Establishing an optimal diagnostic criterion for respiratory sarcopenia using peak expiratory flow rate.

BACKGROUND: The skeletal muscle changes as aging progresses, causing sarcopenia in the older adult population, which affects the respiratory muscles' mass, strength, and function. The optimal cut-off point of peak expiratory flow rate (PEFR) for respiratory sarcopenia (RS) diagnosis in accordance with sarcopenia identification is needed. AIM: To establish an optimal cut-off point of PEFR for RS diagnosis in community-dwelling Asian older women. METHODS: Sarcopenia diagnostic indicators were evaluated according to the Asian Working Group for Sarcopenia 2019 (AWGS) criteria. The respiratory parameters composed of respiratory muscle strength and respiratory function were evaluated by assessing maximal inspiratory pressure (MIP), percent predicted forced vital capacity (Pred FVC), and PEFR. RESULTS: A total of 325 community-dwelling older women were included in this study. PEFR was negatively associated with RS (OR: 0.440; 95% CI: 0.344-0.564). The area under the curve (AUC) of PEFR was 0.772 (p < 0.001). The optimal cut-off point of PEFR for RS diagnosis was 3.4 l/s (sensitivity, 63.8%; specificity, 77.3%). Significant differences were found between the robust, possible sarcopenia, sarcopenia, and RS groups in terms of both sarcopenia diagnostic indicators and respiratory parameters (p < 0.05). CONCLUSIONS: The cut-off point of PEFR can be used as a reasonable standard for RS diagnosis. This study finding can serve as a cornerstone for developing concrete criteria of RS in older women, supporting clinical judgment, which is crucial for providing appropriate treatment through accurate diagnosis.

Novel rAAV vector mediated intrathecal HGF delivery has an impact on neuroimmune modulation in the ALS motor cortex with TDP-43 pathology.

Recombinant adeno-associated virus (rAAV)-based gene therapies offer an immense opportunity for rare diseases, such as amyotrophic lateral sclerosis (ALS), which is defined by the loss of the upper and the lower motor neurons. Here, we describe generation, characterization, and utilization of a novel vector system, which enables expression of the active form of hepatocyte growth factor (HGF) under EF-1α promoter with bovine growth hormone (bGH) poly(A) sequence and is effective with intrathecal injections. HGF's role in promoting motor neuron survival had been vastly reported. Therefore, we investigated whether intrathecal delivery of HGF would have an impact on one of the most common pathologies of ALS: the TDP-43 pathology. Increased astrogliosis, microgliosis and progressive upper motor neuron loss are important consequences of ALS in the motor cortex with TDP-43 pathology. We find that cortex can be modulated via intrathecal injection, and that expression of HGF reduces astrogliosis, microgliosis in the motor cortex, and help restore ongoing UMN degeneration. Our findings not only introduce a novel viral vector for the treatment of ALS, but also demonstrate modulation of motor cortex by intrathecal viral delivery, and that HGF treatment is effective in reducing astrogliosis and microgliosis in the motor cortex of ALS with TDP-43 pathology.

Effects of an urban forest healing program on cancer-related fatigue in cancer survivors.

PURPOSE: This study aimed to examine the effects of an eight-session structured urban forest healing program for cancer survivors with fatigue. BACKGROUND: Cancer-related fatigue (CRF) is a complex and multifactorial common symptom among cancer survivors that limits quality of life (QoL). Although health benefits of forest healing on physiological, physical, and psychological aspect as well as on the immune system have been reported in many studies, there is limited evidence on the efficacy of specialized forest program for cancer survivors. METHOD: A single-blinded, pre-test and post-test control group clinical trial was conducted with -75 cancer survivors assigned to either the forest healing group or the control group. The intervention was an eight-session structured urban forest program provided at two urban forests with easy accessibility. Each session consists of three or four major activities based on six forest healing elements such as landscape, phytoncides, anions, sounds, sunlight, and oxygen. Complete data of the treatment-adherent sample (≥ 6 sessions) was used to examine whether sociodemographic, clinical, physiological (respiratory function, muscle strength, balance, 6-min walking test) and psychological (distress, mood state, sleep quality, QoL) characteristics at baseline moderated the intervention effect on fatigue severity at 9 weeks. RESULTS: Significant time-group interactions were observed muscle strength, balance, 6-min walking test, distress, fatigue, moods, and QoL. The mean difference in fatigue between pre- and post-forest healing program was 9.1 (95% CI 6.2 to 11.9), 11.9 (95% CI 7.6 to 16.1) in moods, and -93.9 (95% CI -123.9 to -64.0) in QoL, showing significant improvements in forest healing group, but no significant improvements in the control group. CONCLUSION: This study suggests that a forest healing program positively impacts the lives of cancer survivors, by addressing both physical and psychological challenges associated with CRF. TRIAL REGISTRATION NUMBER: KCT0008447 (Date of registration: May 19, 2023).

