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Background: Postoperative hemorrhage and thromboembolism are recognized complications following colorectal and abdominal wall surgery, but accurate documentation of their incidence, trends, and outcomes is scant. This is relevant given the increasing number of surgical patients with cardiovascular comorbidity on anticoagulant/antiplatelet therapy., Objective: This study aims to characterize trends in the use of anticoagulant/antiplatelet therapy among patients undergoing major colorectal and abdominal wall surgery within the past decade, and to assess rates of, outcomes following, and risk factors for hemorrhagic and thromboembolic complications., Design and Setting: This is a retrospective cross-sectional study conducted at a single quaternary referral center., Patients: Patients who underwent major colorectal and abdominal wall surgery during three 12-month intervals (2005, 2010, and 2015) were included., Main Outcome Measures: The primary outcomes measured was the rate of complications relating to postoperative hemorrhage or thromboembolism., Results: One thousand one hundred twenty-six patients underwent major colorectal and abdominal wall surgery (mean age, 61.4 years (SD 16.3); 575 (51.1%) male). Overall, 229 (21.7%) patients were on anticoagulant/antiplatelet agents; there was an increase in the proportion of patients on clopidogrel, dual antiplatelet therapy, and novel oral anticoagulants over the decade. One hundred seven (9.5%) cases were complicated by hemorrhage/thromboembolism. Aspirin (OR, 2.22; 95% CI, 1.38-3.57), warfarin/enoxaparin (OR, 3.10; 95% CI, 1.67-5.77), and dual antiplatelet therapy (OR, 2.99; 95% CI, 1.37-6.53) were most implicated with complications on univariate analysis. Patients with atrial fibrillation (adjusted OR 2.67; 95% CI, 1.47-4.85), ischemic heart disease (adjusted OR, 2.14; 95% CI, 1.04-4.40), and mechanical valves (adjusted OR, 7.40; 95% CI 1.11-49.29) were at increased risk of complications on multivariate analysis. The severity of these events was mainly limited to Clavien-Dindo 1 (n = 37) and 2 (n = 46) complications., Limitations: This is a retrospective study with incomplete documentation of blood loss and operative time in the early study period., Conclusions: One in ten patients incurs hemorrhagic/thromboembolic complications following colorectal and abdominal wall surgery. "High-risk" patients are identifiable, and individualized management of these patients concerning multidisciplinary discussion and critical-care monitoring may help improve outcomes. Prospective studies are required to formalize protocols in these "high-risk" patients. See Video Abstract at http://links.lww.com/DCR/A747.

Acute bacterial meningitis is not an uncommon central nervous system infection. In severe cases, it can be associated with various neurological or systemic complications. However, acute spinal cord dysfunction rarely occurs. We report a case of bacterial meningitis complicated with spinal cord infarction despite adequate treatment with antibiotics and corticosteroid therapy. He had residual paraplegia and was fully dependent in the activity of daily living., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Melanoma metastatic to the large bowel (colon, rectum, and anus) is rarely diagnosed, with more than 95% of large bowel metastases identified post-mortem. The incidence, natural history, and survival rates of patients with large bowel melanoma metastases are poorly documented in the literature., Objective: This study aimed to identify the incidence, clinical characteristics, and survival of patients with large bowel melanoma metastases., Methods: A review was undertaken of all patients with melanoma treated over a 50-year period (1964-2014) at a tertiary referral center. Cases selected for study were those diagnosed with melanoma metastases in the colon, rectum, and anus. Primary colorectal and anal melanomas were excluded. Data were retrieved relating to patient demographics, clinical features, and survival., Results: Of 38,279 patients with primary melanoma, 106 patients (0.3%, mean age 51.0 years [standard deviation 16.3], 64 males) developed large bowel metastases. The median interval between diagnosis of primary melanoma and large bowel metastasis was 62.8 months (range 1-476). The most common symptom was rectal bleeding (29.2%), and the large bowel was the sole site of metastasis in 47.2% of patients. Median survival from diagnosis of large bowel metastasis was 31.7 months (range 1-315), and overall survival at 1, 2, and 5 years was 68.1, 45.9, and 26.5%, respectively., Conclusion: Our study provides insights into melanoma metastatic to the colon, rectum, and anus, which had an incidence of 0.3%. There are potentially long intervals between diagnosis of primary melanoma and large bowel metastasis. The most common symptom was rectal bleeding, although some patients were asymptomatic.

Human mesenchymal stem cells (hMSCs) are a critical raw material for many regenerative medicine products, including cell-based therapies, engineered tissues, or combination products, and are on the brink of radically changing how the world of medicine operates. Their unique characteristics, potential to treat many indications, and established safety profile in more than 800 clinical trials have contributed to their current consumption and will only fuel future demand. Given the large target patient populations with typical dose sizes of 10's to 100's of millions of cells per patient, and engineered tissues being constructed with 100's of millions to billions of cells, an unprecedented demand has been created for hMSCs. The fulfillment of this demand faces an uphill challenge in the limited availability of large quantities of pharmaceutical grade hMSCs for the industry-fueling the need for parallel rapid advancements in the biomanufacturing of this living critical raw material. Simply put, hMSCs are no different than technologies like transistors, as they are a highly technical and modular product that requires stringent control over manufacturing that can allow for high quality and consistent performance. As hMSC manufacturing processes are optimized, it predicts a future time of abundance for hMSCs, where scientists and researchers around the world will have access to a consistent and readily available supply of high quality, standardized, and economical pharmaceutical grade product to buy off the shelf for their applications and drive product development-this is "Peak MSC."

Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels. In examining 3,080 tumor samples from 8 cancer types in The Cancer Genome Atlas, rDriver predicted 1,389 driver mutations. Compared with existing tools, rDriver identified more low frequency mutations associated with lineage specific functional properties, timing of occurrence and patient survival. Evaluation of rDriver predictions using engineered cell-line models resulted in a positive predictive value of 0.94 in PIK3CA genes. Our study highlights the importance of integrating multi-omic data in predicting cancer driver mutations and provides a statistically rigorous solution for cancer target discovery and development.

