Case report: Symmetrical and increased lateral sway-based walking training for patients with corpus callosum infarction: a case series.

Introduction: Corpus callosum injury is a rare type of injury that occurs after a stroke and can cause lower limb dysfunction and a decrease in activities of daily living ability. Furthermore, there are no studies that focus on the progress in rehabilitation of the lower limb dysfunction caused by infarction in the corpus callosum and the effective treatment plans for this condition. We aimed to present a report of two patients with lower limb dysfunction caused by corpus callosum infarction after a stroke and a walking training method. Methods: We implemented a walking training method that prioritizes bilateral symmetry and increases lateral swaying before the patients established sitting/standing balance. The plan is a rapid and effective method for improving walking dysfunction caused by corpus callosum infarction. Case characteristics: Following sudden corpus callosum infarction, both patients experienced a significant reduction in lower limb motor function scores and exhibited evident gait disorders. Scale evaluations confirmed that walking training based on symmetrical and increased lateral sway for patients with lower limb motor dysfunction after corpus callosum infarction led to significant symptom improvement. Conclusion: We report two cases of sudden motor dysfunction in patients with corpus callosum infarction. Symmetrical and increased lateral sway-based walking training resulted in substantial symptom improvement, as confirmed by scale assessments.

Escherichia coli LTB26 mutant enhances immune responses to rotavirus antigen VP8 in a mouse model.

Adjuvant is a major supplementary component of vaccines to boost adaptive immune responses. To select an efficient adjuvant from the heat-labile toxin B subunit (LTB) of E. coli, four LTB mutants (numbered LTB26, LTB34, LTB57, and LTB85) were generated by multi-amino acid random replacement. Mice have been intranasally vaccinated with human rotavirus VP8 admixed. Among the four mutants, enzyme-linked immunosorbent assay (ELISA) revealed that LTB26 had enhanced mucosal immune adjuvanticity compared to LTB, showing significantly enhanced immune responses in both serum IgG and mucosal sIgA levels. The 3D modeling analysis suggested that the enhanced immune adjuvanticity of LTB26 might be due to the change of the first LTB α-helix to a ß-sheet. The molecular mechanism was studied using transcriptomic and flow cytometric (FCM) analysis. The transcriptomic data demonstrated that LTB26 enhanced immune response by enhancing B cell receptor (BCR) and major histocompatibility complex (MHC) II+-related pathways. Furthermore, LTB26 promoted Th1 and Th2-type immune responses which were confirmed by detecting IFN-γ and IL-4 expression levels. Immunohistochemical analysis demonstrated that LTB26 enhanced both Th1 and Th2 type immunity. Therefore, LTB26 was a potent mucosal immune adjuvant meeting the requirement for use in human clinics in the future.

Patient-derived organoid elucidates the identical clonal origin of bilateral breast cancer with diverse molecular subtypes.

Bilateral breast cancer (BBC), an infrequent breast cancer subtype, has primarily been studied in terms of incidence, prognosis, and through comparative analysis of synchronous (SBBC) and metachronous (MBBC) manifestations. The advent and application of organoid technology hold profound implications for tumor research and clinical management. This study represents the pioneering use of organoid models in BBC research. We established organoid lines from two surgical tumor specimens of a BBC patient, with one line undergoing detailed pathological and genomic analysis. The BBC organoid from the right breast demonstrated a marker expression profile of ER (-), PR (-), HER-2 (0), and Ki67 index 10%, indicating that it may derived from the TNBC tissue. Whole Exome Sequencing (WES) displayed consistent set of Top10 cancer driver genes affected by missense mutations, frameshift mutation, or splice site mutations in three tumor tissues and the organoid samples. The organoids' single nucleotide polymorphisms (SNPs) were more closely aligned with the TNBC tissue than other tumor tissues. Evolutionary analysis suggested that different tumor regions might evolve from a common ancestral layer. In this case, the development of BBC organoids indicated that simultaneous lesions with diverse molecular profiles shared a high degree of consistency in key tumor-driving mutations. These findings suggest the feasibility of generating BBC organoids representing various molecular types, accurately replicating significant markers and driver mutations of the originating tumor. Consequently, organoids serve as a valuable in vitro model for exploring treatment strategies and elucidating the underlying mechanisms of BBC.

Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China.

INTRODUCTION: Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC). METHODS AND ANALYSIS: The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 µs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073950.

Meningocele in the Parapharyngeal Space: A Case Report and Review of the Literature.

The parapharyngeal space has been described as an inverted pyramid shape with the base of the skull and the great cornu of the hyoid bone at the top. Tumors of the parapharyngeal space account for 0.5% of head and neck tumors and a wide range of tumor types can occur in this area, 80% of which are benign, the most common being pleomorphic adenomas of the salivary glands and neurogenic tumors. We present a 39-year-old woman who was hospitalized due to left-sided neck pain with a feeling of blockage in the left ear and hearing loss for 10 months. Imaging showed that the mass was not connected to the cranium and the patient underwent surgical resection via a transoral approach, where the contents of the mass were found to be cerebrospinal fluid, and meningocele in the parapharyngeal space is a rare occurrence. The patient presented mainly with painful symptoms, which were eventually relieved by nerve block therapy.

Suppressive Role of Pigment Epithelium-derived Factor in a Rat Model of Corneal Allograft Rejection.

BACKGROUND: Immunological rejection is the most common reason for corneal transplantation failure. The importance of T cells in corneal allograft rejection is well demonstrated. Recent studies highlight that pigment epithelium-derived factor (PEDF) plays an immunoregulatory role in ocular diseases by enhancing the suppressive phenotype of regulatory T cells besides its other functions in neurotrophy and antiangiogenesis. METHODS: The effects of PEDF on immune rejection were examined in rat models of corneal transplantation using slit-lamp microscope observation, immunohistochemistry, flow cytometry, and Western blot. In vitro, we demonstrated PEDF reduced alloreactive T-cell activation using real-time polymerase chain reaction, flow cytometry, and Western blot. RESULTS: Topical administration of PEDF provided corneal transplantation rats with an improved graft survival rate of corneal allografts, reduced hemangiogenesis, and infiltration of immune cells in corneas, in particular, type 17 T helper cells while increased regulatory T cells. Moreover, nerve reinnervation within grafts was promoted in PEDF-treated recipient rats. In vitro, PEDF inhibited alloreactive T-cell activation via the c-Jun N-terminal kinase/c-Jun signaling pathway and upregulated the expressions of interleukin-10 and transforming growth factor-ß, emphasizing the suppressive role of PEDF on immune responses. CONCLUSIONS: Our results underscore the feasibility of PEDF in alleviating corneal allograft rejection and further illustrate its potential in managing immune-related diseases.

Associations of evening-type and insomnia symptoms with depressive symptoms among youths.

BACKGROUND: Evening-type and insomnia symptoms are significantly related to each other and independently associated with depressive symptoms, yet few studies have examined the potential interaction between these two conditions. Therefore, we aimed to examine the associations of evening-type and insomnia symptoms with depressive symptoms among Chinese youths, with a specific focus on the joint effects of the two conditions on depressive symptoms. METHODS: Participants aged between 12 and 25 were invited to participate in an online survey from December 15, 2022, to May 26, 2023. Multivariate logistic regression models and additive interaction models were used to examine the independent and joint effects of chronotypes and insomnia symptoms on depressive symptoms, respectively. RESULTS: Of the 6145 eligible youths, the prevalence of evening-type and insomnia symptoms were 24.9 % and 29.6 %, respectively. Both evening-type (adjusted OR, [AdjOR]: 3.21, 95 % CI: 2.80-3.67) and insomnia symptoms (AdjOR: 10.53, 95 % CI: 9.14-12.12) were associated with an increased risk of depressive symptoms. In addition, the additive interaction models showed that there is an enhanced risk of depression related to interaction between evening-type and insomnia symptoms (relative excess risk due to interaction, [RERI]: 11.66, 95 % CI: 7.21-16.11). CONCLUSIONS: The present study provided additional evidence demonstrating the presence of interaction between evening-type and insomnia symptoms, which can lead to a higher risk of depressive symptoms. Our findings argue the need for addressing both sleep and circadian factors in the management of depressive symptoms in young people.

