Chronic insomnia affects 10%–15% of the population, with one-third of Western adults struggling with sleep initiation or maintenance. Binaural beats, which involve two audio frequencies, have shown the potential for enhancing sleep and mood. This study examined the efficacy of customized binaural audio tracks generated using facial analysis software to treat chronic insomnia. Methods: A 45-minute personalized binaural beat audio session was delivered using the Spatial app and headband (SoundHealth) to 20 participants with moderate-to-severe insomnia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and Insomnia Severity Index (ISI) criteria, over four weeks in California. Statistical analysis (paired t-test and linear mixed modeling) was used to compare baseline ISI scores to posttreatment scores, with p<0.05 indicating significance. The study assumed 80% power and aimed to achieve a 7-point ISI reduction. Results: All participants completed the study with no adverse events or full protocol adherence. The cohort was 60% White, with a 3:1 female-to-male ratio and an average age of 51.9 years. The baseline ISI was 19.8, dropping to 8.5 after four weeks, showing an 11.3-point reduction (95% confidence interval [CI]: -15 to -7.6, p<0.001). Mixed modeling indicated a similar ISI decrease of 11.28 points (95% CI: -14.98 to -7.57, p<0.001). The treatment response rate was 70%. Conclusions: Customized binaural beats show promise for insomnia treatment, with no adverse effects and high adherence. Most participants improved to no insomnia or subthreshold insomnia. Further research is needed to validate these results using larger samples and to assess long-term effects.

Chronic insomnia affects 10%–15% of the population, with one-third of Western adults struggling with sleep initiation or maintenance. Binaural beats, which involve two audio frequencies, have shown the potential for enhancing sleep and mood. This study examined the efficacy of customized binaural audio tracks generated using facial analysis software to treat chronic insomnia. Methods: A 45-minute personalized binaural beat audio session was delivered using the Spatial app and headband (SoundHealth) to 20 participants with moderate-to-severe insomnia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and Insomnia Severity Index (ISI) criteria, over four weeks in California. Statistical analysis (paired t-test and linear mixed modeling) was used to compare baseline ISI scores to posttreatment scores, with p<0.05 indicating significance. The study assumed 80% power and aimed to achieve a 7-point ISI reduction. Results: All participants completed the study with no adverse events or full protocol adherence. The cohort was 60% White, with a 3:1 female-to-male ratio and an average age of 51.9 years. The baseline ISI was 19.8, dropping to 8.5 after four weeks, showing an 11.3-point reduction (95% confidence interval [CI]: -15 to -7.6, p<0.001). Mixed modeling indicated a similar ISI decrease of 11.28 points (95% CI: -14.98 to -7.57, p<0.001). The treatment response rate was 70%. Conclusions: Customized binaural beats show promise for insomnia treatment, with no adverse effects and high adherence. Most participants improved to no insomnia or subthreshold insomnia. Further research is needed to validate these results using larger samples and to assess long-term effects.

Chronic insomnia affects 10%–15% of the population, with one-third of Western adults struggling with sleep initiation or maintenance. Binaural beats, which involve two audio frequencies, have shown the potential for enhancing sleep and mood. This study examined the efficacy of customized binaural audio tracks generated using facial analysis software to treat chronic insomnia. Methods: A 45-minute personalized binaural beat audio session was delivered using the Spatial app and headband (SoundHealth) to 20 participants with moderate-to-severe insomnia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and Insomnia Severity Index (ISI) criteria, over four weeks in California. Statistical analysis (paired t-test and linear mixed modeling) was used to compare baseline ISI scores to posttreatment scores, with p<0.05 indicating significance. The study assumed 80% power and aimed to achieve a 7-point ISI reduction. Results: All participants completed the study with no adverse events or full protocol adherence. The cohort was 60% White, with a 3:1 female-to-male ratio and an average age of 51.9 years. The baseline ISI was 19.8, dropping to 8.5 after four weeks, showing an 11.3-point reduction (95% confidence interval [CI]: -15 to -7.6, p<0.001). Mixed modeling indicated a similar ISI decrease of 11.28 points (95% CI: -14.98 to -7.57, p<0.001). The treatment response rate was 70%. Conclusions: Customized binaural beats show promise for insomnia treatment, with no adverse effects and high adherence. Most participants improved to no insomnia or subthreshold insomnia. Further research is needed to validate these results using larger samples and to assess long-term effects.

