Effectiveness of Day Hospital Mentalization-Based Treatment for Patients with Severe Borderline Personality Disorder: A Matched Control Study.
The present study extends the body of evidence regarding the effectiveness of day hospital Mentalization-Based Treatment (MBT) by documenting the treatment outcome of a highly inclusive group of severe borderline personality disorder (BPD) patients, benchmarked by a carefully matched group who received other specialized psychotherapeutic treatments (OPT). Structured diagnostic interviews were conducted to assess diagnostic status at baseline. Baseline, 18-month treatment outcome and 36-month treatment outcome (after the maintenance phase) on psychiatric symptoms (Brief Symptom Inventory) and personality functioning (118-item Severity Indices of Personality Problems) were available for 29 BPD patients assigned to MBT, and an initial set of 175 BPD patients assigned to OPT. Propensity scores were used to determine the best matches for the MBT patients within the larger OPT group, yielding 29 MBT and 29 OPT patients for direct comparison. Treatment outcome was analysed using multilevel modelling. Pre to post effect sizes were consistently (very) large for MBT, with a Cohen's d of -1.06 and -1.42 for 18 and 36 months, respectively, for the reduction in psychiatric symptoms, and ds ranging from 0.81 to 2.08 for improvement in domains of personality functioning. OPT also yielded improvement across domains but generally of moderate magnitude. In conclusion, the present matched control study, executed by an independent research institute outside the UK, demonstrated the effectiveness of day hospital MBT in a highly inclusive and severe group of BPD patients, beyond the benchmark provided by a mix of specialized psychotherapy programmes. Interpretation of the (large) between condition effects warrants cautionary caveats given the non-randomized design, as well as variation in treatment dosages.


Comparative Evaluation of Quality and Metabolite Profiles in Meju Using Starter Cultures of Bacillus velezensis and Aspergillus oryzae.
The production of good Meju soybean paste primarily depends on the selection of raw materials and fermenting microorganisms, which together influence its characteristic metabolites, taste, and aroma. In this study, we analyzed the relationship between properties and metabolites in Meju samples fermented by Aspergillus oryzae alone or with Bacillus velezensis. We developed fast-stable processing techniques to obtain Meju from A. oryzae and B. velezensis using the inoculation method, thereby ensuring safety in the production of soybean paste. The amino-type nitrogen content increased from an initial 180-228 mg% to a final 226-776 mg% during fermentation and was higher in Meju inoculated separately with the fungi and bacteria (C group) than in Meju co-inoculated with both the starters concurrently (D group). The levels of metabolites such as glucose, myo-inositol, glycerol, and fatty acids (palmitic, stearic, oleic, and linoleic acids) in Meju fermented by A. oryzae with B. velezensis were higher than those in Meju fermented by A. oryzae alone. Fungal growth was affected by the inoculated bacteria, which often occurs during the fermentation of co-inoculated Meju.


From body form to biological motion: the apparent velocity of human movement biases subjective time.
In two experiments, we investigated time perception during apparent biological motion. Pictures of initial, intermediate, and final positions of a single movement were presented, with interstimulus intervals that were constant within trials but varied across trials. Movement paths were manipulated by changing the sequential order of body postures. Increasing the path length produced an increase in perceived movement velocity. To produce an implicit measure of apparent movement dynamics, we also asked participants to judge the duration of a frame surrounding the stimuli. Longer paths with higher apparent movement velocity produced shorter perceived durations. This temporal bias was attenuated for nonbody (Experiment 1) and inverted-body (Experiment 2) control stimuli. As an explanation for these findings, we propose an automatic top-down mechanism of biological-motion perception that binds successive body postures into a continuous perception of movement. We show that this mechanism is associated with velocity-dependent temporal compression. Furthermore, this mechanism operates on-line, bridging the intervals between static stimuli, and is specific to configural processing of body form.


Contribution of frontostriatal function to sequence learning in Parkinson's disease: evidence for dissociable systems.
The frontostriatal system appears to play a crucial role in the organization and execution of sequential behaviour, but the precise nature of its contribution remains to be specified. From this perspective, relatively simple modifications of behavioural task parameters may invoke rather profound changes in the recruitment of appropriate neural mechanisms, including the frontostriatal system. This mini-review examines how variations in task requirements for sequence learning and related cognitive tasks can induce significant modifications in the performance of patients with Parkinson's disease. In particular, these observations are used to support a developing argument for neurophysiologically dissociable sequence learning systems in man. One of these mechanisms is sensitive to surface structure, or element-by-element sequence organization, and appears to rely on the frontostriatal system. Another sequence learning mechanism is sensitive to abstract structure, or relationships between repeating sequence elements, and appears to be largely independent of the frontostriatal system.


Distinguishing between overdrive excited and suppressed ventricular beats in guinea pig ventricular myocardium.
Rapid ventricular pacing rates induces two types of beats following pacing cessation: recovery cycle length (RCL) prolongation (overdrive suppression) and RCL shortening (overdrive excitation). The goals of this study were to compare common experimental protocols for studying triggered activity in whole-heart preparations and differentiate between recovery beats using a new methodology. Post-pacing recovery beat cycle length (RCL) and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced suppressed beats: RCL ratio increased with rapid pacing (25 ± 4.0%, n = 10) without changing QRS duration. Rapid pacing during hypercalcemia + hypothermia (5.5 mM and 34°C) produced significantly earlier excited beats (53 ± 14%, n = 5) with wider QRS durations (58 ± 6.3%, n = 5) than suppressed beats. Digoxin + hypothermia (0.75 μM) produced the most excited beats with significantly earlier RCL (44 ± 3.2%, n = 6) and wider QRS (60 ± 3.1%, n = 6) ratios relative to suppressed beats. Increasing pacing further shortened RCL (30 ± 7.8%, n = 6). In a prospective study, TTX (100 nM) increased RCL ratio (15 ± 6.0%, n = 10) without changing the QRS duration of excited beats. The algorithm was compared to a cross-correlation analysis with 93% sensitivity and 94% specificity. This ECG based algorithm distinguishes between triggered and automatic activity.


Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma.
The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. Concentrations of galectin-3, TNF-α, TGF-β, IL-10, and IL-1β were analyzed in samples of blood and stool of 60 patients with CRC. Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-β and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.


Changes in antipsychotic medication in clients of assertive community treatment in Japan: a one-year follow up.
The purpose of the present one-year follow-up study was to describe and investigate the change in the amount of antipsychotic drugs prescribed for ACT (assertive community treatment) clients in Japan. Subjects were 52 clients of ACT from January 2009 to December 2009. Prescription data were collected each month from the time the clients entered into ACT. The results of a Wilcoxon signed-rank test show that the dosage of antipsychotics significantly decreased from 1,131.3 mg to 731.3 mg over the course of the 12 months (Z = -2.505, p = 0.012).


Prospective versus retrospective ECG-gated 64-detector coronary CT angiography: assessment of image quality, stenosis, and radiation dose.
To show that prospective electrocardiographically (ECG)-triggered coronary computed tomographic (CT) angiography (hereafter, prospective CT angiography) is at least as effective as retrospective ECG-gated coronary CT angiography (hereafter, retrospective CT angiography). Institutional review committee approval and informed consent were obtained. Sixty patients with heart rates of less than 75 beats per minute who were referred for coronary CT angiography were enrolled. Both prospective and retrospective CT angiography were performed with a 64-detector scanner. Data acquisition times were recorded. Two independent cardiac radiologists evaluated subjective image quality (1, excellent; 4, poor) and severity of stenosis (0% occlusion, 1%-49% occlusion, 50%-75% occlusion, and >75% occlusion) with the 17-segment American Heart Association classification model. Discrepancies were settled by consensus. Effective radiation doses of prospective and retrospective CT angiography were calculated with volume CT dose index. Data regarding acquisition time and radiation exposure for prospective and retrospective CT angiography were compared. The Student t test was performed, and kappa statistics were calculated. Mean data acquisition time of prospective CT angiography was shorter than that of retrospective CT angiography (5.6 seconds +/- 1.1 [standard deviation] vs 6.7 seconds +/- 1.1, respectively; P < .01). Consensus-determined image quality in coronary artery branches was similar between prospective CT angiography and retrospective CT angiography (1.15 vs 1.13, respectively; P = .992). Excellent agreement between prospective CT angiography and retrospective CT angiography was observed in the detection of significant (>or=50% occlusion) coronary artery stenoses per segment (kappa = 0.882) and in the grading of stenoses per patient (kappa = 0.829). Calculated effective dose with prospective CT angiography was 79% lower than that with retrospective CT angiography (4.1 mSv +/- 1.8 vs 20.0 mSv +/- 3.5, respectively; P < .001). Prospective CT angiography can reduce radiation dose below that of retrospective CT angiography with dose modulation, while maintaining image quality and the ability to assess luminal obstructions in patients with heart rates of less than 75 beats per minute.


Productivity-adjusted life-years and correlates of uncontrolled hypertension at two health facilities in Zambia.
Hypertension has in the recent past surfaced as one of the conditions that has a significant impact on workforce productivity in emerging economies. Zambia is no different and has in the recent past recorded increasing cases. Despite the impact of hypertension being of great importance in regards to productivity, we have scarcity of data and studies on hypertension-related Productivity-Adjusted Life-Years (PALYs) in Zambia and Africa at large. This study assessed the impact of hypertension on PALYs lost and socioeconomic factors associated with nonadherence to antihypertensive medication (NATAM). This was a cross-sectional study of 198 participants from Livingstone University Teaching Hospital and Maramba Clinic situated in Livingstone, Zambia. Structured questionnaires were used to collect data. Productivity index multiplied by years lived was used to calculate PALYs and descriptive statistics were used to summarize sociodemographic, clinical and economic variables. Multivariable logistic regression was used to determine factors associated with NATAM. The participants had a median age (interquartile range (IQR)) of 49 years (41, 59) and 60.1% (n = 119) were females while 39.9% (n = 79) were male. Our estimated PALYs lost per person due to hypertension were 0.2 (IQR 0.0, 2.7). Cumulative PALYs value lost due to the burden of hypertension was estimated to be at $871,239.58 in gross domestic product (GDP). The prevalence of NATAM was 48% (n = 95). The factors that were significantly associated with NATAM were age (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.90, 0.98), female sex (OR 2.52; 95%CI 1.18, 5.40), self-employment (OR 2.57; 95%CI 1.02, 6.45) and absenteeism from work (OR 3.60; 95%CI 1.16, 11.22). Findings in our study highlight a high economic loss of PALYs due to hypertension with a potential to impact GDP negatively. We also found that NATAM reduced productivity and income among individuals of working age further impacting PALYs lost due to hypertension. The factors associated with NATAM were age, sex, employment status and absenteeism from work. This study underscores the need for interventions targeting young people, females, self-employed individuals, and absentees at work to improve adherence to antihypertensive drugs in order to reduce PALYs lost due to hypertension.