Formation mechanism of persistent free radicals during pyrolysis of Fenton-conditioned sewage sludge: Influence of NOM and iron.

The present study provided an innovative insight into the formation mechanism of persistent free radicals (PFRs) during the pyrolysis of Fenton-conditioned sludge. Fenton conditioners simultaneously improve the dewatering performance of sewage sludge and catalyze the pyrolysis of sewage sludge for the formation of PFRs. In this process, PFRs with a total number of spins of 9.533×1019 spins/g DS could be generated by pyrolysis of Fenton-conditioned sludge at 400°C. The direct thermal decomposition of natural organic matter (NOM) fractions contributed to the formation of carbon-centered radicals, while the Maillard reaction produced phenols precursors. Additionally, the reaction between aromatic proteins and iron played a crucial role in the formation of phenoxyl or semiquinone-type radicals. Kinetics analysis using discrete distributed activation energy model (DAEM) demonstrated that the average activation energy for pyrolysis was reduced from 178.28 kJ/mol for raw sludge to 164.53 KJ/mol for Fenton conditioned sludge. The reaction factor (fi) indicated that the primary reaction in Fenton-conditioned sludge comprised of 27 parallel first-order reactions, resulting from pyrolysis cleavage of the NOM fractions, the Maillard reaction, and iron catalysis. These findings are significant for understanding the formation process of PFRs from NOM in Fenton-conditioned sludge and provide valuable insight for controlling PFRs formation in practical applications.

Molecular characterization, expression pattern and immunologic function of CD82a in large yellow croaker (Larimichthys crocea).

Visceral white spot disease (VWND) caused by Pseudomonas plecoglossicida poses a major threat to the sustainable development of large yellow croaker (Larimichthys crocea) aquaculture. Genome-wide association analysis (GWAS) and RNA-seq research indicated that LcCD82a play an important role in resistance to visceral white spot disease in L. crocea, but the molecular mechanism of LcCD82a response to P. plecoglossicida infection is still unclear. In this study, we cloned and validated the Open Reading Frame (ORF) sequence of LcCD82a and explored the expression profile of LcCD82a in various tissues of L.crocea. In addition, two different transcript variants (LcCD82a-L and LcCD82a-S) of LcCD82a were identified that exhibit alternative splicing patterns after P. plecoglossicida infection, which may be closely related to the immune regulation during pathogenetic process of VWND. In order to explore the function of LcCD82a, we purified the recombinant protein of LcCD82a-L and LcCD82a-S. The bacterial agglutination and apoptosis function analysis showed that LcCD82a may involve in extracellular bacterial recognition, agglutination, and at the same time participate in the process of antigen presentation and induction of cell apoptosis. Collectively, our studies demonstrate that LcCD82a plays a crucial role in regulating apoptosis and antimicrobial immunity.

Association of iron deficiency with chronic suppurative otitis media in adults.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a prevalent chronic inflammatory disease globally. Current research suggests a possible association between anaemia and the development of CSOM. OBJECTIVES: The objective of this trial was to investigate the relationship between iron metabolism and chronic suppurative otitis media (CSOM) in adults aged 20-60 years. MATERIALS AND METHODS: A consecutive sampling case-control study was used. The study participants were divided into a case group (42 children diagnosed with CSOM) and a control group (42 children with normal ears). Haemoglobin (Hb), Hematocrit (Hct), mean corpuscular volume of erythrocytes (MCV), serum iron level (SI), unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin (TF), ferritin (Fer) were tested in all the participants, and the results were compared with the normal ranges of the World Health Organization (WHO). The comparative analysis of cases and controls was performed using the Fisher extract test, independence t-test, or Mann-Whitney U test. p-value <.05 was considered statistically significant for correlation. RESULTS: There were 61 patients with CSOM and 61 controls included in the study. In the case group, 16 out of 61 patients (26.2%) had low ferritin levels and in the control group, 1 out of 61 patients (1.6%) had low ferritin levels (p < .001). In the case group, 6 (9.8%) of 61 patients had IDA, and in the control group, there were no patients with IDA among 61 patients (p = .027). There were significant differences in SI, UIBC, and Fer parameters between the groups. CONCLUSIONS: In adult patients, the incidence of iron deficiency was higher in CSOM patients than in controls. Iron deficiency may be considered a potential risk factor for chronic suppurative otitis media, and serum iron parameters should be evaluated in these CSOM patients and further studies should be conducted to better understand the potential link between iron deficiency and CSOM.

