Infant sleep interventions with sleep measurements using actigraphy: A systematic review.

AIM: This review investigated the outcomes and methodological quality of infant sleep intervention studies utilizing actigraphy. BACKGROUND: Parents need appropriate support for infant sleep from nurses. There are few methodological reports of actigraphy in infant sleep intervention studies that objectively measure infant sleep in a natural setting. DESIGN: This was a systematic review study. DATA SOURCES: Ovid MEDLINE, Embase, Cochrane, CINAHL and PsycINFO were searched from database establishment to 30 December 2021. REVIEW METHODS: This systematic review utilized the Cochrane Collaboration review guidelines. RESULTS: Eleven sleep intervention studies were reviewed. Three used extinction-based behavioural interventions, and eight included parental education programs. The infant sleep interventions positively affected the sleep outcomes of both infants and parents. Fairly consistent effects were found on infants' number of awakenings and sleep onset latency. However, parental psychosocial outcomes were inconsistent. All studies reported device placement, the algorithm for analysis, the use of a sleep diary and number of days/nights, but external movements affecting infants' sleep records were insufficiently reported. Only two studies had a low risk of bias. CONCLUSIONS: The infant sleep interventions had positive effects on both infants and their parents. Comprehensive methodological considerations are required for more standardized assessments using actigraphy for infant sleep evaluation.

Responsiveness and Minimal Clinically Important Difference of the Canadian Occupational Performance Measure Among Patients With Frozen Shoulder.

IMPORTANCE: Patient-reported outcome measures provide insights into intervention effects on patients. The Canadian Occupational Performance Measure (COPM) emphasizes identifying priorities in daily activity engagement and evaluating an individual's perception of changes over time. OBJECTIVE: To assess the responsiveness of the COPM and the minimal clinically important difference (MCID) among patients with frozen shoulders. DESIGN: Prospective, single-blind, randomized controlled trial. SETTING: Two physical medicine and rehabilitation clinics. PARTICIPANTS: Ninety-four patients with frozen shoulders enrolled in a previous study. OUTCOMES AND MEASURES: Baseline and 3-mo evaluations of the COPM and other measures. Responsiveness was assessed using effect size (ES) and standardized response mean (SRM). The MCID values were determined through a distribution-based approach, which used the 0.5 standard deviation and ES methods, and an anchor-based approach, which used the receiver operating characteristic curve method. RESULTS: The ES and SRM results indicated that the COPM had high responsiveness. The distribution-based MCID values for COPM Performance and COPM Satisfaction were 1.17 and 1.44, respectively. The anchor-based MCID values were 2.5 (area under the curve [AUC] = 0.78, 95% confidence interval [CI] [0.64-0.91]) and 2.1 (AUC = 0.76, 95% CI [0.60-0.91]), respectively. CONCLUSIONS AND RELEVANCE: The findings suggest that the COPM is a responsive outcome measure for patients with frozen shoulder. The established MCID values for the COPM can be valuable for interpreting changes in patient performance and satisfaction, thus aiding clinical interventions and research planning. Plain-Language Summary: This is the first study to review the effectiveness of the Canadian Occupational Performance Measure (COPM) to determine the success of occupational therapy interventions for people with a frozen shoulder. The findings suggest that the COPM is an effective and valuable tool for clients with a frozen shoulder to understand their experiences and treatment priorities and to detect meaningful changes in their performance and satisfaction after an occupational therapy intervention.

Tuberous sclerosis complex is associated with a novel human tauopathy.

Tuberous sclerosis complex (TSC) is a neurogenetic disorder leading to epilepsy, developmental delay, and neurobehavioral dysfunction. The syndrome is caused by pathogenic variants in TSC1 (coding for hamartin) or TSC2 (coding for tuberin). Recently, we reported a progressive frontotemporal dementia-like clinical syndrome in a patient with a mutation in TSC1, but the neuropathological changes seen in adults with TSC with or without dementia have yet to be systematically explored. Here, we examined neuropathological findings in adults with TSC (n = 11) aged 30-58 years and compared them to age-matched patients with epilepsy unrelated to TSC (n = 9) and non-neurological controls (n = 10). In 3 of 11 subjects with TSC, we observed a neurofibrillary tangle-predominant "TSC tauopathy" not seen in epilepsy or non-neurological controls. This tauopathy was observed in the absence of pathological amyloid beta, TDP-43, or alpha-synuclein deposition. The neurofibrillary tangles in TSC tauopathy showed a unique pattern of post-translational modifications, with apparent differences between TSC1 and TSC2 mutation carriers. Tau acetylation (K274, K343) was prominent in both TSC1 and TSC2, whereas tau phosphorylation at a common phospho-epitope (S202) was observed only in TSC2. TSC tauopathy was observed in selected neocortical, limbic, subcortical, and brainstem sites and showed a 3-repeat greater than 4-repeat tau isoform pattern in both TSC1 and TSC2 mutation carriers, but no tangles were immunolabeled with MC1 or p62 antibodies. The findings suggest that individuals with TSC are at risk for a unique tauopathy in mid-life and that tauopathy pathogenesis may involve TSC1, TSC2, and related molecular pathways.