Erratum: Correction of Authors in the Article "Relevance Index Regional Variation by Each Disease and Its Essential Medical Field: A Retrospective Data Analysis From 2016-2020 in Korea".

This corrects the article on p. e130 in vol. 38, PMID: 37096313.

Relevance Index Regional Variation by Each Disease and Its Essential Medical Field: A Retrospective Data Analysis From 2016-2020 in Korea.

BACKGROUND: To precisely build a healthcare delivery system at regional levels, local patients' healthcare service utilization patterns must be examined. Hence, this study utilized trend analysis of the relevance index of each disease of each essential medical service field at the municipal and provincial levels. METHODS: This study analyzed customized databases released by the National Health Insurance Service from 2016-2020. Diseases defined in the Korean National Burden of Disease (KNBD) study were categorized into the following essential medical service fields: trauma care, cardiocerebrovascular, maternal and neonatal, mental health, infection, cancer, older adults' care and rehabilitation, and others. Relevance index, the percentage of medical service utilization in a region by the residents of that region relative to their total medical service utilization, was examined by region (17 municipal and provincial regions) and disease area. The relevance index was determined based on the number of patients and the total out-of-pocket expenses. RESULT: Eight of the 17 regions showed over a 90.0% relevance index in the infection area. In the cancer area, 14 regions (not including Seoul, Daegu, and Busan) had a relevance index lower than 75.0%. Throughout the analysis period (2016-2020), there were no significant variations in the relevance index. Diseases such as bone and connective tissue cancer (39.0%), neural tube defects (16.7%), and autism (57.1%) had low relevance index in the essential medical service fields. In all 17 regions, the relevance index of inpatients was lower than that of outpatients, and that for out-of-pocket expenses was lower than that based on the number of patients. CONCLUSION: The relevance index of major diseases of each essential medical service field calculated in this study can provide good indicators for monitoring the level of an independent regional healthcare delivery system.

CMOS Detector Staggered Array Module for Sub-Terahertz Imaging on Conveyor Belt System.

A complementary metal-oxide-semiconductor (CMOS) detector array is proposed to improve the sub-terahertz imaging resolution for objects in the conveyor belt system. The image resolution is limited to the implemented configuration, such as the wide spacing in the detector array, the high conveyor belt speed, and the slow response of the signal conditioning block. The proposed array can improve the image resolution in the direction perpendicular to the movement of the belt, which is determined by the size and interval of the detector pixel, by configuring the array into two replaceable columns located at the misaligned horizontal positions. Replaceable detector unit pixels are individually attached to the motherboard after measuring and evaluating the detection performance to construct the proposed array. The intensities of 32 detector pixels placed under the conveyor belt with a width of 160 mm were initially calibrated in every image, including the beam pattern of 0.2 THz signals generated from the gyrotron. The image resolution of the perpendicular direction obtained from the proposed array was measured to be approximately 5 mm at a conveyor belt speed of 16 mm/s, demonstrating a 200% improvement in resolution compared to the conventional linear array under the same conditions.

Effectiveness of multicomponent home-based rehabilitation in older patients after hip fracture surgery: A systematic review and meta-analysis.