Background: Caecal bascule is a rare condition characterized by the inferior pole of the caecum folding on a horizontal axis antero-superiorly towards the ascending colon, potentially causing obstruction. An unusual variant of volvulus, diagnosis is challenging due to its obscurity. We present the experience of an Australian tertiary-referral hospital with the diagnosis/management of caecal bascule, and review cases reported in the literature to raise awareness of this uncommon diagnosis., Methods: Medical records of patients diagnosed with caecal bascule during 2001-2016 were reviewed. Data relating to their presentation, investigations, management and outcomes were obtained. A literature search was conducted through PubMed and Medline databases., Results: Caecal bascule was diagnosed in four patients (median age: 60.5 (range: 48-75) years, two females). Patients presented with abdominal pain (4/4), distension (3/4), vomiting (3/4) and confusion (1/4) over a 1- to 4-day period. Computed tomography identified caecal displacement in three cases, and bascule was diagnosed at laparotomy in all cases. All patients underwent right hemicolectomy, with primary ileo-colic anastomosis in three cases and formation of Abcarian stoma in one case. Median length of stay was 15.5 days (range: 10-24), with no mortality. Fifteen cases of caecal bascule have been reported in the literature to date, with authors suggesting resection as definitive treatment., Conclusion: Correct diagnosis of caecal bascule requires a high index of suspicion and avoids delay of appropriate management. Recent operation, particularly laparoscopic cholecystectomy, may be contributing factors. Resection is recommended, a sentiment echoed by reported cases in the literature., (© 2017 Royal Australasian College of Surgeons.)

Background: It remains unclear whether regional variation exists in the human enteric nervous system (ENS) ie, whether intrinsic innervation varies along the gut. Recent classification of gastrointestinal neuropathies has highlighted inadequacies in the quantification of the human ENS. This study used paired wholemounts to accurately quantify and neurochemically code the hindgut myenteric plexus, comparing human distal colon and rectum., Methods: Paired human descending colonic/rectal specimens were procured from 15 patients undergoing anterior resection. Wholemounts of myenteric plexi were triple-immunostained with anti-Hu/NOS/ChAT antibodies. Images were acquired by motorized epifluorescence microscopy, allowing assessment of ganglionic density/size, ganglionic area density, and neuronal density. 'Stretch-corrected' values were calculated using stretched/relaxed tissue dimensions., Key Results: Tile-stitching created a collage with average area 99 300 000 μm 2 . Stretch-corrected ganglionic densities were similar (colon: median 510 ganglia/100 mm 2 [range 386-1170], rectum: 585 [307-923]; P = .99), as were average ganglionic sizes (colon: 57 593 μm 2 [40 301-126 579], rectum: 54 901 [38 701-90 211], P = .36). Ganglionic area density (colon: 11.92 mm 2 per 100 mm 2 [7.53-18.64], rectum: 9.84 [5.80-17.19], P = .10) and stretch-corrected neuronal densities (colon: 189 neurons/mm 2 [117-388], rectum: 182 [89-361], P = .31) were also similar, as were the neurochemical profiles of myenteric ganglia, with comparable proportions of NOS+ and ChAT+ neurons (P > .10)., Conclusions and Inferences: This study has revealed similar neuronal and ganglionic densities and neurochemical profiles in human distal colon and rectum. Further investigation of other components of the ENS, incorporating additional immunohistochemical markers are required to confirm that there is no regional variation in the human hindgut ENS., (© 2017 John Wiley & Sons Ltd.)

Despite the advancement of the tremor assessment systems, the current technology still lacks a method that can objectively characterize tremors in relative segmental movements. This paper presents a measurement system, which quantifies multi-degrees-of-freedom coupled relative motions of hand-arm tremor, in terms of joint angular displacement. In-laboratory validity and reliability tests of the system algorithm to provide joint angular displacement was carried out by using the two-degrees-of-freedom tremor simulator with incremental rotary encoder systems installed. The statistical analyses show that the developed system has high validity results and comparable reliability performances using the rotary encoder system as the reference. In the clinical trials, the system was tested on 38 Parkinson's disease patients. The system readings were correlated with the observational tremor ratings of six trained medical doctors. The moderate to very high clinical correlations of the system readings in measuring rest, postural and task-specific tremors add merits to the degree of readiness of the developed tremor measurement system in a routine clinical setting and/or intervention trial for tremor amelioration.

Percutaneous endoscopic gastrostomy (PEG) is commonly performed for feeding difficulties, in patients suffering from complications of nasopharyngeal carcinoma and its treatment, namely radiotherapy and surgery. This case report describes the challenges in hemostasis and subsequent re-establishment of enteral access for feeding, in an elderly patient with a history of NPC, treated surgically, followed by radiotherapy, who presented with massive hematemesis following reinsertion of her PEG shortly after an accidental dislodgement. Her previous nasopharyngectomy, wide field radiation therapy, and radical neck dissection precluded nasogastric tube feeding, and the presence of a large hiatus hernia made reinsertion of a new PEG technically challenging. This case highlights the methods used to overcome the above challenges.

Aim: Continence is dependent on anorectal-brain interactions. Consequently, aberrations of the brain-gut axis may be important in the pathophysiology of faecal incontinence (FI) in certain patients. The aim of this study was to assess the feasibility of recording brain responses to rectal mechanical stimulation in patients with FI using functional magnetic resonance imaging (fMRI)., Method: A prospective, cohort pilot study was performed to assess brain responses during rectal stimulation in 14 patients [four men, mean (SD) age 62 (15) years]. Blood oxygen level dependent (BOLD) signals were measured by fMRI during rest and mechanical distension, involving random repetitions of isobaric phasic rectal distensions at fixed (15 and 45 mmHg) and variable (10% above sensory perception threshold) pressures., Results: Increases in BOLD signals in response to high pressure rectal distension (45 mmHg) and maximum toleration were observed in the cingulate gyrus, thalamus, insular cortex, inferior frontal gyrus, cerebellum, caudate nucleus, supramarginal gyrus, putamen and amygdala. Additionally, activation of the supplementary motor cortex and caudate nucleus with inconsistent activity in the frontal lobe was observed., Conclusions: This study has demonstrated the feasibility of recording brain responses to rectal mechanical stimulation using fMRI in patients with FI, revealing activity in widespread areas of the brain involved in visceral sensory processing. The observed activity in the supplementary motor cortex and caudate nucleus, with relative paucity of activity in the frontal lobes, warrants investigation in future studies to determine whether aberrations in cerebral processing of rectal stimuli play a role in the pathogenesis of FI., (Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.)

