Antioxidant and anti-inflammatory properties of an aqueous cyanophyta extract derived from Arthrospira platensis: contribution to bioactivities by the non-phycocyanin aqueous fraction.
The goal for this work was to characterize basic biological properties of a novel Arthrospira platensis-based aqueous cyanophyta extract (ACE), enriched in the known anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor phycocyanin (PC), but also containing a high level of non-PC bioactive compounds. Antioxidant properties were tested in parallel in the Folin-Ciocalteu assay (chemical antioxidant capacity) and in the cellular antioxidant protection (CAP-e) bioassay, where both the PC and the non-PC fractions contributed to the antioxidant capacity and CAP of ACE. In contrast to the COX-2 inhibition seen in the presence of PC, the inhibition of enzymatic activity of the inflammatory mediator Lipoxygenase was associated specifically with the non-PC fraction of ACE. Inhibition of formation of reactive oxygen species (ROS) was evaluated using polymorphonuclear cells from healthy human donors. The inhibition of ROS formation was seen for both the PC and non-PC fractions, with ACE showing the most robust effect. The effects of PC, non-PC, and ACE on clotting and clot lysing was tested using a modified Euglobulin fibrinolytic assay in vitro. In the presence of PC, non-PC, and ACE, the time for clot formation and lysis was not affected; however, the clots were significantly more robust. This effect was statistically significant (p<.05) at doses between 125-500 μg/mL, and returned to baseline at lower doses. Both PC and the non-PC fraction contributed to the antioxidant properties and anti-inflammatory effects, without a negative impact on blood clotting in vitro. This suggests a potential benefit for the consumable ACE extract in assisting the reduction of inflammatory conditions.


Humoral immune responses to Neisseria meningitidis in children.
An understanding of the nature of immunity to serogroup B meningococci in childhood is necessary in order to establish the reasons for poor responses to candidate vaccines in infancy. We sought to examine the nature of humoral immune responses following infection in relation to age. Serum bactericidal activity was poor in children under 12 months of age despite recent infection with Neisseria meningitidis. The highest levels of bactericidal activity were seen in children over 10 years of age. However, infants produced levels of total immunoglobulin G (IgG) and IgG subclass antibodies similar to those in older children in a meningococcal enzyme-linked immunosorbent assay. Most antibody was of the IgG1 and IgG3 subclasses. This striking age dependency of bactericidal antibody response following infection is not apparently due to failure of class switching in infants but might be due to qualitative differences in antibody specificity or affinity.


Climate and suitable clothing.
Climate may be described as refined weather The meteorologist notes the day-to-day variations of the weather components, extracts the principal frequencies which then describe the seasons, and once the average values have been derived over long periods of time, there emerges the concept of climate. Advances in preventive and curative medicine are such that man is left virtually with only his two oldest enemies to combat: his fellow men and the environment and he will be able to give better attention to the former if the latter is neutralised by the supply of suitable clothing designed to keep him comfortable.


Enhancing strength and postocclusive calf blood flow in older people with training with blood-flow restriction.
The response of calf-muscle strength, resting blood flow, and postocclusive blood flow (PObf) were investigated after 4 wk of low-load resistance training (LLRT) with and without blood-flow restriction in a matched-leg design. Ten untrained older individuals age 62-73 yr performed unilateral plantar-flexion LLRT at 25% 1-repetition maximum (1RM). One limb was trained with normal blood flow and the other had blood flow restricted using a pressure cuff above the knee. 1RM, isometric maximal voluntary contraction, and isokinetic strength at 0.52 rad/s increased (p < .05) more after LLRT with blood-flow restriction than with normal blood flow. Peak PObf increased (p < .05) after LLRT with blood-flow restriction, compared with no change after LLRT with normal blood flow. These results suggest that 4 wk of LLRT with blood-flow restriction may be beneficial to older individuals to improve strength and blood-flow parameters.


A region growing vessel segmentation algorithm based on spectrum information.
We propose a region growing vessel segmentation algorithm based on spectrum information. First, the algorithm does Fourier transform on the region of interest containing vascular structures to obtain its spectrum information, according to which its primary feature direction will be extracted. Then combined edge information with primary feature direction computes the vascular structure's center points as the seed points of region growing segmentation. At last, the improved region growing method with branch-based growth strategy is used to segment the vessels. To prove the effectiveness of our algorithm, we use the retinal and abdomen liver vascular CT images to do experiments. The results show that the proposed vessel segmentation algorithm can not only extract the high quality target vessel region, but also can effectively reduce the manual intervention.


Histone H3.3 regulates dynamic chromatin states during spermatogenesis.
The histone variant H3.3 is involved in diverse biological processes, including development, transcriptional memory and transcriptional reprogramming, as well as diseases, including most notably malignant brain tumors. Recently, we developed a knockout mouse model for the H3f3b gene, one of two genes encoding H3.3. Here, we show that targeted disruption of H3f3b results in a number of phenotypic abnormalities, including a reduction in H3.3 histone levels, leading to male infertility, as well as abnormal sperm and testes morphology. Additionally, null germ cell populations at specific stages in spermatogenesis, in particular spermatocytes and spermatogonia, exhibited increased rates of apoptosis. Disruption of H3f3b also altered histone post-translational modifications and gene expression in the testes, with the most prominent changes occurring at genes involved in spermatogenesis. Finally, H3f3b null testes also exhibited abnormal germ cell chromatin reorganization and reduced protamine incorporation. Taken together, our studies indicate a major role for H3.3 in spermatogenesis through regulation of chromatin dynamics.


Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks.
Here we challenge the view that reward-guided learning is solely controlled by the mesoaccumbens pathway arising from dopaminergic neurons in the ventral tegmental area and projecting to the nucleus accumbens. This widely accepted view assumes that reward is a monolithic concept, but recent work has suggested otherwise. It now appears that, in reward-guided learning, the functions of ventral and dorsal striata, and the cortico-basal ganglia circuitry associated with them, can be dissociated. Whereas the nucleus accumbens is necessary for the acquisition and expression of certain appetitive Pavlovian responses and contributes to the motivational control of instrumental performance, the dorsal striatum is necessary for the acquisition and expression of instrumental actions. Such findings suggest the existence of multiple independent yet interacting functional systems that are implemented in iterating and hierarchically organized cortico-basal ganglia networks engaged in appetitive behaviors ranging from Pavlovian approach responses to goal-directed instrumental actions controlled by action-outcome contingencies.


Induction of zonal-specific cellular morphology and matrix synthesis for biomimetic cartilage regeneration using hybrid scaffolds.
Cartilage is anisotropic in nature and organized into distinct zones. Our goal was to develop zonal-specific three-dimensional hybrid scaffolds which could induce the generation of zonal-specific cellular morphology and extracellular matrix (ECM) composition. The superficial and middle zones comprised two layers of hyaluronic acid (HA) hydrogel which enveloped specifically orientated or randomly arranged polylactic acid nanofibre meshes. The deep zone comprised a HA hydrogel with multiple vertical channels. Primary bovine chondrocytes were seeded into the individual zonal scaffolds, cultured for 14 days and then the ECM was analysed. The aligned nanofibre mesh used in the superficial zone induced an elongated cell morphology, lower glycosaminoglycan (GAG) and collagen II production, and higher cell proliferation and collagen I production than the cells in the middle zone scaffold. Within the middle zone scaffold, which comprised a randomly orientated nanofibre mesh, the cells were clustered and expressed more collagen II. The deep zone scaffold induced the highest GAG production, the lowest cell proliferation and the lowest collagen I expression of the three zones. Assembling the three zones and stabilizing the arrangement with a HA hydrogel generated aligned, randomly aggregated and columnar cells in the superficial, middle and deep zones. This study presents a method to induce zonal-specific chondrocyte morphology and ECM production.


Mitochondrial genome characterization of Melipona bicolor: Insights from the control region and gene expression data.
The stingless bee Melipona bicolor is the only bee in which true polygyny occurs. Its mitochondrial genome was first sequenced in 2008, but it was incomplete and no information about its transcription was known. We combined short and long reads of M. bicolor DNA with RNASeq data to obtain insights about mitochondrial evolution and gene expression in bees. The complete genome has 15,001 bp, including a control region of 255 bp that contains all conserved structures described in honeybees with the highest AT content reported so far for bees (98.1%), displaying a compact but functional region. Gene expression control is similar to other insects however unusual patterns of expression may suggest the existence of different isoforms for the mitochondrially encoded 12S rRNA. Results reveal unique and shared features of the mitochondrial genome in terms of sequence evolution and gene expression making M. bicolor an interesting model to study mitochondrial genomic evolution.


Second-year medical students' motivational beliefs, emotions, and achievement.
A challenge for medical educators is to better understand the personal factors that lead to individual success in medical school and beyond. Recently, educational researchers in fields outside medicine have acknowledged the importance of motivation and emotion in students' learning and performance. These affective factors have received less emphasis in the medical education literature. This longitudinal study examined the relations between medical students' motivational beliefs (task value and self-efficacy), achievement emotions (enjoyment, anxiety and boredom) and academic achievement. Second-year medical students (n=136) completed motivational beliefs and achievement emotions surveys following their first and second trimesters, respectively. Academic achievement was operationalised as students' average course examination grades and national board shelf examination scores. The results largely confirmed the hypothesised relations between beliefs, emotions and achievement. Structural equation modelling revealed that task value beliefs were positively associated with course-related enjoyment (standardised regression coefficient [β] = 0.59) and were negatively related to boredom (β= -0.25), whereas self-efficacy beliefs were negatively associated with course-related anxiety only (β = -0.47). Furthermore, student enjoyment was positively associated with national board shelf examination score (β = 0.31), whereas anxiety and boredom were both negatively related to course examination grade (β= -0.36 and -0.27, respectively). The overall structural model accounted for considerable variance in each of the achievement outcomes: R(2) = 0.20 and 0.14 for the course examination grade and national board shelf examination score, respectively. This study suggests that medical students' motivational beliefs and achievement emotions are important contributors to their academic achievement. These results have implications for medical educators striving to understand the personal factors that influence learning and performance in medical training.