Infliximab as rescue medication for patients with severe ulcerative/indeterminate colitis refractory to tacrolimus.
The calcineurin inhibitor tacrolimus and the anti-TNF-antibody infliximab are established options in steroid-refractory ulcerative colitis (UC). To evaluate the efficacy of infliximab-salvage therapy in patients with refractory UC failing to respond to tacrolimus. Twenty-four patients were enrolled in this evaluation. Reasons for tacrolimus therapy were steroid-refractory disease in 19 patients and steroid-dependency in five patients. All patients receiving infliximab had tacrolimus-refractory active disease (Lichtiger score >10) and were treated with 5 mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter, if tolerated. Six of 24 patients (25%) achieved remission following infliximab infusion and four of 24 (17%) had an initial response only, but underwent proctocolectomy later because of loss of response (3) or development of a delayed hypersensitivity reaction (1). Fourteen patients (58%) completely failed to respond with 10 undergoing colectomy. Eight patients experienced side effects under infliximab, including two infectious complications (herpes zoster and herpes pneumonia). Infliximab offers a therapeutic option as rescue therapy in about a quarter of patients with active UC after failing to respond to tacrolimus. This benefit has to be weighed against the risks of infectious complications.


The effect of piezoelectric ultrasonic instrumentation on titanium discs: a microscopy and trace elemental analysis in vitro study.
To evaluate in vitro topographical and composition changes by piezoelectric ultrasonic instrumentation with metallic and plastic tips on machined and moderately roughened titanium surfaces. Twenty machined and moderately roughened laser-marked titanium discs were ultrasonically instrumented with metallic and plastic tips. Surface instrumentation was carried out with controlled pressure for 20 and 30 seconds at two power settings. For each time and power setting, instrumentation was repeated four times with one instrumentation per disc quadrant. Surface topography analysis was performed using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Surface roughness measurements were compared between instrumented and non-instrumented surfaces. Surface element composition and rinsing solutions were evaluated using energy-dispersive spectroscopy (EDS) and trace elemental analysis using inductively coupled plasma mass spectrometry (ICPMS), respectively. SEM photomicrographs and CLSM 3D surface plot images of instrumented machined and moderately roughened surfaces demonstrated severe surface topographical alterations with metallic tips and mild to moderate changes for plastic tip instrumented sites. ICPMS analysis of the rinsing solutions identified titanium and other metal traces with the use of metallic tips, and mainly titanium and carbon when plastic tips were used. Surface EDS analysis showed elemental traces of the ultrasonic tips. Ultrasonic instrumentation with metallic or plastic tips created surface topographical and compositional changes. Different changes in surface topography were noted between the surfaces, as the roughness of the machined surfaces increased while the extent of roughness of the moderately roughened surfaces decreased. The clinical relevance of these changes is yet to be determined.


Here and there: a preliminary note on the prevalence of an alien rhizocephalan parasite at the southern and northern limits of its introduced range.
The Erythrean invasive swimming crab Charybdis longicollis established dense populations in the Levantine Basin of the Mediterranean Sea in the mid 20th century. The crabs were subsequently parasitized by the rhizocephalan Heterosaccus dollfusi , itself an Erythrean alien. In May 2008, the crab populations were sampled at the southern (Israel) and northern (Turkey) limits of its introduced range. The prevalence of infection was 3 times as high, and multiple externae-bearing hosts more than 4 times as many, in Israeli waters as in Turkey. It seems that off the Israeli coast, the water temperature permits the synchronous ontogenetic development of both host and parasite, ensuring the availability of plentiful young, recently-molted, prospective hosts for infection by the short-lived parasite cypris. It is possible that the lower water temperature off Antalya (Turkey) may affect the timing of ontogenetic development of one species or the other, or increase the mortality of infected hosts, resulting in drastically reduced parasite prevalence.


Is Aspiration Thrombectomy Beneficial in Patients Undergoing Primary Percutaneous Coronary Intervention? Meta-Analysis of Randomized Trials.
It is unclear whether intravenous glycoprotein IIb/IIIa inhibitors or ischemic time might modify any clinical benefits observed with aspiration thrombectomy before primary percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction. Electronic databases were searched for trials that randomized ST-segment-elevation myocardial infarction patients to aspiration thrombectomy before PCI versus conventional PCI. Summary estimates were constructed using a DerSimonian-Laird model. Seventeen trials with 20 960 patients were available for analysis. When compared with conventional PCI, aspiration thrombectomy was not associated with a significant reduction in the risk of mortality 2.8% versus 3.2% (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.76-1.04; P=0.13), reinfarction 1.3% versus 1.4% (RR, 0.93; 95% CI, 0.73-1.17; P=0.52), the combined outcome of mortality or reinfarction 4.1% versus 4.6% (RR, 0.90; 95% CI, 0.79-1.02; P=0.11), or stent thrombosis 0.9% versus 1.2% (RR, 0.82; 95% CI, 0.62-1.08; P=0.15). Aspiration thrombectomy was associated with a nonsignificant increase in the risk of stroke 0.6% versus 0.4% (RR, 1.45; 95% CI, 0.96-2.21; P=0.08). Meta-regression analysis did not identify a difference for the log RR of mortality, reinfarction, and the combined outcome of mortality or reinfarction with intravenous glycoprotein IIb/IIIa inhibitors (P=0.17, 0.70, and 0.50, respectively) or with ischemic time (P=0.29, 0.66, and 0.58, respectively). Aspiration thrombectomy before primary PCI is not associated with any benefit on clinical end points and might increase the risk of stroke. Concomitant administration of intravenous glycoprotein IIb/IIIa inhibitors and ischemic time did not seem to influence any potential benefits observed with aspiration thrombectomy.


Regional frequency analysis of short duration rainfall extremes using gridded daily rainfall data as co-variate.
A regional partial duration series (PDS) model is applied for estimation of intensity duration frequency relationships of extreme rainfalls in Denmark. The model uses generalised least squares regression to relate the PDS parameters to gridded rainfall statistics from a dense network of rain gauges with daily measurements. The Poisson rate is positively correlated to the mean annual precipitation for all durations considered (1 min to 48 hours). The mean intensity can be assumed constant over Denmark for durations up to 1 hour. For durations larger than 1 hour, the mean intensity is significantly correlated to the mean extreme daily precipitation. A Generalised Pareto distribution with a regional constant shape parameter is adopted. Compared to previous regional studies in Denmark, a general increase in extreme rainfall intensity for durations up to 1 hour is found, whereas for larger durations both increases and decreases are seen. A subsample analysis is conducted to evaluate the impacts of non-stationarities in the rainfall data. The regional model includes the non-stationarities as an additional source of uncertainty, together with sampling uncertainty and uncertainty caused by spatial variability.


Iterative User Interface Design for Automated Sequential Organ Failure Assessment Score Calculator in Sepsis Detection.
The new sepsis definition has increased the need for frequent sequential organ failure assessment (SOFA) score recalculation and the clerical burden of information retrieval makes this score ideal for automated calculation. The aim of this study was to (1) estimate the clerical workload of manual SOFA score calculation through a time-motion analysis and (2) describe a user-centered design process for an electronic medical record (EMR) integrated, automated SOFA score calculator with subsequent usability evaluation study. First, we performed a time-motion analysis by recording time-to-task-completion for the manual calculation of 35 baseline and 35 current SOFA scores by 14 internal medicine residents over a 2-month period. Next, we used an agile development process to create a user interface for a previously developed automated SOFA score calculator. The final user interface usability was evaluated by clinician end users with the Computer Systems Usability Questionnaire. The overall mean (standard deviation, SD) time-to-complete manual SOFA score calculation time was 61.6 s (33). Among the 24% (12/50) usability survey respondents, our user-centered user interface design process resulted in >75% favorability of survey items in the domains of system usability, information quality, and interface quality. Early stakeholder engagement in our agile design process resulted in a user interface for an automated SOFA score calculator that reduced clinician workload and met clinicians' needs at the point of care. Emerging interoperable platforms may facilitate dissemination of similarly useful clinical score calculators and decision support algorithms as "apps." A user-centered design process and usability evaluation should be considered during creation of these tools.