Effectiveness of personalized treatment stage-adjusted digital therapeutics in colorectal cancer: a randomized controlled trial.

BACKGROUND: Colorectal cancer survivors often experience decline in physical performance and poor quality of life after surgery and during adjuvant therapies. In these patients, preserving skeletal muscle mass and high-quality nourishment are essential to reduce postoperative complications and improve quality of life and cancer-specific survival. Digital therapeutics have emerged as an encouraging tool for cancer survivors. However, to the best of our knowledge, randomized clinical trials applying personalized mobile application and smart bands as a supportive tool to several colorectal patients remain to be conducted, intervening immediately after the surgical treatment. METHODS: This study is a prospective, multi-center, single-blinded, two-armed, randomized controlled trial. The study aims to recruit 324 patients from three hospitals. Patients will be randomly allocated to two groups for one year of rehabilitation, starting immediately after the operation: a digital healthcare system rehabilitation (intervention) group and a conventional education-based rehabilitation (control) group. The primary objective of this protocol is to clarify the effect of digital healthcare system rehabilitation on skeletal muscle mass increment in patients with colorectal cancer. The secondary outcomes would be the improvement in quality of life measured by EORTC QLQ C30 and CR29, enhanced physical fitness level measured by grip strength test, 30-sec chair stand test and 2-min walk test, increased physical activity measured by IPAQ-SF, alleviated pain intensity, decreased severity of the LARS, weight, and fat mass. These measurements will be held on enrollment and at 1, 3, 6 and 12 months thereafter. DISCUSSION: This study will compare the effect of personalized treatment stage-adjusted digital health interventions on immediate postoperative rehabilitation with that of conventional education-based rehabilitation in patients with colorectal cancer. This will be the first randomized clinical trial performing immediate postoperative rehabilitation in a large number of patients with colorectal cancer with a tailored digital health intervention, modified according to the treatment phase and patient condition. The study will add foundations for the application of comprehensive digital healthcare programs focusing on individuality in postoperative rehabilitation of patients with cancer. TRIAL REGISTRATION: NCT05046756. Registered on 11 May 2021.

Association of clinical manifestations of secondary lymphedema and lymph node dissection sites in the lower extremities of patients with melanoma.

BACKGROUND: Lymphedema is a chronic, debilitating disease that often requires life-long management. Predicting clinical manifestations and prognosis is crucial in clinical practice because the treatment of lymphedema should be individualized for best clinical outcome. The aim of this study is to explore the location and severity of lymphedema secondary to inguinal and/or iliac lymph node dissection (LND) in patients with melanoma. METHODS: Patients with melanoma who received LND at a single tertiary medical center between 1 January 2010 and 31 September 2022 were retrospectively reviewed. Patient who received inguinal LND only were designate as the inguinal group while those who received both ilioinguinal LND were included in the ilioinguinal group. Volumetric measurement was used to objectify the severity and location of lymphedema. Clinical data was acquired for 12-15 months of follow-up. RESULTS: Among 81 patients, 43 (53%) had developed lymphedema in the lower extremities at an average of 33 days after the surgery. Initially, patients manifested with medial thigh lymphedema in the inguinal group while patients were presented with whole leg lymphedema in the ilioinguinal group. Lower leg volume of the ilioinguinal group was significantly higher than the inguinal group. After more than 12 months of lymphedema treatment, upper leg volume was higher in the ilioinguinal group than the inguinal group (12.7% vs 5.4%, p < 0.05). CONCLUSION: Lymphedema developed in early post-op period. The ilioinguinal group presented with a larger volume of lymphedema in the distal area of the legs. Even after sufficient treatment, predominant lymphedema remained in the proximal leg for the ilioinguinal group. Patients with both inguinal and iliac LND were associated with more severe lymphedema. Based on the dissection sites, the clinical manifestations and prognosis of leg lymphedema can vary widely. Thus, clinicians should consider the dissection site when approaching melanoma patients with lymphedema.