ERP correlates of shared control mechanisms involved in saccade preparation and in covert attention.
We investigated whether attention shifts and eye movement preparation are mediated by shared control mechanisms, as claimed by the premotor theory of attention. ERPs were recorded in three tasks where directional cues presented at the beginning of each trial instructed participants to direct their attention to the cued side without eye movements (Covert task), to prepare an eye movement in the cued direction without attention shifts (Saccade task) or both (Combined task). A peripheral visual Go/Nogo stimulus that was presented 800 ms after cue onset signalled whether responses had to be executed or withheld. Lateralised ERP components triggered during the cue-target interval, which are assumed to reflect preparatory control mechanisms that mediate attentional orienting, were very similar across tasks. They were also present in the Saccade task, which was designed to discourage any concomitant covert attention shifts. These results support the hypothesis that saccade preparation and attentional orienting are implemented by common control structures. There were however systematic differences in the impact of eye movement programming and covert attention on ERPs triggered in response to visual stimuli at cued versus uncued locations. It is concluded that, although the preparatory processes underlying saccade programming and covert attentional orienting may be based on common mechanisms, they nevertheless differ in their spatially specific effects on visual information processing.


Attitude of physicians towards automatic alerting in computerized physician order entry systems. A comparative international survey.
To analyze the attitude of physicians towards alerting in CPOE systems in different hospitals in different countries, addressing various organizational and technical settings and the view of physicians not currently using a CPOE. A cross-sectional quantitative and qualitative questionnaire survey. We invited 2,600 physicians in eleven hospitals from nine countries to participate. Eight of the hospitals had different CPOE systems in use, and three of the participating hospitals were not using a CPOE system. 1,018 physicians participated. The general attitude of the physicians towards CPOE alerting is positive and is found to be mostly independent of the country, the specific organizational settings in the hospitals and their personal experience with CPOE systems. Both quantitative and qualitative results show that the majority of the physicians, both CPOE-users and non-users, appreciate the benefits of alerting in CPOE systems on medication safety. However, alerting should be better adapted to the clinical context and make use of more sophisticated ways to present alert information. The vast majority of physicians agree that additional information regarding interactions is useful on demand. Around half of the respondents see possible alert overload as a major problem; in this regard, physicians in hospitals with sophisticated alerting strategies show partly better attitude scores. Our results indicate that the way alerting information is presented to the physicians may play a role in their general attitude towards alerting, and that hospitals with a sophisticated alerting strategy with less interruptive alerts tend towards more positive attitudes. This aspect needs to be further investigated in future studies.


Non-invasive metabolomic analysis of breath using differential mobility spectrometry in patients with chronic obstructive pulmonary disease and healthy smokers.
The rapid, accurate and non-invasive diagnosis of respiratory disease represents a challenge to clinicians, and the development of new treatments can be confounded by insufficient knowledge of lung disease phenotypes. Exhaled breath contains a complex mixture of volatile organic compounds (VOCs), some of which could potentially represent biomarkers for lung diseases. We have developed an adaptive sampling methodology for collecting concentrated samples of exhaled air from participants with impaired respiratory function, against which we employed two-stage thermal desorption gas chromatography-differential mobility spectrometry (GC-DMS) analysis, and showed that it was possible to discriminate between participants with and without chronic obstructive pulmonary disease (COPD). A 2.5 dm(3) volume of end tidal breath was collected onto adsorbent traps (Tenax TA/Carbotrap), from participants with severe COPD and healthy volunteers. Samples were thermally desorbed and analysed by GC-DMS, and the chromatograms analysed by univariate and multivariate analyses. Kruskal-Wallis ANOVA indicated several discriminatory (p < 0.01) signals, with good classification performance (receiver operator characteristic area up to 0.82). Partial least squares discriminant analysis using the full DMS chromatograms also gave excellent discrimination between groups (alpha = 19% and beta = 12.4%).


Induction by IL-9 and suppression by IL-3 and IL-4 of the levels of chromosome 14-derived transcripts that encode late-expressed mouse mast cell proteases.
Immature, rIL-3-dependent mouse bone marrow-derived mast cells (BMMC) contain high steady-state levels of the mouse mast cell protease (mMCP) 5 transcript but undetectable levels of the mMCP-1, mMCP-2, or mMCP-4 transcripts even though all four of their genes reside at a locus on chromosome 14. These mast cells can be induced by recombinant c-kit ligand (rKL) to obtain high steady-state levels of the mMCP-4 transcript and by rIL-10 to obtain high steady-state levels of the mMCP-1 and mMCP-2 transcripts. rIL-3 and rKL both elicit the differentiation of progenitor cells into immature BMMC and then stimulate their proliferation. We now report that although rIL-9 alone has no effect on BMMC proliferation as assessed by their incorporation of [3H]thymidine, rIL-9 in combination with rKL enhances the long term viability of BMMC. Furthermore, rIL-9 in the presence of rKL stimulates mouse BMMC to undergo a phenotypic change by inducing accumulation of high steady-state levels of the mMCP-1 and mMCP-2 transcripts. In contrast, in BMMC, the presence of rIL-4 suppresses the rIL-9-induced accumulation of the mMCP-1 and mMCP-2 transcripts, the rIL-10-induced accumulation of the mMCP-1 and mMCP-2 transcripts, and the rKL-induced accumulation of the mMCP-4 transcript, but not the rIL-3-induced accumulation of the mMCP-5 transcript. The presence of rIL-3 also suppresses the rIL-9-induced accumulation of the mMCP-1 and mMCP-2 transcripts. Because of their counter-regulatory actions on the steady-state levels of transcripts that encode three late-expressed serine proteases in BALB/cJ mice, rIL-4 and rIL-3 both inhibit the final stages of differentiation and maturation of mast cells. Because rIL-4, unlike rIL-3, is neither an inducer of early-expressed proteases nor alone a proliferative factor for BMMC, the counterregulatory actions of rIL-3 and rIL-4 on differentiation and maturation of these mouse mast cells are independent of their other functions.


Persistent enhancement of neuron-glia signaling mediated by increased extracellular K+ accompanying long-term synaptic potentiation.
Neuron-glia signaling is important for neural development and functions. This signaling may be regulated by neuronal activity and undergo modification similar to long-term potentiation (LTP) of neuronal synapses, a hallmark of neuronal plasticity. We found that tetanic stimulation of Schaffer collaterals (Sc) in the hippocampus that induced LTP in neurons also resulted in LTP-like persistent elevation of Sc-evoked slow depolarization in perisynaptic astrocytes. The elevated slow depolarization in astrocytes was abolished by NMDA receptor antagonist and K(+) channel inhibitors, but not by Ca(2+) chelator BAPTA loaded in the recorded astrocytes, suggesting involvement of an increased extracellular K(+) accumulation accompanying LTP of neuronal synapses. The increased K(+) accumulation and astrocyte depolarization after LTP induction may reduce the efficiency of glial glutamate transporters, which may contribute to the enhanced synaptic efficacy. The neuronal activity-induced persistent enhancement of neuron-glia signaling may thus have important physiological relevance.


The feasibility and acceptability of a cognitive-behavioural self-help intervention for adolescents with obsessive-compulsive disorder.
Breaking Free from OCD is a cognitive behavioural self-help book for young people with obsessive compulsive disorder (OCD). The book is written for 11-16 year olds as a first step intervention for reducing mild to moderate symptoms of OCD. This report describes a preliminary evaluation of the feasibility and acceptability of the book as a self-help intervention. Using a case-series design, eight 11-16 year olds with OCD were monitored for symptom stability 3 weeks prior to receiving Breaking Free from OCD for use over an 8-week period. Weekly telephone calls were received to complete the CY-BOCS for symptom severity and to monitor adherence to the intervention. The CHOCI and SDQ were sent to participants and their parents pre-, mid- and post-intervention. There was a significant reduction in CY-BOCS symptom severity over the course of the intervention; however, there were no statistically significant changes on the self-report measures. The intervention was well received by the majority of young people who took part. Breaking Free from OCD may help young people with OCD and is an acceptable low intensity intervention. This evaluation is the first step in developing low intensity approaches for child OCD.


Mesh-based Monte Carlo method using fast ray-tracing in Plücker coordinates.
We describe a fast mesh-based Monte Carlo (MC) photon migration algorithm for static and time-resolved imaging in 3D complex media. Compared with previous works using voxel-based media discretization, a mesh-based approach can be more accurate in modeling targets with curved boundaries or locally refined structures. We implement an efficient ray-tracing technique using Plücker Coordinates. The Barycentric coordinates computed from Plücker-formed ray-tracing enables us to use linear Lagrange basis functions to model both media properties and fluence distribution, leading to further improvement in accuracy. The Plücker-coordinate ray-polygon intersection test can be extended to hexahedral or high-order elements. Excellent agreement is found when comparing mesh-based MC with the analytical diffusion model and 3D voxel-based MC code in both homogeneous and heterogeneous cases. Realistic time-resolved imaging results are observed for a complex human brain anatomy using mesh-based MC. We also include multi-threading support in the software and will port it to a graphics processing unit platform in the near future.