BACKGROUND: Hip fracture is a major burden on health care systems worldwide and requires hospitalisation for a long period. OBJECTIVE: The aim was to evaluate the effectiveness of multicomponent home-based rehabilitation compared with different control interventions (in-hospital rehabilitation, active control or usual care) in older patients after hip fracture surgery. DESIGN: Systematic review and meta-analysis of randomised controlled studies. DATA SOURCES: We searched three electronic databases, including Ovid-MEDLINE, Ovid-Embase, CINAHL and the Cochrane Library for relevant articles up to March 2020. REVIEW METHODS: Two investigators independently extracted data and assessed study quality using the risk of bias. Data were analysed using Review Manager 5.3. The current review employs the PRISMA procedure. RESULTS: Out of 2996 studies, 22 articles were relevant for this review and meta-analysis. Among them, five compared the multicomponent home-based rehabilitation with in-hospital rehabilitation, one compared it with active control, six with usual care and ten compared the home exercise only with usual care. There was no significant difference in activities of daily living (ADL) between multicomponent home-based rehabilitation and in-hospital rehabilitation, while multicomponent home-based rehabilitation significantly increased in ADL when compared to usual care. Home exercises also had significant effects on ADL, quality of life(QoL), balance, gait and muscle strength of the knee extensor compared with usual care (p < .05). CONCLUSIONS: Multicomponent home-based rehabilitation is comparable to in-hospital rehabilitation regarding improvements in muscle strength, gait speed, balance, ADL and QoL. RELEVANT TO CLINICAL PRACTICE: Multicomponent home-based rehabilitation is comparable to in-hospital rehabilitation regarding improvements in muscle strength, gait speed, balance, ADL and QoL. Also, high adherence to home exercise may be associated with better clinical outcomes. Therefore, more compliance-oriented multicomponent home-based rehabilitation programmes for older patients after hip fracture must be developed by health care professionals, including physical therapist, to ensure optimum home-based rehabilitation.

A participatory practice study for the improvement of sub-regional health vulnerabilities: a qualitative study.

BACKGROUND: This study aimed to explore the experiences of the residents of Samho-dong with the health environment in the local community, and their in-depth opinions on health promotion using a photovoice methodology. Alternatives to improve health among the residents of Samho-dong were also discussed with the local residents, with the aim of translating suggestions from the discussion into practice. METHODS: A total of 195 photographs taken by the 15 participants over the course of 7 weeks were collected, along with 96 photovoice activity logs and transcription data from 5 rounds of focus group discussions. The photovoice activity logs consisted of the photographer's name, the dates photos were taken, and a series of responses to the following SHOWeD questions: "What do you SEE here?", "What is really HAPPENING?", "How does this situation or scenario affect OUR lives/health?", "WHY does this problem or strength Exist?", "What can we DO about it?". Direct content analysis was used for analysis. RESULTS: The analysis yielded a total of 247 semantic units, which were categorized into the themes, "the good, but insufficiency, living environment in Samho-dong," "the health environment in Samho-dong needs improvement," "small efforts to improve Samho-dong," and "points of improvement for a better Samho-dong". Samho-dong was found to have a poorer walking and transportation infrastructure than other regions, even though it was a town with a large elderly population. The dark streets in the residential complex made participants hesitate to engage in afternoon activities, and the insufficient traffic environment made it difficult to live a natural daily life by solving food, clothing, and shelter. Participants have made various attempts to solve areas that need improvement in the Samho-dong, which has led to actual improvement. It was analyzed that in order to make Samho-dong better, it was necessary to improve the perception of residents in Samho-dong and cooperate with the local community. CONCLUSIONS: This study was significant in that it enabled the in-depth exploration and identification of areas of improvement from the participants' perception of their health environment, considering that as residents, they are the direct stakeholders of the community health environment.

Concurrent-Mode CMOS Detector IC for Sub-Terahertz Imaging System.

A CMOS detector with a concurrent mode for high-quality images in the sub-terahertz region has been proposed. The detector improves output-signal coupling characteristics at the output node. A cross-coupling capacitor is added to isolate the DC bias between the drain and gate. The detector is designed to combine a 180° phase shift based on common source operation and an in-phase output signal based on the drain input. The circuit layout and phase shift occurring in the cross-coupled capacitor during phase coupling are verified using an EM simulation. The detector is fabricated using the TSMC 0.25-µm mixed-signal 1-poly 5-metal layer CMOS process, where the size, including the pad, is 1.13 mm × 0.74 mm. The detector IC comprises a folded dipole antenna, the proposed detector, a preamplifier, and a voltage buffer. Measurement results using a 200-GHz gyrotron source demonstrate that the proposed detector voltage responsivity is 14.13 MV/W with a noise-equivalent power of 34.42 pW/√Hz. The high detection performance helps resolve the 2-mm line width. The proposed detector exhibits a signal-to-noise ratio of 49 dB with regard to the THz imaging performance, which is 9 dB higher than that of the previous CMOS detector core circuits with gate-drain capacitors.