Purpose: Outcomes of acute lower gastrointestinal haemorrhage (ALGIH) are mostly derived from studies performed in the sub-acute/elective rather than the emergency department (ED) setting. The aims of this study were to determine the incidence and outcomes of patients presenting to a tertiary hospital ED with ALGIH and to identify associated clinicopathological risk factors., Method: A retrospective observational cohort study of consecutive patients presenting with ALGIH to a tertiary hospital ED was performed. Primary outcome measures included mortality and hospital (including high dependency [HDU]) admission. Secondary outcome measures included rates of (i) blood transfusion, (ii) radiological/endoscopic investigation(s) and (iii) therapeutic intervention., Results: ALGIH accounted for 949 (512 M, mean age 62.3 years) of 130,262 (0.73%) ED presentations, of which 285 patients (30.1%) were on anti-platelet/coagulant therapy. There were five deaths (0.5%). Hospital admission was required in 498 patients (52.5%), of which 19 (3.8%) required HDU monitoring. Hospital admission was twice as likely in males and four times more likely in patients >75 years old and those taking multiple anti-platelet/coagulant therapy (P < 0.05). Blood product transfusion was required in 172 patients (34.5%), specialist investigations in 230 (46.2%) and therapeutic intervention in 51 (10.2%) (surgery in 24 [4.8%]; endoscopic haemostasis in 20 [4.0%] and angiographic embolisation in 9 [1.8%] patients)., Conclusion: ALGIH accounts for 1% of all ED presentations, with half requiring hospital admission. Mortality and surgical intervention rates are low and although most patients can be managed supportively, access to interventional radiology/endoscopy is important.

Background: Due to a rapidly ageing population in the world, it is increasingly pertinent to promote successful ageing strategies which are cost-effective, easily accessible, and more likely to be acceptable to the elderly. Past research associates exposure to natural environments and horticultural therapy (HT) with positive psychological, social and physical health benefits. This Randomized Controlled Trial (RCT) is designed to evaluate the efficacy of HT in promoting Asian elderly' mental health, cognitive functioning and physical health., Methods/design: 70 elderly participants aged 60 to 85 years old will be randomized to participate in either the active horticultural therapy group or be in the waitlist control. Sessions will be weekly for 12 weeks, and monthly for 3 months. Mental health will be assessed through self-reports of depressive and anxiety symptomatology, life satisfaction, social connectedness and psychological well-being, collaborated with immunological markers. Outcome measures of cognitive functioning and physical health include neuropsychological tests of cognitive function and basic health screening. Outcomes will be assessed at baseline, 3 months and 6 months post-intervention., Discussion: This RCT comprehensively investigates the efficacy of a non-invasive intervention, HT, in enhancing mental health, cognitive functioning and physical health. The results have tremendous potential for supporting future successful ageing programs and applicability to larger populations., Trial Registration: ClinicalTrials.gov NCT02495194 . Trial registration date: July 13, 2015. Retrospectively registered.

It is presumed that extrinsic afferent nerves link the rectum to the central nervous system. However, the anatomical/functional existence of such nerves has never previously been demonstrated in humans. Therefore, we aimed to identify and make electrophysiological recordings in vitro from extrinsic afferents, comparing human rectum to colon. Sections of normal rectum and colon were procured from anterior resection and right hemicolectomy specimens, respectively. Sections were pinned and extrinsic nerves dissected. Extracellular visceral afferent nerve activity was recorded. Neuronal responses to chemical [capsaicin and "inflammatory soup" (IS)] and mechanical (Von Frey probing) stimuli were recorded and quantified as peak firing rate (range) in 1-s intervals. Twenty-eight separate nerve trunks from eight rectums were studied. Of these, spontaneous multiunit afferent activity was recorded in 24 nerves. Peak firing rates increased significantly following capsaicin [median 6 (range 3-25) spikes/s vs. 2 (1-4), P < 0.001] and IS [median 5 (range 2-18) spikes/s vs. 2 (1-4), P < 0.001]. Mechanosensitive "hot spots" were identified in 16 nerves [median threshold 2.0 g (range 1.4-6.0 g)]. In eight of these, the threshold decreased after IS [1.0 g (0.4-1.4 g)]. By comparison, spontaneous activity was recorded in only 3/30 nerves studied from 10 colons, and only one hot spot (threshold 60 g) was identified. This study confirms the anatomical/functional existence of extrinsic rectal afferent nerves and characterizes their chemo- and mechanosensitivity for the first time in humans. They have different electrophysiological properties to colonic afferents and warrant further investigation in disease states., (Copyright © 2016 the American Physiological Society.)

Objectives: To find out whether intrapartum translabial ultrasound examination is painless by comparing pain score of ultrasound-based versus digital vaginal examination of foetal head station., Methods: In 94 women carrying uncomplicated-term singleton pregnancies, labour progress was assessed by translabial ultrasound, followed immediately by conventional digital vaginal examination. Pain scores (0-10) using visual analogue pain scale were obtained for both examinations. Forty-eight and forty-six sets of data were obtained in first and second stage of labour, respectively. The difference in pain scores between digital vaginal examination and translabial ultrasound was analysed., Results: The median pain score for translabial ultrasound was 0 (range 0-8), while that for vaginal examination was 4.5 (range 0-10), p < 0.05. There was no significant difference in pain scores between first and second stages of labour for translabial ultrasound (p = 0.123) and for vaginal examination (p = 0.680). The pain score for vaginal examination was higher than that of translabial ultrasound in 81.9%, similar in 13.8% and lower in 4.3% of cases. There was no statistically significant difference in pain scores obtained for digital vaginal examination by clinicians with different experience (p = 0.941)., Conclusions: Intrapartum translabial ultrasound is generally better tolerated than digital vaginal examination for assessment of labour progress, making it an acceptable adjunctive assessment tool during labour.