Mannose: A Promising Player in Clinical and Biomedical Applications.

Mannose, an isomer of glucose, exhibits a distinct molecular structure with the same formula but a different atom arrangement, contributing to its specific biological functions. Widely distributed in body fluids and tissues, particularly in the nervous system, skin, testes, and retinas, mannose plays a crucial role as a direct precursor for glycoprotein synthesis. Glycoproteins, essential for immune regulation and glycosylation processes, underscore the significance of mannose in these physiological activities. The clinical and biomedical applications of mannose are diverse, encompassing its anti-inflammatory properties, potential to inhibit bacterial infections, role in metabolism regulation, and suggested involvement in alleviating diabetes and obesity. Additionally, mannose shows promise in antitumor effects, immune modulation, and the construction of drug carriers, indicating a broad spectrum of therapeutic potential. The article aims to present a comprehensive review of mannose, focusing on its molecular structure, metabolic pathways, and clinical and biomedical applications, and also to emphasize its status as a promising therapeutic agent.

Longitudinal Changes in Chinese Prosociality.

This article presents three studies using data from the World Values Survey, 128 published studies, and China Family Panel Studies to comprehensively examine the longitudinal dynamics of Chinese prosociality, encompassing prosocial attitudes, tendencies, and behaviors, with the overarching goal of shedding light on the evolving nature of prosociality in the Chinese context. These studies reveal a consistent pattern, illustrating a decline followed by a resurgence in all three aspects, with a nadir around 2014. In addition, the study investigates the intricate relationship between economic inequality, prosocial behavior, and prosocial attitudes. The findings suggest that while economic inequality significantly relates to prosocial behavior, it does not entirely explain its fluctuations. Prosocial attitudes partially mediate the connection between economic inequality and prosocial behavior. These insights suggest that addressing inequality could contribute to a more conducive social environment for societal-level prosociality. However, further research is imperative to explore additional determinants of prosociality shifts.

Comparing the efficacy and safety of three surgical approaches for total hysterectomy (TSATH): protocol for a multicentre, single-blind, parallel-group, randomised controlled trial.

INTRODUCTION: Hysterectomy is the most common surgical procedure in the field of gynaecology. The traditional multiport laparoscopy, transumbilical laparoendoscopic single-site surgery (TU-LESS) and transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy approaches have been implemented to varying degrees in clinical practice. At present, although their feasibility has been proven, there are no large randomised controlled studies on postoperative rehabilitation. This study aims to evaluate postoperative recovery and assess the safety and effectiveness of these three surgical approaches for total laparoscopic hysterectomy. METHOD AND ANALYSIS: This is a multicentre, randomised, single-blind, three-arm, parallel-group, interventional clinical trial. Recruitment will be carried out in five tertiary hospitals in China. Patients diagnosed with benign uterine disease or precancerous lesions will be assigned to the vNOTES group, TU-LESS group and conventional laparoscopy group at a 1:1:1 ratio. The achievement rate of comprehensive indices of enhanced recovery after surgery (ERAS) within 24 hours postoperatively will be considered the primary outcome (the comprehensive indicators of ERAS include fluid intake, passing flatus, urination after catheter removal, ambulation and a Visual Analogue Scale score ≤3.) This study will use a non-inferiority test, with a power (1-ß) of 80% and a margin of -0.15, at a one-sided α of 0.0125. The sample size will be 480 patients (including an assumed 15% dropout rate), calculated according to the primary outcome. ETHICS AND DISSEMINATION: This study was approved on 25 April 2022 by the Medical Ethics Committee of West China Second University Hospital (2022(057)), Sichuan University, Chengdu, China. All participants will be required to provide informed consent before their participation in the study. The results of the trial will be submitted for publication in a peer-reviewed journal and presented at international conferences. PROTOCOL VERSION: V.3.0, 31 August 2023. TRIAL REGISTRATION NUMBER: ChiCTR2200057405.

