Are Pain Beliefs, Cognitions, and Behaviors Influenced by Race, Ethnicity, and Culture in Patients with Chronic Musculoskeletal Pain: A Systematic Review.
Chronic pain has been considered as a biopsychosocial condition in which cognitive and emotional factors as well as biological factors significantly affect perception of pain. Race, ethnicity and culture have a crucial impact on illness beliefs, health care preferences, help-seeking behaviors, and acceptance of medical interventions. The aim of the present study was to systematically review the current evidence regarding the racial, ethnic and cultural alterations and differences in pain beliefs, cognitions, and behaviors in patients with chronic musculoskeletal pain (MSKP). Systematic review. This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines (PRISMA). PubMed and Web of Science were searched. A first screening was conducted based on title and abstract of the articles. In the second screening, full-texts of the remaining articles were evaluated for the fulfilment of the inclusion criteria. The risk of bias was assessed with the modified Newcastle-Ottawa Scale. A total of 11 articles were included. The methodological quality of the included studies ranged from low to moderate. There is moderate evidence that African-Americans use more praying, hoping, and emotion-focused coping strategies than Caucasians. There is also preliminary evidence regarding the differences in some coping strategies such as distraction, catastrophizing, and problem-focused solving between African-Americans and Caucasians. Preliminary evidence exists regarding the differences in pain coping strategies between the US and Portugal; the US and Singapore; and among 4 French-speaking countries. It is found that Spanish patients with fibromyalgia (FM) have more negative illness perceptions than Dutch patients. There is preliminary evidence that Caucasians have higher self-efficacy than African-Americans. There is also preliminary evidence that New Zealanders have more internal health expectancies than patients from the US. Preliminary evidence is demonstrated that Caucasians with rheumatoid arthritis (RA) have more positive control beliefs than African-Americans. Lastly, there is preliminary evidence that patients from the US believe that they are more disabled, while Singaporeans interpret the pain more by a traditional biomedical perspective. Only 11 articles were included. The small number of articles, wide range of assessment methods, and substantial risk of bias in the included studies led the investigator to draw conclusions cautiously. Preliminary to moderate evidence shows the differences in coping strategies, illness perceptions, self-efficacy, fear avoidance beliefs, locus of control, and pain attitudes in different populations. Further prospective and longitudinal studies using standard definitions for race, ethnicity or culture and valid questionnaires for each population are warranted to explore the racial, ethnic and cultural discrepancies in pain beliefs, cognitions, and behaviours. Chronic pain, musculoskeletal pain, pain beliefs, pain cognitions, pain behaviors, race, ethnicity, culture.


[Part II: basic hemodynamic monitoring and the use of pulmonary artery catheter].
Monitoring of vital functions is one of the most important tools in the management of critically ill patients. Nowadays is possible to detect and analyze a great deal of physiologic data using a lot of invasive and non-invasive methods. The intensivist must be able to select and carry out the most appropriate monitoring technique according to the patient requirements and taking into account the benefit/risk ratio. Despite the fast development of non invasive monitoring techniques, invasive hemodynamic monitoring using Pulmonary Artery Catheter still is one of the basic procedures in Critical Care. The aim was to define recommendations about clinical utility of basic hemodynamic monitoring methods and the Use of Pulmonary Artery Catheter. Modified Delphi methodology was used to create and quantify the consensus between the participants. AMIB indicated a coordinator who invited more six experts in the area of monitoring and hemodynamic support to constitute the Consensus Advisory Board. Twenty-five physicians and nurses selected from different regions of the country completed the expert panel, which reviewed the pertinent bibliography listed at the MEDLINE in the period from 1996 to 2004. Recommendations were made based on 55 questions about the use of central venous pressure, invasive arterial pressure, pulmonary artery catheter and its indications in different settings. Evaluation of central venous pressure and invasive arterial pressure, besides variables obtained by the PAC allow the understanding of cardiovascular physiology that is of great value to the care of critically ill patients. However, the correct use of these tools is fundamental to achieve the benefits due to its use.


Revision total knee arthroplasty.
Revision total knee arthroplasties are performed with increasing frequency due to the increasing numbers of primary arthroplasties. To retrospectively analyze 71 patients who underwent 78 revision total knee arthroplasties during the years 1991 to 1999 We evaluated the revised knees using the Knee Society Clinical Rating System after an average follow-up period of 3 years and 9 months (2-10 years). The indications for revision included pain and instability, deep infection of the joint, complaints linked to the patella, or post-trauma to the operated knee. The average knee score (evaluation of the knee joint itself) calculated after the revision was 74.5. The results on the knee score were excellent (> 85) in 48% of patients and poor (< 60) in 22%. The functional results (patient's ability to walk and climb stairs) were only 48.3. Although the revision of total knee replacements is known to be problematic, most patients show good results on knee examination, and reasonable functional results given the factors involved.


Physical activity patterns associated with weight-control status: differences by race and sex.
Physical activity (PA) plays a major role in maintaining energy balance. We examined the patterns of occupational activity, strength training, and lifestyle PA (low, medium, high) by sex and race among persons trying to control their weight (lose weight, stay about the same, not trying to lose/not trying to stay about the same). Population data (N = 9258) from a nationwide telephone survey were collected to examine PA patterns. Domains of PA were analyzed by sex and race. Of those trying to control their weight, approximately 24.0% engaged in strengthening activities 2 to 3 d/wk. Among those trying to lose weight, 48.2% versus 42.2% of men (White and non-White, respectively) and 40.4% versus 35.1% of women (White and non-White, respectively) reported high volumes of PA. PA patterns among persons trying to control their weight vary by sex and race. Adults trying to control their weight are encouraged to increase levels of PA.


Nasopharyngeal carcinomas frequently lack the p16/MTS1 tumor suppressor protein but consistently express the retinoblastoma gene product.
The p16/MTS1 gene is altered by deletion, mutation, or hypermethylation in a wide variety of human cancers. As a result of deficient p16 protein, these cancers lack a critical mechanism for halting G1/S cell cycle progression. In the current study, 59 cases of nasopharyngeal carcinoma were evaluated for expression of the p16 tumor suppressor protein by immunohistochemical analysis of paraffin-embedded tissue. There was no detectable p16 in 38/59 cases (64%), which implies a very high rate of p16 inactivation in this type of cancer. On the other hand, the retinoblastoma gene product, which also regulates the G1 to S phase transition of the cell cycle, was consistently expressed in nasopharyngeal carcinomas by immunohistochemical analysis. These results implicate p16 inactivation but not Rb alteration in the stepwise progression of nasopharyngeal carcinogenesis.


Catalyst-free synthesis and structural and mechanical characterization of single crystalline Ca2B2O5.H2O nanobelts and stacking faulted Ca2B2O5 nanogrooves.
Single crystalline Ca(2)B(2)O(5).H(2)O (CBOH) nanobelts were synthesized for the first time using a facile catalyst-free hydrothermal method at low temperature. After being annealed at 400 degrees C for 10 h, the CBOH nanobelts transformed into curve-shaped Ca(2)B(2)O(5)(CBO) nanogrooves with ordered stacking fault arrays along the [110] direction. The single crystalline CBOH nanobelts and the stacking faulted CBO nanogrooves provided a unique platform for investigating the effects of hydrated H(2)O and stacking faults on the mechanical properties of nanomaterials. Nanoindentation tests were performed directly on individual CBOH nanobelts and CBO nanogrooves to probe their mechanical properties. It was found that the CBOH nanobelts, with the presence of hydrated H(2)O, achieved 28.7% increase in elastic modulus, whereas the stacking faulted CBO nanogrooves, with the absence of hydrated H(2)O, exhibited 99% loss in elastic modulus, compared to bulk CBO.


Baclofen reduces post-synaptic potentials of rat cortical neurones by an action other than its hyperpolarizing action.
1. Intracellular recordings were obtained from neurones in layers 2 and 3 of the rat frontal neocortex in an in vitro slice preparation. Three distinct types of stimulation-evoked post-synaptic potentials were recorded in these neurones: excitatory post-synaptic potentials (e.p.s.p.s); bicuculline-sensitive, chloride-dependent inhibitory post-synaptic potentials (i.p.s.p.s) with times to peak of 20-25 ms (fast(f)-i.p.s.p.s); bicuculline-insensitive, potassium-dependent i.p.s.p.s with bicuculline-insensitive, potassium-dependent i.p.s.p.s with times to peak of 150-250 ms (long(l)-i.p.s.p.s). 2. The effects of baclofen were investigated on seventy-one neurones. Baclofen was applied by ionophoresis or pressure ejection from micropipettes or was added to the superfusion medium. 3. Baclofen depressed stimulation-evoked e.p.s.p.s in fifty-seven of the sixty neurones tested. This effect was associated with an increase in the stimulation intensity required to produce a synaptically evoked action potential for thirty-nine of forty-four neurones. 4. Baclofen depressed f-i.p.s.p.s in thirty-seven of the thirty-nine neurones tested and l-i.p.s.p.s in each one of the seventeen neurones tested. Reversal potential values for each type of i.p.s.p. were not changed by baclofen and its depressions of each were independent of membrane potential (Em). Baclofen reduced the magnitude and the duration of the conductance increases that were associated with f- and l-i.p.s.p.s. 5. Baclofen hyperpolarized forty of seventy-one neurones and produced outward currents in three of four neurones recorded in voltage clamp at holding potentials between -55 and -65 mV. These actions were associated with 10-58% reductions of neuronal input resistance (RN) and 10-20% increases in neuronal input conductance (gN), respectively. Baclofen decreased the direct excitability of twenty-three of twenty-seven neurones tested. Determinations of the reversal potential for baclofen-induced changes of Em indicate that baclofen increases the conductance of rat neocortical neurones to potassium ions. 6. The EC50 for each action of DL-baclofen was approximately 1 microM. L-Baclofen was greater than 100 times more potent than D-baclofen. 7. Concentrations of bicuculline that blocked f-i.p.s.p.s and responses to ionophoretically applied gamma-aminobutyric acid (GABA) had no effect on the depressions of e.p.s.p.s or the hyperpolarizations and decreases in RN that baclofen produced. 8. Baclofen did not reduce the duration of action potentials that were prolonged with intracellular injections of caesium ions or by superfusions with medium that contained 10 mM-tetraethylammonium (TEA).(ABSTRACT TRUNCATED AT 400 WORDS)