Congenital uterine anomalies have been associated with poor reproductive outcome, which include recurrent miscarriage, abruptio placenta, intra-uterine growth restriction and preterm delivery. Here, we report a case: 36 years old, G3P2, known case of uterine didelphys, with history of preterm birth, who successfully carried her pregnancy till term with weekly intramuscular injection of 250 mg hydroxyprogesterone caproate (®Proluton Depot, Zuellig Pharma).

This paper, for the first time, reports integrated conceptual MBCT/biorefinery systems for unlocking the value of organics in municipal solid waste (MSW) through the production of levulinic acid (LA by 5wt%) that increases the economic margin by 110-150%. After mechanical separation recovering recyclables, metals (iron, aluminium, copper) and refuse derived fuel (RDF), lignocelluloses from remaining MSW are extracted by supercritical-water for chemical valorisation, comprising hydrolysis in 2wt% dilute H2SO4 catalyst producing LA, furfural, formic acid (FA), via C5/C6 sugar extraction, in plug flow (210-230°C, 25bar, 12s) and continuous stirred tank (195-215°C, 14bar, 20min) reactors; char separation and LA extraction/purification by methyl isobutyl ketone solvent; acid/solvent and by-product recovery. The by-product and pulping effluents are anaerobically digested into biogas and fertiliser. Produced biogas (6.4MWh/t), RDF (5.4MWh/t), char (4.5MWh/t) are combusted, heat recovered into steam generation in boiler (efficiency: 80%); on-site heat/steam demand is met; balance of steam is expanded into electricity in steam turbines (efficiency: 35%)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: WHO's new classification in 2009: dengue with or without warning signs and severe dengue, has necessitated large numbers of admissions to hospitals of dengue patients which in turn has been imposing a huge economical and physical burden on many hospitals around the globe, particularly South East Asia and Malaysia where the disease has seen a rapid surge in numbers in recent years. Lack of a simple tool to differentiate mild from life threatening infection has led to unnecessary hospitalization of dengue patients., Methods: We conducted a single-centre, retrospective study involving serologically confirmed dengue fever patients, admitted in a single ward, in Hospital Kuala Lumpur, Malaysia. Data was collected for 4 months from February to May 2014. Socio demography, co-morbidity, days of illness before admission, symptoms, warning signs, vital signs and laboratory result were all recorded. Descriptive statistics was tabulated and simple and multiple logistic regression analysis was done to determine significant risk factors associated with severe dengue., Results: 657 patients with confirmed dengue were analysed, of which 59 (9.0%) had severe dengue. Overall, the commonest warning sign were vomiting (36.1%) and abdominal pain (32.1%). Previous co-morbid, vomiting, diarrhoea, pleural effusion, low systolic blood pressure, high haematocrit, low albumin and high urea were found as significant risk factors for severe dengue using simple logistic regression. However the significant risk factors for severe dengue with multiple logistic regressions were only vomiting, pleural effusion, and low systolic blood pressure. Using those 3 risk factors, we plotted an algorithm for predicting severe dengue. When compared to the classification of severe dengue based on the WHO criteria, the decision tree algorithm had a sensitivity of 0.81, specificity of 0.54, positive predictive value of 0.16 and negative predictive of 0.96., Conclusion: The decision tree algorithm proposed in this study showed high sensitivity and NPV in predicting patients with severe dengue that may warrant admission. This tool upon further validation study can be used to help clinicians decide on further managing a patient upon first encounter. It also will have a substantial impact on health resources as low risk patients can be managed as outpatients hence reserving the scarce hospital beds and medical resources for other patients in need., Competing Interests: The authors have declared that no competing interests exist.

Pre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC. Tetrandrine increased MSC PGE2 secretion through the NF-κB/COX-2 signaling pathway. When co-cultured with mouse macrophages (RAW264.7), tetrandrine-primed MSC attenuated the level of TNF-α secreted by RAW264.7. Furthermore, systemic transplantation of primed MSC into a mouse ear skin inflammation model significantly reduced the level of TNF-α in the inflamed ear, compared to unprimed cells. Screening of small molecules to pre-condition cells prior to transplantation represents a promising strategy to boost the therapeutic potential of cell therapy.

The regeneration of whole osteochondral constructs with a physiological structure has been a significant issue, both clinically and academically. In this study, we present a method using rabbit bone marrow stromal cells (BMSCs) cultured on a silk-RADA peptide scaffold in a specially designed two-chambered co-culture well for the generation of multilayered osteochondral constructs in vitro. This specially designed two-chambered well can simultaneously provide osteogenic and chondrogenic stimulation to cells located in different regions of the scaffold. We demonstrated that this co-culture approach could successfully provide specific chemical stimulation to BMSCs located on different layers within a single scaffold, resulting in the formation of multilayered osteochondral constructs containing cartilage-like and subchondral bone-like tissue, as well as the intermediate osteochondral interface. The cells in the intermediate region were found to be hypertrophic chondrocytes, embedded in a calcified extracellular matrix containing glycosaminoglycans and collagen types I, II and X. In conclusion, this study provides a single-step approach that highlights the feasibility of rabbit BMSCs as a single-cell source for multilayered osteochondral construct generation in vitro., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: Fecal incontinence is a chronic and debilitating condition with significant health burden. Despite its clinical relevance, the prevalence of fecal incontinence remains inconsistently described., Objective: This study aimed to systematically review the literature regarding the prevalence of and factors associated with fecal incontinence among community-dwelling adults., Data Sources: A search of the PubMed, Embase, and Cochrane databases was performed., Study Selection: Studies that reported the prevalence of fecal incontinence and/or associated factors in a community-based (ie, unselected) adult population were included. Two independent assessors reviewed eligible articles., Main Outcome Measures: Relevant data were extracted from each study and presented in descriptive form. The main outcome measures included the prevalence of fecal incontinence (adjusted and/or unadjusted), stratified for age and sex if reported; factors associated (and not associated) with fecal incontinence; and study quality, assessed using predefined criteria., Results: Of 3523 citations identified, 38 studies were included for review. The reported median prevalence of fecal incontinence was 7.7% (range, 2.0%-20.7%). Fecal incontinence equally affected both men (median, 8.1%; range, 2.3%-16.1%) and women (median, 8.9%; range, 2.0%-20.7%) and increased with age (15-34 years, 5.7%; >90 years, 15.9%). The study populations and diagnostic criteria used were heterogeneous, precluding any meaningful pooling of prevalence estimates. Study quality assessment revealed 6 high-quality studies, of which only 3 were performed in a representative sample. The median prevalence of fecal incontinence was higher in these studies at 11.2% (range, 8.3%-13.2%). The factors most commonly reported to be associated with fecal incontinence included increasing age, diarrhea, and urinary incontinence., Limitations: Heterogeneity of studies precluded meaningful pooling or meta-analysis of data., Conclusions: Fecal incontinence is a prevalent condition of equal sex distribution, affecting ≈1 in 8 community adults, and has identifiable associated factors. The paucity of high-quality prevalence studies emphasizes the need for future population-based studies that use standardized diagnostic criteria for fecal incontinence.

