants attended. Over half of the participants were women (63.2% n = 527); the mean age was 36.15 ± 9.64. Confirmatory factor and network analysis results show that the two-factor correlated model had a good model fit for the SCI. The SCI had scalar level invariance across gender, having clinical insomnia and poor sleep quality in the Multigroup CFA. ROC curve analysis shows that the SCI has good sensitivity (90.3%) and specificity (91.8%) for cut-off ≤ 15. The intraclass correlation coefficient computed between the first and second SCI total scores was significant (r=0.80 with a 95% confidence interval from 0.78 to 0.87; p < 0.001).Conclusion: The Turkish SCI is a practical self-reported insomnia scale with good psychometric properties that can be used to screen for insomnia disorder.Keywords: questionnaire, insomnia screening, sleep condition indicator, validity, reliability

The literature on zooplankton population dynamics provides more estimation techniques than reliable estimates of population parameters. In this review we show how different techniques relate to each other in terms of underlying models and assumptions. There are two main routes to parameter estimates. The vertical approaches utilize the stage-structure of samples taken at the same point in time. They require assumptions about the constancy in the parameters, but relax assumptions concerning advective influence. The horizontal approaches utilize information provided by the stage structure within samples, as well as information on temporal changes in abundance. They relax assumptions about the constancy of parameters, but advective influences may be introduced. Of the horizontal methods, variants of what are commonly termed cohort methods have been widely used. These provide mathematical simplicity, but are based on more restrictive assumptions than methods fitting predescribed models (delay differential, partial differential equation, and matrix models of population dynamics). Because the quality of estimates, such as of mortality rates, depends upon the quality of the data, some sampling considerations in regard to advection and biases in estimating stage composition are discussed. It is important to reduce the number of parameters to be estimated from census data, thus we review some techniques for independent measurement of stage durations and birth rates. Finally, we provide some general recommendations for future studies. © 1997 Taylor & Francis Group, LLC.

The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet count ≥50 × 10 9 /L, previously treated with ruxolitinib. The trial design included protocol specified strategies to mitigate the risk for gastrointestinal (GI) adverse events (AEs), thiamine supplementation, and encephalopathy surveillance. Due to COVID-19, accrual was cut short with 38 patients enrolled. In the efficacy evaluable population ( n  = 35), nine (25.7%; 95% confidence interval 12.5-43.3) patients achieved primary endpoint of ≥35% spleen volume reduction (SVR) at end of cycle (EOC) 6; and 22 (62.9%) patients showed best overall response of ≥35% SVR up to end of treatment. Sixteen (44.4%) patients showed ≥50% reduction in total symptom score at EOC6 ( n  = 36). Compared to previously reported JAKARTA-2 trial, rates of GI AEs were lower, and no patient developed encephalopathy. Overall, FREEDOM study showed clinically relevant spleen and symptom responses with fedratinib, and effective mitigation of GI AEs.

Insomnia is a highly prevalent sleep disorder. It is the most frequent sleep complaint among Higher Education students. The Sleep Condition Indicator is a self-report tool aimed at assessing insomnia based on the DSM-5 criteria. The principal goal of this study was to establish preliminary psychometric properties of the European Portuguese version of the Sleep Condition Indicator in a sample of Higher Education students. Data from a diverse pool of Higher Education students (N = 537) were collected online over a month. Most participants were women (75%) and aged approximately 27 years. The Sleep Condition Indicator demonstrated good internal consistency (α = 0.85), with all the items accounting significantly for the scale reliability. The most appropriate factor structure considering the ordinal nature of the items was unidimensional, with all items explaining 64% of the total variance. However, a two-factor structure (sleep pattern and sleep-related impact) was also plausible when other statistical estimators were used. The Sleep Condition Indicator correlated significantly with insomnia severity, vulnerability to stress-related sleep disturbance, and self-reported daytime sleepiness. The optimal cut-off point established based on the receiver operating characteristic curve analysis was ≤ 16. A short version comprising only two items was also viable as suggested by the literature. The Sleep Condition Indicator is a reliable and valid tool for screening for insomnia. More studies with other groups are now required, specifically with clinical samples., (© 2024 European Sleep Research Society.)