Oncogenic hypophosphataemic osteomalacia: biomarker roles of fibroblast growth factor 23, 1,25-dihydroxyvitamin D3 and lymphatic vessel endothelial hyaluronan receptor 1.
Oncogenic osteomalacia (OOM) is characterised by tumour production of fibroblast growth factor 23 (FGF23) that results in hypophosphataemia and renal phosphate wasting, reduced 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesis and osteomalacia. Here, we demonstrate the roles of serum FGF23 and 1,25(OH)2D3, together with the lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), as biomarkers for OOM. A previously well 52-year-old man presented with a 2-year history of generalised musculoskeletal pain and proximal myopathy. He had hypophosphataemia, elevated serum alkaline phosphatase activity, low serum 1,25(OH)2D3 and a reduced tubular maximum of phosphate/glomerular filtration rate. These findings indicated a diagnosis of OOM, but magnetic resonance imaging (MRI) and octreotide scintigraphy did not identify any tumours. Treatment with oral phosphate and calcitriol resolved the symptoms and biochemical abnormalities within 6 months. Four years later, he relapsed whilst on treatment with oral phosphate and calcitriol. Serum FGF23 concentration was elevated and MRI identified a 2 cm tumour within Hoffa's fat pad of the left knee. Removal of the tumour resulted in a complete resolution of symptoms and normalisation of the serum biochemical abnormalities including serum FGF23. Histology demonstrated a phosphaturic mesenchymal tumour, mixed connective tissue variant (PMTMCT), which revealed immunostaining with anti-LYVE-1 antibody and hence the presence of lymphatic vessels. Serum FGF23 and 1,25(OH)2D3 were found to be reliable biomarkers for OOM. In addition, the demonstration of lymphatics in the PMTMCT helps to distinguish this tumour from most typical benign haemangiomas.


Therapy of human T-cell acute lymphoblastic leukaemia with a combination of anti-CD7 and anti-CD38-SAPORIN immunotoxins is significantly better than therapy with each individual immunotoxin.
Severe combined immunodeficient (SCID) mice injected i.v. with the human T-ALL cell line CCRF CEM (SCID-CEM mice) develop within 50 days life-threatening multi-organ growth of leukaemia cells. The development of leukaemia in SCID-CEM mice treated with three 10 microg i.v. doses of the anti-CD7 immunotoxin (IT) HB2-SAPORIN or the anti-CD38 IT OKT10-SAPORIN was significantly delayed compared with PBS sham-treated animals but 90% of animals treated with either IT eventually developed disseminated leukaemia cell growth. In contrast treatment of SCID-CEM mice with a combination of both ITs led not only to a significantly greater delay in time to leukaemia development but also in the numbers of animals remaining leukaemia free (60%). The native HB2 and OKT10 antibodies (both murine IgG1antibodies) exerted significant, though relatively weak therapeutic effects, probably mediated through an antibody-dependent cellular cytotoxicity (ADCC) mechanism. Moreover, there was no in vivo additivity of therapeutic effect when both antibodies were used in combination. Apparent, however, was that the combination of HB2-SAPORIN IT with OKT10 antibody led to an intermediate therapeutic effect that was significantly greater than that obtained when either was used alone but significantly less than that obtained when the two IT combination was utilized. This was similarly the case for the combination of OKT10-SAPORIN IT with HB2 antibody though the effect was less pronounced in this instance. This result suggests that the therapeutic effect of IT + antibody treatment results from an additivity between antibody-mediated delivery of saporin combined with a SCID mouse NK cell-mediated ADCC attack on the target cell directed through target cell bound antibody Fc engagement with FcgammaRIII on the NK cell surface. The combination of both ITs however gave the best therapeutic outcome in SCID-CEM mice probably as the result of (i) delivery of greater amounts of saporin to target CEM cells positive for both CD7 and CD38, (ii) delivery of an effective dose of saporin to CEM cells downregulated or negative for one of the target antigens and (iii) through ADCC mechanisms that interact additively with IT action. We have previously proposed that combination IT therapy would be one means of overcoming the problem of heterogeneity of antigen expression within a global tumour cell population and these additional findings support this and provide a further strengthening of the rationale for employing cocktails of ITs for the treatment of human malignancies.


A fast gas-mixing system for breath-to-breath respiratory control studies.
A computer-controlled gas-mixing system that manipulates inspired CO2 and O2 on a breath-to-breath basis has been developed. The system uses pairs of solenoid valves, one pair for each gas. These valves can either be fully shut when a low voltage is applied, or fully open when a high voltage is applied. The valves cycle open and shut every 1/12 s. A circuit converts signals from the computer, which dictates the flows of the gases, into a special form for driving the valve pairs. These signals determine the percentage of time within the 1/12-s cycle each valve spends in a open state and the percentage of time it spends shut, which, in effect, set the average flows of the various gases to the mixing chamber. The delay for response of the system to commanded CO2 or O2 changes is less than 200 ms. The system has application for the manipulation of inspired gas fractions so as to achieve desired end-tidal forcing functions.


Rfx6 maintains the functional identity of adult pancreatic β cells.
Increasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca(2+) channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of "disallowed" genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans.


Effects of red clover (Trifolium pratense) isoflavones on the lipid profile of perimenopausal and postmenopausal women-A systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to clarify the effect of a specific standardised extract of red clover (Trifolium pratense) on the lipid profile of perimenopausal and postmenopausal women. Medline (PubMed), EMBASE, and Cochrane Library electronic databases were searched for papers in English reporting randomized controlled trials published up to 2017. Reference lists from those papers were checked for further relevant publications. Studies were identified and reviewed for their eligibility for inclusion in this review. The changes from baseline in the levels of individual components of the lipid profiles were used to assess differences between the active treatment and placebo groups. Weighted mean differences and 95 % confidence intervals were calculated for continuous data using a random-effects model. Ten eligible studies (twelve comparisons) with 910 peri- and postmenopausal women were selected for systematic review. The meta-analysis showed changes in serum levels: total cholesterol, -0.29 (95 % CI: -0.53 to -0.06) mmol/L [-11.21 (95 % CI: -20.49 to -13.92) mg/dL], p = 0.0136; LDL-cholesterol, -0.13 (95 % CI: -0.35 to 0.09) mmol/L [-5.02 (95 % CI: -13.53 to 3.48) mg/dL], p = 0.2418; triglycerides, -0.15 (95 % CI: -0.32 to 0.01) mmol/L [-13.28 (95 % CI: -28.34 to 0.88) mg/dL], p = 0.0592; and HDL-cholesterol, 0.14 (95 % CI: -0.08 to 0.36) mmol/L [5.41 (95 % CI: -3.09-13.92) mg/dL], p = 0.2103. TheI2 statistic ranged from 87.95%-98.30 %, indicating significant heterogeneity. The results suggest that a red clover extract is efficacious in reducing the concentrations of total cholesterol; however, changes in HDL-C, LDL-C and triglycerides are not as pronounced. Potentially, this means that women takingTrifolium pratense for menopausal symptoms can derive additional benefits from the plant's specific effect that corrects abnormal cholesterol levels. Additional studies are needed to assess its effects on post-menopausal women.


Age-related effects on fitness performance in elite-level soccer referees.
Elite soccer referees usually achieve the peak of their officiating careers at an average age that is considerably older than that observed in competitive matched soccer players. As ageing has been reported to negatively affect physical performance, the aim of this study was to investigate the effect of ageing on fitness performance in elite-level soccer referees. Thirty-six elite-level soccer referees were grouped into young (Y, n = 12), average (A, n = 14), and old (O, n = 10) groups, according to their age and observed for field test performance (countermovement jump [CMJ], 50-m and 200-m sprints, and 12-minute running for distance). Results showed a significant age effect on CMJ (r = -0.52, p < 0.001), 200 m (r = 0.51, p < 0.001), and 12-minute time trial running (r = -0.52, p < 0.001). Y jumped higher than A and O groups (p < 0.05) and were faster than O over 200 m (p < 0.05). No group effect was observed for 12-minute run and 50-m performance (p > 0.05), respectively. Sixteen of the 36 referees were further examined for selected physiological variables and grouped into 2 equal (n = 8) age groups (young and old, Y1 and O1, respectively). Vo(2)max was higher in Y1 (p < 0.05), but O1 attained performances similar to Y1 running at selected blood lactate speeds (4 mmol L(-1), p > 0.05). Although older referees demonstrated acceptable fitness levels, younger officials should ensure that they develop appropriate levels of aerobic and anaerobic fitness to be able to match the demands placed upon them while refereeing throughout their careers. To promote this, fitness test standards should be age related.


The impact of digital technology on psychological treatments and their dissemination.
The psychological treatment of mental health problems is beginning to undergo a sea-change driven by the widespread availability of digital technology. In this paper we provide an overview of the developments to date and those in the pipeline. We describe the various uses of digital interventions and consider their likely impact on clinical practice, clinical services and the global dissemination of psychological treatments. We note the importance of online clinics, blended treatment, digital assessment and digital training.