While mesenchymal stem cells (MSCs) are rapidly cleared from the body following systemic transplantation, their therapeutic benefits typically persist. In this issue, Liu et al. (2015) reveal that the ability of transplanted MSCs to alleviate osteoporosis in systemic lupus erythematosus is maintained through epigenetic changes conferred by secretory action of the MSCs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Cushing's syndrome is known to have a wide spectrum of clinical presentation with debilitating consequences and morbidity if not diagnosed and treated in time. Sometimes the diagnosis of Cushing's syndrome can be challenging to the endocrinologist, especially when the usual battery of biochemical tests and advanced cross-sectional imaging is negative or inconclusive. We described a case in which the use of bilateral inferior petrosal sinus sampling (BIPSS) was conclusive albeit being technically challenging (due to a rare incidental finding of double superior vena cava) and invasive in nature.

From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch's postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.

Accurate prediction of DNA chemical shifts facilitates resonance assignment and allows recognition of different conformational features. Based on the nearest neighbor model and base pair replacement approach, we have determined a set of triplet chemical shift values and correction factors for predicting the proton chemical shifts of B-DNA containing an internal C·C mismatch. Our results provide a reliable chemical shift prediction with an accuracy of 0.07 ppm for non-labile protons and 0.09 ppm for labile protons. In addition, we have also shown that the correction factors for C·C mismatches can be used interchangeably with those for T·T mismatches. As a result, we have generalized a set of correction factors for predicting the flanking residue chemical shifts of pyrimidine·pyrimidine mismatches., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Deception is an impactful social event that has been the focus of an abundance of researches over recent decades. In this paper, an electroencephalography (EEG) study is presented regarding the cognitive processes of an instructed liar/truth-teller during the time window of stimulus (question) delivery period (SDP) prior to their deceptive/truthful responses towards questions related to authentic (WE: with prior experience) and fictional experience (NE: no prior experience). To investigate deception in non-experienced events, the subjects were given stimuli in a mock interview scenario that induced them to fabricate lies. To analyze the data, frequency domain network and connectivity analysis was performed in the source space in order to provide a more systematic level understanding of deception during SDP. This study reveals several groups of neuronal generators underlying both the instructed lying (IL) and the instructed truth-telling (IT) conditions for both tasks during the SDP. Despite the similarities existed in these group components, significant differences were found in the intra- and inter-group connectivity between the IL and IT conditions in either task. Additionally, the response time was found to be positively correlated with the clustering coefficient of the inferior frontal gyrus (44R) in the WE-IL condition and positively correlated with the clustering coefficient of the precuneus (7L) and the angular gyrus (39R) in the WE-IT condition. However, the response time was found to be marginally negatively correlated with the clustering coefficient of the secondary auditory cortex (42L) in the NE-IL condition and negatively correlated with the clustering coefficient of the somatosensory association cortex (5L, R) in the NE-IT condition. Therefore, these results provide complementary and intuitive evidence for the differences between the IL and IT conditions in SDP for two types of deception tasks, thus elucidating the electrophysiological mechanisms underlying SDP of deception from regional, inter-regional, network, and inter-network scale analyses.

Aim: Interest in functional bowel disorders (FBDs) and faecal incontinence (FI) has increased amongst coloproctologists. The study aimed to assess the prevalence of FBDs and FI (including its severity) among Australian primary healthcare seekers using objective criteria., Method: A cross-sectional survey was conducted in a primary care setting in Sydney, Australia. A self-administered questionnaire was used to collect demographic information and diagnose FBDs (irritable bowel syndrome, constipation, functional bloating and functional diarrhoea) based on Rome III criteria. The severity of FI was determined using the Vaizey incontinence score. Associations with medical/surgical history and healthcare utilization were assessed., Results: Of 596 subjects approached, 396 (66.4%) agreed to participate. Overall, 33% had FBD and/or FI. Irritable bowel syndrome was present in 11.1% and these participants were more likely to report anxiety/depression (P < 0.01) and to have had a previous colonoscopy (P < 0.001) or cholecystectomy (P = 0.02). Functional constipation was present in 8.1%, and functional bloating and functional diarrhoea were diagnosed in 6.1%, and 1.5%, respectively. FI was present in 12.1% with the majority (52%) reporting moderate/severe incontinence (Vaizey score > 8). Participants with FI were more likely to have irritable bowel syndrome, urinary incontinence and previous anal surgery (P < 0.01)., Conclusion: FBDs and FI are prevalent conditions amongst primary healthcare seekers and the needs of those affected appear to be complex given their coexisting symptoms and conditions. Currently, the majority do not reach colorectal services, although increased awareness by primary care providers could lead to sufferers being referred for specialist management., (Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.)