Communicable diseases and governance: a tale of two regions.
Regional policies and programmes on communicable disease prevention and control are becoming an important component of global public health. In a comparative fashion, we examined the situation in the European and Southeast Asian contexts, with a focus on the underlying institutional and political backgrounds underpinning the regionalisation of planning and interventions. Our findings document the emergence of two distinctive models of regional integration. While in Europe there is a process of institutionalisation and centralisation, in Southeast Asia the landscape of regional cooperation is characterised by the proliferation of many provisional projects, based on loose agreements and a decentralised structure that emphasises the initiative and sense of ownership of member countries. These two approaches, we conclude, reflect wider differences of political culture between supranational integration in Europe and intergovernmental agreements in Southeast Asia.


TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea-a MASTERMIND study protocol.
Pharmaceutical treatment options for patients with type 2 diabetes mellitus (T2DM) have increased to include multiple classes of oral glucose-lowering agents but without accompanying guidance on which of these may most benefit individual patients. Clinicians lack information for treatment intensification after first-line metformin therapy. Stratifying patients by simple clinical characteristics may improve care by targeting treatment options to those in whom they are most effective. This academically designed and run three-way crossover trial aims to test a stratification approach using three standard oral glucose-lowering agents. TriMaster is a randomised, double-blind, crossover trial taking place at up to 25 clinical sites across England, Scotland and Wales. 520 patients with T2DM treated with either metformin alone, or metformin and a sulfonylurea who have glycated haemoglobin (HbA1c) >58 mmol/mol will be randomised to receive 16 weeks each of a dipeptidyl peptidase-4 inhibitor, sodium-glucose co-transporter-2 inhibitor and thiazolidinedione in random order. Participants will be assessed at the end of each treatment period, providing clinical and biochemical data, and their experience of side effects. Participant preference will be assessed on completion of all three treatments. The primary endpoint is HbA1c after 4 months of therapy (allowing a range of 12-18 weeks for analysis). Secondary endpoints include participant-reported preference between the three treatments, tolerability and prevalence of side effects. This study was approved by National Health Service Health Research Authority Research Ethics Committee South Central-Oxford A, study 16/SC/0147. Written informed consent will be obtained from all participants. Results will be submitted to a peer-reviewed journal and presented at relevant scientific meetings. A lay summary of results will be made available to all participants. 12039221; 2015-002790-38 and NCT02653209.


A randomised controlled study of the post-operative analgesic efficacy of ultrasound-guided pectoral nerve block in the first 24 h after modified radical mastectomy.
Breast cancer has become the most common cancer in women worldwide. Acute post-operative pain following mastectomy remains a challenge for the anaesthesiologist despite a range of treatment options available. The present study aimed to compare the post-operative analgesic efficacy of pectoral nerve (Pecs) block performed under ultrasound with our standard practice of opioids and non-steroidal anti-inflammatory drugs for mastectomy. This randomised controlled study was conducted at a tertiary care teaching hospital in India, after obtaining ethical clearance. Fifty adult female patients posted for elective unilateral modified radical mastectomy were divided into two groups as follows: Group I (general anaesthesia only) and Group II (general anaesthesia plus ultrasound-guided Pecs block), each comprising 25 patients. Post-randomisation, patients in Group I received general anaesthesia, while Group II patients received ultrasound-guided Pecs block followed by general anaesthesia after 20 min. The primary outcome was measured as patient-reported pain intensity using Visual Analogue Scale (VAS) at rest. Statistical analysis was performed using Student's t-test and Mann-Whitney U-test. Data were entered into MS Excel spreadsheet and analysis was performed using the Statistical Package for the Social Sciences version 23.0. VAS score was significantly lower in Group II at rest and on abduction post-operatively at all time intervals (P < 0.001). The 24-h tramadol consumption was significantly less in Group II compared to Group I (114.4 ± 4.63 mg vs. 402.88 ± 74.22, P < 0.0001). Pecs block provided excellent post-operative analgesia in the first 24 h.


Aspergillus fumigatus AcuM regulates both iron acquisition and gluconeogenesis.
Relatively few transcription factors that govern the virulence of Aspergillus fumigatus are known. We constructed 11 A. fumigatus transcription factor mutants and screened them for altered virulence in Galleria mellonella larvae. We discovered that the zinc cluster transcription factor, AcuM, is essential for maximal virulence in this model, as well as in murine models of haematogenously disseminated and invasive pulmonary aspergillosis. Transcriptional profiling experiments suggested that AcuM suppresses sreA and induces hapX to stimulate expression of genes involved in both reductive iron assimilation and siderophore-mediated iron uptake. Consistent with these results, a ΔacuM mutant had reduced iron incorporation, decreased extracellular siderophore production and impaired capacity to grow under iron-limited conditions. Interestingly, an Aspergillus nidulansΔacuM mutant had normal extracellular siderophore production and growth under iron-limited conditions, indicating that AcuM does not govern iron acquisition in this organism. A. fumigatus AcuM also regulated genes involved in gluconeogenesis, and the ΔacuM mutant had impaired growth on gluconeogenic carbon sources. Deletion of sreA in the ΔacuM mutant restored iron uptake, extracellular siderophore production and virulence, but not the defect in gluconeogenesis. Thus, AcuM represses SreA and thereby induces iron acquisition, a process that is essential for the maximal virulence of A. fumigatus.


The Digital Skills, Experiences and Attitudes of the Northern Ireland Social Care Workforce Toward Technology for Learning and Development: Survey Study.
Continual development of the social care workforce is a key element in improving outcomes for the users of social care services. As the delivery of social care services continues to benefit from innovation in assistive technologies, it is important that the digital capabilities of the social care workforce are aligned. Policy makers have highlighted the importance of using technology to support workforce learning and development, and the need to ensure that the workforce has the necessary digital skills to fully benefit from such provisions. This study aims to identify the digital capability of the social care workforce in Northern Ireland and to explore the workforce's appetite for and barriers to using technology for learning and development. This study is designed to answer the following research questions: (1) What is the digital capability of the social care workforce in Northern Ireland? (2) What is the workforce's appetite to participate in digital learning and development? and (3) If there are barriers to the uptake of technology for learning and development, what are these barriers? A survey was created and distributed to the Northern Ireland social care workforce. This survey collected data on 127 metrics that described demographics, basic digital skills, technology confidence and access, factors that influence learning and development, experience with digital learning solutions, and perceived value and challenges of using technology for learning. The survey was opened from December 13, 2018, to January 18, 2019. A total of 775 survey respondents completed the survey. The results indicated a workforce with a high level of self-reported basic digital skills and confidence. Face-to-face delivery of learning is still the most common method of accessing learning, which was used by 83.7% (649/775) of the respondents; however, this is closely followed by digital learning, which was used by 79.0% (612/775) of the respondents. There was a negative correlation between age and digital skills (rs=-0.262; P<.001), and a positive correlation between technology confidence and digital skills (rs=0.482; P<.001). There was also a negative correlation between age and the perceived value of technology (rs=-0.088; P=.02). The results indicated a predominantly motivated workforce in which a sizable portion is already engaged in informal digital learning. The results indicated that lower self-reported basic digital skills and confidence were associated with less interest in engaging with e-learning tools and that a portion of the workforce would benefit from additional basic digital skills training. These promising results provide a positive outlook for the potential of digital learning and development within the social care workforce. The findings provide clear areas of focus for the future use of technology for learning and development of the social care workforce and considerations to maximize engagement with such approaches.


Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy.
Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)-stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss-of-function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within-group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems.


Does the way physicians are paid influence the way they practice? The case of Canadian family physicians' work activity.
To investigate the impact of the mode of remuneration on the work activities of Canadian family physicians on: (a) direct patient care in office/clinic, (b) direct patient care in other settings and (c) indirect patient care. Because the mode of remuneration is potentially endogenous to the work activities undertaken by family physicians, an instrumental variable estimation procedure is considered. We also account for the fact that the determination of the allocation of time to different activities by physicians may be undertaken simultaneously. To this end, we estimate a system of work activity equations and allow for correlated errors. Our results show that the mode of remuneration has little effect on the total hours worked after accounting for the endogeneity of remuneration schemes; however it does affect the allocation of time to different activities. We find that physicians working in non-fee-for-service remuneration schemes spend fewer hours on direct patient care in the office/clinic, but devote more hours to direct patient care in other settings, and more hours on indirect patient care. Canadian family physicians working in non-fee-for-service settings spend fewer hours on direct patient care in the office/clinic, but devote more hours to direct patient care in other settings and devote more hours to indirect patient care. The allocation of time in non-fee-for-service practices may have some implications for quality improvement.


Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2'-deoxycytidine results in increased tumorigenicity.
Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells.


Responses to stimulation of coronary and carotid baroreceptors and the coronary chemoreflex at different ventricular distending pressures in anaesthetised dogs.
Stimulation of left ventricular mechanoreceptors was believed not only to exert important effects on the circulation, but also to influence the responses to baroreceptor reflexes. However, most previous work is flawed due to inadequate localisation of stimuli to specific reflexogenic areas. In this study, we applied a discrete stimulus to left ventricular mechanoreceptors to examine other reflexes known to effect the circulation. Dogs were anaesthetised, artificially ventilated and a cardiopulmonary bypass established. The pressure distending the left ventricle was controlled through an apical cannula with the aortic valve obstructed by a balloon. Changes in ventricular systolic and end-diastolic pressure had only a small effect on vascular resistance, assessed as perfusion pressure in the systemic circulation (flow constant). Responses to changes in carotid or coronary pressure or to stimulation of chemosensitive afferents by injecting veratridine into the coronary circulation were always much larger. Responses to stimulation of these reflexes were little affected by the level of stimulus to the ventricular receptors. These experiments confirm that responses to stimulation of ventricular mechanoreceptors are very small and show that they remain small at different levels of input to other baroreceptive regions. There was no evidence of interaction between ventricular mechanoreceptor reflexes and carotid or coronary baroreceptors or ventricular chemosensitive reflexes.