Velopharyngeal closure analysis using four-dimensional computed tomography: a pilot study of healthy volunteers and adult patients with cleft palate.
Nasopharyngoscopy is a common method to evaluate velopharyngeal closure in patients with cleft palate. However, insertion of a fiberoptic nasopharyngoscope causes discomfort in patients. The aim of this study was to estimate the reliability of short-time exposure images obtained using 320-row area detector computed tomography (320-ADCT) as a novel evaluation method for the assessment of velopharyngeal function. We evaluated five healthy adult volunteers and five postoperative adult patients with cleft palate. During a 3.3-s imaging exposure, the participants were asked to perform two tasks: nasal inspiration and subsequent oral expiration through a catheter into a water-filled cup. The movement of the velopharyngeal structures was recorded during each examination, and the presence of velopharyngeal insufficiency (VPI) and velopharyngeal closure (VPC) patterns were estimated. If VPI was detected, the cross-sectional area was also calculated. Cohen's kappa and weighted kappa coefficients were used to evaluate the concordance of nasopharyngoscopy and 320-ADCT evaluation. Speech pathology evaluation did not reveal hypernasality in any study participant. Micro-VPI was detected by nasopharyngoscopy in one healthy volunteer and two patients. 320-ADCT detected micro-VPI in two more patients. The cross-sectional area of the VPI in these subjects ranged from 2.53 to 16.28 mm2. Nasopharyngoscopy and 320-ADCT were concordant in detecting VPI in eight participants (κ = 0.6) and in assessing VPC patterns in nine (κ = 0.82). Moreover, images obtained using 320-ADCT allowed for reduced dead angle and, thus, easy detection of micro-VPI and Passavant's ridges. Although the radiation exposure cannot be ignored, our novel evaluation method using 320-ADCT enables more detailed evaluation of VPC than nasopharyngoscopy. Future studies should investigate the relationship between 320-ADCT findings and speech pathology evaluations.


Feasibility and limitations of endovascular coil embolization of anterior communicating artery aneurysms: morphological considerations.
The purpose of this study is to analyze anterior communicating artery (AComA) aneurysm morphology and its relationship to the limitations and feasibility of endovascular coil embolization. One hundred twenty-three patients were treated with endovascular coil embolization for AComA aneurysms. Aneurysm morphology was classified into six categories according to the projection of the aneurysm (anterior, posterior/superior, or inferior) and neck size (< 4 mm or >or= 4 mm). The following categories were used: Class A1, anterior projection and neck of aneurysm less than 4 mm; Class A2, anterior projection and neck of aneurysm 4 mm or more; Class B1, posterior (superior) projection and neck of aneurysm less than 4 mm; Class B2, posterior (superior) projection and neck of aneurysm 4 mm or more; Class C1, inferior projection and neck of aneurysm less than 4 mm; and Class C2, inferior projection and neck of aneurysm 4 mm or more. Endovascular procedures were categorized as either successful or unsuccessful according to specific criteria. In addition, patients were followed for recanalization. Clinical follow-up data was obtained at discharge and after 6 months and was classified according to the Glasgow Outcome Scale. Complete or near complete aneurysm occlusion was observed in 108 (88%) patients, partial embolization was performed in three (2.4%) patients, and embolization was attempted in 12 (9.7%) patients. Successful embolization for AComA aneurysms was performed in 86 out of 123 (70%) patients or 77.5% (86 out of 111 patients) of those patients in whom embolization was possible. Statistical analysis demonstrated that anterior projecting aneurysms were more likely to be successfully coiled than either inferior or posterior/superior directed AComA aneurysms. In addition, inferiorly projecting AComA aneurysms and wide-neck aneurysms had a significantly higher rate of recanalization. Endovascular coil embolization of AComA aneurysms shows good outcome in our study. Despite advanced modern techniques, there are limitations in the endovascular approach to AComA aneurysms. Consideration of aneurysm morphology may be used to guide approaches in the treatment of AComA aneurysms.


Long-term mortality risk in individuals with permanent work-related impairment.
Recent estimates indicate that at least one in five activity-limiting injuries occurs at work. Of individuals who suffer these injuries approximately 10% experience some degree of functional impairment. We were interested in investigating long-term mortality risk in individuals with permanent impairment from work injury and to examine whether work disability is a significant explanatory factor. We used a retrospective matched cohort methodology to examine differences in mortality rates between individuals with permanent impairment from a work injury and a group of non-injured controls over a 19-year period. We used a sample of impaired workers to investigate the impact of work disability on mortality risk using percentage of earnings recovery after injury as the key proxy measure. All analyses were stratified by sex. Permanent impairment from a work injury was predictive of premature mortality in both male and female claimants, though the risk was slightly higher among women. Work disability was a key explanatory factor in the rate of death among impaired workers, the effects being more pronounced in men. We also found that higher impairment level was associated with mortality in men but not in women. The study demonstrates the impact of permanent work-related impairment on longevity and identifies work disability as an important determinant of mortality risk. Given the disconnect between impairment ratings derived from standard diagnostic tools and labour-market activity after accident, more research is needed on the specific factors that contribute to work disability, particularly those related to psycho-social health and well-being.


Post-translational isoprenylation of tryptophan.
Bacillus subtilis and related bacilli produce a post-translationally modified oligopeptide, ComX pheromone, that stimulates natural genetic competence controlled by quorum sensing. The ComX pheromones are formed by geranylation or farnesylation on a tryptophan residue at the 3 position of its indole ring. This results in the formation of a tricyclic structure including, a newly formed five-membered ring, similar to proline. Isoprenylation of ComX to form ComX pheromones is essential for pheromonal activity, and is functionally more crucial than its amino acid sequence. The ComX pheromone is the first example of isoprenoidal modifiations of tryptophan residues in living organisms and post-translational isoprenylation of any amino acid in prokaryotes. Because the presence of geranylated compounds is unusual in primary and secondary metabolites outside the plant kingdom, post-translational geranylation in bacilli is unprecedented in nature.


Early detection of SARS-CoV-2 and other infections in solid organ transplant recipients and household members using wearable devices.
The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant-specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2, and other infections are also reviewed.


Preliminary investigation of the effect of pulse rate on judgments of swallowing impairment and treatment recommendations.
Reducing fluoroscopic pulse rate, a method used to reduce radiation exposure from modified barium swallow studies (MBSSs), decreases the number of images available from which to judge swallowing impairment. It is necessary to understand the impact of pulse rate reduction on judgments of swallowing impairment and, consequentially, treatment recommendations. This preliminary study explored differences in standardized MBSS measurements [Modified Barium Swallow Impairment Profile (MBSImP™©) and Penetration Aspiration Scale (PAS) Scores] between two pulse rates: 30 and simulated 15 pulses per second (pps). Two reliable speech-language pathologists (SLPs) scored all five MBSSs. Five SLPs reported treatment recommendations based on those scores. Differences in judgments of swallowing impairment were found between 30 and simulated 15 pps in all five MBSSs. These differences were in six physiological swallowing components: initiation of pharyngeal swallow, anterior hyoid excursion, epiglottic movement, pharyngeal contraction, pharyngeal-esophageal segment opening, and tongue base retraction. Differences in treatment recommendations were found between 30 and simulated 15 pps in all five MBSSs. These findings suggest that there are differences in both judgment of swallowing impairment and treatment recommendations when pulse rates are reduced from 30 to 15 pps to minimize radiation exposure.


Child maltreatment in the time of the COVID-19 pandemic: A proposed global framework on research, policy and practice.
Child protection is and will be drastically impacted by the COVID-19 pandemic. Comprehending this new reality and identifying research, practice and policy paths are urgent needs. The current paper aims to suggest a framework for risk and protective factors that need to be considered in child protection in its various domains of research, policy, and practice during and after the COVID-19 pandemic. From an international collaboration involving researchers and child protection professionals from eight countries, the current paper examines various factors that were identified as playing an important role in the child protection system. Through the use of an ecological framework, the current paper points to risk and protective factors that need further exploration. Key conclusions point to the urgent need to address the protection of children in this time of a worldwide pandemic. Discussion of risk and protective factors is significantly influenced by the societal context of various countries, which emphasizes the importance of international collaboration in protecting children, especially in the time of a worldwide pandemic. The COVID-19 pandemic has stressed the urgent need to advance both theory and practice in order to ensure children's rights to safety and security during any pandemic. The suggested framework has the potential to advance these efforts so that children will be better protected from maltreatment amidst a pandemic in the future.


Cerebrospinal fluid neurofilament light chain levels predict visual outcome after optic neuritis.
Optic neuritis is a good model for multiple sclerosis relapse, but currently no tests can accurately predict visual outcome. The purpose of this study was to examine whether cerebrospinal fluid (CSF) biomarkers of tissue damage and remodelling (neurofilament light chain (NF-L), myelin basic protein, osteopontin and chitinase-3-like-1) predict visual outcome after optic neuritis. We included 47 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, optical coherence tomography (OCT), magnetic resonance imaging (MRI) and lumbar puncture. Biomarkers were measured in CSF by enzyme-linked immunosorbent assay (ELISA). Patients were followed up six months after onset and this included visual tests and OCT. Outcome measures were inter-ocular differences in low contrast visual acuity (LCVA), retinal nerve fibre layer (RNFL) and ganglion cell layer+inner plexiform layer (GC-IPL) thicknesses. CSF NF-L levels at onset predicted inter-ocular differences in follow-up LCVA (β=13.8, p=0.0008), RNFL (β=5.6, p=0.0004) and GC-IPL (β=4.0, p=0.0008). The acute-phase GC-IPL thickness also predicted follow-up LCVA (β=12.9, p=0.0021 for NF-L, β=-1.1, p=0.0150 for GC-IPL). Complete/incomplete remission was determined based on LCVA from 30 healthy controls. NF-L had a positive predictive value of 91% and an area under the curve (AUC) of 0.79 for incomplete remission. CSF NF-L is a promising biomarker of visual outcome after optic neuritis. This could aid neuroprotective/regenerative medical advancements.