Automated ASPECTS calculation may equal the performance of experienced clinicians: a machine learning study based on a large cohort.

OBJECTIVES: The Alberta Stroke Program Early CT Score (ASPECTS) is a semi-quantitative method to evaluate the severity of early ischemic change on non-contrast computed tomography (NCCT) in patients with acute ischemic stroke (AIS). In this work, we propose an automated ASPECTS method based on large cohort of data and machine learning. METHODS: For this study, we collected 3626 NCCT cases from multiple centers and annotated directly on this dataset by neurologists. Based on image analysis and machine learning methods, we constructed a two-stage machine learning model. The validity and reliability of this automated ASPECTS method were tested on an independent external validation set of 300 cases. Statistical analyses on the total ASPECTS, dichotomized ASPECTS, and region-level ASPECTS were presented. RESULTS: On an independent external validation set of 300 cases, for the total ASPECTS results, the intraclass correlation coefficient between automated ASPECTS and expert-rated was 0.842. The agreement between ASPECTS threshold of ≥ 6 versus < 6 using a dichotomized method was moderate (κ = 0.438, 0.391-0.477), and the detection rate (sensitivity) was 86.5% for patients with ASPECTS threshold of ≥ 6. Compared with the results of previous studies, our method achieved a slight lead in sensitivity (67.8%) and AUC (0.845), with comparable accuracy (78.9%) and specificity (81.2%). CONCLUSION: The proposed automated ASPECTS method driven by a large cohort of NCCT images performed equally well compared with expert-rated ASPECTS. This work further demonstrates the validity and reliability of automated ASPECTS evaluation method. CLINICAL RELEVANCE STATEMENT: The automated ASPECTS method proposed by this study may help AIS patients to receive rapid intervention, but should not be used as a stand-alone diagnostic basis. KEY POINTS: NCCT-based manual ASPECTS scores were poorly consistent. Machine learning can automate the ASPECTS scoring process. Machine learning model design based on large cohort data can effectively improve the consistency of ASPECTS scores.

Peroxymonosulfate activation by trace iron(III) porphyrin for facile degradation of organic pollutants via nonradical oxidation.

Nonradical species with great resistance to interference have shown great advantages in complex wastewater treatment. Herein, a novel system constructed by biodegradable tetrakis-(4-carboxyphenyl)-porphyrinatoiron(III) (FeIII-TCPP) and peroxymonosulfate (PMS) was proposed for facile decontamination. Nonradical pathway is observed in FeIII-TCPP/PMS, where 1O2 and high-valent iron-oxo species play dominant roles. The genres and valence of high-valent iron-oxo species, including iron(IV)-oxo porphyrin radical-cationic species [OFeIV-TCPP•+] and iron(IV)-hydroxide species [FeIV-TCPP(OH)], are ascertained, along with their generation mechanism. The axial ligand on the iron axial site affects the ground spin state of FeIII-TCPP, further influencing the thermodynamic reaction pathway of active species. With trace catalyst in micromoles, FeIII-TCPP exhibits high efficiency by degrading bisphenol S (BPS) completely within 5 min, while Co2+/PMS can only achieve a maximum of 26.2% under identical condition. Beneficial from nonradical pathways, FeIII-TCPP/PMS demonstrates a wide pH range of 3-10 and exhibits minimal sensitivity to interference of concomitant materials. BPS is primarily eliminated through ß-scission and hydroxylation. Specifically, 1O2 electrophilically attacks the C-S bond of BPS, while high-valent iron-oxo species interacts with BPS through an oxygen-bound mechanism. This study provides novel insights into efficient activation of PMS by iron porphyrin, enabling the removal of refractory pollutants through nonradical pathway.