Clinical Phenotype of FASTKD2 Mutation.
Mitochondrial disorders (MIDs) are frequently multisystemic in nature and cause significant morbidity and mortality. Accurate assessment of mitochondrial disease prevalence has been difficult in the past. Primary MIDs are due to mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA)-located genes. Here we report cases of two siblings who presented to the pediatric emergency department with status epilepticus. Initially, the elder sibling was treated for metabolic encephalopathy and viral encephalitis, during his admission to the hospital. On treatment with multiple antiepileptic drugs, the status epilepticus subsided. A provisional diagnosis of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes was made. Magnetic resonance imaging showed diffusion restriction in the left temporal lobe, insular cortex, and left lentiform nucleus, which completely resolved on follow-up after 1 month. His sudden demise in May 2019 due to status epilepticus, and a similar case presentation in his younger sibling, prompted us to do a genetic analysis test. The exome sequence revealed FASTKD2 mutation, a rare variant. This case report helps in increasing the awareness among the clinicians about the clinical presentation of FASTKD2 mutation case.


Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats.
A strong link between obesity and dopamine (DA) has been established by studies associating body weight status to variants of genes related to DA signalling. Human and animal studies investigating this relationship have so far focused mainly on the role of DA within the mesolimbic pathway. The aim of this study was to investigate potential DA receptor dysregulation in the brainstem, where these receptors play a potential role in meal termination, during high-fat high-sugar diet (HFHS) exposure. Expression of other key genes, including proopiomelanocortin (POMC), was also analyzed. We randomized rats into three groups; ad libitum access to HFHS (n=24), restricted HFHS access (n=10), or controls (chow-fed, n=10). After 5 weeks, brainstem gene expression was investigated by qRT-PCR. We observed an increase in POMC expression in ad libitum HFHS-fed rats compared to chow-fed controls (p<0.05). Further, expression of DA D2 receptor mRNA was down-regulated in the brainstem of the HFHS ad libitum-fed rats (p<0.05), whereas expression of the DA D1 receptor was upregulated (p<0.05) in these animals compared to chow-fed rats. In control experiments, we observed no effect relative to chow-fed controls on DA-receptor or POMC gene expression in the hypothalamus of HFHS diet-exposed rats, or in the brainstem of acutely food deprived rats. The present findings suggest brainstem POMC to be responsive to palatable foods, and that DA dysregulation after access to energy-dense diets occurs not only in striatal regions, but also in the brainstem, which could be relevant for overeating and for the development and maintenance of obesity.


Intensification of dairy production can increase the GHG mitigation potential of the land use sector in East Africa.
Sub-Saharan Africa (SSA) could face food shortages in the future because of its growing population. Agricultural expansion causes forest degradation in SSA through livestock grazing, reducing forest carbon (C) sinks and increasing greenhouse gas (GHG) emissions. Therefore, intensification should produce more food while reducing pressure on forests. This study assessed the potential for the dairy sector in Kenya to contribute to low-emissions development by exploring three feeding scenarios. The analyses used empirical spatially explicit data, and a simulation model to quantify milk production, agricultural emissions and forest C loss due to grazing. The scenarios explored improvements in forage quality (Fo), feed conservation (Fe) and concentrate supplementation (Co): FoCo fed high-quality Napier grass (Pennisetum purpureum), FeCo supplemented maize silage and FoFeCo a combination of Napier, silage and concentrates. Land shortages and forest C loss due to grazing were quantified with land requirements and feed availability around forests. All scenarios increased milk yields by 44%-51%, FoCo reduced GHG emission intensity from 2.4 ± 0.1 to 1.6 ± 0.1 kg CO2 eq per kg milk, FeCo reduced it to 2.2 ± 0.1, whereas FoFeCo increased it to 2.7 ± 0.2 kg CO2 eq per kg milk because of land use change emissions. Closing the yield gap of maize by increasing N fertilizer use reduced emission intensities by 17% due to reduced emissions from conversion of grazing land. FoCo was the only scenario that mitigated agricultural and forest emissions by reducing emission intensity by 33% and overall emissions by 2.5% showing that intensification of dairy in a low-income country can increase milk yields without increasing emissions. There are, however, risks of C leakage if agricultural and forest policies are not aligned leading to loss of forest to produce concentrates. This approach will aid the assessment of the climate-smartness of livestock production practices at the national level in East Africa.


Epidemiology of adolescent Salvia divinorum use in Canada.
Salvia divinorum is a potent, naturally occurring hallucinogen gaining popularity as a recreational drug in North America. To date, detailed epidemiologic information about the use of this substance among adolescents living outside the United States has been limited. This study provides information on the prevalence and correlates of Salvia divinorum use among adolesecents in Canada using a nationally representative sample. Data were obtained from a representative sample of 42,179 Canadian adolescents aged 12-17 years living across all 10 provinces who completed the Youth Smoking Survey in 2008-09. Overall, 3.8% of adolescents reported using Salvia in the past year and 6.2% had used the substance in their lifetime. A conservative estimate suggests 23.2% of youth were repeat users. Salvia use was highest among youth in British Columbia and Quebec. Comparatively, the prevalence of 12-month Salvia use was higher than 12-month cocaine and amphetamine use but lower than 12-month ecstasy, cannabis, and other hallucinogen use. Correlates of Salvia use included older age, male gender, high available spending money, binge drinking, illicit drug use and smoking in fully adjusted models. Findings suggest low self-esteem may be an important correlate specific to the use of this substance among youth. Salvia divinorum use is prevalent among Canadian adolescents. Salvia may be a significant public health issue in Canada given it is readily available, under limited regulation, and little is known about the abuse liability of the substance, interactions with other substances, and potential complications from use.


Aortic dilatation patterns and rates in adults with bicuspid aortic valves: a comparative study with Marfan syndrome and degenerative aortopathy.
Bicuspid aortic valve (BAV) is related to aortic dilatation, but patterns/rates are conflicting with no comparison among aneurysms of different aetiology. We sought to define ascending aorta dilatation patterns/progression rates in BAV versus other aortopathies (Marfan syndrome (MFS), degenerative aortopathy (DA)). Retrospective, observational study. Aortic dilatation progression was evaluated in two tertiary care centres (US and European) by repeated echocardiography ≥2 years apart in adults with BAV (n=353), matched to MFS (n=50) and DA (n=51) for gender, blood pressure, and minimum follow-up time. At baseline, ascending aortic dilatation was present in 87% of BAV cases: tubular ascending aorta in 60% (irrespective of BAV morphology), and Valsalva sinuses dilatation in 27% (independently linked to typical BAV morphology and male gender (p=0.0001)). After 3.6±1.2 years, the aortic dilatation rate in BAV was higher than expected for the population for all aortic levels (p=0.005) and was maximal at the tubular ascending aorta for BAV (0.42±0.6 mm/year) and DA (0.20±0.3 mm/year), and was maximal at the Valsalva sinuses for MFS (0.49±0.5 mm/year). Maximal aortic dilatation rate was similar between BAV and MFS (p>0.40) and lower in DA (p=0.02) but was heterogeneous in BAV, with 43% of BAV not progressing (vs 20% of MFS, p=0.01). Aortic dilatation rate was not proportionally related to baseline aortic size or BAV type (all models p>0.40). In patients with BAV, tubular ascending aorta dilatation is the most common pattern and exhibits the fastest growing rate, irrespective of valve morphology and function. Dilatation of the Valsalva sinuses is less common and associated with typical BAV morphology and male gender. Aortic dilatation progresses equally fast in BAV (tubular segment) and MFS (Valsalva sinuses), but a significantly higher proportion of BAV patients does not progress at all, irrespective of BAV type. Baseline aortic diameter does not proportionally predict progression rate; systematic follow-up is therefore warranted in patients with BAV.


Roentgen stereophotogrammetric analysis: an accurate tool to assess stent-graft migration.
To evaluate in an in vitro model the feasibility and accuracy of Roentgen stereophotogrammetric analysis (RSA) versus computed tomography (CT) for the ability to detect stent-graft migration. An aortic model was constructed from a 22-mm-diameter Plexiglas tube with 6-mm polytetrafluoroethylene inlays to mimic the renal arteries. Six tantalum markers were placed in the wall of the aortic tube proximal to the renal arteries. Another 6 markers were added to a Gianturco stent, which was cast in Plexiglas and placed inside the aorta and fixed to a micromanipulator to precisely control displacement of the stent along the longitudinal axis. Sixteen migrations were analyzed with RSA software and compared to the micromanipulator. Thirty-two migrations were measured by 3 observers from CT images acquired with 16x0.5-mm beam collimation and reconstructed with a 0.5-mm slice thickness and a 0.4-mm reconstruction interval. Measurements were made with Vitrea postprocessing software using a standard clinical protocol and central lumen line reconstruction. Results of CT were also compared to the micromanipulator. The mean RSA measurement error compared to the micromanipulator was 0.002+/-0.044 mm, and the maximum error was 0.10 mm. There was no statistically significant interobserver variability for CT (p=0.17). The pooled mean (maximum) measurement error of CT was 0.14+/-0.29 (1.00) mm, which was significantly different from the RSA measurement error (p<0.0001). Detection of endograft migration by RSA is feasible and was significantly more accurate than CT in this nonpulsatile in vitro model.