Paclitaxel suppresses the viability of breast tumor MCF7 cells through the regulation of EF1α and FOXO3a by AMPK signaling.
Paclitaxel (Taxol), a potent drug of natural origin isolated from the bark of the Pacific yew, is widely used for treating ovarian, lung and breast cancers. Currently, there is little information regarding the specific mechanism underlying the anticancer activity of paclitaxel. In the present study, we found that 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR), a well-known activator of adenosine monophosphate (AMP)-activated protein kinase (AMPK), downregulated the protein and mRNA levels of elongation factor 1 α (EF1α) in breast cancer MCF7 cells. Paclitaxel increased the phosphorylation of AMPK and also downregulated the expression of EF1α in MCF7 cells. In addition, paclitaxel increased the expression, as well as the phosphorylation of forkhead box O3a (FOXO3a). Phosphorylation of FOXO3a was suppressed in the presence of compound C, a specific AMPK inhibitor, suggesting the involvement of AMPK in paclitaxel-induced FOXO3a phosphorylation. The induction and phosphorylation of FOXO3a by paclitaxel were not observed in EF1α and AMPK knockdown cells. Co-treatment with AICAR resulted in increased susceptibility of cancer cells to paclitaxel-induced suppression of their viability and further enhanced paclitaxel-induced FOXO3a phosphorylation. These results suggest that the antitumor effects of paclitaxel in breast cancer are mediated by activation of the AMPK/EF1α/FOXO3a signaling pathway.


Enhanced extended range underwater imaging via structured illumination.
In this article, the utility of structured illumination in order to enhance the contrast and subsequent range capability of an underwater imaging system is explored. The proposed method consists of transmitting a short pulse of light in a grid like pattern that consists of multiple, narrow, delta-function like beams. The grid pattern can be arranged in either a one-dimensional line or an area as a two-dimensional pattern. Scanning the pattern in time results in the sequential illumination of the entire scene. The receiving system architecture imposes the exact same, grid-like pattern sensitivity on the reflected light with a simple subsequent superposition of the time-sequenced images. The system can be viewed as a parallel implementation of a Laser Line Scan System where multiple beams are projected and received instead of a single one. The performance enhancement over more conventional systems that project either a sheet or an area of light is compared for a challenging underwater environment via computer simulations. The resulting images are analyzed as a function of the spacing between the projected light beams to characterize contrast and resolution. The results indicate that reasonable gains are obtainable for close spacing between the beams while quite significant gains are predicted for larger ones. Structured illumination systems can therefore collect images more rapidly than systems that scan a single beam; however with concomitant trade-offs in contrast and resolution.


Risk factors for disability discharge in enlisted active duty Army soldiers.
The rate of permanent disability retirement in U.S. Army soldiers and the prevalence of combat-related disabilities have significantly increased over time. Prior research on risk factors associated with disability retirement included soldiers retired prior to conflicts in Iraq and Afghanistan. To identify risk factors for disability discharge among soldiers enlisted in the U.S. Army during military operations in Iraq and Afghanistan. In this case-control study, cases included active duty soldiers evaluated for disability discharge. Controls, randomly selected from soldiers with no history of disability evaluation, were matched to cases based on enlistment year and sex. Conditional logistic regression models calculated odds of disability discharge. Attributable fractions estimated burden of disability for specific pre-existing condition categories. Poisson regression models compared risk of disability discharge related to common disability types by deployment and combat status. Characteristics at military enlistment with increased odds of disability discharge included a pre-existing condition, increased age or body mass index, white race, and being divorced. Musculoskeletal conditions and overweight contributed the largest proportion of disabilities. Deployment was protective against disability discharge or receiving a musculoskeletal-related disability, but significantly increased the risk of disability related to a psychiatric or neurological condition. Soldiers with a pre-existing condition at enlistment, particularly a musculoskeletal condition, had increased odds of disability discharge. Risk of disability was dependent on condition category when stratified by deployment and combat status. Additional research examining conditions during pre-disability hospitalizations could provide insight on specific conditions that commonly lead to disability discharge.


Incentives, equity and the Able Chooser Problem.
Health incentive schemes aim to produce healthier behaviours in target populations. They may do so both by making incentivised options more salient and by making them less costly. Changes in costs only result in healthier behaviour if the individual rationally assesses the cost change and acts accordingly. Not all people do this well. Those who fail to respond rationally to incentives will typically include those who are least able to make prudent choices more generally. This group will typically include the least advantaged more generally, since disadvantage inhibits one's effective ability to choose well and since poor choices tend to cause or aggravate disadvantage. Therefore, within the target population, health benefits to the better off may come at the cost of aggravated inequity. This is one instance of a problem I name the Able Chooser Problem, previously emphasised by Richard Arneson in relation to coercive paternalism. I describe and discuss this problem by distinguishing between policy options and their effects on the choice situation of individuals. Both positive and negative incentives, as well as mandates that are less than perfectly effective, require some sort of rational deliberation and action and so face the Able Chooser Problem. In contrast, effective restriction of what options are physically available, as well as choice context design that makes some options more salient or appealing, does not demand rational agency. These considerations provide an equity-based argument for preferring smart design of our choice and living environment to incentives and mandates.


Prospects for measuring the electric dipole moment of the electron using electrically trapped polar molecules.
Heavy polar molecules can be used to measure the electric dipole moment of the electron, which is a sensitive probe of physics beyond the Standard Model. The value is determined by measuring the precession of the molecule's spin in a plane perpendicular to an applied electric field. The longer this precession evolves coherently, the higher the precision of the measurement. For molecules in a trap, this coherence time could be very long indeed. We evaluate the sensitivity of an experiment where neutral molecules are trapped electrically, and compare this to an equivalent measurement in a molecular beam. We consider the use of a Stark decelerator to load the trap from a supersonic source, and calculate the deceleration efficiency for YbF molecules in both strong-field seeking and weak-field seeking states. With a 1 s holding time in the trap, the statistical sensitivity could be ten times higher than it is in the beam experiment, and this could improve by a further factor of five if the trap can be loaded from a source of larger emittance. We study some effects due to field inhomogeneity in the trap and find that rotation of the electric field direction, leading to an inhomogeneous geometric phase shift, is the primary obstacle to a sensitive trap-based measurement.


Effect of microscopic modeling of skin in electrical and thermal analysis of transcranial direct current stimulation.
Transcranial direct current stimulation (tDCS) is a neuromodulation scheme where a small current is delivered to the brain via two electrodes attached to the scalp. The electrode design is an important topic, not only as regards efficacy, but also from a safety perspective, as tDCS may be related to skin lesions that are sometimes observed after stimulation. Previous computational models of tDCS have omitted the effects of microscopic structures in the skin, and the different soak conditions of the electrodes, and model validation has been limited. In this study, multiphysics and multiscale analysis are proposed to demonstrate the importance of microscopic modeling of the skin, in order to clarify the effects of the internal electric field, and to examine temperature elevation around the electrodes. This novel microscopic model of the skin layer took into consideration the effect of saline/water penetration in hair follicles and sweat ducts on the field distribution around the electrodes. The temperature elevation in the skin was then computed by solving the bioheat equation. Also, a multiscale model was introduced to account for macroscopic and microscopic tissues of the head and skin, which was validated by measurement of the head resistance during tDCS. As a result, the electric field in the microscopic model of the skin was less localized when the follicles/ducts were filled with saline instead of hair or tap water. Temperature elevation was also lessened with saline, in comparison with other substances. Saline, which may penetrate the hair follicles and sweat ducts, suppressed the field concentration around the electrodes. For conventional magnitudes of current injection, and a head resistance of less than 10 kΩ, the temperature elevation in the skin when using saline-soaked electrodes was low, less than 0.1 °C, and unlikely to cause adverse thermal effects.


Information functions of an international meeting.
In spite of a number of difficulties and shortcomings, this international meeting was relatively effective for this group of respondents. They benefitted from the informal interaction of participants, from information that pertained to current and planned work, and from the prospects of continued exchange with colleagues in other countries. That the meeting could have been even more valuable was also the consensus. Additional data on another such meeting reinforce these findings and suggest that the results obtained are probably not peculiar to one social science or to this specific meeting. Reports of a small group of sociologists, who received grants from the National Institute of Mental Health to attend the Sixth World Congress of Sociology at Evian in September 1966, showed marked concurrence with those of the psychologists who attended the Moscow congress. For both groups there was the same preponderence of United States and Russian presentations on the program, informal interaction was more productive of useful information than were formally scheduled events, and the main type of information obtained was a broader knowledge of research activity and effort in various countries. The sociologists emphasized even more than did the psychologists the importance of acquiring new points of view and perspectives. More than half the sociologists planned to use information obtained in their current or future work, and a fourth planned international collaborative research efforts; in both these respects they surpassed the percentages found in the data on the psychologists. Finally, all the criticisms voiced by Moscow respondents appeared also among the Evian group, though not in sufficient numbers to constitute a trend. These data suggest that international meetings can and do fill certain information needs in spite of organizational difficulties and the problems attendant upon any large gathering in an environment unfamiliar to most of those who participate.