Background: The Sleep Condition Indicator (SCI), an insomnia measurement tool based on the updated Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria with sound psychometric properties when applied in various populations, was evaluated here among healthcare students longitudinally, to demonstrate its measurement properties and invariance in this particularly high-risk population., Methods: Healthcare students of a Chinese university were recruited into this two-wave longitudinal study, completing the simplified Chinese version of the SCI (SCI-SC), Chinese Regularity, Satisfaction, Alertness, Timing, Efficiency, Duration (RU&#95;SATED-C) scale, Chinese Patient Health Questionnaire-4 (PHQ-4-C), and sociodemographic variables questionnaire (Q-SV) between September and November 2022. Structural validity, measurement invariance (MI), convergent and discriminant validity, internal consistency, and test-retest reliability of the SCI-SC were examined. Subgroups of gender, age, home location, part-time job, physical exercise, and stress-coping strategy were surveyed twice to test cross-sectional and longitudinal MI., Results: We identified 343 valid responses (62.9% female, mean age = 19.650 ± 1.414 years) with a time interval of seven days. The two-factor structure was considered satisfactory (comparative fit index = 0.953-0.989, Tucker-Lewis index = 0.931-0.984, root means square error of approximation = 0.040-0.092, standardized root mean square residual = 0.039-0.054), which mostly endorsed strict invariance except for part-time job subgroups, hence establishing longitudinal invariance. The SCI-SC presented acceptable convergent validity with the RU&#95;SATED-C scale (r ≥ 0.500), discriminant validity with the PHQ-4-C (0.300 ≤ r < 0.500), internal consistency (Cronbach's alpha = 0.811-0.835, McDonald's omega = 0.805-0.832), and test-retest reliability (intraclass correlation coefficient = 0.829)., Conclusion: The SCI-SC is an appropriate screening instrument available for assessing insomnia symptoms among healthcare students, and the promising measurement properties provide additional evidence about validity and reliability for detecting insomnia in healthcare students., (© 2024. The Author(s).)

Background: Hypertensive disorders of pregnancy are a leading cause of perinatal morbidity, and timely treatment of severely elevated blood pressure is recommended to prevent serious sequelae. In acute hypertension marked by increased blood volume, it is unknown whether diuretics used as an adjunct to antihypertensive medications lead to more effective blood pressure control., Objective: This study aimed to evaluate whether the addition of intravenous furosemide to first-line antihypertensive agents reduces systolic blood pressure in acute-onset, severe antenatal hypertension with wide (≥60 mm Hg) pulse pressure., Study Design: In this double-blinded randomized trial, participants received 40 mg of intravenous furosemide or placebo in addition to a first-line antihypertensive agent. The primary outcome was mean systolic blood pressure during the first hour after intervention. Secondary outcomes included corresponding diastolic blood pressure; systolic blood pressure, diastolic blood pressure, and pulse pressure at 2 hours after intervention; total reduction from qualifying blood pressure; duration of blood pressure control; need for additional antihypertensive doses within 1 hour; and electrolytes and urine output. A sample size of 35 participants per group was planned to detect a 15-mm Hg difference in blood pressure., Results: Between January 2021 and March 2022, 65 individuals were randomized: 33 to furosemide and 32 to placebo. Baseline characteristics were similar between the groups. There was no difference in the primary outcome of mean 1-hour systolic blood pressure (147 [14.8] vs 152 [13.8] mm Hg; P=.200). We found a reduction in 2-hour systolic blood pressure (139 [18.5] vs 154 [18.4] mm Hg; P=.007) and a decrease in 2-hour pulse pressure (55 [12.5] vs 67 [15.1]; P=.003) in the furosemide group. Subgroup analysis according to hypertension type showed a significant reduction in 2-hour systolic blood pressure and 2-hour pulse pressure among patients with new-onset hypertension, but not among those with preexisting hypertension. Urine output was greater in the furosemide group, with no difference in electrolytes and creatinine before and after intervention., Conclusion: Intravenous furosemide in conjunction with a first-line antihypertensive agent did not significantly reduce systolic blood pressure in the first hour after administration. However, both systolic blood pressure and pulse pressure at 2 hours were decreased in the furosemide group. These findings suggest that a 1-time dose of intravenous furosemide is a reasonable adjunct to achieve blood pressure control, particularly in patients in whom increased volume is suspected., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the liver, mitochondria are exposed to different concentrations of nutrients due to their spatial positioning across the periportal and pericentral axis. How the mitochondria sense and integrate these signals to respond and maintain homeostasis is not known. Here, we combine intravital microscopy, spatial proteomics, and functional assessment to investigate mitochondrial heterogeneity in the context of liver zonation. We find that periportal and pericentral mitochondria are morphologically and functionally distinct; beta-oxidation is elevated in periportal regions, while lipid synthesis is predominant in the pericentral mitochondria. In addition, comparative phosphoproteomics reveals spatially distinct patterns of mitochondrial composition and potential regulation via phosphorylation. Acute pharmacological modulation of nutrient sensing through AMPK and mTOR shifts mitochondrial phenotypes in the periportal and pericentral regions, linking nutrient gradients across the lobule and mitochondrial heterogeneity. This study highlights the role of protein phosphorylation in mitochondrial structure, function, and overall homeostasis in hepatic metabolic zonation. These findings have important implications for liver physiology and disease., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Sleep problems associated with poor mental health and academic outcomes may have been exacerbated by the COVID-19 pandemic., Aims: To describe sleep in undergraduate students during the COVID-19 pandemic., Method: This longitudinal analysis included data from 9523 students over 4 years (2018-2022), associated with different pandemic phases. Students completed a biannual survey assessing risk factors, mental health symptoms and lifestyle, using validated measures. Sleep was assessed with the Sleep Condition Indicator (SCI-8). Propensity weights and multivariable log-binomial regressions were used to compare sleep in four successive first-year cohorts. Linear mixed-effects models were used to examine changes in sleep over academic semesters and years., Results: There was an overall decrease in average SCI-8 scores, indicating worsening sleep across academic years (average change -0.42 per year; P -trend < 0.001), and an increase in probable insomnia at university entry (range 18.1-29.7%; P -trend < 0.001) before and up to the peak of the pandemic. Sleep improved somewhat in autumn 2021, when restrictions loosened. Students commonly reported daytime sleep problems, including mood, energy, relationships (36-48%) and concentration, productivity, and daytime sleepiness (54-66%). There was a consistent pattern of worsening sleep over the academic year. Probable insomnia was associated with increased cannabis use and passive screen time, and reduced recreation and exercise., Conclusions: Sleep difficulties are common and persistent in students, were amplified by the pandemic and worsen over the academic year. Given the importance of sleep for well-being and academic success, a preventive focus on sleep hygiene, healthy lifestyle and low-intensity sleep interventions seems justified.