Porous semiconductor chalcogenide aerogels.
Chalcogenide aerogels based entirely on semiconducting II-VI or IV-VI frameworks have been prepared from a general strategy that involves oxidative aggregation of metal chalcogenide nanoparticle building blocks followed by supercritical solvent removal. The resultant materials are mesoporous, exhibit high surface areas, can be prepared as monoliths, and demonstrate the characteristic quantum-confined optical properties of their nanoparticle components. These materials can be synthesized from a variety of building blocks by chemical or photochemical oxidation, and the properties can be further tuned by heat treatment. Aerogel formation represents a powerful yet facile method for metal chalcogenide nanoparticle assembly and the creation of mesoporous semiconductors.


Detection of canine Schistosoma japonicum infection using recombinant thioredoxin peroxidase-1 and tandem repeat proteins.
Humans and dogs live very close together and share various pathogens causing zoonotic parasitoses like schistosomiasis. A previous population genetics study done for schistosomes in the Philippines suggested that there is a high transmission level of Schistosoma japonicum among humans and dogs proving that the latter are important reservoirs for this zoonotic parasite. A more sensitive and specific test detecting schistosome infection in dogs will therefore strengthen the zoonotic surveillance, which might help in the possible elimination of this ancient disease. In this study, recombinant thioredoxin peroxidase-1 (SjTPx-1) and tandem repeat proteins (Sj1TR, Sj2TR, Sj4TR, Sj7TR) previously tested on human and water buffalo samples were used to assess its diagnostic applicability to dogs. Fifty-nine dog serum and stool samples were collected in the schistosomiasis-endemic municipalities of Calatrava, Negros Occidental and Catarman, Northern Samar in the Philippines and examined using the ELISA as compared to microscopy and fecal sample-based PCR. Samples positive for Babesia gibsoni and Dirofilaria immitis were also used to check for cross-reaction. Results showed that SjTPx-1 (80% sensitivity, 92.3% specificity) and Sj7TR (73.3% sensitivity, 92.3% specificity) have good potentials for diagnosing S. japonicum infection in dogs. These diagnostic antigens will therefore improve the surveillance in the transmission of the parasites from dogs to humans.


Computational Methods for Detection of Differentially Methylated Regions Using Kernel Distance and Scan Statistics.
Researchers in genomics are increasingly interested in epigenetic factors such as DNA methylation because they play an important role in regulating gene expression without changes in the sequence of DNA. Abnormal DNA methylation is associated with many human diseases. We propose two different approaches to test for differentially methylated regions (DMRs) associated with complex traits, while accounting for correlations among CpG sites in the DMRs. The first approach is a nonparametric method using a kernel distance statistic and the second one is a likelihood-based method using a binomial spatial scan statistic. The kernel distance method uses the kernel function, while the binomial scan statistic approach uses a mixed-effects model to incorporate correlations among CpG sites. Extensive simulations show that both approaches have excellent control of type I error, and both have reasonable statistical power. The binomial scan statistic approach appears to have higher power, while the kernel distance method is computationally faster. The proposed methods are demonstrated using data from a chronic lymphocytic leukemia (CLL) study.


Vascular responses to agonists in rat mesenteric artery from diabetic rats.
The effect of diabetes on vascular smooth muscle function was investigated in the muscular arteries from spontaneously and chemically induced diabetic rats. Isolated ring segments of superior mesenteric arteries from BB diabetic and streptozotocin (STZ)-diabetic rats (12 weeks after onset of diabetes) were used for isometric tension studies. Contractile responses to alpha-adrenoceptor agonists (norepinephrine, methoxamine, phenylephrine, B-HT 920, guanabenz, SKF 89748-A), serotonin, and K+ were significantly higher in STZ-diabetic rat arteries as compared with the controls. In spontaneously diabetic rat arteries only the contractile responses to the putatively selective alpha 2-adrenoceptor agonists, K+ and prostaglandin E1, were significantly increased. pD2 values of the agonists in both groups of diabetic arteries were not significantly different from the respective controls. Nifedipine inhibited all contractile responses in a dose-dependent fashion. The responses to K+ and alpha 2-adrenoceptor agonists were attenuated to a greater extent by nifedipine in both groups of diabetic blood vessels. The calcium channel activator, BAY K 8644, produced a twofold increase in force of contraction in streptozotocin-diabetic and spontaneously diabetic rat arteries as compared with the responses in their respective controls. These results suggest caution in extrapolating all the findings from the streptozocin-induced diabetic model to the spontaneously diabetic model. However, increased activity of calcium channels in vascular muscle cells in both groups of diabetics may be responsible, at least in part, for the increased vascular contractility in diabetes mellitus.


Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep-wake activity in pre-symptomatic Alzheimer's disease.
Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic pupillometry may be a potential biomarker for early diagnosis and progression of AD. We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.


Zebrafish Cacna1fa is required for cone photoreceptor function and synaptic ribbon formation.
Mutations in the human CACNA1F gene cause incomplete congenital stationary night blindness type 2 (CSNB2), a non-progressive, clinically heterogeneous retinal disorder. However, the molecular mechanisms underlying CSNB2 have not been fully explored. Here, we describe the positional cloning of a blind zebrafish mutant, wait until dark (wud), which encodes a zebrafish homolog of human CACNA1F. We identified two zebrafish cacna1f paralogs and showed that the cacna1fa transcript (the gene mutated in wud) is expressed exclusively in the photoreceptor layer. We demonstrated that Cacna1fa localizes at the photoreceptor synapse and is absent from wud mutants. Electroretinograms revealed abnormal cone photoreceptor responses from wud mutants, indicating a defect in synaptic transmission. Although there are no obvious morphological differences, we found that wud mutants lacked synaptic ribbons and that wud is essential for the development of synaptic ribbons. We found that Ribeye, the most prominent synaptic ribbon protein, was less abundant and mislocalized in adult wud mutants. In addition to cloning wud, we identified synaptojanin 1 (synj1) as the defective gene in slacker (slak), a blind mutant with floating synaptic ribbons. We determined that Cacna1fa was expressed in slak photoreceptors and that Synj1 was initially expressed wud photoreceptors, but was absent by 5 days postfertilization. Collectively, our data demonstrate that Cacna1fa is essential for cone photoreceptor function and synaptic ribbon formation and reveal a previously unknown yet critical role of L-type voltage-dependent calcium channels in the expression and/or distribution of synaptic ribbon proteins, providing a new model to study the clinical variability in human CSNB2 patients.


Azacitidine in lower-risk myelodysplastic syndromes.
Azacitidine is the first agent to significantly prolong overall survival (OS) compared with conventional care regimens in patients with higher-risk myelodysplastic syndromes (MDS). Here, we review currently available data on azacitidine treatment in lower-risk MDS. In a phase III study, a subset of patients with lower-risk MDS treated with azacitidine achieved an overall response rate (ORR) of 60% and a longer median OS compared with supportive care (44 vs 27 months). In a phase II study investigating various azacitidine dose schedules, the hematological improvement rate was approximately 50% in lower-risk patients; most patients who achieved transfusion independence were also lower-risk. A further retrospective study reported an ORR of 52% in MDS lower-risk patients who received > or = 4 cycles of therapy. Preliminary data for azacitidine combination therapy with erythropoietin, granulocyte colony-stimulating factor, and valproic acid are intriguing but should be treated with caution. These results suggest the feasibility and effectiveness of azacitidine in the treatment of patients with lower-risk MDS.


Reading comprehension in a large cohort of French first graders from low socio-economic status families: a 7-month longitudinal study.
The literature suggests that a complex relationship exists between the three main skills involved in reading comprehension (decoding, listening comprehension and vocabulary) and that this relationship depends on at least three other factors orthographic transparency, children's grade level and socioeconomic status (SES). This study investigated the relative contribution of the predictors of reading comprehension in a longitudinal design (from beginning to end of the first grade) in 394 French children from low SES families. Reading comprehension was measured at the end of the first grade using two tasks one with short utterances and one with a medium length narrative text. Accuracy in listening comprehension and vocabulary, and fluency of decoding skills, were measured at the beginning and end of the first grade. Accuracy in decoding skills was measured only at the beginning. Regression analyses showed that listening comprehension and decoding skills (accuracy and fluency) always significantly predicted reading comprehension. The contribution of decoding was greater when reading comprehension was assessed via the task using short utterances. Between the two assessments, the contribution of vocabulary, and of decoding skills especially, increased, while that of listening comprehension remained unchanged. These results challenge the 'simple view of reading'. They also have educational implications, since they show that it is possible to assess decoding and reading comprehension very early on in an orthography (i.e., French), which is less deep than the English one even in low SES children. These assessments, associated with those of listening comprehension and vocabulary, may allow early identification of children at risk for reading difficulty, and to set up early remedial training, which is the most effective, for them.


Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens.
Selenium and coenzyme Q10 are important antioxidants in the body. As the intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases, an intervention trial using selenium and coenzyme Q10 for four years was performed. As previously reported, the intervention was accompanied by reduced cardiovascular mortality. The objective of the present study was to analyze cardiovascular mortality for up to 10 years after intervention, to evaluate if mortality differed in subgroups differentiated by gender, diabetes, ischemic heart disease (IHD), and functional class. Four-hundred forty-three healthy elderly individuals were included from a rural municipality in Sweden. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results mortality was registered. Significantly reduced cardiovascular mortality could be seen in those on selenium and coenzyme Q10 intervention. A multivariate Cox regression analysis demonstrated a reduced cardiovascular mortality risk in the active treatment group (HR: 0.51; 95%CI 0.36-0.74; P = 0.0003). The reduced mortality could be seen to persist during the 10-year period. Subgroup analysis showed positive effects in both genders. An equally positive risk reduction could be seen in those with ischemic heart disease (HR: 0.51; 95%CI 0.27-0.97; P = 0.04), but also in the different functional classes. In a 10-year follow-up of a group of healthy elderly participants given four years of intervention with selenium and coenzyme Q10, significantly reduced cardiovascular mortality was observed. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanism explaining the persistency remains to be elucidated. Since this was a small study, the observations should be regarded as hypothesis-generating.


Size and hematological impact of the splenic erythrocyte reservoir in rainbow trout,Oncorhynchus mykiss.
Fish were sampled individually, at rest, following air exposures of up to 8 min, during recovery from a 5 min air exposure or after a 5 minute chase. The spleen was photographedin vivo at rest and following 5 min air exposure in one fish. The effect of individual versus serial sampling from the same tank and of MS222 anaesthesia was also examined. Spleen hemoglobin content (SpHb), spleen somatic index (100 × spleen weight/body weight; SSI), blood hemoglobin concentration (Hb), and hematocrit (Ht), were measured. Mean cell hemoglobin concentration (MCHC), erythrocyte reservoir size, and relative contributions of reservoir release, erythrocyte swelling, and plasma water loss to hemoconcentration were calculated. The splenic reservoir contained 0.54 g Hb/kg body (21% of total body Hb), most of which it released between 1 and 3 minutes after the onset of air exposure. The spleen released more than 95% of the erythrocytes it contained at rest within 8 min. The release accounted for 31% of the 5.65 g/dl rise in Hb and 23% of the 26.6% observed increase in Ht after 8 minutes of air exposure. The balance of the increase was caused by erythrocyte swelling and fluid shifts reducing plasma volume. Animals exercised for 5 min showed changes similar to those in fish air exposed for 5 min. Recovery of all parameters was complete in 3 to 6 h, with the exception of MCHC which recovered in 30 min. Serial sampling produced a decrease in SpHb, and R1Wt and induced a significant hemoconcentration. MS222 did not cause erythrocyte release, but failed to prevent it after handling. Many previous reports of Ht and Hb in resting fish are probably high because they were taken under conditions that would cause the spleen to release its contents.


Species-complex diversification and host-plant associations in Bemisia tabaci: A plant-defence, detoxification perspective revealed by RNA-Seq analyses.
Insect-plant associations and their role in diversification are mostly studied in specialists. Here, we aimed to identify macroevolution patterns in the relationships between generalists and their host plants that have the potential to promote diversification. We focused on the Bemisia tabaci species complex containing more than 35 cryptic species. Mechanisms for explaining this impressive diversification have focused so far on allopatric forces that assume a common, broad, host range. We conducted a literature survey which indicated that species in the complex differ in their host range, with only few showing a truly broad one. We then selected six species, representing different phylogenetic groups and documented host ranges. We tested whether differences in the species expression profiles of detoxification genes are shaped more by their phylogenetic relationships or by their ability to successfully utilize multiple hosts, including novel ones. Performance assays divided the six species into two groups of three, one showing higher performance on various hosts than the other (the lower performance group). The same grouping pattern appeared when the species were clustered according to their expression profiles. Only species placed in the lower performance group showed a tendency to lower the expression of multiple genes. Taken together, these findings bring evidence for the existence of a common detoxification "machinery," shared between species that can perform well on multiple hosts. We raise the possibility that this "machinery" might have played a passive role in the diversification of the complex, by allowing successful migration to new/novel environments, leading, in some cases, to fragmentation and speciation.


Behavioural and molecular endophenotypes in psychotic disorders reveal heritable abnormalities in glutamatergic neurotransmission.
Psychotic disorders such as schizophrenia are biologically complex and carry huge population morbidity due to their prevalence, persistence and associated disability. Defined by features such as delusions and hallucinations, they involve cognitive dysfunction and neurotransmitter dysregulations that appear mostly to involve the dopaminergic and glutamatergic systems. A number of genetic and environmental factors are associated with these disorders but it has been difficult to identify the biological pathways underlying the principal symptoms. The endophenotype concept of stable, heritable traits that form a mechanistic link between genes and an overt expression of the disorder has potential to reduce the complexity of psychiatric phenotypes. In this study, we used a genetically sensitive design with individuals with a first episode of psychosis, their non-affected first-degree relatives and non-related healthy controls. Metabolomic analysis was combined with neurocognitive assessment to identify multilevel endophenotypic patterns: one concerned reaction times during the performance of cognitive and emotional tests that have previously been associated with the glutamate neurotransmission system, the other involved metabolites involved directly and indirectly in the co-activation of the N-methyl-D-aspartate receptor, a major receptor of the glutamate system. These cognitive and metabolic endophenotypes may comprise a single construct, such that genetically mediated dysfunction in the glutamate system may be responsible for delays in response to cognitive and emotional functions in psychotic disorders. This focus on glutamatergic neurotransmission should guide drug discovery and experimental medicine programmes in schizophrenia and related disorders.


Symptom reduction and improved function in chronic CRPS type 1 after 12-week integrated, interdisciplinary therapy.
Background and aims Complex Regional Pain Syndrome (CRPS) often recovers spontaneously within the first year, but when it becomes chronic, available rehabilitative therapies (pharmacological management, physiotherapy, and psychological intervention) have limited effectiveness. This study examined the effect of a 12-week intensive outpatient rehabilitation on pain relief and function in chronic CRPS patients. Rehabilitation program included memantine and morphine treatment (added to patient's prior pain medication) and concurrent psychological and physiotherapeutic intervention. Primary outcome measure was a change in CRPS symptom count and secondary outcomes were motor performance, psychological factors, pain intensity, and quality of life. Methods Ten patients with chronic upper limb CRPS I (median 2.9 years, range 8 months to 12 years) were recruited to the study and were assessed before and after the intervention. Hand motor function of the patients was evaluated by an independent physiotherapist. There were standardized questionnaires for depression, pain anxiety, pain acceptance, quality of life, and CRPS symptom count. In addition, psychological factors were evaluated by a semi-structured interview. Severity of experienced pain was rated at movement and at rest. In addition, a video experiment of a hand action observation was conducted pre- and post-intervention to study possible change in neuronal maladaptation. Intervention consisted of pharmacological, psychological and physiotherapeutic treatment. First, 10 mg daily morphine was started and increased gradually to 30 mg daily, if tolerated. After 30 mg/day or tolerated dose of morphine was achieved, 5 mg daily memantine was started and increased gradually to 40 mg, if tolerated. Psychological intervention consisted of weekly group sessions, using cognitive and behavioral methods (relaxation, behavioral activation, and exposure) and acceptance and commitment therapy (ACT) and daily home practice. Physiotherapeutic intervention consisted of graded motor imagery and physiotherapy exercises with weekly group sessions and/or individual guidance by the physiotherapist, and individual exercise of the affected upper limb. Results Multimodal intensive intervention resulted in significant decrease in CRPS symptom count. The effect was strongest in motor and trophic symptoms (19% decrease after intervention) and in sensory symptoms (18% decrease). Additionally, improvement was seen in some, but not all, secondary outcomes (movement pain, motor symptoms, change in perceptions during video experiment of hand actions, and summary index with motor functioning, pain, and psychological factors). There were no dropouts. Conclusions Intensive 12-week multimodal intervention reduced some CRPS symptoms but was not sufficient to alter patients' rest pain, distress, or quality of life. Implications These results support the efficacy of an interdisciplinary rehabilitation program for pain and function in chronic CRPS patients. After intervention, some CRPS symptoms reduced and function improved, but distress and quality of life were unchanged. This may be due to the relatively short duration of this program; to delayed effects; to particular cognitive problems of CPRS patients; and/or to low distress levels at baseline that make statistically significant reduction less likely.


Discovering Shifts to Suicidal Ideation from Mental Health Content in Social Media.
History of mental illness is a major factor behind suicide risk and ideation. However research efforts toward characterizing and forecasting this risk is limited due to the paucity of information regarding suicide ideation, exacerbated by the stigma of mental illness. This paper fills gaps in the literature by developing a statistical methodology to infer which individuals could undergo transitions from mental health discourse to suicidal ideation. We utilize semi-anonymous support communities on Reddit as unobtrusive data sources to infer the likelihood of these shifts. We develop language and interactional measures for this purpose, as well as a propensity score matching based statistical approach. Our approach allows us to derive distinct markers of shifts to suicidal ideation. These markers can be modeled in a prediction framework to identify individuals likely to engage in suicidal ideation in the future. We discuss societal and ethical implications of this research.


Human DNA polymerase kappa forms nonproductive complexes with matched primer termini but not with mismatched primer termini.
Human DNA polymerase kappa (pol kappa) is a member of the Y family of DNA polymerases that function in translesion synthesis. It synthesizes DNA with moderate fidelity and does not efficiently incorporate nucleotides opposite DNA lesions. Pol kappa has the unusual ability to efficiently extend from mismatched primer termini, and it extends readily from nucleotides inserted by other DNA polymerases opposite a variety of DNA lesions. All of this has suggested that pol kappa functions during the extension step of translesion synthesis. Here, we have carried out pre-steady-state kinetic studies of pol kappa using DNA with matched and mismatched primer termini. Interestingly, we find that mismatches present only a modest kinetic barrier to nucleotide incorporation by pol kappa. Moreover, and quite surprisingly, active-site titrations revealed that the concentration of active pol kappa is very low with matched DNA, and from DNA trapping experiments we determined that this was due to the formation of nonproductive protein.DNA complexes. In marked contrast, we found that the concentration of active pol kappa was six-fold greater with mismatched DNA than with matched DNA. Thus, pol kappa forms nonproductive complexes with matched but not with mismatched DNA. From these observations, we conclude that pol kappa has evolved to specifically function on DNA substrates with aberrant primer-terminal base pairs, such as the ones it would encounter during the extension step of translesion synthesis.