Induced pluripotent stem cells (iPSCs) have the potential to transform drug discovery and healthcare in the 21(st) century. However, successful commercialization will require standardized manufacturing platforms. Here we highlight the need to define standardized practices for iPSC generation and processing and discuss current challenges to the robust manufacture of iPSC products., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Dengue infection is a major cause of morbidity and mortality in Malaysia. To date, much research on dengue infection conducted in Malaysia have been published. One hundred and sixty six articles related to dengue in Malaysia were found from a search through a database dedicated to indexing all original data relevant to medicine published between the years 2000-2013. Ninety articles with clinical relevance and future research implications were selected and reviewed. These papers showed evidence of an exponential increase in the disease epidemic and a varying pattern of prevalent dengue serotypes at different times. The early febrile phase of dengue infection consist of an undifferentiated fever. Clinical suspicion and ability to identify patients at risk of severe dengue infection is important. Treatment of dengue infection involves judicious use of volume expander and supportive care. Potential future research areas are discussed to narrow our current knowledge gaps on dengue infection.

Vaccination is an important strategy in the protection of aquaculture species from major diseases. However, we still do not have a good understanding of the mechanisms underlying vaccine-induced disease resistance. This is further complicated by the presence of several lymphoid organs that play different roles when mounting an immune response. In this study, we attempt to elucidate some of these mechanisms using a microarray-based approach. Asian seabass (Lates calcarifer) were vaccinated against Streptococcus iniae and the transcriptomic changes within the spleen and head kidney at one and seven days post-vaccination were profiled. We subsequently challenged the seabass at three weeks post-vaccination with live S. iniae and similarly profiled the transcriptomes of the two organs after the challenge. We found that vaccination induced an early, but transient transcriptomic change in the spleens and a delayed response in the head kidneys, which became more similar to one another compared to un-vaccinated ones. When challenged with the pathogen, the spleen, but not the head kidneys, responded transcriptomically at 25-29 hours post-challenge. A unique set of genes, in particular those involved in the activation of NF-κB signaling, was up-regulated in the vaccinated spleens upon pathogen challenge but not in the un-vaccinated spleens. A semi-quantitative PCR detection of S. iniae using metagenomic DNA extracted from the water containing the seabass also revealed that vaccination resulted in reduction of pathogen shedding. This result indicated that vaccination not only led to a successful immune defense against the infection, but also reduced the chances for horizontal transmission of the pathogen. In conclusion, we have provided a transcriptomic analysis of how the teleost spleen and head kidneys responded to vaccination and subsequent infection. The different responses from the two organs are suggestive of their unique roles in establishing a vaccine-induced disease resistance.

Overexpression and/or abnormal cleavage of amyloid precursor protein (APP) are linked to Alzheimer's disease (AD) development and progression. However, the molecular mechanisms regulating cellular levels of APP or its processing, and the physiological and pathological consequences of altered processing are not well understood. Here, using mouse and human cells, we found that neuronal damage induced by UV irradiation leads to specific APP, APLP1, and APLP2 decline by accelerating their secretase-dependent processing. Pharmacological inhibition of endosomal/lysosomal activity partially protects UV-induced APP processing implying contribution of the endosomal and/or lysosomal compartments in this process. We found that a biological consequence of UV-induced γ-secretase processing of APP is impairment of APP axonal transport. To probe the functional consequences of impaired APP axonal transport, we isolated and analyzed presumptive APP-containing axonal transport vesicles from mouse cortical synaptosomes using electron microscopy, biochemical, and mass spectrometry analyses. We identified a population of morphologically heterogeneous organelles that contains APP, the secretase machinery, molecular motors, and previously proposed and new residents of APP vesicles. These possible cargoes are enriched in proteins whose dysfunction could contribute to neuronal malfunction and diseases of the nervous system including AD. Together, these results suggest that damage-induced APP processing might impair APP axonal transport, which could result in failure of synaptic maintenance and neuronal dysfunction.

Cell therapies enable unprecedented treatment options to replace tissues, destroy tumors and facilitate regeneration. The greatest challenge facing cell therapy is the inability to control the fate and function of cells after transplantation. We have developed an approach to control cell phenotype in vitro and after transplantation by engineering cells with intracellular depots that continuously release phenotype-altering agents for days to weeks. The platform enables control of cells' secretome, viability, proliferation and differentiation, and the platform can be used to deliver drugs or other factors (e.g., dexamethasone, rhodamine and iron oxide) to the cell's microenvironment. The preparation, efficient internalization and intracellular stabilization of ∼1-μm drug-loaded microparticles are critical for establishing sustained control of cell phenotype. Herein we provide a protocol to generate and characterize micrometer-sized agent-doped poly(lactic-co-glycolic) acid (PLGA) particles by using a single-emulsion evaporation technique (7 h), to uniformly engineer cultured cells (15 h), to confirm particle internalization and to troubleshoot commonly experienced obstacles.

The past decade has seen the first wave of cell-based therapeutics undergo clinical trials with varying degrees of success. Although attention is increasingly focused on clinical trial design, owing to spiraling regulatory costs, tools used in delivering cells and sustaining the cells' viability and functions in vivo warrant careful scrutiny. While the clinical administration of cell-based therapeutics often requires additional safeguarding and targeted delivery compared with traditional therapeutics, there is significant opportunity for minimally invasive device-assisted cell therapy to provide the physician with new regenerative options at the point of care. Herein we detail exciting recent advances in medical devices that will aid in the safe and efficacious delivery of cell-based therapeutics., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Structural magnetic resonance imaging has been employed for evaluation of medial temporal atrophy in patients with Alzheimer's disease (AD). Arterial spin labeling (ASL) technique could detect cerebral perfusion abnormalities in AD., Objective: We hypothesized that combination of hippocampal volumetry and cerebral blood flow yield higher accuracy than either method alone in discriminating AD patients from cognitively normal elderly adults., Materials and Methods: 13 AD patients and 15 healthy controls were studied using a 3-tesla scanner. Standardized T1W 3D volumetric Fast Field Echo and QUASAR ASL sequences were employed for cerebral volumetry and perfusion respectively. Manual Right and left hippocampal volumetry was performed manually by ANALYZE software, with total intracranial volume normalization. ASL data were analyzed by institutional specially-design software to calculate cerebral blood flow of region-of-interests placed at the middle and posterior cingulate gyri., Results: Right and left hippocampal volumes and middle and posterior cingulate gyri cerebral blood flows were significantly lower in the patients than in the controls (independent-samples t-tests, p < 0.05), and prediction accuracies of 89.3%, 82.1%, 75.0% and 71.4% were achieved for each of the above parameters, respectively. In distinguishing patients from controls using corresponding optimized cut-off values, various combinations of these parameters were used to create the Receiver Operating Characteristic curves. The highest area under curve value was 0.944, by combining cerebral blood flow at the middle cingulate gyrus, normalized right and left hippocampal volumes., Conclusions: A 'one-stop-shop' magnetic resonance study of combined hippocampal volumetry and cerebral perfusion has improved efficacy in discriminating AD patients from cognitively normal elderly adults.