Isolation and Characterization of Urinary Extracellular Vesicles from Healthy Donors and Patients with Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) is the most commonly diagnosed malignancy among men in developed countries. The five-year survival rate for men diagnosed with early-stage PCa is approximately 100%, while it is less than 30% for castration-resistant PCa (CRPC). Currently, the detection of prostate-specific antigens as biomarkers for the prognosis of CRPC is criticized because of its low accuracy, high invasiveness, and high false-positive rate. Therefore, it is important to identify new biomarkers for prediction of CRPC progression. Extracellular vesicles (EVs) derived from tumors have been highlighted as potential markers for cancer diagnosis and prognosis. Specifically, urinary EVs directly reflect changes in the pathophysiological conditions of the urogenital system because it is exposed to prostatic secretions. Thus, detecting biomarkers in urinary EVs provides a promising approach for performing an accurate and non-invasive liquid biopsy for CPRC. In this study, we effectively isolated urinary EVs with low protein impurities using size-exclusion chromatography combined with ultrafiltration. After EV isolation and characterization, we evaluated the miRNAs in urinary EVs from healthy donors and patients with CRPC. The results indicated that miRNAs (miR-21-5p, miR-574-3p, and miR-6880-5p) could be used as potential biomarkers for the prognosis of CRPC. This analysis of urinary EVs contributes to the fast and convenient prognosis of diseases, including CRPC, in the clinical setting.

FKBP8 LIRL-dependent mitochondrial fragmentation facilitates mitophagy under stress conditions.

Mitochondrial quality control maintains mitochondrial function by regulating mitochondrial dynamics and mitophagy. Despite the identification of mitochondrial quality control factors, little is known about the crucial regulators coordinating both mitochondrial fission and mitophagy. Through a cell-based functional screening assay, FK506 binding protein 8 (FKBP8) was identified to target microtubule-associated protein 1 light chain 3 (LC3) to the mitochondria and to change mitochondrial morphology. Microscopy analysis revealed that the formation of tubular and enlarged mitochondria was observed in FKBP8 knockdown HeLa cells and the cortex of Fkbp8 heterozygote-knockout mouse embryos. Under iron depletion-induced stress, FKBP8 was recruited to the site of mitochondrial division through budding and colocalized with LC3. FKBP8 was also found to be required for mitochondrial fragmentation and mitophagy under hypoxic stress. Conversely, FKBP8 overexpression induced mitochondrial fragmentation in HeLa cells, human fibroblasts and mouse embryo fibroblasts (MEFs), and this fragmentation occurred in Drp1 knockout MEF cells, FIP200 knockout HeLa cells and BNIP3/NIX double knockout HeLa cells, but not in Opa1 knockout MEFs. Interestingly, we found an LIR motif-like sequence (LIRL), as well as an LIR motif, at the N-terminus of FKBP8 and LIRL was essential for both inducing mitochondrial fragmentation and binding of FKBP8 to OPA1. Together, we suggest that FKBP8 plays an essential role in mitochondrial fragmentation through LIRL during mitophagy and this activity of FKBP8 together with LIR is required for mitophagy under stress conditions.

Neuromuscular Control of Ankle-stabilizing Muscles-specific Effects of Sex and Menstrual Cycle.

The purpose of this study was to examine the differences in neuromuscular control and mechanical properties of the ankle-stabilizing muscles between men and women, and during different phases of menstrual cycle in women. Fifteen women with regular menstrual cycles and 17 male counterparts were included in this study. Electromyographic signals were recorded from the peroneus longus (PL) and tibialis anterior (TA) muscles while performing three balance tasks. Muscle tone, stiffness, and elasticity of muscles were measured using a MyotonPRO in the resting position. Outcomes were measured twice (ovulation and early follicular phases) for women, while measurements were acquired only once for men. Significantly higher tibialis anterior-peroneus longus co-contraction (TA/PL ratio) was observed in all balance tasks in women than in men (p< 0.05); however, significant differences between phases of the menstrual cycle were noted only in the 2 most difficult tasks (p< 0.05). A similar pattern was observed in the postural sway. These results highlight the importance of sex-specific hormonal effects on neuromuscular control and mechanical properties, and as well as the differences during phases of the menstrual cycle. These insights assume significance in the context of developing neuromuscular strategies for the purpose of preventing lower extremity injuries during sports activities.