Background: Considerable comorbidity exists between insomnia and anxiety, and evidence shows that the benefits of CBT for insomnia extend to anxiety. Using data from two large trials of digital CBT (dCBT) for insomnia, we evaluated whether improving sleep is an effective treatment target to reduce both insomnia and anxiety symptoms in individuals with insomnia and clinically significant anxiety., Methods: This was a controlled sub-analysis combining individual participant data from two previous randomised controlled trials of dCBT for insomnia (Sleepio). Participants (N = 2172) with insomnia disorder and clinically significant anxiety symptoms were included in this sub-analysis and received either dCBT or control (usual care or sleep hygiene education). Assessments were evaluated at baseline, post-intervention (week 8 or 10), and follow-up (week 22 or 24). Mediation was evaluated using structural equation models., Results: dCBT for insomnia was superior to control at reducing both insomnia (Hedges' g range = 0.77-0.81; both p < 0.001) and anxiety symptoms (Hedges' g range = 0.39-0.44; both p < 0.001) at all time points. Baseline insomnia symptoms moderated the effects of dCBT on insomnia, however no variables moderated treatment effects on anxiety. Reductions in anxiety symptoms at follow-up were mediated by improvements in sleep at post-intervention (% mediated = 84 %), suggesting a causal pathway., Limitations: Participants did not have a formal anxiety disorder diagnosis and so the effects of dCBT for insomnia on anxiety may differ by anxiety disorder., Conclusions: Addressing sleep using dCBT for insomnia may serve as a treatment target from which to improve anxiety in individuals with insomnia and clinically significant comorbid anxiety., Clinical Trial Registrations: Digital Insomnia therapy to Assist your Life as well as your Sleep (DIALS) - ISRCTN60530898 http://www.isrctn.com/ISRCTN60530898. Oxford Access for Students Improving Sleep (OASIS) - ISRCTN61272251 http://www.isrctn.com/ISRCTN61272251., Competing Interests: Declaration of competing interest The authors declare no Competing Non-Financial Interests but the following Competing Financial Interests. ALH is employed by Big Health Ltd. (Sleepio), receives a salary and is a shareholder. CBM, is employed by Big Health Ltd. and is salaried by the company. CAE is the Co-Founder and Chief Scientist of Big Health Ltd. and is a shareholder, and is salaried by the company. BS offered clinical consultancy to Big Health Ltd. during the course of the OASIS trial. RE is a paid consultant of Big Health Ltd. AIL held a position at the University of Oxford funded by Big Health Inc. when the DIALS trial was being conducted. The digital CBT intervention was made available to all participants at no cost. No other investigators report conflicts of interest. Both original studies were conducted at the University of Oxford, Sleep & Circadian Neuroscience Institute and Department of Psychiatry., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition., Competing Interests: EM and HM have received research grants from Haemonetics Corporation outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marsh, Moore, Moore, Bunch, Aboukhaled, Condon, Al-Fadhl, Thomas, Larson, Bower, Miller, Pearson, Twilling, Reser, Kim, Troyer, Yeager, Thomas, Srikureja, Patel, Añón, Thomas, Miller, Van Ryn, Pamulapati, Zimmerman, Wells, Martin, Seder, Aversa, Greene, March, Kwaan, Fulkerson, Vande Lune, Mollnes, Nielsen, Storm and Walsh.)