Metal-free photoanodes for C-H functionalization.
Organic semiconductors, such as carbon nitride, when employed as powders, show attractive photocatalytic properties, but their photoelectrochemical performance suffers from low charge transport capability, charge carrier recombination, and self-oxidation. High film-substrate affinity and well-designed heterojunction structures may address these issues, achieved through advanced film generation techniques. Here, we introduce a spin coating pretreatment of a conductive substrate with a multipurpose polymer and a supramolecular precursor, followed by chemical vapor deposition for the synthesis of dual-layer carbon nitride photoelectrodes. These photoelectrodes are composed of a porous microtubular top layer and an interlayer between the porous film and the conductive substrate. The polymer improves the polymerization degree of carbon nitride and introduces C-C bonds to increase its electrical conductivity. These carbon nitride photoelectrodes exhibit state-of-the-art photoelectrochemical performance and achieve high yield in C-H functionalization. This carbon nitride photoelectrode synthesis strategy may be readily adapted to other reported processes to optimize their performance.


Long-term results following ankle arthrodesis for post-traumatic arthritis.
Ankle arthrodesis is considered by many to be the standard operative treatment for end-stage ankle arthritis; however, the long-term effect of ankle arthrodesis on other lower-extremity joints remains largely unknown. The purpose of this study was to perform a clinical and radiographic review to determine the effect of ankle arthrodesis on the development of osteoarthritis in other lower-extremity joints. Twenty-three patients who had had an isolated ankle arthrodesis for the treatment of painful posttraumatic arthritis of the ankle were followed for a mean of twenty-two years (range, twelve to forty-four years) after the operation. Each completed standardized, self-reported outcome questionnaires (the Foot Function Index, Western Ontario and McMaster University Osteoarthritis Index [WOMAC], and Short Form-36 [SF-36]), was examined clinically by two of the investigators, and underwent complete radiographic examination of the knee, ankle, and foot bilaterally. The radiographic grade of osteoarthritis was determined for each joint, and the levels of overall activity limitation, pain, and disability were determined for each patient from the clinical findings and questionnaire information. Osteoarthritis of the ipsilateral subtalar (p<0.0001), talonavicular (p<0.0001), calcaneocuboid (p<0.0001), naviculocuneiform (p = 0.0012), tarsometatarsal (p = 0.0009), and first metatarsophalangeal joints (p = 0.0012) was consistently more severe than the osteoarthritis of those joints on the contralateral side. Osteoarthritis did not develop more frequently in the ipsilateral knee or lesser metatarsophalangeal joints than it did on the contralateral side. Significant differences between the two sides were found with regard to overall activity limitation (p<0.0001), pain (p<0.0001), and disability (p<0.0001), with the involved side consistently more symptomatic. To our knowledge, the present series represents the longest follow-up study of ankle arthrodesis to date. Our cohort of patients all had isolated post-traumatic ankle arthritis, and each underwent a successful isolated ankle arthrodesis. At a mean of twenty-two years, the majority of the patients had substantial, and accelerated, arthritic changes in the ipsilateral foot but not the knee. They were often limited functionally by foot pain. Although ankle arthrodesis may provide good early relief of pain, it is associated with premature deterioration of other joints of the foot and eventual arthritis, pain, and dysfunction.


A rapid method of monitoring the acute phase response in a rat model.
The acute phase response (APR) is accompanied by major changes in micronutrient status. It is important to be able to quantitate the degree of APR, which can then be related to the accompanying alterations in micronutrient levels. A rapid and convenient means of achieving this, viz. the use of an animal model in which APR can be induced, would facilitate such an investigation. The aim of the present study was to establish, by means of a rat model, a rapid procedure to identify APR which is less time-consuming and less expensive than the more traditional enzyme-linked immunosorbent assay and radio-immunoassay. Blood was drawn immediately prior to, and at 24, 48, 72 and 96-hour intervals post-inducement of the acute phase. The serum was deproteinised and treated with a dye, Auramine O, which specifically binds the acute phase protein alpha 1-acid glycoprotein (AAG), the latter remaining in solution after deproteinisation. The product formed is a fluorescent addition compound. With fluorescence spectrophotometry, levels of AAG were determined and the extent of APR monitored. A progressive and reproducible increase in AAG was observed, the highest fluorescence intensity recorded after 48 hours; this indicated a mean value (N = 5) of 9.4 mg/ml from zero at baseline. With a spiking approach, a mean AAG recovery of 96% was obtained. The validated methodology, less expensive and less time-consuming than existing procedures, which rapidly detects AAG in rat serum, provides a simple technique for monitoring the APR process in these animals.


Highly efficient hybrid light-emitting device using complex of CdSe/ZnS quantum dots embedded in co-polymer as an active layer.
We propose a highly efficient hybrid light-emitting device (LED) with a single active layer where CdSe/ZnS quantum dots (QDs) are dispersed as a guest material in a conjugated polymer (co-polymer) matrix used for a host material. In our structure, the QDs act on light-emitting chromophores by trapping the migrating excitons in the co-polymer matrix via Förster energy transfer, and improve the charge balance within the co-polymer by trapping the injected electron carriers. Experimental results show that the electroluminescent properties highly depend on the doping density of the QDs within the co-polymer matrix, where the luminance as well as the external current efficiency are initially enhanced with increasing the concentration of the dispersed QDs in the co-polymer solution, and then such properties are degraded due to aggregation of the QDs. We can get the maximum brightness of 9,088 cd/m(2) and the maximum external current efficiency of 7.5 cd/A in mixing ratio of the QDs by 1.0 wt%. The external current efficiency is enhanced by over 15 times and the turn-on voltage is reduced in comparison with the corresponding values for a reference device that uses only a co-polymer as an active layer.


Divergent Responses in the Gap Prepulse Inhibition of the Acoustic Startle Reflex in Two Different Guinea Pig Colonies.
Animal models of tinnitus rely on interpretation of behavioural or reflexive tests to determine the presence of this phantom perception. A commonly used test is the gap prepulse inhibition of acoustic startle (GPIAS), which is often combined with prepulse inhibition (PPI) to ensure that reduced GPIAS suppression is not due to hearing loss caused by the acoustic trauma commonly used to trigger tinnitus development. In our laboratory GPIAS and PPI are routinely used on two colonies of outbred tri-colour guinea pigs. However, our results show that these colonies show divergent results even before any tinnitus-inducing treatment, which impacts their suitability in tinnitus models. Although colony 1 and 2 show similar results in PPI (~95% of animals showing significant suppression), only ~30% of colony 2 also shows significant suppression in GPIAS compared to ~75% of colony 1. Cochlear sensitivity measured using compound action potentials showed no significant differences between colonies. Therefore, peripheral threshold loss was excluded as a possible factor. Our results show that similar strains of laboratory animals can show highly divergent results and GPIAS testing for tinnitus will not work for every animal strain. In addition, our data support the notion that PPI and GPIAS responses may rely on different neural circuitry.


A virtual reality intervention to improve the understanding and empathy for people with dementia in informal caregivers: results of a pilot study.
Informal caregivers often experience psychological distress due to the changing functioning of the person with dementia they care for. Improved understanding of the person with dementia reduces psychological distress. To enhance understanding and empathy in caregivers, an innovative technology virtual reality intervention Through the D'mentia Lens (TDL) was developed to experience dementia, consisting of a virtual reality simulation movie and e-course. A pilot study of TDL was conducted. A pre-test-post-test design was used. Informal caregivers filled out questionnaires assessing person-centeredness, empathy, perceived pressure from informal care, perceived competence and quality of the relationship. At post-test, additional questions about TDL's feasibility were asked. Thirty-five caregivers completed the pre-test and post-test. Most participants were satisfied with TDL and stated that TDL gave more insight in the perception of the person with dementia. The simulation movie was graded 8.03 out of 10 and the e-course 7.66. Participants significantly improved in empathy, confidence in caring for the person with dementia, and positive interactions with the person with dementia. TDL is feasible for informal caregivers and seems to lead to understanding of and insight in the experience of people with dementia. Therefore, TDL could support informal caregivers in their caregiving role.


Function and regulation of retinoic acid-inducible gene-I.
Antiviral innate immunity is triggered by sensing viral nucleic acids. RIG-I (retinoic acid-inducible gene-I) is an intracellular molecule that responds to viral nucleic acids and activates downstream signaling, resulting in the induction of members of the type I interferon (IFN) family, which are regarded among the most important effectors of the innate immune system. Although RIG-I is expressed ubiquitously in the cytoplasm, its levels are subject to transcriptional and post-transcriptional regulation. RIG-I belongs to the IFN-stimulated gene (ISG) family, but certain cells regulate its expression through IFN-independent mechanisms. Several lines of evidence indicate that deregulated RIG-I signaling is associated with autoimmune disorders. Further studies suggest that RIG-I has functions in addition to those directly related to its role in RNA sensing and host defense. We have much to learn and discover regarding this interesting cytoplasmic sensor so that we can capitalize on its properties for the treatment of viral infections, immune disorders, cancer, and perhaps other conditions.


Value-based payment in implementing evidence-based care: the Mental Health Integration Program in Washington state.
To assess the role of value-based payment (VBP) in improving fidelity and patient outcomes in community implementation of an evidence-based mental health intervention, the Collaborative Care Model (CCM). Retrospective study based on a natural experiment. We used the clinical tracking data of 1806 adult patients enrolled in a large implementation of the CCM in community health clinics in Washington state. VBP was initiated in year 2 of the program, creating a natural experiment. We compared implementation fidelity (measured by 3 process-of-care elements of the CCM) between patient-months exposed to VBP and patient-months not exposed to VBP. A series of regressions were estimated to check robustness of findings. We estimated a Cox proportional hazard model to assess the effect of VBP on time to achieving clinically significant improvement in depression (measured based on changes in depression symptom scores over time). Estimated marginal effects of VBP on fidelity ranged from 9% to 30% of the level of fidelity had there been no exposure to VBP (P <.05 for every fidelity measure). Improvement in fidelity in response to VBP was greater among providers with a larger patient panel and among providers with a lower level of fidelity at baseline. Exposure to VBP was associated with an adjusted hazard ratio of 1.45 (95% confidence interval, 1.04-2.03) for achieving clinically significant improvement in depression. VBP improved fidelity to key elements of the CCM, both directly incentivized and not explicitly incentivized by the VBP, and improved patient depression outcomes.


