A time-frame comparison study of surgical volume shifts on female primary stress urinary incontinence surgery.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the surgical volume shifts for primary female stress urinary incontinence (SUI) over a 20-year period (1999-2018) in Taiwan. METHODS: This was a retrospective cohort study based on Taiwan's National Health Insurance Research Database. We divided the time-frame into four periods: first period (1999-2003), second period (2004-2008), third period (2009-2013), and fourth period (2014-2018). The variables included major surgical types for SUI (retropubic urethropexy, pubovaginal sling, midurethral sling, etc.), surgeon gender, specialty, surgical volume (high ≥30, median 5-29, low <5), and hospital accreditation level. Reoperation rates within 1 year were analyzed as an outcome measurement. RESULTS: A total of 51,018 patients were identified. Major surgical types increased significantly during the first three periods and slightly decreased during the fourth period. The proportion of surgical volume shifted from high- to medium-, and low-volume, but it reversed during the fourth period. The proportion of SUI surgeries decreased in medical centers, whereas it increased in regional and local hospitals. The proportion of SUI surgeries by female surgeons increased. Similar phenomena occurred in MUS. As for surgeon specialty, major surgical types were performed by gynecologists and urologists equally, whereas MUS were performed more by gynecologists than by urologists. Unexpectedly, 1-year reoperation rates were higher in high-volume surgeons. CONCLUSIONS: The surgical trend of SUI surgeries shifted from high- to medium-, and low-volume surgeons, medical centers to regional and local hospitals during the study periods. This implied surgical skills and performance spreading, which may have a great influence on patient and healthcare provider choice of treatment.

A Unique Carboxylic-Acid Hydrogen-Bond Network (CAHBN) Confers Glutaminyl Cyclase Activity on M28 Family Enzymes.

Proteins with sequence or structure similar to those of di-Zn exopeptidases are usually classified as the M28-family enzymes, including the mammalian-type glutaminyl cyclases (QCs). QC catalyzes protein N-terminal pyroglutamate formation, a posttranslational modification important under many physiological and pathological conditions, and is a drug target for treating neurodegenerative diseases, cancers and inflammatory disorders. Without functional characterization, mammalian QCs and their orthologs remain indistinguishable at the sequence and structure levels from other M28-family proteins, leading to few reported QCs. Here, we show that a low-barrier carboxylic-acid hydrogen-bond network (CAHBN) is required for QC activity and discriminates QCs from M28-family peptidases. We demonstrate that the CAHBN-containing M28 peptidases deposited in the PDB are indeed QCs. Our analyses identify several thousands of QCs from the three domains of life, and we enzymatically and structurally characterize several. For the first time, the interplay between a CAHBN and the binuclear metal-binding center of mammalian QCs is made clear. We found that the presence or absence of CAHBN is a key discriminator for the formation of either the mono-Zn QCs or the di-Zn exopeptidases. Our study helps explain the possible roles of QCs in life.

A functional chitosan membrane with grafted epigallocatechin-3-gallate and lovastatin enhances periodontal tissue regeneration in dogs.

Currently used guided tissue regeneration (GTR) membranes are mainly used as a barrier to prevent epithelial cells growth into defects before new bone formation. The aim of this study was to develop a tri-layer functional chitosan (CS) membrane with epigallocatechin-3-gallate (EGCG) grafted on the outer layer for bactericidal activity, and lovastatin was included in the middle layer for controlled release. Successful EGCG grafting was demonstrated using Fourier transform infrared spectroscopy and EGCG grafting significantly enhanced adhesion and proliferation of human gingival fibroblasts. The release duration of lovastatin reached 21days. CS-Lovastatin1 produced the highest alkaline phosphatase activity and EGCG14-CS exhibited the best bactericidal activity against periodontopathic bacteria. Finally, the EGCG14-CS-Lovastatin1 membrane showed a higher percentage of bone regeneration than BioMend(®) and control groups in one-walled defects of beagle dogs. These results suggest that the EGCG14-CS-Lovastatin1 membrane has the potential to be used as a novel GTR membrane.

Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs.

Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy.

MicroRNA expression profiling in PBMCs: a potential diagnostic biomarker of chronic hepatitis C.

The expression levels of miR-16, miR-193b, miR-199a, miR-222, and miR-324 in PBMCs were significantly higher in CHC patients compared with healthy controls and significantly different between CHC patients with HCV genotype 1 (GT-1) and non-genotype-1 (non-GT-1). Multivariate logistic regression analysis also showed that patients with high expression levels of the six target miRNAs had an approximately 7.202-fold risk of CHC compared with those with low expression levels of the target miRNAs. We concluded that the expression levels of miR-16, miR-193b, miR-199a, miR-222, and miR-324 target miRNAs in PBMCs of CHC may act as significant risk biomarkers for the development of CHC.

Combined neuromuscular electrical stimulation (NMES) with fiberoptic endoscopic evaluation of swallowing (FEES) and traditional swallowing rehabilitation in the treatment of stroke-related dysphagia.