A novel chitosan adhesive film that incorporates the dye 'Rose Bengal' (RB) was used in conjunction with a green laser to repair transected rat median nerves in vivo. Histology and electrophysiological recording assessed the impact of the laser-adhesive technique on nerves. One week post-operatively, the sham-control group (laser-adhesive technique applied on un-transected nerves) conserved the average number and size of myelinated fibres in comparison to its contralateral side and electrophysiological recordings demonstrated no significant difference with un-operated nerves. Twelve weeks after the laser-adhesive anastomoses, nerves were in continuity with regenerated axons that crossed the anastomotic site., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Optical tweezers were used to scan individual Chronic Myelogenous Leukemia cells to determine if the cell death depends on the scanning conditions. Although increasing the scanning frequency or amplitude means greater force applied to the cells, their effects on cell death are not a simple increasing trend, as observed in the optical microscopy. Indeed, cell death sharply increased at particular screening frequencies and amplitudes, whereas other frequencies or amplitudes were less detrimental. These results suggest that cell damage was more sensitive to certain scanning conditions, rather than simply high-applied forces., (Copyright © 2013 Wiley Periodicals, Inc.)

The antibacterial effect of light emitting diodes (LEDs) in the visible region (461, 521 and 642 nm) of the electromagnetic spectrum was investigated on Escherichia coli O157:H7, Salmonella typhimurium, Listeria monocytogenes and Staphylococcus aureus. The irradiances of the 461, 521 and 642 nm LEDs were 22.1, 16 and 25.4 mW/cm², respectively. Bacterial cultures suspended in tryptic soy broth were illuminated by 10-watt LEDs at a distance of 4.5 cm for 7.5h at 20, 15 and 10 °C. Regardless of the bacterial strains, bacterial inactivation was observed with the range of 4.6-5.2 logCFU/ml at 10 and 15 °C after illumination with the 461 nm LED, while illumination with the 521 nm LED resulted in only 1.0-2.0 log reductions after 7.5h. On the other hand, no antibacterial effect was observed using the 642 nm LED treatment. The photodynamic inactivation by 461 and 521 nm LEDs was found to be greater at the set temperatures of 10 and 15 °C than at 20 °C. The D-values for the four bacterial strains at 10 and 15 °C after the illumination of 461 nm LED ranged from 1.29 to 1.74 h, indicating that there was no significant difference in the susceptibility of the bacterial strains to the LED illumination between 10 and 15 °C, except for L. monocytogenes. Regardless of the illumination temperature, sublethal injury was observed in all bacterial strains during illumination with the 461 and the 521 nm LED and the percentage of injured cells increased as the treatment time increased. Thus, the results show that the antibacterial effect of the LEDs was highly dependent on the wavelength and the illumination temperature. This study suggests the potential of 461 and 521 nm LEDs in combination with chilling to be used as a novel food preservation technology., (© 2013 Elsevier B.V. All rights reserved.)

Background: Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease (RDD) is a rare benign disease with nodal and extranodal involvement., Methods and Results: Herein, we report 3 cases in which the patients presented with nasal masses. In addition, 2 of the 3 patients had subglottic lesions. Only 2 of the 3 patients had cervical lymphadenopathy, which is the commonest presentation of RDD. Histopathology via fine-needle aspiration cytology (FNAC) or open biopsy is required for diagnosis. Emperipolesis with S-100 immunohistochemical staining is characteristic. The disease runs a benign course and the literature reports that treatment can vary from steroids, to cytotoxic chemotherapy to radiotherapy with variable outcomes. Surgical intervention may be necessary for airway protection., Conclusion: RDD is self-limiting, but can sometimes be a life-threatening condition. Treatment should be tailored to the individual patient., (Copyright © 2011 Wiley Periodicals, Inc.)

Hybrid silk scaffolds combining knitted silk fibers and silk sponge have been recently developed for use as ligament-alone grafts. Incorporating an osteoinductive phase into the ends of a ligament scaffold may potentially generate an integrated "bone-ligament-bone" graft and improve graft osteointegration with host bone. To explore the possible application of hydroxyapatite (HA) coating in the fabrication of osteoinductive ends of silk-based scaffold, HA was coated on the hybrid silk scaffold and the effects to the bone-related cells were evaluated. HA could be coated in a uniform and controlled manner on the silk sponge, using an alternate soaking technology, with the amount deposited being dependent on the number of soaking cycles. HA coating also progressively reduced the hydrophobicity of silk surface (decreasing water contact angle from 87° to 42-76°, after 1-3 soaking cycles), making the HA-coated silk scaffold less favorable for initial cell attachments; but the attached cells showed viability and sustained proliferation on the HA-coated scaffold. As demonstrated by real-time polymerase chain reaction and alkaline phosphatase assay, the osteoinductivity of HA-coated silk scaffolds resulted in the osteogenic differentiation of bone marrow mesenchymal stem cells, and the osteoconductivity of HA-coated silk scaffolds supported osteoblasts growth and maintained the properties of mature osteoblasts. These properties of HA-coating demonstrated its possible application in fabricating osteoinductive ends of the silk-based ligament graft to potentially enhance graft-to-host bone integration., (Copyright © 2012 Wiley Periodicals, Inc.)