Purpose: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. Materials and Methods: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. Results: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients.All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients.Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. Conclusions Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β ₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.

X-linked dystonia-parkinsonism (XDP) is an adult-onset debilitating neurodegenerative disorder presenting with motor and nonmotor symptoms. The treatment options for XDP are limited. We described a patient with XDP who underwent a unilateral transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) pallidothalamic tractotomy with a one-year follow-up. The patient reported an immediate improvement in his pain after the procedure. Compared to baseline, there was an improvement in his scores in the dystonia (31%), parkinsonism (35.1%), and activities of daily living (71%) subscales at 1-year follow up. The overall improvement at one year was 46%. There were no adverse events noted. Additional studies with larger sample size and follow-up would be needed to document its long-term safety and efficacy.
Dystonia 3, Torsion, X-Linked ; Dystonic Disorders ; Genetic Diseases, X-Linked

INTRODUCTION: A voluntary cerebral palsy (CP) registry was established in 2017 to describe the clinical characteristics and functional outcomes of CP in Singapore. METHODS: People with CP born after 1994 were recruited through KK Women's and Children's Hospital, National University Hospital and Cerebral Palsy Alliance Singapore. Patient-reported basic demographics, service utilisation and quality of life measures were collected with standardised questionnaires. Clinical information was obtained through hospital medical records. RESULTS: Between 1 September 2017 and 31 March 2020, 151 participants were recruited. A majority (n=135, 89%) acquired CP in the pre/perinatal period, where prematurity (n=102, 76%) and the need for emergency caesarean section (n=68, 50%) were leading risk factors. Sixteen (11%) of the total participants had post-neonatally acquired CP. For predominant CP motor types, 109 (72%) had a spastic motor type; 32% with spastic mono/hemiplegia, 41% diplegia, 6% triplegia and 21% quadriplegia. The remaining (42, 27.8%) had dyskinetic CP. Sixty-eight (45.0%) participants suffered significant functional impairment (Gross Motor Functional Classification System levels IV-V). Most participants (n=102, 67.5%) required frequent medical follow-up (≥4 times a year). CONCLUSION Optimisation of pre- and perinatal care to prevent and manage prematurity could reduce the burden of CP and their overall healthcare utilisation.

BACKGROUND: To date, there is no study comparing outcomes between post-total knee replacement genu recurvatum and fixed flexion. This study aims to provide data that will help in deciding which side to err on when neutral extension is not achieved. METHODS: A prospective cohort study of primary total knee arthroplasties was performed, which compared the 6-month and 2-year clinical outcomes between fixed flexion and genu recurvatum deformities at 6 months. RESULTS: At 6 months, knees in genu recurvatum did better than knees in fixed flexion deformity in terms of knee flexion. However, at 2 years, knees in fixed flexion deformity did better in terms of knee scores and showed better improvement in the degree of deformity. CONCLUSIONS: We conclude that it is better to err on the side of fixed flexion deformity if neutral alignment cannot be achieved.
Aged ; Arthroplasty, Replacement, Knee/*adverse effects/*statistics & numerical data ; Female ; Humans ; Knee Joint/*physiopathology/*surgery ; Male ; Middle Aged ; Prospective Studies ; Range of Motion, Articular ; Treatment Outcome