Dysphagia is common after stroke. Neuromuscular electrical stimulation (NMES) and fiberoptic endoscopic evaluation of swallowing (FEES) for the treatment of dysphagia have gained in popularity, but the combined application of these promising modalities has rarely been studied. We aimed to evaluate whether combined NMES, FEES, and traditional swallowing rehabilitation can improve swallowing functions in stroke patients with moderate to severe dysphagia. Thirty-two patients with moderate to severe dysphagia poststroke (≥3 weeks) were recruited. Patients received 12 sessions of NMES for 1 h/day, 5 days/week within a period of 2-3 weeks. FEES was done before and after NMES for evaluation and to guide dysphagic therapy. All patients subsequently received 12 sessions of traditional swallowing rehabilitation (50 min/day, 3 days/week) for 4 weeks. Primary outcome measure was the Functional Oral Intake Scale (FOIS). Secondary outcome measures included clinical degree of dysphagia, the patient's self-perception of swallowing ability, and the patient's global satisfaction with therapy. Patients were assessed at baseline, after NMES, at 6-month follow-up, and at 2-year follow-up. Twenty-nine patients completed the study. FOIS, degree of dysphagia, and patient's self-perception of swallowing improved significantly after NMES, at the 6-month follow-up, and at the 2-year follow-up (p < 0.001, each compared with baseline). Most patients reported considerable satisfaction with no serious adverse events. Twenty-three of the 29 (79.3 %) patients maintained oral diet with no pulmonary complications at 2-year follow-up. This preliminary case series demonstrated that combined NMES, FEES, and traditional swallowing rehabilitation showed promise for improving swallowing functions in stroke patients with moderate-to-severe dysphagia. The benefits were maintained for up to 2 years. The results are promising enough to justify further studies.

Interactive wiimote gaze stabilization exercise training system for patients with vestibular hypofunction.

BACKGROUND: Peripheral vestibular hypofunction is a major cause of dizziness. When complicated with postural imbalance, this condition can lead to an increased incidence of falls. In traditional clinical practice, gaze stabilization exercise is commonly used to rehabilitate patients. In this study, we established a computer-aided vestibular rehabilitation system by coupling infrared LEDs to an infrared receiver. This system enabled the subjects' head-turning actions to be quantified, and the training was performed using vestibular exercise combined with computer games and interactive video games that simulate daily life activities. METHODS: Three unilateral and one bilateral vestibular hypofunction patients volunteered to participate in this study. The participants received 30 minutes of computer-aided vestibular rehabilitation training 2 days per week for 6 weeks. Pre-training and post-training assessments were completed, and a follow-up assessment was completed 1 month after the end of the training period. RESULTS: After 6 weeks of training, significant improvements in balance and dynamic visual acuity (DVA) were observed in the four participants. Self-reports of dizziness, anxiety and depressed mood all decreased significantly. Significant improvements in self-confidence and physical performance were also observed. The effectiveness of this training was maintained for at least 1 month after the end of the training period. CONCLUSION: Real-time monitoring of training performance can be achieved using this rehabilitation platform. Patients demonstrated a reduction in dizziness symptoms after 6 weeks of training with this short-term interactive game approach. This treatment paradigm also improved the patients' balance function. This system could provide a convenient, safe and affordable treatment option for clinical practitioners.

Lower limb power rehabilitation (LLPR) using interactive video game for improvement of balance function in older people.

Declined balance functions have adverse effects on elderly population. Lower limbs muscle power training is currently an emerging concept in rehabilitation on individuals with decreased balance and mobility. In this prospective, controlled study, we used a human-computer interactive video-game-based rehabilitation device (LLPR) for training of lower limb muscle power in the elderly. Forty (aged >65 years) individuals were recruited from the community. Twenty participants in the exercise group received 30-min training, twice a week, using the LLPR system. The LLPR system allows participants to perform fast speed sit-to-stand (STS) movements. Twenty age-matched participants in the control group performed slow speed STS movements, as well as strengthening and balance exercises, with the same frequency and duration. The results were compared after 12 sessions (6 weeks) of training. The mechanical and time parameters during STS movement were measured using the LLPR system. Modified falls efficacy scale (MFES), Tinetti Performance-Oriented Mobility Assessment (POMA), function reach test, five times sit to stand (FTSS) and Timed Up and Go (TUG) were administered to participants as clinical assessments. Results showed that in the exercise group, all the mechanical and time parameters showed significant improvement. In control group, only the maximal vertical ground reaction force (MVGRF) improved significantly. For clinical assessments (balance, mobility, and self-confidence), exercise group showed significantly better scores. The STS movements in video-game-based training mimic real life situations which may help to transfer the training effects into daily activities. The effectiveness of lower limb muscle training is worthy of further investigation.

Indirubin, an acting component of indigo naturalis, inhibits EGFR activation and EGF-induced CDC25B gene expression in epidermal keratinocytes.