Real-Time Interactive Digital Health Care System for Postoperative Breast Cancer Patients: A Randomized Controlled Trial.

Introduction: Limited range of motion (ROM) of the shoulder occurs commonly after breast cancer surgery, resulting in reduced quality of life and difficulty with activities of daily living. Physical exercise is effective in postoperative breast cancer patients, but no study has assessed the effects of augmented reality (AR)-based telerehabilitation. Therefore, this study aimed to investigate the effect of hospital-home linked rehabilitation therapy using an AR-based digital health care system (UINCARE Home+) in postoperative patients with breast cancer. Methods: This study was a prospective, multicenter, assessor-blinded, randomized controlled trial. Patients who underwent breast cancer surgery were assigned to either the UINCARE Home+ (intervention) group or the brochure-based home rehabilitation (control) group for an 8-week intervention. The study outcomes were the change in ROM of the affected shoulder, pain in the affected shoulder (Numerical Rating Scale [NRS]), functional outcomes (Disabilities of the Arm, Shoulder, and Hand questionnaire [QuickDASH] score), and quality of life (Functional Assessment of Cancer Therapy-Breast [FACT-B] and EuroQoL 5-Dimension 5-Level [EQ-5D-5L] scores), all of which were measured at enrollment and at 4, 8, and 12 weeks thereafter. Results: A total of 100 participants were enrolled in the study (n = 50 in each groups). In both groups, active and passive ROM, NRS, and the QuickDASH, FACT-B, and EQ-5D-5L scores showed significant improvements from baseline to 12 weeks (p < 0.001), but no group differences were detected. Discussion: A home-based exercise program with an AR system improved shoulder dysfunction in breast cancer patients and could be used in conjunction with a traditional hospital-based rehabilitation program. Trial Registration: ClinicalTrials.gov ID: NCT04316156.

Postoperative rehabilitation using a digital healthcare system in patients with total knee arthroplasty: a randomized controlled trial.

INTRODUCTION: Digital healthcare systems based on augmented reality (AR) show promise for postoperative rehabilitation. We compared the effectiveness of AR-based rehabilitation and conventional rehabilitation after total knee arthroplasty (TKA). MATERIALS AND METHODS: We randomly allocated 56 participants to digital healthcare rehabilitation group (DR group) and conventional rehabilitation group (CR group). Participants in the CR group performed brochure-based home exercises for 12 weeks, whereas those in the DR group performed AR-based home exercises that showed each motion on a monitor and provided real-time feedback. The primary outcome was change in 4-m gait speed. The secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, health-related quality of life [assessed by the EuroQoL 5-Dimension 5-Level (EQ5D5L) questionnaire], pain [measured using a numeric rating scale (NRS)], Berg Balance Scale (BBS), range of motion (ROM), and muscle strength. Outcomes were measured at baseline (T0) and 3 (T1), 12 (T2), and 24 (T3) weeks after randomization. RESULTS: There was no significant difference in baseline characteristics of participants between two groups, except age and body mass index. No group difference was observed in 4-m gait speed (0.37 ± 0.19 and 0.42 ± 0.28 for the DR and CR groups, respectively; p = 0.438). The generalized estimating equation model revealed no significant group by time interaction regarding for 4-m gait speed, WOMAC, EQ5D5L, NRS, BBS, ROM, and muscle strength score. All outcomes were significantly improved in both groups (p < 0.001). CONCLUSION: The use of a digital healthcare system based on AR improved the functional outcomes, pain, and quality of life of patients after TKA. AR-based rehabilitation may be useful treatment as an alternative to conventional rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT04513353). Registered on August 9, 2020. http://clinicaltrials.gov/ct2/show/NCT04513353 .

Therapeutic Efficacy of Chinese Patent Medicine Containing Pyrite for Fractures: A Systematic Review and Meta-Analysis.