The thyroid hormone receptor gene (c-erbA alpha) is expressed in advance of thyroid gland maturation during the early embryonic development of Xenopus laevis.
The c-erbA proto-oncogene encodes the thyroid hormone receptor, a ligand-dependent transcription factor which plays an important role in vertebrate growth and development. To define the role of the thyroid hormone receptor in developmental processes, we have begun studying c-erbA gene expression during the ontogeny of Xenopus laevis, an organism in which thyroid hormone has well-documented effects on morphogenesis. Using polymerase chain reactions (PCR) as a sensitive assay of specific gene expression, we found that polyadenylated erbA alpha RNA is present in Xenopus cells at early developmental stages, including the fertilized egg, blastula, gastrula, and neurula. By performing erbA alpha-specific PCR on reverse-transcribed RNAs from high-density sucrose gradient fractions prepared from early-stage embryos, we have demonstrated that these erbA transcripts are recruited to polysomes. Therefore, erbA is expressed in Xenopus development prior to the appearance of the thyroid gland anlage in tailbud-stage embryos. This implies that erbA alpha/thyroid hormone receptors may play ligand-independent roles during the early development of X. laevis. Quantitative PCR revealed a greater than 25-fold range in the steady-state levels of polyadenylated erbA alpha RNA across early stages of development, as expressed relative to equimolar amounts of total embryonic RNA. Substantial increases in the levels of erbA alpha RNA were noted at stages well after the onset of zygotic transcription at the mid-blastula transition, with accumulation of erbA alpha transcripts reaching a relative maximum in advance of metamorphosis. We also show that erbA alpha RNAs are expressed unequally across Xenopus neural tube embryos. This differential expression continues through later stages of development, including metamorphosis. This finding suggests that erbA alpha/thyroid hormone receptors may play roles in tissue-specific processes across all of Xenopus development.


Protein disulfide isomerase like 1-1 participates in the maturation of proglutelin within the endoplasmic reticulum in rice endosperm.
The rice esp2 mutation was previously characterized by the abnormal accumulation of elevated levels of proglutelin and the absence of an endosperm-specific protein disulfide isomerase like (PDIL1-1). Here we show that Esp2 is the structural gene for PDIL1-1 and that this lumenal chaperone is asymmetrically distributed within the cortical endoplasmic reticulum (ER) and largely restricted to the cisternal ER. Temporal studies indicate that PDIL1-1 is essential for the maturation of proglutelin only when its rate of synthesis significantly exceeds its export from the ER, a condition resulting in its build up in the ER lumen and the induction of ER quality control processes which lower glutelin levels as well as those of the other storage proteins. As proglutelin is initially synthesized on the cisternal ER, its deposition within prolamine protein bodies in esp2 suggests that PDIL1-1 helps retain proglutelin in the cisternal ER lumen until it attains competence for ER export and, thereby, indirectly preventing heterotypic interactions with prolamine polypeptides.


Fluoxetine treatment during the postpartal period may have short-term impacts on murine maternal skeletal physiology.
Postpartum depression affects many individuals after parturition, and selective serotonin reuptake inhibitors (SSRIs) are often used as the first-line treatment; however, both SSRIs and lactation are independently associated with bone loss due to the role of serotonin in bone remodeling. Previously, we have established that administration of the SSRI fluoxetine during the peripartal period results in alterations in long-term skeletal characteristics. In the present study, we treated mice with either a low or high dose of fluoxetine during lactation to determine the consequences of the perturbation of serotonin signaling during this time period on the dam skeleton. We found that lactational fluoxetine exposure affected both cortical and trabecular parameters, altered gene expression and circulating markers of bone turnover, and affected mammary gland characteristics, and that these effects were more pronounced in the dams that were exposed to the low dose of fluoxetine in comparison to the high dose. Fluoxetine treatment during the postpartum period in rodents had short term effects on bone that were largely resolved 3 months post-weaning. Despite the overall lack of long-term insult to bone, the alterations in serotonin-driven lactational bone remodeling raises the question of whether fluoxetine is a safe option for the treatment of postpartum depression.


Air-Stable Na x TMO2 Cathodes for Sodium Storage.
Sodium-ion batteries are considered to be the most promising alternative to lithium-ion batteries for large-scale stationary energy storage applications due to the abundant sodium resource in the Earth' crust and as a result, relatively low cost. Sodium layered transition metal oxides (Na x TMO2) are proper Na-ion cathode materials because of low cost and high theoretical capacity. Currently most researchers focus on the improvement of electrochemical performance such as high rate capability and long cycling stability. However, for Na x TMO2, the structure stability against humid atmosphere is essentially important since most of them are instable in air, which is not favorable for practical application. Here we provide a comprehensive review of recent progresses on air-stable Na x TMO2 oxides. Several effective strategies are discussed, and further investigations on the air-stable cathodes are prospected.


Robotic Nudges: The Ethics of Engineering a More Socially Just Human Being.
Robots are becoming an increasingly pervasive feature of our personal lives. As a result, there is growing importance placed on examining what constitutes appropriate behavior when they interact with human beings. In this paper, we discuss whether companion robots should be permitted to "nudge" their human users in the direction of being "more ethical". More specifically, we use Rawlsian principles of justice to illustrate how robots might nurture "socially just" tendencies in their human counterparts. Designing technological artifacts in such a way to influence human behavior is already well-established but merely because the practice is commonplace does not necessarily resolve the ethical issues associated with its implementation.


Evidence against the presence of tight junctions in normal endocrine pancreas.
Tight junctional fibrils were absent in freeze-fracture replicas of rat and human islets in situ, but were easily discerned in collagenase-isolated islets. Disruption of the pancreatic gland and its exposure to trypsin were each found to induce tight junction formation in rat islets. The amount of tight junctions between islet cells declined progressively during culture, but tight junctional structures remained detectable after 1 day of culture. It is suggested that rather than being involved in normal islet cell function tight junctions provide an adaptive mechanism intended to seal and hence to protect islet microdomains against sudden perturbations in local interstitial fluid.


Next-generation dynamic global vegetation models: learning from community ecology.
Dynamic global vegetation models (DGVMs) are powerful tools to project past, current and future vegetation patterns and associated biogeochemical cycles. However, most models are limited by how they define vegetation and by their simplistic representation of competition. We discuss how concepts from community assembly theory and coexistence theory can help to improve vegetation models. We further present a trait- and individual-based vegetation model (aDGVM2) that allows individual plants to adopt a unique combination of trait values. These traits define how individual plants grow and compete. A genetic optimization algorithm is used to simulate trait inheritance and reproductive isolation between individuals. These model properties allow the assembly of plant communities that are adapted to a site's biotic and abiotic conditions. The aDGVM2 simulates how environmental conditions influence the trait spectra of plant communities; that fire selects for traits that enhance fire protection and reduces trait diversity; and the emergence of life-history strategies that are suggestive of colonization-competition trade-offs. The aDGVM2 deals with functional diversity and competition fundamentally differently from current DGVMs. This approach may yield novel insights as to how vegetation may respond to climate change and we believe it could foster collaborations between functional plant biologists and vegetation modellers.


The relationship of race/ethnicity and social class to hormone replacement therapy: results from the Third National Health and Nutrition Examination Survey 1988-1994.
To use a nationally representative sample to examine the prevalence of hormone replacement therapy (HRT) use and its relationship to different markers of social class in American women 60 years of age and older. Nationally representative cross-sectional survey with an in-person interview and medical examination. Between 1988 and 1994, 3,479 women aged 60 to 90+ years were examined as part of the National Health and Nutrition Examination Survey III. Mexican Americans, non-Hispanic blacks and much older women were oversampled to produce reliable estimates for these groups. Overall, the number of women who reported ever having used HRT was 37% [confidence interval (CI), 33%-40%] of all women older than 60 years of age; 40% (CI, 37%-41%) of older, non-Hispanic white women; 20% (CI, 14%-25%) of non-Hispanic black women; and 24% (CI, 20%-29%) of Mexican American women. HRT was used by 43% (CI, 38%-47%) of women 60 to 70 years old, 37% (CI, 32%-41%) of those 71 to 80 years old, and 20% (CI, 13%-26%) of women older than 80. HRT use was lowest among women who did not complete high school or among those in the lowest family income categories. Among women more than 60 years old who reported having a hysterectomy, 51% (CI, 47%-55%) reported using HRT, whereas only 20% (CI, 17%-23%) of those who had a natural menopause reported using HRT. Although many women can benefit from HRT, the number of American women who report they have ever used it remains low. More research is needed to examine the implications of racial differences in compliance, patient and physician attitudes toward HRT, and possible environmental barriers that may prevent use.


Immersive Virtual Reality for Pediatric Procedural Pain: A Randomized Clinical Trial.
Pain management in children often is inadequate, and the single most common painful procedure in children who are hospitalized is needle procedures. Virtual reality (VR) is a promising and engaging intervention that may help to decrease anxiety and pain in children undergoing painful procedures. Our aim for this study is to investigate patient satisfaction and pain reduction by using a three-dimensional VR interactive game as a distraction. In this randomized clinical trial, we enrolled 64 children aged 7 to 16 years who were scheduled for venous cannulation. Patients assigned to the control group were adherent to our standard of care, including topical numbing cream, positioning, and distraction by a specialized pain nurse. In the study group, children were adherent to the standard of care and were distracted by an interactive VR game. Primary outcomes were patient satisfaction and the procedural pain assessed by using a visual analog score; secondary outcomes were the procedural time and any adverse events. We found a high level of patient satisfaction with using the VR custom-made three-dimensional interactive game. All children (28 of 28 [100%]) in the VR group answered that they would prefer VR as a distraction for a later procedure, a borderline significant result compared with that of the control group (26 of 31 [84.9%]). No significant difference was found in pain scores and procedural times between the 2 groups. The number of adverse effects was low, with no significant difference between the 2 groups. We found no difference in pain scores but higher satisfaction when using VR versus standard care as part of a multimodal approach for management of procedural pain in children.


Critical thinking in nursing education: literature review.
The need for critical thinking in nursing has been accentuated in response to the rapidly changing health-care environment. Nurses must think critically to provide effective care while coping with the expansion in role associated with the complexities of current health-care systems. This literature review will present a history of inquiry into critical thinking and research to support the conclusion that critical thinking is necessary not only in the clinical practice setting, but also as an integral component of nursing-education programmes to promote the development of nurses' critical-thinking abilities. The aims of this paper are to: (i) review the literature on critical thinking; (ii) examine the dimensions of critical thinking; (iii) investigate the various critical thinking strategies for their appropriateness to enhance critical thinking in nurses; and (iv) examine issues relating to the evaluation of critical-thinking skills in nursing.


