Efficacy of cognitive behavioral therapy for insomnia in the perinatal period: a meta-analysis of randomized controlled trials.

The meta-analysis aims to explore the effect of cognitive behavioral therapy for insomnia (CBT-I) in the perinatal period. Randomized controlled trials (RCTs) assessed the effects of CBT-I in perinatal women with insomnia, published in English, were eligible. Electronic searches were performed using PubMed, Embase (Elsevier), PsycINFO (Ebsco), and Web of Science (Clarivate Analytics). Insomnia Severity Index (ISI) as the primary outcome was used to estimate the pooled effects and durable efficacy of CBT-I. The secondary outcome measures were Edinburgh Postnatal Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI). Of 46 studies reviewed, seven studies met the inclusion criteria. The meta-analysis indicated significant improvement in insomnia as measured with the ISI (standardized mean difference (SMD) = - 0.62, 95% confidence intervals (CI) - 0.77, - 0.47, I2 = 28%). At the follow-up time point, the meta-analysis indicated the durable efficacy of CBT-I (SMD = - 0.47, 95% CI - 0.90, - 0.03, I2 = 73%). Definite improvement of CBT-I on EPDS (SMD = -0.31, 95% CI - 0.55, - 0.06, I2 = 33%) and PSQI (SMD = - 0.82, 95% CI - 1.27, - 0.38, I2 = 68%) score change post-intervention were found. In sub-analyses, CBT-I had similar effect sizes, independent of possible modifiers (study population, comparison group, delivery format, etc.). This meta-analysis demonstrates that CBT-I is effective in alleviating insomnia, depression, and sleep quality among perinatal women. It is equally important to find that CBT-I has a durable efficacy on insomnia in the perinatal period. However, it is necessary to include larger samples and conduct rigorous RCTs to further explore this issue. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00502-z.

MIS-Net: A deep learning-based multi-class segmentation model for CT images.

The accuracy of traditional CT image segmentation algorithms is hindered by issues such as low contrast and high noise in the images. While numerous scholars have introduced deep learning-based CT image segmentation algorithms, they still face challenges, particularly in achieving high edge accuracy and addressing pixel classification errors. To tackle these issues, this study proposes the MIS-Net (Medical Images Segment Net) model, a deep learning-based approach. The MIS-Net model incorporates multi-scale atrous convolution into the encoding and decoding structure with symmetry, enabling the comprehensive extraction of multi-scale features from CT images. This enhancement aims to improve the accuracy of lung and liver edge segmentation. In the evaluation using the COVID-19 CT Lung and Infection Segmentation dataset, the left and right lung segmentation results demonstrate that MIS-Net achieves a Dice Similarity Coefficient (DSC) of 97.61. Similarly, in the Liver Tumor Segmentation Challenge 2017 public dataset, the DSC of MIS-Net reaches 98.78.

[Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice].

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Bicarbonate-Dependent Detoxification by Mitigating Ammonium-Induced Hypoxic Stress in Triticum aestivum Root.

Ammonium (NH4+) toxicity is ubiquitous in plants. To investigate the underlying mechanisms of this toxicity and bicarbonate (HCO3-)-dependent alleviation, wheat plants were hydroponically cultivated in half-strength Hoagland nutrient solution containing 7.5 mM NO3- (CK), 7.5 mM NH4+ (SA), or 7.5 mM NH4+ + 3 mM HCO3- (AC). Transcriptomic analysis revealed that compared to CK, SA treatment at 48 h significantly upregulated the expression of genes encoding fermentation enzymes (pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH), and lactate dehydrogenase (LDH)) and oxygen consumption enzymes (respiratory burst oxidase homologs, dioxygenases, and alternative oxidases), downregulated the expression of genes encoding oxygen transporters (PIP-type aquaporins, non-symbiotic hemoglobins), and those involved in energy metabolism, including tricarboxylic acid (TCA) cycle enzymes and ATP synthases, but upregulated the glycolytic enzymes in the roots and downregulated the expression of genes involved in the cell cycle and elongation. The physiological assay showed that SA treatment significantly increased PDC, ADH, and LDH activity by 36.69%, 43.66%, and 61.60%, respectively; root ethanol concentration by 62.95%; and lactate efflux by 23.20%, and significantly decreased the concentrations of pyruvate and most TCA cycle intermediates, the complex V activity, ATP content, and ATP/ADP ratio. As a consequence, SA significantly inhibited root growth. AC treatment reversed the changes caused by SA and alleviated the inhibition of root growth. In conclusion, NH4+ treatment alone may cause hypoxic stress in the roots, inhibit energy generation, suppress cell division and elongation, and ultimately inhibit root growth, and adding HCO3- remarkably alleviates the NH4+-induced inhibitory effects on root growth largely by attenuating the hypoxic stress.

