Flexible Ag2Se Thermoelectric Films Enable the Multifunctional Thermal Perception in Electronic Skins.

Skin is critical for shaping our interactions with the environment. The electronic skin (E-skin) has emerged as a promising interface for medical devices to replicate the functions of damaged skin. However, exploration of thermal perception, which is crucial for physiological sensing, has been limited. In this work, a multifunctional E-skin based on flexible thermoelectric Ag2Se films is proposed, which utilizes the Seebeck effect to replicate the sensory functions of natural skin. The E-skin can enable capabilities including temperature perception, tactile perception, contactless perception, and material recognition by analyzing the thermal conduction behaviors of various materials. To further validate the capabilities of constructed E-skins, a wearable device with multiple sensory channels was fabricated and tested for gesture recognition. This work highlights the potential for using flexible thermoelectric materials in advanced biomedical applications including health monitoring and smart prosthetics.

Mn4+/Eu3+ co-doped fluoride toward a blue light-excited optical fiber thermometer.

The ongoing development of ratiometric optical thermometry is mainly trapped in thermally coupled levels of rare-earth ions and inefficient ultraviolet excitation. Herein, a new-type multiple sharp line emitting, blue light-excited K2NaInF6:Mn4+, Eu3+ fluoride phosphor has been reported as a ratiometric thermometer. The f-f transition of Eu3+ paves a steady reference to a highly temperature sensitive Mn4+d-d transition and enables high relative sensitivity of 1.65% K-1 at 573 K. An optical fiber thermometry on a household oven with a relative standard deviation of 0.11% surpasses the standard of precision measurement, showing great potential in practical application. This discovery offers a highly sensitive neotype blue light-excitable ratiometric temperature sensor, that is Mn4+-doped fluoride, promoting practical applications of optical thermometry.

Millimeter-Sized K2MnF6:Si4+, NH4+ Red-Luminescent Crystals with High Absorption Efficiency (AEmax of 93.5%) and External Quantum Efficiency (EQEmax of 68.9%) Grown by Cooling-Induced Crystallization.

Luminescent bulk crystals exhibit fewer grain boundaries and defects compared with conventional microsized powdery ones. Herein, targeting Mn4+-activated fluoride crystals with a sharp line-type red luminescence spectrum, we propose a new cooling-induced crystallization method to grow the fluoride crystals. By this new method, we successfully grew millimeter-sized K2MnF6:Si4+, NH4+ crystals, featuring an AEmax (absorption efficiency) of 93.5% and an EQEmax (external quantum efficiency) of 68.9%, which are among the best values for Mn4+-activated fluoride red phosphors. The influence of doping Si4+ and/or NH4+ in K2MnF6 on the local coordination structure and luminescence properties was studied. The anomalous thermal quenching behaviors were discussed, the luminescence decay from the excited state was compared, and the origin for the high quantum efficiencies was analyzed.

Dynamic Trends and Underlying Factors of COVID-19 Vaccine Booster Hesitancy in Adults: Cross-Sectional Observational Study.

BACKGROUND: COVID-19 vaccine hesitancy reduces vaccination rates, which is detrimental to building herd immunity and halting the spread of COVID-19 and its variations. Most researches have simply identified the reasons affecting COVID-19 vaccination reluctance without delving into its dynamics, which makes forecasting future trends difficult. OBJECTIVE: This study aimed to examine the current COVID-19 vaccine booster hesitancy rate in Chinese adults as well as the dynamics of vaccine hesitancy and its influencing factors. The results of this study will have practical implications for policy responses in mainland China, and effective COVID-19 booster vaccination in specific populations. METHODS: The web-based survey was completed by creating questionnaires and using a stratified random sampling method to collect information from adults (≥18 years old) among 2556 households in 4 geographical regions of China. We collected sociodemographic information, health status, awareness of COVID-19 and its vaccine, self-perceptions, trust in medical staff and vaccine developers, and so on. The odds ratios and 95% CI for the statistical associations were estimated using logistic regression models. RESULTS: Overall, 6659 participants (females: n=3540, 53.2%; males: n=3119, 46.8%) responded. In total, 533 (8%; 95% CI 7.4%-8.7%) participants presented a clear hesitancy in receiving the COVID-19 booster vaccination, while 736 (11.1%; 95% CI 10.3%-11.8%) expressed hesitancy in regular booster vaccination. A higher prevalence of vaccine hesitancy in both booster vaccination and regular booster vaccination was observed among participants with a history of allergies, experiencing chronic disease, lower levels of public health prevention measures or susceptibility or benefits or self-efficiency, higher levels of severity or barriers, and lower trust in both medical staff and vaccine developers (P<.05). The females and participants with higher education levels, higher levels of barriers, lower levels of susceptibility, and lower trust in vaccine developers preferred to have attitudinal changes from acceptance to hesitancy, while people with higher education levels, lower self-report health conditions, experiencing chronic disease, history of allergies, and lower trust in medical staff and developers were all positively associated with constant COVID-19 booster hesitancy. CONCLUSIONS: The prevalence of COVID-19 vaccine booster hesitancy is not high in mainland China. However, there is a slight increment in hesitancy on regular booster vaccination. Conducting targeted information guidance for people with higher education levels and chronic diseases, as well as improving accessibility to booster vaccination and increasing trust in medical staff and vaccine producers may be highly effective in reducing vaccine hesitancy.