Dentin matrix protein 1 (DMP1) is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is considered as an extracellular matrix protein that promotes hydroxyapatite formation and activates intracellular signaling pathway via interacting with αvβ3 integrin. Recent in vitro studies suggested that DMP1 might also act as a transcription factor. In this study, we examined whether full-length DMP1 could function as a transcription factor in the nucleus and regulate odontogenesis in vivo. We first demonstrated that a patient with the DMP1 M1V mutation, which presumably causes a loss of the secretory DMP1 but does not affect the nuclear translocation of DMP1, shows a typical rachitic tooth defect. Furthermore, we generated transgenic mice expressing (NLS)DMP1, in which the endoplasmic reticulum (ER) entry signal sequence of DMP1 was replaced by a nuclear localization signal (NLS) sequence, under the control of a 3.6 kb rat type I collagen promoter plus a 1.6 kb intron 1. We then crossbred the (NLS)DMP1 transgenic mice with Dmp1 null mice to express the (NLS)DMP1 in Dmp1-deficient genetic background. Although immunohistochemistry demonstrated that (NLS)DMP1 was localized in the nuclei of the preodontoblasts and odontoblasts, the histological, morphological and biochemical analyses showed that it failed to rescue the dental and periodontal defects as well as the delayed tooth eruption in Dmp1 null mice. These data suggest that the full-length DMP1 plays no apparent role in the nucleus during odontogenesis.
Animals ; Cell Nucleus ; genetics ; Codon, Initiator ; genetics ; Collagen Type I ; genetics ; Endoplasmic Reticulum ; genetics ; Extracellular Matrix Proteins ; genetics ; Familial Hypophosphatemic Rickets ; genetics ; Gene Targeting ; methods ; Genetic Vectors ; genetics ; Humans ; Introns ; genetics ; Methionine ; genetics ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation ; genetics ; Odontoblasts ; cytology ; Odontogenesis ; genetics ; Periodontal Diseases ; genetics ; Periodontal Ligament ; pathology ; Phosphoproteins ; genetics ; Promoter Regions, Genetic ; genetics ; Tooth Abnormalities ; genetics ; Tooth Eruption ; genetics ; Transcription Factors ; genetics ; Transgenes ; genetics ; Valine ; genetics ; Young Adult

INTRODUCTIONWe aimed to create a definition of neurophobia, and determine its prevalence and educational risk factors amongst medical students and junior doctors in Singapore.

MATERIALS AND METHODSWe surveyed medical students and junior doctors in a general hospital using electronic and paper questionnaires. We asked about knowledge, interest, perceived difficulty in neurology, and confidence in managing neurology patients compared to 7 other internal medicine specialties; quality and quantity of undergraduate and postgraduate neuroscience teaching, clinical neurology exposure, and postgraduate qualifications. Neurophobia was defined as ≤4 composite score of difficulty and confidence with neurology.

RESULTSOne hundred and fifty-eight medical students (63.5%) and 131 junior doctors (73.2%) responded to the questionnaire. Neurophobia prevalence was 47.5% in medical students, highest amongst all medical subspecialties, and 36.6% in junior doctors. Multivariate analysis revealed that for medical students, female gender (OR 3.0, 95% CI, 1.3 to 6.7), low interest (OR 2.5, 95% CI, 1.0 to 6.2), low knowledge (OR 10.1, 95% CI, 4.5 to 22.8), and lack of clinical teaching by a neurologist (OR 2.8, 95% CI, 1.2 to 6.6) independently increased the risk of neurophobia. For doctors, low interest (OR 3.0, 95% CI, 1.3 to 7.0) and low knowledge (OR 2.7, 95% CI, 1.2 to 6.2) independently increased the risk of neurophobia, and female gender was of borderline significance (OR 2.0, 95% CI, 0.9 to 4.6).

CONCLUSIONNeurophobia is highly prevalent amongst Singapore medical students and junior doctors. Low interest and knowledge are independent risk factors shared by both groups; female gender may also be a shared risk factor. The mnemonic GIK (Gender, Interest, Knowledge) identifies the risk factors to mitigate when planning teaching strategies to reduce neurophobia.