Insomnia is a highly prevalent sleep disorder with strong bidirectional associations with depressive symptoms. The circadian preference for eveningness has been shown to be associated with depressive symptoms in insomnia and other mental health conditions. However, there is a lack of studies in insomnia investigating whether objective measures, such as dim light melatonin onset (DLMO) or polysomnographic (PSG) sleep, are associated with depressive symptoms. Therefore, we investigated the associations between subjective measures (questionnaires assessing anxiety, sleep quality and circadian preference, and sleep diary) and depressive symptoms and whether the addition of objective measures (DLMO, PSG parameters) would strengthen the associations with depressive symptoms. In 115 insomnia disorder patients we found that anxiety was strongly associated with depressive symptoms in a model including circadian preference, dysfunctional beliefs of sleep, and self-reported previous depressive symptoms (R 2 = 0.496, p < 0.001). The addition of sleep diary measures did not strengthen the model. We also found that the addition of objective measures (DLMO, PSG parameters) did not improve the subjective associations with depressive symptoms. Our data suggest that objective circadian markers are less important in the prediction of depressive symptoms in insomnia compared to subjective measures.

Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness, may be troubling for patients and/or may be a necessary part of the patient's treatment journey. This pilot trial aims to explore the potential benefit of armodafinil, a wakefulness promoter. Patients were treated with SRT with open label adjunctive armodafinil (150 mg/day). Thirty-three patients from previous studies that have undergone exactly the same SRT intervention acted as controls. The primary outcome measure was the insomnia severity index (ISI), and secondary outcomes were the Epworth sleepiness scale, sleep restriction adherence scale (SRAS), and safety from baseline through to 12 weeks. We recruited 25 patients into the trial. Data for the primary end point (ISI at 12 weeks) was available for 20 of the participants. The baseline insomnia severity index was 20.2 (SD 3.3) and decreased to 9.1 (SE 1.1), with no change, to 10.2 and 11.2 at weeks 6 and 12 respectively (all p > 0.05 compared with baseline). The insomnia severity index values for armodafinil patients were statistically inferior to historical controls at the primary time point of 12 weeks (11.2 vs. 6.7, p < 0.01). Sleep restriction therapy plus armodafinil treatment was associated with frequent minor side effects but was generally safe and acceptable to patients. Sleep restriction therapy was associated with a robust clinical response in the insomnia severity index values for insomnia patients. Based upon historical control data, armodafinil does not appear to have beneficial adjunctive effects in addition to sleep restriction therapy alone., (© 2022 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Land cover and use around the margins of estuaries has shifted since 1950 at many sites in North America due to development pressures from higher population densities. Small coastal watersheds are ubiquitous along estuarine margins and most of this coastal land-cover change occurred in these tidal creek watersheds. A change in land cover could modify the contribution of sediments from tidal creek watersheds to downstream areas and affect estuarine habitats that rely on sediments to persist or are adversely impacted by sediment loading. The resilience of wetlands to accelerating relative sea-level rise depends, in part, on the supply of lithogenic sediment to support accretion and maintain elevation; however, subtidal habitats such as oyster reefs and seagrass beds are stressed under conditions of high turbidity and sedimentation. Here we compare sediment accumulation rates before and after 1950 using 210Pb in 12 tidal creeks across two distinct regions in North Carolina, one region of low relief tidal-creek watersheds where land cover change since 1959 was dominated by fluctuations in forest, silviculture, and agriculture, and another region of relatively high relief tidal-creek watersheds where land-use change was dominated by increasing suburban development. At eight of the creeks, mass accumulation rates (g cm-2 y-1) measured at the outlet of the creeks increased contemporaneously with the largest shift in land cover, within the resolution of the land-cover data set (~5-years). All but two creek sites experienced a doubling or more in sediment accumulation rates (cm yr-1) after 1950 and most sites experienced sediment accumulation rates that exceeded the rate of local relative sea-level rise, suggesting that there is an excess of sediment being delivered to these tidal creeks and that they may slowly be infilling. After 1950, land cover within one creek watershed changed little, as did mass accumulation rates at the coring location, and another creek coring site did not record an increase in mass accumulation rates at the creek outlet despite a massive increase in development in the watershed that included the construction of retention ponds. These abundant tidal-creek watersheds have little relief, area, and flow, but they are impacted by changes in land cover more, in terms of percent area, than their larger riverine counterparts, and down-stream areas are highly connected to their associated watersheds. This work expands the scientific understanding of connectivity between lower coastal plain watersheds and estuaries and provides important information for coastal zone managers seeking to balance development pressures and environmental protections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bost et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Study Objectives: Insomnia, depression, and anxiety show high rates of comorbidity and functional impairment. Transdiagnostic symptom interactions may be implicated in this comorbidity. This network analysis sought to assess how symptoms of insomnia, depression, and anxiety may interact and individually predict impairment across several domains for individuals with insomnia., Methods: Baseline psychometric data from a randomised controlled trial were analysed (N = 1711). A regularized partial correlation network was estimated from the symptom data. Centrality (symptom connectivity), community structure (symptom clustering), and bridging (inter-community connectivity) were assessed. The replicability of the network model was assessed via confirmatory analyses in a holdout sample. Separately, Shapley values were estimated to determine the relative importance of each symptom in predicting functioning (i.e., psychological wellbeing, psychosocial functioning, and physical health impairment)., Results: The most connected nodes were uncontrollable worrying; trouble relaxing; and depressed mood/hopelessness. Five communities were identified with trouble relaxing identified as the bridge symptom between communities. The model showed good fit in the holdout sample. Low energy and depressive affect symptoms (feelings of failure/guilt; depressed mood/hopelessness; anhedonia) were key predictors in the relative importance analysis across multiple domains of impairment., Conclusion: Trouble relaxing may be of clinical and transdiagnostic significance in the context of insomnia. In terms of how symptoms relate to functioning, it was clear that, while low energy and feelings of failure/guilt were prominent predictors, a range of symptoms are associated with functional impairment. Consideration of both symptoms and functional impairment across domains may be useful in determining targets for treatment., Clinical Trial Registration: This is a secondary analysis of an original clinical trial., Trial Registration Number: ISRCTN60530898. Registry URL: https://www.isrctn.com/ISRCTN60530898., Competing Interests: Declaration of competing interest Financial disclosures: CBM is employed by Big Health Inc. and is salaried by the company. CAE is the Co-Founder and Chief Scientist of Big Health Inc. and is a shareholder. ALH is employed by Big Health Inc., is salaried by the company and is a shareholder. Non-financial disclosures: none., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The study aimed to assess the measurement properties of a simplified Chinese version of the Sleep Condition Indicator (SCI-SC) in the community., Methods: A psychometric evaluation through an observational cross-sectional survey design was conducted. Community residents (N = 751) in Hangzhou, China completed the SCI-SC and the simplified Chinese version of the Sleep Quality Questionnaire (SQQ) in July 2021. Data were randomly split into a development sample (N = 375) for model development by exploratory factor analysis (EFA) and a holdout sample (N = 376) for validation by confirmatory factor analysis (CFA). Multi-group CFA (MGCFA) was used to assess configural, metric, scalar, and strict measurement invariance across gender, age, marital status, body mass index (BMI), napping habits, generic exercise, hobby, and administered survey. Moreover, statistical analyses were performed to determine the reliability (alpha and omega) and construct validity of the instrument., Results: Both factor analyses showed a stable solution with two dimensions of Sleep Pattern and Sleep-Related Impact. Good structural validity, robust internal consistency, and construct validity with the SQQ were demonstrated. There was evidence of strict invariance across gender, BMI, napping habits, generic exercise, hobby, and administered survey subgroups, but only metric and scalar invariances were established across age and marital status groups, respectively., Conclusions: The SCI-SC demonstrated promising psychometric properties, with high SQQ concordance and consistent structure of the original version. The SCI-SC can be used by sleep researchers as well as healthcare professionals in various contexts in detecting risks for insomnia disorder in the community.