NiFe-LDH-Decorated Ti-Doped Hematite Photoanode for Enhancing Solar Water-Splitting Efficiency.

Ti-doped α-Fe2O3 nanorods were prepared by a facile hydrothermal method, followed by a NiFe-LDH catalyst that was electrodeposited on the doped α-Fe2O3 nanorods to structure an integrating photoanode Ti:Fe2O3/NiFe-LDH for improving solar PEC water-splitting efficiency. The structure and properties of electrode materials were characterized and the PEC properties of photoanodes were measured. The results show that the photocurrent density of the photoanode enhances 11.25 times at 1.23 V (vs RHE) and the IPCE value enhances 4.10 times at 420 nm compared with pristine α-Fe2O3. The enhancement is attributed to the separating of photogenerated electron-hole, the increase of carrier density, and the acceleration of the carrier transfer rate due to the dual action of doping and catalysis.

Stable Polyhedron-Cluster-Based Rigid Fluoride Framework toward Zero-Thermal-Quenching Near-Infrared Emission for Prolonged LED Applications.

Development of highly thermally stable broadband near-infrared (NIR) luminescence materials is crucial for advancing the prolonged stable application of smart NIR light sources. In this study, a zero-thermal-quenching and reversible temperature-dependent broadband NIR-emitting Cs2NaAl3F12:Cr3+ phosphor is demonstrated, benefiting from its stable polyhedron-cluster-building rigid structure. The excellent thermal stability of Cs2NaAl3F12:Cr3+ is rooted in its stable [Al6Na4F45] cluster building unit, which provides a rigid structure with a weak electron-phonon coupling effect and a wide band gap with a huge thermal activated barrier. Such characteristics are well revealed by multiple studies on crystal structure, electronic structure, Huang-Rhys factor S, configuration coordinate model, and Debye temperature. The incorporation of Li or K instead of Na weakens the luminescence thermal stability, directly proving the importance of the stable [Al6Na4F45] cluster for stable Cr3+ substitution and rigid structure construction. Furthermore, Cs2NaAl3F12:Cr3+ presents much superior thermal stability compared to traditional rigid garnet-type fluorides Na3X2Li3F12:Cr3+ (X = Al, Ga, In). A high-power NIR LED is presented, utilizing the high quantum efficiency (∼71%) and extremely thermally stable broadband NIR emission around 750 nm of Cs2NaAl3F12:Cr3+. It realizes clear vein and cartilage imaging in the human hand, demonstrating its potential in medical diagnosis applications. This result provides important insights for designing new-type rigid crystal structures using stable polyhedron clusters as basic units, advancing the development of highly thermally stable NIR-emitting phosphors.

NiFePB-modified ZnO/BiVO4 photoanode for PEC water oxidation.

Photoelectrochemical (PEC) water splitting has been recognized as the most promising approach for directly converting solar energy into chemical energy, and substantial efforts have been made to develop a highly efficient and low-cost photoanode for enhancement of PEC water splitting efficiency due to sluggish water oxidation reaction kinetics. A ternary NiFePB-modified ZnO/BiVO4 heterojunction photoanode was simply assembled by low-temperature hydrothermal, metal-organic decomposition and electrodeposition methods to improve the water splitting efficiency; its photocurrent density for water oxidation reached 1.66 mA cm-2 at 1.23 V (vs. RHE); in comparison, that of ZnO is only 0.4 mA cm-2. The onset potential manifests a cathodic shift of ∼283 mV compared to ZnO. The IPCE and the ABPE respectively are 3.1 and 6.4 times those of ZnO, respectively. This improvement is ascribed to the efficient separation of photogenerated electrons and holes by the formation of a heterojunction between ZnO and BiVO4 and the enhancement in the oxygen evolution reaction kinetics by the decoration of the co-catalyst NiFePB as a hole acceptor.