Out-of-equilibrium force measurements of dual-fiber optical tweezers.
Optical trapping of micron-size dielectric particles in a dual-fiber tip configuration is presented. Trap oscillation and suspension flow experiments are performed to investigate the linearity of the optical forces. These measurements are completed by standard methods such as Boltzmann statistics or power spectra evaluation. Strong trapping efficiencies of 0.25 and 1.8 pN·μm-1 have been found in the axial and transverse directions, respectively. The values obtained by the different approaches are in good agreement. The measurements show that the optical trapping potential is harmonic over the experimentally attainable distances, i.e., 2.5 and 0.6 μm in the transverse and axial directions, respectively.


Left Atrial Appendage Thrombus Prior to Atrial Fibrillation Ablation in the Era of Direct Oral Anticoagulants.
In atrial fibrillation (AF) patients, the effect of direct oral anticoagulant (DOACs) therapy on the incidence of left atrial appendage thrombus (LAT) remains poorly investigated. This study examined the prevalence and risk factors of LAT in AF patients on DOACs undergoing catheter ablation, and sought an anticoagulation strategy for LAT. Methods and Results: In 407 AF patients on DOACs, transesophageal echocardiography (TEE) was performed 1 day before ablation. If patients had LAT, initial DOACs were switched to dabigatran (300 mg) or warfarin based on their renal function; TEE was repeated after treatment for ≥4 weeks. LAT was detected in 18 patients (4.4%). The prevalence of persistent AF and low-dose treatment/inappropriate dose reduction of DOACs, CHADS2/CHA2DS2-VASc scores, serum N-terminal pro-brain natriuretic peptide levels, and LA dimension/LA volume index significantly increased in patients with LAT vs. those without LAT. AF rhythm on TEE and spontaneous echo contrast also increased in patients with LAT; LA appendage flow velocity decreased. In the multivariate analysis, persistent AF and inappropriately reduced DOAC dose were risk factors for LAT. On repeat TEE, LAT had disappeared in 13 of 16 patients treated with dabigatran and in 2 of 2 patients treated with warfarin. DOACs still carry a finite risk of LAT in AF patients. Inappropriately reduced DOAC dose should be avoided to minimize the thromboembolic risk. Regular-dose dabigatran may have therapeutic efficacy against LAT.


Spinal muscular atrophy: diagnosis, treatment and future prospects.
To report on recent genetic and molecular discoveries and on future prospects for the treatment of spinal muscular atrophy (SMA), thereby helping healthcare professionals to make a quick diagnosis and provide appropriate and timely therapeutic support. Information was collected from scientific articles published in the last 2 decades, retrieved from the databases SciELO, PubMed, and MEDLINE. SMA is a neurodegenerative disorder with autosomal recessive genetic heredity. It is caused by a homozygous deletion of the survival motor neuron (SMN1) gene. This genetic alteration results in reduced levels of the SMN protein, leading to degeneration of alpha motor neurons of the spinal cord and resulting in muscle weakness and progressive symmetrical proximal paralysis. It is known that basic nutritional and respiratory care and physiotherapy can be important to delaying disease progression and prolonging patients' lives. Several drugs are being tested, some new, others, such as valproic acid, already known; paralysis can be halted, but not reversed. SMA is a difficult to diagnose disorder, because it is little known, and treatment is uncertain. Pharmacological treatments and supportive therapies are not yet able to recover motor neurons or muscle cells that have already been lost, but are aimed at delaying disease progression and improving patients' residual muscle function, as well as offering better quality of life and life expectancy.


First Report of a Tospovirus in Mulberry.
Mulberry (Morus alba L.) is an economically important crop grown widely throughout Asia. Various virus-like symptoms including mosaics, vein banding, and chlorotic ringspots have been observed and reported on mulberry trees in China and Japan for decades. However, the etiology of mulberry viral diseases is generally understudied, although two mulberry-infecting viruses, Mulberry latent virus (genus Carlavirus) (2) and Mulberry ringspot virus (genus Nepovirus) (3), have been partially characterized. In a recent (2010 to 2011) field survey in Guangxi Province, China, supported by the local government, the incidence of virus-like diseases of mulberry ranged between 40 and 80%. To identify the viruses infecting mulberry, deep sequencing of small RNAs (4) was conducted using an Illumina Genome Analyzer. Small RNAs were isolated from five samples of mulberry leaves showing various virus-like symptoms and sequenced. Among the contigs assembled, a 445-bp contig (GenBank Accession No. JX268597) was found to share 76.6% nucleotide identity and 83.0% amino acid identity to Groundnut bud necrosis virus (genus Tospovirus, family Bunyaviridae; Accession Nos. U42555 and AAC55521). To obtain a longer cDNA fragment of this virus, a reverse transcription (RT)-PCR was done with primers MV-N-F (5'-AAGCCATCAATGTGCCTCCGGA-3') and MV-N-R (5'-AACACCATGTCTACCGTCCGTC-3') that align to the S-RNA sequence encompassing the nucleocapsid (N) gene and a portion of the intergenic region (IGR) of the Tospovirus. PCR products of about 1,000 bp were successfully amplified from the total RNA of the three mulberry samples (sl-1, xcsy-1, and xcsy-4) showing vein banding symptoms, but not from asymptomatic mulberry (jk-1). These PCR products were cloned and sequenced. The lengths of the amplicons were 1,027 bp (isolate sl-1, JX173786), 987 bp (isolate xcsy-1, JX173787), and 979 bp (isolate xcsy-4, JX173788) and the partial IGRs of the sl-1, xcsy-1, and xcsy-4 isolates were 187 bp, 147 bp, and 139 bp, respectively. The coding regions for the N protein were 831 bp and the deduced proteins of 277 amino acid residues were 100% identical for all three isolates. Since the N protein of this virus shared up to only 74.4% identity to other tospoviruses (74.4% to Capsicum chlorosis virus, ABB83818; and 71.5% to Watermelon bud necrosis virus, ABY79095), it may represent a new member of the Tospovirus genus, temporarily named Mulberry vein banding virus (MuVBV), according to the species demarcation criteria for the Bunyaviridae (1). To the best of our knowledge, this is the first report of a Tospovirus infecting M. alba. In an RT-PCR screening of 48 randomly selected mulberry samples suspected to be virus-infected, 32 were MuVBV-positive. Giving the high incidence and the high yield loss associated with Tospovirus and the presence of thrips, suspected vectors for the virus, MuVBV may represent a substantial threat to the silkworm industry in China. References: (1) M. Q. K. Andrew et al. Virus Taxonomy: 9th Report of the ICTV. Elsevier Academic Press, San Diego, 2012. (2) T. Tsuchizaki. Annu. Phytopath. Soc. Japan 42:304, 1976. (3) T. Tsuchizaki et al. Annu. Phytopath. Soc. Japan 37:266, 1971. (4) Q. Wu et al. PNAS. 107:1606, 2010.


Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains.
Intrinsically disordered proteins are very common and mediate numerous protein-protein and protein-DNA interactions. While it is clear that these interactions are instrumental for the life of the mammalian cell, there is a paucity of data regarding their molecular binding mechanisms. Here we have used short peptides as a model system for intrinsically disordered proteins. Linear free energy relationships based on rate and equilibrium constants for the binding of these peptides to ordered target proteins, PDZ domains, demonstrate that native side-chain interactions form mainly after the rate-limiting barrier for binding and in a cooperative fashion. This finding suggests that these disordered peptides first form a weak encounter complex with non-native interactions. The data do not support the recent notion that the affinities of intrinsically disordered proteins toward their targets are generally governed by their association rate constants. Instead, we observed the opposite for peptide-PDZ interactions, namely, that changes in K(d) correlate with changes in k(off).


Super-Resolution of Cardiac MR Cine Imaging using Conditional GANs and Unsupervised Transfer Learning.
High-resolution (HR), isotropic cardiac Magnetic Resonance (MR) cine imaging is challenging since it requires long acquisition and patient breath-hold times. Instead, 2D balanced steady-state free precession (SSFP) sequence is widely used in clinical routine. However, it produces highly-anisotropic image stacks, with large through-plane spacing that can hinder subsequent image analysis. To resolve this, we propose a novel, robust adversarial learning super-resolution (SR) algorithm based on conditional generative adversarial nets (GANs), that incorporates a state-of-the-art optical flow component to generate an auxiliary image to guide image synthesis. The approach is designed for real-world clinical scenarios and requires neither multiple low-resolution (LR) scans with multiple views, nor the corresponding HR scans, and is trained in an end-to-end unsupervised transfer learning fashion. The designed framework effectively incorporates visual properties and relevant structures of input images and can synthesise 3D isotropic, anatomically plausible cardiac MR images, consistent with the acquired slices. Experimental results show that the proposed SR method outperforms several state-of-the-art methods both qualitatively and quantitatively. We show that subsequent image analyses including ventricle segmentation, cardiac quantification, and non-rigid registration can benefit from the super-resolved, isotropic cardiac MR images, to produce more accurate quantitative results, without increasing the acquisition time. The average Dice similarity coefficient (DSC) for the left ventricular (LV) cavity and myocardium are 0.95 and 0.81, respectively, between real and synthesised slice segmentation. For non-rigid registration and motion tracking through the cardiac cycle, the proposed method improves the average DSC from 0.75 to 0.86, compared to the original resolution images.