Distinct patterns of matrix metalloproteinase-2 and -9 expression in normal human cell lines.
Invasion of surrounding tissues by malignant cells is a complex process mediated by the matrix degrading enzymes. In many solid tumors, the expression of MMPs, especially MMP-2 and MMP-9, is higher in stromal cells than in the tumor cells, suggesting stromal cells as the major source of these enzymes. Cytokines and signal transduction pathways, including those activated by phorbol 12-myristate 13-acetate (PMA), regulate the expression of MMPs. The aim of this study was to examine the pattern of MMP-2 and MMP-9 expression in human normal cells and in PMA-treated cells to determine if specific patterns of expression were associated with tissues of different origin. Epithelial, connective, and muscle tissues were selected since carcinomas, sarcomas, and adenosarcomas are derived from these tissue types, respectively. The cell lines were cultured in their recommended media and supplemented with 10% FBS and antibiotics in 24-well tissue culture plates. At near confluence, the cells were washed and fresh medium added. A parallel set of cultures was treated with PMA. After 24 h of incubation, media were collected and analyzed for MMP-2 and MMP-9 by gelatinase zymography. The results indicate that the normal cell expression of MMP-2 and MMP-9 depends on their primary tissue subtype. All cell lines, regardless of tissue origin, expressed MMP-2. PMA induced MMP-9 expression in glandular epithelia, supportive connective tissue, and muscle tissue cell lines. However, cell lines of endothelial origin and proper connective tissue were insensitive to PMA. These results suggest that MMP-2 and MMP-9 are differentially regulated and an understanding of this may open up avenues to use these enzymes as targets for therapy.


Postoperative Outcomes in Graves' Disease Patients: Results from the Nationwide Inpatient Sample Database.
Current surgical indications for Graves' disease include intractability to medical and/or radioablative therapy, compressive symptoms, and worsening ophthalmopathy. Total thyroidectomy for Graves' disease may be technically challenging and lead to untoward perioperative outcomes. This study examines outcomes in patients with Graves' disease who underwent total thyroidectomy and assesses its safety for this patient population. A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample database from 2006 to 2011. Total thyroidectomy performed in patients with Graves' disease, benign multinodular goiter (MNG), and thyroid cancer was identified. Demographic factors, comorbidities, and postoperative complications were evaluated. Chi-square, one-way analysis of variance, and risk-adjusted multivariable logistic regression were performed. Of 215,068 patients who underwent total thyroidectomy during the study period, 11,205 (5.2%) had Graves' disease, 110,124 (51.2%) MNG, and 93,739 (43.6%) thyroid malignancy. Patients with Graves' disease were younger than MNG and thyroid cancer patients (Mage = 42.8 years vs. 55.5 and 51.0 years; p < 0.01). The Graves' disease group included a higher proportion of women (p < 0.01) and nonwhites (p < 0.01). Postoperatively, Graves' patients had significantly higher rates of hypocalcemia (12.4% vs. 7.3% and 10.3%; p < 0.01), hematomas requiring reoperation (0.7% vs. 0.4% and 0.4%; p < 0.01), and longer mean hospital stay (2.7 days vs. 2.4 and 2.2 days; p < 0.01) compared to MNG and thyroid cancer patients, respectively. On risk-adjusted multivariate logistic regression, Graves' disease was independently associated with a higher risk of vocal-cord paralysis (odds ratio [OR] = 1.36 [confidence interval (CI) 1.08-1.69]), tracheostomy (OR = 1.35 [CI 1.1-1.67]), postoperative hypocalcemia (OR = 1.65 [CI 1.54-1.77]), and hematoma requiring reoperation (OR = 2.79 [CI 2.16-3.62]) compared to MNG patients. High-volume centers for total thyroidectomy were independently associated with lower risk of postoperative complications, including in patients with Graves' disease. Despite low overall morbidity following total thyroidectomy, Graves' disease patients are at increased risk of postoperative complications, including bleeding, vocal-cord paralysis, tracheostomy, and hypocalcemia. These risks appear to be lower when performed at high-volume centers, and thus referral to these centers should be considered. Total thyroidectomy may therefore be a safe treatment option for appropriately selected patients with Graves' disease when performed by experienced surgeons.


Genetic background modulates phenotypic expressivity in OPA1 mutated mice, relevance to DOA pathogenesis.
Dominant optic atrophy (DOA) is mainly caused by OPA1 mutations and is characterized by the degeneration of retinal ganglion cells (RGCs), whose axons form the optic nerve. The penetrance of DOA is incomplete and the disease is marked by highly variable expressivity, ranging from asymptomatic patients to some who are totally blind or who suffer from multisystemic effects. No clear genotype-phenotype correlation has been established to date. Taken together, these observations point toward the existence of modifying genetic and/or environmental factors that modulate disease severity. Here, we investigated the influence of genetic background on DOA expressivity by switching the previously described DOA mouse model bearing the c.1065 + 5G → A Opa1 mutation from mixed C3H; C57BL/6 J to a pure C57BL/6 J background. We no longer observed retinal and optic nerve abnormalities; the findings indicated no degeneration, but rather a sex-dependent negative effect on RGC connectivity. This highlights the fact that RGC synaptic alteration might precede neuronal death, as has been proposed in other neurodegenerative diseases, providing new clinical considerations for early diagnosis as well as a new therapeutic window for DOA. Furthermore, our results demonstrate the importance of secondary genetic factors in the variability of DOA expressivity and offer a model for screening for aggravating environmental and genetic factors.


Interaction of pre and postnatal nutrition on expression of leptin receptor variants and transporter molecules, leptin transport, and functional response to leptin in heifers†.
Perinatal nutrition modulates the hypothalamic neurocircuitries controlling GnRH release, thus programming pubertal maturation in female mammals. Objectives of experiments reported here were to test the hypotheses that prenatal nutrition during mid- to late gestation interacts with postnatal nutrition during the juvenile period in heifer offspring to alter expression of leptin receptor (LepR) variants (ObRa, ObRb, ObRc, ObRt), and lipoprotein transporter molecules (LRP1 and 2) in the choroid plexus, leptin transport across the blood-brain barrier, and hypothalamic-hypophyseal responsiveness to exogenous ovine leptin (oleptin) during fasting. Nutritional programming of heifers employed a 3 x 2 factorial design of maternal (High, H; Low, L; and Moderate, M) x postnatal (H and L) dietary treatments. Results (Expt. 1) demonstrated that prepubertal heifers born to L dams, regardless of postnatal diet, had reduced expression of the short isoform of ObRc compared to H and M dams, with sporadic effects of undernutrition (L or LL) on ObRb, ObRt, and LRP1. Intravenous administration of oleptin to a selected postpubertal group (HH, MH, LL) of ovariectomized, estradiol implanted heifers fasted for 56 hours (Expt. 2) did not create detectable increases in third ventricle CSF but increased gonadotropin secretion in all nutritional groups tested. Previous work has shown that leptin enhances gonadotropin secretion during fasting via effects at both hypothalamic and anterior pituitary levels in cattle. Given the apparent lack of robust transfer of leptin across the blood-brain barrier in the current study, effects of leptin at the adenohypophyseal level may predominate in this experimental model.


Kaposi sarcoma-associated herpesvirus: immunobiology, oncogenesis, and therapy.
Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, is the etiologic agent underlying Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. This human gammaherpesvirus was discovered in 1994 by Drs. Yuan Chang and Patrick Moore. Today, there are over five thousand publications on KSHV and its associated malignancies. In this article, we review recent and ongoing developments in the KSHV field, including molecular mechanisms of KSHV pathogenesis, clinical aspects of KSHV-associated diseases, and current treatments for cancers associated with this virus.


Progress in Definition, Prevention and Treatment of Fungal Infections in Cystic Fibrosis.
Cystic fibrosis (CF) is a chronic lethal multi-system condition; however, most of the morbidity and mortality is dependent on the status of the respiratory system. Progressive respiratory decline is mediated by chronic infection and inflammation, punctuated by important acute events known as pulmonary exacerbations which can lead to accelerated decline. The main bacterial species causing infections include Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae and Achromobacter xylosoxidans. In addition to bacteria, fungi are detected in a significant number of patients. The impact of fungal colonization of the airways is still not completely elucidated, but an increasing body of evidence suggests an important role for moulds and yeasts. Although fungal infections are rare, fungi can cause severe pneumonia requiring appropriate targeted treatment. The most common fungi in respiratory samples of patients with CF are Aspergillus fumigatus, Aspergillus terreus and Scedosporium species for filamentous fungi, and yeasts such as Candida albicans and Candida glabrata. Therapeutic strategies depend on the detected fungus and the underlying clinical status of the patient. The antifungal therapy can range from a simple monotherapy up to a combination of three different drugs. Treatment course may be indicated in some patients for two weeks and in others for up to six months, and in rare cases even longer. New antifungal drugs have been developed and are being tested in clinical studies offering the hope of therapeutic alternatives to existing drugs. Identifying relevant risk factors and diagnostic criteria for fungal colonization and infection is crucial to enabling an adequate prevention, diagnosis and treatment.


[A morphological analysis of the specimens obtained during endomyocardial biopsies in patients with a clinical diagnosis of dilated cardiomyopathy].
The authors summarize experience gained with a study of biopsy specimens obtained on endomyocardial biopsies from 88 patients with a clinical diagnosis of dilated cardiomyopathy. The diagnostic value of the study was equal to 70%. Dilated cardiomyopathy largely masked myocarditis and alcoholic cardiomyopathy which were diagnosed morphologically in 30 and 13% of the patients, respectively. No morphological alterations which would allow one to change the clinical diagnosis of dilated cardiomyopathy were discovered in 26% of cases. It has been shown that endomyocardial biopsy is an important tool of diagnosis. In order to introduce it on a broader scale, it is necessary that quantitative uniform criteria for the diagnosis of endomyocardial diseases, primarily myocarditis, be elaborated.