Background and Objectives: Korean and traditional Chinese medicine state that pyrite is effective for fracture treatment, but supporting clinical data are limited. This systematic review aimed to investigate the therapeutic role of Chinese patent medicine containing pyrite (CPMP) in clinical treatment for fractures. Materials and Methods: Seven electronic databases were searched using the keywords "pyrite", "pyritum", and "zirantong" between inception and December 2022, yielding 29 published clinical studies. Randomized controlled trials that included CPMP were considered eligible regardless of the fracture type. Quality assessment and meta-analysis of the included RCTs were also performed. Results: Most studies showed high heterogeneity (I2 > 50%) and significant results (p < 0.05). Compared to the results of the control group, CPMP was more effective in terms of the primary outcome related to the efficacy rate, including the total effective rate, callus growth rate, bone union, and edema disappearance time (all p < 0.00001) and in terms of secondary outcomes related to pain reduction, namely pain intensity and pain disappearance time, than the control group (both p < 0.01). CPMP was more effective than the control group in terms of erythrocyte sedimentation rate (p < 0.01), hematocrit (p < 0.01), erythrocyte aggregation (p < 0.05), and plasma viscosity (p < 0.05). CPMP did not cause serious side effects, and the incidence of complications was significantly less than that in the control group. Conclusions: CPMP may be a safe and effective alternative treatment for fractures and may be beneficial in preventing postoperative complications, reducing pain, relieving symptoms, and accelerating healing.

Diagnostic Accuracy of Amyloid versus 18 F-Fluorodeoxyglucose Positron Emission Tomography in Autopsy-Confirmed Dementia.

OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of antemortem 11 C-Pittsburgh compound B (PIB) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) versus autopsy diagnosis in a heterogenous sample of patients. METHODS: One hundred one participants underwent PIB and FDG PET during life and neuropathological assessment. PET scans were visually interpreted by 3 raters blinded to clinical information. PIB PET was rated as positive or negative for cortical retention, whereas FDG scans were read as showing an Alzheimer disease (AD) or non-AD pattern. Neuropathological diagnoses were assigned using research criteria. Majority visual reads were compared to intermediate-high AD neuropathological change (ADNC). RESULTS: One hundred one participants were included (mean age = 67.2 years, 41 females, Mini-Mental State Examination = 21.9, PET-to-autopsy interval = 4.4 years). At autopsy, 32 patients showed primary AD, 56 showed non-AD neuropathology (primarily frontotemporal lobar degeneration [FTLD]), and 13 showed mixed AD/FTLD pathology. PIB showed higher sensitivity than FDG for detecting intermediate-high ADNC (96%, 95% confidence interval [CI] = 89-100% vs 80%, 95% CI = 68-92%, p = 0.02), but equivalent specificity (86%, 95% CI = 76-95% vs 84%, 95% CI = 74-93%, p = 0.80). In patients with congruent PIB and FDG reads (77/101), combined sensitivity was 97% (95% CI = 92-100%) and specificity was 98% (95% CI = 93-100%). Nine of 24 patients with incongruent reads were found to have co-occurrence of AD and non-AD pathologies. INTERPRETATION: In our sample enriched for younger onset cognitive impairment, PIB-PET had higher sensitivity than FDG-PET for intermediate-high ADNC, with similar specificity. When both modalities are congruent, sensitivity and specificity approach 100%, whereas mixed pathology should be considered when PIB and FDG are incongruent. ANN NEUROL 2021;89:389-401.

Comorbid neuropathological diagnoses in early versus late-onset Alzheimer's disease.

Co-pathologies play an important role in the expression of the Alzheimer's disease clinical phenotype and may influence treatment efficacy. Early-onset Alzheimer's disease, defined as manifesting before age 65, is viewed as a relatively pure form of Alzheimer's disease with a more homogeneous neuropathological substrate. We sought to compare the frequency of common neuropathological diagnoses in a consecutive autopsy series of 96 patients with early-onset Alzheimer's disease (median age of onset = 55 years, 44 females) and 48 with late-onset Alzheimer's disease (median age of onset = 73 years, 14 females). The UCSF Neurodegenerative Disease Brain Bank database was reviewed to identify patients with a primary pathological diagnosis of Alzheimer's disease. Prevalence and stage of Lewy body disease, limbic age-related TDP-43 encephalopathy (LATE), argyrophilic grain disease, hippocampal sclerosis, cerebral amyloid angiopathy, and vascular brain injury were compared between the two cohorts. We found at least one non-Alzheimer's disease pathological diagnosis in 98% of patients with early-onset Alzheimer's disease (versus 100% of late onset), and the number of comorbid diagnoses per patient was lower in early-onset than in late-onset Alzheimer's disease (median = 2 versus 3, Mann-Whitney Z = 3.00, P = 0.002). Lewy body disease and cerebral amyloid angiopathy were common in both early and late onset Alzheimer's disease (cerebral amyloid angiopathy: 86% versus 79%, Fisher exact P = 0.33; Lewy body disease: 49% versus 42%, P = 0.48, respectively), although amygdala-predominant Lewy body disease was more common in early than late onset Alzheimer's disease (22% versus 6%, P = 0.02). In contrast, LATE (35% versus 8%, P < 0.001), hippocampal sclerosis (15% versus 3%, P = 0.02), argyrophilic grain disease (58% versus 41%, P = 0.052), and vascular brain injury (65% versus 39%, P = 0.004) were more common in late than in early onset Alzheimer's disease, respectively. The number of co-pathologies predicted worse cognitive performance at the time of death on Mini-Mental State Examination [1.4 points/pathology (95% confidence interval, CI -2.5 to -0.2) and Clinical Dementia Rating-Sum of Boxes (1.15 point/pathology, 95% CI 0.45 to 1.84)], across early and late onset cohorts. The effect of sex on the number of co-pathologies was not significant (P = 0.17). Prevalence of at least one APOE ε4 allele was similar across the two cohorts (52% and 54%) and was associated with a greater number of co-pathologies (+0.40, 95% CI 0.01 to 0.79, P = 0.047), independent of age of symptom onset, sex, and disease duration. Females showed higher density of neurofibrillary tangles compared to males, controlling for age of onset, APOE ε4, and disease duration. Our findings suggest that non-Alzheimer's disease pathological diagnoses play an important role in the clinical phenotype of early onset Alzheimer's disease with potentially significant implications for clinical practice and clinical trials design.

High Light Acclimation Mechanisms Deficient in a PsbS-Knockout Arabidopsis Mutant.

The photosystem II PsbS protein of thylakoid membranes is responsible for regulating the energy-dependent, non-photochemical quenching of excess chlorophyll excited states as a short-term mechanism for protection against high light (HL) stress. However, the role of PsbS protein in long-term HL acclimation processes remains poorly understood. Here we investigate the role of PsbS protein during long-term HL acclimation processes in wild-type (WT) and npq4-1 mutants of Arabidopsis which lack the PsbS protein. During long-term HL illumination, photosystem II photochemical efficiency initially dropped, followed by a recovery of electron transport and photochemical quenching (qL) in WT, but not in npq4-1 mutants. In addition, we observed a reduction in light-harvesting antenna size during HL treatment that ceased after HL treatment in WT, but not in npq4-1 mutants. When plants were adapted to HL, more reactive oxygen species (ROS) were accumulated in npq4-1 mutants compared to WT. Gene expression studies indicated that npq4-1 mutants failed to express genes involved in plastoquinone biosynthesis. These results suggest that the PsbS protein regulates recovery processes such as electron transport and qL during long-term HL acclimation by maintaining plastoquinone biosynthetic gene expression and enhancing ROS homeostasis.

Continuous body impedance measurement to detect bladder volume changes during urodynamic study: A prospective study in pediatric patients.

AIMS: To assess the possibility of the body impedance (BI) reflecting bladder volumes (BV) in pediatric patients, the BI signals are measured continuously with the equipment that we have developed and reported previously, during the filling phase of urodynamic study (UDS). METHODS: A total of 30 children (5-12 years old) are included in this prospective study. The equipment uses two dry electrodes embedded inside a strap to collect impedance and electrocardiogram signals. The factors affecting baseline BI and its decreases during UDS have been investigated. RESULTS: The median age is 6.1 years and BI is accurately measured in 27 out of 30 patients (90.0% accuracy). The median value of baseline BI is 1958 Ω. It is higher when they are older, equal to or taller than 125 cm, or non-neurogenic bladder patients. BI decreases as the bladder is filled with saline in 21 patients (77.8%), and remains constant in 6 patients (22.2%). The median age of the Decreased Group is significantly higher than that of Nondecreased Group (p = .036). Height of 125 cm or more is significant in the Decreased Group (p = .020). Heart rates also have been simultaneously measured and revealed a mild decrease during the filling phase. CONCLUSIONS: The baseline BI is affected by the height and age of the children. BI is effectively measured and reflects a change in the BV in older children who are taller than 125 cm, with a small device using a smartphone and a strap.

Detection of early changes in the muscle properties of the pectoralis major in breast cancer patients treated with radiotherapy using a handheld myotonometer.