Effect of Psychological and Medication Therapies for Insomnia on Daytime Functions: A Randomized Clinical Trial.

Importance: Daytime functional impairments are the primary reasons for patients with insomnia to seek treatment, yet little is known about what the optimal treatment is for improving daytime functions and how best to proceed with treatment for patients whose insomnia has not remitted. Objectives: To compare the efficacy of behavioral therapy (BT) and zolpidem as initial therapies for improving daytime functions among patients with insomnia and evaluate the added value of a second treatment for patients whose insomnia has not remitted. Design, Setting, and Participants: In this sequential multiple-assignment randomized clinical trial conducted at institutions in Canada and the US, 211 adults with chronic insomnia disorder were enrolled between May 1, 2012, and December 31, 2015, and followed up for 12 months. Statistical analyses were performed on an intention-to-treat basis in April and October 2023. Interventions: Participants were randomly assigned to either BT or zolpidem as first-stage therapy, and those whose insomnia had not remitted received a second-stage psychological therapy (BT or cognitive therapy) or medication therapy (zolpidem or trazodone). Main Outcomes and Measures: Study outcomes were daytime symptoms of insomnia, including mood disturbances, fatigue, functional impairments of insomnia, and scores on the 36-item Short-Form Health Survey (SF-36) physical and mental health components. Results: Among 211 adults with insomnia (132 women [63%]; mean [SD] age, 45.6 [14.9] years), 104 were allocated to BT and 107 to zolpidem at the first stage. First-stage treatment with BT or zolpidem yielded significant and equivalent benefits for most of the daytime outcomes, including depressive symptoms (Beck Depression Inventory-II mean score change, -3.5 [95% CI, -4.7 to -2.3] vs -4.3 [95% CI, -5.7 to -2.9]), fatigue (Multidimensional Fatigue Inventory mean score change, -4.7 [95% CI, -7.3 to -2.2] vs -5.2 [95% CI, -7.9 to -2.5]), functional impairments (Work and Social Adjustment Scale mean score change, -5.0 [95% CI, -6.7 to -3.3] vs -5.1 [95% CI, -7.2 to -2.9]), and mental health (SF-36 mental health subscale mean score change, 3.5 [95% CI, 1.9-5.1] vs 2.5 [95% CI, 0.4-4.5]), while BT produced larger improvements for anxiety symptoms relative to zolpidem (State-Trait Anxiety Inventory mean score change, -4.1 [95% CI, -5.8 to -2.4] vs -1.2 [95% CI, -3.0 to 0.5]; P = .02; Cohen d = 0.55). Second-stage therapy produced additional improvements for the 2 conditions starting with zolpidem at posttreatment in fatigue (Multidimensional Fatigue Inventory mean score change: zolpidem plus BT, -3.8 [95% CI, -7.1 to -0.4]; zolpidem plus trazodone, -3.7 [95% CI, -6.3 to -1.1]), functional impairments (Work and Social Adjustment Scale mean score change: zolpidem plus BT, -3.7 [95% CI, -6.4 to -1.0]; zolpidem plus trazodone, -3.3 [95% CI, -5.9 to -0.7]) and mental health (SF-36 mental health subscale mean score change: zolpidem plus BT, 5.3 [95% CI, 2.7-7.9]; zolpidem plus trazodone, 2.0 [95% CI, 0.1-4.0]). Treatment benefits achieved at posttreatment were well maintained throughout the 12-month follow-up, and additional improvements were noted for patients receiving the BT treatment sequences. Conclusions and Relevance: In this randomized clinical trial of adults with insomnia disorder, BT and zolpidem produced improvements for various daytime symptoms of insomnia that were no different between treatments. Adding a second treatment offered an added value with further improvements of daytime functions. Trial Registration: ClinicalTrials.gov Identifier: NCT01651442.

The association of insomnia with long COVID: An international collaborative study (ICOSS-II).