Evolution of cell interactions with extracellular matrix during carcinogenesis.
Interaction of cells with extracellular matrix (ECM) largely defines migration capacity of cells and ways of their dissemination in normal tissue processes and during tumor progression. We review current knowledge about structure of cell adhesions with ECM and their alterations during carcinogenesis. We analyze how changes in structure of cell-matrix adhesions and ECM itself lead to acquisition of neoplastic properties by cells. Modern concepts of tumor cell motility and changes in the relationships of cells with ECM during tumor development are presented. Contemporary approaches for influencing the cell-ECM adhesion structures for inhibition of invasion and metastasis are briefly discussed.


Liver function tests and neuropsychologic impairment in substance abusers.
The relationship between residual neuropsychologic dysfunction in alcoholics and subtle changes in liver function during acute phases of treatment was examined. Noncirrhotic alcoholics who exhibited extreme elevations in the liver enzyme gamma-glutamyl transferase (GGT) were found to have greater impairments in tasks of visuoperceptual and conceptual abilities when compared to alcoholics with normal or only mild elevations in GGT. The relationship between acute liver dysfunction and residual neuropsychologic impairment appeared to be independent of age and patterns of drinking. The implications of these findings in relation to treatment planning and prognosis of alcoholics are discussed.


The Effect of Telemedicine on Resource Utilization and Hospital Disposition in Critically Ill Pediatric Transport Patients.
Pediatric transport teams rely on communication to report patient data to medical command officers, who create care plans and determine disposition. Common destinations are the emergency department (ED), pediatric intensive care unit (PICU), or regular inpatient care area (RIPCA). Telephone report does not result in complete understanding of the patient's condition. Further workup in the ED is often required. Telemedicine allows the patient to be directly seen; parents to be interviewed; and laboratory studies, radiographs, and vital signs to be reviewed. We hypothesized that telemedicine would improve understanding of the patient and result in more accurate disposition. Patients within our hospital from 2012 to 2013 were compared with patients transported using our telemedicine program from April 2014 to April 2015. From 2012 to 2013, a total of 4,662 transports were performed. Of these, 4,067 were inbound transports, 2,302 of these patients were sent to ED (56.6%), 1,062 were sent to RIPCA (26%), and 431 were sent to PICU (10.6%). Over a year-long period of telemedicine implementation, 212 patients used telemedicine and were analyzed. ED utilization decreased to 27% (p < 0.0001), PICU increased to 34.4% (p < 0.0001), and RIPCA rates remained the same at 28% (p = 0.203). Of ED dispositions, 58.6% were admitted to RIPCA for further care, 13.7% to PICU for escalation of care, and 24.1% were discharged. Of RIPCA dispositions, 10% had rapid responses; 0 had code blues. Of PICU dispositions, 90.4% had care escalation; 9.6% were observed in the PICU without escalation. Telemedicine use in transported pediatric patients can positively alter disposition patterns.


Clinical and laboratory features of scleroderma patients developing skeletal myopathy.
Skeletal muscle involvement, or myopathy, has been a recognized feature of systemic sclerosis (SSc). We studied retrospectively 302 Japanese patients with SSc to elucidate the clinical and laboratory features in scleroderma patients developing skeletal myopathy during their clinical course. Forty-three patients (14%) developed skeletal myopathy during their course of the disease. The mean age of the patients who developed skeletal myopathy was significantly lower than that of those who did not. The ratio of male to female was significantly higher in the myopathic patients. The patients with diffuse cutaneous SSc were more likely to develop myopathy than those with limited cutaneous SSc. The prevalences of heart involvement, pulmonary fibrosis, diffuse pigmentation of the skin, and contracture of phalanges were significantly greater in those with skeletal myopathy than in those without. None of the patients with skeletal myopathy had anticentromere antibody. These findings suggested that the SSc patients with severe internal organ involvement, such as pulmonary fibrosis and heart disease, and some other complications were prone to develop skeletal myopathy during their clinical course of the disease.


Foot orthoses and physiotherapy in the treatment of patellofemoral pain syndrome: a randomised clinical trial.
Patellofemoral pain syndrome is a highly prevalent musculoskeletal overuse condition that has a significant impact on participation in daily and physical activities. A recent systematic review highlighted the lack of high quality evidence from randomised controlled trials for the conservative management of patellofemoral pain syndrome. Although foot orthoses are a commonly used intervention for patellofemoral pain syndrome, only two pilot studies with short term follow up have been conducted into their clinical efficacy. A randomised single-blinded clinical trial will be conducted to investigate the clinical efficacy and cost effectiveness of foot orthoses in the management of patellofemoral pain syndrome. One hundred and seventy-six participants aged 18-40 with anterior or retropatellar knee pain of non-traumatic origin and at least six weeks duration will be recruited from the greater Brisbane area in Queensland, Australia through print, radio and television advertising. Suitable participants will be randomly allocated to receive either foot orthoses, flat insoles, physiotherapy or a combined intervention of foot orthoses and physiotherapy, and will attend six visits with a physiotherapist over a 6 week period. Outcome will be measured at 6, 12 and 52 weeks using primary outcome measures of usual and worst pain visual analogue scale, patient perceived treatment effect, perceived global effect, the Functional Index Questionnaire, and the Anterior Knee Pain Scale. Secondary outcome measures will include the Lower Extremity Functional Scale, McGill Pain Questionnaire, 36-Item Short-Form Health Survey, Hospital Anxiety and Depression Scale, Patient-Specific Functional Scale, Physical Activity Level in the Previous Week, pressure pain threshold and physical measures of step and squat tests. Cost-effectiveness analysis will be based on treatment effectiveness against resource usage recorded in treatment logs and self-reported diaries. The randomised clinical trial will utilise high-quality methodologies in accordance with CONSORT guidelines, in order to contribute to the limited knowledge base regarding the clinical efficacy of foot orthoses in the management of patellofemoral pain syndrome, and provide practitioners with high-quality evidence upon which to base clinical decisions. Australian Clinical Trials Registry ACTRN012605000463673ClinicalTrials.gov NCT00118521.


Intrinsic and extrinsic techniques for quantification uncertainty of an interpretable GRU deep learning model used to predict atmospheric total suspended particulates (TSP) in Zabol, Iran during the dusty period of 120-days wind.
Total suspended particulates (TSP), as a key pollutant, is a serious threat for air quality, climate, ecosystems and human health. Therefore, measurements, prediction and forecasting of TSP concentrations are necessary to mitigate their negative effects. This study applies the gated recurrent unit (GRU) deep learning model to predict TSP concentrations in Zabol, Iran, during the dust period of the 120-day wind (3 June - 4 October 2014). Three uncertainty quantification (UQ) techniques consisting of the blackbox metamodel, heteroscedastic regression and infinitesimal jackknife were applied to quantify the uncertainty associated with GRU model. Permutation feature importance measure (PFIM), based on the game theory, was employed for the interpretability of the predictive model's outputs. A total of 80 TSP samples were collected and were randomly divided as training (70%) and validation (30%) datasets, while eight variables were used in the TSP prediction model. Our findings showed that GRU performed very well for TSP prediction (with r and Nash Sutcliffe coefficient (NSC) values above 0.99 for both datasets, and RMSE of 57 μg m-3 and 73 μg m-3 for training and validation datasets, respectively). Among the three UQ techniques, the infinitesimal jackknife was the most accurate one, while all the observed and predicted TSP values fell within the continence limitation estimated by the model. PFIM plots showed that wind speed and air humidity were the most and least important variables, respectively, impacting the predictive model's outputs. This is the first attempt of using an interpretable DL model for TSP prediction modelling, recommending that future research should involve aspects of uncertainty and interpretability of the predictive models. Overall, UQ and interpretability techniques have a key role in reducing the impact of uncertainties during optimization and decision making, resulting in better understanding of sophisticated mechanisms related to the predictive model.


Comparison of conventional fenestration discectomy with Transforaminal endoscopic lumbar discectomy for treating lumbar disc herniation:minimum 2-year long-term follow-up in 1100 patients.
To compare the efficacy of conventional interlaminar fenestration discectomy (IFD) with transforaminal endoscopic lumbar discectomy (TELD) for treating lumbar disc herniation (LDH). The clinical data of 1100 patients who had been diagnosed with LDH between January 2012 and December 2017 were retrospectively analysed. IFD was performed on 605 patients in Group A, whereas TELD was performed on 505 patients in Group B. The Oswestry Disability Index, Visual Analogue Scale for pain and modified MacNab criteria were used to evaluate the outcomes. The surgery duration, intraoperative blood loss, postoperative off-bed activity and postoperative length of hospital stay were recorded. The follow-up period ranged from 24 to 60 months, with an average of 43 months. The excellent and good outcome rates were 93.5% in Group A and 92.6% in Group B. There was no significant difference in efficacy between the groups (P > 0.05). However, Group B had significantly less intraoperative blood loss and shorter bed rest duration and postoperative length of hospital stay than Group A (P < 0.05). There were two cases of postoperative recurrence in Group A and three in Group B. Although conventional IFD and TELD had similar levels of efficacy in treating LDH, TELD had several advantages. There was less intraoperative bleeding, shorter length of hospital stay and shorter bed rest duration. It can be considered a safe and effective surgical option for treating LDH.


Nanoparticles: a promising therapeutic approach in atherosclerosis.
Coronary atherosclerosis is the largest cause of mortality and morbidity in industrialised countries. Despite recent advances in medical therapies, the prevention and treatment of atherosclerosis remain suboptimal. Atherosclerosis is considered to be a chronic inflammatory disease of the arterial wall, involving the accumulation of macrophages and excess low density lipoproteins (LDL), the formation of foam cells which create the atheromatous plaque, resulting in stenosis, aneurysm and plaque rupture leading to acute coronary events. Every step in the atherogenesis process is a potential therapeutic target for both the prevention and regression of atherosclerosis. A novel approach is the use of nanoparticles containing drugs, providing new perspectives in targeted modification of these pathways. Nanoparticles are ultrafine particles sized between 1-100 nm. By using specific methods, nanoparticles can be filled with drugs and achieve targeted drug delivery near the diseased area. In this review article we describe the basic actions of nanoparticles, and we discuss their potential applications in atherosclerosis. We also discuss their advantages and we expose the existing toxicity issues, making it clear however, that the use of nanoparticles is one of the most promising therapeutic strategies against atherosclerosis.


