Simulations of extensional flow in microrheometric devices

We present a detailed numerical study of the flow of a Newtonian fluid through microrheometric devices featuring a sudden contraction–expansion. This flow configuration is typically used to generate extensional deformations and high strain rates. The excess pressure drop resulting from the converging and diverging flow is an important dynamic measure to quantify if the device is intended to be used as a microfluidic extensional rheometer. To explore this idea, we examine the effect of the contraction length, aspect ratio and Reynolds number on the flow kinematics and resulting pressure field. Analysis of the computed velocity and pressure fields show that, for typical experimental conditions used in microfluidic devices, the steady flow is highly three-dimensional with open spiraling vortical structures in the stagnant corner regions. The numerical simulations of the local kinematics and global pressure drop are in good agreement with experimental results. The device aspect ratio is shown to have a strong impact on the flow and consequently on the excess pressure drop, which is quantified in terms of the dimensionless Couette and Bagley correction factors. We suggest an approach for calculating the Bagley correction which may be especially appropriate for planar microchannels

Multi-component based cross correlation beat detection in electrocardiogram analysis

BACKGROUND: The first stage in computerised processing of the electrocardiogram is beat detection. This involves identifying all cardiac cycles and locating the position of the beginning and end of each of the identifiable waveform components. The accuracy at which beat detection is performed has significant impact on the overall classification performance, hence efforts are still being made to improve this process. METHODS: A new beat detection approach is proposed based on the fundamentals of cross correlation and compared with two benchmarking approaches of non-syntactic and cross correlation beat detection. The new approach can be considered to be a multi-component based variant of traditional cross correlation where each of the individual inter-wave components are sought in isolation as opposed to being sought in one complete process. Each of three techniques were compared based on their performance in detecting the P wave, QRS complex and T wave in addition to onset and offset markers for 3000 cardiac cycles. RESULTS: Results indicated that the approach of multi-component based cross correlation exceeded the performance of the two benchmarking techniques by firstly correctly detecting more cardiac cycles and secondly provided the most accurate marker insertion in 7 out of the 8 categories tested. CONCLUSION: The main benefit of the multi-component based cross correlation algorithm is seen to be firstly its ability to successfully detect cardiac cycles and secondly the accurate insertion of the beat markers based on pre-defined values as opposed to performing individual gradient searches for wave onsets and offsets following fiducial point location

Reorganisation of Wnt-response pathways in colorectal tumorigenesis

In most colorectal tumours, APC mutation stabilises β-catenin and mimics elements of Wnt growth factor signalling, but the high frequency of epigenetic loss of Wnt antagonists indicates an additional role for ligand-mediated Wnt signalling. Here, we have investigated the expression of key components of β-catenin-independent Wnt response pathways to determine whether their profiles change during the transition from normal mucosa to colorectal adenomas. Transcription of the Wnt/planar cell polarity pathway determinant NKD1 (naked cuticle homologue 1) was induced in adenomas by a median 135-fold and in cancers by 7.4-fold. While some Frizzleds (FZDs) were downregulated in adenomas, the Wnt/Ca2+ receptors FZD3 and FZD6 were induced by a median factor of 6.5 and 4.6, respectively. Naked cuticle homologue 1, FZD3 and FZD6 expression were coordinated in pre-malignant disease, but this relationship was lost in invasive cancers, where FZD induction was seen less frequently. Naked cuticle homologue 1 expression was associated with nuclear localisation of phospho-c-Jun in adenomas. In cultured cells, NKD1 transcription was induced by lithium chloride but FZD3 expression required Wnt growth factor treatment. These data show that Wnt responses are consistently directed towards both β-catenin-independent routes in early colorectal tumorigenesis and elements of this are retained in more advanced cancers. These β-catenin-independent Wnt signalling pathways may provide novel targets for chemoprevention of early colorectal tumours

Common extensor origin release in recalcitrant lateral epicondylitis - role justified?

The aim of our study was to analyse the efficacy of operative management in recalcitrant lateral epicondylitis of elbow. Forty patients included in this study were referred by general practitioners with a diagnosis of tennis elbow to the orthopaedic department at a district general hospital over a five year period. All had two or more steroid injections at the tender spot, without permanent relief of pain. All subsequently underwent simple fasciotomy of the extensor origin. Of forty patients thirty five had improvement in pain and function, two had persistent symptoms and three did not perceive any improvement. Twenty five had excellent, ten had well, two had fair and three had poor outcomes (recurrent problem; pain at rest and night). Two patients underwent revision surgery. Majority of the patients had improvement in pain and function following operative treatment. In this study, an extensor fasciotomy was demonstrated to be an effective treatment for refractory chronic lateral epicondylitis; however, further studies are warranted

Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI)