While evidence shows that dental erosion (DE) is often caused by gastroesophageal reflux disease (GERD), the relationship of DE severity to a patient's symptoms and receipt of appropriate medical treatment for GERD is not clearly understood. The purpose of this study was to evaluate the association between DE and GERD. Eighty participants underwent a Basic Erosive Wear Examination for DE and completed the Patient-Reported Outcomes Measurement Information System (PROMIS) survey on symptoms of gastrointestinal reflux (PROMIS Scale v1.0, Gastrointestinal Gastroesophageal Reflux 13a) in English. Patients with observed erosive patterns were referred for gastroenterologic evaluation. The association between DE and GERD was assessed using multiple regression. The results showed that the extent of DE was positively associated with GERD symptoms (B = 0.585; 95% CI, 0.21-0.96), as measured by the PROMIS survey, in participants without a current diagnosis of GERD. Of the 80 patients in the study, 28 with more severe DE were evaluated in the gastroenterology department. A diagnosis of GERD was established for 27 of the 28, 9 of whom denied a past history of the disease. Twenty patients with GERD underwent upper endoscopy, and esophageal lesions were found in 6 patients (erosive esophagitis in 5 and Barrett esophagus in 1). Patients with clinically identified DE may benefit from medical evaluation and, if necessary, management of GERD. For a subset of patients, DE may be the only clinical indication of untreated or undertreated GERD, which could lead to serious esophageal changes. Dentists should consider referring patients with DE to primary care providers or gastrointestinal specialists to ensure that systemic conditions are identified and managed appropriately., Competing Interests: The views expressed are those of the authors and do not reflect the official views or policy of the Uniformed Services University, US Department of Defense, or its components. The authors do not have any financial interest in any companies discussed in this manuscript.