The isotope-exchange reactions of ox heart phosphofructokinase.
1. Ox heart phosphofructokinase catalyses isotope-exchange reactions at pH6.7 between ADP and ATP, and between fructose 6-phosphate and fructose 1,6-diphosphate, the latter reaction being absolutely dependent on the presence of the magnesium complex of ADP. 2. The reaction kinetics are hyperbolic with respect to substrate concentration for both exchange reactions (within the experimental error). 3. The influence of pH, AMP and citrate suggests that the fructose 6-phosphate-fructose 1,6-diphosphate exchange is subject to effector control, and is abolished by dissociation of the enzyme. 4. These results are discussed in relation to the reaction mechanism of the enzyme.


Bad girl and unmet family planning need among Sub-Saharan African adolescents: the role of sexual and reproductive health stigma.
Adolescent pregnancy contributes to high maternal mortality rates in Sub-Saharan Africa. We explored stigma surrounding adolescent sexual and reproductive health (SRH) and its impact on young Ghanaian women's family planning (FP) outcomes. We conducted in-depth, semi-structured interviews with 63 women ages 15-24 recruited from health facilities and schools in Accra and Kumasi, Ghana. Purposive sampling provided diversity in reproductive/relationship/socioeconomic/religious characteristics. Using both deductive and inductive approaches, our thematic analysis applied principles of grounded theory. Participants described adolescent SRH experiences as cutting across five stigma domains. First, community norms identified non-marital sex and its consequences (pregnancy, childbearing, abortion, sexually transmitted infections) as immoral, disrespectful, and disobedient, resulting in bad girl labeling. Second, enacted stigma entailed gossip, marginalization, and mistreatment from all community members, especially healthcare workers. Third, young sexually active, pregnant, and childbearing women experienced internalized stigma as disgrace, shame and shyness. Fourth, non-disclosure and secret-keeping were used to avoid/reduce stigma. Fifth, stigma resilience was achieved through social support. Collectively, SRH stigma precluded adolescents' use of FP methods and services. Our resulting conceptual model of adolescent SRH stigma can guide health service, public health, and policy efforts to address unmet FP need and de-stigmatize SRH for young women worldwide.


Therapeutic effect and metabolic fingerprinting of triple-negative breast cancer cells following exposure to a novel pH-responsive, gambogic acid-loaded micelle.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and lacks effective therapeutic targets. The use of gambogic acid (GA), a class of active ingredients in traditional Chinese medicine with anti-tumour potential, is limited in tumour therapy owing to its drawbacks and unclear organ toxicity. In this study, we used the pH-responsive amphiphilic block copolymer, PEOz-PCL, to create nanodrugs for GA delivery to MDA-MB-231 cells. The pH-responsive GA-loaded micelles were prepared through nanoprecipitation with a more homogeneous size. The average particle size was 42.29 ± 1.74 nm, and the zeta potential value was 9.88 ± 0.17 mV. The encapsulation rate was 85.06%, and the drug loading rate was 10.63%. The process was reproducible, and sustained release reached 80% in 96 h at pH 5.0. Furthermore, cellular tests using CCK-8, TUNEL, and flow cytometry revealed that pH-responsive GA-loaded micelles killed MDA-MB-231 cells more effectively and had much higher activity and targeting compared with free drugs. Metabolomic analysis of the changes in differential metabolites revealed that pH-responsive GA-loaded micelles may inhibit TNBC cells by causing amino acid anabolism, nucleotide metabolism, and glucose metabolism, as well as by affecting their energy sources. The study outcomes will help understand the mechanism of action and the therapeutic efficacy of pH-responsive GA-loaded micelles in vivo.&#xD.


Red ginseng acidic polysaccharide (RGAP) in combination with IFN-gamma results in enhanced macrophage function through activation of the NF-kappaB pathway.
This study examined the effects of red ginseng acidic polysaccharide (RGAP) on macrophage-mediated cytotoxicity towards murine melanoma B16 cells. RGAP alone had no effect on killing of tumor cells. RGAP treatment increased the production of interleukin-1 (IL-1), IL-6, and nitric oxide (NO) by macrophages, whereas tumor necrosis factor (TNF-alpha) and reactive oxygen species (ROS) production were not changed by RGAP. However, treatment of macrophages with a combination of RGAP and recombinant interferon-gamma (rIFN-gamma) enhanced killing of tumor cells. In addition, the combination treatment showed marked cooperative induction of IL-1, IL-6, TNF-alpha, and NO production. Electrophoretic mobility shift assay analysis revealed that treatment of macrophages with RGAP plus rIFN-gamma induced the activation of the nuclear factor-kappa B (NF-kappaB) transcription factor. In agreement with this, the combination treatment resulted in increased NF-kappaB-p65 expression. The present results demonstrate synergistic effects on macrophage function of RGAP in combination with rIFN-gamma, and suggest that NF-kappaB plays an important role in mediating these effects. These data also support the development of clinical studies of this combination.


[Terconazol in vaginal candidiasis. Comparative study].
The antimycotic action and tolerance to terconazole in patients with vaginal candidiasis, were evaluated in a blind study. The medication was given in vaginal ovules (VO) 240 mg, one dose per day, and 80 mg one daily dose for three days; as compared to chlotrimazole, VO 200 mg, daily dose for three days. The patients presented with vaginal candidiasis demonstrated by Nickerson culture medium. Sixty patients were studied in three equivalent groups. The mates of patients treated with terconazole had no treatment; and the mates of patients treated with chlotrimazole received urinary acidifying medication. Symptomatology and mycologic findings were evaluated at 10 and 28 days post treatment. Mycological cure rates at 10 days were: 90 per cent for the terconazole group, 240 mg, one dose; and 95 per cent for patients with terconazole, 80 mg, daily dose for three days; or chlotrimazole, 200 mg, daily dose for three days. Twenty eight days post-treatment, laboratory tests were positive again: 50%, 40% and 15%, respectively. Recidive in patients treated with terconazole, is explained by lack of treatment in mates. In conclusion, terconazole offers a high percentage of clinical and mycological cure in vaginal candidiasis, and it is indispensable treatment for the mate, in order to avoid recidives.


Lifetime asymptomatic for back pain: the validity of self-report measures in soldiers.
A 5-year prospective observational study in US Army Reserve soldiers. The aims of this study were 2-fold: to evaluate the prevalence of soldiers reporting no previous back pain (BP) on 3 consecutive annual assessments, and to compare these findings to those obtained from a subsequent monthly detailed BP assessment. BP history is a risk factor for future BP and disability. Conversely, subjects reporting a negative history of back troubles are thought to be at low risk for future BP events. Reporting of previous BP is assumed to have high validity. Few studies have critically evaluated the validity of the self-reported "lifetime asymptomatic" status in civilian or military populations. Two hundred eighty-five special operations reserve soldiers were queried annually using standardized US Army Medical Questionnaires, among whom 154 (54%) reported no BP or history thereof over 3 consecutive years. Over the next 18 months these soldiers completed annual US Army Medical Questionnaires, as well as monthly numerical rating scale pain scores, Oswestry Disability Indexes, and questions regarding back injuries. At the study's conclusion, soldiers again completed the annual medical certificate, and the results of this final BP assessment were compared with those from monthly surveillance reports. During monthly surveillance of purported "lifetime asymptomatic" soldiers, the 18-month cumulative percentages reporting BP scores > or = 2, > or = 4, and > or = 6 were 84%, 64%, and 14%, respectively. For Oswestry Disability Index scores, these percentages were 25% for scores > or = 10, and 12% for scores > or = 20. Yet, at the conclusion of the 5-year study, 97% soldiers still described themselves as being "asymptomatic for BP problems." In physically active soldiers self-identified as without back problems, the report of BP using frequent surveillance tools is extremely common. The overwhelming majority of these soldiers appeared to have high resilience to common BP episodes (i.e., returned to usual duties). Episodic BP should be considered a normative rather than exceptional occurrence. Similar to other conditions, long-interval surveys of BP history may underestimate the true prevalence of BP.


Polymorphisms and haplotypes in the human immunoglobulin kappa locus.
By comparing the restriction patterns of the DNA from 23 unrelated individuals 16 polymorphisms were defined which allowed us to differentiate between the duplicated copies Op, Ap, Lp and Od, Ad, Ld of the kappa locus (p for the C kappa proximal, d for the distal copy). Some of these duplication-differentiating polymorphisms or DDP revealed also allelic differences between individuals; they are therefore restriction fragment length polymorphism (RFLP) markers at the same time. Three RFLP in the single copy B-J kappa-C kappa region were included into the study. Three basic haplotypes were derived from the combined genotype data, haplotypes N, G and 11. The latter haplotype in which the whole distal copy of the kappa locus is missing was found three times among the 46 haploid genomes studied. The genotypes of the family members of an individual who is homozygous for haplotype 11 are consistent with Mendelian inheritance. Haplotypes N and G are distinguished from each other by eight RFLP markers. Six additional haplotypes, which were found in one or several individuals each, can be derived from the basic haplotypes N and G by hypothetical recombination and/or mutation events.


Single K+-channel current measurements from brain synaptosomes in lipid bilayers.
Ion channels from a rat brain preparation enriched in presynaptic nerve terminals (synaptosomes) were incorporated into planar lipid bilayers. Experiments examined macroscopic (channel-ensemble) currents as well as single-channel currents. Four single-channel conductances (ranging from 10 to 40 pS) were usually observed, each with distinct kinetic properties. All the observed channels selected for K+ over Cl-. These K+ channels may contribute to the resting K+ conductance of brain nerve terminals. Furthermore, this report demonstrates that the properties of ion channels from mammalian brain can be studied in planar lipid bilayers and suggests that this system can be readily extended to many additional investigations on the electrical properties of brain membranes.