ADV36 adipogenic adenovirus in human liver disease.
Obesity and liver steatosis are usually described as related diseases. Obesity is regarded as exclusive consequence of an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Non-alcoholic fatty liver disease (NAFLD), is a condition whose natural history is related to, but not completely explained by over-nutrition, obesity and insulin resistance. There is evidence that environmental infections, and notably adipogenic adenoviruses (ADV) infections in humans, are associated not only with obesity, which is sufficiently established, but also with allied conditions, such as fatty liver. In order to elucidate the role, if any, of previous ADV36 infection in humans, we investigated association of ADV36-ADV37 seropositivity with obesity and fatty liver in humans. Moreover, the possibility that lifestyle-nutritional intervention in patients with NAFLD and different ADV36 seropositive status, achieves different clinical outcomes on ultrasound bright liver imaging, insulin resistance and obesity was challenged. ADV36 seropositive patients have a more consistent decrease in insulin resistance, fatty liver severity and body weight in comparison with ADV36 seronegative patients, indicating a greater responsiveness to nutritional intervention. These effects were not dependent on a greater pre-interventional body weight and older age. These results imply that no obvious disadvantage - and, seemingly, that some benefit - is linked to ADV36 seropositivity, at least in NAFLD. ADV36 previous infection can boost weight loss and recovery of insulin sensitivity under interventional treatment.


Advanced glycosylation endproducts block the antiproliferative effect of nitric oxide. Role in the vascular and renal complications of diabetes mellitus.
Advanced glycosylation endproducts (AGEs) accumulate on long-lived tissue proteins such as basement membrane collagen and have been implicated in many of the long-term complications of diabetes mellitus. These products originate from glucose-derived Schiff base and Amadori products but undergo a series of complex rearrangement reactions to form ultimately protein-bound, fluorescent heterocycles. AGEs can react with and chemically inactivate nitric oxide (NO), a potent endothelial cell-derived vasodilator and antiproliferative factor. Since mesenchymal cell proliferation is an early and characteristic lesion of diabetic vasculopathy and glomerulopathy, we investigated the possibility that collagen-bound AGEs functionally inactivate the antiproliferative effect of NO. In model cell culture systems, AGEs were found to block the cytostatic effect of NO on aortic smooth muscle and renal mesangial cells. The inactivation of endothelial cell-derived NO by basement membrane AGEs may represent a common pathway in the development of the accelerated vascular and renal disease that accompany long-term diabetes mellitus.


The fission yeast pmk1+ gene encodes a novel mitogen-activated protein kinase homolog which regulates cell integrity and functions coordinately with the protein kinase C pathway.
We have isolated a gene, pmk1+, a third mitogen-activated protein kinase (MAPK) gene homolog from the fission yeast Schizosaccharomyces pombe. The predicted amino acid sequence shows the most homology (63 to 65% identity) to those of budding yeast Saccharomyces Mpk1 and Candida Mkc1. The Pmk1 protein contains phosphorylated tyrosines, and the level of tyrosine phosphorylation was increased in the dsp1 mutant which lacks an attenuating phosphatase for Pmk1. The level of tyrosine phosphorylation appears constant during hypotonic or heat shock treatment. The cells with pmk1 deleted (delta pmk1) are viable but show various defective phenotypes, including cell wall weakness, abnormal cell shape, a cytokinesis defect, and altered sensitivities to cations, such as hypersensitivity to potassium and resistance to sodium. Consistent with a high degree of conservation of amino acid sequence, multicopy plasmids containing the MPK1 gene rescued the defective phenotypes of the delta pmk1 mutant. The frog MAPK gene also suppressed the pmk1 disruptant. The results of genetic analysis indicated that Pmk1 lies on a novel MAPK pathway which does not overlap functionally with the other two MAPK pathways, the Spk1-dependent mating signal pathway and Sty1/Spc1/Phh1-dependent stress-sensing pathway. In Saccharomyces cerevisiae, Mpk1 is involved in cell wall integrity and functions downstream of the protein kinase C homolog. In contrast, in S. pombe, Pmk1 may not act in a linear manner with respect to fission yeast protein kinase C homologs. Interestingly, however, these two pathways are not independent; instead, they regulate cell integrity in a coordinate manner.


Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy.
We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.


Magnetic resonance imaging volumetric assessment of the extent of contrast enhancement and resection in oligodendroglial tumors.
Oligodendrogliomas that enhance on MR images are associated with poor prognosis. However, the importance of the volume of enhancing tumor tissue, and the extent of its resection, is uncertain. The authors examined the prognostic significance of preoperative and residual postoperative enhancing tissue volumes in a large single-center series of patients with oligodendroglioma. They also examined the relationship between enhancement and characteristic genetic signatures in oligodendroglial tumors, specifically deletion of 1p and 19q (del 1p/19q). The authors retrospectively analyzed 100 consecutive cases of oligodendroglioma involving patients who had undergone T1-weighted gadolinium-enhanced MRI at diagnosis and immediately after initial surgical intervention. The presence of preoperative enhancement was determined by consensus. Preoperative and residual postoperative volumes were measured using a quantitative, semiautomated method by a single blinded observer. Intrarater reliability for preoperative volumes was confirmed by remeasurement in a subset of patients 3 months later. Intrarater and interrater reliability for residual postoperative volumes was confirmed by remeasurement of these volumes by both the original and a second blinded observer. Multivariate analysis was used to assess the influence of contrast enhancement at diagnosis and the volume of pre- and postoperative contrast-enhancing tumor tissue on time to relapse (TTR) and overall survival (OS), while controlling for confounding clinical, pathological, and genetic factors. Sixty-three of 100 patients had enhancing tumors at initial presentation. Presence of contrast enhancement at diagnosis was related to reduced TTR and OS on univariate analysis but was not significantly related on multivariate analysis. In enhancing tumors, however, greater initial volume of enhancing tissue correlated with shortened TTR (p = 0.00070). Reduced postoperative residual enhancing volume and a relatively greater resection of enhancing tissue correlated with longer OS (p = 0.0012 and 0.0041, respectively). Interestingly, patients in whom 100% of enhancing tumor was resected had significantly longer TTR (174 vs 64 weeks) and OS (392 vs 135 weeks) than those with any residual enhancing tumor postoperatively. This prognostic benefit was not consistently maintained with greater than 90% or even greater than 95% resection of enhancing tissue. There was no relationship between presence or volume of enhancement and del 1p/19q. In enhancing oligodendrogliomas, completely resecting enhancing tissue independently improves outcome, irrespective of histological grade or genetic status. This finding supports aggressive resection and may impact treatment planning for patients with these tumors.


Interferometric method of suppressing the pattern effect in a semiconductor optical amplifier.
A new idea of using change in index of refraction to suppress gain variation in a saturated semiconductor optical amplifier (SOA) is presented. This kind of gain compensation has the advantage of high speed because it involves two phenomena that always accompany each other. This compensation can be achieved with a nonsymmetrical Mach-Zehnder interferometer structure. Calculated results show that with this structure the input and output power of the SOA can be extended to nearly 10 dB from the former small-signal limit when less than 1-dB gain variation is permitted. Numerical simulations with an advanced dynamic model of the SOA agree with the calculated results.


Relationship between the home environment and fruit and vegetable consumption in children aged 6-12 years: a systematic review.
As numerous factors in the home environment have been related to children's fruit and vegetable (F&V) consumption as a component of a healthy diet, the purpose of the present systematic review was to examine these factors specifically for children aged 6-12 years. Relevant observational studies published in English between January 2007 and December 2015 were obtained through electronic database searches. Studies were included if the researchers reported on a potentially modifiable measure of the home physical, political and sociocultural environment related to child F&V consumption. Of the thirty-three articles reviewed, overall methodological quality was poor with twenty studies rated as weak, mainly due to cross-sectional design (majority of studies), selection bias, convenience sampling and voluntary participation. Half of the studies had strong-moderate ratings for using valid and/or reliable tools while for the other half, psychometric properties were either not reported or weak. The most consistent evidence for children's combined F&V consumption was found for availability and accessibility of F&V, parental role modelling of F&V and maternal intake of F&V. A vast array of home environment components and their influence on children's consumption of fruits and/or vegetables have been studied in recent years. Specific components of the home environment may have more influence than others, but more compelling evidence is needed to draw strong conclusions. Recommendations are made for future studies to be based upon conceptual/theoretical models to provide consistency in defining the home environment and investigation of potential moderators, such as personal or contextual factors.


The effect of generic competition on the price of brand-name drugs.
Literature from the US has shown that brand-name manufacturers do not compete on price once generic competitors become available. This study was undertaken to investigate if this is also true in Canada. Editions of the Ontario Drug Benefit Formulary were used to identify brand-name drugs that lacked generic competition in July 1990 but had acquired one or more generic competitors by December 1998. Prices of the brand-name drugs were compared before generic competition, at the point when generic competition started and subsequent to the initiation of competition. Price changes for 81 different products in 144 separate presentations were analysed. There was no statistically significant change in brand-name prices when generic competition started. The movement of brand-name prices was not influenced by whether the generic was made by the company producing the brand-name product or price freezes imposed by the Ontario government. When generics first became available having four or more generics was associated with a rise in the price of the brand-name drugs compared to having one, two or three generic competitor(s). The lack of price competition may lead to increased costs in the private market. Private insurance companies generally do not require generic substitution and some provinces do not require generic substitution for cash-paying customers. Maintaining higher prices on brand-name drugs impacts on the prices of new patented medications coming onto the Canadian market under the current pricing guidelines of the Patented Medicine Prices Review Board.