BACKGROUND: Topical indigo naturalis ointment is clinically proved to be an effective therapy for plaque-type psoriasis. Indirubin, as the active component of indigo naturalis, inhibits cell proliferation of epidermal keratinocytes. However, the detailed underlying mechanism is not fully understood. OBJECTIVE: To further investigate the anti-proliferating effects of indigo naturalis and indirubin on epidermal keratinocytes. METHODS: The decreased expression of CDC25B in indigo naturalis- or indirubin-treated epidermal keratinocytes, as revealed by cDNA microarray analysis, was studied. The CDC25B expression was examined under different serum concentrations and compared between primary and immortalized keratinocytes. The activation of EGFR and the effect of EGF on the cell proliferation and CDC25B expression were also investigated in epidermal keratinocytes. RT/real-time PCR and western blot method were used to analyze the CDC25B expression at the mRNA and protein levels, respectively. RESULTS: Indigo naturalis and indirubin were confirmed to down-regulate CDC25B expression significantly at both the mRNA and protein levels. The growth-dependent expression of CDC25B was demonstrated by the increased expression in serum-stimulated and immortalized keratinocytes. The activation of EGF receptor, known to be highly expressed in psoriatic lesions, was inhibited by indigo naturalis or indirubin. The cell proliferation and CDC25B expression of epidermal keratinocytes were induced by EGF alone and confirmed to be inhibited by indigo naturalis or indirubin. CONCLUSION: Except being a common therapeutic target in various cancers, CDC25B also plays an important role in the hyper-proliferation of epidermal keratinocytes which can be suppressed by anti-psoriatic drug indigo naturalis and its component, indirubin.

Anxiety, depression and quality of life (QoL) in patients with chronic dizziness.

Mood disorders and the severity of dizziness often interact with each other. However, the impact of age on anxiety and depression in dizzy patients has rarely been explored. The purpose of this study was to evaluate the correlation between the Dizziness Handicap Inventory (DHI) and the Hospital Anxiety and Depression Scale (HADS) in a group of patients with dizziness. The statistical relationships between age and each scale were studied. This cross-sectional study revealed a high correlation between DHI subgroups and HADS subscales. We found statistical correlation between neither age and HADS subscales nor age and DHI subgroups. In addition, Short-Form 36 Health Survey Questionnaires (SF-36) showed a high correlation with the dizziness handicap severity. The present study revealed that age does not influence mood disorders and the severity of dizziness in dizzy patients.

Ageing and neurodegenerative diseases.

Ageing, which all creatures must encounter, is a challenge to every living organism. In the human body, it is estimated that cell division and metabolism occurs exuberantly until about 25 years of age. Beyond this age, subsidiary products of metabolism and cell damage accumulate, and the phenotypes of ageing appear, causing disease formation. Among these age-related diseases, neurodegenerative diseases have drawn a lot of attention due to their irreversibility, lack of effective treatment, and accompanied social and economical burdens. In seeking to ameliorate ageing and age-related diseases, the search for anti-ageing drugs has been of much interest. Numerous studies have shown that the plant polyphenol, resveratrol (3,5,4'-trihydroxystilbene), extends the lifespan of several species, prevents age-related diseases, and possesses anti-inflammatory, and anti-cancer properties. The beneficial effects of resveratrol are believed to be associated with the activation of a longevity gene, SirT1. In this review, we discuss the pathogenesis of age-related neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and cerebrovascular disease. The therapeutic potential of resveratrol, diet and the roles of stem cell therapy are discussed to provide a better understanding of the ageing mystery.

Efficacy of a computerized sensor system for evaluation and training of dizzy patients.

Patients with vestibular hypofunction often experience dizziness and unsteadiness while moving their heads. Appropriate sensors can effectively detect a patient's dynamic visual acuity and associated body balance control. Forty-one vestibular-deficit patients and 10 normal individuals were invited to participate in this study. Questionnaires, clinical assessment scales and objective measures were evaluated on participants' first visits. After 12 sessions of training, all scales were evaluated again on vestibular-deficit patients. The computerized system was composed of sensors, including a gyro and strain gauges, data acquisition accessories and LabVIEW software. Results revealed that the system could effectively distinguish normal subjects from subjects with vestibular deficits. In addition, after a rehabilitation program, subjects' subjective and objective performances were significantly improved. Based on our results, we concluded that the present system, which uses a gyro and strain gauges, may provide an effective method for assessing and treating vestibular-deficit patients.

Clinical features of benign paroxysmal positional vertigo (BPPV) in Taiwan: differences between young and senior age groups.

BPPV is a common cause of vertigo. Several treatment procedures can facilitate recovery. In this study, we aimed to identify the demographic features, resolution and recurrence rates and impacts on daily activities in BPPV patient between young and senior age groups in Taiwan. This retrospective study recruited 218 patients of BPPV. Medical history, canal involvement, treatment required for complete resolution, symptom free period and recurrence rates were evaluated between the two age groups. Up to 80.7% of patients were successfully treated by a single treatment. For patients aged more than 65 years, the recurrence rate was 1.7 times higher than that in the younger age group (p = 0.07). The symptom-free period before recurrence was nearly 2.2 times longer in the senior age group (p = 0.03). Work-related activities were influenced more by BPPV in the younger age group (p = 0.03). We conclude that BPPV is prone to occur and recur in people of senior age. Clinicians should have the knowledge to diagnose different types of BPPV and treat it accordingly to prevent further complications.