Viburnum stellato-tomentosum Extract Suppresses Obesity and Hyperglycemia through Regulation of Lipid Metabolism in High-Fat Diet-Fed Mice.

The potential biological activities of Viburnum stellato-tomentosum (VS), a plant mainly found in Costa Rica, have yet to be reported. Supplementation of VS extract for 17 weeks significantly decreased body weight gain, fat weight, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride levels in high-fat diet (HFD)-fed C57BL/6J mice. The molecular mechanisms underlying the anti-obesity and glucose-lowering effects of VS extract were investigated. VS extract suppressed adipocyte hypertrophy by regulating lipogenesis-related CCAAT/enhancer-binding protein α (C/EBPα) and insulin sensitivity-related peroxisome proliferator-activated receptor γ (Pparg) expression in adipose tissue (AT) and hepatic steatosis by inhibiting C/EBPα and lipid transport-related fatty acid binding protein 4 (FABP4) expression. VS extract enhanced muscular fatty acid ß-oxidation-related AMP-activated protein kinase (AMPK) and PPARα expression with increasing Pparg levels. Furthermore, VS extract contained a much higher content of amentoflavone (AMF) (29.4 mg/g extract) compared to that in other Viburnum species. AMF administration decreased Cebpa and Fabp4 levels in the AT and liver, as well as improved insulin signaling-related insulin receptor substrate 1 (Irs1) and glucose transporter 1 (Glut1) levels in the muscle of HFD-fed mice. This study elucidated the in vivo molecular mechanisms of AMF for the first time. Therefore, VS extract effectively diminished obesity and hyperglycemia by suppressing C/EBPα-mediated lipogenesis in the AT and liver, enhancing PPARα-mediated fatty acid ß-oxidation in muscle, and PPARγ-mediated insulin sensitivity in AT and muscle.

Development of a novel denture care agent with highly active enzyme, arazyme.

BACKGROUND: The importance of efficient denture deposit removal and oral hygiene has been further underscored by the continuous increase of denture wearers. Denture hygiene management has also become an important aspect associated with denture-induced stomatitis. This study aims to evaluate the denture cleaning effect of arazyme, the metalloprotease produced from the Serratia proteamaculans HY-3. We performed growth inhibition tests against oral opportunistic pathogens to be used as a potential oral health care agent. METHODS: The proteolytic activities of arazyme was evaluated over broad ranges of temperature, pH, and denture components compared to those of subtilisin in commercially available denture cleansers. The washing effects of arazyme were also measured by using homogeneously soiled EMPA 105 cottons. To investigate the denture cleaning capability of arazyme, artificially contaminated dentures were treated with arazyme, subtilisin (Everlase 6.0T), and Polident®, respectively. The growth kinetics of Candida albicans, Enterococcus faecalis, Staphylococcus epidermis, and Streptococcus mutans were evaluated in the presence of different concentrations of arazyme to estimate the prevention effects of arazyme against major oral opportunistic pathogens. RESULTS: Arazyme showed strong proteolytic activities over wide temperature and pH ranges compared with the serine protease of the subtilisin family. Arazyme demonstrated efficient removal and decomposition of artificially contaminated dentures and showed explicit washing effects against soiled cottons. Moreover arazyme inhibited the growth of oral opportunistic pathogens, including C. albicans, E. faecalis, S. epidermis, and S. mutans, with more than 80% inhibition against C. albicans, the major cause of denture stomatitis, with 250 mg/mL arazyme. CONCLUSIONS: Arazyme shows promise as a biological oral health care agent with effective cleaning and antimicrobial activities and is a potential source for developing novel denture care agents.

Correlation between the Korean Version of the Trunk Control Measurement Scale and the Selective Control Assessment of the Lower Extremity Scores in Children with Cerebral Palsy.

Background and Objectives: The purpose of this study was to investigate the correlation between the Korean version of the trunk control measurement scale (K-TCMS) and the selective control assessment of the lower extremity (SCALE). Through this, we tried to find out the effect of proximal stabilization on distal motor development. Materials and Methods: Fifty-one children with gross motor function classification system level I-III, diagnosed with cerebral palsy (CP), were studied. The K-TCMS was used to evaluate the body control ability of the children. SCALE was used to quantify selective voluntary motor control (SVMC). Results: Analysis of SCALE and K-TCMS showed a significant positive correlation in all items. Multiple regression analysis showed that the SCALE score decreased as age increased, and that it increased as the static sitting balance ability score and the dynamic sitting balance ability score of the K-TCMS increased significantly (p < 0.05). Conclusions: In children with cerebral palsy, there was a close correlation between trunk control and selective voluntary motor control of the lower extremities. Therefore, when trying to improve the lower extremity function of a child with cerebral palsy, a trunk control intervention should be considered.