Nanoscale characterization of electrical transport at metal/3C-SiC interfaces.
In this work, the transport properties of metal/3C-SiC interfaces were monitored employing a nanoscale characterization approach in combination with conventional electrical measurements. In particular, using conductive atomic force microscopy allowed demonstrating that the stacking fault is the most pervasive, electrically active extended defect at 3C-SiC(111) surfaces, and it can be electrically passivated by an ultraviolet irradiation treatment. For the Au/3C-SiC Schottky interface, a contact area dependence of the Schottky barrier height (ΦB) was found even after this passivation, indicating that there are still some electrically active defects at the interface. Improved electrical properties were observed in the case of the Pt/3C-SiC system. In this case, annealing at 500°C resulted in a reduction of the leakage current and an increase of the Schottky barrier height (from 0.77 to 1.12 eV). A structural analysis of the reaction zone carried out by transmission electron microscopy [TEM] and X-ray diffraction showed that the improved electrical properties can be attributed to a consumption of the surface layer of SiC due to silicide (Pt2Si) formation. The degradation of Schottky characteristics at higher temperatures (up to 900°C) could be ascribed to the out-diffusion and aggregation of carbon into clusters, observed by TEM analysis.


Transthoracic vertebrectomy for metastatic spinal tumors.
Anterior approaches to the spine for the treatment of spinal tumors have gained acceptance; however, in most published reports, patients with primary, metastatic, or chest wall tumors involving cervical, thoracic, or lumbar regions of the spine are combined. The purpose of this study was to provide a clear perspective of results that can be expected in patients who undergo anterior vertebral body resection, reconstruction, and stabilization for spinal metastases that are limited to the thoracic region. Outcome is presented for 72 patients with metastatic spinal tumors who were treated by transthoracic vertebrectomy at The University of Texas M. D. Anderson Cancer Center. The predominant primary tumors included renal cancer in 19 patients, breast cancer in 10, melanoma or sarcoma in 10, and lung cancer in nine patients. The most common presenting symptoms were back pain, which occurred in 90% of patients, and lower-extremity weakness, which occurred in 64% of patients. All patients underwent transthoracic vertebrectomy, decompression, reconstruction with methylmethacrylate, and anterior fixation with locking plate and screw constructs. Supplemental posterior instrumentation was required in seven patients with disease involving the cervicothoracic or thoracolumbar junction, which was causing severe kyphosis. After surgery, pain improved in 60 of 65 patients. This improvement was found to be statistically significant (p < 0.001) based on visual analog scales and narcotic analgesic medication use. Thirty-five of the 46 patients who presented with neurological dysfunction improved significantly (p < 0.001) following the procedure. Thirty-three patients had weakness but could ambulate preoperatively. Seventeen of these 33 regained normal strength, 15 patients continued to have weakness, and one patient was neurologically worse postoperatively. Of the 13 preoperatively nonambulatory patients, 10 could walk after surgery and three were still unable to walk but showed improved motor function. Twenty-one patients had complications ranging from minor atelectasis to pulmonary embolism. The 30-day mortality rate was 3%. The 1-year survival rate for the entire study population was 62%. These results suggest that transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality.


BaCelLo: a balanced subcellular localization predictor.
The knowledge of the subcellular localization of a protein is fundamental for elucidating its function. It is difficult to determine the subcellular location for eukaryotic cells with experimental high-throughput procedures. Computational procedures are then needed for annotating the subcellular location of proteins in large scale genomic projects. BaCelLo is a predictor for five classes of subcellular localization (secretory pathway, cytoplasm, nucleus, mitochondrion and chloroplast) and it is based on different SVMs organized in a decision tree. The system exploits the information derived from the residue sequence and from the evolutionary information contained in alignment profiles. It analyzes the whole sequence composition and the compositions of both the N- and C-termini. The training set is curated in order to avoid redundancy. For the first time a balancing procedure is introduced in order to mitigate the effect of biased training sets. Three kingdom-specific predictors are implemented: for animals, plants and fungi, respectively. When distributing the proteins from animals and fungi into four classes, accuracy of BaCelLo reach 74% and 76%, respectively; a score of 67% is obtained when proteins from plants are distributed into five classes. BaCelLo outperforms the other presently available methods for the same task and gives more balanced accuracy and coverage values for each class. We also predict the subcellular localization of five whole proteomes, Homo sapiens, Mus musculus, Caenorhabditis elegans, Saccharomyces cerevisiae and Arabidopsis thaliana, comparing the protein content in each different compartment. BaCelLo can be accessed at http://www.biocomp.unibo.it/bacello/.


Development of classification models for identifying "true" P-glycoprotein (P-gp) inhibitors through inhibition, ATPase activation and monolayer efflux assays.
P-glycoprotein (P-gp) is an efflux pump involved in the protection of tissues of several organs by influencing xenobiotic disposition. P-gp plays a key role in multidrug resistance and in the progression of many neurodegenerative diseases. The development of new and more effective therapeutics targeting P-gp thus represents an intriguing challenge in drug discovery. P-gp inhibition may be considered as a valid approach to improve drug bioavailability as well as to overcome drug resistance to many kinds of tumours characterized by the over-expression of this protein. This study aims to develop classification models from a unique dataset of 59 compounds for which there were homogeneous experimental data on P-gp inhibition, ATPase activation and monolayer efflux. For each experiment, the dataset was split into a training and a test set comprising 39 and 20 molecules, respectively. Rational splitting was accomplished using a sphere-exclusion type algorithm. After a two-step (internal/external) validation, the best-performing classification models were used in a consensus predicting task for the identification of compounds named as "true" P-gp inhibitors, i.e., molecules able to inhibit P-gp without being effluxed by P-gp itself and simultaneously unable to activate the ATPase function.


Study protocol of a cluster randomised controlled trial investigating the effectiveness of a tailored energy balance programme for recent retirees.
People in transitional life stages, such as occupational retirement, are likely to gain weight and accumulate abdominal fat mass caused by changes in physical activity and diet. Hence, retirees are an important target group for weight gain prevention programmes, as described in the present paper. A systematic and stepwise approach (Intervention Mapping) is used to develop a low-intensity energy balance intervention programme for recent retirees. This one-year, low-intensity multifaceted programme aims to prevent accumulation of abdominal fat mass and general weight gain by increasing awareness of energy balance and influencing related behaviours of participants' preference. These behaviours are physical activity, fibre intake, portion size and fat consumption. The effectiveness of the intervention programme is tested in a cluster randomised controlled trial. Measurements of anthropometry, physical activity, energy intake, and related psychosocial determinants are performed at baseline and repeated at 6 months for intermediate effect, at 12 months to evaluate short-term intervention effects and at 24 months to test the sustainability of the effects. This intervention programme is unique in its focus on retirees and energy balance. It aims at increasing awareness and takes into account personal preferences of the users by offering several options for behaviour change. Moreover, the intervention programme is evaluated at short-term and long-term and includes consecutive outcome measures (determinants, behaviour and body composition).


May Measurement Month 2017: the results of blood pressure screening of 14 845 individuals in Kenya-Sub-Saharan Africa.
Elevated blood pressure (BP) is a growing burden worldwide leading to over 10 million deaths each year. Sub-Saharan Africa has the highest age-adjusted prevalence of hypertension. In Kenya, 24.5% of adults have elevated BP with lack of awareness being the main barrier to achieving satisfactory control rates. May Measurement Month (MMM17) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Screening was coordinated by the Kenya Cardiac Society in 17 sites across the country. Blood pressure measurements, the definition of hypertension and statistical analysis followed the standard MMM protocol. A total of 14 847 individuals were screened. After multiple imputation, 3647 (24.6%) had hypertension. Of individuals not receiving any antihypertensive medication, 2019 (15.3%) were hypertensive. Of individuals receiving antihypertensive medication, 740 (45.5%) had uncontrolled BP. Being diabetic and having a body mass index (BMI) ≥25 kg/m2 were associated with higher BP. Lack of awareness and poor control in those identified is a major challenge in Kenya. The MMM project demonstrated that mass screening for elevated BP is feasible, even in settings with limited resources. The presence of hypertension in a quarter of Kenyan adults with poor awareness and control rates demonstrates the need for programmes to raise awareness in the community.


Determinants of male Aedes aegypti and Aedes polynesiensis (Diptera: Culicidae) response to sound: efficacy and considerations for use of sound traps in the field.
Understanding the mating competitiveness of male mosquitoes in field settings is essential to programs relying on the mass release of modified male mosquitoes, yet studies on male ecology have been hampered by the lack of a convenient trapping method. An existing promising method makes use of the innate attraction of males to female flight tones. Here, we present laboratory, greenhouse, and field experiments on the efficacy of sound traps for the collection of Aedes aegypti (L.) and Aedes polynesiensis Marks, and laboratory experiments with Ae. aegypti on the effects of male age, size, and mating status on responsiveness to a range of frequencies. Age and mating status influenced the overall responsiveness to sound, whereas male size did not. There were no interactions between these factors and sound frequency. A Centers for Disease Control and Prevention miniature light trap modified to produce a tone of 465 Hz collected 76.2% of Ae. aegypti males in laboratory cages, and 49.7% of males in a greenhouse enclosure. In two sets of experiments in laboratory cages, 50.8 and 46.5% of male Ae. polynesiensis were captured with a trap producing a tone of 440 Hz. In the field, CDC miniature light traps or BG-Sentinel traps fitted with a portable speaker producing tones of 440 or 465 Hz captured significantly more male Ae. polynesiensis when placed near a male swarm than did traps that did not produce sound. When the trap was placed at a distance of 16.5 m from the nearest swarm, there was no significant difference in the number of males caught between control and sound-producing traps. The numbers of Ae. aegypti males captured were low under all circumstances in the field.