Elucidating the role of protein kinase C in chronic lymphocytic leukaemia.
While advances have been made in the clinical treatment of chronic lymphocytic leukaemia (CLL) in recent years, it is still an incurable disease and therefore the identification of novel drug therapies is of paramount importance. Understanding the molecular mechanisms that govern the survival of CLL cells is fundamental in achieving this goal. A number of studies indicate that protein kinase C (PKC)- and phosphatidylinositol-3-kinase (PI3K)- mediated signalling pathways are central to CLL cell survival, and as such PKC has gained renewed interest as a potential drug target in CLL. This may be because it represents a closely-related family of ten protein kinases, which due to the redundancy that exists between isoforms offers an opportunity for the design of isoform specific inhibitors drugs that target leukaemic cells whilst showing reduced toxicity for normal cells. Indeed, PKC signalling pathways have already been considered as targets for specific anticancer drugs [1-3]. Therefore, this short review will focus on the effect of modulating PKC activity in CLL cells and explore whether targeting PKCs could represent a valid therapy for this leukaemia.


Social Media: A Path to Health Literacy.
Social media - websites and other online tools called social networks - serve as a tool to connect people and organizations around topics of common interest. Social media platforms offer tremendous opportunity to engage quickly and sometimes in depth with many and diverse stakeholders as people have the ability to communicate back-and-forth from anywhere in the world. As increasing numbers of people receive their news and health information online, it is important to ensure content delivered through online resources is accessible to diverse target audiences. This chapter discusses a mid-sized health literacy nonprofit organizations' social media philosophy and tactics during the past 10 years, as both social media and health literacy strategies evolved continuously. The integration of social media in health literacy program content depends on the use with best evidence health literacy strategies, such as the use of plain language techniques. Strategy and technical considerations for the implementation and integration of social media within a health literate health communications model are discussed.


Ecological differentiation, lack of hybrids involving diploids, and asymmetric gene flow between polyploids in narrow contact zones of Senecio carniolicus (syn. Jacobaea carniolica, Asteraceae).
Areas of immediate contact of different cytotypes offer a unique opportunity to study evolutionary dynamics within heteroploid species and to assess isolation mechanisms governing coexistence of cytotypes of different ploidy. The degree of reproductive isolation of cytotypes, that is, the frequency of heteroploid crosses and subsequent formation of viable and (partly) fertile hybrids, plays a crucial role for the long-term integrity of lineages in contact zones. Here, we assessed fine-scale distribution, spatial clustering, and ecological niches as well as patterns of gene flow in parental and hybrid cytotypes in zones of immediate contact of di-, tetra-, and hexaploid Senecio carniolicus (Asteraceae) in the Eastern Alps. Cytotypes were spatially separated also at the investigated microscale; the strongest spatial separation was observed for the fully interfertile tetra- and hexaploids. The three main cytotypes showed highly significant niche differences, which were, however, weaker than across their entire distribution ranges in the Eastern Alps. Individuals with intermediate ploidy levels were found neither in the diploid/tetraploid nor in the diploid/hexaploid contact zones indicating strong reproductive barriers. In contrast, pentaploid individuals were frequent in the tetraploid/hexaploid contact zone, albeit limited to a narrow strip in the immediate contact zone of their parental cytotypes. AFLP fingerprinting data revealed introgressive gene flow mediated by pentaploid hybrids from tetra- to hexaploid individuals, but not vice versa. The ecological niche of pentaploids differed significantly from that of tetraploids but not from hexaploids.


[Congenital heart disease: from childhood to adulthood].
With the improvement of congenital heart surgery, most children with congenital heart disease will survive into adulthood with a good quality of life. Regular cardiac follow-up is recommended for all patients. The adolescent period coincides often with medium and long term consequences and complications and repeat surgery or catheter interventions might be needed. It is therefore of prime importance to begin the transition process early and to pursue it well into adulthood. We have elaborated a formal transition program adapted to youngsters with congenital heart disease.


Complete genome sequence of bacteriophage MrAaronian isolated from an Arthrobacter globiformis culture.
Arthrobacteriophage MrAaronian contains a 54,509 bp DNA genome with 87 predicted protein-coding genes. MrAaronian has siphovirus morphology and was collected from a flowerbed soil sample in Poughkeepsie, NY, and isolated on an Arthrobacter globiformis B-2979 culture. MrAaronian has > 99% nucleotide identity with cluster AW arthrobacteriophages Michelle, Stayer, Sloopyjoe, and StarLord.


Prodomain-growth factor swapping in the structure of pro-TGF-β1.
TGF-β is synthesized as a proprotein that dimerizes in the endoplasmic reticulum. After processing in the Golgi to cleave the N-terminal prodomain from the C-terminal growth factor (GF) domain in each monomer, pro-TGF-β is secreted and stored in latent complexes. It is unclear which prodomain and GF monomer are linked before proprotein convertase cleavage and how much conformational change occurs following cleavage. We have determined a structure of pro-TGF-β1 with the proprotein convertase cleavage site mutated to mimic the structure of the TGF-β1 proprotein. Structure, mutation, and model building demonstrate that the prodomain arm domain in one monomer is linked to the GF that interacts with the arm domain in the other monomer in the dimeric structure (i.e. the prodomain arm domain and GF domain in each monomer are swapped). Swapping has important implications for the mechanism of biosynthesis in the TGF-β family and is relevant to the mechanism for preferential formation of heterodimers over homodimers for some members of the TGF-β family. Our structure, together with two previous ones, also provides insights into which regions of the prodomain-GF complex are highly structurally conserved and which are perturbed by crystal lattice contacts.


Self-Sensing Cementitious Composites with Hierarchical Carbon Fiber-Carbon Nanotube Composite Fillers for Crack Development Monitoring of a Maglev Girder.
In view of high-performance, multifunctional, and low-carbon development of infrastructures, there is a growing demand for smart engineering materials, making infrastructures intelligent. This paper reports a new-generation self-sensing cementitious composite (SSCC) incorporated with a hierarchically structured carbon fiber (CF)-carbon nanotube (CNT) composite filler (CF-CNT), which is in situ synthesized by directly growing CNT on CF. Various important factors including catalyst, temperature, and gas composition are considered to investigate their kinetic and thermodynamic influence on CF-CNT synthesis. The reciprocal architecture of CF-CNT not only alleviates the CNT aggregation, but also significantly improves the interfacial bonding between CF-CNT and matrix. Due to the synergic and spatially morphological effects of CF-CNT, that is, the formation of widely distributed multiscale reinforcement networks, SSCCs with CF-CNTs exhibit high mechanical properties and electrical conductivity as well as excellent self-sensing performances, particularly enhanced sensing repeatability. Moreover, the SSCCs with CF-CNTs are integrated into a full-scale maglev girder to devise a smart system for crack development monitoring. The system demonstrates high sensitivity and fidelity to capture the initiation of cracks/damage, as well as progressive and sudden damage events until the complete failure of the maglev girder, indicating its considerable potential for structural health monitoring of infrastructures.


Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.
Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.


Validation of cross-genotype neutralization by hepatitis B virus-specific monoclonal antibodies by in vitro and in vivo infection.
Vaccines based on hepatitis B virus (HBV) genotype A have been used worldwide for immunoprophylaxis and are thought to prevent infections by non-A HBV strains effectively, whereas, vaccines generated from genotype C have been used in several Asian countries, including Japan and Korea, where HBV genotype C is prevalent. However, acute hepatitis B caused by HBV genotype A infection has been increasing in Japan and little is known about the efficacy of immunization with genotype C-based vaccines against non-C infection. We have isolated human monoclonal antibodies (mAbs) from individuals who were immunized with the genotype C-based vaccine. In this study, the efficacies of these two mAbs, HB0116 and HB0478, were analyzed using in vivo and in vitro models of HBV infection. Intravenous inoculation of HBV genotype C into chimeric mice with human hepatocytes resulted in the establishment of HBV infection after five weeks, whereas preincubation of the inocula with HB0116 or HB0478 protected chimeric mice from genotype C infection completely. Interestingly, both HB0116 and HB0478 were found to block completely genotype A infection. Moreover, infection by a genotype C strain with an immune escape substitution of amino acid 145 in the hepatitis B surface protein was also completely inhibited by incubation with HB0478. Finally, in vitro analysis of dose dependency revealed that the amounts of HB0478 required for complete protection against genotype C and genotype A infection were 5.5 mIU and 55 mIU, respectively. These results suggested that genotype C-based vaccines have ability to induce cross-genotype immunity against HBV infection.


Bodily self-consciousness and its disorders.
Research in clinical and human neuroscience indicates that important brain mechanisms of self-consciousness are based on the integration of multisensory bodily signals (i.e., bodily self-consciousness: BSC), including signals coming from outside our body (i.e., exteroceptive signals, such as tactile, auditory, and visual information) and the inside of our body (i.e., interoceptive signals). In this chapter, we discuss selected behavioral and neuroimaging studies about how multisensory integration generates and modulates BSC in humans, with particular relevance to parietal mechanisms. We then review the neurology of disorders of BSC after acquired brain damage or dysfunction, ranging from body attentional disorders to delusional and illusory deficits about the patient's own body, associated with a breakdown of the link between the body and the self.