OBJECTIVE: The primary aim was to investigate serial changes in the mechanical properties of the pectoralis major (PM), upper trapezius (UT), and sternoclavicular mastoid muscle (SCM) in breast cancer patients undergoing radiotherapy (RT) using a hand-held myotonometer. The secondary aims were to determine changes in subjective symptoms and to identify correlation with subjective results. DESIGN: A total of 42 breast cancer patients were enrolled in this longitudinal prospective study. Muscle properties of the PM, UT, and SCM were evaluated before RT, immediately after RT, and 4 months post-RT. Subjective symptom scales of pain and stiffness at rest/stretch of each muscle were evaluated. RESULTS: The PM showed significant side-to-side differences; the affected PM showed increased tone, stiffness, and decreased elasticity compared with the unaffected PM. The affected PM and UT showed significant time-dependent interactions. Stiffness of the affected PM at stretching was significantly higher 4 months post-RT than baseline. Only the tone and elasticity of the affected PM were correlated with subjective symptoms. CONCLUSION: In breast cancer patients who received RT after surgery, increased tone, stiffness, and decreased elasticity were observed in the affected PM compared with the unaffected side, which sustained four months post-RT. Change in muscle properties immediately after RT preceded subjective stiffness, which worsened significantly 4 months post-RT compared with baseline.

Salience Network Atrophy Links Neuron Type-Specific Pathobiology to Loss of Empathy in Frontotemporal Dementia.

Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant of frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs), and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.

Predictive role of lymphoscintigraphy undergoing lymphovenous anastomosis in patients with lower extremity lymphedema: a preliminary study.

BACKGROUND: We investigated whether preoperative lymphoscintigraphy could predict the treatment response of unilateral lymphovenous anastomosis (LVA) in patients with lower extremity lymphedema. MATERIALS AND METHODS: A total of 17 patients undergoing lymphoscintigraphy subsequent to LVA was included. As qualitative lymphoscintigraphic indicators, ilioinguinal lymph node uptake, main lymphatic vessel, collateral vessel, and four types of dermal backflow patterns (absent; distal only; proximal only; whole lower limb) were evaluated. Lymph node uptake ratio, extremity uptake ratio, and injection site clearance ratio were obtained as quantitative lymphoscintigraphic indicators at 1 and 2-h after injection. To evaluate therapy response, the volume difference ratio of the whole lower limb at 3 months (early response) and 1 year (late response) was measured. Volume difference ratios (continuous variable and binary variable with a cut-off value of zero) were compared according to the lymphoscintigraphic variables. RESULTS: The group with whole lower limb dermal backflow had a greater volume change than the other groups (p = 0.047). The group with dermal backflow in the whole lower limb OR only in the distal part had a higher rate of volume reduction than the group with dermal backflow only in the proximal part OR absent (p = 0.050). The 2-h extremity uptake ratio was the only indicator that positively correlated with early and late volume difference ratio (p = 0.016, p = 0.001). The rate of volume decrease at 1 year was high in patients with high 2-h extremity uptake ratio (p = 0.027). As the amount of dermal backflow increases, the postoperative therapeutic effect increases (p = 0.040). CONCLUSIONS: Preoperative lymphoscintigraphy is useful to predict both early and late therapy response in patients with lower extremity lymphedema undergoing LVA. Both dermal backflow pattern and extremity uptake ratio may be predictive lymphoscintigraphic indicators.

Effectiveness of interactive augmented reality-based telerehabilitation in patients with adhesive capsulitis: protocol for a multi-center randomized controlled trial.

BACKGROUND: As the primary treatment for adhesive capsulitis, intensive and accurate home exercise is as important as physical therapy in hospitals. Augmented reality (AR)-based telerehabilitation has been implemented recently in various musculoskeletal conditions to increase patient compliance and enable patients to exercise with the correct posture. The objective of this study is to present a protocol for investigating the additive effect of interactive AR-based telerehabilitation in comparison with the usual care for patients with adhesive capsulitis. METHODS: This study presents the protocol of a prospective, multi-center, single-blinded, two-armed randomized controlled trial (RCT). One hundred patients with stage I or II adhesive capsulitis will be recruited at the physical medicine and rehabilitation clinic. Patients will be randomly divided into two groups with 1:1 allocation. The intervention group will receive 3 months of hospital-based physical therapy in conjunction with home-based telerehabilitation. The control group will receive 3 months of hospital-based physical therapy in conjunction with a home-based exercise described in a brochure provided by the hospital. The primary outcome will be the change in passive range of motion (ROM) of the affected shoulder joint from baseline to 12 weeks after baseline assessment. The secondary outcomes will be active ROM, pain measured with the numeric rating scale, shoulder pain and disability index, 36-Item Short Form Survey, EuroQoL-5D-5L, and Canadian Occupational Performance Measure. DISCUSSION: This will be the first RCT study protocol to investigate the effect of telerehabilitation in patients with adhesive capsulitis. The result of this RCT will determine whether AR-based telerehabilitation is more effective than a brochure-based home exercise program and will provide evidence of the usefulness of "telerehabilitation" using hardware (IoT) and software (monitoring platform) technologies to develop "digital therapeutics" for the future. TRIAL REGISTRATION: This trial was retrospectively registered at the Clinicaltrials.gov website on 20 March 2020, with the identifier NCT04316130 .