Comparative analysis of chloroplast and mitochondrial genomes of sweet potato provides evidence of gene transfer.

The increasing number of plant mitochondrial DNA genomes (mtDNA) sequenced reveals the extent of transfer from both chloroplast DNA genomes (cpDNA) and nuclear DNA genomes (nDNA). This study created a library and assembled the chloroplast and mitochondrial genomes of the leafy sweet potato better to understand the extent of mitochondrial and chloroplast gene transfer. The full-length chloroplast genome of the leafy sweet potato (OM808940) is 161,387 bp, with 132 genes annotated, including 87 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The mitochondrial genome (OM808941) was 269,578 bp in length and contained 69 functional genes, including 39 protein-coding genes, 6 rRNA genes, and 24 tRNA genes. 68 SSR loci were found in the leafy sweet potato organelle genome, including 54 in the chloroplast genome and 14 in the mitochondria genome. In the sweet potato mitochondrial genome, most genes have RNA editing sites, and the conversion ratio from hydrophilic amino acids to hydrophobic amino acids is the highest, reaching 47.12%. Horizontal transfer occurs in the sweet potato organelle genome and nuclear genome. 40 mitochondrial genome segments share high homology with 14 chloroplast genome segments, 33 of which may be derived from chloroplast genome horizontal transfer. 171 mitochondrial genome sequences come from the horizontal transfer of nuclear genome. The phylogenetic analysis of organelle genes revealed that the leafy sweet potato was closely related to the tetraploid wild species Ipomoea tabascana and the wild diploid species Ipomoea trifida.

Hair cell-specific Myo15 promoter-mediated gene therapy rescues hearing in DFNB9 mouse model.

Adeno-associated viral (AAV) vectors are increasingly used as vehicles for gene delivery to treat hearing loss. However, lack of specificity of the transgene expression may lead to overexpression of the transgene in nontarget tissues. In this study, we evaluated the expression efficiency and specificity of transgene delivered by AAV-PHP.eB under the inner ear sensory cell-specific Myo15 promoter. Compared with the ubiquitous CAG promoter, the Myo15 promoter initiates efficient expression of the GFP fluorescence reporter in hair cells, while minimizing non-specific expression in other cell types of the inner ear and CNS. Furthermore, using the Myo15 promoter, we constructed an AAV-mediated therapeutic system with the coding sequence of OTOF gene. After inner ear injection, we observed apparent hearing recovery in Otof-/- mice, highly efficient expression of exogenous otoferlin, and significant improvement in the exocytosis function of inner hair cells. Overall, our results indicate that gene therapy mediated by the hair cell-specific Myo15 promoter has potential clinical application for the treatment of autosomal recessive deafness and yet for other hereditary hearing loss related to dysfunction of hair cells.

AAV-Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness.

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure-tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5-year-old patient can be restored to the normal range at 1 month after AAV-OTOF injection, while the 8-year-old patient can hear the conversational sounds. Most importantly, the 5-year-old patient can hear and recognize speech only through the AAV-OTOF-injected ear. This study is the first to demonstrate the safety and efficacy of AAV-OTOF in patients, expands and optimizes current OTOF-related gene therapy and provides valuable information for further application of gene therapies for deafness.

AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial.

BACKGROUND: Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9. METHODS: This single-arm, single-centre trial enrolled children (aged 1-18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing. FINDINGS: Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1-2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40-57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5-4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery. INTERPRETATION: AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.

Inhibition of the HMGB1/RAGE axis protects against cisplatin-induced ototoxicity via suppression of inflammation and oxidative stress.