Epigenetic regulation of dental-derived stem cells and their application in pulp and periodontal regeneration.

Dental-derived stem cells have excellent proliferation ability and multi-directional differentiation potential, making them an important research target in tissue engineering. An increasing number of dental-derived stem cells have been discovered recently, including dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHEDs), stem cells from apical papilla (SCAPs), dental follicle precursor cells (DFPCs), and periodontal ligament stem cells (PDLSCs). These stem cells have significant application prospects in tissue regeneration because they are found in an abundance of sources, and they have good biocompatibility and are highly effective. The biological functions of dental-derived stem cells are regulated in many ways. Epigenetic regulation means changing the expression level and function of a gene without changing its sequence. Epigenetic regulation is involved in many biological processes, such as embryonic development, bone homeostasis, and the fate of stem cells. Existing studies have shown that dental-derived stem cells are also regulated by epigenetic modifications. Pulp and periodontal regeneration refers to the practice of replacing damaged pulp and periodontal tissue and restoring the tissue structure and function under normal physiological conditions. This treatment has better therapeutic effects than traditional treatments. This article reviews the recent research on the mechanism of epigenetic regulation of dental-derived stem cells, and the core issues surrounding the practical application and future use of pulp and periodontal regeneration.

Seeing through the hedge: Phylogenomics of Thuja (Cupressaceae) reveals prominent incomplete lineage sorting and ancient introgression for Tertiary relict flora.

The Eastern Asia (EA) - North America (NA) disjunction is a well-known biogeographic pattern of the Tertiary relict flora; however, few studies have investigated the evolutionary history of this disjunction using a phylogenomic approach. Here, we used 2369 single copy nuclear genes and nearly full plastomes to reconstruct the evolutionary history of the small Tertiary relict genus Thuja, which consists of five disjunctly distributed species. The nuclear species tree strongly supported an EA clade Thuja standishii-Thuja sutchuenensis and a "disjunct clade", where western NA species T. plicata is sister to an EA-eastern NA disjunct Thuja occidentalis-Thuja koraiensis group. Our results suggested that the observed topological discordance among the gene trees as well as the cytonuclear discordance is mainly due to incomplete lineage sorting, probably facilitated by the fast diversification of Thuja around the Early Miocene and the large effective population sizes of ancestral lineages. Furthermore, approximately 20% of the T. sutchuenensis nuclear genome is derived from an unknown ancestral lineage of Thuja, which might explain the close resemblance of its cone morphology to that of an ancient fossil species. Overall, our study demonstrates that single genes may not resolve interspecific relationships for disjunct taxa, and that more reliable results will come from hundreds or thousands of loci, revealing a more complex evolutionary history. This will steadily improve our understanding of their origin and evolution.

Botulinum Toxin Type A for Upper Limb Spasticity in Poststroke Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND AIM: Botulinum toxin type A is considered to be an effective antispasmodic in recent years. We assess the effectiveness of botulinum toxin type A for the treatment of poststroke spasticity in the upper extremity using a meta-analysis. METHODS: We searched several databases including PubMed, Web of Science, Embase, and Cochrane database for relevant studies, up until October 2017. All randomized controlled trials of botulinum toxin type A treat poststroke upper limb spasticity published were included. The primary outcome measure was modified ashworth score at the elbow, finger and wrist, pain score, and barthel index. RESULTS: Ten randomized controlled trials were identified and reported sufficient data for inclusion in the pooled analysis (n = 950). The results of modified ashworth score at different joints, pain score, barthel index showed no difference was found in the effectiveness of botulinum toxin type A compared with placebo in the treatment of the upper limb spasticity after stroke. But modified ashworth score at the elbow was improver in Dysport subgroups (standardized mean difference [SMD] = -.39, 95%CI = -.67 to -.10, P = .008) compared with Botox subgroups (SMD = .08, 95%CI = -.68 to .83, P = .84). CONCLUSIONS: The meta-analysis of these studies showed that the overall effectiveness of botulinum toxin type A does not seem to differ from placebo for poststroke Patients. But the meta-analysis yielded a favorable effect of Dysport compared with placebo based on 4 trials.