Survival and Morbidities in Infants with Birth Weight Less than 500 g: a Nationwide Cohort Study.

BACKGROUND: This study aimed to investigate the survival and morbidities of infants in the Korean Neonatal Network (KNN) with birth weight (BW) < 500 g. METHODS: The demographic and clinical data of 208 live-born infants with a BW < 500 g at a gestational age of ≥ 22 weeks who were treated in the neonatal intensive care units of the KNN between 2013 and 2017 were reviewed. RESULTS: The survival rate of the infants was 28%, with a median gestational age and BW of 243/7 weeks (range, 220/7-336/7) and 440 g (range, 220-499), respectively. Multivariable Cox proportional hazards analysis demonstrated that survival to discharge was associated with longer gestation, higher BW, female sex, singleton gestation, use of any antenatal corticosteroids, and higher Apgar scores at 5 minutes. The overall survival rates were significantly different between the BW categories of < 400 g and 400-499 g. However, there was no significant difference in the incidence of any morbidity between the BW groups. Half of the deaths of infants with BW < 500 g occurred within a week of life, mainly due to cardiopulmonary and neurologic causes. The major causes of death in infants after 1 week of age were infection and gastrointestinal disease. Among the surviving infants, 79% had moderate to severe bronchopulmonary dysplasia, 21% underwent surgical ligation of patent ductus arteriosus, 12% had severe intraventricular hemorrhage (grade III-IV), 38% had sepsis, 9% had necrotizing enterocolitis (stage ≥ 2), and 47% underwent laser treatment for retinopathy of prematurity. The median length of hospital stay was 132 days (range, 69-291), and 53% required assistive devices at discharge. CONCLUSION: Despite recent advances in neonatal intensive care, the survival and morbidity rates of infants with BW < 500 g need further improvement.

Anticancer Effects of Ursi Fel Extract and Its Active Compound, Ursodeoxycholic Acid, in FRO Anaplastic Thyroid Cancer Cells.

Anaplastic thyroid cancer (ATC) is one of the most fatal human malignancies. Ursi Fel (UF) is the bile of a brown bear that has been traditionally used for heat clearance and toxin relief in Korean and Chinese medicines. In this study, we determined the anticancer effects of a UF extract and its active compound, ursodeoxycholic acid (UDCA), in FRO human ATC cells. FRO cells were treated with UF extract and UDCA at different concentrations for various durations. Cell viability was measured using an MTT assay. Cell apoptosis was investigated by flow cytometric analysis following Annexin V and propidium iodide (PI) staining, and Hoechst staining was used to observe nuclear fragmentation. The expression of pro-apoptotic (Bax, caspase-3, cytochrome c, and PARP), anti-apoptotic (Bcl-2), and angiogenetic (TGF-ß, VEGF, N-cadherin, and sirtuin-1) proteins and the phosphorylation of Akt and mechanistic target of rapamycin (mTOR) were determined by western blot analysis. Treatment with UF extract at 10, 25, and 50 µg/mL and UDCA at 25, 50, and 100 µM/mL significantly inhibited the growth of FRO cells in a dose-dependent manner. Flow cytometry and Hoechst staining revealed an increase in the apoptosis of FRO cells mediated by UF extract and UDCA in a dose-dependent manner. UF extract (25 and 50 µg) and UDCA (50 and 100 µM) significantly increased the expression of Bax, caspase-3, cytochrome c, and PARP and inhibited the expression of Bcl-2, TGF-ß, VEGF, N-cadherin, and sirtuin-1 in FRO cells. Furthermore, UF extract and UDCA treatment stimulated Akt phosphorylation and inhibited mTOR phosphorylation in these cells. These results indicate that UF extract and UDCA exert anticancer properties in FRO cells by inducing apoptosis and inhibiting angiogenesis via regulating the Akt/mTOR signaling pathway.