As an anti-tumor drug widely used in the clinic, cisplatin is limited by its ototoxic side effects associated with various factors, including inflammatory responses. Receptor for Advanced Glycation Endproducts (RAGE) recognizes damage-associated molecular patterns (DAMPs) and promotes stress and inflammation. This study intended to determine the potential behavior of the HMGB1/RAGE axis after cisplatin injury and whether it has a protective effect after inhibiting this pathway. We used FPS-ZM1, a RAGE inhibitor, to modulate the axis of HMGB1/RAGE in neonatal mouse cochlear explants and C57BL/6 mice in vivo. Apoptosis was identified by Annexin V-FITC/PI assay, Cleaved Caspase-3, and TUNEL staining. Reactive oxygen species (ROS) level was assessed by MitoSOX Red and CellROX Green assay. The expression of proteins associated with the HMGB1/RAGE axis and apoptosis was observed by western blotting. The expression of inflammatory cytokines was evaluated by qPCR. The protective effect of HMGB1/RAGE knockdown was also assessed on cisplatin-induced ototoxicity. These results demonstrated that cisplatin could activate the HMGB1/RAGE pathway in cochlear hair cells and release inflammatory factors. Pretreatment with FPS-ZM1 alleviated cisplatin-induced ototoxicity in vivo and in vitro. Knocking down HMGB1 and RAGE achieved specific protective effects. Altogether, inhibiting HMGB1/RAGE axis can reverse the increase of ROS accumulation, the activation of apoptosis, and the production of inflammatory reactions after cisplatin injury. FPS-ZM1 could resist the ototoxicity of cisplatin by suppressing the HMGB1/RAGE signal pathway, and it may be considered the new otoprotective potential strategy for hearing loss.

Dietary Ferulic Acid Increases Endurance Capacity by Promoting Skeletal Muscle Oxidative Phenotype, Mitochondrial Function, and Antioxidant Capacity.

SCOPE: Endurance capacity is essential for endurance athletes' achievement and individuals' health. Nutritional supplements are a proven way to enhance endurance capacity. Previous studies have shown that ferulic acid (FA) enhances endurance capacity, but the underlying mechanism is unclear. The study is aimed to investigate the mechanism by which FA increases endurance capacity. METHODS AND RESULTS: Forty mice are divided into control and 0.5% FA-supplemented groups, and an exhaustive swimming test demonstrates increased endurance capacity with FA supplementation. This study investigates the underlying mechanism for this effect of FA. Firstly, RT-PCR and western blot analysis find that FA increases the transformation from fast to slow muscle fiber. Additionally, adenosine triphosphate concentration, metabolic enzyme activity, and mitochondrial DNA analysis find that FA increases mitochondrial biogenesis and activates nuclear factor erythroid 2-related factor (NRF)1 signaling pathway in muscle. Besides, through antioxidant capacity analysis, this study finds that FA activates NRF2 signaling pathway and improves the antioxidant capacity in muscle. Moreover, inhibiting NRF2 eliminates FA's effect on muscle fiber transformation in C2C12 cells. CONCLUSION: Our results suggest that FA increases endurance capacity by promoting skeletal muscle oxidative phenotype, mitochondrial function, and antioxidant capacity, which may be related to the NRF1 and NRF2 signaling pathways.

Synergistic removal performance and mechanism of Cd(II) and As(III) from irrigation water by iron sulfide-based porous biochar.

Since Cd(II) and As(III) have extremely opposite chemical characteristics, it is a huge challenging to simultaneously remove these two ions from aqueous solutions. Therefore, a novel iron sulfide-based porous biochar (FSB) was synthesized and used to evaluate its Cd(II) and As(III) removal performance and mechanisms. The characterization and batch experiments results indicated that FeS was successfully loaded on the surface of biochar and increased its adsorption sites. The iron sulfide-based porous biochar was very favorable for the removal of Cd(II) and As(III) in the weakly acidic environment. The maximum adsorption of Cd(II) and As(III) by FSB was 108.8 mg g-1 and 76.3 mg g-1, respectively, according to the Langmuir and Freundlich isothermal adsorption model, and the adsorption equilibrium time was 12 h and 4 h, respectively, according to the pseudo-second-order kinetic model. In the coexisting ion system, Cd(II) adsorption was suppressed by Ca2+, Mg2+, and humic acid, but enhanced by PO43- and As(III). As(III) adsorption was inhibited by PO43- and humic acid. Precipitation and complexation are the predominant adsorption mechanisms of Cd(II) and As(III), which contribute to the formation of Cd-O, Fe-O-Cd, As-O, Fe-O-As, ternary complex Cd-Fe-As, and stable compounds FeAsO4·2H2O and CdS. Therefore, The iron sulfide-based porous biochar can be an efficient and environmentally friendly candidate for the treatment of Cd(II) and As(III) co-polluted irrigation water.

Combined microscope-endoscopy resection of petrous bone cholesteatoma with temporary facial nerve transposition versus nontransposition.