OBJECTIVE: There is evidence of a strong association between insomnia and COVID-19, yet few studies have examined the relationship between insomnia and long COVID. This study aimed to investigate whether COVID-19 patients with pre-pandemic insomnia have a greater risk of developing long COVID and whether long COVID is in turn associated with higher incident rates of insomnia symptoms after infection. METHODS: Data were collected cross-sectionally (May-Dec 2021) as part of an international collaborative study involving participants from 16 countries. A total of 2311 participants (18-99 years old) with COVID-19 provided valid responses to a web-based survey about sleep, insomnia, and health-related variables. Log-binomial regression was used to assess bidirectional associations between insomnia and long COVID. Analyses were adjusted for age, sex, and health conditions, including sleep apnea, attention and memory problems, chronic fatigue, depression, and anxiety. RESULTS: COVID-19 patients with pre-pandemic insomnia showed a higher risk of developing long COVID than those without pre-pandemic insomnia (70.8% vs 51.4%; adjusted relative risk [RR]: 1.33, 95% confidence interval [CI]: 1.07-1.65). Among COVID-19 cases without pre-pandemic insomnia, the rates of incident insomnia symptoms after infection were 24.1% for short COVID cases and 60.6% for long COVID cases (p < .001). Compared with short COVID cases, long COVID cases were associated with an increased risk of developing insomnia symptoms (adjusted RR: 2.00; 95% CI: 1.50-2.66). CONCLUSIONS: The findings support a bidirectional relationship between insomnia and long COVID. These findings highlight the importance of addressing sleep and insomnia in the prevention and management of long COVID.

Development of an innovative minimally invasive primate spinal cord injury model: A case report.

Spinal cord injury (SCI) animal models have been widely created and utilized for repair therapy research, but more suitable experimental animals and accurate modeling methodologies are required to achieve the desired results. In this experiment, we constructed an innovative dorsal 1/4 spinal cord transection macaque model that had fewer severe problems, facilitating postoperative care and recovery. In essence, given that monkeys and humans share similar genetics and physiology, the efficacy of this strategy in a nonhuman primate SCI model basically serves as a good basis for its prospective therapeutic use in human SCI.

Subtyping at-risk adolescents for predicting response toward insomnia prevention program.

BACKGROUND: Previous study has shown that a brief cognitive-behavioral prevention insomnia program could reduce 71% risk of developing insomnia among at-risk adolescents. This study aimed to evaluate the differential response to insomnia prevention in subgroups of at-risk adolescents. METHODS: Adolescents with a family history of insomnia and subthreshold insomnia symptoms were randomly assigned to a 4-week insomnia prevention program or nonactive control group. Assessments were conducted at baseline, 1 week, and 6- and 12-month after the intervention. Baseline sleep, daytime, and mood profiles were used to determine different subgroups by using latent class analysis (LCA). Analyses were conducted based on the intention-to-treat approach. RESULTS: LCA identified three subgroups: (a) insomnia symptoms only, (b) insomnia symptoms with daytime sleepiness and mild anxiety, and (c) insomnia symptoms with daytime sleepiness, mild anxiety, and depression. The incidence rate of insomnia disorder over the 12-month follow-up was significantly reduced for adolescents receiving intervention in subgroup 3 compared with the controls (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.13-0.99; p = .049) and marginally for subgroup 2 (HR = 0.14; 95% CI: 0.02-1.08; p = .059). In addition, adolescents who received intervention in subgroups 2 and 3 had a reduced risk of excessive daytime sleepiness (subgroup 2: adjusted OR [AdjOR] = 0.45, 95% CI: 0.23-0.87; subgroup 3: AdjOR = 0.32, 95% CI: 0.13-0.76) and possible anxiety (subgroup 2: AdjOR = 0.47, 95% CI: 0.27-0.82; subgroup 3: AdjOR = 0.33, 95% CI: 0.14-0.78) compared with the controls over the 12-month follow-up. CONCLUSIONS: Adolescents at risk for insomnia can be classified into different subgroups according to their psychological profiles, which were associated with differential responses to the insomnia prevention program. These findings indicate the need for further phenotyping and subgrouping at-risk adolescents to develop personalized insomnia prevention.