Evidence of corticofugal tau spreading in patients with frontotemporal dementia.

Common neurodegenerative diseases feature progressive accumulation of disease-specific protein aggregates in selectively vulnerable brain regions. Increasing experimental evidence suggests that misfolded disease proteins exhibit prion-like properties, including the ability to seed corruptive templating and self-propagation along axons. Direct evidence for transneuronal spread in patients, however, remains limited. To test predictions made by the transneuronal spread hypothesis in human tissues, we asked whether tau deposition within axons of the corticospinal and corticopontine pathways can be predicted based on clinical syndromes and cortical atrophy patterns seen in frontotemporal lobar degeneration (FTLD). Sixteen patients with Pick's disease, 21 with corticobasal degeneration, and 3 with FTLD-MAPT were included, spanning a range of clinical syndromes across the frontotemporal dementia (FTD) spectrum. Cortical involvement was measured using a neurodegeneration score, a tau score, and a composite score based on semiquantitative ratings and complemented by an MRI-based cortical atrophy W-map based on antemortem imaging. Midbrain cerebral peduncle and pontine base descending fibers were divided into three subregions, representing prefrontopontine, corticospinal, and parieto-temporo-occipital fiber pathways. Tau area fraction was calculated in each subregion and related to clinical syndrome and cortical measures. Within each clinical syndrome, there were predicted relationships between cortical atrophy patterns and axonal tau deposition in midbrain cerebral peduncle and pontine base. Between syndromes, contrasting and predictable patterns of brainstem axonal tau deposition emerged, with, for example, greater tau in prefrontopontine fibers in behavioral variant FTD and in corticospinal fibers in corticobasal syndrome. Finally, semiquantitative and quantitative cortical degeneration scores predicted brainstem axonal tau deposition based on anatomical principles. Taken together, these findings provide important human evidence in support of axonal tau spreading in patients with specific forms of tau-related neurodegeneration.

Neuropathological correlates of structural and functional imaging biomarkers in 4-repeat tauopathies.

Neurodegenerative dementia syndromes are characterized by spreading of pathological protein deposition along syndrome-specific neural networks. Structural and functional MRI measures can assess the integrity of these networks and have been proposed as biomarkers of disease progression for clinical trials. The relationship between in vivo imaging measures and pathological features, at the single subject level, remains largely unknown. Patient-specific maps of atrophy and seed-based intrinsic connectivity disruption, as compared to normal controls, were obtained for 27 patients subsequently diagnosed with progressive supranuclear palsy (n = 16, seven males, age at death 68.9 ± 6.0 years, imaging-to-pathology interval = 670.2 ± 425.1 days) or corticobasal degeneration (n = 11, two males, age at death 66.7 ± 5.4 years, imaging-to-pathology interval = 696.2 ± 482.2 days). A linear mixed effect model with crossed random effects was used to test regional and single-subject level associations between post-mortem regional measures of neurodegeneration and tau inclusion burden, on the one hand, and regional volume loss and seed-based intrinsic connectivity reduction, on the other. A significant association was found between tau inclusion burden and in vivo volume loss, at the regional level and independent of neurodegeneration severity, in both progressive supranuclear palsy [n = 340 regions; beta 0.036; 95% confidence interval (CI): 0.001, 0.072; P = 0.046] and corticobasal degeneration (n = 215 regions; beta 0.044; 95% CI: 0.009, 0.079; P = 0.013). We also found a significant association between post-mortem neurodegeneration and in vivo volume loss in both progressive supranuclear palsy (n = 340 regions; beta 0.155; 95% CI: 0.061, 0.248; P = 0.001) and corticobasal degeneration (n = 215 regions; beta 0.277; 95% CI: 0.104, 0.450; P = 0.002). We found a significant association between regional neurodegeneration and intrinsic connectivity dysfunction in corticobasal degeneration (n = 215 regions; beta 0.074; 95% CI: 0.005, 0.143; P = 0.035), but no other associations between post-mortem measures of tauopathy and intrinsic connectivity dysfunction reached statistical significance. Our data suggest that in vivo structural imaging measures reflect independent contributions from neurodegeneration and tau burden in progressive supranuclear palsy and corticobasal degeneration. Seed-based measures of intrinsic connectivity dysfunction showed less reliable predictive value when used as in vivo biomarkers of tauopathy. The findings provide important guidance for the use of imaging biomarkers as indirect in vivo assays of microscopic pathology.