SIRT1: The Value of Functional Outcome, Stroke-Related Dementia, Anxiety, and Depression in Patients with Acute Ischemic Stroke.

BACKGROUND: The outcome of ischemic stroke depends on multiple factors and their function of each other. Studies have shown that Sirtuin1 (SIRT1) plays a chief role in the key procedure during ischemia/hypoxia by protecting against cellular stress and controlling the metabolic pathways. AIMS: To explore the alterations in serum SIRT1 concentrations in acute ischemic stroke (AIS) patients and the relationship between SIRT1 and poststroke dementia, anxiety, and depression. METHODS: One hundred and twenty four consecutive patients with clinically diagnosed AIS were recruited to participate in the study. Serum SIRT1 levels were measured using a commercially available ELISA equipment for SIRT1 (Cusabio, Wuhan, China). In 1 year after admission, the severity of stroke was assessed with the National Institutes of Health Stroke Scale score, and the functional outcome was measured by a modified Rankin scale, the Hamilton Anxiety Scale scores were evaluated to define patients with or without anxiety, and the Hamilton Depression Scale scores for depression. RESULTS: We found the levels of serum SIRT1 was significantly higher (P = .036) in AIS patients (.62 ± .77 ng/mL) compared with healthy control subjects (.45 ± .69 ng/mL), but not significantly higher SIRT1 concentration (.58 ± .69 versus .64 ± .81 ng/mL, P = .298) than patients in the unfavorable functional outcome group. CONCLUSIONS: There is no potential diagnostic and prognostic role of SIRT1 in AIS-related dementia, anxiety, and depression. The role of SIRT1 in AIS among human race needs to be further investigated.

Increased Serum Alkaline Phosphatase in Patients with Acute Ischemic Stroke.

BACKGROUND: Stroke is one of the most common causes of disability and death. Higher alkaline phosphatase (ALP) levels have been associated with poor functional outcomes and mortality in previous studies. We investigated alterations in serum ALP concentrations and functional outcomes in patients with acute ischemic stroke (AIS). METHODS: Patients with first-ever AIS were recruited to participate in the study. Serum ALP levels were measured using a Cobas Integra 400 Plus automatic biochemical analyzer, and severity of stroke was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score on admission. Functional outcome was measured using the modified Rankin scale 1 year after admission. RESULTS: Serum ALP concentration was increased in patients with AIS (81.75 ± 20.49 versus 69.93 ± 16.12 U/L, P = .000) and the optimal ALP cutoff point for diagnosing patients with AIS was 81.50 U/L, with a sensitivity of 49.5% and specificity of 78.9%. However, there was no significant correlation between ALP and NIHSS scores (r = .170, P = .085) and ALP was not significantly different between favorable and unfavorable functional outcomes (81.76 ± .60 versus 81.70 ± 20.54 U/L, P = .802). CONCLUSIONS: Serum ALP concentration, which was increased in patients with AIS, might represent a low-potency biomarker for the diagnosis of AIS. However, this was not significantly correlated with NIHSS scores or the functional outcome after 1 year.

Prognostic value of Sirtuin1 in acute ischemic stroke and its correlation with functional outcomes.

BACKGROUND: The blood-brain barrier is impaired in patients with stroke. The release of protein markers such as Sirtuin1 (SIRTl) into circulation may be useful to assess the prognosis of patients with cerebrovascular disease. In this study, we investigated the predictive value of SIRT1 levels in acute ischemic stroke (AIS) patients. METHODS: In all, 101 AIS patients and 38 healthy controls were enrolled, and blood samples were collected within 72 hours of stroke onset. SIRT1 was analyzed using a commercially available enzyme-linked immunosorbent assay kit. On admission, neurological status was assessed by the standardized National Institutes of Health Stroke Scale (NIHSS). Functional outcomes were measured 1 year after admission using the modified Rankin scale. RESULTS: Compared with the control group, SIRT1 was significantly increased in the AIS group (0.63 ±â€Š0.75 vs 0.48 ±â€Š0.80 ng/mL; P ≤ 0.05). However, there was no significant correlation between SIRT1 and NIHSS score at admission (r = -0.01, P = .920). In addition, with an unadjusted odds ratio of 0.862 (95% confidence interval 0.495-1.502), SIRT1 was not significantly correlated with functional outcomes. CONCLUSIONS: Serum concentrations of SIRT1 have no significant predictive value for favorable functional outcome after acute stroke in our study.