Similarities in Clinical and Psychosocial Characteristics of Functional Diarrhea and Irritable Bowel Syndrome With Diarrhea.

BACKGROUND & AIMS: There have been few published studies of clinical and psychological characteristics of patients with functional diarrhea (FDr). We studied the clinical and psychological characteristics of patients with FDr presenting to a tertiary care clinic, and compared symptom profiles of FDr with those of IBS-diarrhea (IBS-D). METHODS: Consecutive patients with a diagnosis of FDr (n = 48) or IBS-D (n = 49), per Rome IV criteria, completed a detailed symptom survey from October 2017 through July 2018. Abdominal pain and diarrhea severity were assessed using patient-reported outcomes measurement information system (PROMIS) questionnaires. Patients with anxiety, depression, or sleep disturbances were identified based on PROMIS T-score of 60 or more. Mean and proportions were compared using the Student t test and chi-square analyses, respectively. RESULTS: A significantly lower proportion of patients with FDr reported abdominal pain (77.1%) than patients with IBS-D (100%, P < .001). The proportion of patients reporting abdominal bloating and level of severity did not differ significantly between groups. Proportions of bowel movements with diarrhea did not differ significantly between groups (P = .54), but the mean diarrhea PROMIS T-score was significantly higher among patients with IBS-D (P = .03). This difference resulted from the significantly higher levels of fecal urgency-related distress reported by patients with IBS-D (P = .007). Proportions of patients with anxiety, depression, or sleep disturbance, and their severities, did not differ significantly between groups. CONCLUSIONS: In an analysis of about 100 patients with FDr or IBS-D, we found overlap in gastrointestinal and psychosomatic symptoms. These 2 entities appear to be a continuum.

Greater Muscle Stiffness during Contraction at Menstruation as Measured by Shear-Wave Elastography.

It is important to measure mechanical properties of muscle, since muscle stiffness is an important component of stabilizing or controlling joint stability. The levels of sex hormones especially estrogen vary over the phase of the menstrual cycle and impact the mechanical properties of soft tissue such as muscle, tendon, and ligaments due to the presence of 17-ß estradiol receptor in human connective tissues. Recently, shear-wave elastography (SWE), based on ultrasound imaging, has been used as an accurate technique for visualizing and assessing tissue stiffness. The purpose of this study was to compare the muscle stiffness at rest and during contraction condition between the early follicular phase (menstruation) and ovulation in young women, measured using SWE. Thirty-seven young women with regular menstrual cycles completed this study throughout one full menstrual cycle. Stiffness of lower limb muscles such as the rectus femoris, biceps femoris, tibialis anterior, and medial gastrocnemius was measured at resting and during contraction conditions using SWE during menstruation and ovulation. All muscles showed significantly greater stiffness during the menstruation than ovulation when muscles were actively contracted (P < 0.05), whereas no significant differences in muscle stiffness at rest were noted across phase of the menstrual cycle. These significant findings suggest that muscular factors are changed with estradiol fluctuations; muscles are less stiff during ovulation where the levels of estradiol peak when muscles in a contraction condition. As muscle stiffness is an important part of joint stability, these differences should be recognized to prevent the risk of musculoskeletal injuries.

Gender-specific differences of normative values of pelvic floor muscle function in healthy adults population: an observational analytical study.

Females and males differ significantly in gross anatomy and physiology of the pelvic floor muscle, and these differences are commonly discussed in the scientific literature. However, less attention is dedicated to investigating the normative values of pelvic floor muscle (PFM) function between females and males. Our study aims to describe the normal reference values of PFM function in females and males of a healthy adult population using transabdominal ultrasound (TAUS). A total of 200 healthy adults, including 71 males and 129 females consented to participate in this study. Bladder base displacement was measured using a sagittal curved linear array 2-5 MHz transducer over the suprapubic region. The amount of bladder base movement on ultrasound was measured in all subjects from freeze frame ultrasound images and considered as an indicator of PFM function. The average age of subjects was (26.1 ± 2.6 years), (24.4 ± 3.7 BMI). Statistical analysis revealed a significant difference in transabdominal ultrasound measurement for PFM function (p = .00000). The bladder base displacement was significantly greater in males compared to females (0.65 ± 0.42 vs. 0.38 ± 0.35, p <.001, 95% CI:0.16-0.38). The present study provides evidence of a gender-related PFM functional differences creating a baseline for the clinic to establish the normal percentile values of PFM function.