Background: Convalescent plasma obtained from individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains neutralizing antibodies to the virus and has been frequently used as a treatment in hospitalized patients with severe COVID-19., Methods: We conducted a retrospective, observational cohort study involving 96 hospitalized patients with severe COVID-19 who were allocated in a 1 : 1 ratio to having received either high antibody concentration convalescent plasma or low antibody concentration convalescent plasma. Quantitative measurements of IgG to the receptor-binding domain (RBD), the S1 subunit of the spike protein, and the SARS-CoV-2 nucleocapsid (N) protein were determined from donor plasma samples. The primary outcome was all-cause mortality within 30 days following convalescent plasma administration in regard to each of the three antibody domains., Results: Within the nucleocapsid antibody domain, death occurred in 22.2% of patients in the low antibody concentration group versus 23.5% in the high antibody concentration group ( p =0.88). Within the RBD antibody domain, death occurred in 22.9% of patients in both the low and the high antibody concentration groups ( p =1.0). Within the S1 subunit antibody domain, death occurred in 27.1% of patients in the low antibody concentration group versus 18.8% in the high antibody concentration group ( p =0.33)., Conclusions: No significant differences were observed between low and high concentration convalescent plasma in regard to overall mortality at 30 days, hospital length of stay, number of ventilator days, and subsequent receipt of invasive mechanical ventilation in patients who were previously not receiving mechanical ventilation. Trial Registration . This study was not associated with a clinical trial due to the retrospective nature of study design., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wesley V Cain et al.)

Antemortem diagnosis of neuroborreliosis in horses has been hindered by both the low sensitivity of PCR testing for Borrelia burgdorferi in CSF and the low specificity of serum:CSF ELISA ratios used to determine intrathecal antibody production against the bacterium. PCR testing of the CSF of an adult horse with acute neurologic disease for the B. burgdorferi flagellin gene was negative. However, we enriched B. burgdorferi DNA through nucleic acid hybrid capture, followed by next-generation sequencing, and identified B. burgdorferi in the CSF of the horse, confirming a diagnosis of neuroborreliosis.

Background: Sleepio is an automated digital program that delivers digital cognitive behavioural therapy for insomnia (dCBT-I). Sleepio has been proven effective in improving sleep difficulties; however, evidence for the possible impact of Sleepio use on healthcare costs in the UK has not, to the authors' knowledge, previously been developed., Aim: To identify the effect of a population-wide rollout of Sleepio in terms of primary care costs in the NHS in England., Design & Setting: The study was conducted in the Thames Valley region of England, where access to Sleepio was made freely available to all residents between October 2018 and January 2020. The study relies on a quasi-experimental design, using an interrupted time series (ITS) to compare the trend in primary care costs before and after the rollout of Sleepio ., Method: Primary care data for people with relevant characteristics from nine general practices in Buckinghamshire was used. Primary care costs include general practice contacts and prescriptions. Segmented regression analysis was used to estimate primary and secondary outcomes., Results: For the 10 705 patients included in the sample, the total saving over the 65-week follow-up period was £71 027. This corresponds to £6.64 per person in the sample or around £70.44 per Sleepio user. Secondary analyses suggest that savings may be driven primarily by reductions in prescribing., Conclusion: Sleepio rollout reduced primary care costs. National adoption of Sleepio may reduce primary care costs by £20 million in the first year. The expected impact on primary care costs in any particular setting will depend on the uptake of Sleepio ., (Copyright © 2022, The Authors.)

Background: Digital cognitive behavioral therapy for insomnia (CBT-i) in people with low back pain (LBP) may be efficacious in improving both sleep and pain; and twin trial designs provide greater precision of treatment effects by accounting for genetic and early environmental factors. We aimed to determine the feasibility of a trial investigating the efficacy of a digital CBT-i program in people with comorbid symptoms of insomnia and LBP, in twins and people from the general community (singletons)., Methods: Thirty-two twins (16 pairs) and 66 singletons with comorbid symptoms of insomnia and LBP (> 6 weeks duration) were randomized to digital CBT-i (intervention) or educational program (control) for 6 weeks. The digital CBT-I, Sleepio (developed by Big Health Inc.), was an online interactive, automated, personalized course comprising of six sessions, once a week. The education program was six emails with general sleep information, once a week. Participants were blinded to their group allocation and offered the alternative intervention at the completion of the study. Feasibility outcomes included recruitment and follow-up rates, data collection and outcome measure completion, contamination (communication about trial interventions), acceptability (adherence), credibility, and participants' experience of the intervention., Results: Sixteen out of 722 contacted twin pairs were recruited (recruitment rate = 2.2%). Twins were recruited between September 2015 and August 2018 (35 months) and singletons between October 2017 and Aug 2018 (10 months). Follow-up rates for post-intervention and 3-month follow-up were 81% and 72% for twins and 82% and 78% for singletons respectively. Adherence rates (percentage of sessions completed out of six) for the digital CBT-i were 63% for twins and 55% for singletons. Contamination (speaking about the study to each other) was present in two twin pairs (13%). Written or verbal feedback (n = 21) regarding the digital CBT-i intervention from participants were positive (n = 11), neutral (n = 5), or negative (n = 6)., Conclusions: Online CBT-i was received favorably with people with comorbid symptoms of insomnia and LBP. While the online data collection was successful, strategies need to be implemented to improve adherence, follow-up, control group credibility (for digital CBT-i), and twin recruitment rates (for twin trials)., Trial Registration: Australian New Zealand Clinical Trials Registry ( ACTRN12615000672550 ). Registered 29 June 2015., (© 2022. The Author(s).)