A novel cell line generated using the CRISPR/Cas9 technology as universal quality control material for KRAS G12V mutation testing.

BACKGROUND: KRAS mutations are the key indicator for EGFR monoclonal antibody-targeted therapy and acquired drug resistance, and their accurate detection is critical to the clinical decision-making of colorectal cancer. However, no proper quality control material is available for the current detection methods, particularly next-generation sequencing (NGS). The ideal quality control material for NGS needs to provide both the tumor mutation gene and the matched background genomic DNA, which is uncataloged in public databases, to accurately distinguish germline polymorphisms and somatic mutations. METHODS: We developed a novel KRAS G12V mutant cell line using the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technique to make up for the deficiencies in existing quality control material and further validated the feasibility of the cell line as quality control material by amplification refractory mutation system (ARMS), Sanger sequencing, digital PCR (dPCR), and NGS. RESULTS: We verified that the edited cell line specifically had the G12V mutation, and the validation results presented a high consistency among the four methods of detection. The three cell lines screened contained the G12V mutation and the mutation allele fractions of G12V-1, G12V-2, and G12V-3 were 52.01%, 82.06%, and 17.29%, respectively. CONCLUSION: The novel KRAS G12V cell line generated using the CRISPR/Cas9 gene editing system is suitable as a quality control material for all current detection methods and provides a new direction in the development of quality control material.

Complementary and alternative therapies for restless legs syndrome: An evidence-based systematic review.

Restless legs syndrome (RLS) is defined as an irresistible urge to move the legs, which is usually accompanied by paresthesias or dysesthesias at least twice weekly, and affects 2%-4% of adults in Europe and North America. This systematic review assesses the current complementary and alternative options for RLS and the potential benefits of those treatments on sleep quality, mood disorder, and quality of life. A systematic search of the PubMed, Embase, Cochrane, and Web of Science databases was conducted. Eighteen studies met the inclusion criterion, which included the use of the international RLS study group criteria. Complementary and alternative therapies have been found to be effective in both primary and secondary RLS. The severity of primary RLS symptoms can be significantly ameliorated by exercise training, transcutaneous spinal direct current stimulation, pneumatic compression devices, light therapy, repetitive transcranial magnetic stimulation, and acupuncture. Pneumatic compression devices and yoga also improve RLS-related disorders. Exercise training is highly efficacious in the reduction of symptom severity in uremic RLS and related effects such as poor quality of life. Endovenous laser ablation may be a good choice for patients with concurrent RLS and superficial venous insufficiency.

Decreased serum proNGF concentration in patients with Parkinson's disease.

Parkinson's disease (PD), a progressive and age-related neurodegenerative condition, is a common neurodegenerative disorder. However, no validated biomarkers for PD have been identified to date. Accumulating evidence supports the role of proNGF-p75NTR-sortilin signaling in the neurodegeneration and pathogenesis of PD. The aim of our study was to investigate alterations in serum proNGF concentrations in PD patients and related anxiety. Seventy-seven consecutive PD patients and 39 healthy controls were enrolled, and clinical data were collected. Modified Hoehn-Yahr Staging Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hamilton Anxiety (HAMA) Scale scores were assessed upon admission. Serum proNGF concentration was compared between that of PD patients and healthy controls. Pearson correlation coefficients were determined to explore the relationship between proNGF concentration and UPDRS, Hoehn-Yahr, and HAMA scores. Received operating characteristic (ROC) curves and proNGF optimal cutoff point were used to distinguish PD and related anxiety. The median concentration of proNGF was significantly lower (p = 0.000) in PD patients (94.91 ng/L, range 85.92-118.06 ng/L) compared with that of healthy controls (106.67 ng/L, range 102.39-122.06 ng/L). The optimal proNGF cutoff point for distinguishing PD patients was 102.29 ng/L, and the sensitivity and specificity values were 87.0 and 100%, respectively. proNGF concentration positively correlated with UPDRS (r = 0.281, p = 0.013), Hoehn-Yahr (r = 0.260, p = 0.023), and HAMA (r = 0.276, p = 0.015) scores. Our results indicate that serum proNGF concentration may represent a biomarker for PD and its role in the pathogenesis of PD thus warrants further investigation.

Clinical and biological significance of circulating tumor cells, circulating tumor DNA, and exosomes as biomarkers in colorectal cancer.