TOM1 Regulates Neuronal Accumulation of Amyloid-ß Oligomers by FcγRIIb2 Variant in Alzheimer's Disease.

Emerging evidences suggest that intraneuronal Aß correlates with the onset of Alzheimer's disease (AD) and highly contributes to neurodegeneration. However, critical mediator responsible for Aß uptake in AD pathology needs to be clarified. Here, we report that FcγRIIb2, a variant of Fcγ-receptor IIb (FcγRIIb), functions in neuronal uptake of pathogenic Aß. Cellular accumulation of oligomeric Aß1-42, not monomeric Aß1-42 or oligomeric Aß1-40, was blocked by Fcgr2b knock-out in neurons and partially in astrocytes. Aß1-42 internalization was FcγRIIb2 di-leucine motif-dependent and attenuated by TOM1, a FcγRIIb2-binding protein that repressed the receptor recycling. TOM1 expression was downregulated in the hippocampus of male 3xTg-AD mice and AD patients, and regulated by miR-126-3p in neuronal cells after exposure to Aß1-42 In addition, memory impairments in male 3xTg-AD mice were rescued by the lentiviral administration of TOM1 gene. Augmented Aß uptake into lysosome caused its accumulation in cytoplasm and mitochondria. Moreover, neuronal accumulation of Aß in both sexes of 3xTg-AD mice and memory deficits in male 3xTg-AD mice were ameliorated by forebrain-specific expression of Aß-uptake-defective Fcgr2b mutant. Our findings suggest that FcγRIIb2 is essential for neuropathic uptake of Aß in AD.SIGNIFICANCE STATEMENT Accumulating evidences suggest that intraneuronal Aß is found in the early step of AD brain and is implicated in the pathogenesis of AD. However, the critical mediator involved in these processes is uncertain. Here, we describe that the FcγRIIb2 variant is responsible for both neuronal uptake and intraneuronal distribution of pathogenic Aß linked to memory deficits in AD mice, showing a pathologic significance of the internalized Aß. Further, Aß internalization is attenuated by TOM1, a novel FcγRIIb2-binding protein. Together, we provide a molecular mechanism responsible for neuronal uptake of pathogenic Aß found in AD.

Effects of Irritable Bowel Syndrome on Daily Activities Vary Among Subtypes Based on Results From the IBS in America Survey.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is associated with significant disease burden and decreased quality of life (QOL). We investigated the effects of IBS on different areas of daily function and compared these among disease subtypes. METHODS: The Life with IBS survey was conducted by Gfk Public Affairs & Corporate Communications from September through October 2015. Respondents met Rome III criteria for constipation-predominant or diarrhea-predominant IBS (IBS-C and IBS-D, respectively). Data were collected from 3254 individuals (mean age, 47 years; 81% female; and 90% Caucasian) who met IBS criteria. RESULTS: Respondents who were employed or in school (n = 1885) reported that IBS symptoms affected their productivity an average of 8.0 days out of the month and they missed approximately 1.5 days of work/school per month because of IBS. More than half the individuals reported that their symptoms were very bothersome. Individuals with IBS-C were more likely than with IBS-D to report avoiding sex, difficulty concentrating, and feeling self-conscious. Individuals with IBS-D reported more avoidance of places without bathrooms, difficulty making plans, avoiding leaving the house, and reluctance to travel. These differences remained when controlling for symptom bothersomeness, age, sex, and employment status. In exchange for 1 month of relief from IBS, more than half of the sample reported they would be willing to give up caffeine or alcohol, 40% would give up sex, 24.5% would give up cell phones, and 21.5% would give up the internet for 1 month. CONCLUSIONS: Although the perceived effects of IBS symptoms on productivity are similar among its subtypes, patients with IBS-C and IBS-D report differences in specific areas of daily function.