[Correlation between 13C-urea breath test and gastric histological findings in Helicobacter pylori positive patients].
13C-urea breath test (UBT), available for diagnosis of Helicobacter pylori (HP) in the stomach, measures the 13CO in the breath in which 13C urea is resolved in the stomach by urease derived from HP. Accordingly UBT is useful for a test of HP infection. This study is aimed at clarifying the relationship between the UBT and gastric histological findings. For this study we selected 63 patients with HP infection who showed both positive UBT and positive histological diagnosis. Briefly in the UBT procedure, the patients were given 13C-urea (100 mg dissolved 100 ml water) in a fasting state and kept in the left decubitus position for 5 minutes, and then the patients were asked to expire into testing bags before and 20 minutes after administration of the urea. Biopsy specimens were taken endscopically from the gastric antrum and the body. The specimens of all patients showed positive CLO test. HP organisms, inflammation, activity, and atrophy of the gastric specimens, were expressed in score from 0 to 3 according to the Update Sydney system. The UBT values were high correlated with the increase of HP organisms. The UBT was 11.8, 26.3, and 37/1000 in the groups with the scores of 0.1, and 2 in the number of HP organisms from the gastric body, respectively. The UBT was 19.2, 22.2, 36.1, 26.7/1000 in the groups with scores of 0, 1, 2, and 3 for the specimens from the antrum, respectively. The results show that there is a positive correlation between the UBT values and HP organisms. As a result, the UBT correlated with the activity score. Grade of gastric mucosal atrophy was expressed histologically in scores of 0,1,2, and 3. The UBT was 29.4, 19.1, 17.5, and 9.3/1000 in the groups with scores 0,1,2, and 3 in the grades of gastric atrophy from the gastric body, respectively. There was a negative correlation between the UBT values and the grade of gastric atrophy. We conclude that the UBT values which indicate the number of HP organisms can be used not only for diagnosis of HP infection but also the quantitative index of HP load.


Changes in Upper Airway Dimensions Following Orthodontic Treatment of Skeletal Class II Malocclusion with Twin Block Appliance: A Systematic Review.
This systematic review intends to evaluate the dimensional changes in upper airway dimensions (UAD) of the respiratory tract subsequent to orthodontic treatment of skeletal Class II malocclusion with Twin Block Appliance (TBA). The quality of reporting systematic reviews and meta-analyses was decided by the PRISMA standards with PROSPERO registration number CRD42017060317. The systematic search included EMBASE, MEDLINE, Psych INFO, Scopus, CINAHL, and other reference journals and review articles. The article search was performed from March 2017 until November 2017. Cochrane's risk of bias in non-randomized studies - of interventions (ROBINS-I) was used to grade the methodological quality of the included studies. The screening procedure identified 302 studies, among which seven studies satisfied the inclusion criteria for eligibility. The UAD at the pretreatment time varied from 7.2 mm to 41.9 mm with a mean of 14.16 mm. The post-treatment change in UAD ranged from 8.2 mm to 43.7 mm with a mean of 15.6 mm. There was a significant increase in UAD following the TBA treatment in the patient group as compared to the control group.


Lung ultrasonography and echocardiography in the Intensive Care Unit: a combined and practical approach.
This article describes some practical applications of critical care ultrasonography that are of interest to the frontline intensivist. Instead of presenting a standard state of the art review article, we present 3 typical clinical cases where combined echocardiography, lung ultrasonography, and other ultrasonography techniques were helpful to the critical care team. The manuscript includes a variety figures and video clips that illustrate the utility of critical care ultrasonography in guiding diagnosis and management of the critically ill patient.


MS/MS analysis and imaging of lipids across Drosophila brain using secondary ion mass spectrometry.
Lipids are abundant biomolecules performing central roles to maintain proper functioning of cells and biological bodies. Due to their highly complex composition, it is critical to obtain information of lipid structures in order to identify particular lipids which are relevant for a biological process or metabolic pathway under study. Among currently available molecular identification techniques, MS/MS in secondary ion mass spectrometry (SIMS) imaging has been of high interest in the bioanalytical community as it allows visualization of intact molecules in biological samples as well as elucidation of their chemical structures. However, there have been few applications using SIMS and MS/MS owing to instrumental challenges for this capability. We performed MS and MS/MS imaging to study the lipid structures of Drosophila brain using the J105 and 40-keV Ar4000+ gas cluster ion source, with the novelty being the use of MS/MS SIMS analysis of intact lipids in the fly brain. Glycerophospholipids were identified by MS/MS profiling. MS/MS was also used to characterize diglyceride fragment ions and to identify them as triacylglyceride fragments. Moreover, MS/MS imaging offers a unique possibility for detailed elucidation of biomolecular distribution with high accuracy based on the ion images of its fragments. This is particularly useful in the presence of interferences which disturb the interpretation of biomolecular localization. Graphical abstract MS/MS was performed during time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis of Drosophila melongaster (fruit fly) to elucidate the structure and origin of different chemical species in the brain including a range of different phospholipid classes (PC, PI, PE) and di- and triacylglycerides (DAG & TAG) species where reference MS/MS spectra provided a potential means of discriminating between the isobaric [M-OH]+ ion of DAGs and the [M-RCO]+ ion of TAGs.


Resilience amongst Australian aboriginal youth: an ecological analysis of factors associated with psychosocial functioning in high and low family risk contexts.
We investigate whether the profile of factors protecting psychosocial functioning of high risk exposed Australian Aboriginal youth are the same as those promoting psychosocial functioning in low risk exposed youth. Data on 1,021 youth aged 12-17 years were drawn from the Western Australian Aboriginal Child Health Survey (WAACHS 2000-2002), a population representative survey of the health and well-being of Aboriginal children, their families and community contexts. A person-centered approach was used to define four groups of youth cross-classified according to level of risk exposure (high/low) and psychosocial functioning (good/poor). Multivariate logistic regression was used to model the influence of individual, family, cultural and community factors on psychosocial outcomes separately for youth in high and low family-risk contexts. Results showed that in high family risk contexts, prosocial friendship and low area-level socioeconomic status uniquely protected psychosocial functioning. However, in low family risk contexts the perception of racism increased the likelihood of poor psychosocial functioning. For youth in both high and low risk contexts, higher self-esteem and self-regulation were associated with good psychosocial functioning although the relationship was non-linear. These findings demonstrate that an empirical resilience framework of analysis can identify potent protective processes operating uniquely in contexts of high risk and is the first to describe distinct profiles of risk, protective and promotive factors within high and low risk exposed Australian Aboriginal youth.


An evaluation of the content and quality of tinnitus information on websites preferred by General Practitioners.
Tinnitus is a prevalent and complex medical complaint often co-morbid with stress, anxiety, insomnia, depression, and cognitive or communication difficulties. Its chronicity places a major burden on primary and secondary healthcare services. In our recent national survey of General Practitioners (GPs) from across England, many reported that their awareness of tinnitus was limited and as a result were dissatisfied with the service they currently provide. GPs identified 10 online sources of information they currently use in clinical practice, but welcomed further concise and accurate information on tinnitus assessment and management. The purpose of this study was to assess the content, reliability, and quality of the information related to primary care tinnitus assessment and management on these 10 websites. Tinnitus related content on each website was assessed using a summative content analysis approach. Reliability and quality of the information was assessed using the DISCERN questionnaire. Quality of information was rated using the validated DISCERN questionnaire. Significant inter-rater reliability was confirmed by Kendall's coefficient of concordance (Wt) which ranged from 0.48 to 0.92 across websites. The website Map of Medicine achieved the highest overall DISCERN score. However, for information on treatment choice, the British Tinnitus Association was rated best. Content analysis revealed that all websites lacked a number of details relating to either tinnitus assessment or management options. No single website provides comprehensive information for GPs on tinnitus assessment and management and so GPs may need to refer to more than one if they want to maximise their coverage of the topic. From those preferred by GPs we recommend several specific websites as the current 'best' sources. Our findings should guide healthcare website providers to improve the quality and inclusiveness of the information they publish on tinnitus. In the case of one website, our preliminary findings are already doing so. Such developments will in turn help facilitate best practice in primary care.


Chronic viral hepatitis and its association with liver cancer.
Chronic infection with hepatitis viruses represents the major causative factor for end-stage liver diseases, including liver cirrhosis and primary liver cancer (hepatocellular carcinoma, HCC). In this review, we highlight the current understanding of the molecular mechanisms that drive the hepatocarcinogenesis associated with chronic hepatitis virus infections. While chronic inflammation (associated with a persistent, but impaired anti-viral immune response) plays a major role in HCC initiation and progression, hepatitis viruses can also directly drive liver cancer. The mechanisms by which hepatitis viruses induce HCC include: hepatitis B virus DNA integration into the host cell genome; metabolic reprogramming by virus infection; induction of the cellular stress response pathway by viral gene products; and interference with tumour suppressors. Finally, we summarise the limitations of hepatitis virus-associated HCC model systems and the development of new techniques to circumvent these shortcomings.


Vasopressor Infusion During Prone Spine Surgery and Acute Renal Injury: A Retrospective Cohort Analysis.
Hypotension is associated with acute kidney injury, but vasopressors used to treat hypotension may also compromise renal function. We therefore tested the hypothesis that vasopressor infusion during complex spine surgery is not associated with impaired renal function. In this retrospective cohort analysis, we considered adults who had complex spine surgery between January 2005 and September 2014 at the Cleveland Clinic Main Campus. Our primary outcome was postoperative estimated glomerular filtration rate. Secondarily, we evaluated renal function using Acute Kidney Injury Network criteria. We obtained data for 1814 surgeries, including 689 patients (38%) who were given intraoperative vasopressors infusion for ≥30 minutes and 1125 patients (62%) who were not. Five hundred forty patients with and 540 patients without vasopressor infusions were well matched across 32 potential confounding variables. In matched patients, vasopressor infusions lasted an average of 173 ± 100 minutes (SD) and were given a median dose (1st quintile, 3rd quintile) of 3.4-mg (1.5, 6.7 mg) phenylephrine equivalents. Mean arterial pressure and the amounts of hypotension were similar in each matched group. The postoperative difference in mean estimated glomerular filtration rate in patients with and without vasopressor infusions was only 0.8 mL/min/1.73 m (95% CI, -0.6 to 2.2 mL/min/1.73 m) (P = .28). Intraoperative vasopressor infusion was also not associated with increased odds of augmented acute kidney injury stage. Clinicians should not avoid typical perioperative doses of vasopressors for fear of promoting kidney injury. Tolerating hypotension to avoid vasopressor use would probably be a poor strategy.