Colorectal cancer (CRC) has been the fourth leading cause of cancer-related mortality worldwide. Owing to clonal evolution and selection, CRC treatment needs multimodal therapeutic approaches and due monitoring of tumor progression and therapeutic efficacy. Liquid biopsy, involving the use of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes, may offer a promising noninvasive alternative for diagnosis and for real-time monitoring of tumor evolution and therapeutic response compared to traditional tissue biopsy. Monitoring of the disease processes can enable clinicians to readily adopt a strategy based on optimal therapeutic decision-making. This article provides an overview of the significant advances and the current clinical and biological significance of CTCs, ctDNA, and exosomes in CRC, as well as a comparison of the main merits and demerits of these three components. The hurdles that need to be resolved and potential directions to be followed with respect to liquid biopsies for detection and therapy of CRC are also discussed.

Synthetic Circulating Cell-free DNA as Quality Control Materials for Somatic Mutation Detection in Liquid Biopsy for Cancer.

BACKGROUND: Detection of somatic genomic alterations in tumor-derived cell-free DNA (cfDNA) in the plasma is challenging owing to the low concentrations of cfDNA, variable detection methods, and complex workflows. Moreover, no proper quality control materials are available currently. METHODS: We developed a set of synthetic cfDNA quality control materials (SCQCMs) containing spike-in cfDNA on the basis of micrococcal nuclease digestion carrying somatic mutations as simulated cfDNA and matched genomic DNA as genetic background to emulate paired tumor-normal samples in real clinical tests. Site-directed mutagenesis DNA that contained 1500-2000 bases with single-nucleotide variants or indels and genomic DNA from CRISPR/Cas9 edited cells with EML4-ALK rearrangements was fragmented, quantified, and added into micrococcal nuclease-digested DNA derived from HEK293T cells. To prove their suitability, the SCQCMs were compared with patient-derived plasma samples and validated in a collaborative study that encompassed 11 laboratories. RESULTS: The results of SCQCM analysis by next-generation sequencing showed strong agreement with those of patient-derived plasma samples, including the size profile of cfDNA and the quality control metrics of the sequencing data. More than 95% of laboratories correctly detected the SCQCMs with EGFR T790M, L858R, KRAS G12D, and a deletion in exon 19, as well as with EML4-ALK variant 2. CONCLUSIONS: The SCQCMs were successfully applied in a broad range of settings, methodologies, and informatics techniques. We conclude that SCQCMs can be used as optimal quality controls in test performance assessments for circulating tumor DNA somatic mutation detection.

Treatment of insomnia with tricyclic antidepressants: a meta-analysis of polysomnographic randomized controlled trials.

BACKGROUND: Insomnia represents a significant public health burden worldwide. Antidepressants have often been the insomnia treatment of choice in recent decades. Some tricyclic antidepressants (TCAs) have been shown to improve sleep efficiency. OBJECTIVE: Assess the efficacy and safety of TCAs for the treatment of insomnia using a meta-analysis of randomized control trials (RCTs). METHODS: Relevant studies were identified in electronic databases such as PubMed, Cochrane, Embase, and Web of Science, up until July 2016. We included all polysomnographic (PSG) RCTs using TCAs to treat insomnia. The primary outcome measure was the total sleep time (TST), although other polysomnographic measures were also investigated. Next-day somnolence and dropout rates were also assessed. RESULTS: The meta-analysis included nine RCTs. TCAs significantly improved TST compared with placebo (SMD = 0.61, 95% CI = 0.50-0.71, P < 0.00001). Participants receiving TCAs were not more likely to drop out than those receiving a placebo because of adverse side effects (1.71% vs 1.19%, RR = 1.37, 95% CI = 0.67-2.80, P = 0.39) or any other reason (7.08% vs 8.20%; RR = 0.86, 95% CI = 0.60-1.23, P = 0.42). However, the incidence of somnolence was higher in participants receiving TCAs (6.06% vs. 3.21%; RR = 1.82, 95% CI = 1.10-3.00, P = 0.02). CONCLUSIONS: Based on our limited data analysis with two medications at particular doses (most studies included extremely low doxepin), we assert that TCAs can be an effective pharmacological treatment for insomnia. TCAs were found to improve sleep outcome measures, with the notable exception of an 82% increase in somnolence. Overall TCAs have very problematic and dangerous side effects, while TCAs were not found to increase the dropout rate compared with the placebo.