Objectives: Colorectal cancer (CRC) screening uptake in Scotland is 56%. This study examined whether psychological factors were associated with CRC screening uptake., Design: Cross-sectional observational study., Setting: This study used data from the Healthy AGeing In Scotland (HAGIS) pilot study, a study designed to be representative of Scottish adults aged 50 years and older., Participants: 908 (505 female) Scottish adults aged 50-80 years (mean age=65.85, SD=8.23), who took part in the HAGIS study (2016-2017)., Primary and Secondary Outcome Measures: Self-reported participation in CRC screening was the outcome measure. Logistic regression was used to test whether scores on measures of health literacy, cognitive ability, risk aversion, time preference (eg, present oriented or future oriented) and personality were associated with CRC screening when these psychological factors were entered individually and simultaneously in the same model., Results: Controlling for age, age-squared, sex, living arrangement, and sex*living arrangement, a one-point increase in risk aversion (OR=0.66, 95% CI 0.51 to 0.85) and present orientation (OR=0.86, 95% CI 0.80 to 0.94) was associated with reduced odds of screening. Higher scores on health literacy (OR per one-point increase=1.20, 95% CI 1.09 to 1.31), cognitive ability (OR per SD increase=1.51, 95% CI 1.25 to 1.81) and the intellect personality trait (OR per one-point increase=1.05, 95% CI 1.01 to 1.09) were associated with increased odds of screening. Higher risk aversion was the only psychological variable that was associated with CRC screening participation when all psychological variables were entered in the same model and remained associated with CRC screening when additionally adjusting for deprivation and education. A backward elimination model retained two psychological variables as correlates of CRC screening: risk aversion and cognitive ability., Conclusion: Individuals who are more risk averse are less likely to participate in free, home CRC screening., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Arsenic (As) is commonly sequestered at the sediment-water interface (SWI) in mining-impacted lakes through adsorption and/or co-precipitation with authigenic iron (Fe)-(oxy)hydroxides or sulfides. The results of this study demonstrate that the accumulation of organic matter (OM) in near-surface sediments also influences the mobility and fate of As in sub-Arctic lakes. Sediment gravity cores, sediment grab samples, and porewaters were collected from three lakes downstream of the former Tundra gold mine, Northwest Territories, Canada. Analysis of sediment using combined micro-X-ray fluorescence/diffraction, K-edge X-ray Absorption Near-Edge Structure (XANES), and organic petrography shows that As is associated with both aquatic (benthic and planktonic alginate) and terrestrially derived OM (e.g., cutinite, funginite). Most As is hosted by fine-grained Fe-(oxy)hydroxides or sulfide minerals (e.g., goethite, orpiment, lepidocrocite, and mackinawite); however, grain-scale synchrotron-based analysis shows that As is also associated with amorphous OM. Mixed As oxidation states in porewater (median = 62% As (V), 18% As (III); n  = 20) and sediment (median = 80% As (-I) and (III), 20% As (V); n  = 9) indicate the presence of variable redox conditions in the near-surface sediment and suggest that post-depositional remobilization of As has occurred. Detailed characterization of As-bearing OM at and below the SWI suggests that OM plays an important role in stabilizing redox-sensitive authigenic minerals and associated As. Based on these findings, it is expected that increased concentrations of labile OM will drive post-depositional surface enrichment of As in mining-impacted lakes and may increase or decrease As flux from sediments to overlying surface waters., Supplementary Information: The online version contains supplementary material available at 10.1007/s12665-022-10213-2., Competing Interests: Conflict of interestThe 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., (© The Author(s) 2022.)