An abasic site is the most common lesion in DNA. It is also an intermediate product formed during base excision repair. Previously, we demonstrated that strand slippage can occur in primer-template model systems containing any kind of natural templating bases, suggesting deletion and expansion errors are possible in any kind of sequences during DNA replication. In this study, nuclear magnetic resonance spectroscopic investigations have been performed to study the intrinsic effect of a templating abasic residue on strand slippage in primer-template models. A DNA hairpin model system containing an abasic site and a 5'-overhang region was used to mimic the situation that a dNTP has just been incorporated opposite the abasic site. Our results show that, after dNTP incorporation, strand slippage occurs regardless of the type of terminal base pair formed. Compared to natural templating bases, abasic sites possess a higher slippage propensity, implicating a higher chance of expansion or deletion errors during DNA replication.

The ligament-bone interface is a complex structure that comprises ligament, fibrocartilage, and bone. We hypothesize that mesenchymal stem cells cocultured in between ligament and bone cells, on a hybrid silk scaffold with sections suitable for each cell type, would differentiate into fibrocartilage. The section of scaffold for osteoblast seeding was coated with hydroxyapatite. A trilineage coculture system (osteoblasts-BMSCs-fibroblasts) on a hybrid silk scaffold was established. RT-PCR results and immunohistochemistry results demonstrated that BMSCs cocultured between fibroblasts and osteoblasts had differentiated into the fibrocartilaginous lineage. The morphological change was also observed by SEM observation. A gradual transition from the uncalcified to the calcified region was formed in the cocultured BMSCs from the region that directly interacted with fibroblasts to the region that directly interacted with osteoblasts. The role of transforming growth factor β3 (TGF-β3) in this trilineage coculture model was also investigated by supplementing the coculture system with 10 ng/mL TGF-β3. The TGF-treated group showed similar results of fibrocartilaginous differentiation of BMSCs with coculture group without TGF-β3 supplement. However, no calcium deposition was found in the cocultured BMSCs in the TGF-treated group. This may indicate TGF-β3 delayed the mineralization process of chondrocytes.

Body donation is important for medical education and academic research. However, it is relatively rare in Hong Kong when compared with many Western countries. Comprehensive research has been performed on the motivation for body donation in Western countries; however, there is still insufficient research on body donation in Hong Kong to provide information on how to increase the body-donation rate. To understand the factors involved in the decision to donate one's body, the authors interviewed a registered donor and the daughter of another donor in Hong Kong. The authors interpreted the information collected in light of the available published reports, which mostly focus on body donation in Western countries. Despite the consistency of some demographic factors and motivations between the participants in our study and those investigated in the published reports from Western countries, there are differences in education level and socioeconomic status between the donors in our study and those from Western studies. The authors also suggest that Confucianism and Buddhism in Chinese culture may motivate potential body donors in Hong Kong. Other important factors that influence the body-donation decision may include family members' body donation, registration as organ donors, and good doctor-patient relationships. Although case report studies have their limitations, this study allows us to explore the complexity of events and establish the interconnectivity of factors involved in body donation, which could not be achieved in previous survey-based studies., (Copyright © 2012 American Association of Anatomists.)

Thrombolysis using tissue plasminogen activator (tPA) has been the key treatment for patients with acute ischemic stroke for the past decade. Recent studies, however, suggest that this clot-busting protease also plays various roles in brain physiological and pathophysiological glutamatergic-dependent processes, such as synaptic plasticity and neurodegeneration. In addition, increasing evidence implicates tPA as an important neuromodulator of the N-methyl-d-aspartate (NMDA) receptors. Here, we demonstrate that recombinant human tPA cleaves the NR2B subunit of NMDA receptor. Analysis of NR2B in rat brain lysates and cortical neurons treated with tPA revealed concentration- and time-dependent degradation of NR2B proteins. Peptide sequencing studies performed on the cleaved-off products obtained from the tPA treatment on a recombinant fusion protein of the amino-terminal domain of NR2B revealed that tPA-mediated cleavage occurred at arginine 67 (Arg(67)). This cleavage is tPA-specific, plasmin-independent, and removes a predicted ~4-kDa fragment (Arg(27)-Arg(67)) from the amino-terminal domain of the NR2B protein. Site-directed mutagenesis of putative cleavage site Arg(67) to Ala(67) impeded tPA-mediated degradation of recombinant protein. This analysis revealed that NR2B is a novel substrate of tPA and suggested that an Arg(27)-Arg(67)-truncated NR2B-containing NMDA receptor could be formed. Heterologous expression of NR2B with Gln(29)-Arg(67) deleted is functional but exhibits reduced ifenprodil inhibition and increased glycine EC(50) with no change in glutamate EC(50). Our results confirmed NR2B as a novel proteolytic substrate of tPA, where tPA may directly interact with NR2B subunits leading to a change in pharmacological properties of NR2B-containing NMDA receptors.

While silk-based microfibrous scaffolds possess excellent mechanical properties and have been used for ligament tissue-engineering applications, the microenvironment in these scaffolds is not biomimetic. We hypothesized that coating a hybrid silk scaffold with an extracellular matrix (ECM)-like network of self-assembling peptide nanofibers would provide a biomimetic three-dimensional nanofibrous microenvironment and enhance ligament tissue regeneration after bone marrow-derived mesenchymal stem cell (BMSC)-seeding. A novel scaffold possessing a triple structural hierarchy comprising macrofibrous knitted silk fibers, a silk microsponge, and a peptide nanofiber mesh was developed by coating self-assembled RADA16 peptide nanofibers on a silk microfiber-reinforced-sponge scaffold. Compared with the uncoated control, RADA-coated scaffolds showed enhanced BMSC proliferation, metabolism, and fibroblastic differentiation during the 3 weeks of culture. BMSC-seeded RADA-coated scaffolds showed an increasing temporal expression of key fibroblastic ECM proteins (collagen type I and III, tenascin-C), with a significantly higher tenascin-C expression compared with the controls. BMSC-seeded RADA-coated scaffolds also showed a temporal increase in total collagen and glycosaminoglycan production (the amount produced being higher than in control scaffolds) during 3 weeks of culture, and possessed 7% higher maximum tensile load compared with the BMSC-seeded control scaffolds. The results indicate that the BMSC-seeded RADA-coated hybrid silk scaffold system has the potential for use in ligament tissue-engineering applications.