BACKGROUND: The inFLUenza Patient Reported Outcome (FLU-PRO) measure is a daily diary assessing signs/symptoms of influenza across six body systems: Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, developed and tested in adults with influenza. OBJECTIVES: This study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI). METHODS: Data from the prospective, observational study used to develop and test the FLU-PRO in influenza virus positive patients were analyzed. Adults (≥18 years) presenting with influenza symptoms in outpatient settings in the US, UK, Mexico, and South America were enrolled, tested for influenza virus, and asked to complete the 37-item draft FLU-PRO daily for up to 14-days. Analyses were performed on data from patients testing negative. Reliability of the final, 32-item FLU-PRO was estimated using Cronbach's alpha (α; Day 1) and intraclass correlation coefficients (ICC; 2-day reproducibility). Convergent and known-groups validity were assessed using patient global assessments of influenza severity (PGA). Patient report of return to usual health was used to assess responsiveness (Day 1-7). RESULTS: The analytical sample included 220 ILI patients (mean age = 39.3, 64.1% female, 88.6% white). Sixty-one (28%) were hospitalized at some point in their illness. Internal consistency reliability (α) of FLU-PRO Total score was 0.90 and ranged from 0.72-0.86 for domain scores. Reproducibility (Day 1-2) was 0.64 for Total, ranging from 0.46-0.78 for domain scores. Day 1 FLU-PRO scores correlated (≥0.30) with the PGA (except Gastrointestinal) and were significantly different across PGA severity groups (Total: F = 81.7, p<0.001; subscales: F = 6.9-62.2; p<0.01). Mean score improvements Day 1-7 were significantly greater in patients reporting return to usual health compared with those who did not (p<0.05, Total and subscales, except Gastrointestinal and Eyes). CONCLUSIONS: Results suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness

Cerebrospinal Fluid B Cells Correlate with Early Brain Inflammation in Multiple Sclerosis

Background: There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS). Methodology/Principal Findings: In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF) cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS), relapsing-remitting (RR) and chronic progressive (CP) MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD1382) and plasma blasts (CD19+CD138+) in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matri

Bioactive Hydrogel Marbles

Liquid marbles represented a signifcant advance in the manipulation of fuids as they used particle flms to confne liquid drops, creating a robust and durable soft solid. We exploit this technology to engineering a bioactive hydrogel marble (BHM). Specifcally, pristine bioactive glass nanoparticles were chemically tuned to produce biocompatible hydrophobic bioactive glass nanoparticles (H-BGNPs) that shielded a gelatin-based bead. The designed BHM shell promoted the growth of a bone-like apatite layer upon immersion in a physiological environment. The fabrication process allowed the efcient incorporation of drugs and cells into the engineered structure. The BHM provided a simultaneously controlled release of distinct encapsulated therapeutic model molecules. Moreover, the BHM sustained cell encapsulation in a 3D environment as demonstrated by an excellent in vitro stability and cytocompatibility. The engineered structures also showed potential to regulate a pre-osteoblastic cell line into osteogenic commitment. Overall, these hierarchical nanostructured and functional marbles revealed a high potential for future applications in bone tissue engineering.Portuguese Foundation for Science and Technology − FCT (Grant Nos SFRH/BD/73174/2010 and SFRH/BD/73172/2010, respectively), from the program POPH/FSE from QREN. The authors would like to acknowledge the support of the European Research Council grant agreement ERC-2014-ADG-669858 for project ATLASinfo:eu-repo/semantics/publishedVersio

The opposite effects of fluvoxamine and sertraline in the treatment of psychotic major depression: a case report

<p>Abstract</p> <p>Background</p> <p>Psychotic major depression is a clinical subtype of major depressive disorder. A number of clinical studies have demonstrated the efficacy of the combination of an antidepressant (for example, a tricyclic antidepressant or selective serotonin reuptake inhibitor (SSRI)) and an atypical antipsychotic or electroconvulsive therapy (ECT) in treating psychotic major depression. In several studies, monotherapy of SSRIs such as fluvoxamine has been shown to be effective in the treatment of psychotic major depression.</p> <p>Methods</p> <p>We report on a 36-year-old Japanese woman in whom fluvoxamine (a SSRI with sigma-1 receptor agonist) and sertraline (a SSRI with sigma-1 receptor antagonist) showed the opposite effects on psychotic symptoms in the treatment of psychotic major depression.</p> <p>Results</p> <p>Symptoms of depression and psychosis in the patient who was non-respondent to antipsychotic drugs improved after fluvoxamine monotherapy. At 3 years later, a switch to sertraline from fluvoxamine dramatically worsened the psychotic symptoms in the patient. Then, a switch back to fluvoxamine from sertraline improved these symptoms 1 week after fluvoxamine treatment.</p> <p>Conclusion</p> <p>Doctors should consider the monotherapy of sigma-1 receptor agonist fluvoxamine as an alternative approach to treating psychotic major depression.</p

Air Trapping on Chest CT Is Associated with Worse Ventilation Distribution in Infants with Cystic Fibrosis Diagnosed following Newborn Screening

BACKGROUND: In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF. METHODS: Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M(1)/M(0) and M(2)/M(0), respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping. RESULTS: Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M(2)/M(0) but not LCI or M(1)/M(0). There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes. CONCLUSION: These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF