Conventional spiral and low-dose computed mandibular tomography for dental implant planning.
Absorbed doses to radiosensitive organs in the head and neck from pre-implant conventional hypocycloidal, conventional spiral and computed tomography (CT) were measured with thermoluminescent dosimeters in an anthropomorphic phantom head. From conventional tomography organ doses, except to the major salivary glands, were below 0.2 mGy. They were considerably higher with CT than conventional tomography. Tomographic images of posterior lower jaw regions were evaluated regarding measurement reliability in conventional spiral tomograms. Observers measured the distance marginal crest-mandibular canal, marked their measuring points and estimated the length of an intended Brånemark implant. The variability between observers, mainly due to the intra-observer variation, decreased with multiple readings and optimized image quality. The suggested implant length was the same as the one inserted in 70% of the cases. Tomographic images from mandibular body segments were used to test the influence of radiation exposure and scanning mode on image quality in CT and compare the quality of the CT images with that in conventional spiral tomograms. Mandibular canal and marginal bone crest visibility was unaffected by radiation dose in CT examinations. Differences among CT scanning modes and between CT and conventional spiral tomography were highly significant. Frontal CT scans or conventional spiral tomograms were preferred. In cross-sectional images of the posterior lower jaw image quality in conventional spiral and reformatted CT at 40 mAs and 80 mAs was compared. Observers graded the acceptability of images for implant planning and traced the contours of the mandibular body and canal. Conventional, spiral tomograms were subjectively preferred over reformatted CT images. Differences between CT images at different mAs settings were not statistically significant. The mandibular canal was more frequently untraceable in high-dose CT. The use of tomography for dental implant planning was studied by means of a survey among oral radiology clinics in Sweden and implantology clinics in other countries. It was used by 93.4% but varied markedly between and within anatomic regions. CT was used by 73%. Radiation doses varied considerably within and between different CT brands. The availability rather than the clinical need strongly influenced the choice of technique. From the point of view of radiation dose and information necessary for implant planning conventional spiral tomography is to be preferred over reformatted CT. However, when CT is the only technique at hand, it can be performed with a lower than standard mA-setting.


Clinical Characteristics and Treatment Outcomes of Congenital Cholesteatoma.
Since its introduction in 2002, the staging system for congenital cholesteatoma, as defined by Potsic, has been used widely owing to its simplicity and predictability. The aim of the present study was to analyze the clinical characteristics and surgical treatment outcomes of congenital cholesteatoma and to correlate them with postoperative recurrence. A retrospective chart review was performed for 38 patients who were diagnosed with congenital cholesteatoma and who underwent surgical resection between August 2007 and November 2014 at the Department of Otorhinolaryngology of our hospital. The mean age of the patients was 7.9±8.2 years, and the number of males and females was 20 and 18, respectively. The mean follow-up period was 30±26 months. Of the 38 patients, 9 (24%) had residual or recurrent cholesteatoma during follow-up examination after primary surgery. The results showed that the size (≥4 mm) of the lesion was significantly correlated with residual or recurrent disease (p=0.026). The disease extent (single vs. multiple quadrant involvement), type (closed vs. open type), and stage; applied surgical method (with mastoidectomy vs. without mastoidectomy); and preoperative hearing level (normal vs. abnormal) were not significantly correlated with residual or recurrent disease. The disease extent, type, and stage; applied surgical methods; and preoperative hearing level were not significantly correlated with residual or recurrent disease. The size (≥4 mm) of congenital cholesteatoma was significantly correlated with residual or recurrent disease.


A novel approach to ECG classification based upon two-layered HMMs in body sensor networks.
This paper presents a novel approach to ECG signal filtering and classification. Unlike the traditional techniques which aim at collecting and processing the ECG signals with the patient being still, lying in bed in hospitals, our proposed algorithm is intentionally designed for monitoring and classifying the patient's ECG signals in the free-living environment. The patients are equipped with wearable ambulatory devices the whole day, which facilitates the real-time heart attack detection. In ECG preprocessing, an integral-coefficient-band-stop (ICBS) filter is applied, which omits time-consuming floating-point computations. In addition, two-layered Hidden Markov Models (HMMs) are applied to achieve ECG feature extraction and classification. The periodic ECG waveforms are segmented into ISO intervals, P subwave, QRS complex and T subwave respectively in the first HMM layer where expert-annotation assisted Baum-Welch algorithm is utilized in HMM modeling. Then the corresponding interval features are selected and applied to categorize the ECG into normal type or abnormal type (PVC, APC) in the second HMM layer. For verifying the effectiveness of our algorithm on abnormal signal detection, we have developed an ECG body sensor network (BSN) platform, whereby real-time ECG signals are collected, transmitted, displayed and the corresponding classification outcomes are deduced and shown on the BSN screen.


Platelet aggregation in the cerebral microcirculation: effect of aspirin and other agents.
After a certain period of time filtered ultraviolet light produces platelet aggregation in microvessels on the cerebral surface of the mouse, but only when sodium fluorescein is first injected intravascularly to provide a light-absorbing, heat-generating target. The platelet aggregates fluoresce. They occur only in the illuminated field and adhere to arteriolar and venular walls. Vasoconstriction is not detected prior to or up to 30 seconds after aggregation. Electron microscopy reveals damaged endothelium and undamaged red cells, as well as aggregates consisting almost exclusively of platelets in varying stages of aggregation, pseudopod formation, and degranulation. The time between onset of the noxious stimulus and recognition of the first aggregate can be measured as the vessels are observed microscopically. This "time of aggregation" is prolonged by pentobarbital as opposed to urethane anesthesia, and also is related to time elapsed after craniotomy. We also found that aspirin and indomethacin significantly prolong time to first aggregate, but only on the arteriolar side of the circulation. This is so even though the composition of the aggregates is the same on both the arteriolar and venular sides. Heparin has no effect.


Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats.
Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST) and electrophysiological recording aged eight weeks. The results of the FST showed neonatal DEX treatment increased depression-like behaviour in adulthood. After acute stress evoking, the percentage of time spent free floating is significantly increased in the DEX treated group compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059, showed significant rescue effects including reduced depression-like behaviour and restoration of LTP to within normal range. In conclusion, our results suggested that MAPK signalling cascade in the LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function, which may result in adverse consequences in adult age, such as the enhancement of susceptibility for a depressive disorder in later life.


Eating behaviours and attitudes following prolonged exposure to television among ethnic Fijian adolescent girls.
There are no published studies evaluating the impact of introduction of television on disordered eating in media-naïve populations. To assess the impact of novel, prolonged exposure to television on disordered eating attitudes and behaviours among ethnic Fijian adolescent girls. A prospective, multi-wave cross-sectional design was used to compare two samples of Fijian schoolgirls before and after prolonged regional television exposure with a modified 26-item eating attitudes test, supplemented with a semi-structured interview to confirm self-reported symptoms. Narrative data from a subset of respondents from the exposed sample were analysed for content relating television exposure to body image concerns. Key indicators of disordered eating were significantly more prevalent following exposure. Narrative data revealed subjects' interest in weight loss as a means of modelling themselves after television characters. This naturalistic experiment suggests a negative impact of television upon disordered eating attitudes and behaviours in a media-naïve population.


The anti-asthmatic potential of flavonol kaempferol in an experimental model of allergic airway inflammation.
Flavonol kaempferol possesses a broad spectrum of potent pharmacological activities that seem to be effective in the modulation of allergic respiratory diseases. In our study, an experimental animal model of ovalbumin (OVA)-induced allergic airway inflammation in guinea pigs was used to determine the anti-asthmatic potential of kaempferol. The parameters of specific airway resistance (sRaw) and cough reflex response were evaluated in vivo. In vitro, an assessment of tracheal smooth muscle (TSM) contractility and analyses of inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, IFN-γ), transforming growth factor (TGF-β1), immune cells count and ciliary beating frequency (CBF) were performed. Both single (6, 20 mg/kg b. w. p. o.) and long-term administered doses of kaempferol (20 mg/kg b. w. p. o., 21 days) suppressed sRaw provoked by histamine in conscious animals. The administration of kaempferol for 21 days attenuated histamine-induced TSM contractility in vitro and ameliorated the progression of chronic airway inflammation by decreasing the levels of IL-5, IL-13, GM-CSF, eosinophil count in bronchoalveolar lavage (BAL) fluid and TGF-β1 protein level in lung tissue. Kaempferol also eliminated the alterations in cough reflex sensitivity invoked by OVA-sensitization, but it did not affect CBF. The results demonstrate that flavonol kaempferol can modulate allergic airway inflammation and associated asthma features (AHR, aberrant stimulation of cough reflex).


Communication Ambassadors-an Australian Social Media Initiative to Develop Communication Skills in Early Career Scientists.
Science communication is a skill set to be developed through ongoing interactions with different stakeholders across a variety of platforms. Opportunities to engage the general public are typically reserved for senior scientists, but the use of social media in science communication allows all scientists to instantaneously disseminate their findings and interact with online users. The Communication Ambassador program is a social media initiative launched by the Australian Society for Microbiology to expand the online presence and science communication portfolios of early-career scientists. Through their participation in the program, a rotating roster of Australian microbiologists have broadened the online reach of the Society's social media channels as well as their own professional networks by attending and live-tweeting microbiology events throughout the year. We present the Communication Ambassador program as a case study of coordinated social media activity in science communication to the general public, and describe the potential for its applications in science education and training.


Regulation of ATP hydrolysis by the ε subunit, ζ subunit and Mg-ADP in the ATP synthase of Paracoccus denitrificans.
F1FO-ATP synthase is a crucial metabolic enzyme that uses the proton motive force from respiration to regenerate ATP. For maximum thermodynamic efficiency ATP synthesis should be fully reversible, but the enzyme from Paracoccus denitrificans catalyzes ATP hydrolysis at far lower rates than it catalyzes ATP synthesis, an effect often attributed to its unique ζ subunit. Recently, we showed that deleting ζ increases hydrolysis only marginally, indicating that other common inhibitory mechanisms such as inhibition by the C-terminal domain of the ε subunit (ε-CTD) or Mg-ADP may be more important. Here, we created mutants lacking the ε-CTD, and double mutants lacking both the ε-CTD and ζ subunit. No substantial activation of ATP hydrolysis was observed in any of these strains. Instead, hydrolysis in even the double mutant strains could only be activated by oxyanions, the detergent lauryldimethylamine oxide, or a proton motive force, which are all considered to release Mg-ADP inhibition. Our results establish that P. denitrificans ATP synthase is regulated by a combination of the ε and ζ subunits and Mg-ADP inhibition.


Microstructure of Polymers by Tritium Autoradiography.
Polystyrene, polypropylene, and polyethylene, containing tritiumlabeled additives and crystallized in thin films, were examined with autoradiographic stripping film. In the structures formed by isotactic polystyrene, tritiated atactic polymer concentrated in specific patterns in the outer regions. Polypropylene spherulites showed marked differences in the distribution of the tritiated additive, dilauryl thiodipropionate, whenever their optical properties also differed. Autoradiographs of polyethylene spherulites containing low molecular weight tritiated polyethylene exhibited concentric ring patterns similar to those observed on viewing the polymer film in a polarizing microscope.


Quality of life and sexuality after bilateral sacrospinous fixation with vaginal hysterectomy for treatment of primary pelvic organ prolapse.
To investigate the quality of life (QoL) and sexuality in women affected by pelvic organ prolapse (POP) and treated by bilateral sacrospinous ligament fixation (SSLF) with vaginal hysterectomy. This is a prospective observational study carried out at Isparta City Hospital from July 2017 to December 2018. A total of 26 sexually active women with symptomatic uterine prolapse POP-Q (Pelvic Organ Prolapse Quantification) stage II or higher requiring surgery were included in the study. Short Form Health Survey (SF-36) was used preoperatively and at 6 months to examine the impacts of vaginal reconstruction on QoL. To assess sexual functioning, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) was used preoperatively and at 6 months. A significant improvement of POP-Q landmarks was found between pre- and posttreatment at 6 months of follow-up. The patients reported QoL improvement at the follow-up for all the categories of physical functioning, bodily pain, physical health, general health, vitality, social activity, emotional state, and mental health with respect to the baseline values (P < .001). The results of PISQ-12 demonstrated a significant improvement for all the three fields: behavioral emotive factor, physical factor, and partner-related factor, and the total score at 6 months after surgery (P < .001). This study clearly demonstrates that bilateral SSLF is able to significantly improve both QoL and sexual function in patients with POP. Improvement in sexuality and QoL after surgery may be explained by correction of avoidance of sexual intercourse due to prolapse and physical recovery.


A Performance-Based Incentives System for Village Health Workers in Kisoro, Uganda.
Village health worker (VHW) programs in Uganda have achieved limited success, due in part to a reliance on volunteerism and a lack of standardized incentive mechanisms. However, how to best incentivize VHWs remains unclear. Doctors for Global Health developed a performance-based incentives (PBI) system to pay its VHWs in Kisoro, Uganda, based on performance of tasks or achievement of targets. 1. To describe the development of a PBI system used to compensate VHWs. 2. To report cost and health services delivery outcomes under a PBI system. 3. To provide qualitative analysis on the successes and challenges of PBI. Internal organization records from May 2016 to April 2017 were retrospectively reviewed. The results of descriptive and analytic statistics were reported. Qualitative analysis was performed by the authors. In one year, 42 VHWs performed 23,703 remunerable health actions, such as providing care of minor ailments and chronic disease. VHWs earned on average $237. The total cost to maintain the program was $29,844, or $0.72 per villager. There was 0% VHW attrition. Strengths of PBI included flexibility, accountability, higher VHW earnings, and improved monitoring and evaluation. PBI is a feasible and sustainable model of compensating VHWs. At a time where VHW programs are sorely needed to address limitations in healthcare resources, yet are facing challenges with workforce compensation, PBI may serve as a model for others in Uganda and around the world.


Primate comparative neuroscience using magnetic resonance imaging: promises and challenges.
Primate comparative anatomy is an established field that has made rich and substantial contributions to neuroscience. However, the labor-intensive techniques employed mean that most comparisons are often based on a small number of species, which limits the conclusions that can be drawn. In this review we explore how new developments in magnetic resonance imaging have the potential to apply comparative neuroscience to a much wider range of species, allowing it to realize an even greater potential. We discuss (1) new advances in the types of data that can be acquired, (2) novel methods for extracting meaningful measures from such data that can be compared between species, and (3) methods to analyse these measures within a phylogenetic framework. Together these developments will allow researchers to characterize the relationship between different brains, the ecological niche they occupy, and the behavior they produce in more detail than ever before.


International Consortium for Health Outcome Measurement Set of Outcomes That Matter to People Living With Inflammatory Arthritis: Consensus From an International Working Group.
The implementation of value-based health care in inflammatory arthritis requires a standardized set of modifiable outcomes and risk-adjustment variables that is feasible to implement worldwide. The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary working group that consisted of 24 experts from 6 continents, including 6 patient representatives, to develop a standard set of outcomes for inflammatory arthritis. The process followed a structured approach, using a modified Delphi process to reach consensus on the following decision areas: conditions covered by the set, outcome domains, outcome measures, and risk-adjustment variables. Consensus in areas 2 to 4 were supported by systematic literature reviews and consultation of experts. The ICHOM Inflammatory Arthritis Standard Set covers patients with rheumatoid arthritis (RA), axial spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). We recommend that outcomes regarding pain, fatigue, activity limitations, overall physical and mental health impact, work/school/housework ability and productivity, disease activity, and serious adverse events be collected at least annually. Validated measures for patient-reported outcomes were endorsed and linked to common reporting metrics. Age, sex at birth, education level, smoking status, comorbidities, time since diagnosis, and rheumatoid factor and anti-citrullinated protein antibody lab testing for RA and JIA should be collected as risk-adjustment variables. We present the ICHOM inflammatory arthritis Standard Set of outcomes, which enables health care providers to implement the value-based health care framework and compare outcomes that are important to patients with inflammatory arthritis.


Low back pain among nurses working in clinical settings of Africa: systematic review and meta-analysis of 19 years of studies.
Nurses in Africa are arguably the most important frontline healthcare workers available in most healthcare facilities, performing a broad range of tasks. Such tasks are considerably presumed in the causation of workload. Nursing is listed among the highly risky professions for developing low back pain. The nursing profession is ranked within the top ten professions which have a great risk of low back pain. Hence, this review aimed to ascertain whether low back pain is a significant concern for nurses in African healthcare facilities. A comprehensive literature search of different databases with no date limit was conducted from September to November 2018 using the PRISMA guideline. The quality of the included studies was assessed using a 12-item rating system. Subgroup and sensitivity analyses were performed. Cochran's Q and the I2 test were used to assess heterogeneity. The presence of publication bias was evaluated by using Egger's test and visual inspection of the symmetry in funnel plots. In this review, 19 studies from different African regions with a total sample size of 6110 nurses were included. All the studies were carried out between 2000 and 2018. Among these, the lowest and the highest prevalence were found to be 44.1 and 82.7% respectively. The estimation of the prevalence rate of low back pain among nurses using the random-effects model was found to be 64.07% (95% CI: 58.68-69.46; P-value < 0.0001). Heterogeneity of the reviewed studies was I2 = 94.2% and heterogeneity Chi-squared = 310.06 (d.f = 18), P-value < 0.0001. The subgroup analyses showed that the highest prevalence of LBP among nurses was from West African region with prevalence rates of 68.46% (95% CI: 54.94-81.97; P-value < 0.0001) and followed by North Africa region with prevalence rate of 67.95% (95% CI: 55.96-79.94; P-value < 0.0001). Even though the overall prevalence of the present study is lower when compared to the Western and Asian studies, it indicated that the prevalence of low back pain among nurses is substantial.


SARS-CoV-2 receptor networks in diabetic and COVID-19-associated kidney disease.
COVID-19 morbidity and mortality are increased via unknown mechanisms in patients with diabetes and kidney disease. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Because ACE2 is a susceptibility factor for infection, we investigated how diabetic kidney disease and medications alter ACE2 receptor expression in kidneys. Single cell RNA profiling of kidney biopsies from healthy living donors and patients with diabetic kidney disease revealed ACE2 expression primarily in proximal tubular epithelial cells. This cell-specific localization was confirmed by in situ hybridization. ACE2 expression levels were unaltered by exposures to renin-angiotensin-aldosterone system inhibitors in diabetic kidney disease. Bayesian integrative analysis of a large compendium of public -omics datasets identified molecular network modules induced in ACE2-expressing proximal tubular epithelial cells in diabetic kidney disease (searchable at hb.flatironinstitute.org/covid-kidney) that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. The diabetic kidney disease ACE2-positive proximal tubular epithelial cell module overlapped with expression patterns seen in SARS-CoV-2-infected cells. Similar cellular programs were seen in ACE2-positive proximal tubular epithelial cells obtained from urine samples of 13 hospitalized patients with COVID-19, suggesting a consistent ACE2-coregulated proximal tubular epithelial cell expression program that may interact with the SARS-CoV-2 infection processes. Thus SARS-CoV-2 receptor networks can seed further research into risk stratification and therapeutic strategies for COVID-19-related kidney damage.


The Postoperative Morbidity Index: a quantitative weighing of postoperative complications applied to urological procedures.
The reporting of post-operative complications in the urological field is lacking of a uniform quantitative measure to assess severity, which is essential in the analysis of surgical outcomes. The purpose of this study was to evaluate the feasibility of estimating quantitative severity weighing of post-operative complications after common urologic procedures. Using a large healthcare system's quality database, complications were identified in eleven common urologic procedures (e.g., insertion or replacement of inflatable penile prosthesis, nephroureterectomy, partial nephrectomy, percutaneous nephrostomy tube placement, radical cystectomy, radical prostatectomy, renal/ureteral/bladder extracorporeal shockwave lithotripsy (ESWL), transurethral destruction of bladder lesion, transurethral prostatectomy, transurethral removal of ureteral obstruction, and ureteral catheterization) from January 1, 2011 to December 31, 2011. Complications were classified by the Expanded Accordion Severity Grading System, which was then quantified by validated severity weighting scores. The Postoperative Morbidity Index (PMI) for each procedure was calculated where an index of 0 would indicate no complication in any patient and an index of 1 would indicate that all patients died. This study included 654 procedures of which 148 (22%) had one or more complications. As would be expected, a more complex procedure like radical cystectomy possessed a higher PMI (0.267), while a simpler procedure like percutaneous nephrostomy tube placement possessed a lower PMI (0.011). The PMI of the additional nine procedures fell within the range of these PMIs. These PMIs could be used to compare surgeons, hospitals or procedures. Quantitative severity weighing of post-operative complications for urologic procedures is feasible and may provide exceptionally informative data related to outcomes.


Exchange-correlation generalized gradient approximation for gold nanostructures.
We compare the performance of different exchange-correlation functionals, based on the Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation, for the structural and electronic properties of gold nanostructures. In particular we consider PBEsol (constructed to correctly describe solid-state systems) and PBEint [Phys. Rev. B 82, 113104 (2010)] which was recently introduced for hybrid interfaces and preserves the correct second-order gradient expansion of exchange energy (as in PBEsol) providing as well a significant nonlocality for higher density variation (as in PBE). We find that the PBEint functional gives a well balanced description of atomization energies, structural properties, energy differences between isomers, and bulk properties. Results indicate that PBEint is expected to be the most accurate functional for medium and large size gold clusters of different shapes.


Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease.
Calpains are calcium-dependent enzymes that determine the fate of proteins through regulated proteolytic activity. Calpains have been linked to the modulation of memory and are key to the pathogenesis of Alzheimer disease (AD). When abnormally activated, calpains can also initiate degradation of proteins essential for neuronal survival. Here we show that calpain inhibition through E64, a cysteine protease inhibitor, and the highly specific calpain inhibitor BDA-410 restored normal synaptic function both in hippocampal cultures and in hippocampal slices from the APP/PS1 mouse, an animal model of AD. Calpain inhibition also improved spatial-working memory and associative fear memory in APP/PS1 mice. These beneficial effects of the calpain inhibitors were associated with restoration of normal phosphorylation levels of the transcription factor CREB and involved redistribution of the synaptic protein synapsin I. Thus, calpain inhibition may prove useful in the alleviation of memory loss in AD.


Polyurethane versus silicone catheters for central venous port devices implanted at the forearm.
We aimed to analyse short and long-term complications of polyurethane (PU) versus silicone catheters used in totally implantable venous-access ports (TIVAPs) implanted at the forearm. Retrospective analysis of 698 consecutively implanted TIVAPs was performed. Primary end-points were defined as rates of major complications associated with either type of central venous port catheter. Technical success rate, device service interval as well as minor complications not requiring port explantation were defined as secondary end-points. A total of 698 port devices were implanted in 681 patients, 396 equipped with a PU catheter, 302 with a silicone catheter. The technical success rate was 99.9% with no major periprocedural complications. During follow-up a total of 211 complications in 146 patients were observed (1.0/1000 catheter days), 183 occurred associated with PU catheters (1.8/100 catheter days), 28 (0.3/1000 catheter days) with silicone catheters (log rank test p < 0.0001). Catheter-related bloodstream infections as well as thrombotic complications occurred significantly more frequently with PU catheters, while silicone catheters exhibited a trend towards a higher rate of mechanical failure such as disconnection or catheter rupture. Major complications requiring explantation of the device occurred more frequently with PU-based catheters (10.6%) compared to silicone catheter carrying ports (4.6%, log rank test p < 0.001). PU catheters are more susceptible to catheter-related infections and exhibit a higher thrombogenicity, compared to silicone catheters. Silicone catheters instead exhibit a trend towards decreased mechanical stability.


Human performance on conjunctive fixed-interval fixed-ratio schedules.
Eighteen young adults performed a lever-pulling task for money. Subjects were initially exposed to a fixed-interval 80-second schedule and subsequently to one of three conjunctive schedules in which the added fixed-ratio requirement was set at either 10, 80, or 120 responses. Three fixed-interval response patterns emerged: high constant rate, intermediate rate, or low rate, with most subjects displaying the last. Conjunctive performance was related to the subjects' prior fixed-interval patterns and the conjunctive ratio requirements. Low-rate subjects tended to optimize reinforcement (maximum reinforcers for minimum responses) on conjunctive schedules. Response rate was directly related to ratio requirements. Subjects' performance closely corresponded to their verbal statements of the contingencies.


Global optimization point-set registration based on translation/rotation decoupling for image-guided surgery applications.
In image-guided surgery systems, image-to-patient spatial registration is to get the spatial transformation between the image space and the actual operating space. Although the image-to-patient spatial registration methods using paired point or surface matching are used in some image-guided neurosurgery systems, the key problem is that the global optimization registration result cannot be achieved. Therefore, this paper proposes a new rotation invariant feature for decoupling rotation and translation space, based on which global optimization point set registration method is proposed. The new rotation invariant features, constructed based on the edges and the angles, are the rotation invariant, which has high feature resolution. Some of them are not only the rotation invariant, but also the translation invariant. To obtain the global optimal solution, branch and bound search strategy is used to search the parameter space of the translation and the computational cost is reduced simultaneously. The registration accuracy of the spatial registration method is analyzed by comparing the difference between the estimated transform and the standard transform to calculate the registration error. To validate the performance of the spatial registration method proposed, the registration performance was analyzed by comparing the experimental results with the results of the two mainstream registration methods (the iterative closest point [ICP] registration method and the coherent point drift method). In the experiments, the comparison was based on the registration accuracy and the execution time. We show our registration method can obtain higher accuracy in a shorter time in most cases. At the same time, when using ICP to further refine our results, the ICP method can converge in a very short time, which also shows that our method provides a good initial pose for the ICP method and can help the ICP converge to the global optimal solution faster. Our method can achieve an average rotation error of 0.124 degrees and an average translation error of 0.38 mm on 10 clinical data. The results reveal that the surface registration method based on translation rotation decoupling can achieve superior performance regarding both the registration accuracy and the time efficiency in the image-to-patient spatial registration.


Calcium phosphate cement composites in revision hip arthroplasty.
Loosening of the femoral component in a total hip arthroplasty with concomitant bone loss can pose a problem for revision surgery due to inadequate structure in the remaining femur. While impaction allografting has shown promise, it has also shown serious complications, especially with moderate to severe bone loss. It may be possible to stabilize the graft layer with a bioresorbable cement to improve clinical results. This study examines the mechanical properties of a potential morsellized bone-bioresorbable composite. Morsellized bone was mixed with a commercially available bioresorbable cement (alpha-BSM, Etex Corp.) in compositions of 0%, 25%, 50% and 75% bone. Unconfined compression and diametral tensile and confined compression tests were performed to determine the composite mechanical properties. The composition containing 50% bone tended to exhibit the highest uniaxial strengths, as well as the highest confined compression modulus. The uniaxial compressive strength and stiffness of this composition was in the range of cancellous bone. Uniaxial compressive modulus decreased with increasing bone fraction whereas elongation exhibited the opposite trend. Bone fraction had a significant effect on compressive strength (p < 0.0001), compressive modulus (p < 0.0001), elongation (p < 0.01), tensile strength (p < 0.0001) and confined compressive modulus (p = 0.04). The addition of a bioresorbable cement to the allograft layer may improve the properties of the layer, preventing early subsidence seen in some clinical studies of impaction allografting, and therefore improving the clinical results. Further testing is required to evaluate the in vitro mechanical performance, as well as in vivo remodelling characteristics.


Ethanol production from cotton-based waste textiles.
Ethanol production from cotton linter and waste of blue jeans textiles was investigated. In the best case, alkali pretreatment followed by enzymatic hydrolysis resulted in almost complete conversion of the cotton and jeans to glucose, which was then fermented by Saccharomyces cerevisiae to ethanol. If no pretreatment applied, hydrolyses of the textiles by cellulase and beta-glucosidase for 24 h followed by simultaneous saccharification and fermentation (SSF) in 4 days, resulted in 0.140-0.145 g ethanol/g textiles, which was 25-26% of the corresponding theoretical yield. A pretreatment with concentrated phosphoric acid prior to the hydrolysis improved ethanol production from the textiles up to 66% of the theoretical yield. However, the best results obtained from alkali pretreatment of the materials by NaOH. The alkaline pretreatment of cotton fibers were carried out with 0-20% NaOH at 0 degrees C, 23 degrees C and 100 degrees C, followed by enzymatic hydrolysis up to 4 days. In general, higher concentration of NaOH resulted in a better yield of the hydrolysis, whereas temperature had a reverse effect and better results were obtained at lower temperature. The best conditions for the alkali pretreatment of the cotton were obtained in this study at 12% NaOH and 0 degrees C and 3 h. In this condition, the materials with 3% solid content were enzymatically hydrolyzed at 85.1% of the theoretical yield in 24 h and 99.1% in 4 days. The alkali pretreatment of the waste textiles at these conditions and subsequent SSF resulted in 0.48 g ethanol/g pretreated textiles used.


iNKT cell development is orchestrated by different branches of TGF-beta signaling.
Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-beta controls the differentiation program of iNKT cells. We demonstrate that TGF-beta signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-beta involves the concerted action of different pathways of TGF-beta signaling. Whereas the Tif-1gamma branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1gamma/Smad4-independent branch. Thus, these three different branches of TGF-beta signaling function in concert as complementary effectors, allowing TGF-beta to fine tune the iNKT cell differentiation program.


Understanding surface site structures and properties by first principles calculations: an experimental point of view!
The characterization of the active sites in heterogeneous catalysts is highly challenging and hinders the rational development and design of better catalysts. One approach to achieve this goal is Surface Organometallic Chemistry (SOMC), which allows generation of well-defined active sites characterized at the molecular level using spectroscopic methods. Due to many advances in the field and the increase of computational power, Computational Chemistry (CompChem) plays a key role in providing an atomistic understanding of these systems and the nature of the active sites. In this perspective, we discuss how CompChem has been essential in helping us to understand a broad range of systems from the surface chemistry of the support materials themselves, to the structure, spectroscopic signatures and activity of single-site catalysts and supported metallic nanoparticles.


Structure of the SARS coronavirus nucleocapsid protein RNA-binding dimerization domain suggests a mechanism for helical packaging of viral RNA.
Coronavirus nucleocapsid proteins are basic proteins that encapsulate viral genomic RNA to form part of the virus structure. The nucleocapsid protein of SARS-CoV is highly antigenic and associated with several host-cell interactions. Our previous studies using nuclear magnetic resonance revealed the domain organization of the SARS-CoV nucleocapsid protein. RNA has been shown to bind to the N-terminal domain (NTD), although recently the C-terminal half of the protein has also been implicated in RNA binding. Here, we report that the C-terminal domain (CTD), spanning residues 248-365 (NP248-365), had stronger nucleic acid-binding activity than the NTD. To determine the molecular basis of this activity, we have also solved the crystal structure of the NP248-365 region. Residues 248-280 form a positively charged groove similar to that found in the infectious bronchitis virus (IBV) nucleocapsid protein. Furthermore, the positively charged surface area is larger in the SARS-CoV construct than in the IBV. Interactions between residues 248-280 and the rest of the molecule also stabilize the formation of an octamer in the asymmetric unit. Packing of the octamers in the crystal forms two parallel, basic helical grooves, which may be oligonucleotide attachment sites, and suggests a mechanism for helical RNA packaging in the virus.


A retrospective study of the prevalence of bovine fasciolosis at major abattoirs in Botswana.
A retrospective study covering a period of ten years (2001-2010) was conducted using postmortem meat inspection records of the Department of Veterinary Services in Gaborone to determine the prevalence of bovine fasciolosis in Botswana. Meat inspection records of monthly and annual returns from the two main export abattoirs in the country were examined, as well as the data collected on the total number of cattle slaughtered and the number of livers condemned due to Fasciola gigantica infection. Only 1250 of the approximately 1.4 million cattle slaughtered were infected with F. gigantica (0.09%, 95% confidence intervals [CI] 0.0% - 0.3%). No distinct seasonal pattern was observed in condemnation rates of livers. However, the pattern of distribution of fasciolosis was higher (but not significant) in cattle that originated from areas with high rainfall and more permanent water bodies than those from relatively low rainfall areas with a transitory water system. It is recommended that a longitudinal survey should be carried out at the abattoirs and farms to determine the prevalence of the disease in cattle of different ages, sex and breed as well as the place of origin in the country. The present study indicated that the prevalence of fasciolosis in cattle is low and the disease is therefore of less significance in Botswana than other African countries for which information is available.


Permanent global amnesia: case report.
To present a case of permanent global amnesia related to hippocampal damage. Permanent global amnesia is a very rare condition of unknown etiology; lesions restricted to the hippocampus are uncommon, which hinders investigations of this pattern of memory loss. This case is unusually well documented, as the patient underwent extensive neuropsychological evaluations. A cheerful right-handed, 83-year-old retired electrician was first evaluated in 1990 for progressive difficulty in learning new information and in recalling events over the preceding 3-4 years. Tests over the next 5 years showed that the impairment was confined to episodic declarative memory. New verbal information could be stored only in episodic memory in a restricted manner, limited by short-term memory capacity. A relatively mild retrograde amnesia was detected. Semantic and implicit memory was spared, as were other functions evaluated. The patient's language and executive function were strikingly efficient. Magnetic resonance imaging of the brain showed bilateral atrophy of the hippocampi and amygdalae, ruling out conditions such as tumour growth. A diagnosis of permanent global amnesia was made. In the ensuing years, the retrograde amnesia worsened, but no new deficits were identified. This case, the first with a detailed cognitive examination, is evidence of a relatively pure hippocampal pattern for memory loss in permanent global amnesia.


The Effect of Platelet-Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial.
Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery, and preliminary evidence suggests that it might have a beneficial role in hair regrowth. Here, we report the results of a randomized, evaluator-blinded, placebo-controlled, half-head group study to compare, with the aid of computerized trichograms, hair regrowth with PRP versus placebo. The safety and clinical efficacy of autologous PRP injections for pattern hair loss were investigated. PRP, prepared from a small volume of blood, was injected on half of the selected patients' scalps with pattern hair loss. The other half was treated with placebo. Three treatments were administered to each patient at 30-day intervals. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki67 evaluation. Patients were followed for 2 years. Of the 23 patients enrolled, 3 were excluded. At the end of the 3 treatment cycles, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 33.6 hairs in the target area, and a mean increase in total hair density of 45.9 hairs per cm² compared with baseline values. No side effects were noted during treatment. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles 2 weeks after the last PRP treatment compared with baseline value (p < .05). We also observed an increase of Ki67(+) keratinocytes in the epidermis and of hair follicular bulge cells, and a slight increase of small blood vessels around hair follicles in the treated skin compared with baseline (p < .05). Relapse of androgenic alopecia was not evaluated in all patients until 12 months after the last treatment. After 12 months, 4 patients reported progressive hair loss; this was more evident 16 months after the last treatment. Those four patients were re-treated. Our data clearly highlight the positive effects of PRP injections on male pattern hair loss and absence of major side effects. PRP may serve as a safe and effective treatment option against hair loss; more extensive controlled studies are needed. Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery, and preliminary evidence suggests that it might have a beneficial role in hair regrowth. Here, the results of a randomized, placebo-controlled, half-head group study to compare the hair regrowth with PRP versus placebo are reported. Hair regrowth was quantified by a blinded evaluator using computerized trichograms. The safety and clinical efficacy of autologous PRP injections for pattern hair loss were investigated. Of the 23 patients enrolled, 3 were excluded. At the end of the 3 treatment cycles, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 33.6 hairs in the target area and a mean increase in total hair density of 45.9 hairs per cm² compared with baseline values. No side effects were noted during treatment. The data clearly highlight the positive effects of PRP injections on male pattern hair loss and absence of major side effects. PRP may serve as a safe and effective treatment option against hair loss; more extensive controlled studies are needed.


Derivation and validation of a clinical diagnostic tool for the identification of older community-dwellers with hypovitaminosis D.
Hypovitaminosis D is highly prevalent among seniors. Although evidence is insufficient to recommend routine vitamin D screening in seniors, universal vitamin D supplementation is not desirable either. To rationalize vitamin D determination, our objective was to elaborate and test a clinical diagnostic tool for the identification of seniors with hypovitaminosis D without using a blood test. Derivation of a clinical diagnostic tool using artificial neural networks (multilayer perceptron; MLP) in randomized training subgroup of Prévention des Chutes, Réseau 4' cohort, and validation in randomized testing subgroup. Health Examination Centers of health insurance, Lyon, France. A total of 1924 community-dwellers aged ≥ 65 years without vitamin D supplements, consecutively recruited between 2009 and 2012. Hypovitaminosis D defined as serum 25-hydroxyvitamin (25OHD) concentration ≤ 75 nmol/L, ≤ 50 nmol/L, or ≤ 25 nmol/L. A set of clinical variables (age, gender, living alone, individual deprivation, body mass index, undernutrition, polymorbidity, number of drugs used daily, psychoactive drugs, biphosphonates, strontium, calcium supplements, falls, fear of falling, vertebral fractures, Timed Up and Go, walking aids, lower-limb proprioception, handgrip strength, visual acuity, wearing glasses, cognitive disorders, sad mood) were recorded. Several MLPs, based on varying amounts of variables according to their relative importance, were tested consecutively. A total of 1729 participants (89.9%) had 25OHD ≤ 75 nmol/L, 1288 (66.9%) had 25OHD ≤ 50 nmol/L, and 525 (27.2%) had 25OHD ≤ 25 nmol/L. MLP using 16 clinical variables was able to diagnose hypovitaminosis D ≤ 75 nmol/L with accuracy = 96.3%, area under curve (AUC) = 0.938, and κ = 79.3 indicating almost perfect agreement. It was also able to diagnose hypovitaminosis D ≤ 50 nmol/L with accuracy = 81.5, AUC = 0.867, and κ = 57.8 (moderate agreement); and hypovitaminosis D ≤ 25 nmol/L with accuracy = 82.5, AUC = 0.385, and κ = 55.0 (moderate agreement). We elaborated an algorithm able to identify, from 16 clinical variables, seniors with hypovitaminosis D.


Dielectric properties and electronic absorption: a comparison of novel azo- and oxo-bridged phthalocyanines.
The novel two homologous phthalocyanine (Pc) series (azo- and oxo-bridged) substituted with a 5-bromo-2-methoxyphenyl moiety were synthesized and characterized. The physical and chemical properties of the Pcs were compared with each other for the first time. The ac response of the Pcs was also studied by impedance measurements over a temperature range of 300-500 K. The real and imaginary parts of the impedance were found to be dependent on both frequency and temperature. The impedance spectra of the samples displayed semicircular arcs in the complex plane plot at all temperatures, with their centres lying below the real axis at a particular angle of depression indicating the distribution of relaxation times. Measurements showed that the dielectric permittivity of azo-bridged phthalocyanines is significantly higher than that of the oxo-bridged homologs. This result can be attributed to the limited electron delocalization ability of oxo-bridged homologs.


Visual Feedback Attenuates Mean Concentric Barbell Velocity Loss and Improves Motivation, Competitiveness, and Perceived Workload in Male Adolescent Athletes.
Weakley, JJS, Wilson, KM, Till, K, Read, DB, Darrall-Jones, J, Roe, GAB, Phibbs, PJ, and Jones, B. Visual feedback attenuates mean concentric barbell velocity loss and improves motivation, competitiveness, and perceived workload in male adolescent athletes. J Strength Cond Res 33(9): 2420-2425, 2019-It is unknown whether instantaneous visual feedback of resistance training outcomes can enhance barbell velocity in younger athletes. Therefore, the purpose of this study was to quantify the effects of visual feedback on mean concentric barbell velocity in the back squat and to identify changes in motivation, competitiveness, and perceived workload. In a randomized-crossover design (Feedback vs. Control), feedback of mean concentric barbell velocity was or was not provided throughout a set of 10 repetitions in the barbell back squat. Magnitude-based inferences were used to assess changes between conditions, with almost certainly greater differences in mean concentric velocity between the Feedback (0.70 ± 0.04 m·s) and Control (0.65 ± 0.05 m·s) observed. In addition, individual repetition mean concentric velocity ranged from possibly (repetition number 2: 0.79 ± 0.04 vs. 0.78 ± 0.04 m·s) to almost certainly (repetition number 10: 0.58 ± 0.05 vs. 0.49 ± 0.05 m·s) greater when provided feedback, whereas almost certain differences were observed in motivation, competitiveness, and perceived workload, respectively. Providing adolescent male athletes with visual kinematic information while completing resistance training is beneficial for the maintenance of barbell velocity during a training set, potentially enhancing physical performance. Moreover, these improvements were observed alongside increases in motivation, competitiveness, and perceived workload providing insight into the underlying mechanisms responsible for the performance gains observed. Given the observed maintenance of barbell velocity during a training set, practitioners can use this technique to manipulate training outcomes during resistance training.


Fatigue life and damage tolerance of postbuckled composite stiffened structures with indentation damage.
The fatigue life and damage tolerance of composite stiffened panels with indentation damage are investigated experimentally using single-stringer compression specimens. The indentation damage was induced to one of the two flanges of the stringer of every panel. The advantages of indentation compared to impact are the simplicity of application, less dependence on boundary conditions, better controllability, and repeatability of the imparted damage. The tests were conducted using advanced instrumentation, including digital image correlation, passive thermography, and in situ ultrasonic scanning. Specimens with initial indentation damage ranging between 32 and 56 mm in length were tested quasi-statically and in fatigue, and the effects of cyclic load amplitude and damage size were studied. A means of comparison of the damage propagation rates and collapse loads based on a stress intensity measure and the Paris law is proposed. The stress intensity measure provides the means to compare the collapse loads of specimens with different damage types and damage sizes, while the Paris law is used to compare the damage propagation rates in specimens subjected to different cyclic loads. This approach enables a comparison of different tests and the potential identification of the effects that influence the fatigue lives and damage tolerance of postbuckled structures with defects.


Immersive 3D exposure-based treatment for spider fear: A randomized controlled trial.
Stereoscopic 3D gives the viewer the same shape, size, perspective and depth they would experience viewing the real world and could mimic the perceptual threat cues present in real life. This is the first study to investigate whether an immersive stereoscopic 3D video exposure-based treatment would be effective in reducing fear of spiders. Participants with a fear of spiders (N = 77) watched two psychoeducational videos with facts about spiders and phobias. They were then randomized to a treatment condition that watched a single session of a stereoscopic 3D immersive video exposure-based treatment (six 5-min exposures) delivered through a virtual reality headset or a psychoeducation only control condition that watched a 30-min neutral video (2D documentary) presented on a computer monitor. Assessments of spider fear (Fear of Spiders Questionnaire [FSQ], Behavioral Approach Task [BAT], & subjective ratings of fear) were completed pre- and post-treatment. Consistent with prediction, the stereoscopic 3D video condition outperformed the control condition in reducing fear of spiders showing a large between-group effect size on the FSQ (Cohen's d = 0.85) and a medium between-group effect size on the BAT (Cohen's d = 0.47). This provides initial support for stereoscopic 3D video in treating phobias.


Salinization effects on coastal ecosystems: a terrestrial model ecosystem approach.
In coastal areas, intrusion/irrigation with seawater can threaten biodiversity along with crop yields, and the leaching of salts from areas affected by these processes can increase the salinity of water bodies nearby. The aims of this study were to evaluate the effects of salinization on coastal soil ecosystems due to saline intrusion/irrigation. Terrestrial model ecosystems were used to simulate two soil salinization scenarios: (i) seawater intrusion and irrigation with distilled water and (ii) seawater intrusion and irrigation with saline water. Three sampling periods were established: T0-after acclimation period; T1-salinization effects; and T2-populations' recovery. In each sampling period, the abundance of nematodes, enchytraeids, springtails, mites and earthworms, and plant biomass were measured. Immediate negative effects on enchytraeid abundance were detected, especially at the higher level of saltwater via intrusion+irrigation. Eight weeks after the cessation of saline irrigation, the abundance of enchytraeids fully recovered, and some delayed effects were observed in earthworm abundance and plant biomass, especially at the higher soil conductivity level. The observed low capacity of soil to retain salts suggests that, particularly at high soil conductivities, nearby freshwater bodies can also be endangered. Under saline conditions similar to the ones assayed, survival of some soil communities can be threatened, leading to the loss of biodiversity.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.


Increase in viral load, viral integration, and gain of telomerase genes during uterine cervical carcinogenesis can be simultaneously assessed by the HPV 16/18 MLPA-assay.
Oncogenic human papillomavirus (HPV) infection is the most important risk factor in cervical carcinogenesis cases; high viral loads, viral integration into the host genome, and gain of the telomerase-related genes, TERT and TERC, are all factors associated with progression to cancer. A recently developed multiparameter HPV 16/18 multiplex ligation-dependent probe amplification (MLPA) assay, which allows the simultaneous assessment of these factors, was applied to a series of 67 normal and (pre)malignant frozen uterine cervical samples, as well as to 91 cytological preparations, to test the ability of the MLPA assay to identify high-risk lesions on the basis of these factors. Validation was performed using quantitative PCR, the PapilloCheck and fluorescence in situ hybridization. Only 5 out of 37 normal tissue samples or low-grade cervical lesions (ie, CIN1 and condyloma) showed either an HPV16 viral load higher than 25 copies per cell, viral integration, and/or gain of one of the telomerase-related genes, whereas for the high-grade cervical lesions, one or more of these risk factors was found in 25 of 30 cases. The HPV MLPA assay showed a sensitivity of 83% and a specificity of 86% in frozen cervical specimens. Furthermore, the feasibility of the MLPA assay was shown for cytological samples, where in 57% of high-grade squamous intraepithelial lesion cases, the high-risk factors were detected using this assay.


Muscle: an independent contributor to the neuromuscular spinal muscular atrophy disease phenotype.
Spinal muscular atrophy (SMA) is a pediatric-onset neuromuscular disorder caused by insufficient survival motor neuron (SMN) protein. SMN restorative therapies are now approved for the treatment of SMA; however, they are not curative, likely due to a combination of imperfect treatment timing, inadequate SMN augmentation, and failure to optimally target relevant organs. Here, we consider the implications of imperfect treatment administration, focusing specifically on outcomes for skeletal muscle. We examine the evidence that muscle plays a contributing role in driving neuromuscular dysfunction in SMA. Next, we discuss how SMN might regulate the health of myofibers and their progenitors. Finally, we speculate on therapeutic outcomes of failing to raise muscle SMN to healthful levels and present strategies to restore function to this tissue to ensure better treatment results.


[Organization of stress fibrils in cultured fibroblasts studied by using an actin filament-fragmenting protein].
Earlier we isolated a 1:1 complex of 90 kD-protein and actin from bovine brain. This complex was able to fragment actin filaments. Effects of this complex on the cytoskeleton of mouse and quail embryo fibroblasts are described. The cells were extracted with Triton X-100, and the resulting cytoskeletons were treated with the complex. Tetramethylrhodaminylphalloin and actin antibody staining failed to detect actin in preparations treated with the 90 kD protein-actin complex. Electrophoretic data confirmed actin solubilization upon this treatment. Immunofluorescent microscopy showed that actin solubilization was accompanied by extraction of vinculin and alpha-actinin from focal contacts and stress-fibers. In contrast, myosin distribution in treated cytoskeletons did not differ significantly from that in control extracted cells: in both the cases myosin was found mainly in the stress-fibers. Thus, myosin localization in stress-fibers does not depend on actin and is probably controlled by some other cytoskeletal component(s).


Obstructive sleep apnoea.
Obstructive sleep apnoea (OSA) is increasing in prevalence due to rising obesity. While OSA is a disorder primarily of the upper airway during sleep, its pathophysiological impact on other body systems is increasingly recognised. There has been interest in the prevalence of OSA in different ophthalmic conditions and possible causation has been postulated. As OSA is common, it can be expected that people with co-existent OSA will be found in any ophthalmic disease population studied. To determine with confidence the significance of finding patients with OSA in a particular cohort requires a well matched control group, ideally matched for age, obesity, gender and co-morbidities. Only if one can say with certainty that the prevalence of OSA is higher in a group with a particular co-existent ophthalmic disease can we begin to speculate about possible mechanisms for the overlap in these conditions. Possible mechanisms for how OSA might affect the eye are discussed in this review. The current literature is reviewed with respect to diabetic retinopathy, glaucoma, floppy eyelid syndrome, non-arteritic ischaemic optic neuropathy, keratoconus and AMD. Associations with OSA have been found, but robust prospective studies using multi-channel sleep studies to diagnose OSA are lacking. Gaps remain in the evidence and in our knowledge. It is hoped that this review will highlight the need for ophthalmologists to consider OSA in their patients. It also makes recommendations for future research, especially to consider whether therapies for OSA can also be effective for ophthalmic disorders.


Importance of parent talk on the development of preterm infant vocalizations.
To determine the sound environment of preterm infants cared for in the NICU and to test the hypothesis that infants exposed to more adult language will make more vocalizations. This was a prospective cohort study of 36 infants who had a birth weight of ≤1250 g. Sixteen-hour recordings of the infant sound environment were made in the NICU from a digital language processor at 32 and 36 weeks' postmenstrual age. Adult word counts, infant vocalizations, and conversational turns were analyzed. Infant vocalizations are present as early as 32 weeks. Both adult word counts per hour and infant vocalizations per hour increase significantly between 32 and 36 weeks. Infant exposure to language as a percentage of time was small but increased significantly. When a parent was present, infants had significantly more conversational turns per hour than when a parent was not present at both 32 and 36 weeks (P < .0001). Preterm infants begin to make vocalizations at least 8 weeks before their projected due date and significantly increase their number of vocalizations over time. Although infant exposure to language increased over time, adult language accounted for only a small percentage of the sounds to which an infant is exposed in the NICU. Exposure to parental talk was a significantly stronger predictor of infant vocalizations at 32 weeks and conversational turns at 32 and 36 weeks than language from other adults. These findings highlight the powerful impact that parent talk has on the appearance and increment of vocalizations in preterm infants in the NICU.


Using SCC antigen and CRP levels as prognostic biomarkers in recurrent oral cavity squamous cell carcinoma.
Squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels have been successfully used to stratify risk groups in primary oral squamous cell carcinoma (OSCC) patients; however, related biomarkers have rarely been investigated in recurrent OSCC. The purpose of the present study was to analyze the relationships of SCC-Ag and CRP levels at the time of recurrence with clinical factors and prognosis. We retrospectively recruited patients with recurrence in a cohort of 534 OSCC patients between March 2001 and July 2013. One hundred patients had recurrence. The serum SCC-Ag and CRP levels were measured at the time of cancer diagnosis, 3 to 6 months after treatment with clinical disease-free, and at the time of recurrence. The SCC-Ag levels were significantly lowered after treatment (paired t-test: p = 0.001) and re-elevated at the time of recurrence (paired t-test: p = 0.027). An SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L at the time of recurrence were significantly associated with recurrent tumor status (P<0.001), recurrent nodal metastasis (χ2 trend test: P = 0.020), distant metastasis (P<0.001), and overall survival (P<0.001). Moreover, the influence of both elevated SCC-Ag and CRP levels on overall survival (P<0.001, H.R. [95% CI]: 5.406 [2.210-13.222]) still existed after adjusting for the recurrent tumor stage and patient age. The present study demonstrates that concurrent high levels of both SCC-Ag and CRP at the diagnosis of recurrence acts as a predictor of recurrent tumor status, recurrent advanced tumor stage, distant metastasis, and survival after the diagnosis of recurrence. This study expands the applicability of these two markers in the risk stratification in recurrent OSCC.


Association of Triple Therapy With Improvement in Cholesterol Profiles Over Two-Year Followup in the Treatment of Early Aggressive Rheumatoid Arthritis Trial.
To evaluate long-term changes in cholesterol levels in patients with early rheumatoid arthritis (RA) who were randomized to begin treatment with methotrexate (MTX) monotherapy, MTX plus etanercept, or triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed in 416 patients participating in the TEAR trial, during 102 weeks of followup. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated-measures analysis with mixed-effect linear models to model within-subject covariance over time. Mixed-effect models controlling for traditional cardiovascular (CV) risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in the 28-joint Disease Activity Score, the C-reactive protein level, or the erythrocyte sedimentation rate were associated with increases in levels of HDL cholesterol, LDL cholesterol, and total cholesterol in all treatment groups (P < 0.001-0.035). Triple therapy was strongly associated with higher levels of HDL cholesterol, lower levels of LDL cholesterol, and higher ratios of total cholesterol:HDL cholesterol (P < 0.001 for all) compared to MTX monotherapy or MTX plus etanercept therapy over the 2-year followup. Decreases in RA disease activity over long-term followup were associated with increases in cholesterol levels in patients with early RA treated with either biologic or nonbiologic therapies. The use of triple therapy during 2 years of followup was associated with higher HDL cholesterol levels, lower LDL cholesterol levels, and lower total cholesterol:HDL cholesterol ratios compared to those observed in patients who received MTX monotherapy or MTX plus etanercept combination therapy. Additional studies are needed to assess the effects of these cholesterol changes on CV events in patients with RA.


Venous thromboembolism: classification, risk factors, diagnosis, and management.
Venous thromboembolism (VTE) is categorised as deep venous thrombosis (DVT) and pulmonary embolism (PE). VTE is associated with high morbidity and causes a huge financial burden on patients, hospitals, and governments. Both acquired and hereditary risks factors contribute to VTE. To diagnose VTE, noninvasive cost-effective diagnostic algorithms including clinical probability assessment and D-dimer measurement may be employed followup by compression ultrasonography for suspected DVT patients and multidetector computed tomography angiography for suspected PE patients. There are pharmacological and mechanical interventions to manage and prevent VTE. The pharmacological approaches mainly target pathways in coagulation cascade nonspecifically: conventional anticoagulants or specifically: new generation of anticoagulants. Excess bleeding is one of the major risk factors for pharmacological interventions. Hence, nonpharmacological or mechanical approaches such as inferior vena cava filters, graduated compression stockings, and intermittent pneumatic compression devices in combination with pharmacological interventions or alone may be a good approach to manage VTE.


Characterization of a novel family of ciliary body glycoproteins.
To isolate and characterize ciliary body epithelial antigens reactive with a monoclonal antibody, 2B4.14.1. A mouse monoclonal antibody generated against human corneal endothelium, 2B4.14.1 reacts with nonpigmented epithelium of human and guinea pig ciliary bodies. The ciliary body proteins reactive with 2B4.14.1 were identified by Western blotting and were partially purified by affinity chromatography with 2B4.14.1 coupled to a solid support matrix. Carbohydrate components of the antigenic molecules were analyzed by lectin chromatography and by digestion with the enzymes N-glycosidase F and endoglycosidase F. The cellular and subcellular distribution of the antigens was examined by immunoperoxidase staining and by immunoelectron microscopy of ultracryotome sections of ciliary body. 2B4.14.1 reacted with families of guinea pig and human ciliary body glycoproteins with estimated molecular weights ranging from 250 to 325 kD. In Western blots of samples reduced before electrophoresis, the high molecular weight bands were replaced by weakly reactive bands at 115 to 130 and 210 kD, indicating that the 2B4.14.1 ligands have disulfide bonds. 2B4.14.1 ligands from both guinea pig and human ciliary body were bound by immobilized lectins, including concanavalin A, Datura stramonium lectin, and Lens culinaris hemagglutinin, which recognize components of N-linked oligosaccharides. Guinea pig ciliary body antigens digested with N-glycosidase F and endoglycosidase F failed to react with 2B4.14.1 in Western blots, confirming the presence of N-linked oligosaccharide chains and indicating that they form an integral part of the 2B4.14.1-reactive antigenic site. Molecular weight shifts of glycosidase-digested antigens were consistent with the presence of two to four N-linked oligosaccharide units. In immunoperoxidase-stained sections of guinea pig and human ciliary body, 2B4.14.1 reacted primarily with nonpigmented epithelial cells. Staining of guinea pig epithelial cells was fairly uniform; staining of human epithelial cells was concentrated on the basal surface. By immunoelectron microscopy, a majority of the 2B4.14.1 antigenic reactivity was localized immediately external to the nonpigmented epithelial cell plasma membrane. 2B4.14.1 reacts with a novel family of high molecular weight glycoproteins associated with the nonpigmented epithelial cell surface in guinea pig and human ciliary body.


Perimenopausal risk factors and future health.
Lifestyle changes around the time of menopause have the potential to impact on morbidity and eventual mortality. Here we review this topic to identify how such changes may improve health at perimenopause and beyond. Searches were performed in Medline and other databases. Each subject summary was presented to the ESHRE Workshop Group, where omissions or disagreements were resolved by discussion. Body weight increases because the decline in physical activity during the perimenopause is greater than the concomitant decline in energy intake. It is imperative to stop smoking before menopause because the risk of acute myocardial infarction rises sharply thereafter. Cardiovascular events can be reduced by managing risk factors, such as hypertension and increased lipids and body weight. Breast cancer risk is increased to a similar extent by hormone use, decreased physical activity, increased calorie intake and alcohol use, all reflecting lifestyle decisions. Smoking, alcohol and exercise may increase or decrease risk of aging brain disorders, especially dementia and Parkinson's disease, while stress is consistently associated with increased risk and a prudent diet is consistently associated with reduced risk. Osteoarthritis frequency increases after 50 years of age and risk is elevated 3-fold by obesity, while risk of osteoporosis can be minimized by smoking cessation, adequate vitamin D intake and regular weight-bearing exercise. Lifestyle changes around the time of the perimenopause can reduce the likelihood and severity of heart disease and chronic illness in later years and the cost of care of elderly women.


The safety of maximal exercise testing.
Previous reports on the safety of exercise testing have been based on surveys from different testing facilities with a variety of testing protocols and patient types. From 1971 through 1987, 71,914 maximal exercise tests conducted in a population with a low prevalence of known coronary heart disease under uniform conditions at a single medical facility resulted in six major cardiac complications including one death. No complications have occurred in the past 10 years in 45,000 maximal tests. The overall cardiac complication rate in men and women is 0.8 complications per 10,000 tests with 95% confidence intervals of 0.3-1.9 complications per 10,000 tests. Maximal exercise testing appears safer than some previously published reports have suggested and seems to be getting safer with time.


Good vibrations: oscillatory phase shapes perception.
In the current study, we provide compelling evidence to answer the long-standing question whether perception is continuous or periodic. Spontaneous brain oscillations are assumed to be the underlying mechanism of periodic perception. Depending on the phase angle of the oscillations, an identical stimulus results in different perceptual outcomes. Past results, however, can only account for a correlation of perception with the phase of the ongoing brain oscillations. Therefore, it is desirable to demonstrate a causal relation between phase and perception. One way to address this question is to entrain spontaneous brain oscillations by applying an external oscillation and then demonstrate behavioral consequences of this oscillation. We conducted an auditory detection experiment with humans, recorded the electroencephalogram (EEG) concurrently and simultaneously applied oscillating transcranial direct current stimulation at 10Hz (α-tDCS). Our approach revealed that detection thresholds were dependent on the phase of the oscillation that was entrained by α-tDCS. This behavioral effect was accompanied by an electrophysiological effect: α-power was enhanced after α-tDCS as compared to a pre-stimulation period. By showing a causal relation between phase and perception, our results extend findings of previous studies that were only able to demonstrate a correlation. We found that manipulation of the phase resulted in different detection thresholds, which supports the notion that perception can be periodically modulated by oscillatory processes. This demonstrates that tDCS can serve as a tool in neuroscience to extend the knowledge of the functional significance of brain oscillations.


Weight loss by Ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold.
Mitochondria play a key role in diverse processes including ATP synthesis and apoptosis. Mitochondrial function can be studied using inhibitors of respiration, and new agents are valuable for discovering novel mechanisms involved in mitochondrial regulation. Here, we screened small molecules derived from slime molds and other microorganisms for their effects on mitochondrial oxygen consumption. We identified Ppc-1 as a novel molecule which stimulates oxygen consumption without adverse effects on ATP production. The kinetic behavior of Ppc-1 suggests its function as a mitochondrial uncoupler. Serial administration of Ppc-1 into mice suppressed weight gain with no abnormal effects on liver or kidney tissues, and no evidence of tumor formation. Serum fatty acid levels were significantly elevated in mice treated with Ppc-1, while body fat content remained low. After a single administration, Ppc-1 distributes into various tissues of individual animals at low levels. Ppc-1 stimulates adipocytes in culture to release fatty acids, which might explain the elevated serum fatty acids in Ppc-1-treated mice. The results suggest that Ppc-1 is a unique mitochondrial regulator which will be a valuable tool for mitochondrial research as well as the development of new drugs to treat obesity.


Annatto (Bixa orellana) δ-TCT supplementation protected against embryonic DNA damages through alterations in PI3K/ Akt-Cyclin D1 pathway.
Protective action by annatto-derived delta-tocotrienol (δ-TCT) and soy-derived alpha-tocopherol (α-TOC) through the regulation of PI3K/Akt-Cyclin D1 pathway against the nicotine-induced DNA damages is the focus of the present study. Nicotine, which has been widely reported to have numerous adverse effects on the reproductive system, was used as reproductive toxicant. 48 female balb/c mice (6-8 weeks) (23-25 g) were randomly divided into 8 groups (G1-G8; n = 6) and treated with either nicotine or/and annatto δ-TCT/soy α-TOC for 7 consecutive days. On Day 8, the females were superovulated and mated before euthanized for embryo collection (46 hours post-coitum). Fifty 2-cell embryos from each group were used in gene expression analysis using Affymetrix QuantiGene Plex2.0 assay. Findings indicated that nicotine (G2) significantly decreased (p < 0.05) the number of produced 2-cell embryos compared to control (G1). Intervention with mixed annatto δ-TCT (G3) and pure annatto δ-TCT (G4) significantly increased the number of produced 2-cell embryos by 127 % and 79 % respectively compared to G2, but these were lower than G1. Concurrent treatment with soy α-TOC (G5) decreased embryo production by 7 %. Supplementations with δ-TCT and α-TOC alone (G6-G8) significantly increased (p < 0.05) the number of produced 2-cell embryos by 50 %, 36 % and 41 % respectively, compared to control (G1). These results were found to be associated with the alterations in the PI3K/Akt-Cyclin D1 gene expressions, indicating the inhibitory effects of annatto δ-TCT and soy α-TOC against the nicotinic embryonic damages. To our knowledge, this is the first attempt on studying the benefits of annatto δ-TCT on murine preimplantation 2-cell embryos.


A pilot study to determine medical laser generated air contaminant emission rates for a simulated surgical procedure.
The U.S. Occupational Safety and Health Administration (OSHA) estimates that half a million health-care workers are exposed to laser surgical smoke each year. The purpose of this study was to establish a methodology to (1) estimate emission rates of laser-generated air contaminants (LGACs) using an emission chamber, and to (2) perform a screening study to differentiate the effects of three laser operational parameters. An emission chamber was designed, fabricated, and assessed for performance to estimate the emission rates of gases and particles associated with LGACs during a simulated surgical procedure. Two medical lasers (Holmium Yttrium Aluminum Garnet [Ho:YAG] and carbon dioxide [CO2]) were set to a range of plausible medical laser operational parameters in a simulated surgery to pyrolyze porcine skin generating plume in the emission chamber. Power, pulse repetition frequency (PRF), and beam diameter were evaluated to determine the effect of each operational parameter on emission rate using a fractional factorial design. The plume was sampled for particulate matter and seven gas phase combustion byproduct contaminants (benzene, ethylbenzene, toluene, formaldehyde, hydrogen cyanide, carbon dioxide, and carbon monoxide): the gas phase emission results are presented here. Most of the measured concentrations of gas phase contaminants were below their limit of detection (LOD), but detectable measurements enabled us to determine laser operation parameter influence on CO2 emissions. Confined to the experimental conditions of this screening study, results indicated that beam diameter was statistically significantly influential and power was marginally statistically significant to emission rates of CO2 when using the Ho:YAG laser but not with the carbon dioxide laser; PRF was not influential vis-a-vis emission rates of these gas phase contaminants.


c.1643_1644delTG XPC mutation is more frequent in Moroccan patients with xeroderma pigmentosum.
Xeroderma pigmentosum is a rare autosomal recessive disease characterized by hypersensitivity to UV light which is due to alterations of the nucleotide excision repair pathway. Eight genes (XPA to XPG and XPV) are responsible for the disease. Among them, the XPC gene is known to be the most mutated in Mediterranean patients. The aim of this study was to determine the frequency of the most common XPC mutation and describe the clinical features of Moroccan patients with xeroderma pigmentosum. Twenty four patients belonging to 21 unrelated Moroccan families and 58 healthy subjects were investigated. After clinical examination, the screening for the c.1643_1644delTG (p.Val548AlafsX25) mutation in the XPC gene was performed by PCR and automated sequencing of exon 9 in all patients and controls. The molecular analysis showed that among the 24 patients, 17 were homozygous for the c.1643_1644delTG mutation and all their tested parents were heterozygous, whereas the others (7 patients) did not carry the mutation. The frequency of this mutation was estimated to be 76.19 % (16/21 families). None of the 58 healthy individuals carried this mutation. In addition, clinical investigation showed that the majority of the patients bearing this mutation have the same clinical features. Our results revealed that the p.Val548AlafsX25 mutation is the major cause (76.19 %) of xeroderma pigmentosum in Moroccan families. This would have an important impact on improving management of patients and their relatives.


Influence of pesticide use in fruit orchards during blooming on honeybee mortality in 4 experimental apiaries.
Samples of dead honey bees (Apis mellifera L.) were collected periodically from 4 different locations during citrus and stone fruit trees blooming season to evaluate the potential impact of agrochemicals on honey bee death rate. For the determination of mortality, dead honey bee traps were placed in front of the experimental hives entrance located in areas of intensive agriculture in Valencian Community (Spain). A total of 34 bee samples, obtained along the monitoring period, were analyzed by means of QuEChERS extraction method and screened for 58 pesticides or their degradation products by LC-MS/MS. An average of four pesticides per honey bee sample was detected. Coumaphos, an organophosphate acaricide used against varroosis in the experimental hives, was detected in 94% of the samples. However, this acaricide was unlikely to be responsible for honey bee mortality because its constantly low concentration during all the monitoring period, even before and after acute mortality episodes. The organophosphates chlorpyrifos and dimethoate, as well as the neonicotinoid imidacloprid, were the most frequently detected agrochemicals. Almost 80% of the samples had chlorpyrifos, 68% dimethoate, and 32% imidacloprid. Maximum concentrations for these three compounds were 751, 403, 223 ng/g respectively. Influence of these pesticides on acute honey bee mortality was demonstrated by comparing coincidence between death rate and concentrations of chlorpyrifos, dimethoate and imidacloprid.


Learning Concave Conditional Likelihood Models for Improved Analysis of Tandem Mass Spectra.
The most widely used technology to identify the proteins present in a complex biological sample is tandem mass spectrometry, which quickly produces a large collection of spectra representative of the peptides (i.e., protein subsequences) present in the original sample. In this work, we greatly expand the parameter learning capabilities of a dynamic Bayesian network (DBN) peptide-scoring algorithm, Didea [25], by deriving emission distributions for which its conditional log-likelihood scoring function remains concave. We show that this class of emission distributions, called Convex Virtual Emissions (CVEs), naturally generalizes the log-sum-exp function while rendering both maximum likelihood estimation and conditional maximum likelihood estimation concave for a wide range of Bayesian networks. Utilizing CVEs in Didea allows efficient learning of a large number of parameters while ensuring global convergence, in stark contrast to Didea's previous parameter learning framework (which could only learn a single parameter using a costly grid search) and other trainable models [12, 13, 14] (which only ensure convergence to local optima). The newly trained scoring function substantially outperforms the state-of-the-art in both scoring function accuracy and downstream Fisher kernel analysis. Furthermore, we significantly improve Didea's runtime performance through successive optimizations to its message passing schedule and derive explicit connections between Didea's new concave score and related MS/MS scoring functions.


Vasohibin-1 as a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer.
We previously reported high expression of vasohibin-1 (VASH1), which is specifically expressed in activated vascular endothelial cells, was a prognostic indicator of disease progression in prostate cancer. The aim of this study was to assess whether VASH1 expression at the area of normal prostatic tissue as well as that of intratumoral tissue could reflect the grade of malignancy of prostate cancer. Pathological upgrade of Gleason Score ≥7 by radical prostatectomy was observed in 48 patients (upgraded group). The median VASH1 densities of the intratumoral and normal areas were 9.7 ± 9.5 and 13.3 ± 11.8, respectively, and the median MVDs were 58.6 ± 20.3 and 64.1 ± 23.5, respectively. We detected a strong positive correlation with each other for both VASH1 density (ρ = 0.589, p < 0.001) and MVD (ρ = 0.342, p < 0.001). VASH1 density was significantly higher in the upgreaded group than in the non-upgraded group regardless of prostatic location (intratumoral area: p < 0.001, normal area: p < 0.001). Even if the tumor volume was low in biopsy samples, VASH1 density reflected the grade of malignancy throughout the prostate. These results suggested that VASH1 expression could be a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer. Among the 1177 patients who underwent radical prostatectomy, 104 patients diagnosed with Gleason Score ≤6 and positive cores ≤3 were included. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD), and those with activated endothelial cells as VASH1 density using prostatic biopsy samples, and evaluated the association between their expressions and clinicopathological findings.


The influence of birthweight, past poststreptococcal glomerulonephritis and current body mass index on levels of albuminuria in young adults: the multideterminant model of renal disease in a remote Australian Aboriginal population with high rates of renal disease and renal failure.
Australian Aborigines in remote areas have very high rates of kidney disease, which is marked by albuminuria. We describe a 'multihit' model of albuminuria in young adults in one remote Aboriginal community. Urinary albumin/creatinine ratios (ACRs) were measured in 655 subjects aged 15-39 years and evaluated in the context of birthweights, a history of 'remote' poststreptococcal glomerulonephritis (PSGN; ≥5 years earlier) and current body mass index (BMI). Birthweight had been <2.5 kg (low birthweight, LBW) in 25.4% of subjects and 22.8% had a remote history of PSGN. ACR levels rose with age. It exceeded the microalbuminuria threshold in 33.6% of subjects overall (25% of males and 45% of females). In multivariate models, birthweight (inversely), remote PSGN and current BMI were all independent predictors of ACR levels. The effects of birthweight and PSGN and their combination were expressed through amplification of ACR levels in relation to age and around the group median BMI of 20.8 kg/m(2). In people with BMI <20.8 (57.8% of all males and 40.3% of the females), LBW and PSGN alone had minimal effects on ACR, but in combination they strikingly amplified ACR in relation to age. Those with BMI ≥20.8 (which included 42.2% of the males and 59.7% of the females) had higher ACR levels, and both LBW and a PSGN history, separately and in combination, were associated with striking further amplification of ACR in the context of age. Much of the great excess of disease in this population is explained by high rates of the early life risk factors, LBW and PSGN. Their effects are expressed through amplification of ACR in the context of increasing age and are further moderated by levels of current body size. Both early life risk factors are potentially modifiable.


Massive parallel sequencing questions the pathogenic role of missense variants in dilated cardiomyopathy.
Germline genetic variants are an important cause of dilated cardiomyopathy (DCM). However, recent sequencing studies have revealed rare variants in DCM-associated genes also in individuals without known heart disease. In this study, we investigate variant prevalence and genotype-phenotype correlations in Swedish DCM patients, and compare their genetic variants to those detected in reference cohorts. We sequenced the coding regions of 41 DCM-associated genes in 176 unrelated patients with idiopathic DCM and found 102 protein-altering variants with an allele frequency of <0.04% in reference cohorts; the majority were missense variants not previously described in DCM. Fifty-five (31%) patients had one variant, and 24 (14%) patients had two or more variants in the analysed genes. Detection of genetic variants in any gene, and in LMNA, MYH7 or TTN alone, was associated with early onset disease and reduced transplant-free survival. As expected, nonsense and frameshift variants were more common in DCM patients than in healthy individuals of the reference cohort 1000 Genomes Europeans. Surprisingly however, the prevalence, conservation and pathogenicity scores, and localization of missense variants were similar in DCM patients and healthy reference individuals. To our knowledge, this is the first study to identify correlations between genotype and prognosis when sequencing a large number of genes in unselected DCM patients. The similar distribution of missense variants in DCM patients and healthy reference individuals questions the pathogenic role of many variants, and suggests that results from genetic testing of DCM patients should be interpreted with caution.


Mindfulness meditation and the immune system: a systematic review of randomized controlled trials.
Mindfulness meditation represents a mental training framework for cultivating the state of mindful awareness in daily life. Recently, there has been a surge of interest in how mindfulness meditation improves human health and well-being. Although studies have shown that mindfulness meditation can improve self-reported measures of disease symptomatology, the effect that mindfulness meditation has on biological mechanisms underlying human aging and disease is less clear. To address this issue, we conducted the first comprehensive review of randomized controlled trials examining the effects of mindfulness meditation on immune system parameters, with a specific focus on five outcomes: (1) circulating and stimulated inflammatory proteins, (2) cellular transcription factors and gene expression, (3) immune cell count, (4) immune cell aging, and (5) antibody response. This analysis revealed substantial heterogeneity across studies with respect to patient population, study design, and assay procedures. The findings suggest possible effects of mindfulness meditation on specific markers of inflammation, cell-mediated immunity, and biological aging, but these results are tentative and require further replication. On the basis of this analysis, we describe the limitations of existing work and suggest possible avenues for future research. Mindfulness meditation may be salutogenic for immune system dynamics, but additional work is needed to examine these effects.


Diaqua-bis-(4-meth-oxy-benzoato-κO)bis-(nicotinamide-κN)cobalt(II) dihydrate.
In the mononuclear title compound, [Co(C(8)H(7)O(3))(2)(C(6)H(6)N(2)O)(2)(H(2)O)(2)]·2H(2)O, the Co(II) ion is located on a crystallographic inversion center. The asymmetric unit is completed by one 4-meth-oxy-benzoate anion, one nicotinamide (NA) ligand and one coordinated and one uncoordinated water mol-ecule. All ligands act in a monodentate mode. The four O atoms in the equatorial plane around the Co(II) ion form a slightly distorted square-planar arrangement, while the slightly distorted octa-hedral coordination is completed by the two pyridine N atoms of the NA ligands in the axial positions. The dihedral angle between the carboxyl-ate group and the attached benzene ring is 6.47 (7)°, while the pyridine and benzene rings are oriented at a dihedral angle of 72.80 (4)°. An O-H⋯O hydrogen bond links the uncoordinated water mol-ecule to one of the carboxyl-ate groups. In the crystal structure, inter-molecular O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional network.


Bidirectional Influences of Cranberry on the Pharmacokinetics and Pharmacodynamics of Warfarin with Mechanism Elucidation.
Cranberry is a dietary supplement popularly used for the prophylaxis of urinary tract infection. Interestingly, cranberry-warfarin interactions in clinical reports have shown bidirectional outcomes. (±) Warfarin, a widely prescribed anticoagulant, but with a narrow therapeutic index, contains equal amounts of S- and R-warfarin, of which S-warfarin is more active. The aim of this study was to investigate the effects of different ingestion times of cranberry on the pharmacokinetics and pharmacodynamics of warfarin. Rats were orally administered (±) warfarin (0.2 mg/kg) with and without cranberry (5.0 g/kg) at 0.5 h prior to the warfarin, and at 10 h after the warfarin. The plasma concentrations of S- and R-warfarin were determined by LC/MS. The results indicate that cranberry ingested at 0.5 h before (±) warfarin significantly decreased the systemic exposures of S-warfarin and R-warfarin. Conversely, when cranberry was ingested at 10 h after (±) warfarin, the elimination of S-warfarin was significantly inhibited, and the anticoagulation effect of (±) warfarin was significantly enhanced. The results of the mechanism studies indicate that cranberry activated the breast cancer resistance protein (BCRP), which mediated the efflux transports of S-warfarin and R-warfarin. Moreover, the metabolites of cranberry inhibited cytochrome P450 (CYP) 2C9, the main metabolizing enzyme for S-warfarin. In conclusion, cranberry affected the pharmacokinetics of (±) warfarin in a bidirectional manner by activating the BCRP by CJ during absorption and inhibiting the BCRP and CYP2C9 by CMs during elimination, depending on the ingestion time of CJ. The combined use of cranberry with warfarin should be avoided.


T2* relaxometry and volume predict semi-quantitative histological scoring of an ACL bridge-enhanced primary repair in a porcine model.
Magnetic resonance imaging (MRI) variables, such as T2* and volume, can predict the healing ligament structural properties. How these MR variables relate to semi-quantitative histology of the healing ACL is yet unknown. We hypothesized that T2* and volume would predict the histological scoring of a healing ACL. Yucatan minipigs underwent ACL transection and received bridge-enhanced ACL repair or no treatment. The surgical legs were harvested after 52 weeks and imaged using a high resolution 2-echo sequence. For each ligament, the volume and median T2* values were determined. The ACL specimens were then histologically analyzed using the advanced Ligament Maturity Index (LMI). The T2* of the healing ligaments significantly predicted the total LMI score as well as the cell, collagen and vessel sub-scores; R(2) = 0.78, 0.67, 0.65, and 0.60, respectively (p ≤ 0.001). The ligament volume also predicted the total LMI score, cell, and collagen sub-scores; R(2) = 0.39, 0.33, 0.37, and 0.60, respectively (p ≤ 0.001). A lower ligament T2* or a higher volume was associated with higher histological scores of the healing ligaments. This study provides a critical step in the development of a non-invasive method to evaluate ligament healing on a microscopic scale.