Insomnia disorder with objective short sleep duration (less than 6 h of objective sleep or sleep efficiency less than 85%) has been considered as a biologically severe subtype of insomnia associated with a higher risk of cardiometabolic disease morbidity. This systematic review and meta-analysis firstly compared insomnia disorder with objective short and normal sleep duration, and subsequently, objective short sleep duration with and without insomnia disorder, and their associations with hypertension, type 2 diabetes and body mass index. A systematic search of five databases yielded 2345 non-duplicated articles, of which 11 individual studies were used for the qualitative review and 10 individual studies for the meta-analysis. The sample size varied from 30 to 4994 participants. A higher risk of hypertension (RR 1.54, 95% CI: [1.30; 1.82] p < 0.0001) and type 2 diabetes (RR 1.63 [1.37; 1.94], p < 0.0001) was associated with insomnia disorder with objective short sleep compared to normal sleep duration, but not for body mass index. Comparisons between insomnia disorder with objective short sleep and objective short sleep without insomnia disorder showed no significant differences. However, the majority of these studies were cross-sectional, and there is a need for more cohort study data., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Insomnia has a bidirectional relationship with broader mental health functioning, including anxiety and depression. Yet, poor sleep has historically been neglected as a specific treatment target in mental health programmes (Freeman, Sheaves, Waite, Harvey, & Harrison, 2020)., Method: All patients over a 12-month period entering the Improving Access to Psychological Therapies (IAPT) service endorsing a 'poor sleep' questionnaire item at assessment, were offered a self-guided digital sleep intervention, Sleepio, in addition to routine care. Sleepio is based on the principles of Cognitive Behavioural Therapy for Insomnia (CBT-I). Propensity score matching established a non-Sleepio control group matched on demographic and baseline clinical measures., Results: Patients who signed up to Sleepio (n = 510) achieved significantly better outcomes on core clinical metrics (PHQ-9, GAD-7, WSAS) than controls. IAPT recovery rates 1 (on PHQ-9 and GAD-7) were 64.7%, versus 58% in the control group. Duration of clinical contact time was marginally elevated overall in the Sleepio group but by less than 1 h CONCLUSIONS: Significant clinical benefit was associated with the introduction of an evidence-based digital sleep intervention alongside other mental health interventions for depression and anxiety. Widespread deployment was achieved with immediate availability, minimal additional clinical time or staff training. This approach provides a feasible and highly scalable model for improving mental health outcomes in clinical services., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Consumption of a diet with high adherence to a Mediterranean diet pattern (MDP) has been associated with a favorable gastrointestinal tract (GIT) microbiome. A healthy GIT microbiome in pregnancy, as defined by increased alpha diversity, is associated with lower chance of adverse perinatal outcomes. This study aimed to evaluate the impact of adherence to an MDP on GIT microbial diversity longitudinally throughout pregnancy., Methods: Adherence to MDP was scored by the Alternate Mediterranean (aMED) Diet Quality Score, after being applied to a validated Food Frequency Questionnaire. Association of aMED Scores with GIT alpha diversity profiles were compared linearly and across time using a linear mixed model, including covariates of age, body mass index (BMI), ethnicity, and parity., Results: Forty-one participants of Filipino, Japanese, Native Hawaiian, and Non-Hispanic White descent provided dietary information and microbiome samples during each trimester of pregnancy. Alpha diversity profiles changed over gestation, with decreased microbial diversity in the third trimester. aMED scores positively correlated with Chao1 Index and Observed Species Number (r = 0.244, p = 0.017, and r = 0.233, p = 0.023, respectively). The strongest association was detected in the third trimester (Chao 1: r = 0.43, p = 0.020, Observed Species Number: r = 0.41, p = 0.026). Participants with higher aMED scores had higher relative abundance of Acidaminoacaeae at the family level (p = 0.0169), as well as higher abundance of several species known to increase production of short chain fatty acids within the GIT., Conclusions: Adherence to MDP pattern is associated with increased maternal GIT microbial diversity, and promotes the abundance of bacteria that produce short chain fatty acids. Increased consumption of fruits, vegetables and legumes with low red meat consumption were key components driving this association. The effect of nutrition however, was less of an effect than pregnancy itself. Further studies are needed to determine if adherence to a Mediterranean diet translates not only into microbial health, but also into reduced risk of adverse pregnancy outcomes., (© 2021. The Author(s).)

Sleep restriction therapy (SRT) is an established treatment for insomnia that has been used in clinical practise for over 30 y. It is commonly delivered as part of multicomponent cognitive-behavioural therapy (CBT-I) but has also been linked to beneficial effects as a standalone intervention. In order to quantify the efficacy of SRT we performed a comprehensive meta-analysis of randomised controlled trials (RCTs) comparing SRT to minimally active or non-active control groups. Primary outcomes were self-reported insomnia severity and sleep diary metrics at post-treatment. Weighted effect sizes were calculated with Hedges' g and risk of bias was assessed by two independent raters with the Cochrane tool. Our search yielded eight RCTs meeting inclusion/exclusion criteria. Random effects models revealed large treatment effects in favour of SRT versus control for insomnia severity measured with the insomnia severity index (g = -0.93; 95% CI = -1.15, -0.71), sleep efficiency (g = 0.91; 95% CI = 0.52, 1.31), sleep onset latency (g = -0.62; 95% CI = -0.84, -0.40), and wake-time after sleep onset (g = -0.83; 95% CI = -1.11, -0.55). No effects were found for total sleep time (g = 0.02; 95% CI = -0.29, 0.34). Results should be interpreted in the context of the small number of comparisons (≤6 per outcome), high risk of bias (6 out of 8 studies met criteria for high risk), and heterogeneity in study design and SRT administration. Only a small number of studies provided outcomes at follow-up (n ≤ 3), hindering assessment of long-term effects. Sleep restriction therapy effectively improves insomnia severity and sleep continuity in the short term; more studies are needed to assess if effects are sustained at long-term follow-up (>3 m). Post-treatment effect sizes appear as large as multicomponent CBT-I. To reduce risk of bias, future studies should consider testing the effects of SRT against control groups that are matched for non-specific treatment effects. Large-scale pragmatic trials are also needed to test if SRT is effective in clinical practise and to quantify effects on daytime functioning and quality of life., (Copyright © 2021 Elsevier Ltd. All rights reserved.)