Benefits of Two 24-Week Interactive Cognitive-Motor Programs on Body Composition, Lower-Body Strength, and Processing Speed in Community Dwellings at Risk of Falling: A Randomized Controlled Trial.
This 24-week randomized controlled trial study evaluated the effects of two interactive cognitive−motor programs on body composition, lower-body strength, and processing speed in community dwellings at risk of falling. Forty-eight participants (75.0 ± 5.4 years) were allocated into EG1 (psychomotor intervention program), EG2 (combined program (psychomotor intervention + whole-body vibration)), and a control group. EG programs induced significant improvements in bone mass, lower-body strength, and processing speed (p < 0.05), with similar treatment effects on lower-body strength and processing speed and higher bone mineral content and density within EG2. The fall rate decreased in EG1 (44.2%) and EG2 (63%) (p < 0.05). After the 12-week no-intervention follow-up, improvements in lower-body strength were reversed in both EGs, but those in processing speed were maintained, mainly in EG2 (p < 0.05). In conclusion, both programs were accepted and well tolerated. The combined program led to additional benefits in bone mass. Both programs positively impacted physical and cognitive risk factors for falls and injuries. They induced similar improvements in lower-body strength and processing speed, decreasing the fall rate. These findings suggest that both programs are successful for fall and injury prevention in the studied population.


Anatolian honey is not only sweet but can also protect from breast cancer: Elixir for women from artemis to present.
Natural products with bioactive components are widely studied on various cancer cell lines for their possible cytotoxic effects, recently. Among these products, honey stands out as a valuable bee product containing many active phenolic compounds and flavonoids. Numerous types of multifloral honey and honeydew honey are produced in Turkey owing to its abundant vegetation. Therefore, in this study, we investigated the cytotoxic effects of particular tree-originated honeys from chestnut, cedar, pine, and multifloral honey on cell lines representing different types of the most common cancer of women, breast cancer, MCF7, SKBR3, and MDAMB-231, and fibrocystic breast epithelial cell line, MCF10A as a control. All honey samples were analyzed biochemically. The dose- (1, 2.5, 5, 7.5, and 10 µg/mL) and time (24th, 48th, and 72nd hours)-dependent effects of ethanol/water solutions of the honey samples were scrutinized. Cell viability/cytotoxicity was evaluated by the water soluble tetrazolium Salt-1 (WST-1) method. Apoptotic status was detected by Annexin V-PI assay using FACSCalibur. The statistical analysis was performed using GraphPad Prism 6 and the clustering data analysis with the R programming language. The biochemical analyses of the honey samples showed that the tree-originated honey samples contained more total phenolic compounds than the multifloral honey. Phenolic content of the honey types increases in order of multifloral, pine, cedar, and chestnut, respectively, which is compatible with their cytotoxic affectivity and dark color. In addition, the antioxidant capacity of the studied honey types was observed to increase in order of multifloral < pine < cedar ≅ chestnut. According to the WST-1 data, chestnut honey induced cytotoxicity over 50% on all the cell lines, including the control MCF10A cells, even with low doses (honey concentrations starting from 1 µg/mL) (P < 0.0001). Similarly, Cedar honey was observed to be the second most effective honey in this study. Cedar honey, with the dose of 1 µg/mL, was detected statistically highly significant on MCF10A, MCF7, and SKBR3. In contrast, pine honey showed dramatically significant cytotoxicity only on the MDAMB 231 cells with a 1 µg/mL dose at the same time point (P = 0.018). While pine honey caused an anticancer effect on the MCF-7 and SKBR3 cancer cell lines with a 2.5-5 µg/mL dose (P < 0.0001), like cedar and chestnut honeys, it increased the viability of the MCF10A control cells with the doses of 2.5-5 µg/mL. It only showed cytotoxicity with higher doses (10 µg/mL) on the MCF10A cell line (P < 0.0001). Moreover, we have observed that the multifloral and artificial honey samples were mostly ineffective or increased cell viability with the doses of 1-5 µg/mL. Apoptotic effects of the other honey samples on the MCF-7 cell line were found as chestnut> pine> cedar> multifloral in the Annexin V-propidium iodide (PI) analysis. Chestnut, cedar, and pine honey displayed a remarkably cytotoxic effect on breast cancer cell lines, MCF7, SKBR3, and even on the most aggressive MDAMB 231, representing the triple negative breast cancer, which lacks of targeted anticancer therapy. The chestnut and cedar honeys stand out to be the most cytotoxic on all cell lines, while pine honey was found to be the least toxic on control cells with appropriate toxicity on the cancer cells. © 2017 IUBMB Life, 69(9):677-688, 2017.


ERK1/2 drives IL-1β-induced expression of TGF-β1 and BMP-2 in torn tendons.
Diseased and injured tendons develop fibrosis, driven by factors including TGF-β, BMPs and CTGF. IL-1β and its signal transducer Erk1/2 are known to regulate TGF-β expression in animal tendons. We utilised tissues and cells isolated from patients with shoulder tendon tears and tendons of healthy volunteers to advance understanding of how inflammation induces fibrosis in diseased human tendons. ERK1/2 expression was reduced in torn (diseased) compared to healthy patient tendon tissues. We next investigated the fibrotic responses of tendon-derived cells isolated from healthy and diseased human tendon tissues in an inflammatory milieu. IL-1β treatment induced profound ERK1/2 signalling, TGFB1 and BMP2 mRNA expression in diseased compared to healthy tendon-derived cells. In the diseased cells, the ERK1/2 inhibitor (PD98059) completely blocked the IL-1β-induced TGFB1 and partially reduced BMP2 mRNA expression. Conversely, the same treatment of healthy cells did not modulate IL-1β-induced TGFB1 or BMP2 mRNA expression. ERK1/2 inhibition did not attenuate IL-1β-induced CTGF mRNA expression in healthy or diseased tendon cells. These findings highlight differences between ERK1/2 signalling pathway activation and expression of TGF-β1 and BMP-2 between healthy and diseased tendon tissues and cells, advancing understanding of inflammation induced fibrosis during the development of human tendon disease and subsequent repair.


Efficacy of controlled-release paroxetine in the treatment of late-life depression.
Depression is the second most common neuropsychiatric disorder in older Americans, with significant clinical and public health costs. Despite advances in treatment, late-life depression remains a clinical challenge. Although the selective serotonin reuptake inhibitors (SSRIs) are the most common pharmacologic intervention for late-life depression, few placebo-controlled trials have assessed the efficacy of SSRIs for this condition. In this 12-week, multicenter, placebo-controlled, flexible-dose, double-blind, randomized trial, 319 elderly patients (mean age = 70 years) were treated with controlled-release paroxetine (paroxetine CR) up to 50 mg/day (N = 104), immediate-release paroxetine (paroxetine IR) up to 40 mg/day (N = 106), or placebo (N = 109). Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D). The primary efficacy measure was change from baseline to endpoint in HAM-D total score. The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 (95% confidence interval [CI] = -4.47 to -0.73, p = .007) at the week 12 last-observation-carried-forward (LOCF) endpoint. The adjusted difference between paroxetine IR and placebo was -2.8 (95% CI = -4.65 to -0.99, p = .003) at week 12. Paroxetine CR and IR were more effective than placebo, with mean +/- SD endpoint HAM-D total scores of 10.0 +/- 7.41 and 10.0 +/- 7.10, respectively, for the active treatments compared with 12.6 +/- 7.34 for placebo. Response, defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale, was achieved by 72% of paroxetine CR patients (LOCF; p < .002 vs. placebo), 65% of paroxetine IR patients (p = .06 vs. placebo), and 52% of placebo patients. Remission, defined as a HAM-D total score < or = 7, was achieved by 43% of paroxetine CR patients (LOCF; p = .009 vs. placebo), 44% of paroxetine IR patients (p = .01 vs. placebo), and 26% of placebo patients. In a post hoc analysis, mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients (duration > 2 years) and those with short-term (< or = 2 years) depression. Dropout rates due to adverse events were 12.5% for paroxetine CR, 16.0% for paroxetine IR, and 8.3% for placebo. Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients, including those with chronic depression.


Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAc beta 1-4Gal found in some glycolipids.
Pneumonia is one of the most common causes of death from infectious disease in the United States. To examine the possible role of carbohydrates as adhesion receptors for infection, several pulmonary pathogenic bacteria were studied for binding to glycosphingolipids. Radiolabeled bacteria were layered on thin-layer chromatograms of separated glycosphingolipids, and bound bacteria were detected by autoradiography. The classic triad of infectious bacteria found in cystic fibrosis, Pseudomonas aeruginosa, Haemophilus influenzae, and Staphylococcus aureus, along with other bacteria commonly implicated in typical pneumonia, such as Streptococcus pneumoniae, Klebsiella pneumoniae, and certain Escherichia coli, bind specifically to fucosylasialo-GM1 (Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Cer), asialo-GM1 (Gal beta 1-3GalNAc beta 1-4Gal beta-1-4Galc beta 1-1Cer), and asialo-GM2 (GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer). Bacteria maintained in nutrient medium bind better than the same cells suspended in buffer. They do not bind to galactosylceramide, glucosylceramide, lactosylceramide, trihexosylceramide, globoside, paragloboside, Forssman glycosphingolipid, or several other glycosphingolipids tested, including the gangliosides GM1, GM2, GM3, GD1a, GD1b, GT1b, and Cad. The finding that these pathogens do not bind to lactosylceramide suggests that beta 1-4-linked GalNAc, which is positioned internally in fucosylasialo-GM1 and asialo-GM1 and terminally in asialo-GM2, is required for binding. beta-N-Acetylgalactosamine itself, however, is not sufficient for binding, as the bacteria did not bind to globoside, which contains the terminal sequence GalNAc beta 1-3Gal. These data suggest that these bacteria require at least terminal or internal GalNAc beta 1-4Gal sequences unsubstituted with sialyl residues for binding. Other bacteria, including Mycoplasma pneumoniae, Streptococcus pyogenes, Salmonella species, and some E. coli, do not bind to the GalNAc beta 1-4Gal sequence. The biological relevance of these data is suggested by our finding that substantial amounts of asialo-GM1 occur in human lung tissue.


Hybrid mesoporous nanorods with deeply grooved lateral faces toward cytosolic drug delivery.
Nanocarriers with high local curvatures hold a great potential of inducing effective penetration of intracellular barriers and cytosolic delivery of membrane-impermeable drugs. However, the fine control of the sharp edges and their morphological effects inside cells remains largely unexplored. Herein, a nanocarrier system of hybrid mesoporous nanorods with six-arm star-shaped end faces and groove-patterned lateral faces was developed to maximize surface regions with high local curvatures for enhancing membrane destabilization. Specifically, twisted (right-handed) nanorods (TNR, diameter ∼120, aspect ratio 4-5) with a hexagon cross-section from a templated synthesis were modified by amino groups to promote surface coating of a wet-adhesive polymer, i.e. polydopamine (PDA). An edge-preferential deposition of PDA by local curvature effects led to the protective etching of silica, and in turn, the formation of nanorods with varying groove depths at different volumes of the aqueous coating solution. Finally, branched polyethylene imine (PEI) was grafted on the exterior surface of the nanorods for enhancing the dispersity and cellular uptake rate. As verified by elaborate in vitro investigations, the configuration of nanorods with the sharpest edges/deepest grooves can be rotated to a lying-down/upright mode in order to minimize/maximize the membrane tension during the interaction with membranes, which consequently resulted in highly efficient lysosomal escape despite the relatively lower uptake degree. The successful delivery of vorinostat (SAHA, a FDA-approved histone deacetylase inhibitor) and inhibition of cancer cells demonstrated the attractive ability of the nanocarriers in drug delivery.


Effect of laparoscopy on the risk of small-bowel obstruction: a population-based register study.
To investigate the incidence and risk factors for small-bowel obstruction (SBO) after certain surgical procedures. A population-based retrospective register study. Small-bowel obstruction causes considerable patient suffering. Risk factors for SBO have been identified, but the effect of surgical technique (open vs laparoscopic) on the incidence of SBO has not been fully elucidated. The Inpatient Register held by the Swedish National Board of Health and Welfare was used. The hospital discharge diagnoses and registered performed surgical procedures identified data for cholecystectomy, hysterectomy, salpingo-oophorectomy, bowel resection, anterior resection, abdominoperineal resection, rectopexy, appendectomy, and bariatric surgery performed from January 1, 2002, through December 31, 2004. Data on demographic characteristics, comorbidity, previous abdominal surgery, and death were collected. Episodes of hospital stay and surgery for SBO within 5 years after the index surgery. A total of 108,141 patients were included. The incidence of SBO ranged from 0.4% to 13.9%. Multivariate analysis revealed age, previous surgery, comorbidity, and surgical technique to be risk factors for SBO. Laparoscopy exceeded other risk factors in reduction of the risk of SBO for most of the surgical procedures. Open surgery seems to increase the risk of SBO at least 4 times compared with laparoscopy for most of the abdominal surgical procedures studied. Other factors such as age, previous abdominal surgery, and comorbidity are also of importance.


Packing of metalized polymer nanofibers for aneurysm embolization.
Aneurysmal subarachnoid hemorrhage (SAH) is the extravasation of blood into the subarachnoid space and is fatal in most cases. Platinum coils have been used to fill the hemorrhage site and prevent the extravasation of blood. Here we explored the use of Pt-coated polymer nanofibers (NF) to prevent blood extravasation and were able to achieve improved results in vitro. The polymer nanofibers were produced via electrospinning and were subsequently electroplated with Pt, resulting in metalized nanofibers. These nanofibers were installed within a microfluidic channel, and the resulting reduction in the permeability was evaluated using a fluid similar to blood. Based on the obtained results, these newly developed nanofibers are expected to decrease the operation cost for SAH, owing to their reduced size and low material cost. Furthermore, it is expected that these nanofibers will be used in a smaller amount during SAH operation while having the same preventive effect. This should reduce the operational risk associated with the multiple steps required to place the Pt coils at the SAH site. Finally, the underlying hydrodynamic mechanism responsible for the reduced permeability of the synthesized nanofibers is described.


Effect of phenoxybenzamine on development of adipose tissue in lean and obese Zucker rats.
Young male Zucker lean (Fa/-) and obese (fa/fa) rats were fed the alpha-adrenergic blocking agent phenoxybenzamine as a dietary admixture for 35 days. In lean and obese rats, phenoxybenzamine treatment decreased significantly body weight gain, food consumption, grams of carcass fat, and grams of carcass protein. Lean rats exhibited reduced fat cell size and number in retroperitoneal, epididymal, and inguinal fat depots. Obese rats treated with phenoxybenzamine exhibited significantly decreased numbers of fat cells in the retroperitoneal, epididymal, and inguinal fat depots and a small decreased cell size in the inguinal fat depot only. The levels of carcass fat and protein and fat cell number in obese and lean rats treated with phenoxybenzamine for 35 days were similar to pretreatment values in agreement with the lack of body weight gain. Although values in agreement with the lack of body weight gain. Although rats exhibited marked decreases in fat accumulation during phenoxybenzamine treatment, fat cell size and number returned to control values during the posttreatment period with a marked hyperplasia occurring particularly in the retroperitoneal fat depot of obese rats. Serum levels of insulin were suppressed and free fatty acid levels increased in obese rats during phenoxybenzamine treatment, suggesting a stimulation of the sympathoadrenal system. This study shows that despite severe restrictions in fat cell proliferation during the rapid-growth phase of the obese Zucker rat, the mechanisms for cellular proliferation and fat deposition remain intact.


Presence of plaque, gingivitis and caries in Sudanese children with congenital heart defects.
The objective of this study is to assess the presence of plaque, gingivitis, and caries in a group of Sudanese children with congenital heart defects CHDs (cases) and compare them to children without CHDs (controls). This analytical cross-sectional study included cases (N = 111, with a mean age of 7.2 ± 3.0 years) and controls (N = 182, with a mean age of 7.2 ± 2.8 years) from Khartoum, Sudan. Examinations were done by two calibrated dentists using plaque index, gingival index, and WHO (World Health Organization) caries diagnostic criteria (dmft/DMFT index: decayed, missing, and filled teeth). Children with CHDs (cases) had statistically significantly higher mean number of sites with plaque and gingivitis than children without CHDs (controls), although almost all children experienced plaque. Cases also experienced significantly higher mean dmft/DMFT than controls (age group 1, 3-7 years: 3.7 vs 2.3 and age group 2, 8-12 years: 1.3 vs 0.6). The Significant Caries Indices in cases (age groups 1 and 2) were also significantly higher than among controls (SiC 8.2 vs 5.9 and 1.8 vs 0.8, respectively). Fillings were totally lacking among cases and scarce among controls. The findings clearly showed that this group of Sudanese children with CHDs was more severely affected with gingivitis and caries than the control group without CHDs. These results are cause for concern in children at risk of developing systemic infections and serious complications related to poor oral health. These findings provide important baseline data for planning appropriate dental preventive strategies for Sudanese children with CHDs.


'All in the same boat'? Patient and carer attitudes to peer support and social comparison in Motor Neurone Disease (MND).
This paper explores attitudes to peer support among people with Motor Neurone Disease (MND) and their family carers. It reports findings from a secondary analysis of data from two UK interview studies conducted by the authors. The process of secondary analysis is reported in detail. 48 people with MND and 22 carers were interviewed in 2005-2007. The authors identified narrative extracts on peer support from their own datasets and exchanged them for independent thematic analysis. Subsequent discussion, drawing on literature on support groups and social comparison, led to an exploration of two overarching themes: valuing camaraderie and comparison, and choosing isolation. Findings suggest that social comparison theory is a useful framework for analysing attitudes to MND support groups, but that on its own it is insufficient. 'Valuing camaraderie and comparison' explains how support groups offer practical and social support, as well as beneficial opportunities for social comparison. Seeing others coping well with the condition can provide hope, while downward comparison with those worse off can also make people feel better about their own situation. However, most people are also shocked and saddened by seeing others with the condition. Tension of identity can occur when group membership starts to define the individual as 'a person with MND, rather than the person I am that happens to have MND'. Choosing isolation can be a deliberate defensive strategy, to protect oneself from witnessing one's possible future. Levels of involvement may change over time as people struggle with their changing needs and fears.