PURPOSE: The narrow supralabyrinthine space affects surgical procedures. To study the effect of temporary transposition of geniculate ganglion of facial nerve versus nontransposition on lesion recurrence and facial nerve function in patients with petrous bone cholesteatoma. METHODS: A total of 18 patients with petrous bone cholesteatoma involving the facial nerve were treated in our hospital from November 2016 to March 2023. The main surgical method is the extended supralabyrinthine approach assisted by a microscope and an endoscope. We collected and retrospectively analyzed their medical records. RESULTS: Temporary facial nerve transposition was performed in five patients, and nontransposition was performed in 13 patients. Cholesteatoma recurred in three patients with facial nerve nontransposition, whereas none in patients with facial nerve transposition. In this study, except for one case with a second operation, postoperative facial paralysis in other cases was improved to varying degrees, and there was no significant difference between the two groups. CONCLUSION: Temporary transposition of geniculate ganglion of facial nerve will not affect the postoperative nerve function of patients and can reduce the possibility of cholesteatoma recurrence of the petrous bone.

Drug screening identifies aldose reductase as a novel target for treating cisplatin-induced hearing loss.

Cisplatin is a frequently used chemotherapeutic medicine for cancer treatment. Permanent hearing loss is one of the most serious side effects of cisplatin, but there are few FDA-approved medicines to prevent it. We applied high-through screening and target fishing and identified aldose reductase, a key enzyme of the polyol pathway, as a novel target for treating cisplatin ototoxicity. Cisplatin treatment significantly increased the expression level and enzyme activity of aldose reductase in the cochlear sensory epithelium. Genetic knockdown or pharmacological inhibition of aldose reductase showed a significant protective effect on cochlear hair cells. Cisplatin-induced overactivation of aldose reductase led to the decrease of NADPH/NADP+ and GSH/GSSG ratios, as well as the increase of oxidative stress, and contributed to hair cell death. Results of target prediction, molecular docking, and enzyme activity detection further identified that Tiliroside was an effective inhibitor of aldose reductase. Tiliroside was proven to inhibit the enzymatic activity of aldose reductase via competitively interfering with the substrate-binding region. Both Tiliroside and another clinically approved aldose reductase inhibitor, Epalrestat, inhibited cisplatin-induced oxidative stress and subsequent cell death and thus protected hearing function. These findings discovered the role of aldose reductase in the pathogenesis of cisplatin-induced deafness and identified aldose reductase as a new target for the prevention and treatment of hearing loss.

Huaier improves the efficacy of anti-PD-L1 Ab in the treatment of hepatocellular carcinoma by regulating tumor immune microenvironment.

BACKGROUND: Combination therapy is an effective method for augmenting the efficacy of immune checkpoint inhibitors (ICIs). Huaier is a commonly used Chinese patent medicine with substantial antitumor effects. The combination of Huaier and ICIs may increase the efficacy of ICIs against hepatocellular carcinoma (HCC). METHODS: The major components of Huaier were detected by high-performance liquid chromatography-mass spectrometry. The optimal antitumor dose of Huaier was investigated in H22-bearing mice. Next, Huaier was combined with anti-CD8α antibody (Ab) or anti-PD-L1 Ab to observe the antitumor effect. The safety of these combination drugs was evaluated through blood biochemical tests and hematoxylin and eosin staining of histological sections. RT-qPCR, immunohistochemistry, flow cytometry, and transcriptome sequencing were performed to investigate the potential action mechanism of anti-PD-L1 Ab combined with Huaier against HCC. RESULTS: HPLC-MS/MS identified 333 components of Huaier, including carboxylic acids and derivatives, thienothiophenes, phenols, flavonoids and so on. Huaier exhibited significant antitumor effects, with the strongest effect noted at a dose of 4 g/kg. Huaier boosted CD8+ T cells infiltration into the tumor. Next, CD8+ T cells were depleted by with anti-CD8α Ab, and the antitumor effect of Huaier was suppressed. Flow cytometry results revealed that CD8+ T cells were reduced in the Huaier+anti-CD8α Ab group, with the antitumor effect of this group being inhibited. This indicated that CD8+ T cells were key players in the antitumor activity of Huaier. Meanwhile, Huaier inhibited microvessel density (MVD), downregulated vascular endothelial growth factor A (VEGFA), and upregulated PD-L1 in tumor tissues. Finally, Huaier combined with anti-PD-L1 Ab exhibited a greater antitumor effect in the H22-bearing mice. And the results of liver and kidney function tests and histological section analysis unveiled that the safety of these drugs was excellent. According to the transcriptome sequencing results, Huaier combined with anti-PD-L1 Ab possibly exerted anti-HCC effects through immunomodulation, immune response, and so on. CONCLUSIONS: Huaier exhibited a significant antitumor effect. It promoted CD8+ T cells infiltration, upregulated PD-L1 expression, downregulated VEGFA expression, and inhibited MVD, thereby playing a significant antitumor immunoregulatory effect. The combination of Huaier and anti-PD-L1 Ab has significant antitumor effects, and this regimen has good safety. Therefore, Huaier combined with anti-PD-L1 Ab is a promising therapeutic approach against HCC.

Functional Connectivity Alterations and Molecular Characterization of the Anterior Cingulate Cortex in Tinnitus Pathology without Hearing Loss.

Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole-brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate-induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high-gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.

Dynamic change of vestibular function and the long-term prognosis of vestibular neuritis.

AIM: To comprehensively evaluate the dynamic change of vestibular function during long-term follow-up of vestibular neuritis, as well as the co-relationship with the outcomes of vestibular neuritis (VN), which provides the recommendations for vestibular function tests during the course of VN. METHODS: A prospective cohort study was conducted on 16 patients with acute VN. Caloric test, vHIT, rotatory chair tests, VEMP, dizziness handicap inventory (DHI) score, and dynamic dizzy scales (VAS-DD) was first performed within 7 days of neuritis onset, which were further re-evaluated during the 6-12 months of follow-up. The dynamic changes on multiple objective vestibular examinations were analyzed during the acute and recovery stage of VN. We further evaluated the co-relationship between the vestibular dysfunction scales and the prognosis of VN. RESULTS: In more than 6 months of follow-up, 44% of the ultralow frequency, 94% of the low-to-mid frequency, and 44% of the high-frequency function of the horizontal semicircular canal returned to normal (p < 0.05). The change degree in symmetry of the rotatory chair test was correlated with the gain of the horizontal semicircular canal on the vHIT and the unilateral weakness (UW) value on the caloric test (p < 0.05). The change in DHI score was correlated with the phase; change in VAS-DD level correlated with the symmetry and TC of the rotatory chair test at VN recovery stage (p < 0.05). There was no significant correlation between the change in DHI score or change in VAS-DD and the degree of vestibular function recovery (p > 0.05). CONCLUSION: In general, vestibular function improved during the course of VN. The rotatory chair test can be used to evaluate the overall function of the vestibular system and the compensatory state in patients with VN.

Varying mechanical forces drive sensory epithelium formation.

The mechanical cues of the external microenvironment have been recognized as essential clues driving cell behavior. Although intracellular signals modulating cell fate during sensory epithelium development is well understood, the driving force of sensory epithelium formation remains elusive. Here, we manufactured a hybrid hydrogel with tunable mechanical properties for the cochlear organoids culture and revealed that the extracellular matrix (ECM) drives sensory epithelium formation through shifting stiffness in a stage-dependent pattern. As the driving force, moderate ECM stiffness activated the expansion of cochlear progenitor cell (CPC)-derived epithelial organoids by modulating the integrin α3 (ITGA3)/F-actin cytoskeleton/YAP signaling. Higher stiffness induced the transition of CPCs into sensory hair cells (HCs) through increasing the intracellular Ca2+ signaling mediated by PIEZO2 and then activating KLF2 to accomplish the cell specification . Our results identify the molecular mechanism of sensory epithelium formation guided by ECM mechanical force and contribute to developing therapeutic approaches for HC regeneration.

Perspectives and experiences of mothers of school-age children with asthma: a qualitative study.

INTRODUCTION AND AIMS: This study aimed to explore the perspectives and experiences of mothers of school-age children with asthma in care. METHODS: A phenomenological study was conducted using qualitative research methods from August 2021 to November 2021. Mothers (from Sichuan, China) of school-aged children with asthma who sought outpatient care at the pediatric asthma clinic were purposively sampled based on their occupation, education level, and duration of their child's illness. Semi-structured face-to-face interviews were conducted in consultation room A07 of the pediatric asthma clinic. The interviews were audio-recorded, transcribed verbatim, and analyzed thematically. RESULTS: 23 mothers expressed interest, but data saturation was reached after recruiting 15 mothers.Four main themes encompassing ten sub-themes emerged from the analysis: (1) Negative psychological burden, with sub-themes including anxiety shock, fear of death, guilt, and stigma. (2) Family dysfunction, with sub-themes including impaired quality of life, family emotional crisis, and heavy economic burden. (3) Difficulty in seeking medical treatment. (4) Active response, with sub-themes including emotional adjustment, family empowerment, and social support. CONCLUSIONS: In this sample, the caregiving experience of mothers of school-age children with asthma is diverse and complex, reflected not only in personal psychological aspects but also in family functioning and social support. Taking into account various factors, such as addressing psychological well-being, emphasizing family and social support, and promoting the sharing of positive experiences, may result in more effective alleviation of caregiving stress for mothers of school-age children with asthma.